There have been a number of recent developments in cell and gene therapy, as detailed in our bimonthly newsletter, Cell and Gene Therapy Business Outlook.

1. EdiGene, a gene-editing company based in Beijing, China, has entered a non-exclusive, worldwide license agreement with Boston Children’s Hospital (BCH) for intellectual property rights covering the upregulation of fetal hemoglobin by disrupting a key gene. Upregulation of fetal hemoglobin is a potential treatment for many genetic diseases resulting from abnormal hemoglobin structures (hemoglobinopathies), essentially replacing the defective hemoglobin molecule with its fetal version.  Fetal hemoglobin production typically stops after birth, but can be restarted by disrupting expression of the BCL11A  EdiGene plans to use this technology to develop ET-01, a gene-editing therapy for the treatment of transfusion-dependent β-thalassemia.
2. Iovance Biotherapeutics, based in San Carlos, CA, has announced that the U.S. FDA has cleared its IND application for IOV-4001, its first genetically modified tumor-infiltrating lymphocyte (TIL therapy), for the treatment of unresectable or metastatic melanoma and stage III or IV non-small cell lung cancer (NSCLC). IOV-4001 uses TALEN gene editing technology, licensed from Paris-based Cellectis, to inactivate the PDCD1 gene encoding PD-1 protein. PD-1 is an immune checkpoint, and blocking its expression can increase the T cell response against cancer cells.  Iovance expects to begin clinical studies of IOV-4001 in 2022, and the company has a substantial preclinical pipeline of TALEN-edited TIL therapies in development. (See Cell and Gene Therapy Business Outlook 1, issue 12, p. 13 for more on Cellectis’ TALEN technology platform.)
3. NexImmune, a clinical-stage biotech company based in Gaithersburg, MD, has announced a research and evaluation collaboration with The Laura and Isaac Perlmutter Cancer Center at NYU Langone Health. The collaboration will evaluate NexImmune’s artificial antigen presenting cells (aAPCs) by examining their ability to expand anti-tumor T cell populations in samples provided by melanoma patients.  NexImmune’s Artificial Immune Modulation (AIM) platform is designed to mimic the activity of natural antigen presenting cells by using nanoparticles to present immune signaling molecules to T cells.
4. Ossium Health, a clinical-stage bioengineering company based in San Francisco, CA, has announced that the U.S. FDA has accepted its IND application for OSSM-001, an allogeneic, bone marrow-derived, mesenchymal stem cell (MSC) therapy for the treatment of refractory perianal fistulas in patients with Crohn’s disease. Ossium plans to initiate a Phase I clinical trial by the end of 2022.
5. Catamaran Bio, based in Cambridge, MA, is expanding its CAR-NK research collaboration with Branden Moriarity, PhD, of the University of Minnesota. The company is developing off‑the-shelf chimeric antigen receptor natural killer (CAR-NK) cell therapies to treat cancer using the TcBuster transposon platform, a nonviral genetic modification system, to engineer the CAR-NK cells. Catamaran has licensed the TcBuster platform from Bio-Techne Corporation, and Moriarity’s team have adapted it for use in human immune cells.  The next steps in the collaboration will further develop the TcBuster system, as well as optimize the manufacture of CAR-NK cells.  Catamaran has also exclusively licensed University of Minnesota’s patent rights for innovative cell expansion technologies which do not require feeder cells.
6. Kairos Pharma, a clinical-stage biopharmaceutical company based in Los Angeles, CA, has announced that KROS 201, its investigational activated T cell (ATC) therapy, has received FDA approval for a Phase I clinical trial for the treatment of recurrent glioblastoma. KROS 201 consists of autologous helper and killer T cells that have been primed and activated in vitro to target cancer stem cell-specific antigens, then re-infused intravenously into patients.
7. SCG Cell Therapy, based in Singapore, has announced that the China National Medical Products Administration (NMPA) has cleared its IND application for SCG101, the company’s first T-cell receptor (TCR) T-cell therapy targeting hepatitis B virus (HBV) antigens for the treatment of HBV-related hepatocellular carcinoma (HCC). SCG101 is an autologous TCR-T cell therapy which targets specific HBV epitopes. HBV viral DNA can integrate into host hepatocyte genomes during HBV infection, compromising the genome’s integrity and often leading to HCC.  SCG101 redirects T cells to target HBV antigens displayed on malignant hepatocyte cell surfaces as a potential treatment for HBV-related HCC.
8. Novartis, based in Basel, Switzerland, has signed an initial agreement with Carisma Therapeutics, based in Philadelphia, PA, to manufacture its HER2-targeted chimeric antigen receptor macrophage (CAR-M) cell therapy. Carisma is developing engineered macrophage-based therapeutics for cancer, and its lead candidate, CT-0508, is an ex vivo, gene-modified, autologous CAR-M cellular therapy for the treatment of solid tumors that overexpress HER2. CT-0508 is currently in Phase I clinical development and is the first CAR-M therapy to enter clinical trials.  Under the initial agreement, Carisma Therapeutics’ manufacturing process will move to Novartis’ Cell Therapy Site in Morris Plains, NJ, with clinical manufacturing planned to begin in 2023.
9. CKD Bio, based in Seoul, South Korea, has announced a contract manufacturing organization (CMO) deal with EnhancedBio, also based in Seoul, to produce ionizable lipids for use in engineered ionizable lipid nanoparticle (EN-LNP) delivery systems.   The EN-LNP platform can be used to deliver a variety of gene therapy materials, including mRNA, siRNA, and CRISPR systems, and can be tailored for delivery to specific target cells.  The technology was developed by Lee Hyuk-jin, PhD, and his team at Ehwa Womans University College of Pharmacy and is licensed to EnhancedBio.  Under the terms of the agreement, CKD Bio will exclusively produce and supply ionizable lipids to EnhancedBio for a period of 10 years, and EnhanceBio will develop an siRNA-based anticancer therapeutic using CKD Bio’s ionizable lipids.
10. Selecta Biosciences, based in Watertown, MA, has announced that the U.S. FDA has removed a clinical hold on its Phase I/II clinical trial of SEL-302 for the treatment methylmalonic acidemia (MMA), a rare metabolic disease that affects the body’s ability to metabolize certain amino acids and fats. SEL-302 consists of two components: MMA-101, an AAV-based gene therapy that delivers a functional copy of the MMUT gene encoding methylmalonyl-CoA mutase to treat MMA, plus ImmTOR, Selecta’s nanoparticle-based system that delivers rapamycin to immune cells to promote immune tolerance and allow AAV vectors to be re-dosed.  The trial had not yet been initiated, as the hold was placed in connection with an FDA request for additional information about the product candidate. With the hold lifted, Selecta plans to initiate the trial soon.
11. Cellevolve Bio, a cell therapy development and commercialization company based in San Francisco, CA, and Seattle Children’s Therapeutics, a non-profit therapeutics development group at Seattle Children’s, have announced a collaboration to develop and commercialize a group of novel multiplex CARs for the treatment of pediatric central nervous system (CNS) cancers. Early clinical GMP research on novel CARs will take place at Seattle Children’s Cure Factory facility, and lentiviral vector manufacturing will occur at its new VectorWorks facility. The two companies will collaborate to advance Seattle Children’s BrainChild research project, which currently has three pediatric programs in Phase I clinical development for indications in brain and CNS tumors; EGFR-positive recurrent or refractory (R/R) pediatric CNS tumors; and diffuse intrinsic pontine glioma (DIPG), diffuse midline glioma (DMG), or R/R CNS tumors.  Under the agreement, Seattle Children’s Therapeutics will be responsible for early-stage discovery, preclinical development, and Phase I clinical development, while Cellevolve will take over for Phase II and subsequent clinical development, with the participation of Seattle Children’s Therapeutics.  Cellevolve will provide financial support for Seattle Children’s Therapeutics, including milestone payments, and Seattle Children’s will receive an equity stake in Cellevolve.  In return, Cellevolve will retain global licensing rights to any commercial assets from the collaboration.  Seattle Children’s Therapeutics hopes to launch a fourth clinical program with the new funding.
12. Cambridge, MA-based gene-editing company eGenesis has announced a research collaboration with the University of Miami Leonard M. Miller School of Medicine to evaluate its gene-edited pancreatic Human Compatible (HuCo) islet cells in a clinically relevant diabetes model, with an eye towards later human clinical trials. HuCo organs and cells are derived from genetically-modified nonhuman animals (most often pigs), and eGenesis intends to revolutionize organ transplantation with their technology platform.  The company uses gene-editing technology such as CRISPR to overcome the challenges which have plagued xenotransplantation efforts to date, and has previously-established, ongoing partnerships with Massachusetts General Hospital and Duke University School of Medicine.
13. Twist Bioscience, based in South San Francisco, CA, and Kriya Therapeutics, based in Redwood City, CA, have announced an agreement to discover new antibodies for oncology therapies to be delivered using adeno-associated viral (AAV) gene therapy. The collaboration will combine Twist’s antibody libraries with Kriya’s proprietary vector engineering platform to discover novel antibodies against specific targets of interest to be delivered with Kriya’s gene therapy technology.
14. Novartis, based in Basel, Switzerland, and Voyager Therapeutics, based in Cambridge, MA, have signed a license option agreement for three next-generation adeno-associated virus (AAV) capsids targeting neurological diseases, with options to license capsids for two other targets. The capsids were discovered through Voyager’s proprietary directed-evolution TRACER (Tropism Redirection of AAV by Cell-type-specific Expression of RNA) platform, and data suggest they may demonstrate improved distribution to neurons in the cortex and deeper brain regions.  Novartis will have the right to evaluate novel capsids and to exercise license options to capsids for exclusive use in Novartis-developed gene therapies for three disease targets, with the option to license capsids for two additional disease targets under the same terms.  In return, Voyager will receive an upfront payment, payments for each exercised option, milestone payments, and sales-based royalties.