On February 28, 2023 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to bringing a first-in-class pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies to patients with cancer and autoimmune disorders, reported business highlights and financial results for the fourth quarter and full year ended December 31, 2022 (Press release, Fate Therapeutics, FEB 28, 2023, View Source [SID1234627841]).
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"We have focused our operations on advancing our most innovative and differentiated programs for patients with cancer and autoimmune disorders, and we have substantially reduced our expenses with the intent of providing the necessary cash runway to achieve key clinical milestones across our multiplexed-engineered, iPSC-derived CAR NK and CAR T-cell product candidates," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "We are now enrolling multi-dose treatment cohorts with FT576 for multiple myeloma, including in combination with CD38-targeted monoclonal antibody therapy to promote dual-antigen targeting and selective depletion of activated host immune cells. We also plan to submit an IND application in the middle of 2023 for FT522, which incorporates our proprietary ADR technology designed to enable patient dosing with reduced conditioning chemotherapy, and intend to initiate clinical development in B-cell lymphoma with plans to expand clinical investigation to severe autoimmune disorders. In addition, we are excited with the progress of our iPSC-derived CAR T-cell pipeline for the treatment of hematologic malignancies and solid tumors. Dose escalation is continuing in our landmark Phase 1 study of FT819, with interim clinical data showing a favorable safety profile and demonstrating complete responses in heavily pre-treated patients with aggressive B-cell lymphoma. Finally, we plan to submit an IND application in 2023 for FT825/ONO-8250 under our collaboration with ONO Pharmaceutical, which incorporates seven novel synthetic controls designed to more effectively attack solid tumors."
NK Cell Programs
Multi-dose Treatment Cohorts Enrolling in FT576 Phase 1 Study for Multiple Myeloma. At the 2022 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December, the Company presented interim Phase 1 clinical data from the first nine patients treated with a single dose of FT576, its multiplexed-engineered, BCMA-targeted chimeric antigen receptor (CAR) NK cell product candidate for relapsed / refractory multiple myeloma. Clinical data from the single-dose treatment cohorts in heavily pre-treated patients (median of 5 prior lines of therapy; range 3-10) showed encouraging clinical evidence of BCMA-targeted activity and a favorable safety profile indicating the potential for administration in the outpatient setting. Of the six patients treated with a single dose of FT576 as monotherapy (n=3 at 100 million cells; n=3 at 300 million cells), one patient treated at 300 million cells who was triple-refractory and had received five prior lines of therapy achieved a very good partial response (VGPR). In addition, three patients were treated with a single dose of FT576 at 100 million cells in combination with CD38-targeted monoclonal antibody (mAb) therapy to promote dual-antigen targeting of plasma cells, with one patient achieving a partial response (PR). Notably, translational data from the single-dose combination cohort showed rapid and selective depletion of CD38-positive patient immune cells through the first month of therapy, suggesting that CD38-targeted mAb therapy may also serve as a conditioning agent to potentially mitigate the risk of rejection of FT576. The Company is currently enrolling two-dose treatment cohorts as monotherapy and in combination with CD38-targeted mAb therapy at 300 million cells per dose and, upon clearance, the Company plans to open and assess three-dose treatment cohorts starting at 1 billion cells per dose.
IND Submission Planned in Mid-2023 for FT522 CD19-targeted CAR NK Cell Program. The Company has leveraged its unique ability to create multiplexed-engineered iPSC lines in its development of FT522, a next-generation CD19-targeted CAR NK cell program incorporating five novel synthetic controls of cell function designed to increase NK cell potency, enhance functional persistence, and reduce or eliminate the need to administer conditioning chemotherapy to patients. FT522 is the first product candidate to incorporate the Company’s proprietary alloimmune defense receptor (ADR) technology for which the Company presented preclinical data at the 2022 ASH (Free ASH Whitepaper) Annual Meeting in December demonstrating that ADR-armed, iPSC-derived CAR NK cells have the potential to proliferate, functionally persist, and durably kill tumor cells while resisting rejection by allo-reactive immune cells. Overall, the novel synthetic controls integrated into FT522 have the potential to significantly improve safety and clinical benefit, facilitate ease of combination with standard-of-care regimens including CD20- and CD38-targeted mAb therapy, and enable use in the treatment of B-cell lymphoma, multiple myeloma, and severe autoimmune disorders. The Company intends to submit an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) in mid-2023 to commence a Phase 1 study of FT522 in combination with CD20-targeted mAb therapy for the treatment of B-cell lymphoma, including without administration of intensive conditioning chemotherapy to patients.
T-cell Programs
Dose Escalation Continuing in FT819 Phase 1 Study for B-cell Malignancies. The landmark clinical trial is the first-ever clinical investigation of a T-cell product candidate manufactured from a clonal master iPSC line. FT819 incorporates several first-of-kind features including the integration of a novel CD19-targeted 1XX CAR construct into the T-cell receptor alpha constant (TRAC) locus, which is intended to promote uniform CAR expression, enhance T-cell potency, and prevent graft-versus-host disease. At the 2022 ASH (Free ASH Whitepaper) Annual Meeting, the Company presented interim clinical data from its ongoing Phase 1 study of FT819, which showed a favorable safety profile and demonstrated objective responses in heavily pre-treated patients, including in patients who were not eligible for or had previously failed autologous CD19-targeted CAR T-cell therapy. Of the eight patients with aggressive large B-cell lymphoma (median of 4.5 prior lines of therapy; range 3-7) treated with a single dose of FT819 ranging from 90 million cells to 360 million cells: two patients were naïve to CAR T-cell therapy, one of whom achieved a complete response (CR); and six patients were previously treated with CAR T-cell therapy, two of whom achieved an objective response including a CR in a patient with diffuse large B-cell lymphoma previously treated with seven prior lines of therapy and who did not respond to autologous CD19-targeted CAR T-cell therapy. Dose escalation is currently ongoing in single-dose treatment regimens at 540 million cells in B-cell lymphoma and at 180 million cells in chronic lymphocytic leukemia.
2023 IND Submission Planned for FT825/ONO-8250 HER2-targeted CAR T-cell Solid Tumor Program. At the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting held in November 2022, the Company presented preclinical data of FT825/ONO-8250, a multiplexed-engineered, iPSC-derived CAR T-cell product candidate targeting human epidermal growth factor receptor 2 (HER2)-expressing solid tumors that the Company is co-developing under its collaboration with ONO Pharmaceutical Co., Ltd. (ONO). The product candidate incorporates seven novel synthetic controls designed to enhance effector cell function and overcome unique challenges in treating solid tumors with cell-based cancer immunotherapies, including cell trafficking, tumor infiltration, and immune cell suppression in the tumor microenvironment. Preclinical data of FT825/ONO-8250 presented at SITC (Free SITC Whitepaper) highlighted the differentiated targeting profile of its novel HER2-targeted binding domain as well as the potential of its synthetic CXCR2 receptor to promote cell trafficking, its synthetic TGFβ receptor to redirect immunosuppressive signals in the tumor microenvironment, and its synthetic interleukin-7 receptor fusion protein to induce T-cell activation. The parties are conducting IND-enabling activities for FT825/ONO-8250, and expect to submit an IND application to the FDA in 2023 to commence a Phase 1 study for the treatment of patients with HER2-positive solid tumors.
Corporate Developments
Termination of Janssen Collaboration. On January 3, 2023, the Company received notice of termination from Janssen Biotech, Inc. ("Janssen") of the Collaboration and Option Agreement dated April 2, 2020 by and between the Company and Janssen, pursuant to which Janssen and the Company had agreed to collaborate to develop iPSC-derived CAR NK- and CAR T-cell product candidates for the treatment of cancer, which will take effect April 3, 2023. During the fourth quarter of 2022, Janssen exercised its second commercial option for a collaboration product under the agreement, for which the Company expects to receive a $10 million milestone payment. In addition, during the fourth quarter of 2022, Janssen authorized the submission of, and the FDA allowed, an IND application for a first collaboration product for the treatment of B-cell lymphoma, for which the Company expects to receive a $3 million milestone payment. As a result of the collaboration’s termination, during the first quarter of 2023, the Company and Janssen are winding down all collaboration activities, including discontinuing development of all collaboration products, at the expense of Janssen.
Pipeline Prioritization and Restructuring. On January 5, 2023, the Company completed a strategic review of its NK cell programs and elected to advance its most innovative and differentiated product candidates. As a result of this program prioritization as well as the termination of the Janssen collaboration, the Company is discontinuing development of its FT516, FT596, FT538, and FT536 NK cell programs and is reducing its workforce in the first quarter of 2023 to approximately 220 employees. The Company expects to incur charges of approximately $12 million to $16 million for severance and other employee termination-related costs in the first quarter of 2023.
Fourth Quarter 2022 Financial Results
Cash & Investment Position: Cash, cash equivalents and investments as of December 31, 2022 were $441.2 million. In addition, as of December 31, 2022, cash receivables from the Company’s collaborations with Janssen and ONO were $38.5 million, which includes $22.5 million from the exercise of certain options and $3.0 million from the achievement of a regulatory milestone during the fourth quarter of 2022.
Total Revenue: Revenue was $44.4 million for the fourth quarter of 2022, which was derived from the Company’s collaborations with Janssen and ONO. During the fourth quarter, the Company recognized one-time revenue of: $12.5 million in connection with the Company and ONO each exercising their respective options for development and commercialization of FT825/ONO-8250; and $13.0 million in connection with the exercise of an option by Janssen and the achievement of a regulatory milestone under the Janssen collaboration.
R&D Expenses: Research and development expenses were $87.2 million for the fourth quarter of 2022, which includes $12.4 million of non-cash stock-based compensation expense.
G&A Expenses: General and administrative expenses were $21.6 million for the fourth quarter of 2022, which includes $7.0 million of non-cash stock-based compensation expense.
Shares Outstanding: Common shares outstanding were 97.3 million, and preferred shares outstanding were 2.8 million, as of December 31, 2022. Each preferred share is convertible into five common shares.
Today’s Conference Call and Webcast
The Company will conduct a conference call today, Tuesday, February 28, 2023 at 5:00 p.m. ET to review financial and operating results for the quarter and full year ended December 31, 2022. In order to participate in the conference call, please register using the conference link here. The live webcast can be accessed under "Events & Presentations" in the Investors section of the Company’s website at www.fatetherapeutics.com. The archived webcast will be available on the Company’s website beginning approximately two hours after the event.
About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, multiplexed-engineered cell products that are selectively designed, incorporate novel synthetic controls of cell function, and are intended to deliver multiple mechanisms of therapeutic importance to patients. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s platform combines multiplexed engineering and single-cell selection of human iPSCs to create clonal master iPSC lines. Analogous to master cell lines used to mass produce biopharmaceutical drug products such as monoclonal antibodies, the Company utilizes its clonal master iPSC lines as a renewable cell source to manufacture multiplexed-engineered cell products which are well-defined and uniform in composition, can be stored in inventory for off-the-shelf availability, can be combined and administered with other therapies, and can potentially reach a broad patient population. As a result, the Company’s platform is uniquely designed to overcome numerous limitations associated with the manufacture of cell therapies using patient- or donor-sourced cells. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 400 issued patents and 450 pending patent applications.
About FT576
FT576 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 four functional components: a proprietary chimeric antigen receptor (CAR) optimized for NK cell biology that targets B-cell maturation antigen (BCMA); 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; an IL-15 receptor fusion (IL-15RF) that augments NK cell activity; and the deletion of the CD38 gene (CD38KO), which promotes persistence and function in high oxidative stress environments. In preclinical studies, FT576 has demonstrated that the high-avidity binding of the BCMA-targeted CAR construct enables sustained tumor control against various multiple myeloma cell lines, including in long-term in vivo xenograft mouse models. Additionally, in combination with daratumumab, FT576 has shown complete tumor clearance and improved survival compared to primary BCMA-targeted CAR T cells in a disseminated xenograft model of multiple myeloma. FT576 is being investigated in a multicenter Phase 1 clinical trial for the treatment of relapsed / refractory multiple myeloma as a monotherapy and in combination with daratumumab (NCT05182073).
About FT819
FT819 is an investigational, universal, off-the-shelf, T-cell receptor (TCR)-less CD19 chimeric antigen receptor (CAR) T-cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line, which is engineered with the following features designed to improve the safety and efficacy of CAR19 T-cell therapy: a novel 1XX CAR signaling domain, which has been shown to extend T-cell effector function without eliciting exhaustion; integration of the CAR19 transgene directly into the T-cell receptor alpha constant (TRAC) locus, which has been shown to promote uniform CAR19 expression and enhanced T-cell potency; and complete bi-allelic disruption of TCR expression for the prevention of graft-versus-host disease. FT819 demonstrated antigen-specific cytolytic activity in vitro against CD19-expressing leukemia and lymphoma cell lines comparable to that of primary CAR T cells, and persisted and maintained tumor clearance in the bone marrow in an in vivo disseminated xenograft model of lymphoblastic leukemia. FT819 is being investigated in a multicenter Phase 1 clinical trial for the treatment of relapsed / refractory B-cell malignancies, including B-cell lymphoma, chronic lymphocytic leukemia, and acute lymphoblastic leukemia (NCT04629729).