▎WuXiEdited by Kant Content Team

Recently, the global cell and gene therapy (CGT) field has seen a series of advancements. The U.S. FDA approved Pfizer's one-time gene therapy Beqvez (fidanacogene elaparvovec) for treating adults aged 18 or older with moderate to severe hemophilia B. The candidate cell therapy CardiAMP for treating chronic myocardial ischemia achieved positive clinical trial results.At the 6-month primary follow-up endpoint,The average reduction in angina attacks was 82%. This article will provide a brief introduction to some of the key advancements, for readers' reference only.

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◇ U.S. FDAApprovalPfizer’s one-time gene therapy Beqvez (fidanacogene elaparvovec) is used to treat adult patients aged 18 years or older with moderate to severe hemophilia B who are receiving prophylactic treatment with coagulation factor IX (FIX), or have had life-threatening bleeding episodes, or recurrent severe spontaneous bleeding events. These patients have tested negative for neutralizing antibodies against the adeno-associated virus serotype Rh74var (AAVRh74var) capsid using an FDA-approved assay.

The U.S. FDA approval of Beqvez was primarily based on the results of the single-arm, open-label Phase 3 clinical trial, BENEGENE-2.According to data released by Pfizer in December 2022, the gene therapy reduced patients' annualized bleeding rate (ABR) by 71% and the annualized infusion rate of clotting factors by 92%.

▲InIn the BENEGENE-2 trial,Beqvez Reduces Patients' Annualized Bleeding Rate (Image Source: Reference [9])

Beqvez is a novel gene therapy that contains bioengineered adeno-associated virus capsids andFIXHigh-activity variant of the gene.For patients with hemophilia B, the goal of this gene therapy is to enable them to produce their own FIX protein through a one-time treatment, rather than requiring regular intravenous infusions of FIX as with the current standard treatment. In December 2014, Pfizer acquired Beqvez from Spark Therapeutics for a $20 million upfront payment. Beqvez was approved for marketing by Health Canada in January this year and is currently under review by the European Medicines Agency (EMA).

◇ BioCardia Announces Primary Endpoint Results from the Roll-In Cohort of the Open-Label Trial for Its CardiAMP Cell Therapy Candidate for Treating Chronic Myocardial Ischemia. The results show,Compared with before treatment, the patients' exercise tolerance increased by an average of 107 seconds, and at the primary follow-up endpoint of 6 months, the incidence of angina pectoris decreased by an average of 82%.All patients responded positively to the treatment, showing improved exercise tolerance and reduced angina attacks.The press release pointed out that the results of these early open-label trials were better compared to the currently FDA-approved therapies in the United States.

CardiAMP is a cell therapy that delivers a patient's own bone marrow cells to the heart through a minimally invasive catheter procedure, stimulating the body's natural healing response.Previously, CardiAMP cell therapy received the FDA's Breakthrough Therapy Designation for the treatment of ischemic heart failure.

◇ Arsenal Biosciences announced that its T-cell therapy AB-2100 for the treatment of clear cell renal cell carcinoma (ccRCC) has completed the first patient dosing in a multicenter, open-label Phase 1/2 clinical trial.AB-2100 utilizes the company's CITE (CRISPR Electroporation Integration of Transgenes) technology to engineer T cells, enabling them to selectively target tumors and overcome the suppressive tumor microenvironment.These characteristics will potentially enable the patient's immune system to eliminate ccRCC cells without harming normal tissues.

◇ Aurion Biotech recently announced that all participants in the phase 1/2 clinical trial of its investigational therapy AURN001 have completed dosing.AURN001 is a cell therapy combination product consisting of allogeneic human corneal endothelial cells and the ROCK inhibitor Y-27632.It is expected to be injected into the eye as a one-time therapy for the treatment of corneal edema secondary to corneal endothelial dysfunction. This disease is a disabling condition that impairs vision and affects millions of patients worldwide.

◇ NKGen Biotech announced that the U.S. FDA has approved the IND application for its investigational natural killer (NK) cell therapy SNK01 for the treatment of Parkinson's disease.SNK01 is an autologous, non-genetically engineered NK cell product. It exhibits enhanced cytotoxicity and expression of activating receptors, representing a potential new approach for the treatment of Parkinson's disease.The company is expected to launch a Phase 1 clinical trial for Parkinson's disease in the second half of 2024.

◇ Replay and MD Anderson Cancer Center jointly announced that the U.S. FDA has approved the IND application for PRAME TCR/IL-15 NK (SY-307).PRAME TCR/IL-15 NK (SY-307) is an engineered T cell receptor (TCR) NK cell therapy developed from umbilical cord blood NK cells for the treatment of relapsed/refractory myeloid malignancies. These cells express a high-affinity TCR targeting the PRAME tumor-associated neoantigen.PRAME is highly immunogenic and expressed in a variety of different cancer types, including hematologic malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), as well as solid tumors like melanoma, sarcoma, ovarian cancer, endometrial cancer, lung cancer, and breast cancer. A Phase 1/2 study of the candidate therapy for the treatment of relapsed/refractory AML and MDS patients is expected to commence in the third quarter of 2024.

◇ Latus Bio, a biotechnology company focused on developing novel gene therapy candidates for the treatment of central nervous system (CNS) diseases, announced the initial completion of a $54 million Series A financing round. Latus’ proprietary technology aims to directly address the challenges faced by current AAV-based gene therapies—including reliance on high-dose injections, potential off-target toxicity caused by high doses, and difficulties in scaling production—by conducting large-scale, parallel, and unbiased screening of novel adeno-associated virus (AAV) capsids directly in non-human primates.In preclinical non-human primate models, Latus' capsid variants demonstrated high gene expression in precise areas of the central nervous system, with target cell specificity and minimal off-target activity.Based on these preclinical data, Latus Therapeutics plans to use a low dose of its candidate product in clinical studies, aiming to enhance the safety of gene therapy and achieve successful manufacturing.

This round of financing was led by 8VC and DCVC Bio, with participation from Samsung Life Science Fund, The Children’s Hospital of Philadelphia Foundation, Benjamin Franklin Technology Partners, Modi Ventures, and Gaingels. The CEO of Latus Therapeutics is P. Peter Ghoroghchian, M.D., Ph.D., a physician-scientist and serial biotech entrepreneur with extensive experience in advancing innovative therapies from platform identification through preclinical discovery to successful clinical development.

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◇ Astellas and Poseida Therapeutics jointly announced that Xyphos Biosciences, a wholly-owned subsidiary of Astellas, has signed a research collaboration and licensing agreement with Poseida. The agreement aims to jointly develop a novel convertible chimeric antigen receptor (convertibleCAR) cell therapy program by combining the innovative cell therapy platforms of both companies.

According to the terms of the agreement,The two companies plan to combine Poseida's proprietary allogeneic CAR-T platform with Xyphos' ACCEL technology to jointly develop two convertible CAR candidates for the treatment of solid tumors.Xyphos will pay for the costs incurred by Poseida in the research collaboration and take charge of the development and future commercialization of the collaborative products. Poseida will receive a $50 million upfront payment and is eligible for up to $550 million in potential development and sales milestone payments.

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References:

[1] U.S. FDA Approves Pfizer’s BEQVEZ™ (fidanacogene elaparvovec-dzkt), a One-Time Gene Therapy for Adults with Hemophilia B. Retrieved April 26, 2024, from https://www.pfizer.com/news/press-release/press-release-detail/us-fda-approves-pfizers-beqveztm-fidanacogene-elaparvovec

[2] BioCardia’s CardiAMP Cell Therapy Chronic Myocardial Ischemia Trial Results Show Patient Benefits in Important Outcomes. Retrieved May 6, 2024, from https://www.globenewswire.com/news-release/2024/05/01/2873082/0/en/BioCardia-s-CardiAMP-Cell-Therapy-Chronic-Myocardial-Ischemia-Trial-Results-Show-Patient-Benefits-in-Important-Outcomes.html

[3] Arsenal Biosciences Announces First Patient Dosed in Phase 1/2 Clinical Trial of AB-2100 in Development as a Treatment for Clear-cell Renal Cell Carcinoma. Retrieved May 6, 2024, from https://www.businesswire.com/news/home/20240430131934/en/

[4] Aurion Biotech Announces Completion of Enrollment in Phase 1 / 2 Clinical Trial. Retrieved May 6, 2024, from https://www.businesswire.com/news/home/20240430312515/en

[5] NKGen Biotech Announces FDA Clearance of Investigational New Drug (IND) Application for SNK01 NK Cell Therapy in Parkinson’s Disease. Retrieved April 30, 2024, from https://www.globenewswire.com/news-release/2024/04/29/2871205/0/en/NKGen-Biotech-Announces-FDA-Clearance-of-Investigational-New-Drug-IND-Application-for-SNK01-NK-Cell-Therapy-in-Parkinson-s-Disease.html

[6] Replay and MD Anderson announce FDA clearance of IND application for first-in-class PRAME-targeted T-Cell Receptor Natural Killer (TCR-NK) cell therapy for hematological malignancies. Retrieved April 30, 2024, from https://www.globenewswire.com/news-release/2024/04/30/2872029/0/en/Replay-and-MD-Anderson-announce-FDA-clearance-of-IND-application-for-first-in-class-PRAME-targeted-T-Cell-Receptor-Natural-Killer-TCR-NK-cell-therapy-for-hematological-malignancies.html

[7] Astellas and Poseida Therapeutics Enter Into Research Collaboration and License Agreement to Develop Novel Allogeneic Cell Therapies in Oncology. Retrieved May 6, 2024, from https://www.prnewswire.com/news-releases/astellas-and-poseida-therapeutics-enter-into-research-collaboration-and-license-agreement-to-develop-novel-allogeneic-cell-therapies-in-oncology-302133127.html

[8] Latus Launches with State-of-the-Art Gene Therapy Development Technologies, Two Lead Product Candidates, and an Initial $54 Million in Series A Financing. Retrieved May 6, 2024, from https://www.businesswire.com/news/home/20240502968167/en

[9] Efficacy and Safety of Fidanacogene Elaparvovec in Adults With Moderately Severe or Severe Hemophilia B: Results From the Phase 3 BENEGENE-2 Gene Therapy Trial. Retrieved January 4, 2024 from https://genetherapy.isth.org/efficacy-and-safety-of-fidanacogene-elaparvovec-in-adults-with-moderately-severe-or-severe-hemophilia-b-results-from-the-phase-3-benegene-2-gene-therapy-trial

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