13 Need-to-Know Developments in Cell and Gene Therapy

The following  are recent developments in Cell and Gene Therapy, from the latest issue of  Cell and Gene Therapy Business Outlook 

Cell and Gene Therapy Business Outlook

Adicet Bio, based in Boston, MA, reported positive interim data from its Phase I dose escalation study of ADI-001, a gamma delta CAR T-cell therapy targeting CD20 for the treatment of B-cell non-Hodgkin’s lymphoma. Of the six patients enrolled in the ADI-001 study, the first two who received the lowest dose did not reach the day 28 assessment and therefore were not evaluated. Three of the four evaluable patients achieved responses, including two complete responses and one partial response that investigators characterized as a borderline complete response. ADI-001 infusions were generally well-tolerated, with no dose-limiting toxicities, graft-versus-host disease, immune effector cell-associated neurotoxicity syndrome, or grade III or higher cytokine release syndrome reported. Two days after reporting the interim data, Adicet announced an underwritten follow-on public offering of 6,250,000 shares of its common stock at a price of $14.00 per share. Gross proceeds from the offering are expected to be $87.5 million.

Quell Therapeutics, based in London, England, has announced that it has raised $156 million in an oversubscribed series B financing round. The financing round was co-led by Jeito Capital, Ridgeback Capital Investments, SV Health Investors, and Fidelity Management & Research Company, with participation from founding investor Syncona. New investors include British Patient Capital through its Future Fund: Breakthrough program, Janus Henderson Investors, Monashee Investment Management, Point72, and funds managed by Tekla Capital Management. Quell is developing engineered T regulatory (Treg) cell therapies for treating immune system disorders, and the financing will be used to fund a Phase I/II clinical trial of QEL-001, a CAR Treg cell therapy candidate designed to induce durable immune tolerance and prevent organ rejection in liver transplant patients. The funding will also be used to advance other candidates in the areas of transplantation, neuroinflammatory diseases, and autoimmune disease, accelerate development of Quell’s autologous, engineered Treg platform, and further develop an allogeneic CAR Treg platform.

Acepodia, a clinical-stage biotechnology company based in Alameda, CA, has announced the closing of a $109 million Series C financing round led by Digital Mobile Venture with other new and existing investors, bringing its total to date to $166 million, including a $47 million Series B round in March 2021. Investors have included Ridgeback Capital Investments, 8VC, DEFTA Partners, CDIB Capital Healthcare, Maxpro, E-Sun Venture, BioEngine Venture, Samuel Chen, Yahoo founder Jerry Yang, and Foxconn founder Terry Gou. Acepodia is developing Antibody Cell Effector (ACE) therapies using its Antibody-Cell Conjugation (ACC) platform, which attaches tumor-targeting antibodies directly to the surface of immune cells such as natural killer (NK) cells or gamma delta T cells without the need for genetic engineering. Acepodia says that it will use the funds to further validate the company’s ACC technology and advance its pipeline ACE therapies for cancer patients with limited treatment options.

ViaCyte, based in San Diego, CA, has published promising preliminary results of an ongoing Phase I/II clinical trial demonstrating that its PEC-Direct stem cell-derived therapy can produce insulin in people with severe type 1 diabetes (T1D). PEC-Direct (VC-02) is ViaCyte’s lead product candidate and consists of the company’s PEC-01 cells contained within a non-immunoprotective implantation device which permits direct vascularization of the cell therapy to allow for robust and consistent engraftment. PEC-01 cells are a functional replacement for insulin-producing beta cells and other blood glucose-regulating islet cells of the pancreas and are derived from ViaCyte’s proprietary pluripotent stem cell (PSC) line. (Because the host’s immune system identifies these cells as foreign, this therapy requires long-term immunosuppression and is only indicated for patients with high-risk T1D.) The findings were published December 2nd in Cell Stem Cell and Cell Reports Medicine.

AviadoBio, based in London, England, has announced the completion of a £58.6 million ($80 million) Series A financing round, following an initial £12 million ($16.5 million) seed financing. The financing was led by New Enterprise Associates and co-led by Monograph Capital with participation from LSP, as well as seed investors Advent Life Sciences, Dementia Discovery Fund, F-Prime Capital, JJDC, and medical research charity LifeArc. AviadoBio specializes in developing therapies for people living with neurodegenerative disorders, combining gene therapy with a neuroanatomy-led approach to drug delivery. The funds will be used to advance its lead program in frontotemporal dementia (FTD) into the clinic, as well as progress its preclinical programs for other disorders, including amyotrophic lateral sclerosis (ALS).

CODA Biotherapeutics, a preclinical-stage biopharmaceutical company based in South San Francisco, CA, has announced it has closed on $28 million in financing led by Pacira BioSciences, along with the company’s existing investors, MPM Capital and Versant Ventures, and a new venture debt round with Silicon Valley Bank. As part of the financing deal, Pacira’s chairman and CEO David Stack will join CODA’s board of directors. CODA is developing a chemogenetic gene therapy approach for treating neurological disorders, using a neurosurgically administered adeno-associated virus (AAV) to deliver an engineered, inhibitory receptor to modulate specific neuronal circuits. The receptor is designed remain silent in transduced cells but will specifically inhibit neurons in a dose-dependent manner when exposed to a novel, orally bioavailable small-molecule drug. A few days after the financing announcement, CODA presented preclinical data suggesting their chemogenetic gene therapy platform can control focal seizures in vivo using the mouse intrahippocampal KA focal epilepsy model, which replicates many features of human temporal lobe epilepsy.

Integra Therapeutics, a biotechnology spin-off of Pompeu Fabra University (UPF) based at the Barcelona Biomedical Research Park (PRBB), has completed its first round of funding for €4.5 million with Advent France Biotechnology (France), Invivo Capital (Spain) and Takeda Ventures (USA). Integra founded in late 2020 based on technology developed in the Translational Synthetic Biology Lab led by Marc Güell, PhD, The company says the funding will be used to complete the prototype of its new gene editing platform, carry out preclinical validation using in vivo and ex vivo models, and manage its patent portfolio in 2022 and 2023. The company plans to open a Series A financing round after that to seek regulatory approval and begin clinical trials.

FUJIFILM Diosynth Biotechnologies, a contract development and manufacturing organization (CDMO) is investing £400 million ($533 million) to expand operations at its U.K. facility in Billingham, part of a ¥ 90 billion ($850 million) investment plan that Tokyo-based FUJIFILM announced in June. The expansion will add quality control labs, office space and storage to the campus. A new cell culture facility will triple the site’s existing capacity with the addition of four 2,000-liter and two 500-liter single-use bioreactor production capabilities for the manufacture of both monoclonal antibodies and new antibody treatments. The expansion will also multiply Fujifilm’s U.K. gene therapy production capabilities by tenfold, its microbial fermentation capacity by almost two-thirds, and add new vaccine manufacturing capabilities, including mRNA vaccines. The new facilities are expected to be operational by late 2023 or early 2024, and to create up to 350 new highly-skilled jobs.

Krystal Biotech, a Pittsburgh, PA-based clinical-stage biotech specializing in re-dosable gene therapies for rare diseases, has announced the price of its underwritten follow-on public offering of 2,666,667 shares at a public offering price of $75.00 per share. Gross proceeds from the offering are expected to be approximately $200 million, which the company says it intends to use to prepare for potential commercialization of VYJUVEKTM for dystrophic epidermolysis bullosa, to advance the clinical development of KB105 in TGM1-deficient autosomal recessive congenital ichthyosis (ARCI), to advance preclinical development of KB104 for Netherton syndrome, to advance development of KB407 for cystic fibrosis and KB408 for alpha-1 antitrypsin deficiency, to accelerate its respiratory pipeline, to invest in new technology development, and to complete development of its 2nd good manufacturing practices certified (GMPC) manufacturing facility.

Help Therapeutics, based in Nanjing, China, has announced the completion of $25 million in Series C financing. The financing was led by Ming Bioventures, followed by Share Capital, Beisen Medical Fund, and Jolmo Capital, with additional support from prior investor Purple Bull Startups, with Hoyue Capital acting as the exclusive financial advisor for this round. Help specializes in developing induced pluripotent stem cell (iPSC) therapies in the fields of heart failure and tumor immunity, and the financing will be used to help the company conduct clinical trials of its iPSC heart cell injection therapy, and to advance its iPSC immune cell therapy to the clinic.

CRISPR Therapeutics, based in Zug, Switzerland with U.S. R&D headquartered in Cambridge, MA, has received U.S. FDA regenerative medicine advanced therapy (RMAT) designation for CTX110, its allogeneic CAR-T cell therapy for the treatment of relapsed or refractory CD19+ B-cell malignancies. CTX110 is a healthy donor-derived, gene-edited allogeneic CAR-T cell therapy targeting CD19, an antigen ubiquitously expressed on B cells. The therapy is wholly owned by CRISPR Therapeutics, and is currently undergoing a Phase I, single-arm, multicenter, open-label clinical trial.

Selecta Biosciences, a clinical-stage biotechnology company based in Boston, MA, has announced that the U.S. FDA has placed 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 MMA-101, an AAV-based gene therapy delivering a functional copy of the MMUT gene encoding methylmalonyl-CoA mutase to treat MMA, plus ImmTOR, Selecta’s nanoparticle-based system which delivers rapamycin to immune cells to promote immune tolerance and allow AAV vectors to be re-dosed. The FDA has asked for additional information on the chemistry, manufacturing, and controls (CMC) related to the MMA-101 product candidate. The clinical trial had not yet been initiated, and will not move forward until all of the FDA’s questions have been resolved.

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