UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington D. C. 20549
 
FORM 10-K
 
x
ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
 
For the year ended December 31, 2015
 
¨
TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
 
For the transition period from
 
Commission file number 000-55413
 
 
Cell Source, Inc.
(Exact name of registrant as specified in its charter)
 
Nevada
 
32-0379665
(State or other jurisdiction of incorporation or organization)
 
(I.R.S. Employer
Identification No.)
 
5 Kineret Street
Bnei Brak Israel 5126237
(Address of principal executive offices)
 
011 972 3 562-1755
(Issuer's telephone number)
 
Securities registered pursuant to Section 12(b) of the Act:  None
 
Securities registered pursuant to Section 12(g) of the Act: Common stock, $0.001 par value
 
Indicate by check mark whether the registrant is a well-known seasoned issuer as defined in Rule 405 of the Securities Act. o    Yes þ No
 
Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. o Yes þ     No
 
Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days.  þ    Yes o No
 
Indicate by check mark whether the registrant has submitted electronically and posted on its corporate Web site, if any, every Interactive Data File required to be submitted and posted pursuant to Rule 405 of Regulation S-T (§ 232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit and post such files).  þ   Yes  ¨    No
 
Indicate by check mark if disclosure of delinquent filers pursuant to Item 405 of Regulation S-K is not contained herein, and will not be contained, to the best of registrant’s knowledge, in definitive proxy or information statements incorporated by reference in Part III of this Form 10-K or any amendment to this Form 10-K .  o
 
Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, or a smaller reporting company.  See the definitions of “large accelerated filer”, “accelerated filer”, and “smaller reporting company” in Rule 12b-2 of the Exchange Act.
 
Large accelerated filer o
Accelerated filer o
Non-accelerated filer o
Smaller reporting company  þ
 
Indicate by check mark whether the registrant is a shell company (as defined by Rule 12b-2 of the Exchange Act).  ¨   Yes    þ    No  
 
As of June 30, 2015, the aggregate market value of the issued and outstanding common stock held by non-affiliates of the registrant was $19,579,741, based on the closing sale price as reported on the OTC Markets.
 
As of April 8, 2016, there were 23,929,256 shares of common stock outstanding.
 
DOCUMENTS INCORPORATED BY REFERENCE - None.
 

 
 

 
 
CELL SOURCE, INC.
 
FORM 10-K
 
FOR THE FISCAL YEAR ENDED DECEMBER 31, 2015
 
INDEX
 
   
Page
 
PART I
 
     
Item 1.
Business.
1
Item 1A.
Risk Factors.
33
Item 1B.
Unresolved Staff Comments.
43
Item 2.
Properties.
44
Item 3.
Legal Proceedings.
44
Item 4.
Mine Safety Disclosures.
44
     
 
PART II
 
     
Item 5.
Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities.
45
Item 6.
Selected Financial Data.
46
Item 7.
Management’s Discussion and Analysis of Financial Condition and Results of Operations.
46
Item 7A.
Quantitative and Qualitative Disclosures About Market Risk.
54
Item 8.
Financial Statements and Supplementary Data.
54
Item 9.
Changes in and Disagreements With Accountants on Accounting and Financial Disclosure.
54
Item 9A.
Controls and Procedures.
54
Item 9B.
Other Information.
55
     
 
PART III
 
     
Item 10.
Directors, Executive Officers, and Corporate Governance.
56
Item 11.
Executive Compensation.
58
Item 12.
Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters.
60
Item 13.
Certain Relationships and Related Transactions, and Director Independence.
60
Item 14.
Principal Accounting Fees and Services.
62
     
 
PART IV
 
     
Item 15.
Exhibits, Financial Statement Schedules
63
     
Signatures
 
65


 
 

 

PART I

ITEM 1. BUSINESS.
 
Overview
 
TTSI Corporate History
 
Cell Source, Inc. (the "Company") is a Nevada corporation formed on June 6, 2012 under the name Ticket to See, Inc. ("TTSI"). Prior to the Share Exchange (as defined below), we did not have any significant assets or operations. Cell Source, Inc. is the parent company of Cell Source Ltd. ("Cell Source Israel"). Cell Source Israel was founded in Israel in 2011 in order to commercialize a suite of inventions relating to certain cancer treatments.
 
Share Exchange
 
On June 30, 2014 (the “Closing Date”), TTSI entered into and closed a Share Exchange Agreement (the “Share Exchange Agreement”) with Cell Source Israel and 100% of the shareholders of Cell Source Israel (the “CSL Shareholders”) whereby Cell Source Israel became the wholly-owned subsidiary of TTSI and TTSI changed its name to Cell Source, Inc. (the "Share Exchange"), and whereby certain CSL Shareholders, holding 18,245,923 of the outstanding shares of Cell Source Israel, transferred to the Company an aggregate of 18,245,923 shares of Cell Source Israel’s ordinary shares, each of nominal value of NIS 0.01 (“CSL Ordinary Shares”) in exchange for an aggregate of 18,245,923 newly issued shares of the Company's Common Stock, par value $0.001 per share (the “Company Common Stock” or the "Common Stock"). The aggregate of 18,245,923 shares of newly issued Company Common Stock represents 78.5% of the outstanding shares of Company Common Stock following the Closing Date. In addition, outstanding five (5) year warrants to acquire 4,859,324 CSL Ordinary Shares at an exercise price of $0.75 per share (the "CSL Warrants") were exchanged for newly issued warrants to purchase shares of Company Common Stock (the “Company Warrants”), which Company Warrants contain substantially similar terms as the CSL Warrants. In addition, outstanding warrants to acquire 2,043,835 CSL Ordinary Shares held by Yair Reisner, Ph.D. and Yeda Research and Development Company Limited were exchanged for warrants to purchase shares of Company Common Stock (the “Researcher Company Warrants”), which Researcher Company Warrants contain substantially similar terms as their warrants to acquire CSL Ordinary Shares. The aggregate of 6,903,159 Company Warrants and Researcher Company Warrants represented 77.5% of the outstanding warrants to purchase Common Stock of the Company following the Closing Date.
 
Cell Source Israel's Private Placement
 
Beginning in November 2013, Cell Source Israel collected and entered into a series of subscription agreements (the “Subscription Agreement”) with certain accredited investors (the “Investors”) in a private placement offering (the “Private Placement”). Cell Source Israel held closings of the Private Placement between December 9, 2013 through April 7, 2014, pursuant to which Cell Source Israel sold an aggregate of 4,759,324 Units (the "Units"), at a purchase price of $0.75 per Unit, for gross proceeds of $3,569,475. Each Unit consists of one (1) share of CSL Ordinary Shares and one (1) CSL Warrant. Each CSL Warrant entitled the holder to purchase one (1) share of CSL Ordinary Shares for a five (5) year period at an exercise price of $0.75 per share. In connection with the Private Placement, Cell Source Israel relied upon the exemption from securities registration provided by Section 4(a)(2) of the Securities Act of 1933, as amended (the “Securities Act”) and Rule 506 as promulgated under the Securities Act for transactions not involving a public offering.
 
Under the Subscription Agreement, the Investors were granted the following rights for a period of five (5) years commencing on the closing of the Private Offering: (i) in the event any shares of CSL Ordinary Shares or securities convertible, exchangeable or exercisable for CSL Ordinary Shares are issued at a price less than $0.75 per share (“Adjustment Event”), subject to certain adjustments, then additional CSL Ordinary Shares, or equivalents, will be issued to the Investors such that the aggregate holdings of the Investors is equal to the aggregate holding had such Investors initially purchased at the applicable lower price by which securities were issued in the Adjustment Event (except that certain issuances set forth in the Subscription Agreement would not be an Adjustment Event); and (ii) upon any financing by Cell Source whereby CSL Ordinary Shares or securities convertible into CSL Ordinary Shares are issued or sold (a “Subsequent Financing”), Investors have the right to participate in such Subsequent Financing (subject to customary exemptions).  The Investors were also granted the right to elect up to two (2) independent board members. On May 29, 2014, the majority of the Investors granted certain groups of shareholders the right to elect, subject to the closing of the Share Exchange Agreement, Yoram Drucker, Itamar Shimrat, David Zolty, Ben Friedman and Dennis Brown to the Board of Directors of the Company. Furthermore, pursuant to the Subscription Agreement, in the event that the Registration Statement, as defined below, is declared effective, the Company was obligated to issue to certain founders of Cell Source Israel (Isaac Braun, Saar Dickman, Itamar Shimrat and Yoram Drucker) warrants to purchase an aggregate of 3,000,000 shares of Company Common Stock at an exercise price of $0.75 per share, subject to the same adjustments and terms as the Company Warrants.
 

 
1

 

In connection with the Private Placement, Cell Source Israel also entered into a Registration Rights Agreement (the “Registration Rights Agreement”) with the Investors, pursuant to which Cell Source Israel agreed to file a registration statement (the “Registration Statement”), registering for resale (i) all CSL Ordinary Shares, or securities into which they were exchanged, that were included in the Units; and (ii) all CSL Ordinary Shares, or equivalent securities, issuable upon exercise of the Investor Warrants or upon exercise of warrants into which the Investor Warrants were exchanged.  The Company filed the Registration Statement on August 8, 2014 and it was declared effective by the Securities and Exchange Commission on November 10, 2014.
 
As a result of the Share Exchange, the Company assumed the obligations of Cell Source Israel under the Subscription Agreement and Registration Rights Agreement.
 
In July and August 2014, the Company, Cell Source Israel and the majority of the Investors entered into Amendment No. 1 (the “RRA Amendment”) to the Registration Rights Agreement in order to amend a definition in the Registration Rights Agreement to more accurately reflect the understanding of the parties.  Pursuant to the RRA Amendment, the definition relating to the deadline to file the Registration Statement was corrected such that the Company became obligated to file the Registration Statement on or prior to the 60th day after the closing of the Share Exchange Agreement (the “Registration Filing Date”).  The RRA Amendment did not change any other term of the Registration Rights Agreement, including the obligation of the Company to get the Registration Statement declared effective within 120 days of the Registration Filing Date.
 
The foregoing descriptions of the Private Placement and related agreements and transactions do not purport to be complete and are qualified in their entirety by reference to the complete text of such agreements.
 
Implications of being an Emerging Growth Company
 
As a company with less than $1.0 billion in revenue during our last fiscal year, we qualify as an “emerging growth company” as defined in the Jumpstart Our Business Startups Act, or JOBS Act, enacted in April 2012. An “emerging growth company” may take advantage of reduced reporting requirements that are otherwise applicable to public companies. These provisions include, but are not limited to:

·  
being permitted to present only two years of audited financial statements and only two years of related Management’s Discussion & Analysis of Financial Condition and Results of Operations in this report on Form 10-K;
·  
not being required to comply with the auditor attestation requirements of Section 404 of the Sarbanes-Oxley Act of 2002, as amended, or the Sarbanes-Oxley Act;
·  
reduced disclosure obligations regarding executive compensation in our periodic reports, proxy statements and registration statements; and
·  
exemptions from the requirements of holding a nonbinding advisory vote on executive compensation and stockholder approval of any golden parachute payments not previously approved.
 
We may take advantage of these provisions until the last day of our fiscal year following the fifth anniversary of the date of the first sale of our common equity securities pursuant to an effective registration statement under the Securities Act of 1933, as amended, or the Securities Act, which such fifth anniversary will occur in 2018. However, if certain events occur prior to the end of such five-year period, including if we become a “large accelerated filer,” our annual gross revenues exceed $1.0 billion or we issue more than $1.0 billion of non-convertible debt in any three-year period, we will cease to be an emerging growth company prior to the end of such five-year period.
 
We have elected to take advantage of certain of the reduced disclosure obligations and may elect to take advantage of other reduced reporting requirements in future filings. As a result, the information that we provide to our stockholders may be different than you might receive from other public reporting companies in which you hold equity interests.
 
In addition, Section 107 of the JOBS Act also provides that an “emerging growth company” can take advantage of the extended transition period provided in Section 7(a)(2)(B) of the Securities Act for complying with new or revised accounting standards. In other words, an “emerging growth company” can delay the adoption of certain accounting standards until those standards would otherwise apply to private companies. However, we are choosing to “opt out” of such extended transition period, and as a result, we will comply with new or revised accounting standards on the relevant dates on which adoption of such standards is required for non-emerging growth companies. Section 107 of the JOBS Act provides that this decision to opt out of the extended transition period for complying with new or revised accounting standards is irrevocable.
 

 
2

 

Notwithstanding the above, we are also currently a “smaller reporting company”, meaning that we are not an investment company, an asset-backed issuer, nor a majority-owned subsidiary of a parent company that is not a smaller reporting company, and has a public float of less than $75 million and annual revenues of less than $50 million during the most recently completed fiscal year. Some of the reduced disclosure and other requirements available to us as a result of the JOBS Act may continue to be available to us after we are no longer considered an “emerging growth company”. Specifically, similar to “emerging growth companies”, “smaller reporting companies” are able to provide simplified executive compensation disclosures in their filings; are exempt from the provisions of Section 404(b) of the Sarbanes-Oxley Act requiring that independent registered public accounting firms provide an attestation report on the effectiveness of internal control over financial reporting; and have certain other decreased disclosure obligations in their SEC filings, including, among other things, only being required to provide two years of audited financial statements in annual reports. Decreased disclosures in our SEC filings due to our status as an “emerging growth company” or “smaller reporting company” may make it harder for investors to analyze our results of operations and financial prospects.
 
Cell Source Israel Corporate History
 
Prior to the Share Exchange, Cell Source Israel was a privately held company located in Tel Aviv, Israel. Cell Source Israel was founded in 2011 in order to commercialize a suite of inventions that were the result of over ten (10) years of research at the Weizmann Institute of Science in Rehovot, Israel (“Weizmann Institute”). Pursuant to a Research and License Agreement by and between Cell Source Israel and Yeda Research and Development Company Limited ("Yeda"), dated October 3, 2011, as amended on April 1, 2014 (the “Yeda License Agreement”), Yeda, the commercial arm of the Weizmann Institute, granted Cell Source Israel an exclusive license to certain patents, discoveries, inventions, and other intellectual property generated (together with others) by Yair Reisner, Ph.D. (“Dr. Reisner”), head of the Immunology Department at the Weizmann Institute.
 
Our Business
 
We are a cell therapy company focused on immunotherapy and regenerative medicine. Our technology seeks to address one of the most fundamental challenges within human immunology:  how to tune the immune response such that it tolerates selected desirable foreign cells, but continues to attack all other (undesirable) targets.  In simpler terms, many potentially life-saving treatments have limited effectiveness today because the patient’s immune system rejects them. Today, rejection is partially overcome using aggressive immune suppression treatments that leave the patient exposed to many dangers by compromising their immune system. The ability to overcome rejections without having to compromise the rest of the immune system may open the door to effective treatment of a number of severe medical conditions which are characterized by this need. These include:
 
·  
Haematological malignancies (leukemias, lymphomas, etc.). One of the most effective treatments for these conditions is bone marrow transplantation. However, this is a risky and difficult procedure primarily because of potential conflicts between host and donor immune systems.
·  
Non-malignant haematological conditions (such as sickle cell anemia) which could also be largely treated by bone marrow transplantation if the procedure did not pose such threatening conflicts between host and donor immune systems.
·  
Organ failure and transplantation. A variety of conditions can be treated by the transplantation of vital organs. However, transplantation is limited both by the problem of rejection and an insufficient supply of available donor organs.
 
Discussion
 
Haematological Malignancies
 
Haematological malignancies (blood cancers) comprise a variety of lymphomas and leukemias. A very important treatment protocol for these malignancies involves the use of hematopoietic stem cell transplantation (“HSCT”). To the best of our knowledge, over 1,000,000 bone marrow transplantations have been performed worldwide with the annual number of procedures exceeding 60,000(table below). Our technology will be immediately applicable to, at a minimum, the roughly 30,000 worldwide bone marrow transplants that are allogeneic (using cells taken from another individual).
 
 
 
3

 
 
 
Source:Worldwide Network for Blood and Marrow Transplantations
 
HSCT often has a curative effect when successful. However, it is very risky. HSCT involves destroying the patient’s native immune system with radiation or chemotherapy (myeloablation) before the transplantation, and then suppressing immune response (immunosuppression) with drugs to manage the conflicts between host and donor cells, often for the rest of the patient’s life. The majority of patients are unable to find a matched family donor. Approximately 35-40% of all unrelated donor transplant patients die within a year of transplantation.  Most of these deaths (table below) are caused not by cancer, but by other factors, the most prevalent of with are GvHD (Graft versus Host Disease) and infections.


 
4

 
 
 
 
Myeloablation and immunosuppression are dangerous and difficult to tolerate, especially in patients over age 50. Therefore HSCT has been used mainly with younger patients
 
This means that:
 
 
a)
many blood cancer patients are not candidates for the primary treatment (HSCT) that represents a potential cure;
 
b)
there is high mortality among those patients who are candidates for HSCT and do undergo the procedure; and
 
c)
those patients who successfully undergo and survive HSCT take dangerous, expensive, and quality-of-life reducing immunosuppression medications, typically for a prolonged period of time.
 
There is widespread awareness of the need for improved immune-system management technologies for HSCT - both to improve outcomes of transplantations for the traditional target set of patients and to expand the use of the procedure by making transplantation safe enough to become appropriate for a broader set of patients.

We aspire to use Veto Cell technology to dramatically improve the outcomes of the allogeneic transplantations already being performed, and thereby to rapidly penetrate the current market. However, our target population greatly exceeds those patients who currently undergo HSCT, as the firm’s tolerizing technology could potentially make allogeneic transplantation an option for a much larger proportion of the diseased population. The following table shows the prevalence of the specific haematological malignancies on which we will focus:

 
 
5

 


Initial Malignancy Indications
(note estimates for North America and EU only)
 
Prevalence
(Number patients)
   
Annual Bone Marrow
Transplantations
 
                 
Non-Hodgkin’s Lymphoma
   
808,000
     
11,000
 
Multiple Myeloma
   
188,000
     
16,500
 
Acute Myeloid Leukemia
   
119,000
     
8,500
 
    Total
   
1,115,000
     
36,000
 

Source: National Cancer Institute, World Health Organization, Leukemia & Lymphoma Sociey, European Journal of Cancer
 
For the purposes of this document, it is assumed that the immediate candidates for Cell Source-enabled HSCT will be the subset of cancer patients that today receive transplantations as part of their cancer treatment (rightmost column in table above). We believe that these patients will benefit from Veto Cell adjunct therapy, as such therapy aspires to improve the success and reduce the risk and mortality of a procedure that they are having anyway. With time, as Veto Cell treatment becomes more widespread and data is accumulated, we believe that the percentage of patients that will be referred for Veto Cell enabled HSCT will increase significantly.
 
It is also important to note that incidence of these diseases is increasing, with up to a 77 percent increase in the number of newly diagnosed hematologic malignancies among the older population expected to occur over the next 20 years.  See Mohamed L. Sorror et al., Long-term Outcomes Among Older Patients Following Nonmyeloablative Conditioning and Allogeneic Hematopoietic Cell Transplantation for Advanced Hematologic Malignancies , J. Am. Med. Ass'n, Nov. 2, 2011, at 1874.
 
HSCT Market Trends
 
There are four important market trends affecting the haematological malignancies market:
 
(1)            
As noted above, increasing incidence of these disorders in the West, largely driven by the aging population.
 
(2)
Improvement and proliferation of HSCT treatments.
 
(3)
A “virtuous circle” of lowered death rate due to better transplantations leading to more aggressive focus on HSCT.
 
(4)
The growing use of “reduced intensity conditioning,” i.e., lower myoablative dosing, which makes the procedure more survivable for older patients (see table below).
 
 
 
6

 
 
 
However, despite the above trends, the use of HSCT, especially allogeneic, remains limited because of the risks associated with the myeloablative treatments required to reduce the host immune response and GVHD. This means that the “gold-standard” of treatment is largely unavailable to the age cohort that makes up the majority of sufferers of these diseases.
 
The Company aspires to address this issue in a distinctive manner by significantly reducing the need for myeloablative treatment and avoiding the risk of GVHD, thereby improving the outlook for allogeneic transplantations and enabling their use in a much larger population set.
 
Relevant Non-Malignant Diseases
 
While Hematological malignancies represent the Company's initial focus, the Company's selective immune response blocking technology may also be effective in treating certain non-malignant blood and immune system disorders. This would represent an additional growth opportunity for the Company.
 
The target non-malignant diseases are widespread. The Company's first non-malignant disorder target is expected to be sickle cell anemia. This is a serious and relatively common disease.
 
Sickle cell anemia can be treated by HSCT which replaces the defective bone marrow cells. However, because of HSCT’s riskiness, the procedure is currently used only in extreme cases. If successful in enabling safer HSCT, the Company will make this treatment available to a broader set of sickle cell anemia sufferers. As the therapy would be introduced in the form of bone marrow transplantation, we assume that only patients with relatively severe forms of the disease will initially be candidates. As such, only a minority of sickle cell anemia patients will be treatment candidates.

 
 
7

 

A second target within non-malignant disorders is support of organ transplantations (kidney, liver, etc.). Approximately 60,000 such procedures are conducted in North America and the EU each year. As with bone marrow transplantations, organ transplantations require substantial immunosuppression to prevent rejection. This ongoing treatment is dangerous, quality-of-life reducing, and costly. The Company's Veto Cell technology can potentially be used to selectively reduce immune response to the transplanted organ, thus reducing the need for aggressive immunosuppression post transplantation.
 
Market Access and Channels
 
The market for transplantation therapies is relatively concentrated. There are approximately 1,600 transplantation centers worldwide, of which some 700 are in North America and Western Europe.
 
A relatively small subset of these (often termed “Centers of Excellence”) tends to set the practice standards for the entire transplantation community. Therefore, as discussed in the “Strategy” section, the Company plans to focus its initial penetration strategy on a relatively small group of influential centers.
 
Reimbursement issues for our therapies are expected to be relatively straightforward. Once clinical effectiveness and regulatory approval are established, the value-proposition for payors and providers is expected to be clear and compelling. Issues connected with immunosuppression and rejection constitute a major component of bone marrow transplantation costs, and significant improvement in this area is expected to bring substantive cost-savings for payors.
 
Sector Focus
 
We are in the general space of cell therapies. This is an emerging field, described by industry analysts as having “Blockbuster potential for regenerative treatments in indications with high level of unmet need.” (Datamonitor.)
 
Within the cell therapy field, our initial focus is on allogeneic therapies (treatments using donor derived-as opposed to patient derived-cells), with a focus on haploidentical transplantations (transplantations that use cells from partially matched-as opposed to fully matched-donors and recipients). While potentially valuable, allogeneic therapies are relatively complex, risky, and expensive. A key driver of this complexity and associated costs is the conflict between host and donor immune systems, as discussed above.
 
Our technology, which in preclinical studies, and in the case of the Megadose Drug Combination in a first-in-human proof of concept, has shown the ability to enable tolerance of donor cells without affecting other immune processes, is fundamentally enabling. We expect it to significantly increase the safety, reduce the cost, and therefore broaden the scope of indications for such procedures.
 
Over time, we aspire to apply these technologies to autologous therapies (the processing and re-transplantation of an individual’s own cells) for example for the treatment of B cell malignancies. All of these treatments would take the form of non-invasive cell suspension treatments administered intravenously. The currently planned treatment modality of fully personalized medicine (i.e., using the patient’s own cells or those of a donor provided expressly by that patient) could, in some cases, eventually be supplanted by a more generic “off the shelf” modality offering which would be marketed as a pre-packaged suspension of cells and medium, taken and stored in advance for each cell “type” and then shipped to patients with the same “type” who have never met the donor. This delivery model is a longer term aspiration for us and is beyond the scope of our current market share projections.
 
Our Value Drivers
 
Our current positioning in the cell-therapy and cancer therapy value chain is typical of an early clinical stage company: developing, validating and attaining regulatory approvals for the various applications of our technology platforms. Going forward, once the products are commercialized, physician and patient interest in these treatments is expected to drive insurer reimbursement for patients - a key demand lever. The generic value chain for biotechnology development commences with an invention which is formulated, patented and successful in pre-clinical animal trials. We have already passed this stage with our core platforms (Veto Cell and Organsource) for which we have an exclusive license to use from Yeda, the owner of these patents. The next steps in development include human trials (first testing safety and then efficacy). Finally, the offering earns regulatory approval and patient treatment, along with the ensuing revenues, can commence. This can be a particularly lengthy process in the United States and therefore some medical treatments are approved in Europe or Asia and generate revenues there prior to commencing U.S. sales. Recently passed “fast track” regulation in the U.S. is aimed at getting critical treatments for life threatening conditions to patients more quickly.
 
Our successful preclinical validation of the Megadose Drug Combination treatment and the Veto Cell treatment involved basic laboratory research including both in-vivo (live) animal trials and in-vitro (in a glass dish) human cell trials. This validates the protocol prior to commencing human clinical trials. Human clinical trials fine-tune the treatment protocol and confirm both safety and efficacy in treating patents. In parallel, the patents on the core technology go into the national phase in various countries and are emended with claims associated with exact treatment protocols, bolstering the protection afforded by already issued patents on the base technology.

 
 
8

 

In some cases, successful biotech companies have been able to capitalize on positive human clinical results (even prior to full approval for patient treatment) by either signing lucrative non-dilutive distribution option deals or by being partially or fully acquired by larger market participants. There is no indication or assurance that we are currently under consideration for any option or acquisition deal.
 
We are poised to commence seeking approval for the Veto Cell based treatments.
 
We have had positive preclinical results for three of our cell therapy treatments and for our organ generation and regeneration treatments. Yeda, the proprietary owners of the patents underlying our technologies from whom we license our patents, has been granted patents for its original Veto Cell and for organ generation. The revised versions of the Veto Cell, additional organs for “Organsource,” and the combination of the Megadose treatment with a set of currently FDA approved drugs (as a combined treatment) are the subject of patent applications which have been granted in some jurisdictions and are pending in others. These newer patent applications leverage the priority of the already granted parents for organ generation, Veto Cell and Megadose, respectively. We plan to conduct human clinical trials. If these trials are successful, they will demonstrate both safety (the patients survived and were not harmed) and initial indications of efficacy (there are signs of successful engraftment, and in the case of cancer patients prolonging the progression free period).
 
Science and Technology Overview
 
The patent portfolio that we license from Yeda, includes a variety of cell therapy applications. Each platform already has been granted patents and has further patents pending. The total relevant patent portfolio consists of 15 patent “families” (i.e. grouping of similar patent applications in different territorial jurisdictions) which currently include, 24 granted patents, 5 allowed patents, and a further 78 pending patents. The patents for the Veto Cell and Megadose Drug Combination and T-regulatory cells are already licensed. On March 29, 2016, we recently exercised our option and now exclusively license the technology from Yeda related to the organ platform. We currently license all of the patents related to our Anti Third Party Veto Cell technology from Yeda. The key terms of the agreement pursuant to which we license all of Yeda’s patents related to our technology is set forth in the section entitled “Intellectual Property” herein. The license period (per product, per country) is for the full life of the patents, and expires at the later of the patent expiration date in that country or 15 years after the date that the FDA or local equivalent regulatory authority in each country approves that particular product for sale in that country. As long as Cell Source pays either a nominal license fee of $50,000 per year (total for use of all the products) or pays royalties on product sales on at least one product as per the license agreement, the license will remain in effect continuously and expire only with the expiration of the patent or 15 years after regulatory approval (later of the two) per product per country as described above. Cell Source voluntarily sponsors research at the Weizmann Institute for the sake of developing its products and treatments from initial invention through to finalization of human treatment protocols. Cell Source extended the initial research period, which originally terminated in October 2014, for an additional four years through October 2018.
 
Although Yeda has applied for and been granted various patents related to our technology, a granted patent only provides Yeda, and the Company by virtue of its exclusive license, the right to use the underlying invention. However, in order for our cell-therapy and cancer therapy to be legally sold and administered to patients, the FDA or similar regulatory agencies must approve its use. In other words, having a patent provides legal “freedom to operate” for a certain technology, and may provide the ability to prevent others from using the same technology without the patent holder’s permission. However, in order to legally manufacture and distribute products, a company must go through all of the typical approval steps delineated in the “Overview” section above.
 
The following sections provide an overview of each platform. Further information on the underlying science is available upon written request and the execution of an appropriate nondisclosure agreement.
 
Our primary focus is the Veto Cell platform. When we licensed the Veto Cell platform at our inception, we also were granted an exclusive option to license from Yeda the Organsource platform. On March 29, 2016, we recently exercised the option and now exclusively license this technology from Yeda.
 
Our licensed technology portfolio consists of 15 patent families, 24 granted patents 5 allowed patents and a further 78 pending patents. We recently exercised our option such that we exclusively license the patents for the organ regeneration platform.  The following table lists the patents and patent applications that Yeda holds and which we have a license to use in each of the below-referenced countries:
 

 
9

 

Name: VETO CELLS EFFECTIVE IN PREVENTING GRAFT REJECTION AND DEVOID OF GRAFT VERSUS HOST POTENTIAL
                     
Country
 
Patent Number
 
Filed
 
Expires
 
Status
 
Assignee
                     
USA (Basic)
 
6,544,506
 
05-Jan-2000
 
05-Jan-2020
 
Granted
 
Yeda Research and Development Co. Ltd.
                     
USA (National Phase)
 
7,270,810
 
28-Dec-2000
 
1-Dec-2021
 
Granted
 
Yeda Research and Development Co. Ltd.
                     
Europe
 
1244803
 
28-Dec-2000
 
28-Dec-2020
 
Granted
 
Yeda Research and Development Co. Ltd.
                     
Israel
 
150440
 
28-Dec-2000
 
28-Dec-2020
 
Granted
 
Yeda Research and Development Co. Ltd.
  
Name: USE OF ANTI THIRD PARTY CENTRAL MEMORY T CELLS FOR ANTI-LEUKEMIA/LYMPHOMA TREATMENT
 
Country
 
Patent Number
 
Filed
 
Expires
 
Status
 
Assignee
                     
USA
 
2013-0171108-A1
 
08-Sep-2011
 
08-Sep-2031
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Japan
 
2013-527738
 
08-Sep-2011
 
08-Sep-2031
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Canada
 
2,810,632
 
08-Sep-2011
 
08-Sep-2031
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
China
 
CN 103282047 A 9
 
08-Sep-2011
 
08-Sep-2031
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Republic of Korea
 
2013-7008892
 
08-Sep-2011
 
08-Sep-2031
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Israel
 
225102
 
08-Sep-2011
 
08-Sep-2031
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Brazil
 
BR 11 2013 005756 4
 
08-Sep-2011
 
08-Sep-2031
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Mexico
 
MX/a/2013/002668
 
08-Sep-2011
 
08-Sep-2031
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Singapore
 
188473
 
08-Sep-2011
 
08-Sep-2031
 
Granted
 
Yeda Research and Development Co. Ltd.
                     
Europe
 
26138013
 
08-Sep-2011
 
08-Sep-2031
 
Allowed
 
Yeda Research and Development Co. Ltd.
                     
Hong Kong
 
14100513.2
 
08-Sep-2011
 
08-Sep-2031
 
Pending
 
Yeda Research and Development Co. Ltd.
 
Name: ANTI THIRD PARTY CENTRAL MEMORY T CELLS, METHODS OF PRODUCING SAME AND USE OF SAME IN TRANSPLANTATION AND DISEASE TREATMENT
 
Country
 
Patent Number
 
Filed
 
Expires
 
Status
 
Assignee
                     
USA
 
2014-0212398-A1
 
06-Sep-2012
 
06-Sep-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Europe    2753351    06-Sep-2012    06-Sep-2032    Pending    Yeda Research and Development Co. Ltd. 
                     
Hong Kong
 
1200099A
 
06-Sep-2012
 
06-Sep-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Japan
 
2014-529143
 
06-Sep-2012
 
06-Sep-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Canada
 
2,848,121
 
06-Sep-2012
 
06-Sep-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
China
 
CN 103930130 A
 
06-Sep-2012
 
06-Sep-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Australia
 
2012305931
 
06-Sep-2012
 
06-Sep-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Republic of Korea
 
10-2014-7009267
 
06-Sep-2012
 
06-Sep-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
New Zealand
 
622749
 
06-Sep-2012
 
06-Sep-2032
 
Granted
 
Yeda Research and Development Co. Ltd.
                     
South Africa
 
2014/01993
 
06-Sep-2012
 
06-Sep-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
India
 
577/MUMNP/2014
 
06-Sep-2012
 
06-Sep-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Israel
 
231397
 
06-Sep-2012
 
06-Sep-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Russian Federation
 
2014110897
 
06-Sep-2012
 
06-Sep-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Brazil
 
BR 11 2014 005355 3
 
06-Sep-2012
 
06-Sep-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Mexico
 
MX/a/2014/002771
 
06-Sep-2012
 
06-Sep-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Singapore
 
11201400513P
 
06-Sep-2012
 
06-Sep-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
 

 
10

 
 
 
Name: ANTI THIRD PARTY CENTRAL MEMORY T CELLS, METHODS OF PRODUCING SAME AND USE OF SAME IN TRANSPLANTATION AND DISEASE TREATMENT
 
Country
 
Patent Number
 
Filed
 
Expires
 
Status
 
Assignee
                     
USA
 
2011-0212071-A1
 
29-Oct-2009
 
29-Oct-2029
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Europe
 
2365823
 
29-Oct-2009
 
29-Oct-2029
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Israel
 
212587
 
29-Oct-2009
 
29-Oct-2029
 
Allowed
 
Yeda Research and Development Co. Ltd.
                     
India
 
905/MUMNP/2011
 
29-Oct-2009
 
29-Oct-2029
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
China
 
ZL200980153053.4
 
29-Oct-2009
 
29-Oct-2029
 
Granted
 
Yeda Research and Development Co. Ltd.
                     
Russian Federation
 
2506311
 
29-Oct-2009
 
29-Oct-2029
 
Granted
 
Yeda Research and Development Co. Ltd.
 
Name: GENETICALLY MODIFIED ANTI-THIRD PARTY CENTRAL MEMORY T CELLS AND USE OF SAME IN IMMUNOTHERAPY
 
Country
 
Patent Number
 
Filed
 
Expires
 
Status
 
Assignee
                     
USA
 
62/193,207
 
16-Jul-2015
 
16-Jul-2035
 
Pending
 
Yeda Research and Development Co. Ltd.
 
USE OF ANTI THIRD PARTY CENTRAL MEMORY T CELLS
                     
Country
 
Patent Number
 
Filed
 
Expires
 
Status
 
Assignee
                     
USA
 
62/193,229
 
16-Jul-2015
 
16-Jul-2035
 
Pending
 
Yeda Research and Development Co. Ltd.
 
Name: UNIVERSAL DONOR-DERIVED TOLEROGENIC CELLS FOR INDUCING NON-SYNGENEIC TRANSPLANTATION TOLERANCE
 
Country
 
Patent Number
 
Filed
 
Expires
 
Status
 
Assignee
                     
US
 
8,916,147
 
21-Aug-2006
 
21-Aug-2026
 
Granted
 
Yeda Research and Development Co. Ltd.
                     
US (Divisional)
 
2015-0104471-A1
 
21-Aug-2006
 
21-Aug-2026
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Europe
 
1928479
 
21-Aug-2006
 
21-Aug-2026
 
Allowed
 
Yeda Research and Development Co. Ltd.
                     
Europe (Divisional)
 
2514315
 
21-Aug-2006
 
21-Aug-2026
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Israel
 
189688
 
21-Aug-2006
 
21-Aug-2026
 
Granted
 
Yeda Research and Development Co. Ltd.
 
Name: A COMBINATION THERAPY FOR A STABLE AND LONG TERM ENGRAFTMENT
                     
Country
 
Patent Number
 
Filed
 
Expires
 
Status
 
Assignee
                     
Singapore
 
11201403459X
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Mexico
 
MX/a/2014/007647
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Brazil
 
BR 11 2014 015960 2
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Russian Federation
 
2014128479
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Israel
 
233303
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
India
 
1468/MUMNP/2014
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
South Africa
 
2014/05071
 
20-Dec-2012
 
20-Dec-2032
 
Granted
 
Yeda Research and Development Co. Ltd.
                     
New Zealand
 
627272
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Republic of Korea
 
10-2014-7020449
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Australia
 
2012355990
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
China
 
CN 104470542 A
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Canada
 
2,859,953
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Japan
 
2014-548337
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Europe
 
2793914
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
 
 
 
11

 
 
 
USA
 
2014-0363437-A1
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Hong Kong
 
15103467.1
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
 
Name: A COMBINATION THERAPY FOR A STABLE AND LONG TERM ENGRAFTMENT USING SPECIFIC PROTOCOLS FOR T/B CELL DEPLETION
                     
Country
 
Patent Number
 
Filed
 
Expires
 
Status
 
Assignee
                     
Singapore
 
11201403456U
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Mexico
 
MX/a/2014/007648
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Brazil
 
BR 11 2014 015959 9
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Russian Federation
 
2014129632
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Israel
 
233302
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
India
 
1467/MUMNP/2014
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
South Africa
 
2014/05298
 
20-Dec-2012
 
20-Dec-2032
 
Granted
 
Yeda Research and Development Co. Ltd.
                     
New Zealand
 
627549
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Republic of Korea
 
10-2014-7020448
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Australia
 
2012355989
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
China
 
CN 104093314 A 4
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Canada
 
2,859,952
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Japan
 
2014-548336
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Europe
 
EP2797421
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
USA
 
2014-0369974-A1
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Hong Kong
 
15103468.0
 
20-Dec-2012
 
20-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
 
Name: METHODS OF TREATING DISEASE BY TRANSPLANTATION OF DEVELOPING ALLOGENEIC OR XENOGENEIC ORGANS OR TISSUES
                     
Country
 
Patent Number
 
Filed
 
Expires
 
Status
 
Assignee
                     
Mexico
 
319957
 
04-Mar-2004
 
04-Mar-2024
 
Granted
 
Yeda Research and Development Co. Ltd.
                     
Mexico (Divisional)
 
MX/a/2014/001950
 
04-Mar-2004
 
04-Mar-2024
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Europe
 
2216033
 
04-Mar-2004
 
04-Mar-2024
 
Granted
 
Yeda Research and Development Co. Ltd.
 
 Name: METHODS OF TREATING DISEASE BY TRANSPLANTATION OF ALLOGENEIC OR XENOGENEIC ORGANS OR TISSUES
                     
Country
 
Patent Number
 
Filed
 
Expires
 
Status
 
Assignee
                     
Europe
 
2402019
 
04-Mar-2004
 
04-Mar-2024
 
Granted
 
Yeda Research and Development Co. Ltd.
                     
Israel
 
170622
 
04-Mar-2004
 
04-Mar-2024
 
Granted
 
Yeda Research and Development Co. Ltd.
 
Name: THERAPEUTIC TRANSPLANTATION USING DEVELOPING, HUMAN OR PORCINE, RENAL OR HEPATIC, GRAFTS
 
Country
 
Patent Number
 
Filed
 
Expires
 
Status
 
Assignee
                     
USA
 
7,780,993
 
19-Jan-2005
 
23-Apr-2023
 
Granted
 
Yeda Research and Development Co. Ltd.
                     
USA (Divisional)
 
8,951,572
 
19-Jan-2005
 
19-Jan-2025
 
Granted
 
Yeda Research and Development Co. Ltd.
                     
USA (Divisional)
 
2015-0190546-A1
 
19-Jan-2005
 
19-Jan-2025
 
Pending
 
Yeda Research and Development Co. Ltd.

 
 
12

 


Name: DISEASE TREATMENT VIA DEVELOPING NON-SYNGENEIC GRAFT TRANSPLANTATION
 
Country
 
Patent Number
 
Filed
 
Expires
 
Status
 
Assignee
                     
USA
 
8,974,779
 
02-Oct-2005
 
02-Oct-2023
 
Granted
 
Yeda Research and Development Co. Ltd.
                     
USA (Divisional)
 
2015-0174294-A1
 
02-Oct-2005
 
02-Oct-2023
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Europe
 
1809734
 
02-Oct-2005
 
02-Oct-2025
 
Granted
 
Yeda Research and Development Co. Ltd.
                     
Europe (Divisional)
 
2453008
 
02-Oct-2005
 
02-Oct-2025
 
Granted
 
Yeda Research and Development Co. Ltd.
                     
Hong Kong (Divisional)
 
HK1170534
 
02-Oct-2005
 
02-Oct-2025
 
Granted
 
Yeda Research and Development Co. Ltd.
                     
Israel
 
182363
 
02-Oct-2005
 
02-Oct-2025
 
Granted
 
Yeda Research and Development Co. Ltd.
 
Name: MAMMALIAN FETAL PULMONARY CELLS AND THERAPEUTIC USE OF SAME
                     
Country
 
Patent Number
 
Filed
 
Expires
 
Status
 
Assignee
                     
USA
 
HK1170534
 
06-Dec-2012
 
06-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Europe
 
2788009
 
06-Dec-2012
 
06-Dec-2032
 
Allowed
 
Yeda Research and Development Co. Ltd.
                     
Japan
 
2014-545442
 
06-Dec-2012
 
06-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Canada
 
2,857,930
 
06-Dec-2012
 
06-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
China
 
CN 104105493 A
 
06-Dec-2012
 
06-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Australia
 
2012348574
 
06-Dec-2012
 
06-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Republic of Korea
 
10-2014-7018702
 
06-Dec-2012
 
06-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
New Zealand
 
627071
 
06-Dec-2012
 
06-Dec-2032
 
Allowed
 
Yeda Research and Development Co. Ltd.
                     
South Africa
 
02014/04958
 
06-Dec-2012
 
06-Dec-2032
 
Granted
 
Yeda Research and Development Co. Ltd.
                     
India
 
1366/MUMNP/2014
 
06-Dec-2012
 
06-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Israel
 
233022
 
06-Dec-2012
 
06-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Russian Federation
 
2014127338
 
06-Dec-2012
 
06-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Brazil
 
BR 11 2014 014033 2
 
06-Dec-2012
 
06-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Mexico
 
MX/a/2014/006756
 
06-Dec-2012
 
06-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Singapore
 
11201402902V
 
06-Dec-2012
 
06-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Philippines
 
1- 2014-501309
 
06-Dec-2012
 
06-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
                     
Hong Kong
 
15103466.2
 
06-Dec-2012
 
06-Dec-2032
 
Pending
 
Yeda Research and Development Co. Ltd.
 
 
 
13

 

Platform I - Veto Cell
 
Background
 
Our Veto Cell technology is a next generation cell therapy technology that enables the selective attenuation of the immune system. In other words, pre-clinical studies suggest that the treatment has the ability to reduce the immune response to selective “threats,” with low risk for adverse side effects.
 
What makes the Veto Cell approach distinctive is the degree to which it leverages the inherent specificity of the human immune system. The immune system defends the body by creating a specific stream of T-cell clones for each of millions of individual threats. A given T-cell will attack only its specific target, ignoring all other threats. Our technology might enable the physician to selectively attenuate immune response, thus effectively “switching-off” an individual stream of T-cell clones without affecting any other such streams of T-cell clones dispatched by the immune system to attack unwanted incursions.
 
The technology is based on the discovery that certain T-cells have the property of attracting and proactively neutralizing immune attacks on them.
 
The technology has achieved distinctive results in animal live trial models. See, e.g., Thorsten Zenz, Exhausting T cells in CLL, BLOOD, Feb. 28, 2013, at 1485. If it succeeds in human clinical trials, we believe that it may have meaningful and potentially broad impact on the field of bone marrow transplantation:
 
 
1.
Significantly improve outcomes of transplantations by reducing host rejection rate of T-cell depleted bone marrow, markedly reducing both the risk of GVHD and the need for using aggressive amounts of immunosuppression medications. This would significantly reduce the bone marrow transplant mortality rate (currently 50%) and therefore lead to broader use of this treatment.
 
2.
Substantively increase the number of transplantations by enabling lower myeloablative conditioning and therefore making the therapy accessible to older and sicker patients (who today may not survive ablation).
 
3.
Further increase the number of transplantations by making transplantation appropriate for other indications (for which today transplantation would be considered an inappropriately risky treatment).
 
In addition, our Veto Cell technology may possibly play a role in the treatment of a number of serious and currently poorly treated non-malignant diseases. Furthermore, initial animal trials have shown potential anti-lymphoma activity.  Finally, based on preclinical studies with using genetically modified cells, we believe that Veto Cells will be able to act as critical enabler for other cell therapies being developed by third parties, most notably CAR-T cell therapy, which has recently shown strong initial indications of being effective in cancer treatment.
 
Mechanism
 
Our Veto Cell is a CD8 central memory anti-3rd party T-cell that has five critical properties:
 
 
1.
It has an outer surface coating that triggers attack by specific host T-cells (and only those specific T-cells).
 
2.
It can annihilate an attacking T-cell without itself being damaged (specifically, it exposes or releases a death-signaling molecule when an attacking T-cell binds to it).
 
3.
It has been oriented to attack cells of a simulated third party (i.e., neither host nor donor) and thus exhibits markedly reduced risk of GVHD or graft rejection.
 
4.
It is long-lived and endures in the body for extended periods.
 
5.
It migrates to the thymus and lymph nodes.
 
The outcome is that when a large number of these cells are introduced into the body, they effectively eliminate the T-cell clones that the immune system dispatches to attack the desirable, transplanted bone marrow cells.
 
Thus, for example, if a population of Veto CellVeto Cells is derived from a donor, they will express the same peptide as do the donor’s cells. Therefore, the specific stream of host T-cells that would ordinarily attack the donor stem-cells, are instead directed to “decoy” Veto CellVeto Cells and disabled before they reach the transplantation.

Described in a Blood editorial as a “substantial advance in Cell Therapy," a notable characteristic of our Veto Cell is that this mechanism is quite specific. Only those specific T-cell clones that were generated to attack cells from this specific donor are disabled. The rest of the immune system essentially remains intact.
 
This is in marked contrast with conventional immunosuppression which degrades the entire immune system and is therefore associated with severe risk of infection and, in the case of bone marrow transplantations, high mortality.

 
 
14

 

This effect is long-lived. Firstly, the Veto CellVeto Cells themselves are long-lived memory cells. Secondly, when infused with bone marrow cells the latter migrate to the thymus where, over time, they create a new “identity” in the host and initiate “chimerism,” where the host and donor cells peacefully co-exist. This chimerism has the effect of "educating" new T-cells being generated by the thymus to tolerate donor cells. This tolerance can become permanent.  Furthermore, by inducing permanent tolerance to donor cells, Veto Cells may be able to enable both acceptance (i.e. mitigate both host rejection and GvH rejection) and thus persistence (i.e. extended survival resulting in enhanced efficacy) of important cell therapy treatments such as CAR-T cells, TCRs and NK cells in treating both blood cell and solid tumor cancers.
 
Target Indications
 
Our Veto Cell technology, an intravenously administered cell suspension, if successful, could initially be used in bone marrow and other transplantations associated with malignant disorders (i.e., cancers). At a later stage, Veto Cell technology may be applied to selected non-malignant conditions. The following sections provide a brief overview of the use of the Veto Cell technology in both of these scenarios.
 
i. Bone Marrow Transplantation

In order to describe the effect of Veto CellVeto Cells in transplantation, it is helpful to first briefly review the state of the art:
 
In a conventional bone marrow transplant, the recipient first receives myeloablative conditioning - powerful chemotherapy and/or radiation therapy intended to destroy his/her own bone marrow cells. This has a threefold purpose:
 
 
1.
It destroys the host T-cells so they will not attack (reject) the donor bone marrow cells.
 
2.
It makes space in the host bone marrow for the new donor cells.
 
3.
It destroys diseased host blood cells so that they do not proliferate and cause relapse following the procedure.
 
In practice however, there are two major problems:
 
·  
Host rejection - the myeloablative conditioning does not destroy all of the host T-cells. Those that remain may aggressively attack the donor bone marrow cells before they can engraft.
·  
“Graft versus Host Disease” (GVHD) -the transplanted cells include donor T-cells which recognize the host's body as foreign and attack it.
 
Both rejection and GVHD are potentially life-threatening complications in and of themselves and also lead to the use of dangerous and costly immunosuppression medications. The Megadose technology addresses the foregoing two problems by introducing an extremely large population of selected donor cells into the host. This overwhelms the remaining host immune system, and therefore, reduces the risk of rejection. It also reduces the risk of GVHD, as the donor cells are selected so as to minimize the number of accompanying T-cells.
 
Megadose is a well-developed technology and is now used in clinical treatments where a “mismatched” bone marrow blood cancer transplantation is in order.
 
ii. Veto Cell in Transplantation
 
The Veto Cell technology is a next generation of the Megadose concept. In a transplantation scenario, a population of donor Veto Cells is created to "escort" the bone marrow cells when they are transplanted. This population is created by identifying donor cells with Veto Cell properties, exposing them to simulated 3rd party cells (i.e., selecting only those that react to a third person and therefore by definition will not react to either host or donor), and expanding their population in the lab.

 
 
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The Veto Cells are then introduced into the host along with the transplanted stem cells. The host mounts its normal immune response to the donor cells by generating a population of T-cell clones that will bind to any cells expressing markers from this specific donor. In a conventional transplantation, these T-cells would bind to and destroy donor stem-cells thus causing rejection of the transplant.
 
However, when the transplantation is accompanied by large numbers of Veto Cells, this rejection mechanism is “ambushed." Since the Veto Cells express the same donor markers as the stem-cells, the host T-cell clones will attempt to bind to the donor-derived Veto Cells as noted above, which act as decoys by attracting and then counterattacking and killing the clones before they ever reach the bone barrow transplantation.
 
iii. Direct Anti-Cancer Effect
 
A further effect of Veto Cells has been noted in mouse and in-vitro studies: donor Veto Cells selectively attack host lymphoma malignant cells. This effect has been robust in animals, in fact completely eradicating lymphoma in mouse models (see Development Status section below).
 
The direct anti-cancer effect has been documented for several human B cell malignant lines, however, preliminary experiments with human anti-3rd party veto cells prepared in a slightly different protocol than that used for the mouse studies, indicate that further optimization and verification are required before killing fresh human B-CLL or myeloma tumor cells could become a feasible option.
 
If this effect transfers to human patients, it may have significant therapeutic value for the above disorders, which as noted hereafter in the Marketing Strategy section, are among the largest blood cancer markets.

iv. Enabling Third Party Cell Therapies

Based on preclinical studies using genetically modified cells, in July of 2015 Yeda filed two U.S. provisional patent applications, which are also licensed exclusively by Cell Source on a worldwide basis.  These patent applications show the ability of Veto Cells to enhance the performance of cell therapy treatments involving genetically modified receptors.  When combined with CAR-T or TCR cell therapy for example, these would potentially greatly enhance the ability of these treatments to be used in an allogeneic or “off-the-shelf” setting, and also increase their efficacy by avoiding both rejection and GvHD, thus increasing their persistence (survival in the patient’s body). This combined Veto Cell + CAR-T or similar treatment could result in broadly applicable effective treatments for many of the most prevalent solid tumor cancers and well as blood cell cancers. 

v. In Non-Malignant Diseases
 
As discussed above, there are two major categories of non-malignant disorders that the Veto Cell technology aspires to address: non-malignant hematological disorders and organ transplantations.
 
In the case of organ transplantations and congenital non-malignant hematological disorders, the goal of the Veto CellVeto Cells is to enable transplantation (bone marrow or organ) by reducing host/donor immune system conflicts.  This could potentially allow for mismatched (partial vs. full identity match between donor and host) kidney transplants, for example, and also obviate the need for lifelong daily anti-rejection medication which is the current standard of care. Such an outcome could improve quality of life, reduce cost of care and significantly increase life expectancy for a broader audience of prospective transplant recipients.
 
In the case of congenital non-malignant diseases such as sickle cell anemia, the body’s bone marrow produces “flawed” cells. An effective treatment is HSCT which replaces the flawed host bone marrow with healthy donor cells. These cells then produce healthy blood cells, basically curing the anemia. As noted elsewhere however, today HSCT is a risky procedure because of the graft/host immune conflicts. It is therefore used infrequently to treat sickle cell disease. The Veto Cell tolerizing technology would increase the target population for this treatment by significantly reducing these conflicts and by extension the procedure’s risk. Likewise, if permanent tolerance to donor hematopoietic cells is induced under safe conditions, the new immune status could permit acceptance of a kidney from the same donor, without further requirement for a toxic immune suppression currently used in organ transplantation. This means that patients who today are required to take expensive and sometimes debilitating anti-rejection medication daily for the rest of their lives would no longer have to do so.
 
Development Status
 
The Veto Cell platform has been extensively tested by in vitro studies (on both human and mouse disease) and confirmed in animal trials. The results appear to be consistently effective.
 

 
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1. Including chimerism:
 
The following images show some example data from the Veto Cell animal studies. Skin of black mice has been grafted onto the backs of white mice. The data show that T-cells from host and donor mice are fully coexisting in the treatment group using the Veto Cells (“chimerism”).


 
2. Success bone marrow transplantation under reduced levels of immune suppression:
 
The anti-rejection effect in the data below shows mice with lymphoma treated with Veto Cell therapy.
 
The control group mice (left side) all die by day 27. By contrast, the Veto Cell treatment group (right side) show far better results.
 

 
17

 
 
 
Administration
 
We envision that Veto Cell therapy will be administered in an in-patient setting, typically as part of the existing preparation procedures for bone marrow transplantations. Blood will be taken from the donor. The frozen blood will be sent to a regional Company center where the Veto Cells will be developed and expanded - a process that lasts up to two weeks. The Veto Cells will then be sent to the transplantation center where they will be infused to the patient intravenously along with the transplantation.
 
Patent Status
 
The first generation Veto Cell is protected by granted patents in the US and Europe.  The second generation Veto Cell has granted patents in China and the Russian Federation. There are currently multiple additional pending patents in various countries.
 
Development Roadmap
 
The Veto Cell platform roadmap comprises two main programs as outlined in the table below. The specific clinical trials planned for each are detailed in the Clinical Trials section of this document. 
 
 
 
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Offering
 
Objective
 
Major Activities
   
Estimated start date
Anti-rejection Veto Cell
 
Validate and introduce new commercial treatment to increase engraftment of allogeneic bone marrow transplantations
 
1.    Regulatory approval and treatment protocols
2.    Conduct human clinical trials
3.    Develop plan for commercial exploitation
 
Commence a formal company-sponsored Phase I/II clinical trial by 2017
Interim analysis within 18 months thereafter
 
               
Veto – CAR-T Cell Therapy
 
Validate the possibility of combining Veto Cell treatment with CAR-T cell treatment for both blood cell cancer and solid tumor cancer treatment
 
4.    Engender partnership with Car-T cell provider
5.    Validate combined treatment model in preclinical trials
6.    Develop joint production and treatment protocol
 
Discussions with prospective partners underway
If preclinical studies are successful , human trials would be the next step
 
Platform II - Organsource
 
Overview
 
Organsource is Yeda's patented technology, as referenced above. Yeda has been granted patents in the United States and Europe. Organsource addresses the growing shortage of organs for human transplantation. A second approach using embryonic cells in a single cell suspension to reconstitute healthy tissue in existing organs has an allowed patent in Europe. On March 29, 2016, Cell Source exercised its option and now exclusively licenses this technology from Yeda.
 
The key discovery has potential uses:
 
·  
Embryonic tissue (taken from an animal or human fetus during gestation), which can be identified as organ precursors that will grow into specific organs (e.g., kidney, liver, pancreas), can be harvested at a very specific moment in the gestation period where they have just then become “committed” organ precursors and thus have not yet begun to generate the acute levels of rejection otherwise typical for xenotransplant (i.e., between species) which have been problematic in other earlier studies transplanting porcine tissue into humans.  These pre-organs can be successfully transplanted into a host, even of another species, and grow into functional organs in the host with only the level of organ rejection associated with an allogeneic organ donor, which can currently be managed through medication. Incidentally, this post transplantation rejection could potentially be further reduced by using Veto Cells.
·  
Veto Cell Individual cells (taken from either human or animal embryos or possibly adult human donors) can be infused in a single-cell suspension and in a patient with a diseased organ (e.g. lung) and used to regeneration healthy lung tissue to correct non-malignant organ diseases.
 
This means that porcine embryonic tissue can potentially become a source for human organ replacement. Also, human or animal cell could potentially be used to treat diseases such as emphysema by growing healthy tissue in an existing lung.
 
Background
 
The main focus of the Organsource work to in the early years of the research was demonstrating that organ precursor tissue can be successfully transplanted into both rodents and primates from pigs.
 
Pigs have long been considered the ideal source of organs for human transplantation for two reasons:
 
·  
Their organs are similarly sized to humans, and
·  
They have large litters so can provide extensive supply (unlike for example monkeys).
 
However, others’ previous experimental efforts to transplant porcine organs into primates have shown only limited success because a certain marker on pig blood vessels causes a hyper-immune response in primates (which, for example, have immediately killed organ recipients in trials with monkeys).
 

 
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Mechanism
 
The embryonic tissue technology avoids the hyper rejection problem by extracting embryonic pig tissue in a highly specific development window. Cells within this momentary window can grow inside the host using blood vessels of the host, not donor, origin. Therefore, they do not trigger the host hyper-immune response. However these embryonic organ precursors have developed sufficient organ differentiation to act as pre-organs in the host, and they grow into functional developed organs, in the case of primates, within a few months.
 
Specifically, a mouse with Type 1 diabetes received a transplanted porcine pre-pancreas, which grew into a full sized pancreatic organ largely composed of beta cells which secrete insulin, thus effectively treating diabetes in the mouse. Similar results have also been achieved in monkeys.

The single-cell suspension technology uses niches in the organ (similar to a bone marrow transplant) to grow new, healthy tissue thus restoring organ capacity. In mice, this has shown the ability to reconstitute bronchioles in damaged mouse lungs using human embryonic cells and demonstrating successful engraftment and functionality in the new tissue. 

Target Indications
 
Embryonic tissue could theoretically provide a significant new source of transplantation organs for major human organ needs.  ork so far indicates positive results for growing a pancreas to replace one in which beta cells have been chemically disabled leading to a disease similar to that found in Type 1 Diabetes.

The single cell suspension approach could be used to correct major diseases in the lung, liver or pancreas by reconstituting healthy tissue to replace diseased tissue, thus effectively reversing damage caused by the disease.
 
Development Status
 
Organsource is at an early stage of development relative to the Veto Cell platform. However, in-vitro results and animal trials have shown positive progress. For example:
 
·  
Porcine spleen tissue was successfully implanted into a mouse, effectively treating hemophilia.
·  
Embryonic lung cells have shown effectiveness in repairing injured mouse lungs and are currently being tested on cystic-fibrosis mice. In principal, these could potentially be used to effectively treat several major lung diseases.
·  
Porcine pancreatic cells were successfully infused into monkeys where they effectively corrected chemically induced diabetes. The chart below shows exogenous insulin requirements of the subject animal (vertical axis) as a function of the number of days following the transplantation (horizontal axis).
 
Note that within days of the transplantation, the insulin requirements drop sharply, indicating that the porcine cells are now producing insulin in the monkey, and 10 months after transplantation the monkey is diabetes free. Considering that in these experiments the recipient body weight is small, and a large dose of tissue was used for transplantation, it could be argued that our approach might not be feasible for treating large human adults. In other words, the number of porcine pancreases required for the dosage for treating a large human being may prove to be prohibitive.
 


 
 
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Administration
 
Administration of Organsource is may be less invasive than a typical organ transplantation procedure. In the case of smaller organs such as the pancreas, Organsource transplantation requires only a relatively minor procedure. This is because precursor cells rather than full grown organs are being introduced.
 
Since the embryonic implants can promptly attract blood vessels they therefore can be placed in sites in the body nearer to the surface of the skin instead of deeper internal sites such as the pancreatic cavity.

For the single cell suspension, administration can be entirely intra-venous.
 
Patent status
 
For the tissue replacement technology, patents have been granted in the US, Europe, Mexico, Hong Kong and Israel. For the single cell suspension for organ reconstitution, patents have been granted in South Africa and allowed in Europe and New Zealand, with applications pending in the US and multiple territorial jurisdictions.
 
Development Roadmap
 
Our Organsource roadmap is to continue development of the lung regeneration technology, then expand to pancreas and liver. In parallel Cell Source aspires to partner with a larger player to develop the embryonic tissue based organ replacement technology.
 
Products and Services
 
Currently, we do not have any products, and there is no assurance that we will be able to develop any products.
 
The following products are currently planned:
 
1. “Anti-rejection” Veto Cell tolerance therapy for both matched and mismatched allogeneic bone marrow transplantations.

This is our flagship (as an initial platform for increasing transplantation success) and is focused on allogeneic bone marrow transplantations.
 
Treatment will comprise a course of infusions of Veto Cells derived from the donor and processed in a Company (or subcontracted) facility that will be accessible to the transplantation center at the time of transplantation.
 
2. “Anti-cancer” Veto + CAR-T cell therapy for blood cell and solid tumor cancers.

This therapy is expected to comprise a course of infusions of donor derived cells that is expected to be combined with CAR-T cell therapy provided by a third party.

3. “Anti-rejection” Veto Cell tolerance therapy for both matched and mismatched organ transplantation.

This treatment would be combined with bone marrow transplantation in order to broaden the prospective donor pool and mitigate the need for chronic post-transplant anti-rejection therapy

4. Veto Cell tolerance therapy for non-malignant disorders.

This is the application of Veto Cell technology to treatment of non-malignant (i.e., non-cancerous) diseases. As discussed in the Technology section, a custom treatment would be developed for each selected disorder. 

Target indications for Veto Cell therapy for nonmalignant disorders are likely to be: tolerizing therapy for allogeneic transplantations for sickle cell anemia and aplastic anemia (by using bone marrow transplantations as referenced in no. 2 above) and tolerizing therapy for conventional organ transplantations.

5. Organ regeneration therapy to address major organ diseases.

This could be used for replacing a diseased pancreas to treat diabetes or repairing a damaged lung to treat emphysema, for example. 
 
The treatment would involve surgery for organ replacement or an intra-venous drip for organ reconstitution.

 
 
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Our Overall Development Status and Future Development Program
 
Prior to commercializing its products, the Company must conduct human clinical trials and obtain FDA approval and/or approvals from comparable foreign regulatory authorities.
 
Generally speaking, as a preclinical biotechnology firm, Cell Source needs to go through several necessary steps in order to commercialize its products and commence revenue generation. These steps are per product, but can run in parallel for multiple products, which are each in different stages of the development “pipeline”, so that, for example, when a certain product is already in a human clinical trial, another product may still be in preclinical development and a third may be awaiting regulatory approval to commence human trials. These can also take place in parallel, and varied stages, for the same product in different geographic jurisdictions. The typical steps per product (and range of time frame for each) are:
 
 
1.
Complete development of human treatment protocol (2-5 years)
 
2.
Apply for and receive approval to commence human trials (9-18 months)
 
3.
Recruit patients (1-6 months)
 
4.
Conduct Phase I trials showing safety of product (1-2 years)
 
5.
Apply for and receive approval to conduct trials showing product efficacy (6-12 months)
 
6.
Data collecting and analysis (6-12 months)
 
7.
Conduct Phase II efficacy trials (2-3 years)
 
8.
Data collecting and analysis (6-12 months)
 
9.
Apply for and receive approval to conduct trials showing efficacy in larger numbers of patients (6-12 months)
 
10.
Conduct Phase III efficacy trials with larger numbers of patients (2-4 years)
 
11.
Data collecting and analysis (6-12 months)
 
12.
Apply for and receive approval for production scale manufacturing facilities (6-12 months)
 
13.
Contract third party or establish own production facilities (6-30 months)
 
14.
Contract third party or establish own distribution platform (6-18 months)
 
15.
Commence manufacturing and distribution (6-12 months)
 
Notably, steps 12-15 can be conducted in parallel with some of the steps above. In the case of Cell Source and other firms that treat terminal patients with either rare diseases or those for which there is currently no effective treatment, or where preclinical studies indicate a reasonable expectation to increase life expectancy and survival rates by a substantive margin, several of these steps can be combined and or shortened, subject to regulatory discretion. For example, Phase I and II (safety and efficacy) can be combined in a single concurrent step; approvals for subsequent steps can be accelerated; in some countries patients can already be treated commercially after the end of Phase II, foregoing the requirement for Phase III data.
 
The specific detailed next steps the company must take to get the treatments or products to market include the following:
 
In the case of the Megadose Drug Combination, the Hematology and Bone Marrow Transplantation Unit of the University of Parma in Italy on May 14, 2014 requested and on October 23, 2014 obtained approval from the Italian Medicine Association (the Italian equivalent of the U.S. FDA) to conduct human clinical trials using the “Megadose + Drug Combination.” While we are not mentioned in the application nor in the approval, we may indirectly benefit from the outcome of the trial, if successful, although we are not the sponsor of this trial. There are no written or verbal agreements between the hospital and Cell Source regarding the use of the technology. That said, Cell Source is aware and in favor of the hospital plans to use the technology and would of course find a positive initial outcome encouraging. Since the treatment is being done on compassionate grounds as a non-commercial clinical trial, there is no legal requirement for the hospital to obtain approval to use the treatment protocol. The hospital has successfully treated a cancer patient using the Megadose Drug Combination technology that Cell Source exclusively licenses from Yeda Research & Development Ltd., commercial arm of the Weizmann Institute of Science.  While Cell Source is not a sponsor of the trial, the results provide a positive initial indication with respect to the technology. The patient received a bone marrow transplantation from a haploidentical or “mismatched” donor under a reduced intensity conditioning regimen (i.e., a relatively low level of immune suppression treatment). There was successful initial engraftment of the transplantation in the absence of GVHD. Cell Source plans to file an IND for the Veto Cell treatment in 2016.  To date, we have not submitted any drug applications to the FDA and do not have anything pending for approval with the FDA. Cell Source itself has not had any contact with any regulator anywhere regarding treatment approvals or clinical trials associated with regulatory approvals. We are aware that the aforementioned hospital in Italy has independently requested approval to conduct a trial with the same protocol that we plan to use, but we are not mentioned in the application, nor in the approval. However, we may indirectly benefit from the outcome of the trial, if successful, although we are not the sponsor of this trial. There are no written or verbal agreements between the hospital and Cell Source regarding the use of the technology. That said, Cell Source is aware and in favor of the hospital plans to use the technology and would find a positive initial outcome encouraging. Since the treatment is being done on compassionate grounds as a non-commercial clinical trial, there is no legal requirement for the hospital to obtain approval to use the treatment protocol.
 
 
 
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For the Veto Cell application for reducing rejection in Bone Marrow Transplants, Cell Source expects to commence a Phase I/II human clinical study in Italy, and subsequently in Germany, starting sometime in 2017.  Cell Source anticipates that Phase I/II studies will last until 2019 or 2020. These would be followed by completion of Phase II and Phase III, which would last another 2-3 years each, so that full approval, if successful, would be expected sometime in 2025. In Germany there is a possibility of approval for commercial use on a “compassionate grounds” basis at the end of Phase II, which could take place by 2023. In the US, Cell Source plans to commence the IND approval process with the FDA in 2016, which could last until between 2021 and 2024. Cell Source also aspires to enter into a collaboration with respect to combining CAR-T cell therapy with Veto Cell therapy and commence pre-clinical proof of concept trials in 2016. If successful, this could lead to a commencement of a combined FDA trial in 2017 or 2018 and could last until 2025 or 2026.

It is possible that Cell Source treatments could qualify for any or all of Fast Track, Breakthrough Therapy, Accelerated Approval and Priority Review designation under the FDA, which would hasten their approval if successful.

The costs for each step of development, in terms of clinical trials, are delineated below:
 
Cell Source estimates the cost of clinical trials alone to be up to $5 million over the coming two years and another $25-50 million in order to reach commercialization for both the Veto Cell and Organsource products. This would mean that Cell Source will need to secure one or more significant capital infusions in order to reach the point that meaningful revenues could be generated.
 
The following table summarizes the development plan for the coming few years:

 
Competition
 
The development and commercialization of new cell therapies is highly competitive. Our products are focused on treatment of blood cancers, non-malignant blood disorders and organ transplantations. Various products are currently marketed for the treatment of blood cancers. A number of companies are also developing new treatments. In addition to competition from a variety of other nascent unconventional medical treatments, we also face competition from established pharmaceutical and biotechnology companies, as well as from academic institutions, government agencies and private and public research institutions worldwide. For instance, our competitors include the technology developed by Micromet, Inc., which was since acquired by Amgen Inc. and the Chimeric Antigen Receptor (CAR) technology currently being developed by Kite Pharma, Inc. in collaboration with Amgen, Inc. and by Novartis, JUNO and others.
 
Many of our competitors have significantly greater financial resources and expertise in research and development, manufacturing, pre-clinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do. Earlier stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. While our commercial opportunities may be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer side effects or are less expensive than our own products, we believe that if our human trials show efficacy at the same levels of our animal trials, we would have the potential to develop at least a niche market share.
 
 
 
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We expect that our ability to compete effectively will depend upon our capacity to:
 
·  
successfully and complete adequate and well-controlled clinical trials that demonstrate statistically significant safety and efficacy and to obtain all requisite regulatory approvals in a timely and cost-effective manner;
·  
effectively use patents and possibly exclusive partnership agreements with important third party treatment providers and collaborations partners  to maintain a stable competitive stance for our Technology;
·  
attract and retain appropriate clinical and commercial personnel and service providers; and
·  
establish adequate distribution relationships for our products.
 
Failure in efficiently developing and executing these capabilities may have an adverse effect on our business, financial condition or results of operations.
 
Strategy Overview
 
Our strategy is based on two underlying drivers: (a) that animal studies show Veto Cell technology to be consistently effective; and (b) that the lead indications (certain blood cancers) are relatively common, have high mortality and have limited treatment options today.
 
Based on the foregoing drivers, we have developed a business plan with the objective of obtaining regulatory approvals and subsequently launching product sales with a focus on the United States, Europe and Asia.
 
 Key Strategy Elements
 
We are pursuing a staged entry strategy. The first several years will be narrowly focused, both in terms of market segments (Blood cancer either directly or through bone marrow transplantation) and products (Veto Cell platform for BMT and direct cancer treatment).
 
Subsequently, we plan to broaden the segmentation strategy to include additional bone marrow transplantation indications, major organ transplants combined with BMT, selected genetic non-malignant diseases and, in partnership with one or more CAR-T cell provider, solid tumor cancers. The product strategy can also be broadened to include Veto the Organsource platform.
 
Our strategy can be summarized as follows:
 
Strategy Element
   
Introductory period
(years 1 -3 post FDA approval)
   
Years 4+
             
Market Segments
 
Lymphoma and Leukemia
Solid tumors e.g. breast cancer.
 
Same as before plus broader set of solid tumor targets, diabetes, emphysema and other major non-malignant organ disease; sickle cell anemia
             
Product Rollout
 
Veto Cell therapy for B-cell malignancies
Veto+CAR-T Veto Cell therapy for both blood cell and solid tumor cancers
 
Veto Cell tolerizing treatment for BMT and organ transplantation
Veto Cell therapy for cancer and non-malignant disorders; organsource for major organ regeneration   
             
Customer/ Geographic Focus
 
North America
Western Europe
China
 
North America, Western & Eastern Europe, Australia/New Zealand, Russia, Brazil, selected Asian markets
             
Channels/Go to Market
 
Direct relationships with leading transplantation centers
International production and distribution through partners
 
Partnership with global market leaders
 
             
Pricing
 
Consistent with other cell therapy offerings currently associated with transplantations and immuno-oncology
 
Potentially higher volume, lower cost for “off the shelf” offerings
 
 
 
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Operations
 
 
 
 
Three production centers:
    - US
    - Western Europe
    - Far East
Initial capacity leased from major transplantation centers.
 
Regional production centers owned or JV with partners
 
 
Segment Selection
 
Within the general market for immune therapies, we have selected target market segments (i.e., medical conditions) for initial focus based on two (2) key criteria:
 
 
1.
Severity of unmet medical need: degree of severity of the indication and the effectiveness of existing treatments. These criteria help determine the proper regulatory pathway.
 
2.
Technology relevance: relative value of the ability to manage immune response to the treatment of a given indication.
 
We will initially focus on indications that score highly with respect to both criteria (e.g., Multiple Myeloma). These conditions may qualify for Fast Track status with the FDA, and, due to the cost of current treatment alternatives, could potentially support profitable price points for effective new treatments.
 
Product Rollout
 
Cell Source plans to seek approval initially in Europe (Italy and Germany) and the US, and, in parallel but with a delayed start, in and China and possibly Taiwan. A successful parallel Phase I/II trial in the US and Europe, which could be concluded by 2019, would serve as a strong foundation for trials in other countries. Limited sales on a “compassionate grounds” basis may commence as early as 2020 in Europe and Asia, and, depending on qualification for Breakthrough Therapy or other Accelerated Approval designation, may be available in the U.S. by 2022. Full approval by the FDA in the U.S. can take as long as 8 years, or 2025.
 
Future products may include Veto Cell tolerance inducement therapy for allogeneic bone marrow transplantations and Veto + CAR-T cell therapy for lymphoma, leukemia and solid tumor cancers.
 
Following the initial market penetration and establishment of solid market positioning, we plan to broaden the product offering to address a wider variety of indications which may include custom Veto Cell developments for specific collaborations with other cell therapy treatments and continued work on Organsource. For example, we believe that one area in which we could broaden our product offerings is to utilize our Veto Cell technology, if successful in humans, to address the rejection problems being faced by companies developing CAR-T, TCR and similar cell therapy products, as an enabler for these treatments to help them overcome some of the rejection and persistence related performance issues their technology currently seems to be facing. If our Veto Cell technology proves to be successful in humans, we plan to continue to explore such potential applications in the future.
 
Customer/Geographic Focus
 
Assuming positive clinical trials, we will initially focus our sales efforts of Veto Cell anti-rejection therapy on centers dealing with late stage B-cell malignancies High profile, high volume HSCT facilities can be targeted to market this treatment.
 
Current plans are to introduce the products first in North America and Western Europe, and, perhaps concurrently, in China. Focusing on key transplantation facilities in target geographic markets will allow us to both refine the administration of our products and bolster our reputation in respective markets.
 
After the introductory period, we plan to expand its activities in its initial markets while simultaneously broadening geographic coverage. In Stage 2, we plan to initiate active marketing efforts in the remaining Western European countries, Japan, Australia, Eastern Europe, Russia and Brazil.
 
Marketing Strategy
 
The initial target market is concentrated and networked. It comprises the approximately 40 leading transplantation centers in the target geographies. As discussed in the “Market Access” and “Channels” section, these centers are well connected to each other and tend to quickly share innovations and best practices.
 

 
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The planned penetration strategy is to introduce Veto Cell into the best-known and most influential centers in North America and Western Europe, and benefit from the exposure and industry leadership provided by these centers.
 
This initial penetration strategy includes incorporating these centers into the clinical trials so as to expose and involve their medical leadership.
 
In the longer term, we plan to drive use and awareness within and across the broader oncology community in order to encourage oncologists to refer their patients to centers that already use our products and therapies and to encourage pull-influence on additional centers to adopt our products and therapies.
 
The broader provider community will be addressed by attending conventions where research and best clinical practices are shared, seminars are conducted, and networking opportunities are provided for the physicians.

Operating Strategy
 
Veto Cell doses are to be prepared by Cell Source facilities or qualified production partners. This is to both protect trade-secrets and directly control quality during the initial stages.
 
The graphic below outlines the general operating model in each geographic market.
 
 
Patient care facilities send frozen cells (donor and/or host depending on application) to a Cell Source processing center. Most likely, the first processing center will consist of lab space leased from a large transplantation center. Such a transplantation center has appropriate equipment and infrastructure, along with available production capacity, and will also represent an immediate market for our offerings for use in their own procedures. The Cell Source processing center processes the cells and sends the treated cells and appropriate protocols back to the caregiver for infusion at time of transplantation.
 
In the introductory period, we plan on establishing one center in the U.S.), one in Western Europe (most likely Germany), and one in the Far East. Specific locations and timing are to be determined. Initially, we plan to outsource production capacity from existing facilities at or adjacent to large hospitals. Subsequently, sales from these centers can justify and fund stand-alone facilities.
 
The general goal of the initial centers is to support the FDA process, provide full coverage for the North American and European markets, and provide access to the developing Chinese market. Following the introductory period in each respective market, we may elect to migrate the production facilities from leased space in transplantation center laboratories to company-owned stand-alone facilities.
 
In general, we assume a capital cost per stand-alone production facility of $8 million. This estimate is based, in part, on the projected high costs of GMP “clean rooms,” each of which can cost $1 million to set up. We will need to obtain financing in order to fund the setup of such facilities. There can be no assurance that financing will be available in amounts or on terms acceptable to us, if at all.
 
 
 
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Clinical Trials Overview
 
We will initially focus our clinical trials on bone marrow transplantation for patients suffering form certain lymphomas and leukemias, for which our Veto Cell technology constitutes a potential breakthrough. These two indications have unmet needs as evidenced by the valuations of leading CAR-T players who thus far have chiefly presented data treating these diseases.

We aspire to initiate a company-sponsored "Phase 1/2" clinical trials by 2017. These trials combine traditional Phase 1 safety trials with Phase 2 efficacy trials inasmuch as they are safety trials conducted on sick patients, so they are able to both establish safety and show initial indications of efficacy concurrently. The goal is to demonstrate safety and initial efficacy in several indications. Management has structured the trials such that an additional goal of showing initial markers pointing to prolonging progression-free survival may be possible already within Phase 1/2.

The chart below provides an overview of the current trials plan, which can of course vary based on both finalization of human protocols and timing or regulatory approvals:
 
Trial Plans
 
Trials are planned for Italy, Germany and the US. Multiple trials are planned on at least 16 patients. Patients are expected to be age 50 and older. The conditions chosen are ones which are associated with high mortality in this patient age-group today. This means that we may obtain a limited scope of patient reimbursement from government insurance in Europe on compassionate grounds for the treatment of said age group upon successful completion of Phase 2 trials. We plan to focus on mismatched bone marrow transplantation under reduced intensity conditioning (reduced levels of immune suppression treatment) for B-cell malignancies. Once a partnership is in place and we conclude successful preclinical trials for Veto + CAR-T cell therapy, we would launch parallel trials for both blood cell cancer (e.g., Multiple Myeloma) and solid tumor (e.g. Breast Cancer) patients. 

Regulatory Issues Overview
 
We seek regulatory approval from the U.S. FDA, the European Medicines Agency (“EMA”) in Europe and similar agencies elsewhere to both produce and sell our products.
 
Key approvals in Europe, where both treatment and limited insurance reimbursement may be possible at the end of Phase 2 trials, are expected to accelerate approval by the U.S. FDA. Given the importance of the U.S. market, we will conduct trials with a view to conforming with FDA guidelines so as to utilize clinical data gathered outside the U.S. in seeking to qualify for FDA approval.

 
 
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In the longer-term, we may also seek regulatory approval for selected Organsource applications.

Regulatory Process and Expectations
 
We will develop our clinical trial protocols with the support of experienced FDA and EMA consultants.
 
The clinical trials outlined in the previous section are designed to lead to regulatory approval for Veto Cell-based therapy in treating blood cancers and bone marrow transplantation applications.
 
Interim Revenue Opportunities
 
As noted above, while the clear focus is to conclude Phase 3 approval for cancer treatments, the Company is also exploring complementary “quick win” opportunities for generating revenue before additional FDA approvals are received, namely:
 
 
1.
Treating European patients after the end of Phase 2 (in some cases possibly with insurance reimbursement available); and
 
2.
Potential upfront and milestone driven licensing revenues from collaborations with third parties (e.g. with one or more CAR-T provider for Veto-CAR-T cell therapy development).
 
Intellectual Property
 
Pursuant to the Yeda License Agreement, Yeda granted the Company an exclusive license to certain patents, discoveries, inventions and other intellectual property generated (together with others) by Dr. Reisner as head of the Immunology Department at the Weizmann Institute. Under the Yeda License Agreement, The Company grants Yeda an industry-standard 4% royalty on sales of patented products. Currently, the Company voluntarily funds research (on its own behalf) and the Weizmann Institute for the preclinical development of its products, and plans to do so in the foreseeable future. Should the Company elect to curtail such funding, it would have to pay a $50,000 annual license fee until such times as payment of royalties commences. The Yeda License Agreement also requires the Company to proceed with the development of the technologies on a timely basis.
 
The license period (per product, per country) is for the full life of the patents, and expires at the later of the patent expiration date in that country or 15 years after the date that the FDA or local equivalent regulatory authority in each country approves that particular product for sale in that country. As long as Cell Source pays either a nominal license fee of $50,000 per year (total for use of all the products) or pays royalties on product sales on at least one product as per the license agreement, the license will remain in effect continuously and expire only with the expiration of the patent or 15 years after regulatory approval (later of the two) per product per country as described above. Cell Source voluntarily sponsors Research at the Weizmann Institute for the sake of developing its products and treatments from initial invention through to finalization of human treatment protocols. Cell Source has recently extended the initial research period, which terminated in October of 2014, for a further four years through October 2018.
 
Also under the Yeda License Agreement, the Company agreed to fund Yeda’s research until October 3, 2018, with an aggregate annual payment of $800,000 paid in quarterly $200,000 installments. However, in the event that the Company and Yeda execute a new research and license agreement, then the Company will annually fund research in the amount of $900,000 until Oct. 3, 2018. Such a new research and license agreement must be in accordance with the Evaluation and Exclusive Option Agreement by and between the Company and Yeda, dated Oct. 3, 2011, as amended on April 1, 2014 and June 22, 2014 (the “E&O Agreement). Among other things, the E&O Agreement granted Cell Source an option to negotiate a commercial license in the field of organ transplantation with Yeda (the “Option to Negotiate”). The Option to Negotiate requires an initiation fee of $200,000 payable to Yeda, which may be paid on the later of (i) the date on which the Option to Negotiate is granted and (ii) the date on which the Company receives an aggregate investment amount of at least $10,000,000. Pursuant to an amendment to the license agreement, the Option to Negotiate was exercised as of March 29, 2016.
 
If the Company fails to achieve any one of the milestones set forth in the Yeda License Agreement, which are listed below, then Yeda will be entitled to (i) modify the related license such that it will become non-exclusive or (ii) terminate the Yeda License Agreement upon thirty (30) days written notice:
 
 
(a)
Within three (3) years of the signature of the Yeda License Agreement to commence Phase I clinical trials;
 
(b)
Within five (5) years of the signature of the Yeda License Agreement to commence Phase II clinical trials with respect to the a licensed product, unless the Company shall have invested, during such five (5) year period, above an aggregate amount of at least US$5,000,000 in research and development;
 
(c)
Within either (8) years of the signature of the Yeda License Agreement to receive a FDA, EMEA or CFDA approval in respect of at least one (1) Product;
 
(d)
To achieve commercialization of at least one (1) Product within twelve (12) months of the date of FDA, EMEA or CFDA approval; or

 
 
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(e)
In case of a commercial sale of any Product having commenced, there shall be a period of twelve (12) months or more during which no sales of any Product shall take place (except as a result of force majeure or other factors beyond the control of the Company).
 
Additionally, the Yeda License Agreement also provides that:
 
·  
Funding the Research. Within 60 days of receiving any capital investment in the Company in excess of $2,000,000, provided that the Company has not paid Yeda by that date an option initiation fee of $200,000, as set forth in the E&O Agreement, Cell Source will pay Yeda 20% from such excess investment up to the sum of $200,000 (the “Additional Research Payment”). The Additional Research Payment shall be allocated by Yeda to support research activities of Dr. Reisner and can be offset in full by payment of the option initiation fee.
·  
Title. All right, title and interest in and to the Licensed Information and the Patents (as those terms are defined in the Yeda License Agreement) and all right, title and interest in and to any drawings, plans, diagrams, specifications, other documents, models, or any other physical matter in any way containing, representing or embodying any of the foregoing, vest and shall vest in Yeda and subject to the license granted in the Yeda License Agreement.
·  
Patents. Both Yeda and the Company shall consult with one another on the filing of patent applications for any portion of Licensed Information and/or corresponding to patent application existing at the time the Yeda License Agreement was executed. Yeda shall retain outside patent counsel that will be approved by Cell Source, to prepare, file and prosecute patent applications. All applications will be filed in Yeda’s name.
·  
Patents; Patent Infringements. Where the Company determines that a third party is infringing one or more of the Patents or is sued, in prosecuting or defending such litigation, the Company must pay any expenses or costs or other liabilities incurred in connection with such litigation (including attorney’s fees, costs and other sums awarded to the counterparty in such action). The Company agreed to indemnify Yeda against any such expenses or costs or other liabilities.
·  
License. With regard to the expiration of Patents, a Product is deemed to be covered by a Patent so long as such Product is protected by “Orphan Drug” status (or the like). The Company has an exclusive worldwide license under the Licensed Information and the Patents for the development, manufacture and sales of the Products. License remains in force in each country with respect to each Product until the later of (i) the expiration of the last Patent in such country covering such Product or (ii) the expiration of a 15-year period commencing the day FDA New Drug Approval is received for a Product in such country.
 
The Company may grant a Sublicense only with the prior written consent, which shall not be withheld unreasonably provided that:
 
 
i.
the proposed Sublicense is for monetary consideration only;
 
ii.
the proposed Sublicense is to be granted in a bona fide arm’s length commercial transaction;
 
iii.
a copy of the agreement granting the Sublicense and all amendments thereof shall be made available to Yeda, 14 days before their execution and Cell Source shall submit to Yeda copies of all such Sublicenses and all amendments thereof promptly upon execution thereof; and
 
iv.
the proposed Sublicense is made by written agreement, the provisions of which are consistent with the terms of the License and contain, inter alia, the following terms and conditions, including: the Sublicense shall expire automatically on the termination of the License for any reason.
 
However, Yeda’s prior written consent is not needed if the sublicense is limited to China, and the Company grants it to a Chinese affiliated entity of the Company.
 
·  
Termination. The Yeda License Agreement terminates on the later of: (i) the expiration of the last of the Patents or (ii) the expiry of a continuous period of 20 years during which there shall not have been a First commercial sale of any product in any country. Yeda may terminate by written notice, effective immediately, if the Company challenges the validity of any of the Patents. If a challenge is unsuccessful, then in addition to Yeda’s right to termination, the Company shall pay to Yeda liquidated damages in the amount of $8,000,000. Either the Company or Yeda may terminate the Yeda License Agreement and the License by serving a written notice upon (i) occurrence of a material breach or (ii) the granting of a winding-up order. Additionally, Yeda may terminate for failure to reimburse Yeda for patent application and/or prosecution expenses.

Our technology portfolio includes a patented platform termed “Veto Cell” (more formally described as “Anti 3rd party central memory T cell”), which is an immune tolerance biotechnology that enables the selective blocking of immune responses. Specifically, Veto Cells are specially prepared human cells that selectively protect specific targets from undesirable immune system attack.

 
 
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We had an exclusive option to license the “Organsource” platform developed by Dr. Reisner and his team under a similar Research & License Agreement. We exercised our option on March 29, 2016 and now exclusively license this technology from Yeda. This is a longer-horizon technology that shows significant promise for enabling the sourcing of embryonic cellular material from both animals and humans that can be used to both grow functional major organs in the body of a foreign “host” and regenerate existing diseased or damaged organs. This technology was used to grow pancreases in both rodents and primates, thereby curing them of juvenile diabetes, and has been used to regenerate human lung tissue.
 
For a list of all the patents and pending patents that Yeda holds and which we have a license to use, please refer to the table in the section entitled “Science and Technology Overview” above.

Patents & Proprietary Rights
 
Our success will depend in part on our ability to protect our existing product candidates and the products we acquire or license by obtaining and maintaining a strong proprietary position. To develop and maintain our position, we intend to continue relying upon patent protection, orphan drug status, Hatch-Waxman exclusivity, trade secrets, know-how, continuing technological innovations and licensing opportunities. We intend to seek patent protection whenever available for any products or product candidates and related technology we acquire in the future.
 
We may also seek orphan drug status whenever it is available. If a product which has an orphan drug designation subsequently receives the first regulatory approval for the indication for which it has such designation, the product is entitled to orphan exclusivity, meaning that the applicable regulatory authority may not approve any other applications to market the same drug for the same indication, except in very limited circumstances, for a period of seven years in the U.S. and Canada, and 10 years in the EU. Orphan drug designation does not prevent competitors from developing or marketing different drugs for the same indication or the same drug for a different clinical indication.
 
It is our policy to require our employees, consultants, outside scientific collaborators, sponsored researchers and other advisors to execute confidentiality agreements upon the commencement of employment or consulting relationships with us. These agreements provide that all confidential information made known to the individual during the course of the individual’s relationship with us is to be kept confidential and may not be disclosed to third parties except in specific circumstances. In the case of employees, the agreements provide that all inventions conceived by the individual shall be our exclusive property.
 
Government Regulation and Product Approval
 
We have not submitted any drug applications to the FDA and do not have anything pending for approval with the FDA. Cell Source itself has not had any contact with any regulator anywhere regarding treatment approvals or clinical trials associated with regulatory approvals. We are aware that a hospital in Italy has independently requested and received approval to conduct a trial with the same protocol that we plan to use, but we are not mentioned in the application nor in the approval. However, we may indirectly benefit from the outcome of the trial, if successful, although we are not the sponsor of this trial. There are no written or verbal agreements between the hospital and Cell Source regarding the use of the technology. That said, Cell Source is aware and in favor of the hospital plans to use the technology and would find a positive initial outcome encouraging. Since the treatment is being done on compassionate grounds as a non-commercial clinical trial, there is no legal requirement for the hospital to obtain approval to use the treatment protocol.
 
Cell Source plans to apply for approval for human clinical trials in 2016 to show initial safety, and possibly efficacy, results in Europe and the US. As of the date of this filing, the company has had no contact with any regulator regarding such approvals.
 
Regulation by governmental authorities in the U.S. and other countries is a significant factor, affecting the cost and time of our research and product development activities, and will be a significant factor in the manufacture and marketing of any approved products. All of our products require regulatory approval by governmental agencies prior to commercialization. In particular, our products are subject to rigorous pre-clinical and clinical testing and other approval requirements by the FDA and similar regulatory authorities in other countries. Various statutes and regulations also govern or influence the manufacturing, safety, reporting, labeling, transport and storage, record keeping and marketing of our products. The lengthy process of seeking these approvals, and the subsequent compliance with applicable statutes and regulations, require the expenditure of substantial resources. Any failure by us to obtain, or any delay in obtaining, the necessary regulatory approvals could harm our business.

The regulatory requirements relating to the testing, manufacturing and marketing of our products may change from time to time and this may impact our ability to conduct clinical trials and the ability of independent investigators to conduct their own research with support from us.

 
 
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The clinical development, manufacturing and marketing of our products are subject to regulation by various authorities in the U.S., the E.U. and other countries, including, in the U.S., the FDA, in Canada, Health Canada, and, in the E.U., the EMEA. The Federal Food, Drug, and Cosmetic Act, the Public Health Service Act in the U.S. and numerous directives, regulations, local laws and guidelines in Canada and the E.U. and elsewhere govern the testing, manufacture, safety, efficacy, labeling, storage, record keeping, approval, advertising and promotion of our products. Product development and approval within these regulatory frameworks takes a number of years and involves the expenditure of substantial resources.
 
Regulatory approval will be required in all the major markets in which we seek to develop our products. At a minimum, approval requires the generation and evaluation of data relating to the quality, safety, and efficacy of an investigational product for its proposed use. The specific types of data required and the regulations relating to this data will differ depending on the territory, the treatment candidate involved, the proposed indication and the stage of development.
 
In general, new cell compositions are tested in animals until adequate evidence of safety is established to support the proposed clinical study protocol designs. Clinical trials for new products are typically conducted in three sequential phases that may overlap. In Phase I, the initial introduction of the pharmaceutical into either healthy human volunteers or patients with the disease (typically 20 to 50 subjects), the emphasis is on testing for safety (adverse effects), dosage tolerance, metabolism, distribution, excretion and clinical pharmacology. Phase II involves studies in a limited patient population (typically 50 to 200 patients) to determine the initial efficacy of the pharmaceutical for specific targeted indications, to determine dosage tolerance and optimal dosage and to identify possible adverse side effects and safety risks. Once a treatment protocol shows preliminary evidence of some efficacy and is found to have an acceptable safety profile in Phase II evaluations, Phase III trials are undertaken to more fully evaluate clinical outcomes in a larger patient population in adequate and well-controlled studies designed to yield statistically sufficient clinical data to demonstrate efficacy and safety.
 
In the U.S., specific pre-clinical data, manufacturing and chemical data, as described above, need to be submitted to the FDA as part of an IND application, which, unless the FDA objects, will become effective thirty (30) days following receipt by the FDA. Phase I studies in human volunteers may commence only after the application becomes effective. Prior regulatory approval for human healthy volunteer studies is also required in member states of the E.U. Currently, in each member state of the E.U., following successful completion of Phase I studies, data are submitted in summarized format to the applicable regulatory authority in the member state in respect of applications for the conduct of later Phase II studies. In many places in Europe, a two tiered approval system mandates approval at the regional level prior to applying for national approval. Regional approval cycle times, including multiple iterations where questions are answered and the specific details of the protocol may be fine-tuned, can last several months prior to applying to the national (federal government level) regulator. The national regulatory authorities in the E.U. typically have between one and three months in which to raise any objections to the proposed study, and they often have the right to extend this review period at their discretion. In the U.S., following completion of Phase I studies, further submissions to regulatory authorities are necessary in relation to Phase II and III studies to update the existing IND. Authorities may require additional data before allowing the studies to commence and could demand that the studies be discontinued at any time if there are significant safety issues. In addition to the regulatory review, a study involving human subjects has to be approved by an independent body. The exact composition and responsibilities of this body will differ from country to country. In the U.S., for example, each study will be conducted under the auspices of an independent institutional review board at each institution at which the study is conducted. This board considers among other things, the design of the study, ethical factors, the privacy of protected health information as defined under the Health Insurance Portability and Accountability Act, the safety of the human subjects and the possible liability risk for the institution. Equivalent rules to protect subjects’ rights and welfare apply in each member state of the EU, where one or more independent ethics committees, which typically operate similarly to an institutional review board, will review the ethics of conducting the proposed research. These ethical review committees typically exist at the regional level, where approval is required prior to applying for national approval. Other regulatory authorities around the rest of the world have slightly differing requirements involving both the execution of clinical trials and the import/export of pharmaceutical products. It is our responsibility to ensure we conduct our business in accordance with the regulations of each relevant territory.
 
By leveraging existing pre-clinical and clinical data, we are seeking build upon an existing pre-clinical safety and efficacy database to accelerate our research. In addition, our focus on an end-stage population which has no current treatment options, commercialization, may result in relatively shorter approval cycle times. Approval by the FDA in this category generally has been based on objective response rates and duration of responses rather than demonstration of survival benefit. As a result, trials of drugs to treat end-stage refractory cancer indications have historically involved fewer patients and generally have been faster to complete than trials of drugs for other indications. We are aware that the FDA and other similar agencies are regularly reviewing the use of objective endpoints for commercial approval and that policy changes may impact the size of trials required for approval, timelines and expenditures significantly. The trend over the past few years has been to shorten approval cycles for terminal patients in the U.S. by employing a “fast track” approach.

 
 
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In order to gain marketing approval, we must submit a dossier to the relevant authority for review, which is known in the U.S. as an NDA and in the EU as a marketing authorization application, or MAA. The format is usually specific and laid out by each authority, although in general it will include information on the quality of the chemistry, manufacturing and pharmaceutical aspects of the product as well as the non-clinical and clinical data. Once the submitted NDA is accepted for filing by the FDA, it undertakes the review process that takes ten (10) months, unless an expedited priority review is granted which takes six (6) months to complete. Approval can take several months to several years, if multiple ten (10) month review cycles are needed before final approval is obtained, if at all.
 
The approval process can be affected by a number of factors. The NDA may be approvable requiring additional pre-clinical, manufacturing data or clinical trials which may be requested at the end of the ten (10) month NDA review cycle, thereby delaying marketing approval until the additional data are submitted and may involve substantial unbudgeted costs. The regulatory authorities usually will conduct an inspection of relevant manufacturing facilities, and review manufacturing procedures, operating systems and personnel qualifications. In addition to obtaining approval for each product, in many cases each drug manufacturing facility must be approved. Further inspections may occur over the life of the product. An inspection of the clinical investigation sites by a competent authority may be required as part of the regulatory approval procedure. As a condition of marketing approval, the regulatory agency may require post-marketing surveillance to monitor for adverse effects or other additional studies as deemed appropriate. After approval for the initial indication, further clinical studies are usually necessary to gain approval for any additional indications. The terms of any approval, including labeling content, may be more restrictive than expected and could affect the marketability of a product.
 
The FDA offers a number of regulatory mechanisms that provide expedited or accelerated approval procedures for selected drugs in the indications on which we are focusing our efforts. These include accelerated approval under Subpart H of the agency’s NDA approval regulations, fast track drug development procedures and priority review. At this time, we have not determined whether any of these approval procedures will apply to any of our current treatment candidates.
 
The U.S., E.U. and other jurisdictions may grant orphan drug designation to drugs intended to treat a “rare disease or condition,” which, in the U.S., is generally a disease or condition that affects no more than 200,000 individuals. In the E.U., orphan drug designation can be granted if: the disease is life threatening or chronically debilitating and affects no more than fifty (50) in 100,000 persons in the E.U.; without incentive it is unlikely that the drug would generate sufficient return to justify the necessary investment; and no satisfactory method of treatment for the condition exists or, if it does, the new drug will provide a significant benefit to those affected by the condition. If a product that has an orphan drug designation subsequently receives the first regulatory approval for the indication for which it has such designation, the product is entitled to orphan exclusivity, meaning that the applicable regulatory authority may not approve any other applications to market the same drug for the same indication, except in very limited circumstances, for a period of seven years in the U.S. and ten (10) years in the EU. Orphan drug designation does not prevent competitors from developing or marketing different drugs for the same indication or the same drug for different indications. Orphan drug designation must be requested before submitting an NDA or MAA. After orphan drug designation is granted, the identity of the therapeutic agent and its potential orphan use are publicly disclosed. Orphan drug designation does not convey an advantage in, or shorten the duration of, the review and approval process; however, this designation provides an exemption from marketing authorization (NDA) fees.
 
We are also subject to numerous environmental and safety laws and regulations, including those governing the use and disposal of hazardous materials. The cost of compliance with and any violation of these regulations could have a material adverse effect on our business and results of operations. Although we believe that our safety procedures for handling and disposing of these materials comply with the standards prescribed by state and federal regulations, accidental contamination or injury from these materials may occur. Compliance with laws and regulations relating to the protection of the environment has not had a material effect on our capital expenditures or our competitive position. However, we are not able to predict the extent of government regulation, and the cost and effect thereof on our competitive position, which might result from any legislative or administrative action pertaining to environmental or safety matters.
 
In various countries, animal rights activism has led to either formal or informal boycotting of certain types of animal trials. As we rely on animal experiments as precursors to human trials.
 
Employees
 
Other than our Chief Executive Officer, we currently do not have full-time employees, but retain the services of independent contractors/consultants on a contract-employment basis. However, our Board of Directors intends to negotiate an employment package for our Chief Executive Officer, Itamar Shimrat in the near future. Our ability to manage growth effectively will require us to continue to implement and improve our management systems and to recruit and train new employees. Although we have done so in the past and expect to do so in the future, there can be no assurance that we will be able to successfully attract and retain skilled and experienced personnel. We anticipate that in the near future, other key personnel will enter into employment agreements with the Company on customary terms.

 
 
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ITEM 1A. RISK FACTORS.
 
An investment in the Company’s Common Stock involves a high degree of risk. You should carefully consider the risks described below as well as other information provided to you in this Annual Report on Form 10-K, including information in the section of this document entitled “Information Regarding Forward Looking Statements.” The risks and uncertainties described below are not the only ones facing us. Additional risks and uncertainties not presently known to us or that we currently believe are immaterial may also impair our business operations. If any of the following risks actually occur, our business, financial condition or results of operations could be materially adversely affected, the value of our Common Stock could decline, and you may lose all or part of your investment.
 
Risks related to our Business and our Industry
 
We have a limited operating history and a history of operating losses, and expect to incur significant additional operating losses.
 
Our planned principal operations are the development and commercialization of new cell therapy products focused on treatment of blood cancers, certain non-malignant disorders and organ transplantations and regeneration. We are currently conducting research and development activities in order to facilitate the transition of the patent technology we license from the laboratory to clinical trials. We have a limited operating history. Therefore, there is limited historical financial information upon which to base an evaluation of our performance. Our prospects must be considered in light of the uncertainties, risks, expenses, and difficulties frequently encountered by companies in their early stages of operations. We have generated net losses since we began operations, including $2,504,105 for the year ended December 31, 2015. We expect to incur substantial additional net expenses over the next several years as our research, development, and commercial activities increase. The amount of future losses and when, if ever, we will achieve profitability are uncertain. Our ability to generate revenue and achieve profitability will depend on, among other things, successful completion of the preclinical and clinical development of our product candidates; obtaining necessary regulatory approvals from the U.S. Food and Drug Administration (the “FDA”) and international regulatory agencies; successful manufacturing, sales, and marketing arrangements; and raising sufficient funds to finance our activities. If we are unsuccessful at some or all of these undertakings, our business, prospects, and results of operations may be materially adversely affected.
 
We may need to secure additional financing.
 
We anticipate that we will incur operating losses for the foreseeable future. Our historical cash burn rate was approximately $150,000 per month. However, we estimate that our current burn rate is approximately $200,000 per month. As of December 31, 2015, we had cash in the amount of $6,944. Based on our current resources, we will not be able to continue to operate without additional immediate funding. If we are not successful in securing additional financing, we may be required to delay significantly, reduce the scope of or eliminate one or more of our research or development programs, downsize our general and administrative infrastructure, or seek alternative measures to avoid insolvency, including arrangements with collaborative partners or others that may require us to relinquish rights to certain of our technologies, product candidates or products.
 
Our auditors have issued a “going concern” audit opinion.
 
Our independent auditors have indicated, in their report on our December 31, 2015 consolidated financial statements, that there is substantial doubt about our ability to continue as a going concern. A “going concern” opinion indicates that the financial statements have been prepared assuming we will continue as a going concern and do not include any adjustments to reflect the possible future effects on the recoverability and classification of assets, or the amounts and classification of liabilities that may result if we do not continue as a going concern. Therefore, you should not rely on our consolidated balance sheet as an indication of the amount of proceeds that would be available to satisfy claims of creditors, and potentially be available for distribution to shareholders, in the event of liquidation.
 
We are an early-stage company with an unproven business strategy and may never achieve commercialization of our candidate products or profitability.
 
We are at an early stage of development and commercialization of our technologies and product candidates. We have not yet begun to market any products and, accordingly, have not begun to generate revenues from the commercialization of our products. Our products will require significant additional clinical testing and investment prior to commercialization. A commitment of substantial resources by ourselves and, potentially, our partners to conduct time-consuming research and clinical trials will be required if we are to complete the development of our product candidates. There can be no assurance that any of our product candidates will meet applicable regulatory standards, obtain required regulatory approvals, be capable of being produced in commercial quantities at reasonable costs or be successfully marketed. Most of our product candidates are not expected to be commercially available for several years, if at all.

 
 
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We are dependent on our collaborative partners and service providers the loss of which would hurt our business.
 
Our strategy is to enter into various arrangements with corporate and academic collaborators, licensors, licensees, service providers and others for the research, development, clinical testing and commercialization of our products. We intend to or have entered into agreements with academic, medical and commercial organizations to research, develop and test our products. In addition, we intend to enter into corporate partnerships to commercialize the Company’s core products. There can be no assurance that such collaborations can be established on favorable terms, if at all.
 
Should any collaborative partner or service provider fail to appropriately research, develop, test or successfully commercialize any product to which the Company has rights, our business may be adversely affected. Failure of a collaborative partner or service provider to successfully conduct or complete their activities or to remain a viable collaborative partner or commercialize enterprise for any particular program could delay or halt the development or commercialization of any products arising out of such program. While management believes that collaborative partners and service providers will have sufficient economic motivation to continue their activities, there can be no assurance that any of these collaborations or provisions of required services will be continued or result in successfully commercialized products.
 
Notably, we maintain an exclusive worldwide license to certain intellectual property owned by Yeda pursuant to the Yeda License Agreement, as further discussed in the “Intellectual Property” section hereinafter. If we should default under the License Agreement, then our rights to Yeda’s intellectual property would extinguish, and we would lose all rights to operate the licenses. In such an event, we would effectively cease to operate unless we re-obtained licensing with Yeda.
 
In addition, there can be no assurance that the collaborative research or commercialization partners will not pursue alternative technologies or develop alternative products either on their own or in collaboration with others, including our competitors, as a means for developing treatments for the diseases or conditions targeted by our programs.
 
Our ability and our collaborators' ability to sell therapeutic products will depend to a large extent upon reimbursement from health care insurance companies.
 
Our success may depend, in part, on the extent to which reimbursement for the costs of therapeutic products and related treatments will be available from third-party payers such as government health administration authorities, private health insurers, managed care programs, and other organizations. Over the past decade, the cost of health care has risen significantly, and there have been numerous proposals by legislators, regulators, and third-party health care payers to curb these costs. Some of these proposals have involved limitations on the amount of reimbursement for certain products. Similar federal or state health care legislation may be adopted in the future and any products that we or our collaborators seek to commercialize may not be considered cost-effective. Adequate third-party insurance coverage may not be available for us or our collaborative partners to establish and maintain price levels that are sufficient for realization of an appropriate return on investment in product development.
 
We do not own any patents and rely on the patents we license from Yeda Research and Development Limited.
 
We do not currently own any patents and only have an exclusive worldwide license to certain intellectual property owned by Yeda pursuant to a license agreement between us and Yeda. Under the license agreement with Yeda, Yeda retains ownership of the licensed patents. If we were to default under the license agreement, then our rights to Yeda’s intellectual property would be extinguished and we would lose all rights to operate the license. In such an event, we would effectively cease to operate unless we re-obtained licensing with Yeda.
 
We are dependent on protecting our proprietary rights.
 
Our success and competitive position and future overall revenues will depend in part on our ability to obtain and maintain patent protection over the patents that we have an exclusive license to use for our product candidates, methods, process and other technologies to preserve our trade secrets, to prevent third parties from infringing on our proprietary rights and to operate without infringing the proprietary rights of third parties. Although our patents and related technologies are owned by Yeda, under our exclusive license agreement, we are required to pay all patent related expenses for applications, renewals, etc., as well as any and all legal or other costs associated with the defending and protecting such proprietary rights. However, we cannot predict:
 
·  
the degree and range of protection any patents will afford us against competitors, including whether third parties will find ways to invalidate or otherwise circumvent the patents that we license;
·  
whether  or  not  others  will  obtain  patents  claiming  aspects  similar  to  those covered by the patents that we license; or
·  
whether we will need to initiate litigation or administrative proceedings, which may be costly whether we win or lose.

 
 
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For a complete list of the patents that we license from Yeda, please see the section entitled “Science and Technology Overview” of this Annual Report on Form 10-K.
 
We may be required to obtain licenses from third parties to avoid infringing patents or other proprietary rights. No assurance can be given that any licenses required under any such patents or proprietary rights would be made available, if at all, on terms we find acceptable. If we do not obtain such licenses, we could encounter delays in the introduction of products, or could find that the development, manufacture or sale of products requiring such licenses could be prohibited.
 
A number of pharmaceutical, biopharmaceutical and biotechnology companies and research and academic institutions have developed technologies, filed patent applications or received patents on various technologies that may be related to or affect our business. Some of these technologies, applications or patents may conflict with our technologies or patent applications. Such conflict could limit the scope of the patents, if any, that we may be able to obtain. Such conflict may also result in the denial of our patent applications. In addition, if patents that cover our activities are issued to other companies, there can be no assurance that we would be able to obtain licenses to these patents at a reasonable cost or be able to develop or obtain alternative technology. If we do not obtain such licenses, we could encounter delays in the introduction of products, or could find that the development, manufacture or sale of products requiring such licenses could be prohibited. In addition, we could incur substantial costs in defending ourselves in suits brought against us on patents that our products might infringe or in filing suits against others to have such patents declared invalid.
 
Patent applications in the U.S. are maintained in secrecy and not published if either: i) the application is a provisional application or, ii) the application is filed and we request no publication, and certify that the invention disclosed “has not and will not” be the subject of a published foreign application. Otherwise, U.S. applications or foreign counterparts, if any, publish 18 months after the priority application has been filed. Since publication of discoveries in the scientific or patent literature often lag behind actual discoveries, we cannot be certain that we or any licensor were the first creator of inventions covered by pending patent applications or that we or such licensor was the first to file patent applications for such inventions. Moreover, we might have to participate in interference proceedings declared by the U.S. Patent and Trademark Office to determine priority of invention, which could result in substantial cost to us, even if the eventual outcome were favorable to us. There can be no assurance that our patents, if issued, would be held valid or enforceable by a court or that a competitor’s technology or product would be found to infringe such patents.
 
Much of our know-how and technology may not be patentable. To protect our rights, we require employees, consultants, advisors and collaborators to enter into confidentiality agreements. There can be no assurance, however, that these agreements will provide meaningful protection for our trade secrets, know-how or other proprietary information in the event of any unauthorized use or disclosure. Further, our business may be adversely affected by competitors who independently develop competing technologies, especially if we obtain no, or only narrow, patent protection.
 
We are subject to various government regulations.
 
The manufacture and sale of human therapeutic and diagnostic products in the U.S., Canada and foreign jurisdictions are governed by a variety of statutes and regulations. These laws require approval of manufacturing facilities, controlled research and testing of products and government review and approval of a submission containing manufacturing, preclinical and clinical data in order to obtain marketing approval based on establishing the safety and efficacy of the product for each use sought, including adherence to current Good Manufacturing Practice (or cGMP) during production and storage, and control of marketing activities, including advertising and labeling.
 
The products we are currently developing will require significant development, preclinical and clinical testing and investment of substantial funds prior to their commercialization. The process of obtaining required approvals can be costly and time-consuming, and there can be no assurance that future products will be successfully developed and will prove to be safe and effective in clinical trials or receive applicable regulatory approvals. Markets other than the U.S. and Canada have similar restrictions. Potential investors and shareholders should be aware of the risks, problems, delays, expenses and difficulties which we may encounter in view of the extensive regulatory environment which controls our business.
 
We may become subject to increased government regulation.
 
Increased government regulation could: (i) reduce our revenues; (ii) increase our operating expenses; and (iii) expose us to significant liabilities. We cannot be sure what effect any future material noncompliance by us with any future laws and regulations or any material changes in current laws and regulations could have on our business, operating results and financial condition.
 

 
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If we are unable to keep up with rapid technological changes in our field or compete effectively, we will be unable to operate profitably.
 
We are engaged in a rapidly changing field. Other products and therapies that will compete directly with the products that we are seeking to develop and market currently exist or are being developed. Competition from fully integrated pharmaceutical companies and more established biotechnology companies is intense and is expected to increase. Most of these companies have significantly greater financial resources and expertise in discovery and development, manufacturing, preclinical and clinical testing, obtaining regulatory approvals and marketing than us. Smaller companies may also prove to be significant competitors, particularly through collaborative arrangements with large pharmaceutical and established biopharmaceutical or biotechnology companies. Many of these competitors have significant products that have been approved or are in development and operate large, well-funded discovery and development programs. Academic institutions, governmental agencies and other public and private research organizations also conduct research, seek patent protection and establish collaborative arrangements for therapeutic products and clinical development and marketing. These companies and institutions compete with us in recruiting and retaining highly qualified scientific and management personnel. In addition to the above factors, we will face competition based on product efficacy and safety, the timing and scope of regulatory approvals, availability of supply, marketing and sales capability, reimbursement coverage, price and patent position. There is no assurance that our competitors will not develop more effective or more affordable products, or achieve earlier patent protection or product commercialization, than our own.
 
Other companies may succeed in developing products earlier than ourselves, obtaining Health Canada, European Medicines Agency (the “EMEA”) and FDA approvals for such products more rapidly than we will, or in developing products that are more effective than products we propose to develop. While we will seek to expand our technological capabilities in order to remain competitive, there can be no assurance that research and development by others will not render our technology or products obsolete or non-competitive or result in treatments or cures superior to any therapy we develop, or that any therapy we develop will be preferred to any existing or newly developed technologies.
 
Clinical trials for our product candidates are expensive and time consuming, and their outcome is uncertain.
 
The process of obtaining and maintaining regulatory approvals for new therapeutic products is expensive, lengthy and uncertain. Costs and timing of clinical trials may vary significantly over the life of a project owing to any or all of the following non-exclusive reasons:
 
·  
the duration of the clinical trial;
·  
the number of sites included in the trials;
·  
the countries in which the trial is conducted;
·  
the length of time required and ability to enroll eligible patients;
·  
the number of patients that participate in the trials;
·  
the number of doses that patients receive;
·  
the drop-out or discontinuation rates of patients;
·  
per patient trial costs;
·  
third party contractors failing to comply with regulatory requirements or meet their contractual obligations to us in a timely manner;
·  
our final product candidates having different properties in humans than in laboratory testing;
·  
the need to suspend or terminate our clinical trials;
·  
insufficient or inadequate supply of quality of necessary materials to conduct our trials;
·  
potential additional safety monitoring, or other conditions required by FDA or comparable foreign regulatory authorities regarding the scope or design of our clinical trials, or other studies requested by regulatory agencies;
·  
problems engaging institutional review boards (“IRB”) to oversee trials or in obtaining and maintaining IRB approval of studies;
·  
the duration of patient follow-up;
·  
the efficacy and safety profile of a product candidate;
·  
the costs and timing of obtaining regulatory approvals; and
·  
the costs involved in enforcing or defending patent claims or other intellectual property rights.
 
Late stage clinical trials are especially expensive, typically requiring tens of millions of dollars, and take years to reach their outcomes. Such outcomes often fail to reproduce the results of earlier trials. It is often necessary to conduct multiple late stage trials, including multiple Phase III trials, in order to obtain sufficient results to support product approval, which further increases the expense. Sometimes trials are further complicated by changes in requirements while the trials are under way (for example, when the standard of care changes for the disease that is being studied in the trial). Accordingly, any of our current or future product candidates could take a significantly longer time to gain regulatory approval than we expect, or may never gain approval, either of which could delay or stop the commercialization of our product candidates.
 
 
 
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We may be required to suspend or discontinue clinical trials due to unexpected side effects or other safety risks that could preclude approval of our product candidates.
 
Our clinical trials may be suspended at any time for a number of reasons. For example, we may voluntarily suspend or terminate our clinical trials if at any time we believe that they present an unacceptable risk to the clinical trial patients. In addition, the FDA or other regulatory agencies may order the temporary or permanent discontinuation of our clinical trials at any time if they believe that the clinical trials are not being conducted in accordance with applicable regulatory requirements or that they present an unacceptable safety risk to the clinical trial patients.
 
Administering any product candidate to humans may produce undesirable side effects. These side effects could interrupt, delay or halt clinical trials of our product candidates and could result in the FDA or other regulatory authorities denying further development or approval of our product candidates for any or all targeted indications. Ultimately, some or all of our product candidates may prove to be unsafe for human use. Moreover, we could be subject to significant liability if any volunteer or patient suffers, or appears to suffer, adverse health effects as a result of participating in our clinical trials.
 
We may not receive regulatory approvals for our product candidates or there may be a delay in obtaining such approvals.
 
Our products and our ongoing development activities are subject to regulation by regulatory authorities in the countries in which we or our collaborators and distributors wish to test, manufacture or market our products. For instance, the FDA will regulate the product in the U.S. and equivalent authorities, such as the EMA, will regulate in Europe. Regulatory approval by these authorities will be subject to the evaluation of data relating to the quality, efficacy and safety of the product for its proposed use, and there can be no assurance that the regulatory authorities will find our data sufficient to support product approval.
 
The time required to obtain regulatory approval varies between countries. In the U.S., for products without “Fast Track” status, it can take up to eighteen (18) months after submission of an application for product approval to receive the FDA’s decision. Even with Fast Track status, FDA review and decision can take up to twelve (12) months.
 
Different regulators may impose their own requirements and may refuse to grant, or may require additional data before granting, an approval, notwithstanding that regulatory approval may have been granted by other regulators. Regulatory approval may be delayed, limited or denied for a number of reasons, including insufficient clinical data, the product not meeting safety or efficacy requirements or any relevant manufacturing processes or facilities not meeting applicable requirements as well as case load at the regulatory agency at the time.
 
Delays in our clinical trials could result in us not achieving anticipated developmental milestones when expected, increased costs and delay our ability to obtain regulatory approval and commercialize our product candidates.
 
Delays in our ability to commence or enroll patients for our clinical trials could result in us not meeting anticipated clinical milestones and could materially impact our product development costs and delay regulatory approval of our product candidates. We do not know whether planned clinical trials will be commenced or completed on schedule, if at all. Clinical trials can be delayed for a variety of reasons, including:

·  
delays in the development of manufacturing capabilities for our product candidates to enable their consistent production at clinical trial scale;
·  
delays in the commencement of clinical trials as a result of clinical trial holds or the need to obtain additional information to complete an Investigational New Drug Application (IND);
·  
delays in obtaining regulatory approval to commence new trials;
·  
adverse safety events experienced during our clinical trials;
·  
insufficient efficacy during trials leading to withdrawal of product candidate;
·  
delays in obtaining clinical materials;
·  
slower than expected patient recruitment for participation in clinical trials; and
·  
delays in reaching agreement on acceptable clinical trial agreement terms with prospective sites or obtaining institutional review board approval.
 
If we do not successfully commence or complete our clinical trials on schedule, the price of our common stock may decline.
 
Preclinical studies and Phase 1 or 2 clinical trials of our product candidates may not predict the results of subsequent human clinical trials.
 
Preclinical studies, including studies of our product candidates in animal models, may not accurately predict the result of human clinical trials of those product candidates. In particular, promising animal studies suggesting the efficacy of our products may not predict the ability of these products to treat humans. Our technology may be found not to be efficacious when studied in human clinical trials.

 
 
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To satisfy FDA or foreign regulatory approval standards for the commercial sale of our product candidates, we must demonstrate in adequate and controlled clinical trials that our product candidates are safe and effective. Success in early clinical trials, including Phase 2 trials, does not ensure that later clinical trials will be successful. Our initial results from Phase 1/2 clinical trials also may not be confirmed by later analysis or subsequent larger clinical trials. A number of companies in the pharmaceutical industry have suffered significant setbacks in advanced clinical trials, even after obtaining promising results in earlier clinical trials.
 
Our product candidates must undergo rigorous clinical testing, the results of which are uncertain and could substantially delay or prevent us from bringing them to market.
 
Before we can obtain regulatory approval for a product candidate, we must undertake extensive clinical testing in humans to demonstrate safety and efficacy to the satisfaction of the FDA or other regulatory agencies. Clinical trials of new drug candidates sufficient to obtain regulatory marketing approval are expensive and take years to complete.
 
We cannot be certain of successfully completing clinical testing within the time frame we have planned, or at all. We may experience numerous unforeseen events during, or as a result of, the clinical trial process that could delay or prevent us from receiving regulatory approval or commercializing our product candidates, including the following:
 
·  
our clinical trials may produce negative or inconclusive results, and we may decide, or regulators may require us, to conduct additional clinical and/or preclinical testing or to abandon programs;
·  
the results obtained in earlier stage clinical testing may not be indicative of results in future clinical trials;
·  
clinical trial results may not meet the level of statistical significance required by the FDA or other regulatory agencies;
·  
enrollment in our clinical trials for our product candidates may be slower than we anticipate, resulting in significant delays and additional expense;
·  
we, or regulators, may suspend or terminate our clinical trials if the participating patients are being exposed to unacceptable health risks; and
·  
the effects of our product candidates on patients may not be the desired effects or may include undesirable side effects or other characteristics that may delay or preclude regulatory approval or limit their commercial use, if approved.

Completion of clinical trials depends, among other things, on our ability to enroll a sufficient number of patients, which is a function of many factors, including:
 
·  
the therapeutic endpoints chosen for evaluation;
·  
the eligibility criteria defined in the protocol;
·  
the perceived benefit of the investigational drug under study;
·  
the size of the patient population required for analysis of the clinical trial’s therapeutic endpoints;
·  
our ability to recruit clinical trial investigators and sites with the appropriate competencies and experience;
·  
our ability to obtain and maintain patient consents; and
·  
competition for patients by clinical trial programs for other treatments.
 
We may experience difficulties in enrolling patients in our clinical trials, which could increase the costs or affect the timing or outcome of these clinical trials. This is particularly true with respect to diseases with relatively small patient populations.
 
We may in the future conduct clinical trials for our products or product candidates outside the United States and the FDA may not accept data from such trials.
 
We may in the future choose to conduct one or more of our clinical trials outside the United States. Although the FDA may accept data from clinical trials conducted outside the United States, acceptance of such study data by the FDA is subject to certain conditions. For example, the study must be well designed and conducted and performed by qualified investigators in accordance with ethical principles. The study population must also adequately represent the U.S. population, and the data must be applicable to the U.S. population and U.S. medical practice in ways that the FDA deems clinically meaningful. Generally, the patient population for any clinical studies conducted outside of the United States must be representative of the population for whom we intend to label the product in the United States. In addition, such studies would be subject to the applicable local laws and FDA acceptance of the data would be dependent upon its determination that the studies also complied with all applicable U.S. laws and regulations. There can be no assurance the FDA will accept data from trials conducted outside of the United States. If the FDA does not accept any such data, it would likely result in the need for additional trials, which would be costly and time consuming and delay aspects of our business plan.
 
 
 
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We may fail to comply with regulatory requirements.
 
Our success will be dependent upon our ability, and our collaborative partners’ abilities, to maintain compliance with regulatory requirements, including cGMP, and safety reporting obligations. The failure to comply with applicable regulatory requirements can result in, among other things, fines, injunctions, civil penalties, total or partial suspension of regulatory approvals, refusal to approve pending applications, recalls or seizures of products, operating and production restrictions and criminal prosecutions.

Regulatory approval of our product candidates may be withdrawn at any time.
 
After regulatory approval has been obtained for medicinal products, the product and the manufacturer are subject to continual review, including the review of adverse experiences and clinical results that are reported after our products are made available to patients, and there can be no assurance that such approval will not be withdrawn or restricted. Regulators may also subject approvals to restrictions or conditions, or impose post-approval obligations on the holders of these approvals, and the regulatory status of such products may be jeopardized if such obligations are not fulfilled. If post-approval studies are required, such studies may involve significant time and expense.
 
The manufacturer and manufacturing facilities we use to make any of our products will also be subject to periodic review and inspection by the FDA or EMA, as applicable. The discovery of any new or previously unknown problems with the product, manufacturer or facility may result in restrictions on the product or manufacturer or facility, including withdrawal of the product from the market. We will continue to be subject to the FDA or EMA requirements, as applicable, governing the labeling, packaging, storage, advertising, promotion, recordkeeping, and submission of safety and other post-market information for all of our product candidates, even those that the FDA or EMA, as applicable, had approved. If we fail to comply with applicable continuing regulatory requirements, we may be subject to fines, suspension or withdrawal of regulatory approval, product recalls and seizures, operating restrictions and other adverse consequences.
 
There may not be a viable market for our products.
 
We believe that there will be many different applications for our products. We also believe that the anticipated market for our products will continue to expand. These assumptions may prove to be incorrect for a variety of reasons, including competition from other products and the degree of our products’ commercial viability.
 
We rely on key personnel and, if we are unable to retain or motivate key personnel or hire qualified personnel, we may not be able to grow effectively.
 
We are dependent on our Chief Executive Officer, Itamar Shimrat, our Executive Chairman, Dennis Brown, and on scientific and drug development consultants, including Professor Yair Reisner, the loss of services of one or more of whom could materially adversely affect us.
 
Other than our Chief Executive Officer, we currently do not have full-time employees, but we retain the services of independent contractors/consultants on a contract-employment basis. Our ability to manage growth effectively will require us to continue to implement and improve our management systems and to recruit and train new employees. Although we have done so in the past and expect to do so in the future, there can be no assurance that we will be able to successfully attract and retain skilled and experienced personnel.
 
We may be subject to foreign exchange fluctuation.
 
We maintain our accounts in both U.S. dollars and Israeli shekels. A portion of our expenditures are in foreign currencies, most notably in U.S. dollars, and therefore we are subject to foreign currency fluctuations, which may, from time to time, impact our financial position and results. We may enter into hedging arrangements under specific circumstances, typically through the use of forward or futures currency contracts, to minimize the impact of increases in the value of the U.S. dollar. In order to minimize our exposure to foreign exchange fluctuations we may hold sufficient U.S. dollars to cover our expected U.S. dollar expenditures.
 
We may be exposed to potential product and clinical trials liability.
 
Our business exposes us to potential product liability risks, which are inherent in the testing, manufacturing, marketing and sale of therapeutic products. Human therapeutic products involve an inherent risk of product liability claims and associated adverse publicity. While we will continue to take precautions we deem appropriate, there can be no assurance that we will be able to avoid significant product liability exposure. We do not currently maintain liability insurance coverage as such insurance is expensive and difficult to obtain. In the event clinical trials are commenced, we plan to obtain liability insurance coverage in the jurisdictions applicable to such clinical trials. However, when we seek such insurance, it may not be available on acceptable terms, if at all. The inability to obtain sufficient insurance coverage on reasonable terms or to otherwise protect against potential product liability claims could prevent or inhibit our ability to conduct clinical trials in certain jurisdiction or the commercialization of our current or potential
 
 
39

 
 
products. A product liability claim brought against us in a clinical trial or a product withdrawal could have a material adverse effect upon us and our financial condition. Should the insurance coverage be insufficient in amount or scope to address multiple and diverse claims, liabilities not covered by insurance could represent a significant financial liability for Cell Source. Since Yeda does not conduct human trials, there is no need for Cell Source to have insurance for trials there. When Cell Source begins to contract facilities at hospitals to conduct human trials on its behalf, it will ensure that full and proper insurance coverage will be in place with respect to such clinical facilities. Cell Source plans to insure its participation in any and all clinical trials, above and beyond whatever insurance coverage is already held by the institutions and facilities providing services with respect to such clinical trials.
 
We may become subject to liabilities related to risks inherent in working with hazardous materials.
 
Our discovery and development processes involve the controlled use of hazardous and radioactive materials. We are subject to federal, state, provincial and local laws and regulations governing the use, manufacture, storage, handling and disposal of such materials and certain waste products. Although we believe that our safety procedures for handling and disposing of such materials comply with the standards prescribed by such laws and regulations, the risk of accidental contamination or injury from these materials cannot be completely eliminated. In the event of such an accident, we could be held liable for any damages that result and any such liability could exceed our resources. We are not specifically insured with respect to this liability. Although we believe that we are in compliance in all material respects with applicable environmental laws and regulations and currently do not expect to make material capital expenditures for environmental control facilities in the near-term, there can be no assurance that we will not be required to incur significant costs to comply with environmental laws and regulations in the future, or that our operations, business or assets will not be materially adversely affected by current or future environmental laws or regulations.
 
Risks Related to Our Common Stock
 
There is not an active liquid trading market for the Company’s Common Stock.
 
The Company is required to report under the Exchange Act and its Common Stock is eligible for quotation on the OTC Markets. However, there is no regular active trading market in the Company’s Common Stock, and we cannot give an assurance that an active trading market will develop. If an active market for the Company’s Common Stock develops, there is a significant risk that the Company’s stock price may fluctuate dramatically in the future in response to any of the following factors, some of which are beyond our control:
 
·  
variations in our quarterly operating results;
·  
announcements that our revenue or income are below analysts’ expectations;
·  
general economic slowdowns;
·  
sales of large blocks of the Company’s Common Stock; and
·  
announcements by us or our competitors of significant contracts, acquisitions, strategic partnerships, joint ventures or capital commitments.
 
Our Common Stock is subject to the “penny stock” rules of the Securities and Exchange Commission, which may make it more difficult for stockholders to sell our Common Stock.
 
The SEC has adopted Rule 15g-9 which establishes the definition of a “penny stock,” for the purposes relevant to us, as any equity security that has a market price of less than $5.00 per share, subject to certain exceptions. For any transaction involving a penny stock, unless exempt, the rules require that a broker or dealer approve a person’s account for transactions in penny stocks, and the broker or dealer receive from the investor a written agreement to the transaction, setting forth the identity and quantity of the penny stock to be purchased.
 
In order to approve a person’s account for transactions in penny stocks, the broker or dealer must obtain financial information and investment experience objectives of the person, and make a reasonable determination that the transactions in penny stocks are suitable for that person and the person has sufficient knowledge and experience in financial matters to be capable of evaluating the risks of transactions in penny stocks.
 
The broker or dealer must also deliver, prior to any transaction in a penny stock, a disclosure schedule prescribed by the SEC relating to the penny stock market, which, in highlight form sets forth the basis on which the broker or dealer made the suitability determination, and that the broker or dealer received a signed, written agreement from the investor prior to the transaction.
 
Generally, brokers may be less willing to execute transactions in securities subject to the “penny stock” rules. This may make it more difficult for investors to dispose of the Company’s Common Stock if and when such shares are eligible for sale and may cause a decline in the market value of its stock.

 
 
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Disclosure also has to be made about the risks of investing in penny stocks in both public offerings and in secondary trading and about the commissions payable to both the broker-dealer and the registered representative, current quotations for the securities and the rights and remedies available to an investor in cases of fraud in penny stock transactions. Finally, monthly statements have to be sent disclosing recent price information for the penny stock held in the account and information on the limited market in penny stock.
 
We may not be able to attract the attention of brokerage firms because we became a public company by means of a reverse acquisition.
 
Because we became public through a “reverse acquisition," securities analysts of brokerage firms may not provide coverage of us since there is little incentive to brokerage firms to recommend the purchase of our Common Stock. No assurance can be given that brokerage firms will want to conduct any secondary offerings on behalf of the Company in the future.
 
Applicable regulatory requirements, including those contained in and issued under the Sarbanes-Oxley Act of 2002, may make it difficult for the Company to retain or attract qualified officers and directors, which could adversely affect the management of its business and its ability to obtain or retain listing of its Common Stock.
 
The Company may be unable to attract and retain those qualified officers, directors and members of board committees required to provide for effective management because of the rules and regulations that govern publicly held companies, including, but not limited to, certifications by principal executive officers. The enactment of the Sarbanes-Oxley Act has resulted in the issuance of a series of related rules and regulations and the strengthening of existing rules and regulations by the SEC, as well as the adoption of new and more stringent rules by the stock exchanges. The perceived increased personal risk associated with these changes may deter qualified individuals from accepting roles as directors and executive officers.
 
Further, some of these changes heighten the requirements for board or committee membership, particularly with respect to an individual’s independence from the corporation and level of experience in finance and accounting matters. The Company may have difficulty attracting and retaining directors with the requisite qualifications. If the Company is unable to attract and retain qualified officers and directors, the management of its business and its ability to obtain or retain listing of our shares of Common Stock on any stock exchange (assuming the Company elects to seek and are successful in obtaining such listing) could be adversely affected.
 
If the Company fails to maintain an effective system of internal controls, it may not be able to accurately report its financial results or detect fraud. Consequently, investors could lose confidence in the Company’s financial reporting and this may decrease the trading price of its stock.
 
The Company must maintain effective internal controls to provide reliable financial reports and detect fraud. The Company has been assessing its internal controls to identify areas that need improvement. It is in the process of implementing changes to internal controls, but has not yet completed implementing these changes. Failure to implement these changes to the Company’s internal controls or any others that it identifies as necessary to maintain an effective system of internal controls could harm its operating results and cause investors to lose confidence in the Company’s reported financial information. Any such loss of confidence would have a negative effect on the trading price of the Company’s stock.
 
Voting power of our shareholders is highly concentrated by insiders.
 
Our officers, directors and affiliates currently own approximately 38% of our outstanding common stock. Such concentrated control of the Company may adversely affect the value of our ordinary shares. If you acquire our ordinary shares, you may have no effective voice in our management. Sales by our insiders or affiliates, along with any other market transactions, could affect the value of our ordinary shares.
 
We do not intend to pay dividends for the foreseeable future.
 
We have paid no dividends on our Common Stock to date and it is not anticipated that any dividends will be paid to holders of our Common Stock in the foreseeable future. While our future dividend policy will be based on the operating results and capital needs of the business, it is currently anticipated that any earnings will be retained to finance our future expansion and for the implementation of our business plan. As an investor, you should take note of the fact that a lack of a dividend can further affect the market value of our stock, and could significantly affect the value of any investment in our Company.
 
Our articles of incorporation allow for our board to create a new series of preferred stock without further approval by our stockholders, which could adversely affect the rights of the holders of our Common Stock.
 
Our Board of Directors has the authority to fix and determine the relative rights and preferences of preferred stock. Our Board of Directors have the authority to issue up to 10,000,000 shares of our preferred stock terms of which may be determined by the Board without further stockholder approval. As a result, our Board of Directors could authorize the issuance of a series of preferred stock that would grant to holders the preferred right to our assets upon liquidation, the right to receive dividend payments before dividends are distributed to the holders of Common Stock and the right to the redemption of the shares, together with a premium, prior to the redemption of our Common Stock.
 
 
 
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In addition, our Board of Directors could authorize the issuance of a series of preferred stock that has greater voting power than our Common Stock or that is convertible into our Common Stock, which could decrease the relative voting power of our Common Stock or result in dilution to our existing stockholders. Although we have no present intention to issue any additional shares of preferred stock or to create any additional series of preferred stock, we may issue such shares in the future.
 
You may experience dilution of your ownership interests because of the future issuance of additional shares of common stock.
 
In the future, we may issue additional authorized but previously unissued equity securities, resulting in the dilution of the ownership interests of our shareholders. We may also issue additional shares of our securities that are convertible into or exercisable for Common Stock, as the case may be, in connection with hiring or retaining employees, future acquisitions, future sales of its securities for capital raising purposes, or for other business purposes. The future issuance of any such additional shares of Common Stock may create downward pressure on the value of our securities. There can be no assurance that we will not be required to issue additional shares of Common Stock, warrants or other convertible securities in the future in conjunction with any capital raising efforts, including at a price (or exercise prices) below the price at which our shares may be valued or are trading in a public market.
 
As an issuer of “penny stock," the protection provided by the federal securities laws relating to forward looking statements does not apply to us.
 
Although federal securities laws provide a safe harbor for forward-looking statements made by a public company that files reports under the federal securities laws, this safe harbor is not available to issuers of penny stocks. As a result, we will not have the benefit of this safe harbor protection in the event of any legal action based upon a claim that the material provided by us contained a material misstatement of fact or was misleading in any material respect because of our failure to include any statements necessary to make the statements not misleading. Such an action could hurt our financial condition.
 
Our issuance of Common Stock upon exercise of warrants or options may depress the price of our Common Stock.
 
As of December 31, 2015, we have 23,929,256 shares of Common Stock issued and outstanding and warrants to purchase 13,118,159 shares of Common Stock. The issuance of shares of Common Stock upon exercise of outstanding warrants or options could result in substantial dilution to our stockholders, which may have a negative effect on the price of our Common Stock.
 
We will incur increased costs as a result of operating as a public company, and our management will be required to devote substantial time to new compliance initiatives.
 
As a public company, we are incurring significant legal, accounting and other expenses that we did not incur as a private company. Since we are subject to the filing requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934 (the “Exchange Act”), as amended, we file reports with the Securities and Exchange Commission.  As a result, we file annual, quarterly and current reports with respect to our business and financial condition and establish and maintain effective disclosure and financial controls and corporate governance practices. Compliance with the Exchange Act and the rules and regulations under the Exchange Act have substantially increased our legal and financial compliance costs and made some activities more time-consuming and costly. Our management and other personnel devote a substantial amount of time to these compliance initiatives. For example, we expect that these rules and regulations may make it more difficult and more expensive for us to obtain director and officer liability insurance. We estimate that we will incur between $1 million and $2.5 million annually in expenses in response to these requirements.
 
If we take advantage of specified reduced disclosure requirements applicable to an "emerging growth company" under the JOBS Act, the information that we provide to stockholders may be different than they might receive from other public companies.
 
As a company with less than $1 billion in revenue during our last fiscal year, we qualify as an "emerging growth company" under the JOBS Act. As an emerging growth company, we may take advantage of specified reduced disclosure and other requirements that are otherwise applicable generally to public companies. These provisions include:
 
·  
Only two years of audited financial statements in addition to any required unaudited interim financial statements with correspondingly reduced "Management's Discussion and Analysis of Financial Condition and Results of Operations" disclosure;
·  
Reduced disclosure about our executive compensation arrangements;
·  
No non-binding advisory votes on executive compensation or golden parachute arrangements;
·  
Exemption from the auditor attestation requirement in the assessment of our internal control over financial reporting.

 
 
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We may take advantage of these exemptions for up to five years or such earlier time that we are no longer an emerging growth company. We would cease to be an emerging growth company if we have more than $1 billion in annual revenues, we have more than $700 million in market value of our stock held by non-affiliates, or we issue more than $1 billion of non-convertible debt over a three-year period. We may choose to take advantage of some but not all of these reduced burdens. We have not taken advantage of any of these reduced reporting burdens in this Report on Form 10-K, although we may choose to do so in future filings. If we do, the information that we provide stockholders may be different than you might get from other public companies in which you hold stock.
 
If we fail to maintain an effective system of internal control over financial reporting, we may not be able to accurately report our financial results or prevent fraud. As a result, stockholders could lose confidence in our financial and other public reporting, which would harm our business and the trading price of our common stock.
 
Effective internal controls over financial reporting are necessary for us to provide reliable financial reports and, together with adequate disclosure controls and procedures, are designed to prevent fraud. Any failure to implement required new or improved controls, or difficulties encountered in their implementation could cause us to fail to meet our reporting obligations. In addition, any testing by us conducted in connection with Section 404 of the Sarbanes-Oxley Act, or the subsequent testing by our independent registered public accounting firm, may reveal deficiencies in our internal controls over financial reporting that are deemed to be material weaknesses or that may require prospective or retroactive changes to our consolidated financial statements or identify other areas for further attention or improvement. Inferior internal controls could also cause investors to lose confidence in our reported financial information, which could have a negative effect on the trading price of our common stock.
 
We will be required to disclose changes made in our internal controls and procedures on a quarterly basis and our management will be required to assess the effectiveness of these controls annually. However, for as long as we are an “emerging growth company” under the JOBS Act, our independent registered public accounting firm will not be required to attest to the effectiveness of our internal controls over financial reporting pursuant to Section 404. We could be an emerging growth company for up to five years. An independent assessment of the effectiveness of our internal controls could detect problems that our management's assessment might not. Undetected material weaknesses in our internal controls could lead to financial statement restatements and require us to incur the expense of remediation.
 
FORWARD-LOOKING STATEMENTS
 
Statements contained in this Annual Report on Form 10-K may be “forward-looking statements.” Forward-looking statements include, but are not limited to, statements that express our intentions, beliefs, expectations, strategies, predictions or any other statements relating to our future activities or other future events or conditions. These statements are based on current expectations, estimates and projections about our business based, in part, on assumptions made by management. These statements are not guarantees of future performance and involve risks, uncertainties and assumptions that are difficult to predict. Therefore, actual outcomes and results may, and are likely to, differ materially from what is expressed or forecasted in the forward-looking statements due to numerous factors, including those described above and those risks discussed from time to time in this Annual Report on Form 10-K, including the risks described under “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operation” in this Annual Report on Form 10-K and in other documents which we file with the Securities and Exchange Commission. In addition, such statements could be affected by risks and uncertainties related to:
 
·  
our ability to raise funds for general corporate purposes and operations, including our clinical trials;
·  
the commercial feasibility and success of our technology;
·  
our ability to recruit qualified management and technical personnel;
·  
the success of our clinical trials;
·  
our ability to obtain and maintain required regulatory approvals for our products; and
·  
the other factors discussed in the “Risk Factors” section and elsewhere in this Annual Report on Form 10-K.

Any forward-looking statements speak only as of the date on which they are made, and except as may be required under applicable securities laws, we do not undertake any obligation to update any forward-looking statement to reflect events or circumstances after the date of this current report.
 
ITEM 1B. UNRESOLVED STAFF COMMENTS.
 
Not applicable.
 

 
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ITEM 2. PROPERTIES.
 
Our corporate headquarters is located at 5 Kineret Street, Bnei Brak, Israel 5126237, and the telephone number at such address is (972) 3 562-1755. Currently our corporate headquarters are located at the offices of our general counsel. We do not own or lease this office space and are provided access to these offices as needed. Because we are a small company, this space is adequate for our current needs. 

ITEM 3. LEGAL PROCEEDINGS.
 
We are not involved in any pending legal proceeding or litigations and, to the best of our knowledge, no governmental authority is contemplating any proceeding to which we are a party or to which any of our properties is subject, which would reasonably be likely to have a material adverse effect on us.

ITEM 4. MINE SAFETY DISCLOSURES.
 
Not applicable.
 

 
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PART II
 
ITEM 5. MARKET FOR REGISTRANT'S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES.
 
Our common stock is quoted under the symbol “CLCS” on the OTCQB. There has been no active trading of our common stock.
 
There was no reported trading in our common stock prior to March 13, 2014. Since March 13, 2014, there has been limited trading in our common stock. The following table sets forth the range of high and low bid prices of our common stock as reported and summarized on the OTCQB for the periods indicated. These prices are based on inter-dealer bid and asked prices, without markup, markdown, commissions, or adjustments and may not represent actual transactions.
 
2015 Fiscal Year 
 
   
High
   
Low
 
             
First Quarter ended March 31, 2015
  $ 1.35     $ 0.20  
Second Quarter ended June 30, 2015
  $ 1.60     $ 0.73  
Third Quarter ended September 30, 2015
  $ 1.39     $ 1.00  
Fourth Quarter ended December 31, 2015
  $ 1.60     $ 1.05  
 
2014 Fiscal Year 
 
   
High
   
Low
 
             
First Quarter ended March 31, 2014
  $ 0.10 ***   $ 0.10 ***
Second Quarter ended June 30, 2014
  $ 3.50     $ 0.10  
Third Quarter ended September 30, 2014
  $ 2.00     $ 0.75  
Fourth Quarter ended December 31, 2014
  $ 0.95     $ 0.32  
 
*** There was no reported trading in our common stock prior to March 13, 2014
 
Transfer Agent
 
Our transfer agent is Globex Transfer, LLC, 780 Deltona Blvd., Suite 202, Deltona, FL 32725.

Holders
 
As of April 8, 2016, there were 104 holders of record of our common stock.
 
Dividends
 
We have never declared or paid any cash dividends on our common stock. We currently intend to retain future earnings, if any, to finance the expansion of our business. As a result, we do not anticipate paying any cash dividends in the foreseeable future.
 
Warrants
 
As of December 31, 2015, we had warrants to purchase an aggregate of 13,118,159 shares of common stock outstanding with a weighted average exercise price of $0.63 per share.
 
Securities Authorized for Issuance Under Equity Compensation Plans
 
Equity Compensation Plan Information
 
As of the date of the filing of this Annual Report on Form 10-K, we do not have any equity compensation plan.
 
Sales of Unregistered Securities
 
In 2015 and through March 2016, the Company held several closings under a Subscription Agreement (the “Bridge Note Subscription Agreement”) entered into by the Company and various accredited investors (the “Purchasers”). The Company closed on an aggregate of $722,500 of convertible promissory notes (the “Notes”) to the Purchasers. The Notes are convertible into Common Stock at the option of the Purchasers and are also subject to automatic conversion upon the occurrence of: (i) the closing of an offering of equity securities pursuant to which the Company receives an aggregate amount of funds totaling $5,000,000 or more (a “Qualified Financing”); (ii) the closing of  a transaction (including but not limited to the Company’s entry into a joint venture or partnership agreement or the sublicensing of the Company’s intellectual property) pursuant to which the Company receives or expects to receive a total aggregate of at least $4,000,000 (a “Strategic Transaction”); or (iii) eighteen (18) months from the date of Note issuance (the “Maturity Date”). The Notes bear an interest rate of 10% per annum, which becomes payable on the Maturity Date.
 
 
 
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In addition, upon automatic conversion of the Notes, following a Qualified Financing or Strategic Transaction, the holders shall receive five-year warrants to purchase that number of shares of common stock into which the Notes are convertible and such warrants shall have an exercise price equal to one hundred ten percent (110%) of the per-share common stock price underlying them, at which the Company sells its securities in the Qualified Financing or $0.825 in the case of a Strategic Transaction. In the event of conversion upon the Maturity Date, the conversion price of the Notes shall be equal to the quotient obtained by dividing $15 million by the aggregate number of outstanding shares of the Company’s Common Stock, measured on a fully-diluted basis, on the date immediately preceding the Maturity date. Furthermore, upon automatic conversion due to the Maturity date, the holders shall receive five-year warrants to purchase the number of common shares into which the Notes are convertible and such warrants shall have a conversion price equal to the Maturity Conversion Price.

The net proceeds from the Private Placement were used for general corporate purposes. The Company relied on the exemption from registration under Section 4(a)(2) of the Securities Act or Rule 506 of Regulation D for purposes of the Private Placement.

The foregoing description of the terms of the Bridge Note Subscription Agreement and the Notes does not purport to be complete and is subject to, and qualified in its entirety by reference to the Bridge Note Subscription Agreement and the Notes which are filed herewith as Exhibit 10.29 and Exhibit 10.30, and are incorporated herein by reference.

On October 7, 2015, the Company issued one-year convertible notes payable in the aggregate principal amount of $250,000. The notes bear interest at a rate of 6% per annum. For a period of fifteen (15) business days beginning on the maturity date, at the option of the holder, the principal and any accrued and unpaid interest may be converted into common stock at a conversion price of $0.75 per share. In consideration of the loans, an aggregate of 250,000 shares of common stock were issued by the Company to the purchasers of the notes payable.

On November 10, 2015, the Company issued warrants to purchase an aggregate of 2,400,000 shares of common stock at an exercise price of $0.75 per share to certain founders of Cell Source Limited. The warrants expire on November 10, 2019.

Issuer Purchases of Equity Securities
 
None.
 
ITEM 6.  SELECTED FINANCIAL DATA.
 
Not applicable. 
 
ITEM 7. MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS.
 
This Management Discussion and Analysis (“MD&A”) contains “forward-looking statements," which represent our projections, estimates, expectations or beliefs concerning among other things, financial items that relate to management’s future plans or objectives or to our future economic and financial performance. In some cases, you can identify these statements by terminology such as “may,” “should,” “plans,” “believe,” “will,” “anticipate,” “estimate,” “expect,” “project” or “intend,” including their opposites or similar phrases or expressions.
 
You should be aware that these statements are projections or estimates as to future events and are subject to a number of factors that may tend to influence the accuracy of the statements. These forward-looking statements should not be regarded as a representation by the Company or any other person that the events or plans of the Company will be achieved. You should not unduly rely on these forward-looking statements, which speak only as of the date of this MD&A. Except as may be required under applicable securities laws, we undertake no obligation to publicly revise any forward-looking statement to reflect circumstances or events after the date of this MD&A or to reflect the occurrence of unanticipated events. You should, however, review the factors and risks we describe under “Risk Factors” in this Annual Report on Form 10-K. Actual results may differ materially from any forward looking statement.

 
 
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Overview
 
Our wholly-owned subsidiary, Cell Source Israel was founded in 2011 as a privately held company located in Tel Aviv, Israel. Our business is based on over ten (10) years of prominent research at the Weizmann Institute, the commercial arm of Yeda, from whom we license patented technology. Our exclusive, world-wide license provides us with access to certain discoveries, inventions and other intellectual property generated by Dr. Reisner, formerly Head of the Immunology Department at the Weizmann Institute, together with others. Dr. Reisner leads a team at the Weizmann Institute to continue the development of these technologies in order to facilitate the transition of those technologies from the laboratory to clinical trials. Our Scientific Advisory Board is chaired by Dr. Terry Strom, Professor of Medicine and Surgery at Harvard Medical School and Director of The Transplant Institute at Beth Israel Deaconess Medical Center, the founding President of the American Society of Transplantation, from which he received a Lifetime Achievement Award, and past President of the Clinical Immunology Society.  Its other members include Dr. Robert Negrin, Director of Bone and Marrow Transplantation and Professor of Medicine at Stanford University who is a past President of the American Society of Bone and Marrow Transplantation and the International Society of Cellular Therapy; Dr. Steven Burakoff, Director of the Tisch Cancer Institute at Mount Sinai Medical Center, Professor of Cancer Medicine at the Icahn School of Medicine, past Professor of Medicine at Harvard Medical School and Director of the NYU Cancer Institute, who won the American Association of Immunologists Lifetime Achievement Award; Dr. Herman Waldman, Department Head and Professor Emeritus of Pathology and Head of the Therapeutic Immunology Group at Oxford Medical School, former Cambridge  Immunology Professor and SCRIP Lifetime Achievement Award winner; and Dr. Hermann Einsele, Professor and Director of Internal Medicine at Julius Maximilian University, Würzburg, Germany, a former visiting professor at the Fred Hutchinson Cancer Research Center in Seattle, Director of the German and member of the European Blood and Marrow Transplantation Groups.
 
Our lead prospective product is our patented Veto Cell immune system management technology, which is an immune tolerance biotechnology that enables the selective blocking of immune responses. The Company’s target indications include: lymphoma, multiple myeloma and BCLL (a form of leukemia), facilitating transplantation acceptance (initially bone -marrow transplantation and subsequently organ transplantation), and ultimately treating a variety of non-malignant diseases.
 
Cell Source, under its exclusive license with Yeda Research & Development Ltd., commercial arm of the Weizmann Institute of Science, has recently filed two new provisional patent applications that extend the usage of Veto Cell technology as a critical enabler for other cell therapy treatments. One patent application highlights, based on preclinical data, the ability of Veto Cells to accompany other cell therapy treatments and help them overcome rejection and avoid Graft vs. Host Disease (GvHD) in an allogeneic (using a third party donor) treatment setting. The other patent application involves a genetically modified Veto Cell that can have sustained survival in the patient’s body while avoiding rejection and GvHD. This second application holds the potential to make CAR-T cells, which to date been effective primarily in an autologous (patient’s own cells) setting, succeed in an allogeneic setting.
 
Cell Source is actively exploring collaborations with larger biopharmaceutical firms where Veto Cell technology can significantly enhance the efficacy of cell therapy treatments for a variety of indications. This may allow Cell Source to complement the development of its own treatment candidates with parallel development with partners, thus multiplying the potential impact of this technology in the clinic.
 
Prior to commercializing its products, the Company must conduct human clinical trials and obtain FDA approval and/or approvals from comparable foreign regulatory authorities.
 
Generally speaking, as a preclinical biotechnology firm, Cell Source needs to go through several necessary steps in order to commercialize its products and commence revenue generation. These steps are per product, but can run in parallel for multiple products, which are each in different stages of the development “pipeline”, so that, for example, when a certain product is already in a human clinical trial, another product may still be in preclinical development and a third may be awaiting regulatory approval to commence human trials. These can also take place in parallel, and varied stages, for the same product in different geographic jurisdictions. The typical steps per product (and range of time frame for each) are: 
 
 
1.
Complete development of human treatment protocol (2-5 years)
 
2.
Apply for and receive approval to commence human trials (9-18 months)
 
3.
Recruit patients (1-6 months)
 
4.
Conduct Phase I trials showing safety of product (1-2 years)
 
5.
Apply for and receive approval to conduct trials showing product efficacy (6-12 months)
 
6.
Data collecting and analysis (6-12 months)
 
7.
Conduct Phase II efficacy trials (2-3 years)
 
8.
Data collecting and analysis (6-12 months)
 
9.
Apply for and receive approval to conduct trials showing efficacy in larger numbers of patients (6-12 months)
 
10.
Conduct Phase III efficacy trials with larger numbers of patients (2-4 years)
 
11.
Data collecting and analysis (6-12 months)
 
12.
Apply for and receive approval for production scale manufacturing facilities (6-12 months)

 
 
47

 

 
13.
Contract third party or establish own production facilities (6-30 months)
 
14.
Contract third party or establish own distribution platform (6-18 months)
 
15.
Commence manufacturing and distribution (6-12 months)
 
Please note that steps 12-15 can be conducted in parallel with some of the steps above. In the case of Cell Source and other firms that treat terminal patients with either rare diseases or those for which there is currently no effective treatment, or where preclinical studies indicate a reasonable expectation to increase life expectancy and survival rates by a substantive margin, several of these steps can be combined and or shortened, subject to regulatory discretion. For example, Phase I and II (safety and efficacy) can be combined in a single concurrent step; approvals for subsequent steps can be accelerated; in some countries patients can already be treated commercially after the end of Phase II, foregoing the requirement for Phase III data as a prerequisite.
 
Although we have provided estimated timeframes for each step above, no assurances can be made that such timeframes are accurate or that they would not be delayed for one or more reasons. At any stage of a human clinical trial, there could be problems with either safety or efficacy of treatment. In these instances the Company could be required to reformulate the treatment and proceed with additional patients, which could involve a delay of months or years, depending on whether we would have to seek approval from the very beginning of the approval process. There can also be a delay of up to 1 to 2 years between phases of a human clinical trial, as the regulator may wish to take additional time to review the approval of a subsequent stage. Furthermore, if a significant modification to the treatment is required, the application process begins again from the very first stage. If the treatment is not effective at all or if it’s harmful to patients, even after modifications are made, it is possible that the trials may be halted completely and the product candidates permanently withdrawn. While the timescales presented here are representative of the typical experience, there is no assurance that there will not be significant delays at any stage or step in the process or a complete failure of trials.
 
The specific detailed next steps the company must take to get the treatments or products to market include the following:
  
We have not submitted any drug applications to the FDA and do not have anything pending for approval with the FDA. Cell Source itself has not had any contact with any regulator anywhere regarding treatment approvals or clinical trials associated with regulatory approvals. We are aware that a hospital in Italy in May, 2014 independently requested and in September, 2014 received approval to conduct a trial with the same protocol that we plan to use, but we are not mentioned in the application nor in the approval. However, we may indirectly benefit from the outcome of the trial, if successful, although we are not the sponsor of this trial. There are no written or verbal agreements between the hospital and Cell Source regarding the use of the technology. That said, Cell Source is aware and in favor of the hospital plans to use the technology and would of course find a positive initial outcome encouraging. Since the treatment is being done on compassionate grounds as a non-commercial clinical trial, there is no legal requirement for the hospital to obtain approval to use the treatment protocol. The hospital has successfully treated a cancer patient using the Megadose Drug Combination technology that Cell Source exclusively licenses from Yeda Research & Development Ltd., commercial arm of the Weizmann Institute of Science.  While Cell Source is not a sponsor of the trial, the results provide a positive initial indication with respect to the technology. The patient received a bone marrow transplantation from a haploidentical or “mismatched” donor under a reduced intensity conditioning regimen (i.e., a relatively low level of immune suppression treatment). There was successful initial engraftment of the transplantation in the absence of GVHD.
 
For the Veto Cell application for reducing rejection in Bone Marrow Transplants, Cell Source expects to commence Phase I/II human clinical studies in Italy, Germany and the US starting sometime in 2017.  Cell Source anticipates that Phase I/II studies will last until 2019 or 2020. These would be followed by completion of Phase II and Phase III, which would last another 2-3 years each, so that full approval, if successful, would be expected sometime in 2025. In Germany there is a possibility of approval for commercial use on a “compassionate grounds” basis at the end of Phase II, which could take place by 2023. In the US, Cell Source plans to commence the IND approval process with the FDA in 2016, which could last until between 2021 and 2024. Cell Source also aspires to enter into a collaboration with respect to combining CAR-T cell therapy with Veto Cell therapy and commence pre-clinical proof of concept trials in 2016. If successful, this could lead to a commencement of a combined FDA trail in 2017 or 2018 and could last until 2025 or 2026.

It is possible that Cell Source treatments could qualify for any or all of Fast Track, Breakthrough Therapy, Accelerated Approval and Priority Review designation under the FDA, which would hasten their approval if successful.

The costs for each step of development, in terms of clinical trials, are delineated below:
 
Cell Source estimates the cost of clinical trials alone to be up to $5-10 million in each of the coming two years and another $25-50 million in order to reach commercialization for both the Anti-rejection  Veto Cell and the Veto Cell + CAR-T cell products. This would mean that Cell Source will need to secure one or more significant capital infusions in order to reach the point that meaningful revenues could be generated.
 
Cell Source will require additional financing for any and all of the steps described above.

 
 
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Recent Developments
 
On October 7, 2015, the Company issued one-year convertible notes payable in the aggregate principal amount of $250,000. The notes bear interest at a rate of 6% per annum. For a period of fifteen (15) business days beginning on the maturity date, at the option of the holder, the principal and any accrued and unpaid interest may be converted into common stock at a conversion price of $0.75 per share. In consideration of the loans, an aggregate of 250,000 shares of common stock, with an aggregate issuance date value of $71,400, were issued by the Company to the purchasers of the notes payable and were recorded as a debt discount with a corresponding credit to equity. In connection with the Company’s sequencing policy, the conversion options of the notes, with an aggregate issuance date value of $600, were determined to be derivative liabilities.

From November 2015 to March 2016, the Company closed on an aggregate of $722,500 in principal amount of convertible notes to investors, which are payable eighteen (18) months from the date of issuance (the “Maturity Date”) and bear interest at a rate of 10% per annum (the “10% Convertible Notes”). The 10% Convertible Notes shall be automatically converted into shares of the Company’s common stock upon the earlier of (i) the closing of an offering of equity securities pursuant to which the Company receives an aggregate of at least $5,000,000 in gross proceeds (“Qualified Financing”); (ii) the closing of a strategic transaction (including but not limited to the Company’s entry into a joint venture or partnership agreement or the sublicensing of the Company’s intellectual property) pursuant to which the Company, directly or indirectly, receives, or expects to receive within eighteen months, cash, assets or other consideration with a total aggregate value of at least $4,000,000 (“Strategic Transaction”); or (iii) the Maturity Date of the 10% Convertible Notes. In the event the 10% Convertible Notes are converted upon the occurrence of a Qualified Financing (the “QF Conversion Shares”), the conversion price of the 10% Convertible Notes shall be the lesser of (i) seventy percent (70%) of the price per share or per unit (assuming the unit includes one share of common stock or the price per unit divided by the number of shares of common stock underlying such unit) at which the Company sells its securities in a Qualified Financing; or (i