Allogene Therapeutics Presents Preclinical Data for ALLO-329, an Allogeneic CD19/CD70 Dual CAR T for the Treatment of Autoimmune Disease at the American College of Rheumatology (ACR) Convergence
Allogene Therapeutics presented preclinical data for ALLO-329, a novel dual CAR T cell therapy targeting both CD19+ B-cells and CD70+ activated T cells for autoimmune diseases. The therapy demonstrated effective depletion of target cells and reduction in IgG and IgM without requiring lymphodepletion in preclinical models. Using proprietary Dagger® technology, ALLO-329 showed resistance to rejection and enhanced persistence. The company plans to submit an IND application in Q1 2025, with proof-of-concept expected by year-end 2025.
Allogene Therapeutics ha presentato dati preclinici per ALLO-329, una nuova terapia con cellule CAR T duale che colpisce sia le cellule B CD19+ che le cellule T attivate CD70+ per le malattie autoimmuni. La terapia ha dimostrato una efficace deplezione delle cellule bersaglio e una riduzione di IgG e IgM senza la necessità di linfodeplezione nei modelli preclinici. Utilizzando la tecnologia proprietaria Dagger®, ALLO-329 ha mostrato resistenza al rigetto e una maggiore persistenza. L'azienda prevede di presentare una domanda IND nel primo trimestre del 2025, con una prova di concetto attesa entro la fine del 2025.
Allogene Therapeutics presentó datos preclínicos de ALLO-329, una nueva terapia de células CAR T dual que apunta tanto a las células B CD19+ como a las células T activadas CD70+ para enfermedades autoinmunes. La terapia demostró una efectiva depleción de células objetivo y reducción de IgG e IgM sin requerir linfodepleción en modelos preclínicos. Utilizando la tecnología propietaria Dagger®, ALLO-329 mostró resistencia al rechazo y una mejor persistencia. La compañía planea presentar una solicitud IND en el primer trimestre de 2025, con una prueba de concepto esperada para finales de 2025.
알로진 테라퓨틱스는 자가면역 질환을 대상으로 하는 CD19+ B세포와 CD70+ 활성화 T세포 모두를 겨냥한 새로운 이중 CAR T 세포 요법인 ALLO-329의 전임상 데이터를 발표했습니다. 이 요법은 전임상 모델에서 세포 표적 제거와 IgG 및 IgM의 감소를 효과적으로 보여주었으며, 림프탈출 없이 이루어졌습니다. 독점 기술인 Dagger®를 사용한 ALLO-329는 거부 반응에 대한 저항성과 지속성을 향상시킨 것으로 나타났습니다. 회사는 2025년 1분기에 IND 신청을 제출할 계획이며, 2025년 연말까지 개념 증명이 예상됩니다.
Allogene Therapeutics a présenté des données précliniques pour ALLO-329, une nouvelle thérapie par cellules CAR T duale ciblant à la fois les cellules B CD19+ et les cellules T activées CD70+ pour les maladies auto-immunes. La thérapie a démontré une déplétion efficace des cellules cibles et une réduction des IgG et IgM sans nécessiter de lymphodéplétion dans les modèles précliniques. En utilisant la technologie propriétaire Dagger®, ALLO-329 a montré une résistance au rejet et une persistance améliorée. L'entreprise prévoit de soumettre une demande d'IND au premier trimestre 2025, avec une preuve de concept attendue d'ici la fin de 2025.
Allogene Therapeutics hat präklinische Daten zu ALLO-329 präsentiert, einer neuartigen dualen CAR-T-Zelltherapie, die sowohl CD19+ B-Zellen als auch CD70+ aktivierte T-Zellen bei Autoimmunerkrankungen anvisiert. Die Therapie zeigte eine effektive Depletion der Zielzellen sowie eine Reduktion von IgG und IgM, ohne dass eine Lymphodepletion in präklinischen Modellen erforderlich war. Durch die proprietäre Dagger®-Technologie zeigte ALLO-329 eine Widerstandsfähigkeit gegen Abstoßung und eine verbesserte Persistenz. Das Unternehmen plant, im ersten Quartal 2025 einen IND-Antrag einzureichen, mit einem Machbarkeitsnachweis, der bis Ende 2025 erwartet wird.
- Demonstrated robust CAR expression and specific cytotoxic activity against both target cell types
- Successfully eliminated CD70+ alloreactive T cells, showing enhanced persistence
- Effective B cell eradication and reduction in IgG and IgM production
- Achieved engraftment and B cell depletion without lymphodepletion
- Highly consistent manufacturing process through CRISPR-mediated integration
- Still in preclinical stage, with clinical trials not starting until 2025
- Faces competition in the autoimmune CAR T space
Insights
The preclinical data for ALLO-329 represents a significant advancement in CAR T-cell therapy for autoimmune diseases. The dual-targeting mechanism of both CD19+ B-cells and CD70+ T cells addresses multiple pathways of autoimmune dysfunction, potentially offering superior efficacy compared to single-target approaches.
The incorporation of Dagger® technology is particularly noteworthy as it could eliminate the need for lymphodepletion - a major advancement that would significantly reduce treatment-related complications and improve the therapy's safety profile. The successful demonstration of B cell depletion, antibody reduction and resistance to rejection in preclinical models suggests a robust therapeutic potential.
The planned IND submission in Q1 2025 with proof-of-concept expected by year-end 2025 provides a clear development timeline. The "off-the-shelf" nature of this allogeneic therapy could significantly improve accessibility and reduce manufacturing complexities compared to autologous approaches.
This development positions Allogene strategically in the competitive autoimmune CAR T space. The dual-targeting approach differentiates ALLO-329 from competitors focusing on single targets, potentially creating a significant market advantage. The technology could address multiple autoimmune conditions, substantially expanding the addressable market beyond current CAR T applications.
The elimination of lymphodepletion requirement could be a major commercial differentiator, potentially leading to broader adoption and improved reimbursement prospects. Manufacturing consistency through CRISPR-mediated integration suggests scalability advantages, important for commercial success in the allogeneic cell therapy space.
- ALLO-329 Induces Deep, Transient Depletion of CD19+ B Cells and CD70+ T Cells, and Reduction in IgG and IgM without Lymphodepletion in Humanized Murine Models
- Proprietary Dagger® Technology Enables ALLO-329 to Overcome Rejection and Expand the Presence of Alloreactive T Cells
- Presented Data Demonstrates that ALLO-329 Could Be Effective in Treating Autoimmune Diseases with Reduced or No Lymphodepleting Chemotherapy
- ALLO-329 Investigational New Drug (IND) Submission Planned for Q1 2025
SOUTH SAN FRANCISCO, Calif., Nov. 18, 2024 (GLOBE NEWSWIRE) -- 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, today announced preclinical data for ALLO-329, an investigational allogeneic CD19/CD70 dual CAR T cell therapy being evaluated as a treatment for autoimmune diseases. The data, presented at the American College of Rheumatology (ACR) Convergence 2024, demonstrate the potential of ALLO-329 to specifically address key challenges associated with current autologous CAR T cell therapies in development for patients with autoimmune disease and highlights the promise of an allogeneic CAR T to reset the immune system.
ALLO-329 is the first CAR T designed to target both CD19+ B-cells and CD70+ activated T cells. Targeting of B cells has been shown to induce durable, treatment-free remissions in patients with certain autoimmune diseases. CD70 is expressed in activated T cells, which have been implicated in immune responses, including in autoimmunity. Simultaneous elimination of CD70+ T cells may enhance the therapeutic benefit and expand the list of addressable indications.
CD70+ activated T cells also include alloreactive T-cells – the patient’s cells that would attack and reject an allogeneic CAR-T. ALLO-329 is designed to effectively eliminate alloreactive T-cells and render ALLO-329 resistant to rejection. Incorporation of Dagger® technology into ALLO-329 is intended to reduce or eliminate lymphodepletion prior to cell infusion.
“The CAR T space for autoimmune disease is highly competitive, with many approaches focusing only on isolated aspects of autoimmune pathogenesis,” said Zachary Roberts, M.D., Ph.D., EVP, Research and Development and Chief Medical Officer of Allogene. “What sets ALLO-329 apart is its ability to target a greater spectrum of immune dysfunction, addressing both B cells and activated T-cells involved in the disease process, potentially improving disease outcomes with reduced or even no lymphodepletion. Coupled with its “off-the-shelf” accessibility, ALLO-329 has the potential to meet the substantial needs of a broad patient population. These preclinical findings reinforce our excitement as we move this therapy toward clinical development across multiple autoimmune conditions.”
Key findings from the preclinical evaluation of ALLO-329 include:
- High CAR expression and cytotoxic activity: ALLO-329 produced through site-specific integration of a dual CAR construct into the TRAC locus demonstrated robust CAR expression and specific cytotoxic activity against both CD19+ B cells and CD70+ T cells in vitro and in vivo.
- Resistance to rejection: In mixed lymphocyte reaction (MLR) assays, ALLO-329 successfully eliminated CD70+ alloreactive T cells, demonstrating resistance to rejection and enhanced persistence compared to CD19 CAR T cells.
- B cell depletion and antibody reduction: ALLO-329 effectively eradicated B cells derived from healthy donors and patients with systemic lupus erythematosus (SLE) in vitro and in vivo, leading to a reduction in IgG and IgM production.
- Potential to eliminate lymphodepletion: In humanized pre-clinical models, ALLO-329 demonstrated engraftment, B cell depletion, and expansion even without lymphodepletion.
- Manufacturability: CRISPR-mediated, T-cell receptor alpha (TRAC) site-specific transgene integration leads to a highly consistent, dual CAR T-expressing product.
Based on these promising preclinical results, the Company plans to file an investigational new drug (IND) application with the FDA in the first quarter of 2025 and expects to have proof-of-concept by year-end 2025.
About ALLO-329
ALLO-329 is a CD19/CD70 dual AlloCAR T™ investigational product being developed for the treatment of autoimmune diseases. ALLO-329 utilizes CRISPR-based site-specific integration for dual CAR expression. This approach targets both CD19+ B cells and CD70+ T cells, which play a role in autoimmune disease pathogenesis. Additionally, ALLO-329 incorporates Allogene's clinically validated Dagger® technology, designed to reduce or eliminate the need for lymphodepletion, a pre-treatment regimen that may be a significant barrier to CAR T cell therapy adoption in autoimmune indications.
About Allogene Therapeutics
Allogene 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 and autoimmune disease. Led by a management team with significant experience in cell therapy, Allogene is developing a pipeline of “off-the-shelf” CAR T cell 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 and LinkedIn.
Cautionary Note on Forward-Looking Statements for Allogene
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 “potential,” “develop,” “promise,” “designed to,” “explore,” “expects,” “plans,” “intends,” “may,” “could,” “would,” 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: the timing of filing Investigational New Drug applications relating to ALLO-329 and the progress and success of such clinical program; clinical outcomes, which may materially change as more patient data become available; the design and potential benefits of ALLO-329 and our Dagger™ technology including the ability overcome rejection and expand the presence of alloreactive T-cells, to enhance engraftment, expansion and persistence of AlloCAR T cells, the ability to resist rejection of AlloCAR T cells by the host immune cells and the expected benefits therefrom, or the ability to target CD19+ B-cells and CD70+ activated T-cells that will induce durable, treatment-free remissions or enhance the therapeutic benefits in autoimmune disease, and our plans to deploy the Dagger™ technology; the potential that our dual CAR targeting B- and T-cell components of autoimmune disease will allow for broader application of CAR T across multiple autoimmune conditions; the potential benefits of AlloCAR T products; the ability of our product candidates to treat autoimmune disease; the potential for off-the-shelf CAR T products; our ability to deliver cell therapy on-demand, more reliably, and at greater scale to more patients. 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 limited nature of our pre-clinical data and the extent to which such data may or may not be validated in any future clinical trial; our product candidates may cause undesirable side effects or have other properties that could halt their clinical development, prevent their regulatory approval or limit their commercial potential; the extent to which the Food and Drug Administration disagrees with our clinical or regulatory plans or the import of our clinical results, which could cause future delays to our clinical trials, including initiation of clinical trials, or require additional clinical trials; we may encounter difficulties enrolling patients in our clinical trials; we may not be able to demonstrate the safety and efficacy of our product candidates in our clinical trials, which could prevent or delay regulatory approval and commercialization; and challenges with manufacturing or optimizing manufacturing of our product candidates. These and other risks are discussed in greater detail in Allogene’s filings with the SEC, including without limitation under the “Risk Factors” heading in its Quarterly Report on Form 10-Q for the quarter ended September 30, 2024. 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.
AlloCAR T™ and Dagger™ are trademarks of Allogene Therapeutics, Inc.
Allogene Media/Investor Contact:
Christine Cassiano
EVP, Chief Corporate Affairs & Brand Strategy Officer
Christine.Cassiano@allogene.com
FAQ
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