We check out emerging companies that aim to overcome CAR-T’s limits with expansions into autoimmune indications, in vivo cell engineering and off-the-shelf therapies.
CAR-T therapies took the world by storm in the last decade as a brand new type of immunotherapy for blood cancer.
The therapies involve extracting a patient’s immune T cells, engineering them to hunt down cancer and reinfusing them into the patient. The cells are specifically equipped with a fusion protein known as a chimeric antigen receptor (CAR) that boosts the cell’s ability to bind to targets such as CD19. By doing this, the therapy has shown big promise in helping patients to survive what would have been an untreatable illness.
The market for CAR-T therapies is expected to grow from $8.4 billion in 2023 to a huge $107.9 billion in 2033, according to Precedence Research. This growth is expected to be driven by rising cancer cases in addition to a growing number of product approvals including Gilead’s Yescarta and Novartis’ Kymriah.
However, current CAR-T therapies have a number of limitations. For example, they are limited to treating forms of blood cancer and are difficult to manufacture at scale. Additionally, they can risk the immune system overreacting and causing harm to the patient in cytokine release syndrome. Earlier this year, the US Food and Drug Administration also linked commercial CAR-T therapies to very rare cases of T cell malignancies.
There are many newcomers to the CAR-T space that aim to overcome the limitations of current treatments with newer forms of technology including off-the-shelf therapies, targeting autoimmune conditions and even delivering the CAR-T therapy in vivo. Check our list for some of the upcoming CAR-T players drawing in major investments.
Cargo Therapeutics
Founded: 2019
Headquarters: San Carlos, California, US
Set up by experts from Stanford University, Cargo is developing cell therapies that are more durable, safer and have a more reliable supply than current CAR-T therapies.
Its lead candidate, firicabtagene autoleucel (firi-cel) is an autologous therapy that targets the tumor antigen CD22, which could treat cancers that are resistant to CD19-targeting CAR-T therapies. The candidate is in phase 2 development for the treatment of patients with large B-cell lymphoma and whose disease relapsed or was refractory to previous CAR T-cell therapies.
Cargo also aims to develop its lead candidate for the treatment of earlier stages of cancer, in addition to programs deploying engineered therapies that are better able to penetrate resistance by tumors.
Cargo Therapeutics raised an impressive, upsized Series A round of $200 million last year, attracting the likes of co-leads Third Rock Ventures, RTW and Perceptive Xontogeny Venture Fund. Later in the same year, Cargo took the leap to the Nasdaq, raising $281.3 million in an initial public offering (IPO).
Earlier this year, Cargo Therapeutics raised an additional $110.0 million in a private placement as it plans to run a phase 2 study of its CAR-T candidate.
Capstan Therapeutics
Founded: 2021
Headquarters: San Diego, California, US
Rather than engineering T cells in the lab to fight cancer, Capstan Therapeutics uses an alternative approach: programming T cells directly in the body. The firm does this by encoding cancer-targeting CARs in a messenger RNA (mRNA) vector and delivering it into patients via lipid nanoparticles. Once the therapy is delivered into the body, it triggers the production of anti-CD19 CARs in T cells.
Using an in vivo approach is designed to deplete the body of harmful B cells without the common drawbacks of CAR-T cells engineered in the lab, such as the high cost and need for specialized infrastructure.
The company launched with a Series A and seed funding worth $165 million and followed up with a $175 million Series B round in March this year. The B round, led by RA Capital Management with new investors including Forbion and Johnson & Johnson Innovation, is being used to fund the development of its in vivo CAR-T therapy candidate CPTX2309 for the treatment of autoimmune disorders.
Capstan also has its crosshairs on other therapeutic areas for its technology including cancer, fibrosis and the treatment of heritable blood disorders.
Kyverna Therapeutics
Founded: 2018
Headquarters: Emeryville, California, US
Despite advances in treatment standards over the decades, traditional treatments for autoimmune diseases come with side effects or depend on immunosuppression, which leaves patients susceptible to infections. By using CAR-T to selectively destroy harmful immune cells, the company aims to develop a safer and more precise treatment for autoimmune conditions.
Kyverna’s lead CAR-T therapy candidate is in phase 1/2 trials for the treatment of lupus nephritis and systemic sclerosis. It is also in phase 2 testing for the treatment of the autoimmune conditions myasthenia gravis and multiple sclerosis.
The company raised $25 million in a Series A round in 2020 and a $85 million Series B round in 2022. Its Series B total went up to $145 million last year in an extension including new investors Bain Capital Life Sciences and GordonMD Global Investments LP. The funding was aimed to bankroll the clinical development of anti-CD19 CAR T-cell therapies for autoimmune diseases.
This year, Kyverna took the plunge into public markets, bagging $319.0 million in a Nasdaq IPO. The company will use the proceeds to advance the clinical development of its lead candidate therapy, take its second candidate into clinical trials, and fund other research and development.
Ucello Bio
Founded: 2020
Headquarters: Chengdu, China
Ucello is on a mission to usher in off-the-shelf CAR-T therapies that can tackle manufacturing problems of traditional autologous CAR-T therapies. Some of these challenges include the fact that patients with late stage blood cancers may lack eligible T cells for harvesting or are unable to receive the cell transplant.
The company is developing off-the-shelf CAR-T therapies based on umbilical cord blood stem cells from donors. By doing this, it aims to make the production process easier compared to autologous methods and help late-stage patients to fight back against the cancer.
Ucello Bio raised RMB 160 million ($22 million) in a Series A round 2022 led by Matrix Partners China. Last year, the company followed up with a Series A+ round of RMB 150 million ($20.6 million) to finance the development of its pipeline. The round was led by Juke Investment with contributions from Guozhong Capital and Penglai Capital and previous investors.
In early clinical testing, the company notes that its lead allogeneic CAR-T therapy UC101 has shown promise in terms of efficacy and safety.
Verismo Therapeutics
Founded: 2021
Headquarters: Philadelphia, Pennsylvania, US
Verismo was spun out of the University of Pennsylvania by the inventors of Kymriah. The firm is building CAR-T therapies based on its so-called KIR-CAR platform, which engineers T cells to express proteins modified from tumor-busting natural killer (NK) cells. In this way, the therapy could overcome the limits of current therapies and withstand the immunosuppressive environments of solid tumors.
Verismo raised $17 million in a pre-Series A financing round in mid-2023. The round was co-led by DongKoo Bio, HLB Innovation and HLB and took Verismo’s total winnings to $50 million.
The financing was earmarked for a phase 1 clinical trial of the company’s CAR-T therapy candidate called SynKIR-110 for the treatment of solid tumors. The company also aimed to use the investment to bankroll the preclinical development of a blood cancer program.
Verismo’s CAR-T platform can also be blended with other emerging approaches such as in vivo gene engineering and cell reprogramming to create more sophisticated immunotherapies.
