Cell therapy offers another option for addressing the most difficult blood cancer cases, but such treatments, which are engineered from a patient’s own immune cells, don’t yet work on solid tumors. Neogene Therapeutics is developing technology with the potential to bring cell therapies to solid tumors and it now has $110 million to advance its research toward human testing.
The experimental therapies of Amsterdam-based Neogene target neoantigens, which are, as the term suggests, new antigens. These proteins arise from the mutations that drive cancer and they’re abundant on the surface of cancer cells but absent on healthy cells. That distinction makes for an ideal cancer drug, as specifically targeting these proteins should avoid toxic effects to healthy tissue, says Neogene CEO Carsten Linnemann.
If you’ve heard of neoantigens in the context of cancer research before, perhaps it was related to cancer vaccines. Gritstone Oncology (NASDAQ: GRIT) and Neon Therapeutics, now a subsidiary of BioNTech (NASDAQ: BNTX), are among the companies developing cancer vaccines intended to prompt an immune response to the neoantigens on a patient’s tumors. These vaccines are personalized, based on the mutations that characterize each patient’s cancer.
Neogene is going after the same target with a similar personalized approach, but with a twist. Whereas the goal of cancer vaccines is to stimulate immune cells that multiply in the patient, Neogene aims to multiply its immune cells in the lab. Those cells are then infused into a patient.
The first generation of cell therapies made from a patient’s own immune cells are chimeric antigen receptor T cells, or CAR Ts, which are engineered to target a protein on the surface of cancerous B cells called CD19. These therapies are made by taking T cells from a patient, introducing a gene that expresses a receptor that binds to CD19, multiplying those cells in a lab, and then reinfusing those cells back into the patient. One reason that cell therapies haven’t worked in solid tumors is that not all solid tumor cells express CD19.
Like CAR T, Neogene’s experimental cell therapies are made from a patient’s own immune cells. But the startup takes personalization a few steps further. Neogene engineers into a patient’s immune cells the gene for the receptor that binds to neoantigens.
The neoantigens found on cancer cells are specific to each patient, Linnemann says. Neogene identifies the T cell receptors that bind to these proteins by isolating the receptors from the tumor biopsies that are routinely taken from patients during treatment. The company uses DNA sequencing, DNA synthesis, and genetic screening tools to find the genes that code for the neoantigen receptors. Linnemann says Neogene’s technology allows the company to find receptors for every patient.
“It’s really a personalized treatment where you have to find all components for every patient individually,” he says.
One of the knocks on CAR T therapies is that producing them takes weeks. The personalized nature of a Neogene therapy means that it requires even more time. Linnemann says it’s hard to estimate how much longer it takes compared to CAR T because Neogene is too far away from clinical testing. But he acknowledges that the manufacturing time will be a challenge for the company.
“Once we know these kinds of treatments work, it will be important to compress these timelines,” he says. “Many of these patients don’t have much time. If these kinds of treatments prove to be effective it will be important to provide them as fast as possible.”
The nature of Neogene’s approach means that the company hasn’t yet even tested its technology in animals. As a fully personalized drug that’s different for each patient, the usual principles of testing an experimental therapy in animals don’t apply, Linnemann says. Neogene plans to do some animal testing but Linnemann says the company needs FDA guidance about what preclinical research is required from the company to support an application to advance to human testing. He estimates that clinical testing is two years away. The new capital will be used to support preclnical research and advance as far as early clinical testing.
Neogene is not alone in the quest to bring cell therapies to solid tumors. TCR² Therapeutics (NASDAQ: TCRR) is developing T cell receptor therapies for both solid tumors and blood cancers. In July, the Cambridge, MA-based biotech reported encouraging preliminary data from a Phase 1 study testing TC-210 in solid tumors expressing the protein mesothelin. Eureka Therapeutics of Emeryville, CA, raised $45 million in funding in June to advance to clinical tests of its cell therapies for solid tumors.
Neogene was founded in 2018, based on the research of company co-founder Ton Schumacher. He and Linnemann previously co-founded T-Cell Factory, a Dutch company that Kite Pharma acquired in 2015 for its technology that discovers tumor-specific T cell receptors. In 2017, Kite’s Yescarta went on to become the second CAR T therapy to win FDA approval.
There are other cell therapy connections in Neogene’s roots. The company’s early investors include Arie Belldegrun and David Chang. Belldegrun, Kite’s founder and former president and CEO, went on to co-found Allogene Therapeutics (NASDAQ: ALLO), a South San Francisco company developing allogeneic cell therapies, which are made from the immune cells of healthy donors. Chang, also a former Kite executive, is Allogene’s co-founder, president, and CEO.
Neogene completed a seed financing last year that the company says enabled its technology to reach proof of concept. The funding came from Vida Ventures, TPG Capital and Two River Group—firms that previously teamed up to back Allogene. Neogene’s new capital announced this week, a Series A round of financing, was co-led by EcoR1 Capital, Jeito Capital and Syncona. Polaris Partners and Pontifax also participated, as did the company’s seed investors.
Image: iStock/Janoka82
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