After decades of research, cell and gene therapies are gaining momentum in the biotech industry. Here are five investor-favorite private startups with products already in clinical development.
While conventional drugs are often effective at controlling symptoms or modifying a disease, there are many conditions where their benefits are limited, such as rare genetic disorders.
One way to close the gap is with cell and gene therapies. Cell therapies involve administering cells engineered as living drugs to patients, which can come from the patients themselves (autologous cells) or from healthy donors (allogeneic cells). Depending on the type of therapy, the infused cells could fight cancer or even reverse organ damage by rebuilding damaged tissue.
Gene therapies, on the other hand, involve delivering a therapeutic gene directly into a patient’s body, such as a healthy version of a mutated gene that causes a genetic disease. With a single dose, the goal is to restore normal life to patients with conditions such as haemophilia B and genetic blindness.
While cell and gene therapies are still an emerging field, their potential is already making itself known in the biotech industry. This is especially true for autologous CAR-T cell therapies, in which patients’ T cells are genetically engineered in the laboratory to fight cancer more effectively and then infused back into the patient. The first CAR-T therapies, Yescarta and Kymriah, were approved by the US Food and Drug Administration (FDA) in 2017 for the treatment of rare forms of blood cancer, and four more have since been approved.
CAR-T therapies are just the tip of the iceberg. In 2022 alone, the FDA greenlit a record five cell and gene therapies, including the first gene therapy for hemophilia B. In 2023, as many as 18 cell and gene therapies could receive regulatory decisions around the world.
However, it hasn’t been easy for cell and gene therapy companies; global investment in space fell from $22.7 billion in 2021 to $12.6 billion in 2022. However, there have been large funding rounds targeting startups, with CAR T particularly attractive to investors.
Here’s a look at five of the best-funded cell and gene startups that already have clinical development underway.
1. Castle Creek Biosciences
Founded: 2018 | Headquarter: Exton, Pennsylvania, United States
Castle Creek Biosciences was founded under the umbrella of startup creator Paragon Biosciences. The company develops cell and gene therapies for incurable rare diseases, with a focus on recessive dystrophic epidermolysis bullosa (RDEB). RDEB occurs when a patient has a mutation in a gene for a type of collagen protein, and it leaves the sufferer highly prone to blisters and sores.
To combat RDEB, Castle Creek is developing ex vivo gene therapy in which a therapeutic gene is delivered to a patient’s skin cells outside the body and then reinfused into the patient. Gene therapy is delivered to cells using a type of viral vector called lentiviral vectors.
Meanwhile, Castle Creek is also targeting the hereditary metabolic disease type 1 (HT1) tyrosinemia with preclinical in vivo gene therapies, using another lentiviral vector to deliver a therapeutic gene directly to liver cells.
The company aims to complete a Phase III trial of its ex vivo treatment for RDEB and is funding the development with help from a $112.8 million funding round that closed in May 2022. The company had initially planned to list on the Nasdaq in late 2021, but plunging stocks in the global biotech industry led Castle Creek to change its plans.
To pump its cell and gene therapy muscles, Castle Creek also acquired preclinical gene therapy company Novavita Thera in early 2022.
2. Frontera Therapeutics
Founded: 2019 | Headquarter: Bedford, Massachusetts, USA
Frontera Therapeutics was founded by a team that includes its current CEO, Yong Dai, who helped take gene therapy company Prevail Therapeutics to the Nasdaq in 2019 and an acquisition deal with Eli Lilly in 2020.
With bases in the United States and China, Frontera is developing gene therapies for a broad range of indications including genetically blind conditions, blood disorders and metabolic disorders. Its gene therapies are delivered to their target tissues in the body using adeno-associated viral (AAV) vectors. The company modifies the genomes of viral vectors to give them desired characteristics such as reduced immunogenicity and to improve the efficacy of gene therapy.
To fuel its mission, the company raised $160 million in a Series B funding round in July 2022. Frontera is using the proceeds to perform a Phase I trial of its lead gene therapy candidate, FT-001, to the treatment of hereditary retinal disease Leber congenital amaurosis-2 (LCA-2). To address LCA-2, FT-001 is designed to be injected into the subretinal space and deliver a healthy copy of the mutated gene that causes the condition. The first results of the clinical trial are expected by the end of 2023.
Frontera is also testing its second candidate, FT-003, in a Phase I study for the treatment of neovascular or wet age-related macular degeneration, with similar results expected in late 2023.
3. Sotio Biotech
Founded: 2010 | Headquarter: Prague, Czechia
Sotio Biotech burst onto the biotech scene in late 2021 with an impressive funding round totaling $317 million, one of the largest private biotech funding rounds ever in Europe.
Sotio is developing a range of cancer immunotherapies, including fusion proteins, antibody-drug conjugates, and CAR-T therapies. The CAR-T program aims to make CAR-T cells effective against solid tumors, which has so far been an elusive goal in the field because tumors can suppress the action of T cells.
To overcome this obstacle, Sotio engineers his CAR-T therapies with additional modifications to genes that regulate T-cell growth and survival to make them more resistant and effective against solid tumors.
Although Sotios’ CAR-T candidates are less advanced than its lead fusion protein candidate, the company is now enrolling patients with specific types of advanced solid tumors in a Phase I/II study of its most advanced candidate, BOXR1030. The expected completion date for the trials is mid-2024.
Founded: 2016 | Headquarter: Paris, France
Traditional gene therapies are designed to deliver the healthy version of a mutated gene into a patient. For diseases caused by only one type of mutation, this is adequate. However, some genetic diseases arise due to different mutations in different patients, making it more difficult for a company to correct them all with a single gene therapy.
SparingVision is developing its own answer to this problem in the genetically blind condition retinitis pigmentosa, which can be caused by 80 different types of mutations. The company’s lead candidate, SPVN06, is designed to slow disease by promoting the production of protective molecules in photoreceptor cells. By providing these genes, the therapy could counteract the disease regardless of the mutation that caused it.
SparingVision caught the attention of venture capital firms in September 2022 when the company raised a Series B round worth $75.5 million. The company aims to use the funding to fund the first human studies of its two most advanced programs, as well as a gene-editing collaboration with Intellia Therapeutics that kicks off in 2021.
In late 2022, SparingVisions lead candidate SPVN06 was cleared by the FDA for testing in humans. The company plans to start a Phase I/II study this year, with the first safety data expected by the end of 2023.
5. Tessa Therapeutics
Founded: 2012 | Headquarter: Singapore
While autologous CAR T therapies can be highly effective in patients with forms of blood cancer, these patient-derived therapies take precious weeks to produce. Allogeneic CAR T therapies can be delivered much faster, but donor-derived CAR T cells are more prone to attack the patient’s body in graft versus host disease (GvHD).
In 2022, Tessa Therapeutics raised a $126 million Series A funding round to help it overcome this challenge. The Singapore-based company is developing allogeneic CAR T cells that are derived from donors but are less harmful to the host than other allogeneic cells. That’s because Tessas therapy comes from a type of T cell that targets cells infected with the Epstein-Barr virus.
Tessas lead allogeneic therapy, TT11X, is currently in a Phase 1 study for the treatment of CD30-positive lymphomas. The company also has an autologous CAR T-cell therapy, TT11, for the treatment of classical Hodgkin’s lymphoma, which is currently in Phase II trials. In January 2023, however, the company decided to redouble its focus on the allogeneic route and leave its autologous work open for collaborative development.
Acknowledgments: Thanks to Cedric Moreau, partner at venture capital firm Sofinnova Partners, and Fady Riad, analyst and CEO of consulting firm Centurion Life Sciences, for suggestions on companies to include.
Jonathan Smith is a freelance science journalist based in the UK and Spain. Previously he worked in Berlin as a reporter and news editor at Labiotech, a website covering the biotech industry. Previously, he completed a PhD in behavioral neurobiology at the University of Leicester and freelanced for the UK-based organizations Research Media and the Society of Experimental Biology. He also has a degree in neuroscience and worked for a year at the Eisai pharmaceutical company in a student internship.
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