Signaling proteins called cytokines can trigger a powerful anticancer response, but the challenge with cytokine therapy is to prevent this effect beyond the tumor. Avenge Bio’s technology can elicit potent but targeted cytokine responses in a way unlike other biotech companies working in this increasingly competitive field of drug research. Ovarian cancer is the biotech’s first target, and the startup emerged from stealth with a $45 million funding round that will support plans to bring its lead drug candidate into human trials later this year.
The company recently announced A round The financing was led by Perceptive Xontogeny and CAM Capital.
Like many biotech companies pursuing cytokine therapies, Natick, Mass.-based Avenge’s focus is on a cytokine called interleukin 2 (IL-2). This signaling protein is secreted by activated T cells and functions to regulate various immune cells. In cancer, IL-2 stimulates immune cells to respond to tumors. Engineered versions of IL-2 have been available as cancer immunotherapy for decades, but with limitations. These treatments do not last long in the body. Furthermore, while engineered IL-2 elicits an immune response against cancer cells, it also has toxic effects on healthy cells when circulating throughout the body. Many companies developing new approaches to IL-2 are engineered versions of cytokines that circulate systemically but provide more targeted and long-lasting effects.
Avenge Bio’s experimental treatment is a locally administered cell therapy. The company works with immune effector cells, which are found throughout the body and respond to injury by producing cytokines. The cells, designed to produce IL-2, are encapsulated in a polymer that controls cytokine dosage and production, said Heffernan, former CEO of pain drug biotech Collegium Pharmaceuticals. The treatment is carried out by implanting these engineered cells into the tumor site. Because these cells don’t circulate systemically, Heffernan said Avenge’s therapy avoids causing toxic effects throughout the body. This approach would allow clinicians to deliver higher, more powerful doses to patients, he added.
“If you give it systematically, you don’t get off-target effects,” he said. “The idea is that you can reduce potential toxicity at higher doses than systemic doses.”
Avenge’s lead drug candidate is AVB001. Its origins are personal to Heffernan, whose wife was diagnosed with ovarian cancer in 2015. He said her cancer responded to the standard of care, namely debulking surgery and chemotherapy. But he noted that patients with ovarian cancer who do not respond to standard care or who have relapsed after initial treatment have few treatment options, and he is motivated to find new treatment options.
Heffernan’s search for alternative ovarian cancer treatments led him to the work of Robert Edwards, whose research at the University of Pittsburgh included ovarian cancer. Edwards has tested IL-2 injected into the peritoneum, the tissue that lines the abdominal cavity and pelvic wall.Heffernan said that although Edwards’ research Showing that local administration can work in ovarian cancer, producing responses in 6 of 24 patients, was done using commercially available IL-2, an engineered version with limited durability and toxicity.
Edwards worked with Rice University bioengineering professor Omid Veiseh, whose research includes delivering therapeutics, Heffernan said. Veiseh developed a method to encapsulate cells, while Avenge’s technology, called LOCOcyte, was licensed from Rice. The company uses the technology to encapsulate immune effector cells that produce IL-2. Avenge’s preclinical data in monkeys suggest that the cells can colonize the peritoneal cavity and escape the systemic circulation, Heffernan said. Furthermore, studies have shown that this approach generates local and systemic immune responses without triggering systemic toxicity.
The quest for better IL-2 immunotherapies is gaining interest from a growing number of biotech companies that have raked in cash in the past year. Werewolf Therapeutics, whose lead drug candidate is a version of IL-2, is designed to activate only at the tumor site and last longer after activation, which raised $120 million from its IPO last spring. Asher Bio achieves its targeted approach through Engineering cytokines to bind only to desired immune cells. Asher’s Promising Preclinical Data Prove Convincing Raised a $108 million funding round last September. Meanwhile, Xilio Therapeutics shields healthy tissue from its version of IL-2 using a “mask” that doesn’t fall off until it reaches the tumor microenvironment. Xilio went public in October, raising more than $117 million.
While Avenge is currently behind its IL-2 rivals, the startup’s different approach could have advantages. Heffernan noted that AVB001 stimulated the production of human IL-2, rather than using an engineered version of the cytokine. The native human IL-2 should provide greater potency and a stronger immune response than the engineered version, he said. The immune response from Avenge’s cell therapy also lasted 15 to 30 days — longer than the immune response from an infusion of IL-2, Heffernan said.
Seed investor Longitude Capital, which originally backed Avenge, also participated in the Series A, which added new investors Rock Springs Capital and Pappas Capital. Heffernan said the cash will support the planned Phase 1 development of AVB001 in ovarian cancer, as well as two other programs. One will test AVB001 in lung cancer, and the other preclinical program will test IL-12 as a cell therapy in pancreatic and ovarian cancers and other solid tumors.
LOCOcyte is a platform technology that can be used to produce other cytokines. Heffernan added that while the technology is an off-the-shelf approach, it also offers some potential for customization. For example, a patient might take IL-2 first and then IL-15 a month later. Alternatively, patients may be given doses that produce two different cytokines simultaneously, or encapsulated cells from a single dose may sequentially produce different cytokines. Avenge isn’t pursuing those options right now, but Heffernan said the technology makes them possible.
“If this concept works in ovarian cancer, producing high levels of natural cytokines near the tumor, if this works, that would be a very new concept,” Heffernan said. “If this works, then there’s a good chance our other programs in pleural cancer, pancreatic cancer, will work too.”
Photo by Vengeful Creatures
