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This Week in Cell and Gene Therapy: 12 Recent Developments

The following are a dozen developments in the cell and gene therapy market from Volume 1, Issue 14 of Cell and Gene Therapy Business Outlook, published January 10, 2022.


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  1. Allogene Therapeutics, based South San Francisco, CA, has announced that the Food and Drug Administration has cleared the company to resume clinical trials its CAR-T cell therapies. In October of 2021, the FDA placed a hold on all of Allogene Therapeutics’ allogeneic CAR-T cell clinical trials following a report of a chromosomal abnormality in a patient treated with ALLO-501A, a TALEN (Transcription Activator-Like Effector Nuclease)-edited CAR-T cell therapy targeting CD19 for the treatment of relapsed or refractory non-Hodgkin lymphoma (NHL). (See Cell and Gene Therapy Business Outlook 1, issue 12, p. 13 for more information this therapy.) Allogene has since thoroughly investigated the abnormality, and concluded it was an isolated event unrelated to the therapy’s administration and had no clinical significance. Allogene says the abnormality involved regions of the T cell receptor and immunoglobulin genes that naturally undergo rearrangement during T cell or B cell maturation.  The FDA agrees with Allogene’s findings.
  2. SK Group’s holding company, SK Inc., based in Seoul, South Korea, has invested $350 million in the Philadelphia, PA-based Center for Breakthrough Medicines (CBM), making the Korean company the second-largest stakeholder in the U.S. gene therapy company. CBM is a contract development manufacturing organization (CDMO) established in 2019, and offers plasmid DNA and viral vector manufacturing in addition to process and analytical development, good manufacturing process (GMP) testing, cell therapy bioprocessing, and cell banking services for a full product’s life cycle.  SK says the deal with the CBM will help build toward SK’s goal of becoming the world’s leading CDMO with a chemical and biologic drug value chain across the United States, Europe, and Asia by 2025.
  3. ONK Therapeutics, based in Galway, Ireland, has announced that is has closed $21.5 million in Series A financing, led by current investors Acorn Bioventures and ALSHC, who were joined by new investor Cormorant Asset Management. The financing will enable the company to advance three programs currently in preclinical development: ONKT102, for relapsed/refractory multiple myeloma; ONKT103, for solid tumors such as ovarian cancer, non-small cell lung cancer (NSCLC), and breast cancer; and ONKT104, for acute myelogenous leukemia (AML).  ONK was recently granted a US patent for their cytokine-inducible SH2-containing (CISH) knockout (KO) in natural killer (NK) cells, and has since launched two new programs based on their CISH KO NK cell technology: ONKT105, knocking out the CISH gene in cord blood-derived NK cells; and ONKT106, knocking out the CISH gene in induced pluripotent stem cell (iPSC)-derived NK cells.  NK cells require cytokines signaling to maintain activity and function, but the high doses required can be toxic.  The CISH gene encodes a negative regulator of cytokines, and knocking this gene out in NK cells has been shown to make them hypersensitive to cytokine stimulation, lowering the dose required to maintain their expansion and anti-tumor functions.   (See Cell and Gene Therapy Business Outlook 1, issue 7, p. 23 for more information on ONK Therapeutics’ CISH KO technology and the company’s development pipeline.)  ONK’s shareholders include Acorn Bioventures, Cormorant Asset Management, ALSHC (principally Seamus Mulligan), and Enterprise Ireland.
  4. Univercells, based in Brussels, Belgium, has announced that it has acquired SynHelix, based in Évry-Courcouronnes, France.  SynHelix is developing a unique proprietary enzyme-based DNA synthesis technology as an alternative to bacterial DNA amplification, promising automated, one-step gigaprep-scale production of long DNA fragments.  SynHelix will become a separate legal entity called Quantoom Research Center, a new affiliate of the Univercells Group, after the acquisition.  SynHelix’s DNA synthesis platform will complement the RNA platform being developed by another Univercells affiliate, Quantoom Biosciences’ end-to-end RNA production  SynHelix was supported by AdBio partners (formerly Advent France Biotechnology), a French life sciences venture capital firm, before the acquisition, and the founders of both SynHelix and AdBio will become minority shareholders of Univercells after the acquisition.
  5. Ray Therapeutics, based in San Diego, CA, has announced the closing of $6 million in seed financing, led by 4BIO Capital. The financing will be used to advance its optogenetic therapy, Ray-001, into clinical trials for the treatment of retinitis pigmentosa (RP). Preclinical studies indicate that Ray-001 could be a one-time treatment that is sustainable for a lifetime. Rather than attempting to repair the specific genetic defect responsible for RP, Ray-001 is a mutation-independent optogenetic therapy that bypasses the defective photoreceptors entirely by targeting other retinal cells along the vision circuit pathway.  The therapy is administered via intravitreal injection, where it diffuses from the vitreous into the retina to transduces the retinal ganglion cells (RGCs).  Over 100 mutations in more than 70 different genes can lead to RP, and no effective treatment is available.
  6. Curocell, based in Daejeon, South Korea, has begun construction of a new 17,325 square-meter CAR-T Center in Dungok Residential & Industrial Area in Daejeon International Science & Business Belt. The center will house a GMP facility for commercial manufacturing of CAR-T cell therapies and an R&D center for further pipeline development.  Construction is expected to be completed by the first half of 2023, with the center fully operational by 2024.  Curocell plans to use the facility for in-house development and production of their CAR-T therapies, and to expand their business to reach a global market.  Curocell is a clinical-stage company, and their lead CAR-T product, CRC01 (anbalcabtagene autoleucel), is currently in a Phase Ⅰ clinical trial in South Korea for the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL), with Phase II scheduled to begin in the first half of 2022.
  7. Emendo Biotherapeutics, based in New York, and Seattle Children’s Research Institute have announced a research collaboration to study priming treatments for hematopoietic stem cells (HSCs) extracted from patients with severe congenital neutropenia (SCN). Emendo has developed EMD-101, a CRISPR-based treatment for ELANE-related SCN (SCN1). SCN1 is an autosomal dominant disease caused by a mutation in one allele of the ELANE gene which encodes neutrophil elastase, preventing hematopoietic stem cells (HSCs) from differentiating into neutrophils.  HSCs require priming before transplantation, which is typically achieved with granulocyte colony stimulating factor (G-CSF). G-CSF also increases neutrophil count and is commonly administered as a treatment for SCN, however.  The collaboration will therefore evaluate priming treatments for HSCs extracted from SCN patients, with the goal of developing a clinical trial protocol for Emendo’s SCN1 gene therapy.  Such a trial is expected to begin in late 2022, pending regulatory approval, and Seattle Children’s Research Institute has preferred rights to serve as the clinical trial site.
  8. Novartis, based in Basel, Switzerland, will acquire London-based Gyroscope Therapeutics, a clinical-stage gene therapy company specializing in the treatment of geographic atrophy (GA) secondary to dry age-related macular degeneration (AMD). GA is an advanced form of dry AMD, which is a leading cause of irreversible vision loss in people over 55.  Gyroscope has developed GT005, a one-time adeno-associated serotype 2 (AAV2)-based gene therapy for the treatment of treatment of GA, currently being  evaluated in one Phase I/II and two Phase II clinical trials.  An overactive complement system is believed to play a role in GA, leading to inflammation which damage eye tissues.  GT005 treats GA by increasing production of a protein called Complement Factor I (CFI), which regulates the activity of the complement system.  Under the acquisition agreement, Novartis will make an upfront payment of $800 million, with additional milestone payments of up to $700 million. Novartis and Gyroscope will continue to operate as separate and independent companies until the deal closes.
  9. Ambys Medicines, based in South San Francisco, CA, has announced today announced the completion of a $47 million extension of its Series A financing, bringing its total Series A funding to $107 million. The funding was led by Third Rock Ventures with participation from Takeda, Schroders Capital, Laurion Capital, Smilegate Investment, and Alexandria Venture Investments, among others.  Ambys is a cell therapy company specializing in treating liver disease with mature hepatocytes to or even replace liver function.  The funding will support the company’s lead program, AMI-918, through pre-IND studies, with the goal of initiating a Phase I/II clinical trial in the 2nd quarter of 2023.  AMI-918 is an allogeneic liver-cell therapy consisting of mature hepatocytes that function in vivo as healthy liver cells and is designed for the treatment of acute liver disease.  Ambys’ second program is designed to treat chronic liver disease by extending the durability of replacement cells and by improving dosing and administration without the need for immunosuppressive therapy, the company says.
  10. EXUMA Biotech, a clinical-stage biotech company based in West Palm Beach, FL, has announced the completion of a $41 million Series B2 financing, bringing the company’s total financing raised since its inception to approximately $130 million. New investors included Americo Life in addition to existing investors. The funding will be used to support development of EXUMA’s autologous subcutaneous rapid point-of-care (rPOC) chimeric antigen receptor T- and NK-like (CAR-TaNK) platform, which does not require lymphodepleting chemotherapy, can be manufactured in less than six hours, and may produce a lower systemic cytokine burden during expansion than conventional CAR-based therapies. EXUMA will also continue clinical investigation of its tumor metabolism regulated (TMR) CAR-T technology targeting solid tumors, which uses the tumor microenvironment to activate the CARs, limiting damage to healthy tissue by reducing on-target, off-tumor toxicity.  Two TMR CAR-T products, CCT301-38 (targeting receptor tyrosine kinase AXL) and CCT301-59 (targeting receptor tyrosine kinase-like orphan receptor 2) are currently being evaluated in clinical trials at Shanghai Public Health Clinical Center sponsored by Shanghai PerHum Therapeutics.
  11. Pfizer, based in New York, has announced the death of a patient participating in the non-ambulatory cohort of a Phase Ib clinical trial of its mini-dystrophin gene therapy candidate PF-06939926 in Duchenne muscular dystrophy (DMD). (See Cell and Gene Therapy Business Outlook 1, issue 8, p. 31 for more information on Pfizer’s PF-06939926 and DMD.) Screening and dosing in the clinical trial have been paused while Pfizer investigates the incident with the trial site investigator and independent External Data Monitoring Committee, and the U.S. FDA has placed PF-06939926’s IND on clinical hold.
  12. Lineage Cell Therapeutics, based in Carlsbad, CA, has announced that the company and its subsidiary, Jerusalem, Israel-based Cell Cure Neurosciences, have inked an exclusive worldwide collaboration and license agreement with Swiss giant Roche and South San Francisco, CA-based Roche Group member Genentech, for the development and commercialization of a retinal pigment epithelium (RPE) cell therapy for the treatment of ocular disorders, including advanced dry age-related macular degeneration (AMD) with geographic atrophy (GA). Under the agreement, Genentech take over clinical development and commercialization of Lineage’s OpRegen program, currently in a Phase I/IIa clinical trial in patients with advanced dry AMD with GA. Lineage will complete activities related to the current clinical trial and handle certain manufacturing activities. In exchange, Genentech will pay Lineage $50 million up front, with up to $620 million in additional milestone payments, plus tiered double-digit royalties.