13 Recent Developments in Cell and Gene Therapy as of April 8, 2022

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. Bristol Myers Squibb, based in New York, NY, has announced that the European Commission (EC) has granted Marketing Authorization for Breyanzi (lisocabtagene maraleucel; liso-cel), its CD19-targeted chimeric antigen receptor (CAR)-T cell immunotherapy, as a third-line treatment for adults with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), and follicular lymphoma grade 3B (FL3B). Breyanzi is Bristol Myers Squibb’s second CAR-T cell therapy to be approved in the EU, joining Abecma’s approval in August of last year as a fourth-line treatment for adults with R/R multiple myeloma.
2. Kite, a Gilead Company based in Santa Monica, CA, has announced that the U.S. FDA has approved its CD19-targeted chimeric antigen receptor (CAR)-T cell therapy Yescarta (axicabtagene ciloleucel) for the treatment of large B-cell lymphoma (LBCL) that is refractory to, or that has relapsed within 12 months of, first-line chemo-immunotherapy. Yescarta is the first CAR-T cell therapy for to be approved by the FDA for initial treatment of relapsed or refractory (R/R) LBCL, and the first therapy to demonstrate improvement over the current standard of care (SOC) in almost 30 years.  The therapy was initially approved by the FDA in 2017 as a third-line therapy for R/R LBCL.
3. JW Therapeutics, based in Shanghai, China, has announced it has received IND clearance from the National Medical Products Administration (NMPA) of China for a pivotal clinical trial of Carteyva (relmacabtagene autoleucel), its autologous chimeric antigen receptor (CAR)-T cell therapy targeting CD19 as a second-line treatment for relapsed/refractory (R/R) large B-Cell lymphoma (LBCL). The Phase III trial’s primary endpoint will be event-free survival (EFS), while secondary endpoints will include complete response rate (CRR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), pharmacokinetics, and safety.
4. Anixa Biosciences, based in San Jose, CA, has announced the initiation of a Phase I clinical trial evaluating its novel chimeric antigen receptor (CAR)-T cell therapy for the treatment of ovarian cancer. The therapy’s design differs a bit from traditional CARs, which typically feature an antigen binding domain comprised of a single-chain variable fragment (scFv) derived from an antibody.  Instead of an antibody-derived scFv, the CAR utilizes a ligand to target the follicle stimulating hormone receptor (FSHR), which is expressed exclusively on ovarian cells. The approach is known as chimeric endocrine receptor (CER)-T cell therapy, since the interaction is mediated by ligand-receptor binding rather than antibody-antigen binding. The therapy was developed at Philadelphia’s Wistar Institute by Alfredo Perales-Puchalt, MD, PhD, and José Conejo-Garcia, MD, PhD, and the Phase I trial will take place at Moffitt Cancer Center in Tampa, FL.
5. Myeloid Therapeutics and Prime Medicine, both based in based in Cambridge, MA, have announced an exclusive option and research collaboration agreement to develop Myeloid’s proprietary RetroT platform. RetroT is an RNA-based, retrotransposon-mediated gene-insertion technology that delivers genetic sequences and integration enzymes with a single mRNA strand, and has the potential to insert entire genes into a genome. Under the agreement, Myeloid receives a $45 million upfront payment from Prime, as well as future milestone payments and royalties.  In exchange, Prime will have the exclusive option to gain control of intellectual property from the collaboration to be used alongside its own Prime Editing platform, which adapts CRISPR/Cas technology to perform genome editing operations.
6. Novartis, based in Basel, Switzerland, has announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended the European Commission to approve its chimeric antigen receptor (CAR)-T cell therapy Kymriah (tisagenlecleucel) as a third-line treatment for adults with relapsed or refractory (R/R) follicular lymphoma (FL). The European Commission will make its final decision in approximately two months, and approval would be applicable to all 27 EU member states plus Iceland, Norway, and Liechtenstein.  Kymriah has already been approved in the EU for two other indications: the treatment of children and young adults with B cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post-transplant, or in second or later relapse; and as a third-line treatment for adults with R/R diffuse large B cell lymphoma (DLBCL).
7. Legend Biotech Corporation, based in Somerset, NJ, has announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended Janssen Pharmaceutica’s marketing authorization of its chimeric antigen receptor (CAR)-T cell therapy CARVYKTI (ciltacabtagene autoleucel, or cilta-cel) as a fourth-line treatment for adults with relapsed and refractory (R/R) multiple myeloma (MM). CARVYKTI is a genetically modified, autologous T-cell immunotherapy with a CAR design featuring two single-domain antibodies targeting B-cell maturation antigen (BCMA), which is primarily expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B-cells and plasma cells. In December 2017, Legend entered into an exclusive worldwide license and collaboration agreement with Janssen Biotech to develop and commercialize CARVYKTI. In February 2022, CARVYKTI was approved by the U.S. FDA as a fifth-line treatment for adults with R/R MM.
8. Exothera, a viral vector contract manufacturing and development organization (CDMO) based in Charleroi, Belgium, has received Good Manufacturing Practices (GMP) certification for its facilities in Jumet, Belgium, from the Federal Agency for Medicines and Health Products (FAMHP). Exothera is a subsidiary of Univercells, and the facilities occupy with a combined area of 8,600 square meters (92,570 square feet) across two buildings on Univercells’ Jumet campus.  The GMP-qualified manufacturing space is one of Europe’s largest, with an area totaling 2,100 square meters (22,600 square feet).
9. FUJIFILM Corporation, based in Tokyo, Japan, has announced that Santa Ana, CA-based FUJIFILM Irvine Scientific will acquire Warminster, PA-based Shenandoah Biotechnology, a manufacturer of recombinant proteins, including cytokines and growth factors. FUJIFILM Irvine is a key player in the development and manufacture of serum-free and chemically defined cell culture media.  Shenandoah Biotechnology has recently launched their cGMP, ISO 9001:2015-certified CTG Grade line of cytokines and growth factors, and FUJIFILM says the acquisition will help the company establish a leading position in the advanced therapy market.  Terms of the deal, which was expected to close in late March, were not disclosed.
10. AlloVir, a clinical-stage allogeneic T-cell immunotherapy company based in Waltham, MA, has announced the initiation of a Phase III clinical study evaluating its lead product posoleucel for the prevention of multiple types of viral infection. Posoleucel is an off-the-shelf, allogeneic multi-virus-specific T-cell (VST) therapy targeting six viral pathogens which can be life-threatening in immunocompromised individuals: adenovirus (AdV), BK virus (BKV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6), and JC virus (JCV).  Posoleucel’s ability to prevent clinically significant viral infections and end-organ diseases in high-risk, allogeneic hematopoietic cell transplant (allo-HCT) patients will be evaluated.  The trial will enroll approximately 300 adult and pediatric patients, and marks the third ongoing Phase III trial evaluating posoleucel, in addition to an ongoing Phase II trial.  Posoleucel has been granted Regenerative Medicine Advanced Therapy (RMAT) and Orphan Drug designations by the U.S. FDA, and PRIority Medicines (PRIME) and Orphan Medicinal Product designations by the European Medicines Agency.
11. Akron BioProducts, based in Boca Raton, FL, and Vor Bio, a clinical-stage cell and genome engineering company based in Cambridge, MA, have announced plans to develop and manufacture current good manufacturing practices (cGMP)-compliant nucleases. Akron is a leading manufacturer of cGMP-compliant cell and gene therapy products, and the collaboration will expand the company’s portfolio of off-the-shelf gene editing solutions.   Vor specializes in engineered hematopoietic stem cell (eHSC) and chimeric antigen receptor (CAR)-T cell therapies, and hopes to likewise diversify its collection of nucleases to be used to create engineered cell therapies.
12. RootPath, a synthetic biology company based in Waterton, MA, has emerged from stealth, unveiling new technology enabling high-throughput gene synthesis. The company’s PathFinder DNA Assembly platform can program tens of thousands of short synthetic DNA fragments to self-assemble into thousands of long genes simultaneously, and its Nano Toothpick platform can screen synthetic gene products for single-base errors and recover the error-free molecules.  Together, the two technologies overcome the challenges presented by the synthesis of long genes at high-fidelity.  RootPath’s lead therapeutic candidates are fully personalized T cell therapies based on synthetic tumor-infiltrating lymphocytes (TILs), which the company presented in March at the Keystone Symposium’s Cancer Immunotherapy: Decoding the Cancer Immunity Interactome in a session and poster titled, “Functional decoding of tumor immune repertoire through massively parallel TCR gene synthesis and screening.” Other applications the company is pursuing for the technology include antibody discovery, enzyme design, and gene therapy optimization.  RootPath was founded in 2017 and raised $7 million in seed funding from investors including Sequoia China, Volcanics Venture, Baidu Ventures, and Nest.Bio Ventures. In January 2020 the company raised $11 million in Series A financing, followed by a $50 million Series B round in September 2021, for a total of $68 million in financing.
13. Inscripta, based in Boulder, CO, has executed a licensing agreement with Penn State Research Foundation, Penn State’s licensing entity, for technology developed by Yinong Yang, PhD, professor of plant pathology in the College of Agricultural Sciences. The technology expands the capabilities of CRISPR/Cas gene editing systems by enabling the simultaneous expression of multiple guide RNAs (gRNAs).  Taking advantage of transfer RNA processing machinery, multiple gRNAs are interspersed with tRNAs, which are then cleaved at the tRNA-gRNA junctions by tRNA-processing enzymes to release the gRNAs.  The agreement licenses the new technology for use with Inscripta’s trademarked MAD7 nuclease, to which the company provides free access for any R&D use.