What You Need to Know in Cell and Gene Therapy Right Now

In this post, we update on and analyze some of the recent stories in the news regarding Cell and Gene Therapy.  For detailed updates, additional news analysis, scientific innovations and market opportunity updates, subscribe to Cell and Gene Therapy Business Outlook from Science and Medicine Group.

• Avantor, based in Radnor, PA, has agreed to purchase the Vernon Hills, IL-based Masterflex bioprocessing business and related assets of Antylia Scientific in an all-cash deal valued at $2.9 billion ($2.7 billion with anticipated tax benefits). Masterflex manufactures peristaltic pumps and aseptic single-use fluid-transfer technologies, and its 2022 revenues are estimated to top approximately $300 million.  The purchase will strengthen Avantor’s offerings across all bioproduction platforms, including monoclonal antibodies, cell and gene therapy, and mRNA, according to the company. It will also support manufacturing of both therapies and vaccines, including COVID-19.  Earlier this year Avantor acquired German-based Ritter GmbH, a manufacturer of robotic and liquid handling consumables, for more than $1 billion.
• The FDA has placed a clinical hold on BioMarin’s BMN 307, an investigational gene therapy designed to permanently maintain normal blood phenylalanine levels in phenylketonuria (PKU) patients. The treatment uses AAV5, an adeno-associated virus (AAV) viral vector to target cells in the liver and deliver a functional copy the PAH gene encoding the enzyme phenylalanine hydroxylase.  The hold came in response to liver tumors, with evidence of AAV integration into the genome, reported in mouse studies.  BioMarin has emphasized that cancers caused by AAV integration have not been reported in larger animals or humans.
• BioLife Solutions, based in Bothell, WA, has closed on its acquisition of Indianapolis, IN-based Sexton Biotechnologies (which spun off from Cook Regentec in 2019). This is their sixth acquisition in the last 2.5 years. The acquisition is part of BioLife’s strategy to assemble a portfolio of class-defining bioproduction tools and services for the cell and gene therapy and broader biopharma markets, company representatives said. Sexton’s bioproduction portfolio includes proprietary closed vials for cell therapy final-dose packaging, human platelet lysate (HPL) media, a bio-defined replacement for fetal bovine serum or human serum used in cell manufacturing, and automated cell processing machines. The company’s products are currently embedded in more than 50 ongoing clinical trials of new cell and gene therapies, BioLife said.
• Yokohama, Japan-based Reprocell and Osaka-based Texcell Japan (a subsidiary of French-based Texcell Group) have signed a Strategic Collaboration Agreement for induced pluripotent stem cell (iPSC) master cell bank (MCB) manufacturing. Under the terms of the agreement, Reprocell can outsource part of the MCB manufacturing process at Texcell’s GMP facility to meet the increasing demand for GMP iPSC MCBs. The agreement supplements a Master Service Agreement the two companies previously signed.
• Tokyo-based Astellas Pharma is pausing screening and dosing of more participants in a clinical trial for its AT132 gene therapy to treat X-linked myotubular myopathy (XLMTM). Last year three children died of liver failure after receiving the highest dose, and the FDA placed the study on clinical hold. The FDA lifted the hold in December of last year to continue the study at a lower dose, but Astellas has placed the program on a voluntary hold after a report that a low-dose patient experienced a serious adverse event in the form of unusual liver function.
• STEMCELL Technologies (based in Vancouver, Canada) and Madison, WI-based WiCell have partnered to launch human pluripotent stem cell (hPSC) characterization and banking services. These services aim to reduce variability and improve reproducibility for various downstream applications, including disease modeling, drug discovery, toxicology screening, and regenerative medicine research. The collaboration will make it easier for pluripotent stem cell researchers to characterize new or existing cell lines and create fully characterized banks of hPSCs, according to both organizations.  Initially, the services only will be offered in the U.S.

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• Natick, MA-based HebeCell has announced that it has raised $53 million in a Series A financing round led by Beijing-based Jacobio Pharmaceuticals, who will collaborate with HebeCell to advance off-the-shelf pluripotent stem cell-derived chimeric antigen receptor-expressing natural killer (PSC-CAR-NK) cell products to clinics. The companies plan to develop PSC-CAR-NK therapies for cancer, viral infection, and autoimmune diseases. Funds will be used to speed up HebeCell’s R&D program, investigational new drug application, clinical application, and marketing as the company grows its operations both in the US and internationally.
• NeuExcell Therapeutics and Spark Therapeutics, a Roche subsidiary based in Philadelphia, PA, have announced a collaboration to develop a gene therapy for Huntington’s disease. NeuExcell Therapeutics is a gene therapy company focused on neurodegenerative diseases, with headquarters in State College, PA, and Shanghai, China. Under the terms of the agreement, Spark will gain access to NeuExcell’s neuroregenerative gene therapy platform and will collaborate with NeuExcell’s research team.  Spark has the option to license the exclusive worldwide rights to NeuExcell’s Huntington’s disease program, and NeuExcell is eligible to receive upfront, license fee, R&D, and sales milestone payments worth up to approximately $190 million, plus product royalties. Defying conventional wisdom that mammalian adult neurons cannot be replaced, NeuExcell’s neuroregenerative gene therapy platform performs in vivo astrocyte-to-neuron conversion by introducing neural transcription factor(s) with an AAV vector.  While neurons cannot regenerate by themselves, surrounding glial cells like astrocytes can divide and supply a renewable source for generating new neurons through trans-differentiation.  NeuExcell’s development pipeline includes major neurodegenerative diseases such as stroke, Huntington’s disease, amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, Parkinson’s disease, traumatic brain injury, spinal cord injury, and glioma.  The company recently raised more than $10 million in a series pre-A funding round led by Co-Win Ventures, and has announced that it has added two members to its board of directors: Dr. Xin Huang and Jonathan Sun.
• NovaRock Biotherapeutics, based in Ewing Township, NJ, has granted an exclusive license to New York-based Flame Biosciences to develop, manufacture, and commercialize NovaRock’s NBL-015, a fully human anti-Claudin 18.2 monoclonal antibody to treat pancreatic and gastric cancer. NBL-015 has been optimized to achieve enhanced antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antibody-dependent cellular phagocytosis (ADCP) effects.  Its Investigational New Drug Application was approved by the FDA in May 2021. Flame Biosciences will have exclusive rights to NBL-015 outside of greater China (including mainland China, Hong Kong, Macau, and Taiwan), and will be responsible for the development, regulatory approval, and commercialization of NBL-015, according to the companies. NovaRock will also collaborate with Flame on the discovery and preclinical development of two new candidates based on NovaRock’s NovaTE bispecific antibody technology platform,  designed to selectively activate the antigen-experienced T cells in the tumor microenvironment. NovaRock will subsequently grant Flame exclusive rights to further develop, manufacture, and commercialize licensed products.  NovaRock will receive an upfront payment of $7.5 million, with up to $172.5 million in development milestone payments and $460 million in sales milestone payments, plus royalties.  Lead candidates from the collaboration are expected to enter clinical development in late 2023.
• The FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee met September 2^nd-3^rd to discuss toxicity risks associated with adeno-associated virus (AAV) vector.  Topics included cancer risks caused by vector genome integration, liver toxicity, thrombotic microangiopathy, and neurotoxicity. While the committee did not advise that the FDA should slow down clinical trials, they did make recommendations for more extensive testing in animals, improved screening of clinical trial participants, and more thorough follow-up of treated patients.
• Vertex Pharmaceuticals, based in Boston, MA, and Arbor Biotechnologies, based in Cambridge, MA, have announced a new agreement to develop ex vivo engineered cell therapies based on Arbor’s CRISPR gene editing technologies. The agreement expands upon a previous partnership the two companies established in 2018 and grants Vertex rights to use Arbor’s technology to research and develop ex vivo engineered cell therapy programs, including programs for generating fully differentiated, insulin-producing hypoimmune islet cells for the treatment of type 1 diabetes, for developing next-generation approaches in sickle cell disease and beta thalassemia, and for the treatment of other diseases, according to the companies.  In addition to an upfront cash payment, Arbor will be eligible to receive up to $1.2 billion in potential milestone payments across up to seven potential programs. Vertex will also invest in Arbor in the form of a convertible note and will pay tiered royalties on future net sales of products resulting from the collaboration.