close
close

TG Therapeutics Receives FDA Approval for Phase 1 Multiple Sclerosis Trial for Allogeneic CAR-T Azer-Cel

The FDA has approved an Investigational New Drug (IND) application submitted by TG Therapeutics for azercabtagene zapreleucel (azer-cel), an investigational allogeneic chimeric antigen receptor T-cell (CAR-T) therapy, for a Phase 1 clinical trial in patients with progressive multiple sclerosis (MS).1

Azer-cel was originally developed by Precision BioSciences but licensed to TG Therapeutics for further development as a potential treatment for autoimmune diseases and other non-cancer indications. With the IND approval, TG Therapeutics now intends to initiate a Phase 1 clinical trial before the end of the year.

“We would like to congratulate TG Therapeutics on the IND approval for azer-cel in patients with progressive MS,” said Michael Amoroso, MBA, CEO of Precision BioSciences, in a statement.1 “We believe that expanding allogeneic CAR-T treatments to autoimmune diseases has the potential to unlock new therapies for patients with chronic diseases. We look forward to TG Therapeutics initiating a clinical trial for azer-cel in autoimmune diseases as we focus on advancing our own wholly-owned in vivo gene editing pipeline, including our planned IND and/or clinical trial application submission for PBGENE-HBV for hepatitis B this year.”

Precision received an upfront payment and potential short-term gain valued at $17.5 million for licensing azer-cel to TG Therapeutics. In addition, the deal includes the potential for additional milestone payments of up to $288 million, as well as the potential for royalties.

Azer-cel is not the only cell therapy currently being developed to treat MS. Just earlier this month, the FDA approved Indapta Therapeutics' IND application to evaluate its g-natural killer (g-NK) cell therapy IDP-023 in patients with progressive multiple sclerosis (MS).2 IDP-023 is a universal, allogeneic NK cell therapy that exhibits highly robust, antibody-dependent cell-mediated cytotoxicity, inherent antiviral activity, and an NKG2C receptor that targets HLA-E-expressing cells. It consists of naturally occurring g-minus NK cells that arise from epigenetic alterations resulting from exposure to cytomegalovirus.

Another study evaluating a novel therapy for MS is IASO Bio's recently approved Phase 1/2 study of its (CAR) T-cell therapy equecabtagene autoleucel (Eque-Cel), which received IND approval in July 2024.3 Eque-cel is a fully human anti-BCMA CAR-T cell therapy that was initially investigated for the treatment of multiple myeloma and is also currently being used to treat other forms of autoimmune diseases of the central nervous system, including neuromyelitis optica spectrum disorders, myasthenia gravis, immune-mediated necrotizing myopathy and generalized myasthenia gravis.

Kyverna Therapeutics is also investigating the potential of its CAR-T therapy KYV-101 to treat MS.4 It showed a manageable safety profile and demonstrated expansion-dependent effects of CAR-T cells on CD19+ target cells in the central nervous system of MS patients treated by researchers at the University Hospital Hamburg. KYV-101 is an autologous, fully human CD19 CAR-T cell therapy being investigated for the treatment of B cell-driven autoimmune diseases.

Precision BioSciences focuses its efforts on advancing in vivo gene therapy products based on its ARCUS platform. CGTLive® previously spoke with Gary Owens, MS, Deputy Director of Gene Therapy Discovery at Precision Biosciences, about the potential of the ARCUS platform in Duchenne muscular dystrophy (DMD) at the 2023 American Society of Gene and Cell Therapy (ASGCT) Annual Meeting, held May 16-20 in Los Angeles.5 Owens outlined the preclinical results he presented at the conference and the key implications of the research for the healthcare community. He highlighted that the DMD model mice treated with the ARCUS approach achieved a maximum force output (MFO) in the gastrocnemius muscle that reached 86% of the values ​​of healthy control mice, a significant improvement over the MFO of untreated DMD model mice.

REFERENCES
1. Precision BioSciences Announces Investigational New Drug Authorization by Partner TG Therapeutics to Investigate Azer-Cel for Multiple Sclerosis. Press release. Precision BioSciences, Inc. August 9, 2024. Retrieved August 14, 2024. https://investor.precisionbiosciences.com/news-releases/news-release-details/precision-biosciences-announces-investigational-new-drug
2. Indapta Therapeutics Announces FDA Clearance of IND for Phase 1 Trial of IDP-023 for Progressive Multiple Sclerosis. Press release. Indapta Therapeutics. August 6, 2024. https://www.businesswire.com/news/home/20240806112913/en/Indapta-Therapeutics-Announces-FDA-Clearance-of-IND-for-Phase-1-Trial-of-IDP-023-for-Progressive-Multiple-Sclerosis
3. IASO Bio Receives US FDA Approval of Investigational New Drug Application for EquecabtageneAutoleucel for Multiple Sclerosis. Press release. IASO Bio. July 23, 2024. https://www.prnewswire.com/news-releases/iaso-bio-receives-us-fda-approval-of-investigational-new-drug-application-for-equecabtagene-autoleucel-for-multiple-sclerosis-302204711.html
4. Fischbach F, Richter J, Pfeffer LK, et al. CD19-targeted chimeric antigen receptor T cell therapy in two patients with multiple sclerosis. Med. Published online March 29, 2024. doi: 10.1016/j.medj.2024.03.002
5. Lewis W, Owens G, Jordan-Steele M, et al. ARCUS-mediated excision of the “hot spot” region of the human dystrophin gene for the treatment of Duchenne muscular dystrophy (DMD). Presented at: American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting. May 16-20, 2023; Los Angeles, CA.

You may also like...