What does the second generation of cancer immunotherapy look like? For Tim Clackson, president of a new biotech launching today, it will hopefully include protein-based drugs that stimulate the immune system to attack tumors in a more targeted way—by only powering up at the site of the tumor, and not throughout the body.
Akrevia Therapeutics of Cambridge, MA, announced today a $30 million Series A funding round that will help Clackson and his team develop biologics with engineered “on/off” switches. The immune-stimulating drugs would circulate through the body in an inactivated state. When they arrive at the tumor, they would undergo specific biochemical changes, such as the removal of a key protein group, that flip the drug’s switch to “on.” Then the therapy would go to work.
The financing was led by F-Prime Capital Partners and Atlas Venture. Clackson, a former long-time executive at ARIAD Pharmaceuticals, also serves as Akrevia’s head of research and development, with Nessan Bermingham, former CEO of CRISPR drug developer Intellia Therapeutics (NASDAQ: NTLA), serving as executive chairman.
Clackson hopes that cancer immunotherapies that do their work only at tumor sites, rather than systemically, will solve a couple of key problems dogging the field today. For one, some immunotherapies work remarkably well at boosting T-cell responses against tumors, but are also active throughout the body, causing serious side effects. He says turning drugs on only when they’re located at tumors should focus their activity where they’re needed, and dial down activity where they aren’t, reducing toxicity.
Secondly, current immunotherapies don’t work in many cancer patients, and one possible reason is that the drugs don’t boost T-cell activity enough or don’t call in enough T cells. Clackson says that Akrevia’s drugs, including engineered versions of natural immune-stimulating proteins called cytokines and chemokines, could enhance these anti-tumor immune responses, because the drugs’ activity would be focused only on the tumor. “Targeting is one of the key challenges as we enter the second era of immune-oncology,” Clackson says. “Targeting is key to maximizing the potential [of immunotherapy].”
Akrevia’s lead drug is an antibody that blocks CTLA-4, which acts as a brake on immune responses, and is the target of the first checkpoint inhibitor (a type of cancer immunotherapy), ipilimumab (Yervoy), that was approved by the FDA, in 2011. His team has a long road ahead, but Clackson hopes that Akrevia’s drug could one day be as or more effective than ipilimumab, but with a better safety profile and a wider range of doses.
The startup’s technology is based on the work of John Williams, a protein engineer and structural biologist at City of Hope in Duarte, CA, who uses sophisticated laboratory and software tools to rapidly and precisely design proteins. Ulrich Rodeck, who studies cancer immunology at Thomas Jefferson University, is also a co-founder.
Clackson declined to say which cancers his company is targeting or what Akrevia’s other programs are, just that the new financing will allow his team to grow and work on multiple programs.