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. Antengene, a commercial-stage biopharmaceutical company based in Shanghai, China, has announced a pre-clinical research collaboration with Celularity, a clinical-stage cell therapy company based in Florham Park, NJ.  Celularity is developing off-the-shelf, cryopreserved, placental-derived allogeneic cell therapies, and the two companies will evaluate potential therapies combining Antengene’s bispecific antibody with Celularity’s human placental hematopoietic stem cell-derived natural killer (NK) cell therapy platform.  Antengene believes its bispecific antibody can potentially activate NK cells while crosslinking immune checkpoint inhibitors in the tumor microenvironment, and synergize with antibodies targeting tumor-associated antigens to enhance the anti-tumor response. The company expects the combination therapy to increase the proliferation and persistence of NK cells in the tumor microenvironment. In related news, Celularity recently announced it had dosed the first patient in a Phase I/IIa clinical trial evaluating its allogeneic NK cell therapy CYNK-101 for the treatment of HER2+ gastroesophageal junction cancer.
  2. Xenetic Biosciences, based in Framingham, MA, and VolitionRx, an epigenetics-based  diagnostics company based in Henderson, NV have announced a research and development collaboration to develop cell therapies for the treatment of cancer targeting neutrophil extracellular traps (NETs).  NETs are sticky weblike structures produced by activated neutrophils which trap immunogenic targets to impede their further spread into the body.  Elevated levels of NETs are associated with cancer pathogenesis and can inhibit cancer therapeutics, resulting in poor prognosis in a variety of cancers.  NETs are comprised of long stretches of DNA and globular protein, and Xenetic has been developing cancer therapies using human recombinant DNase I enzyme to break down NETs, administered either systemically or secreted by chimeric antigen rector T (CAR T) cells.  The collaboration will evaluate the potential combination of Volition’s Nu.Q NETs platform (a diagnostic test designed to rapidly identify elevated levels of NETs in patients) with Xenetic’s DNase-Armored CAR T platform (CAR T cells engineered to secrete DNase I) to develop proprietary cell therapies for the treatment of solid cancers.   Under the agreement, Volition will fund a research program and the two companies will share the proceeds resulting from the successful commercialization of any products from the collaboration.
  3. AGC Biologics, a global contract development and manufacturing organization (CDMO) headquartered in Bothell, WA, has announced a new partnership with Altheia Science, a cell and gene therapy company based in Milan, Italy.  Altheia specializes in the development of autoimmunity treatments, with a particular focus on the modulation of PD-L1 expression.  At AGC Biologics’ Milan facility, patients’ hematopoietic stem and progenitor cells will be transduced ex vivo with a lentiviral vector (LVV) to express human PD-L1, advancing Altheia’s LVV-based PD-L1 therapy into clinical trials.
  4. Mustang Bio, a clinical-stage cell and gene therapy company based in Worcester, MA, has announced that the first patient has been successfully treated with MB-110, an ex vivo lentiviral gene therapy for the treatment of recombination activating 1 severe combined immunodeficiency (RAG1-SCID). RAG1-SCID is a rare genetic immunodeficiency disorder caused by null mutations in the RAG1 gene which result in drastically reduced V(D)J recombination, the mechanism by which B and T cells generate their diverse range of antibodies and T cell receptors.  MB-110 uses a lentiviral vector (LV-RAG1) to transduce a patient’s hematopoietic stem cells (HSCs) to express a functional copy of the human RAG1 gene.  After treatment, the patient was able to create a functioning immune system, and is responding normally to standard vaccinations for newborns.  The therapy is currently being evaluated in a Phase I/II European multicenter clinical trial and was developed by Frank Staal, PhD, whose laboratory at Leiden University Medical Centre (LUMC) has on ongoing relationship with Mustang.
  5. ERS Genomics, a CRISPR/Cas9 licensing company based in Dublin, Ireland, has announced a new licensing agreement with Lepton Pharmaceuticals, an RNA therapeutics company based in Zikhron Ya’akov, Israel.  Lepton specializes in using small, non-coding RNA molecules such as small interfering RNAs (siRNAs) and microRNAs (miRNAs) to precisely regulate gene expression.  The company has developed a proprietary Castling Technology platform (named after the chess move), whereby beneficial miRNA sequences are swapped into regions normally occupied by harmful miRNA sequences.  Biological pathways that would normally induce the expression of these harmful miRNAs will now induce expression of beneficial miRNAs in their place.  Since miRNAs can affect the expression of hundreds of coding genes at once, Castling allows a single gene editing event to significantly affect the overall gene expression pattern of a cell.  The licensing agreement allows Lepton to develop and commercialize products and services using CRISPR/Cas9 technology to perform Castling edits within cells. Financial terms were not disclosed.
  6. Replicate Bioscience, an RNA therapeutics company based in San Diego, CA, and Precision NanoSystems, a supplier of lipid nanoparticle (LNP) delivery systems based in Vancouver, BC, have announced a licensing agreement to speed the development of self-replicating RNA (srRNA) therapies.  Replicate specializes in srRNA therapies to prevent drug resistance in cancer and to treat autoimmune diseases, inflammatory disorders, and other diseases.   Precision’s resources include a proprietary library of ionizable lipids and compositions, a scalable microfluidic manufacturing platform, technical support, and CDMO services.  Under the licensing agreement, Precision will provide LNP delivery solutions for the scale-up and manufacture of up to 15 of Replicate’s srRNA therapies in exchange for milestone payments, royalties, and sublicensing income sharing.
  7. Oxford BioMedica, a cell and gene therapy company based in Oxford, UK, has announced an amended expanded License and Clinical Supply Agreement (LSA) with Seattle, WA-based Juno Therapeutics (a wholly owned subsidiary of Bristol-Myers Squibb)  The original LSA, announced in March 2020, granted Juno Therapeutics a non-exclusive license to use Oxford Biomedica’s LentiVector platform in its CAR-T and TCR-T cell therapy programs, and included a five-year Clinical Supply Agreement.  Under that agreement, Oxford Biomedica received $10 million up front, with eligibility to receive up to $86 million in development and milestone payments, and up to $131 million in sales-based milestone payments, plus an undisclosed royalty on net sales.  Oxford Biomedica is also eligible to receive payments from process development, scale-up projects, and GMP manufacture of lentiviral vectors for clinical trials.  The original LSA covered four undisclosed projects, and this amendment adds two additional programs.  The amended terms include an undisclosed target nomination fee for Oxford Biomedica, as well as potential milestone payments.
  8. Vertex Pharmaceuticals, based in Boston, MA, and Verve Therapeutics, a clinical-stage gene editing company based in Cambridge, MA, have announced a four-year research collaboration to discover and develop an in vivo gene editing therapy for an undisclosed liver disease.  Under the agreement, Verve will be responsible for the discovery, research, and early preclinical development of the therapy, while Vertex will cover the program costs and handle subsequent development, manufacturing, and commercialization.  Verve will receive $60 million up front (including a $35 million equity investment), up to $66 million in success payments, up to $340 million in milestone payments, and tiered royalties on any future net sales.
  9. Coinciding with the official announcement of its $160 million Series B financing round, Frontera Therapeutics, based in Bedford, MA, has announced that the FDA has accepted the company’s IND application for its first-in-human clinical trial to evaluate FT-001, the company’s lead gene therapy candidate for the treatment of a rare genetic retinal disease.  Frontera is developing adeno-associated virus (AAV)-based gene therapies for indications in ophthalmology, hematology, neuromuscular diseases, and metabolic diseases, and has raised $195 million in total financing since its 2019 founding.   OrbiMed and Creacion Ventures participated in the $35 million Series A round, and Series B investors included Boyu Capital, Sequoia China, OrbiMed, Creacion Ventures, and other investors. In December of 2021, the company completed construction of a 4,000 square-meter facility with GMP manufacturing capabilities and clinical testing labs in Suzhou, China.
  10. Avista Therapeutics, a recent spinout of University of Pittsburgh Medical Center (UPMC) based in Pittsburgh, PA, has announced a partnership with Swiss healthcare company Roche to develop novel adeno-associated virus (AAV) gene therapy vectors for the treatment of eye diseases.  Under the agreement, Avista will develop intravitreally-delivered AAV capsids to match a capsid profile defined by Roche using its single-cell AAV engineering (scAAVengr) platform. The scAAVengr platform is a high-throughput, computationally guided, in vivo capsid discovery technology from which Avista plans to develop a proprietary pipeline based on AAV variants which can target individual retinal cell types.  These new capsids will be distinct from that internal pipeline, and Roche will have the right to evaluate and license these novel capsids from Avista, and will also handle preclinical, clinical, and commercialization activities for any gene therapy programs utilizing the novel capsids.  In exchange, Avista will receive $7.5 million up front, additional potential payments during the research phase of the partnership, and potential milestone payments and royalties.  The total value for the deal could exceed $1 billion.