On November 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 reported financial results for the quarter ended September 30, 2023 (Press release, Allogene, NOV 2, 2023, View Source [SID1234636727]).
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"Our experience continues to deepen as we successfully execute across our platform, creating a code for allogeneic cell therapy that can be applied not just in the industry’s first potentially pivotal trial of an allogeneic CAR T product candidate, but in other harder modes such as earlier line trials, solid tumors, and next-generation products and indications," said David Chang, M.D., Ph.D., President, Chief Executive Officer and Co-Founder of Allogene. "We look forward to the months ahead and sharing these insights, potentially unlocking new opportunities and broadening patient access to CAR T therapy."
Pipeline Updates
Anti-CD19 AlloCAR T Program
ALPHA2 is the industry’s first potentially pivotal Phase 2 allogeneic CAR T clinical trial. This global trial for the ALLO-501A product candidate will enroll approximately 100 patients who have received at least two prior lines of therapy and have not received prior anti-CD19 therapy.
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 investigational ALLO-647 30 mg, daily for 3 days). 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. Enrollment is expected to be completed by the 1H 2024 with the first data readout by the end of 2024.
The Company announced it will have two poster presentations from the ALPHA/ALPHA2 trials focused on lymphodepletion in allogeneic cell therapy at the 65th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) December 2023.
The first poster is a comprehensive safety review of all 85 patients treated in the Phase 1 ALPHA/ALPHA2 studies in relapsed/refractory (r/r) Large B Cell Lymphoma (LBCL) and follicular lymphoma (FL) to characterize the overall safety profile when ALLO-647 is added to standard lymphodepletion.
The second poster showcases translational results from ALPHA2 generated through a collaboration with The University of Texas MD Anderson Cancer Center. This study compared expansion kinetics among 11 allogeneic CAR T recipients treated with the ALLO-501A product candidate in the ALPHA2 trial. The study revealed the impact of recipient alloreactive CD8+ T cells in allogeneic CAR T rejection. Results of this study could help define strategies to improve allogeneic CAR T expansion, persistence and efficacy.
Long-term follow up data was previously presented from the Phase 1 ALPHA/ALPHA2 trials in LBCL and has been extensively characterized in presentations earlier this year at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, European Hematology Association (EHA) (Free EHA Whitepaper) Congress, and International Conference on Malignant Lymphoma (ICML) in Lugano.
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 investigational allogeneic CAR T product to induce complete responses at rates and durability similar to approved autologous therapies. Treatment with the ALLO-501/501A product candidates 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, enrolling in the United States and Europe, is expected to support licensure of ALLO-647, the Company’s investigational 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. The trial 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).
Anti-CD70 AlloCAR T Program
The Phase 1 dose escalation TRAVERSE trial in 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 is ongoing. Dose escalation in the TRAVERSE trial is expected to be completed by early 2024. The Company intends to target an academic forum in early 2024 to provide an update from this trial.
Next Generation Technologies and Targets
Cloak and Dagger Platform Technologies
The Company recently announced three poster presentations from its next generation AlloCAR T Platform at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting. The meeting will spotlight its novel, targeted Cloak and Dagger platform technologies designed to enhance engraftment, expansion and persistence of AlloCAR T cells.
These innovative approaches are intended to simplify lymphodepletion for allogeneic CAR T products and may provide a path to further expand the potential of off-the-shelf CAR T products beyond current targets and indications.
The Cloak platform technology is designed to prevent AlloCAR T cells from being recognized by host T cells without triggering substantial natural killer (NK) cell rejection while preserving CAR T cell function.
The Dagger platform technology, a feature of our ALLO-316 candidate, is designed to engineer AlloCAR T cells to selectively eliminate CD70 positive, 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.
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-182
SITC will also include a review of research which provided early validation of ALLO-182, an AlloCAR T candidate currently in the IND-enabling phase of development targeting Claudin18.2 for the treatment of patients with gastric and pancreatic cancers.
Corporate Updates
The Company has recently announced two new appointments to the leadership team. In August, the Company announced Earl Douglas as General Counsel, overseeing all aspects of the Company’s legal function. Following the close of the third quarter, the Company announced Geoffrey Parker as Executive Vice President, Chief Financial Officer, overseeing the Company’s financial operations and business development activities.
Third Quarter Financial Results
The Company had $497.7 million in cash, cash equivalents, and investments as of September 30, 2023.
Research and development expenses were $46.0 million for the third quarter of 2023, which includes $6.7 million of non-cash stock-based compensation expense.
General and administrative expenses were $17.0 million for the third quarter of 2023, which includes $8.6 million of non-cash stock-based compensation expense.
Net loss for the third quarter of 2023 was $61.3 million, or $0.37 per share, including non-cash stock-based compensation expense of $15.4 million.
2023 Financial Guidance
As previously provided, the Company expects a decrease in cash, cash equivalents, and investments of approximately $230 million in 2023. Based on current assumptions, the Company continues to expect its cash runway to fund operations into 2H 2025. 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.