Fate Therapeutics Reports Fourth Quarter 2019 Financial Results and Operational Progress with 2020 Outlook
Reported Initial Clinical Data from FT500 Phase 1 Study in Advanced Solid Tumors, Supporting Safety and Tolerability of Multi-dose Treatment Paradigm for Off-the-shelf, iPSC-derived NK Cells
First Patients Treated with FT516, the First-ever Engineered iPSC-derived Cellular Immunotherapy, for AML and for B-cell Lymphoma in Combination with Rituximab
Initiated Enrollment of First-in-human Clinical Trial of FT596, the First-ever Cellular Immunotherapy Engineered with Three Active Anti-tumor Modalities
“In 2019, we made tremendous progress in pioneering the clinical development of off-the-shelf, iPSC-derived cancer immunotherapy. Our FT500 program demonstrated that multiple doses of iPSC-derived NK cells can be delivered off-the-shelf to a patient in a safe manner without patient matching. Additionally, our FT516 program provided initial clinical evidence that engineered iPSC-derived NK cells may confer anti-tumor activity and deliver clinically meaningful benefit to patients. We also showed the unmatched scalability of our proprietary iPSC product platform, having manufactured hundreds of cryopreserved, infusion-ready doses of our iPSC-derived NK cell product candidates at a low cost per dose in our new GMP manufacturing facility,” said
- Encouraging Safety, Tolerability and Immunogenicity Data from FT500 Phase 1 Study Announced. In December, the Company reported initial clinical data from the dose-escalation stage of the FT500 Phase 1 study for the treatment of advanced solid tumors as of a
November 28, 2019data cutoff (n=8 monotherapy; n=4 in combination with checkpoint inhibitor therapy). The multi-dose treatment course, consisting of three once-weekly doses of FT500 over up to two 30-day cycles, was well-tolerated, and there were no dose-limiting toxicities, no FT500-related Grade ≥3 adverse events (AEs) or serious adverse events (SAEs), and no incidents of cytokine release syndrome, neurotoxicity, or graft-versus-host disease, reported in the 12 patients. Additionally, based on assessments of the patients’ T-cell compartment and antibody repertoire, an adverse immune response against FT500 was not evident over the multi-dose treatment course. The Company has amended the FT500 clinical protocol to include IL-2 administration to support NK cell activity, and is initiating the dose-expansion stage of the FT500 Phase 1 study in patients who are refractory to, or have relapsed following, checkpoint inhibitor therapy at 300 million cells per dose in combination with the checkpoint inhibitor on which the patient failed or progressed.
- Initial Patients Treated with FT516, the First-ever Engineered, iPSC-derived Cellular Immunotherapy. In December, the Company announced that the first two patients were treated with FT516, the Company’s off-the-shelf NK cell cancer immunotherapy derived from a clonal master iPSC line engineered to express a novel high-affinity, non-cleavable CD16 (hnCD16) Fc receptor. Each patient received three once-weekly doses of FT516 over a 30-day cycle, and there were no FT516-related Grade ≥3 adverse events (AEs) or serious adverse events (SAEs), and no incidents of cytokine release syndrome, neurotoxicity, or graft-versus-host disease, reported by investigators. Each patient was eligible to receive a second 30-day cycle of three once-weekly doses of FT516. The FT516 study is an open-label, multi-dose Phase 1 clinical trial as a monotherapy for the treatment of AML and in combination with CD20-directed monoclonal antibodies for the treatment of advanced B-cell lymphoma.
- FT516 Clinical Investigation Expanded to Solid Tumors. In January, the Company announced that the
U.S. Food and Drug Administration(FDA) allowed its second IND application for FT516, enabling clinical investigation of FT516 in combination with PDL1-, PD1-, EGFR- and HER2-targeting monoclonal antibody (mAb) therapies across a broad range of solid tumors. The Company intends to initially evaluate FT516 in combination with avelumab in patients with advanced solid tumors who are refractory to, or have relapsed following, at least one line of anti-PDL1 mAb therapy. The multi-dose treatment course consists of three once-weekly doses of FT516 over up to two 30-day cycles.
- Patient Enrollment Initiated in FT596 Phase 1 Study for Advanced B-cell Malignancies. The Company is currently conducting an open-label Phase 1 clinical trial of FT596, the Company’s first off-the-shelf, iPSC-derived chimeric antigen receptor (CAR) NK cell cancer immunotherapy and the first cellular immunotherapy engineered with three active anti-tumor modalities, to be cleared for clinical investigation by the FDA. In addition to a proprietary CAR targeting CD19, FT596 expresses a hnCD16 Fc receptor for coincident targeting of additional tumor-associated antigens expressed on cancer cells, such as CD20, to overcome antigen escape. FT596 also expresses an interleukin-15 receptor fusion (IL-15RF), a potent cytokine complex that promotes survival, proliferation and trans-activation of NK cells and CD8 T cells without the need for systemic cytokine support.
- FT596 Clinical Supply Successfully Produced in Newly-launched, In-house GMP Facility. In preparation for Phase 1 initiation, the Company produced over 300 cryopreserved, infusion-ready doses of FT596, at a low cost per dose, in its newly-launched Good Manufacturing Practice (GMP) facility. FT596 met stringent release criteria, and the cryopreserved, infusion-ready doses demonstrate robust cell viability and potency, and exhibit high levels of cell-surface expression of both CAR19 and hnCD16 targeting receptors, upon thaw. The Company’s GMP facility, located in
San Diego, California, is custom designed to use clonal master iPSC lines as a renewable cell source for the consistent and scaled manufacture of off-the-shelf NK cell and CAR T-cell products.
- IND-enabling Data Presented for FT538, the First CRISPR-edited, iPSC-derived Cellular Immunotherapy. At the 2019
American Society of Hematology(ASH) Annual Meeting in December, the Company presented preclinical data for FT538, the Company’s off-the-shelf NK cell cancer immunotherapy for multiple myeloma. FT538 is derived from a clonal master iPSC line engineered with hnCD16 and IL-15RF, and edited for complete elimination of CD38 expression to mitigate anti-CD38 antibody-mediated fratricide. The Company intends to submit an IND application to the FDA for clinical investigation of FT538 in combination with anti-CD38 mAb therapy in the second quarter of 2020.
- FT819 Master Engineered iPSC Bank Generated and Fully Characterized. FT819 is the Company’s first off-the-shelf, iPSC-derived CAR T-cell product candidate, and is derived from a clonal master engineered iPSC line engineered with a novel 1XX CAR targeting CD19 inserted into the T-cell receptor alpha constant (TRAC) locus, and edited for complete elimination of T-cell receptor (TCR) expression. At ASH, scientists from the Company and
Memorial Sloan Kettering Cancer Centerpresented new in vivo preclinical data demonstrating that, in a xenograft model of disseminated lymphoblastic leukemia, FT819 enhanced tumor clearance and extended survival as compared to primary CAR19 T cells. The Company intends to submit an IND application to the FDA for clinical investigation of FT819 in the second quarter of 2020.
Fourth Quarter 2019 Financial Results
- Cash & Investment Position: Cash, cash equivalents and investments as of
December 31, 2019were $260.9 million, compared to $201.0 millionas of December 31, 2018. The increase was driven primarily by $162.4 millionin net cash proceeds received by the Company from its September 2019public offering of common stock. These proceeds were offset by the Company’s use of cash to fund operating activities and to fully retire its debt facility.
- Total Revenue: Revenue was
$2.8 millionfor the fourth quarter of 2019, compared to $1.7 millionfor the same period in 2018. Revenue for the fourth quarter of 2019 was derived from the Company’s collaboration with Ono Pharmaceutical.
- R&D Expenses: Research and development expenses were
$25.2 millionfor the fourth quarter of 2019, compared to $14.1 millionfor the same period in 2018. The increase in R&D expenses was attributable primarily to an increase in employee compensation, including share-based compensation, and in expenses associated with the clinical development and manufacture of the Company’s product candidates and the conduct of research activities, including under the collaboration with Ono Pharmaceutical.
- G&A Expenses: General and administrative expenses were
$6.7 millionfor the fourth quarter of 2019, compared to $4.3 millionfor the same period in 2018. The increase in G&A expenses was attributable primarily to an increase in employee compensation, including share-based compensation.
- Shares Outstanding: Common shares outstanding were 75.7 million as of
December 31, 2019and 64.7 million as of December 31, 2018. Preferred shares outstanding as of December 31, 2019and December 31, 2018were 2.8 million, each of which is convertible into five shares of common stock.
Today's Conference Call and Webcast
The Company will conduct a conference call today,
About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that can be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with cycles of other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely capable of overcoming numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 300 issued patents and 150 pending patent applications.
FT500 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line. The product candidate is being investigated in an open-label, multi-dose Phase 1 clinical trial for the treatment of advanced solid tumors (NCT03841110). The study is designed to assess the safety and tolerability of three once-weekly doses of FT500 as a monotherapy and in combination with one of three FDA-approved immune checkpoint inhibitor (ICI) therapies – nivolumab, pembrolizumab or atezolizumab – in patients that have failed prior ICI therapy. Despite the clinical benefit conferred by approved ICI therapy against a variety of tumor types, these therapies are not curative and, in most cases, patients either fail to respond or their disease progresses on these agents. One common mechanism of resistance to ICI therapy is associated with loss-of-function mutations in genes critical for antigen presentation. A potential strategy to overcome resistance is through the administration of allogeneic NK cells, which have the inherent capability to recognize and directly kill tumor cells with these mutations.
FT516 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to express a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies. CD16 mediates antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. ADCC is dependent on NK cells maintaining stable and effective expression of CD16, which has been shown to undergo considerable down-regulation in cancer patients. In addition, CD16 occurs in two variants, 158V or 158F, that elicit high or low binding affinity, respectively, to the Fc domain of IgG1 antibodies. Numerous clinical studies with FDA-approved tumor-targeting antibodies, including rituximab, trastuzumab and cetuximab, have demonstrated that patients homozygous for the 158V variant, which is present in only about 15% of patients, have improved clinical outcomes. FT516 is being investigated in an open-label, multi-dose Phase 1 clinical trial as a monotherapy for the treatment of acute myeloid leukemia and in combination with CD20-directed monoclonal antibodies for the treatment of advanced B-cell lymphoma (NCT04023071). Additionally, the FDA has allowed investigation of FT516 in an open-label, multi-dose Phase 1 clinical trial in combination with monoclonal antibody therapy, including PDL1-, PD1-, EGFR- and HER2-targeting therapeutic antibodies, across a broad range of solid tumors.
FT596 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with three anti-tumor functional modalities: a proprietary chimeric antigen receptor (CAR) optimized for NK cell biology, which contains a NKG2D transmembrane domain, a 2B4 co-stimulatory domain and a CD3-zeta signaling domain, that targets B-cell antigen CD19; a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; and an IL-15 receptor fusion (IL-15RF) that promotes enhanced NK cell activity. In preclinical studies of FT596, the Company has demonstrated that dual activation of the CAR19 and hnCD16 targeting receptors, in combination with IL-15RF signaling, convey synergistic anti-tumor activity. Increased degranulation and cytokine release were observed upon dual receptor activation in lymphoma cancer cells as compared to activation of each receptor alone, indicating that multi-antigen engagement may elicit a deeper and more durable response. Additionally, in a humanized mouse model of lymphoma, FT596 in combination with the anti-CD20 monoclonal antibody rituximab showed enhanced killing of tumor cells in vivo as compared to rituximab alone. FT596 is being investigated in an open-label Phase 1 clinical trial as a monotherapy, and in combination with rituximab, for the treatment of advanced B-cell lymphoma and in combination with obinutuzumab for the treatment of chronic lymphocytic leukemia (NCT04245722).
This release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 including statements regarding the Company’s results of operations, financial condition and sufficiency of its cash and cash equivalents to fund its operations, as well as statements regarding the advancement of and plans related to its product candidates, clinical studies and preclinical research and development programs, the Company’s progress, plans and timelines for the manufacture and clinical investigation of its product candidates, the timing for the Company’s receipt of data from its clinical trials and preclinical studies, the Company’s development and regulatory strategy, and the therapeutic and market potential of the Company’s product candidates. These and any other forward-looking statements in this release are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that results observed in prior studies of the Company’s product candidates, including preclinical studies and clinical trials, will not be observed in ongoing or future studies involving these product candidates, the risk of a delay or difficulties in the manufacturing of the Company’s product candidates or in the initiation of, or enrollment of patients in, any clinical studies, the risk that the Company may cease or delay preclinical or clinical development of any of its product candidates for a variety of reasons (including requirements that may be imposed by regulatory authorities on the initiation or conduct of clinical trials or to support regulatory approval, difficulties or delays in patient enrollment in current and planned clinical trials, difficulties in manufacturing or supplying the Company’s product candidates for clinical testing, and any adverse events or other negative results that may be observed during preclinical or clinical development), and the risk that the Company’s expenditures may exceed current expectations for a variety of reasons. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Company’s actual results to differ from those contained in the forward-looking statements, see the risks and uncertainties detailed in the Company’s periodic filings with the
Availability of Other Information about
Investors and others should note that the Company routinely communicates with investors and the public using its website (www.fatetherapeutics.com) and its investor relations website (ir.fatetherapeutics.com) including, without limitation, through the posting of investor presentations,
Condensed Consolidated Statements of Operations and Comprehensive Loss
(in thousands, except share and per share data)
|Three Months Ended||Year Ended|
|December 31,||December 31,|
|Research and development||25,209||14,095||87,770||56,024|
|General and administrative||6,671||4,307||23,637||15,808|
|Total operating expenses||31,880||18,402||111,407||71,832|
|Loss from operations||(29,078||)||(16,741||)||(100,727||)||(67,092||)|
|Other income (expense):|
|Total other income, net||776||714||2,578||494|
|Other comprehensive income (loss):|
|Unrealized gain (loss) on available-for-sale securities, net||(29||)||12||24||1|
|Net loss per common share, basic and diluted||$||(0.37||)||$||(0.25||)||$||(1.44||)||$||(1.19||)|
|Weighted–average common shares used to
compute basic and diluted net loss per share
Condensed Consolidated Balance Sheets
|December 31,||December 31,|
|Cash and cash equivalents||$||99,814||$||190,514|
|Short-term investments and related maturity receivables||121,613||10,493|
|Prepaid expenses and other current assets||5,662||3,689|
|Total current assets||227,089||205,196|
|Operating lease right-of-use asset||22,752||—|
|Other long-term assets||12,993||7,836|
|Liabilities and stockholders’ equity|
|Accounts payable and accrued expenses||$||20,519||$||15,131|
|Deferred revenue, current portion||2,787||7,588|
|CIRM award liability, current portion||2,808||2,106|
|Operating lease liability, current portion||1,692||—|
|Long-term debt, current portion||—||2,438|
|Total current liabilities||27,806||27,263|
|Deferred revenue, net of current portion||3,775||7,500|
|CIRM award liability, net of current portion||702||1,404|
|Operating lease liability, net of current portion||25,235||—|
|Long-term debt, net of current portion||—||12,446|
|Other long-term liabilities||—||3,950|
|Total liabilities and stockholders’ equity||$||302,274||$||213,032|
Stern Investor Relations, Inc.
Source: Fate Therapeutics, Inc.