CD52

Comprehensive Review of All Patients in the Phase 1 ALPHA/ALPHA2 Trials Demonstrate that Adding Investigational ALLO-647 to Standard Lymphodepletion Can Yield Durable Responses and a Safety Profile Comparable to Approved Autologous CAR T TherapiesCompany Received Fast Track Designation for ALLO-647 for Use in Adult Patients with Relapsed/Refractory Large B-Cell Lymphoma in November 2023 SOUTH SAN FRANCISCO, Calif., Dec. 09, 2023 (GLOBE NEWSWIRE) -- Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T™) products for cancer, today announced the presentation of data from a comprehensive safety review of patients treated in the Phase 1 ALPHA/ALPHA2 trials with ALLO-501/501A at the 65th Annual Meeting of the American Society of Hematology (ASH) in San Diego, CA. The safety review, which encompasses all 87 Phase 1 patients treated in both relapsed/refractory (r/r) Large B Cell Lymphoma (LBCL) and follicular lymphoma (FL), demonstrates that investigational ALLO-647 added to standard lymphodepletion can safely provide a window for the expansion and persistence of AlloCAR T cells, and has the potential to induce deep and durable remissions in relapsed and treatment-refractory cancers. "We believe in the immense potential of off-the-shelf CAR T products to not only address the limitations of current autologous CAR T cell therapy, but to also provide greater access to patients in need,” said Zachary Roberts, M.D., Ph.D., Executive Vice President of Research & Development and Chief Medical Officer of Allogene. “We fully understand the importance of lymphodepletion to achieving optimal outcomes, and ALLO-647 is just the first generation of our innovative approaches to enhancing lymphodepletion to promote expansion of CAR T cells.” The inclusion of our ALLO-647 candidate in the lymphodepletion regimen is designed to selectively prevent host rejection of allogeneic CAR T cell products. As previously presented in the Phase 1 ALPHA/ALPHA2 studies1, CAR T cell-naive patients with r/r LBCL were able to obtain a durable response, including a complete remission rate of 42% and a median duration of response of 23.1 months. In the studies, lymphodepletion consisted of three daily doses of fludarabine 30 mg/m2 and cyclophosphamide 300-500 mg/m2 (FC) and 39, 60, or 90 mg of ALLO-647 in divided doses prior to ALLO-501/501A infusion. The addition of ALLO-647 to standard lymphodepletion did not result in adverse events beyond those commonly observed with autologous CAR T cell therapy. No unexpected safety concerns were observed. Neutropenia and anemia were the most common any-grade treatment-emergent adverse events (or TEAEs) and neutropenia, anemia, and thrombocytopenia were the most common Grade 3 or higher TEAEs. Grade 3 or higher cytopenias decreased over time from Day 28 to Month 4 and were consistent across all subsets of patients. Incidence of Grade 3 or higher cytopenias were consistent with that reported for autologous CAR T cell therapy.2-4 Safety: TEAEs of Special Interest TEAEs, n (%)All (N=87)LBCLFL (n=26)All LBCL (n=61)CAR T Cell–Naive Pts Who ReceivedALLO-501/501A Manufactured WithThe Phase 2 Selected Process (n=33)Any GradeGrade ≥3Any GradeGrade ≥3Any GradeGrade ≥3Any GradeGrade ≥3CRS21 (24)1 (1)17 (28)1 (2)8 (24)04 (15)0ICANS1 (1)01 (2)00000Neurotoxicity24 (28)3 (3)19 (31)3 (5)13 (39)2 (6)5 (19)0GvHD00000000IRR48 (55)5 (6)31 (51)4 (7)16 (48)3 (9)17(65)1 (4)Infections50 (57)18 (21)34 (56)13 (21)19 (58)5 (15)16 (62)5 (19) There were no reports of graft-versus-host disease (GvHD) or Grade 3 or higher immune effector cell-associated neurotoxicity syndrome (ICANS). In total, 24% of patients experienced low-grade CRS, and there was 1 Grade 3 CRS event. Infection events were primarily low grade and manageable, with the most common being cytomegalovirus reactivation with an any-grade incidence of 25% and a Grade 3 or higher incidence of 9%. Incidence of infections were consistent with that reported for autologous therapy following lymphodepletion (12%-33% percent of patients).3-5 Eight patients experienced fatal adverse events not related to study treatment. The EXPAND trial, currently enrolling in the United States and Europe, is expected to support licensure of ALLO-647, used in conjunction with standard low-dose FC 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). Separately, the Company announced that the U.S. Food and Drug Administration (FDA) granted Fast Track Designation (FTD) for the investigation of ALLO-647 in adult patients with r/r LBCL based on its potential to enhance standard lymphodepletion. FTD designation is intended to accelerate the development and review of treatments for serious and life-threatening diseases where no treatment exists or where the treatment in discovery may be better than what is currently available. ALLO-647 is investigated as a lymphodepleting agent in combination with flu/cy prior to infusion of allogeneic CD19-directed CAR T cells with genomes edited to knock out CD52. About ALLO-501 and ALLO-501AALLO-501 and ALLO-501A are anti-CD19 AlloCAR TTM investigational products for the treatment of large B cell lymphoma. ALLO-501A, a next-generation anti-CD19 AlloCAR TTM product, eliminates the rituximab recognition domains in ALLO-501, which could allow for use in a broader patient population, including NHL patients with recent rituximab exposure. This product candidate is currently being studied in an ongoing potentially pivotal Phase 2 trial. In June 2022, the U.S. Food and Drug Administration granted Regenerative Medicine Advanced Therapy (RMAT) designation to ALLO-501A in r/r LBCL. About Allogene TherapeuticsAllogene Therapeutics, with headquarters in South San Francisco, is a clinical-stage biotechnology company pioneering the development of allogeneic chimeric antigen receptor T cell (AlloCAR T™) products for cancer. Led by a management team with significant experience in cell therapy, Allogene is developing a pipeline of “off-the-shelf” CAR T product candidates with the goal of delivering readily available cell therapy on-demand, more reliably, and at greater scale to more patients. For more information, please visit www.allogene.com, and follow @AllogeneTx on X (formerly Twitter) and LinkedIn. Cautionary Note on Forward-Looking Statements This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. The press release may, in some cases, use terms such as "predicts," "believes," "potential," "proposed," "continue," "estimates," "anticipates," "expects," "plans," "intends," "may," “can,” "could," "might," "will," "should,” “designed to” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Forward-looking statements include statements regarding intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: Allogene’s ability to deliver readily available off-the shelf cell therapy on-demand, more reliably, and at greater scale to more patients; the potential safety profile of the Company’s lymphodepletion and cell dose regimen; and the modes of action, the therapeutic effects and safety profile of Allogene’s product candidates including their ability to treat cancers at various stages or to treat broad populations. Various factors may cause material differences between Allogene’s expectations and actual results, including risks and uncertainties related to: our product candidates are based on novel technologies, which makes it difficult to predict the time and cost of product candidate development and obtaining regulatory approval; the FDA may disagree with our regulatory plan and we may fail to obtain regulatory approval of our CAR T cell product candidates; and our clinical trials may fail to demonstrate the safety and efficacy of any of our product candidates, which would prevent or delay regulatory approval and commercialization. These and other risks are discussed in greater detail in Allogene’s filings with the SEC, including without limitation under the “Risk Factor” Heading in its Form 10-Q filed for the quarter ended September 30, 2023, being filed with the SEC today. Any forward-looking statements that are made in this press release speak only as of the date of this press release. Allogene assumes no obligation to update the forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release. Caution should be exercised regarding statements comparing autologous CAR T data. There are differences in the clinical trial design, patient populations, published data, follow-up times and the product candidates themselves, and the results from the clinical trials of autologous products may have no interpretative value on Allogene’s existing or future results. AlloCAR T™ and Alloy™ are trademarks of Allogene Therapeutics, Inc. Allogene’s AlloCAR T™ programs utilize Cellectis technologies. ALLO-501 and ALLO-501A are anti-CD19 products being jointly developed under a collaboration agreement between Servier and Allogene based on an exclusive license granted by Cellectis to Servier. Servier grants to Allogene exclusive rights to ALLO-501 and ALLO-501A in the U.S. 1. Locke FL, Lekakis L, Eradat H, et al. Durable Responses with Anti-CD19 Allogeneic CAR T ALLO-501/501A in Phase 1 Trials of Relapsed/Refractory Large B-Cell Lymphoma (r/r LBCL). Oral presentation at the International Conference on Malignant Lymphoma. June 13-17, 2023. Abstract 48. 2. Logue JM, et al. Haematologica. 2021;106(4):978-986. 3. KYMRIAH. Prescribing Information. Novartis Pharmaceuticals Corp.; 2022. 2022. 4. BREYANZI. Prescribing Information. Juno Therapeutics, Inc.;5. YESCARTA. Prescribing information. Kite Pharma, Inc; 2022. Allogene Media/Investor Contact:Christine CassianoEVP, Chief Corporate Affairs & Brand Strategy OfficerChristine.Cassiano@allogene.com Additional Allogene Media Contacts:Leslie BryantLeslie.Bryant@allogene.com Madeleine GoldsteinMadeleine.Goldstein@allogene.com

Beam Therapeutics has begun human testing in the U.S. of a first-of-its-kind gene editing medicine for cancer, the company said Tuesday.Beam, a pioneering developer of a precise gene editing technique known as base editing, said in a short statement that its dosed its first patient in a study of the treatment, called BEAM-201. The trial involves patients with an aggressive form of blood cancer known as T-cell acute lymphoblastic leukemia/T-cell lymphoblastic lymphoma, or T-ALL/T-LL. It will eventually enroll about 100 participants, according to a federal database.The studys start makes BEAM-201 the first base editing therapy to enter clinical testing in the U.S., and marks the first time patients have received a cell therapy made by multiplex editing, in which several genes are edited. The edits are designed to eliminate expression of four genes known as CD7, TRAC, PDCD1 and CD52.Beam claims this approach could lead to a more powerful and durable treatment. In its statement, the company noted BEAM-201s potential to sidestep a variety of issues associated with cell therapies, like propensity for the modified cells to kill one another, or become weaker as time goes on.Beam also believes the simultaneous edits could yield a more potent donor-derived, or off the shelf, cell therapy. Such allogeneic treatments would be more convenient than the personalized CAR-T therapies on the market, but results to date havent proven theyre more powerful at killing cancer cells.We believe that the full therapeutic potential of CAR-T therapies, including the ability to utilize an allogeneic source of T cells, will only be unlocked through higher levels of cellular engineering enabled by multiple simultaneous genetic edits, said CEO John Evans, in a statement.Yet Beam has struggled to meet development timelines amid Food and Drug Administration scrutiny of base editing, and in some cases is trying to catch more advanced competitors.In sickle cell disease, the company is behind gene-based medicines from Bluebird bio and Vertex Pharmaceuticals that could be approved later this year. Beams slower than expected progress enrolling patients in an early study of its sickle cell therapy, dubbed BEAM-101, drew a disproportionate amount of investor attention/scrutiny when Beam reported quarterly earnings last month, wrote Stifel analyst Dae Gon Ha.Testing of BEAM-201 has also been held up. Its first clinical study was supposed to begin last year, but the FDA paused development in August 2022 and asked for a variety of technical information from preclinical experiments before the company could proceed. The clinical hold was lifted four months later.Beam isnt alone in dealing with regulatory scrutiny. The FDA has slowed early U.S. tests of several emerging gene editing treatments in recent years, often requesting additional information to allay safety concerns. But the resolution of Beams issue and subsequent dosing of a patient could indicate FDAs comfort with intricate and novel editing technologies, wrote Stifel analyst Ha.Ha believes progress with BEAM-201 can lay an important foundation for Beam to progress, as the therapy could demonstrate the impact multiplex editing can have. Still, we suspect investors also ascribe minimal, if any, value, to the drug, he wrote.At about $24 apiece, Beam shares have lost roughly 40% of their value this year. '

Abcuro plans to set aside part of the new funds to start a third trial for ABC008, this time in in T- and NK-cell lymphomas.  Abcuro will draw on an oversubscribed series B round to continue the journey of its anti-KLRG1 candidate through clinical trials for a muscle disease and cancers. The latest round of $155 million follows a $42 million series A co-led by Sanofi Ventures in 2021. Back then, the company was focused on getting its lead candidate ABC008 into a proof-of-mechanism trial for a muscle inflammation disease called sporadic inclusion body myositis (IBM). Since then, the monoclonal antibody has made it into a phase 2/3 study for the same condition, and Abcuro plans to use some of its new financial firepower to complete the trial. While other autoimmune-focused biotechs are targeting CD25, CD2, CD52 and ICOS in an attempt to drive the depletion of cytotoxic T cells, Abcuro has stacked its chips on KLRG1. The company’s logic is that KLRG1 expression is restricted to highly cytotoxic late-differentiated effector memory and effector T cells. Because IBM is driven by T-cell attacks on muscle fibers that lead to loss of hand function and ability to walk, it’s made for a good proving ground for the concept. So far, the bet seems to be paying off, with the company pointing earlier this year to phase 1 data that showed “near complete depletion of blood target cells [that] persisted with repeat dosing.” Still, the real proof will be when the phase 2/3 study begins the efficacy stage in the coming months. The company is also overseeing a phase 1/2 clinical trial of ABC008 in T-cell large granular lymphocytic leukemia, with plans to set aside part of the new funds to start a third trial in T- and NK-cell lymphomas.  Sanofi was back on board as one of the investors for the series B round, which this time was led by Redmile Group and Bain Capital Life Sciences. “Support from such a strong group of investors will allow us to complete our development programs in diseases where there are few to no treatment options available,” CEO Alex Martin said in the release. “We’re committed to executing on our clinical trials including our registrational trial in inclusion body myositis,” added Martin, who joined the biotech in October after stints as CEO at Palladio Biosciences and Realm Therapeutics.