8 Recent Developments in Cell and Gene Therapy

There have been a number of recent developments in cell and gene therapy, as detailed in our bi monthly newsletter, Cell and Gene Therapy Business Outlook.  New approvals in various countries, and technology licenses.

• Bristol-Myers Squibb K.K., a Tokyo-based subsidiary of Bristol-Myers Squibb (BMS), has announced that Japan’s Ministry of Health, Labour and Welfare has approved Abecma (idecabtagene vicleucel), a chimeric antigen receptor (CAR) T cell immunotherapy targeting B-cell maturation antigen (BCMA), for the treatment of adult patients with relapsed or refractory (R/R) multiple myeloma (MM) who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody, and have either experienced disease progression on the last therapy or relapse after the last therapy.  BMS is the only company with two CAR T cell therapies approved in Japan:  Breyanzi, targeting CD19 for R/R large B-cell lymphoma1 and R/R follicular lymphoma, and now Abecma, targeting BCMA for R/R MM.
• Neurophth Therapeutics, based in Wuhan, China has announced it has received U.S. FDA clearance of its investigational new drug (IND) application for its in vivo gene replacement therapy NR082 (rAAV2-ND4). NR082 is a novel recombinant adeno-associated viral serotype 2 vector (rAAV2) containing a codon-optimized of NADH-dehydrogenase subunit 4 (ND4) gene, to be administered by ophthalmic injection for the treatment of Leber hereditary optic neuropathy (LHON) associated with a mutation in the ND4 NR082 was the first adeno-associated virus 2 (AAV2) gene therapy investigational new drug application approval in China, with the first patient dosed in June 2021. The U.S. FDA granted orphan-disease designation NR082 in September of 2020.
• Eikonoklastes Therapeutics, based in Cincinnati, OH, has announced a license agreement with the University of California San Diego (UCSD) to add a novel gene therapy for the treatment of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s Disease. The company emerged from stealth with seed financing in July of 2020, and raised a Series A financing round in June 2021.   Its first therapeutic candidate was a novel immune conjugate platform called L-ICON3 for the treatment of Triple Negative Breast Cancer (TNBC), which was discovered and engineered by scientific founder Zhiwei Hu, MD, PhD.  The newly licensed gene therapy technology was invented by Brian Head, PhD, Professor in the Department of Anesthesiology at UCSD, whose laboratory has been studying neuron-targeted caveolin-1 as a gene therapy for ALS, age-related neurodegenerative disorders such as Alzheimer’s disease, and traumatic brain injury.
• Allogene Therapeutics, based in South San Francisco, CA, and Antion Biosciences, based in Geneva, Switzerland, have announced an exclusive collaboration and global license agreement to use Antion’s proprietary microRNA (miRNA)-based “miCAR” technology to develop multiplex gene silencing for allogeneic CAR T products. In preclinical studies, Antion’s miCAR platform has demonstrated the ability to silence multiple gene targets in a single step.  Allogene plans to leverage Antion’s miCAR with other technologies to develop allogeneic CAR T therapies. Under the agreement, Antion will exclusively collaborate with Allogene on oncology products for a defined period and Allogene will have exclusive worldwide rights to products developed during the collaboration. In exchange, Allogene will pay Antion an upfront cash payment and provide a preferred equity investment, along with milestone payments, and single-digit royalties on any product sales.
• Takeda Pharmaceutical Company, based in Osaka, Japan, has announced the exercise of its option to acquire Adaptate Biotherapeutics, a London-based company developing antibody-based therapeutics for the modulation of variable delta 1 (Vδ1) gamma delta (γδ) T cells. Takeda will obtain Adaptate’s antibody-based γδ T cell engagers, which are designed to specifically modulate γδ T cell-mediated immune responses at tumor sites while sparing damage to healthy cells. Takeda recently exercised an option to acquire GammaDelta Therapeutics, a London-based company developing allogeneic γδ T cell therapies, and this new acquisition solidifies Takeda’s foothold in a highly specialized field.  Takeda plans to combine GammaDelta’s γδ T cell therapy-based platform and Adaptate’s antibody-based γδ T cell engager platform with its own R&D positions to become a leader in the application of γδ T cell therapies against cancer.
• Castle Creek Biosciences, a late-clinical stage cell and gene therapy company based in Exton, PA, has acquired Rochester, MN-based Novavita Thera, a preclinical gene therapy company specializing in rare liver and metabolic diseases. The acquisition will add in vivo capabilities to Castle Creek’s existing ex vivo technology platform, and expand its development pipeline from skin and connective tissue disorders into rare liver diseases. Castle Creek will develop a lentiviral-based gene therapy called LV-FAH for the treatment hereditary tyrosinemia type 1 (HT1).  HT1 is a rare genetic metabolic disorder caused by a deficiency of the enzyme fumarylacetoacetate hydrolase (FAH), which leads to accumulation of tyrosine and its metabolites in the liver.  LV-FAH is administered to the liver through the portal vein, where it transduces hepatocytes with a functional copy of the human FAH  Castle Creek plans to submit an IND application to the U.S. FDA for LV-FAH in the treatment of HT1.
• Moderna, based in Cambridge, MA, and Carisma Therapeutics, based in Philadelphia, PA, have announced a strategic collaboration for in vivo engineered chimeric antigen receptor monocyte (CAR-M) therapeutics for the treatment of cancer. Moderna specializes in messenger RNA (mRNA)-based therapeutics and vaccines, while Carisma is developing engineered macrophage-based therapeutics for cancer. Carisma’s lead candidate is CT-0508, an ex vivo gene-modified autologous CAR-Macrophage cellular therapy for the treatment of solid tumors that overexpress human epidermal growth factor receptor 2 (HER2). CT-0508 is currently in Phase I clinical development and is the first CAR-Macrophage therapy to enter clinical trials.  The collaboration will leverage Moderna’s expertise in mRNA and lipid nanoparticle (LNP) delivery with Carisma’s expertise in engineered macrophage biology to develop an off-the-shelf approach to engineer a patient’s own monocytes and macrophages in vivo.  Under the agreement, Moderna will pay Carisma $45 million up front, along with a $35 million investment in the form of a convertible note.  Carisma will also receive research funding and milestone payments, plus royalties on net sales. Carisma will be responsible for the discovery and optimization of candidates, while Moderna will lead clinical development and commercialization.  Moderna will be able to select up to twelve targets under the agreement.
• Pfizer, based in New York, and Beam Therapeutics, based in Cambridge, MA, have announced an exclusive four-year research collaboration on three targets for rare genetic diseases of the liver, muscle, and central nervous system. The collaboration will combine Beam’s proprietary in vivo mRNA and lipid nanoparticle (LNP) delivery technologies with Pfizer’s experience in developing and manufacturing medicines and vaccines.  Under the agreement, Beam will receive an upfront payment of $300 million and is eligible milestone payments of up to $1.35 billion, if Pfizer exercises its opt-in rights for all three targets,. Beam is also eligible for royalties on net sales. The collaboration’s term is four years, with an optional extension of one year.