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19 Need-To-Know Developments in Cell and Gene Therapy

The following are recent developments in Cell and Gene Therapy, from Volume 1, Issue 13 of Cell and Gene Therapy Business Outlook, published December 22, 2021

  1. Arrowhead Pharmaceuticals, based in Pasadena, CA, has completed a purchase of 13 acres in the Verona Technology Park in Verona, WI, where it plans to invest between $200 million and $250 million to build a 140,000 square-foot drug manufacturing facility and a 115,000 square-foot laboratory and office facility to support its process development and analytical activities, creating about 250 new jobs in the local area. The company expects to begin construction is in the first quarter of 2022, with completion of the lab and office space anticipated in the first quarter of 2023, and the manufacturing facility in the fourth quarter of 2023. The new Arrowhead campus will support the company’s growing pipeline and establish manufacturing capabilities for its targeted RNAi molecule (TRiM) drug candidates while the company continues to operate its R&D facilities in Madison, WI, and San Diego, CA.  Arrowhead’s TRiM platform treats genetic diseases by using  RNA interference (RNAi) to silence the genes that cause them.
  2. Abeona Therapeutics, New York-based a gene and cell therapy company, has announced the pricing of an underwritten public offering of 44,700,000 shares and warrants to purchase 44,700,000 shares at a price of $0.39 per one share of stock and one warrant to purchase one share. The warrants have an exercise price of $0.39 per share and can be exercised immediately, with an expiration date five years from the date of issuance. The offering is expected to close on December 21, 2021, with proceeds of approximately $17.5 million. Abeona will use the funds to continue clinical development of pipeline products which include EB-101, an autologous, gene-corrected cell therapy for recessive dystrophic epidermolysis bullosa currently in Phase III development; ABO-102, an AAV-based gene therapy for Sanfilippo syndrome type A (MPS IIIA) currently in Phase I/II development; ABO-101, an AAV-based gene therapy for Sanfilippo syndrome type B (MPS IIIB) currently in Phase I/II development; and preclinical programs for indications in juvenile Batten disease (CLN3), cystic fibrosis (CF), retinal diseases, and undisclosed targets.
  3. Spark Therapeutics, a Roche company based in Philadelphia, PA, has announced plans to invest $575 million to build a new, state-of-the-art gene therapy center on Drexel University’s campus. The center will be located at the intersection of 30th and Chestnut Streets, with a 99-year ground lease of Drexel University’s F Lot. The planned 500,000 square-foot multi-story building will more than double Spark’s campus in Philadelphia to a projected one million square feet.  The announcement kicks off a long-term partnership between Spark and Drexel University, and the new facility is anticipated to begin construction in the fourth quarter of 2022.
  4. BioMarin Pharmaceutical, based in San Rafael, CA, and Skyline Therapeutics (formerly Geneception), based in Shanghai, China, have announced a multi-year strategic collaboration to discover, develop, and commercialize adeno-associated virus (AAV)-based gene therapies for genetic cardiovascular diseases. Skyline Therapeutics’ proprietary AAV vector engineering and design technology and manufacturing capability will be combined with BioMarin’s experience in gene therapy development, cardiovascular biology, and insights into genetic diseases to develop gene therapies targeting dilated cardiomyopathies (DCM), a group of progressive diseases which result in an enlarged heart with reduced circulatory efficiency.  Under the agreement, BioMarin and Skyline will collaborate on discovery and research through to IND application, after which each company will be responsible for clinical development in their pre-defined territories (United States, Europe, and Latin America for BioMarin, and the Asia-Pacific region for Skyline).  Skyline Therapeutics will receive an undisclosed upfront payment and an equity investment from BioMarin, along with potential milestone payments and royalties on future sales by BioMarin in its territories.
  5. Chugai Pharmaceutical, based in Tokyo, Japan, has announced a license agreement with Basel, Switzerland-based Roche for delandistrogene moxeparvovec (SRP-9001), an investigational gene therapy for Duchenne muscular dystrophy (DMD) currently being developed by Roche and Cambridge, MA-based Sarepta Therapeutics. Under the agreement, Chugai will have exclusive marketing rights in Japan for delandistrogene moxeparvovec in exchange for an upfront fee and milestone payments. Sarepta and Roche are currently conducting a global Phase III clinical trial for delandistrogene moxeparvovec for the treatment of DMD, and Sarepta will handle future clinical studies, including in Japan. Chugai will be responsible for the regulatory filing and marketing in Japan.
  6. Philadelphia, PA-based iECURE, has announced that it has entered into an exclusive agreement with the University of Pennsylvania (Penn) to develop next-generation lipid nanoparticles (LNP) for liver gene editing applications. The agreement grants iECURE exclusive rights to gene editing in the liver using LNP technology developed in collaboration with the laboratory of Michael Mitchell, PhD, at Penn. New startup iECURE is a mutation-agnostic in vivo “knock-in” gene editing company, and was founded in 2020 in collaboration with Penn’s Gene Therapy Program, directed by James M. Wilson, MD, PhD. Mitchell’s laboratory has already collaborated for many years with Penn’s Gene Therapy Program and will continue that collaboration with the new partnership.  The new agreement expands iECURE potential pipeline of programs with Penn from 13 to 15.
  7. Inceptor Bio, based in Research Triangle Park, NC, has announced that it has executed an in-licensing agreement with the University of California, Santa Barbara (UCSB) for a chimeric antigen receptor macrophage (CAR-M) technology invented by the laboratory of Denise Montell, PhD. Macrophages play a key role in innate immunity, attacking and engulfing (through a process called phagocytosis) anything that does not display surface markers characteristic of healthy cells. They also initiate adaptive immune responses by displaying antigens and secreting cytokines to recruit other immune cells.  CARs combine the functions of tumor-specific antigen binding and macrophage activation into a single receptor molecule, and program the macrophages to selectively target and engulf cancer cells.  The macrophages then recruit other cells to generate a coordinated immune response against the cancer cells, attacking even difficult-to-treat solid tumors.
  8. New York-based Pfizer has announced the opening of a new 85,500 square-foot clinical manufacturing facility in Durham, NC, part of its $800 million investment to build three scalable, state-of-the-art gene therapy manufacturing facilities with 300,000 square feet of capacity to support its continued investment in that field. The new facility will house Pfizer’s BioTherapeutics Pharmaceutical Sciences Group and is expected to create more than 50 new jobs supporting Pfizer’s gene therapy and biologics portfolio, with approximately 40 employees relocating from Pfizer’s Chapel Hill site.  With these investments, Pfizer has built up one of the world’s largest production capacities for gene therapy vectors, with a total bioreactor manufacturing capacity of 22,000 liters.  Pfizer’s worldwide R&D capacity includes locations in La Jolla, CA; Boulder, CO; St Louis, MO; Pearl River, NY; Groton, CT; and Cambridge and Andover, MA.
  9. Genenta Science, a clinical-stage biotech company based in Milan, Italy, has gone public, selling 2.4 million American depositary shares (ADSs), at $11.50 each to generate total proceeds of about $36 million. Genenta specializes in hematopoietic stem-cell gene therapies for the treatment of solid tumor cancers, and its lead candidate, Temferon, is currently in a Phase I/IIa dose-escalation clinical trial for the treatment of newly diagnosed glioblastoma multiforme (GBM), a common brain cancer.  Temferon modifies autologous hematopoietic stem and progenitor cells (HSPCs) by ex vivo gene transfer to create tumor-infiltrating Tie2 expressing monocytes (TEMs) which carry a payload of IFN-α, a proinflammatory therapeutic.
  10. Myrtelle, based in Wakefield, MA, has announced that it entered into an exclusive worldwide licensing agreement with New York-based Pfizer for rAAV-Olig001-ASPA, an investigational recombinant adeno-associated virus (rAAV)-based gene therapy for the treatment of Canavan disease. Canavan disease is a fatal childhood genetic neurological disorder caused by a defective ASPA gene encoding the enzyme aspartoacylase.  Aspartoacylase deficiency interferes with growth of the myelin sheath around the nerve fibers of the brain, resulting in spongy degeneration of the white matter in the brain.  The investigational gene therapy targets oligodendrocytes, which responsible for producing myelin, directly with a proprietary AAV vector designed to restore ASPA gene function.  Myrtelle is currently conducting a Phase I/II clinical of the gene therapy in children with Canavan disease at Dayton Children’s Hospital in Dayton, Ohio.
  11. Neochromosome, a wholly owned subsidiary of Opentrons Labworks based in New York, and Mekonos, based in San Francisco, CA, have formed a new partnership to advance cell engineering for personalized cell therapies. The partnership will test and optimize the delivery of Neochromosome’s de novo synthesized “Big-DNA” cargo directly into the nuclei of human induced pluripotent stem cells (hiPSCs) using Mekonos’ proprietary Iris technology for ex vivo delivery of large DNA payloads. The companies say their cell-based therapies have the potential to treat a variety of diseases, including diabetes, Parkinson’s, and cancer. The research collaboration launches in January 2022 in the San Francisco Bay Area, with initial results expected mid-year.
  12. Novartis, based in Basel, Switzerland, has terminated its agreement with Melbourne, Australia-based Mesoblast to develop, commercialize and manufacture remestemcel-L for the treatment of acute respiratory distress syndrome (ARDS), including that associated with COVID-19. Remestemcel-L is an investigational cell therapy composed of culture-expanded allogeneic mesenchymal stromal cells (MSCs) derived from bone marrow of an unrelated donor.  The treatment had previously been rejected by the FDA for the treatment of graft-vs-host disease in late 2020, but Mesoblast had hopes that a 300-patient, Phase III clinical trial evaluating Remestemcel-L for the treatment of COVID-19-related ARDS would lead to an Emergency Use Authorization (EUA) by the FDA. The clinical trial failed to meet its primary endpoint, however, and Novartis has backed out the deal.  Based on the trial’s observed mortality reduction with remestemcel-L in patients aged under 65 with COVID-related ARDS, Mesoblast is still optimistic about the drug’s potential, and is preparing to launch another Phase III trial in order to pursue an EUA for the treatment of COVID-related ARDS.
  13. Accellix, based in Jerusalem, Israel, has raised $10 million from BroadOak Capital Partners. Accellix is a biotechnology company that provides flow cytometry results in a compact, easy-to-use platform for use by cell therapy companies on the manufacturing floor and at the point-of-need. Their products streamline a complex but necessary part of cell analysis, providing more robust outcomes and reducing overall quality-control costs in cell therapy manufacturing.  The investment is part of BroadOak’s fifth fund and marks the firm’s third investment in the last six months in the rapidly growing market of tools and services for cell and gene therapy development and manufacturing.  BroadOak previously invested in Accellix as part of a prior fund.
  14. Rejuveron Life Sciences, a Zürich-based biotech company, has funded a further $20 million in Francisco-based Endogena Therapeutics’ $29 million Series A financing, strengthening its support to a near-majority holding. Endogena specializes in endogenous regenerative therapeutics targeting degenerative diseases of the eye, and Endogena will use the funding to advance its two lead programs. EA-2353 is an endogenous photoreceptor regeneration treatment for retinitis pigmentosa (RP) and is scheduled to enter human trials in the first half of 2022.  EA-2351 is a pre-clinical treatment for geographic atrophy (GA), an advanced form of age-related macular degeneration (AMD).
  15. Cambridge, MA-based bluebird bio’s investigational therapy bb1111 (lovotibeglogene autotemcel) is beginning to show promising results as a potential permanent cure for sickle cell disease (SCD). In a Dec 12 paper published in The New England Journal of Medicine, researchers led by Julie Kanter, MD, at the University of Alabama at Birmingham (UAB) report that patients treated with bb1111 are showing signs of stable expression of normal hemoglobin. The therapy consists of autologous transplantation of hematopoietic stem and progenitor cells (HSPCs) transduced with the BB305 lentiviral vector encoding HbAT87Q, a modified β-globin gene which produces a form of hemoglobin less likely to cause sickling when it’s expressed alongside the mutated hemoglobin gene responsible for SCD (HbS). A few days after publication of those results, bluebird announced that the FDA had placed a partial, temporary clinical hold on the gene therapy due to an ongoing investigation by bluebird into an adolescent patient with persistent, non-transfusion-dependent anemia following treatment with the drug.  Enrollment and dosing for SCD patients 18 and older are unaffected by the hold, and those studies will continue as planned.
  16. Smart Immune, based in Paris, France, has announced a research collaboration with New York’s Memorial Sloan Kettering Cancer Center (MSK). The clinical-stage company specializes in a proprietary ex-vivo biomimetic “thymus-in-a-dish” technology to create ProTcells, which are allogeneic T-cell progenitors designed to reset a rapid, safe, and full immune reconstitution.  The MSK collaboration will expand Smart Immune’s ProTcell pipeline with a CAR-ProTcell platform which uses its progenitor ProTcells instead of mature T-cells to generate a naïve, long lasting, exhaustion-free CAR-T cell population.  MSK will develop the first mouse-to-mouse model CAR-ProTcell proof-of-concept, and Smart Immune will handle the humanized model proof-of-concept.  The company says the work has the potential to expedite the clinical development of next generation CAR-T cells combining long-term persistence, natural protection against infections, and low risk of graft-versus-host disease (GvHD) in allogeneic setting.
  17. Aziyo Biologics, a commercial-stage regenerative medicine company based in Silver Spring, MD, has announced the closing of approximately $14.0 million of previously announced private investment in public equity (PIPE) financing. The financing was led by a fund affiliated with Birchview Capital, with participation from existing investors including funds affiliated with Deerfield Management Company and HighCape Capital.  Aziyo specializes in products to improve outcomes for patients undergoing cardiovascular, orthopedic, and reconstructive surgery, with a focus on patients receiving implantable medical devices.
  18. PDC*line Pharma, a clinical stage biotech company based in Liège, Belgium and Grenoble, France has announced the completion of its Series B2 round of financing, €11.8 million ($13.7 million) in financing was led by Korea Investment Partners, a leading multi-billion dollar South-Korean fund, and also included a syndicate of new South Korean investors in life sciences: Alpha Holdings, Brain Asset Management, and Hansongneotech Co. Ltd. Existing investors Noshaq Group (ex-Meusinvest), Sambrinvest (the Charleroi investment fund), SFPI-FPIM (the Belgian Federal Holding and Investment Company), SRIW (The Regional Investment Company of Wallonia), and Smart Korea UTC BioHealthcare Venture Fund also participated. The company has also received a €5.7M ($6.6M) grant in repayable aid from the Walloon Region of Belgium, bringing the B2 round total to €17.5 million ($20.3 million).  Together with €20 million ($23.2 million) in B1 fundraising from January 2020, the company has raised a total of €37.5M million in this Series B round.  The company’s lead candidate, PDC*lung01, consists of PDC*line’s professional antigen-presenting cells loaded with HLA-A2 restricted peptides derived from seven shared tumor antigens, and is currently in a Phase Ib/II clinical trial for the treatment of non-small cell lung cancer.
  19. TrinCE, a new spin-off of Ghent University (UGent) based in Ghent, Belgium, has raised €4 million ($4.5 million) from Novalis Biotech Acceleration, Qbic II, and private investors. The company’s LumiPore transfection platform uses photothermal nanoparticles in combination with laser illumination to transiently heat and permeabilize cell membranes.  The platform has demonstrated efficient cytosolic delivery of a wide variety of molecules up to 500 kDa, including antisense oligonucleotides (ASOs), small interfering RNA (siRNA), peptides, antibodies, proteins, and quantum dots into virtually any cell type, including hard-to-transfect cells such as immune cells for cell therapies.