On August 2, 2023 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) products for cancer, reported a corporate update and announced financial results for the quarter ended June 30, 2023 (Press release, Allogene, AUG 2, 2023, View Source [SID1234633636]).
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"The last few months have been exciting for cell therapy as the transformative potential of an allogeneic CAR T product becomes more evident. Within this framework, we are thrilled that our off-the-shelf CD19 AlloCAR T data continues to demonstrate what I believe to be both first-in-class and best-in class promise in hematological cancers," said David Chang, M.D., Ph.D., President, Chief Executive Officer and Co-Founder of Allogene. "We remain focused on advancing the industry’s first potentially pivotal allogeneic CAR T trials in order to enable more patients to receive cell therapy."
Pipeline Updates
ALLO-501A: Anti-CD19 AlloCAR T Program
The Company is enrolling patients in the industry’s first potentially pivotal Phase 2 allogeneic CAR T clinical trial with ALLO-501A across sites in the United States and Canada. The European Medicines Agency (EMA) recently approved the ALPHA2 Clinical Trial Application (CTA) and patient enrollment in Europe is expected to begin in Q3 2023 and in Australia by year-end.
The single-arm ALPHA2 trial in relapsed/refractory (R/R) large B cell lymphoma (LBCL) utilizes a single dose of ALLO-501A (120 million CAR+ cells) following lymphodepletion with FCA90 (fludarabine, 30 mg/m2; cyclophosphamide 300 mg/m2; and ALLO-647 30 mg, daily for 3 days). This trial will enroll approximately 100 patients who have received at least two prior lines of therapy and have not received prior anti-CD19 therapy. The primary endpoint is overall response rate (ORR), and the key secondary endpoint is duration of response (DoR). Patients may receive treatment as an outpatient at the investigator’s discretion. The Company expects to complete enrollment in 1H 2024 with the first data readout by the end of 2024.
Long-term follow up data from the Phase 1 ALPHA/ALPHA2 trials in LBCL was presented at both the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting with an encore presentation at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress, and the International Conference on Malignant Lymphoma (ICML) Lugano in June 2023. The Phase 1 trials enrolled heavily pre-treated patients with a median of three prior lines of therapy. Data from 33 CAR T-naïve LBCL patients receiving Alloy cell product including 12 patients treated with the Phase 2 regimen, are the first to demonstrate the potential for an allogeneic CAR T product to induce complete responses at rates and durability similar to approved autologous therapies. Treatment with ALLO-501/501A was generally well tolerated with no incidence of Grade 3 or greater cytokine release syndrome, and no cases of immune effector cell-associated neurotoxicity syndrome or graft versus host disease. Cytopenia and infections were manageable and comparable to the experience with autologous CAR T cell therapies in patients with r/r LBCL.
The EXPAND trial is also underway to support licensure of ALLO-647, the Company’s anti-CD52 monoclonal antibody used in conjunction with standard low-dose FC (fludarabine, 30 mg/m2 and cyclophosphamide 300 mg/m2, daily for 3 days) lymphodepletion regimens to control premature rejection of AlloCAR T cells by the patient’s immune system. At the ASCO (Free ASCO Whitepaper) and Lugano data presentations, the Company’s proprietary lymphodepletion strategy was shown to promote robust AlloCAR T cell expansion and best-in-class longest persistence without incurring significant changes in infectious or immunosuppressive complications as compared to autologous CAR T therapies.
The EXPAND trial, which is designed to demonstrate the contribution of ALLO-647 to the standard low dose FC lymphodepletion, will enroll approximately 70 patients with r/r LBCL who will be randomized to lymphodepletion with FCA90 (which includes 90 mg of ALLO-647) versus FC alone before receiving a single 120 million cell dose of ALLO-501A. The primary endpoint of the study is progression free survival (PFS).
ALLO-316: Anti-CD70 AlloCAR T Program
The ongoing Phase 1 dose escalation TRAVERSE study is enrolling patients with advanced or metastatic renal cell carcinoma (RCC) who have progressed on standard therapies including an immune checkpoint inhibitor and a VEGF-targeting therapy. Initial data from TRAVERSE were presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) conference in April and demonstrated the potential of an allogeneic CAR T product to treat CD70 expressing RCC. In this trial, ALLO-316 showed early anti-tumor activity with deepening responses over time and a trend toward greater tumor shrinkage in patients with higher levels of CD70 expression.
The Dagger effect, which is a feature of ALLO-316, enables ALLO-316 CAR T cells to target and eliminate alloreactive host immune cells, thereby mitigating potential premature rejection of AlloCAR T cells by the patient’s immune system. Translational results shared at AACR (Free AACR Whitepaper) suggest this unique immunomodulatory effect of ALLO-316 contributed to robust AlloCAR T cell expansion and persistence, and clinical remissions.
The TRAVERSE trial is now deploying an investigational in vitro companion diagnostic (IVD) assay designed to prospectively assess CD70 expression levels in patients. Dose escalation in the TRAVERSE trial is expected to be completed in 2023.
Based on preclinical results demonstrating the ability to combine anti-CD19 and other AlloCARs with the Dagger technology, the Company intends to explore this approach to potentially enhance the activity of next generation AlloCAR T products candidates, including those that target other hematological and solid tumors.
ALLO-715: Anti-BCMA AlloCAR T Program
The Company previously presented ALLO-715 Phase 1 data from the UNIVERSAL trial which was the first study to demonstrate that an allogeneic anti-BCMA CAR T could produce response rates in multiple myeloma similar to an approved autologous CAR T therapy. As treatments in multiple myeloma advance, the Company is evaluating manufacturing process improvement across its BCMA candidates to achieve an improved competitive profile.
Second Quarter Financial Results
The Company had $544.5 million in cash, cash equivalents, and investments as of June 30, 2023, which includes net proceeds of approximately $87.9 million raised in the second quarter from an at-the market (ATM) equity financing facility. Based on current expectations, the Company expects its cash runway to fund operations into 2H 2025.
Research and development expenses were $62.0 million for the second quarter of 2023, which includes $6.9 million of non-cash stock-based compensation expense.
General and administrative expenses were $18.5 million for the second quarter of 2023, which includes $9.7 million of non-cash stock-based compensation expense.
Net loss for the second quarter of 2023 was $78.0 million, or $0.53 per share, including non-cash stock-based compensation expense of $16.6 million.
2023 Financial Guidance
As previously reported, the Company expects a decrease in cash, cash equivalents, and investments of approximately $230 million in 2023. GAAP Operating Expenses are expected to be approximately $340 million, including estimated non-cash stock-based compensation expense of approximately $80 million. These estimates exclude any impact from potential business development activities.
Conference Call and Webcast Details
Allogene will host a live conference call and webcast today at 2:00 p.m. Pacific Time / 5:00 p.m. Eastern Time to discuss financial results and provide a business update. If you would like the option to ask a question on the conference call, please use this link to register. Upon registering for the conference call, you will receive a personal PIN to access the call, which will identify you as the participant and allow you the option to ask a question. The listen-only webcast will be made available on the Company’s website at www.allogene.com under the Investors tab in the News and Events section. Following the live audio webcast, a replay will be available on the Company’s website for approximately 30 days.