On March 14, 2024 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) products for cancer and autoimmune disease, reported a corporate update and provided financial results for the quarter and year ended December 31, 2023 (Press release, Allogene, MAR 14, 2024, View Source [SID1234641153]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"We are more enthusiastic than ever about the potential for allogeneic CAR T to transform the field," said David Chang, M.D., Ph.D., President, Chief Executive Officer and Co-Founder of Allogene. "From our innovative ALPHA3 trial which is designed to embed cema-cel as part of a curative first-line regimen for patients with large B cell lymphoma, to specifically creating a CAR T that can meet the unique needs of patients with autoimmune disease and reduce reliance on lymphodepletion, our development approach focuses on the distinctive attributes of an off-the-shelf alternative and creates an advantage for our AlloCAR T programs."
Core Program Updates
Cema-Cel: Pivotal ALPHA3 1L Consolidation Trial in Large B Cell Lymphoma (LBCL)
The Company continues to focus on the development of its investigational product cemacabtagene ansegedleucel, or cema-cel (previously known as ALLO-501A) as part of the first line (1L) treatment plan for LBCL patients who are likely to relapse following 1L chemoimmunotherapy.
This innovative trial takes advantage of the unique attributes of cema-cel, the only allogeneic cell therapy product with Phase 1 data comparable to that of an autologous therapy. With off-the-shelf availability and convenience, cema-cel will be administered as a one-time infusion immediately upon detection of minimal residual disease (MRD) at the completion of six cycles of R-CHOP or equivalent 1L chemoimmunotherapy. The potential outcome of this consolidation treatment could improve the cure rate and uniquely position cema-cel to become the standard "7th cycle" of frontline treatment available to all eligible patients with MRD.
The design of the ALPHA3 1L consolidation trial builds upon the results demonstrated in the cema-cel Phase 1 ALPHA2 trial and will leverage an investigational, cutting-edge diagnostic test for MRD developed by Foresight Diagnostics. ALPHA3 will randomize approximately 230 patients who are in clinical remission but remain MRD positive at the end of standard 1L chemoimmunotherapy to either consolidation with cema-cel or the current standard of care, observation, which means to "watch and wait" for the disease to relapse. The primary endpoint of the ALPHA3 trial is event free survival (EFS). The trial will initially test two lymphodepletion regimens (one with standard fludarabine and cyclophosphamide plus ALLO-647 and one without ALLO-647). One lymphodepletion arm will be discontinued following a planned interim analysis in mid-2025 designed to select the most appropriate regimen for this patient population.
Start-up activities for the ALPHA3 trial are underway and the trial is expected to begin in mid-2024. The ALPHA3 trial will be conducted in a wide array of cancer treatment centers, including community cancer centers where most earlier line patients seek care.
Cema-Cel: Phase 1 ALPHA2 Trial in Chronic Lymphocytic Leukemia (CLL)
In the first quarter, the Company began enrollment in the ALPHA2 trial of the investigational product cema-cel in patients with relapsed/refractory (r/r) CLL. While recent autologous CD19 CAR T data has been a positive step for patients with relapsed/refractory (r/r) CLL, T cell dysfunction and high circulating leukemia burden often found in patients with CLL, make the isolation of functional T cells for autologous CAR T manufacturing difficult. As a result, this trial has been driven by investigator enthusiasm for an allogeneic CAR T to potentially boost the curative power of CAR T.
Initial data readout from Phase 1 ALPHA2 CLL cohort (n=12) is projected by year-end 2024.
ALLO-329: CD19 Dagger in Autoimmune Disease (AID)
The Company has applied its deep understanding of CAR T research and development to design next-generation allogeneic CAR T investigational products that the Company believes can sustain the scale of the AID market while also meeting the unique requirements for these patients where they seek care.
ALLO-329, the Company’s first AlloCAR T investigational product for AID, incorporates the Dagger technology which is intended to reduce or eliminate the need for lymphodepletion while targeting CD19+ B-cells and CD70+ activated T-cells, both of which play a role in AID.
As part of its overarching AID 2.0 platform, the Company also announced a non-exclusive, global gene editing licensing agreement with Arbor Biotechnologies, Inc. for use of their proprietary CRISPR-based gene-editing technology.
ALLO-329 is expected to enter Phase 1 clinical trials in early 2025.
ALLO-316: TRAVERSE Trial in Renal Cell Carcinoma (RCC)
Building upon the field’s understanding of how certain drugs can act as a "safety key" to mitigate treatment-associated adverse events without compromising CAR T function or efficacy, the Company has developed and implemented a diagnostic and treatment algorithm in its solid tumor trial that may mitigate the treatment-associated hyperinflammatory response without compromising the CAR T function needed to eradicate solid tumors with ALLO-316 in renal cell carcinoma (RCC).
Details on this potentially cornerstone discovery in the Phase 1 TRAVERSE trial is planned for a publication in Q2 2024. A more comprehensive data update from the ongoing trial with the updated protocol is planned for later in 2024.
Financial Updates
As noted in the February 16, 2024 press release, the Company has now issued restated financials for the years ended December 31, 2020, 2021 and 2022 and interim quarters during 2022 and 2023 due to non-cash accounting adjustments associated with the December 2020 formation of the Allogene Overland Biopharm joint venture in Asia. These restated financial statements have no impact on the Company’s cash, cash equivalents and marketable investments, cash runway or business operations.
2023 Fourth Quarter and Year-End Financial Results
Research and development expenses were $54.7 million for the fourth quarter of 2023, which includes $7.0 million of non-cash stock-based compensation expense. For the full year of 2023, research and development expenses were $242.9 million, which includes $31.9 million of non-cash stock-based compensation expense.
General and administrative expenses were $17.2 million for the fourth quarter of 2023, which includes $8.2 million of non-cash stock-based compensation expense. For the full year of 2023, general and administrative expenses were $71.7 million, which includes $34.0 million of non-cash stock-based compensation expense.
Net loss for the fourth quarter of 2023 was $85.8 million, or $0.51 per share, including non-cash stock-based compensation expense of $15.2 million and $13.2 million in non-cash impairment of long-lived asset expense. For the full year of 2023, net loss was $327.3 million, or $2.09 per share, including non-cash stock-based compensation expense of $66.0 million and $13.2 million in non-cash impairment of long-lived asset expense.
The Company had $448.7 million in cash, cash equivalents, and investments as of December 31, 2023.
2024 Financial Guidance
The Company expects a decrease in cash, cash equivalents, and investments of approximately $190 million in 2024. Based on current assumptions, the Company continues to expect its cash runway to fund operations into 2026. GAAP Operating Expenses are expected to be approximately $280 million, including estimated non-cash stock-based compensation expense of approximately $60 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.