Signaling proteins referred to as cytokines can set off a strong anti-cancer response, however the problem of cytokine remedy is preserving that impact from going past the tumor. Avenge Bio’s know-how can elicit a potent however focused cytokine response differently than different biotechs working on this more and more aggressive sector of drug analysis. Ovarian most cancers is the biotech’s first goal, and the startup has emerged from stealth with $45 million that may help plans to convey its lead drug candidate into human testing later this yr.
The corporate’s lately introduced Collection A spherical of financing was led by Perceptive Xontogeny and CAM Capital.
Like lots of the biotechs pursuing cytokine therapies, the main focus of Natick, Massachusetts-based Avenge is a cytokine referred to as interleukin 2 (IL-2). Secreted by activated T cells, this signaling protein performs a task regulating varied immune cells. In most cancers, IL-2 stimulates immune cells to reply to tumors. Engineered variations of IL-2 have been obtainable for many years as a most cancers immunotherapy, however with limitations. These therapies don’t final lengthy within the physique. Additionally, whereas engineered IL-2 elicits an immune response to most cancers cells, it additionally causes poisonous results in wholesome cells because it circulates all through the physique. Most of the firms growing new approaches to IL-2 are engineering variations of the cytokine that flow into systemically however supply a extra focused and sturdy impact.
Avenge Bio’s experimental remedy is a cell remedy that’s administered domestically. The corporate works with immune effector cells, a sort of cell discovered all through the physique that responds to damage by producing cytokines. These cells, that are engineered to supply IL-2, are encapsulated in a polymer that controls the dosing and the manufacturing of the cytokine, stated Heffernan, the previous CEO of ache drug biotech Collegium Prescribed drugs. The remedy is run by implanting these engineered cells on the web site of the tumor. As a result of these cells don’t flow into systemically, Heffernan stated Avenge’s remedy avoids sparking poisonous results all through the physique. He added that this strategy will allow clinicians to provide sufferers greater, extra highly effective doses.
“You’re not getting the off-target results that you just get in the event you give it systemically,” he stated. “The thought is you lower the potential toxicity at a lot greater doses than you might ever get systemically.”
Avenge’s lead drug candidate is AVB001. Its origins are private to Heffernan, whose spouse was recognized with ovarian most cancers in 2015. He stated that her most cancers responded to the usual of care, which is debulking surgical procedure adopted by chemotherapy. However he famous that ovarian most cancers sufferers whose illness doesn’t reply to straightforward of care or comes again following preliminary remedy have few therapeutic choices and he was motivated to search out new ones.
Heffernan’s quest for various ovarian most cancers therapies led him to the work of Robert Edwards, whose analysis on the College of Pittsburgh consists of ovarian most cancers. Edwards had examined IL-2 dosed into the peritoneum, the tissue lining the belly cavity and pelvic wall. Heffernan stated that whereas Edwards’ analysis confirmed native administration might work in ovarian most cancers, producing responses in six of 24 sufferers, it was carried out with a commercially obtainable IL-2, an engineered model that has sturdiness and toxicity limitations.
Edwards had collaborated with Omid Veiseh, a Rice College professor of bioengineering whose analysis consists of the supply of therapeutics, Heffernan stated. Veiseh had developed a strategy to encapsulate cells and Avenge’s know-how, referred to as LOCOcyte, was licensed from Rice. The corporate makes use of that know-how to encapsulate the immune effector cells that produce IL-2. Heffernan stated that Avenge has preclinical information in monkeys exhibiting that these cells could possibly be implanted within the peritoneal cavity and stored out of systemic circulation. Moreover, the research confirmed that this strategy yielded native and systemic immune responses with out sparking systemic toxicity.
Pursuit of higher IL-2 immunotherapy is drawing curiosity from a rising variety of biotech firms which have reeled in substantial sums of money prior to now yr. Werewolf Therapeutics, whose lead drug candidate is a model of IL-2 engineered to activate solely on the web site of a tumor and to last more upon activation, raised $120 million from its IPO final spring. Asher Bio achieves its focused strategy by engineering the cytokine in order that it solely binds to the specified immune cell. Asher’s promising preclinical information proved compelling sufficient to spark a $108 million spherical of funding final September. In the meantime, Xilio Therapeutics spares wholesome tissue from the results of its model of IL-2 with a “masks” that doesn’t come off till it reaches the tumor microenvironment. Xilio went public in October, elevating greater than $117 million.
Although Avenge at the moment trails its IL-2 rivals, the startup’s completely different strategy might have benefits. Heffernan notes that AVB001 sparks the manufacturing of human IL-2 quite than utilizing an engineered model of the cytokine. Native, human IL-2 ought to supply extra efficiency and a stronger immune response in comparison with engineered variations, he stated. The immune response produced by Avenge’s cell remedy additionally lasts for 15 to 30 days—longer than what’s potential with infused IL-2 therapies, Heffernan stated.
Longitude Capital, the seed investor that originally backed Avenge, additionally participated within the Collection A spherical, which added new buyers Rock Springs Capital and Pappas Capital. Heffernan stated that the money will help the deliberate Part 1 improvement of AVB001 in ovarian most cancers, in addition to two further packages. One among them will take a look at AVB001 in lung cancers and the opposite preclinical program will take a look at a cell remedy for IL-12 in pancreatic and ovarian cancers in addition to different strong tumors.
LOCOcyte is a platform know-how that can be utilized to supply different cytokines. Heffernan added that whereas the know-how is an off-the-shelf-approach, it additionally provides the potential for some customization. For instance, a affected person is perhaps dosed with IL-2 first, after which with IL-15 a month later. Alternatively, a affected person is perhaps given a dose that produces two completely different cytokines on the similar time, or the encapsulated cells from a single dose may make completely different cytokines in sequence. Avenge shouldn’t be pursuing these choices now, however Heffernan stated the know-how makes them potential.
“If this idea works in ovarian most cancers, producing excessive ranges of native cytokines in proximity to the tumor, if that works it’s a really new idea,” Heffernan stated. “If that works, then different packages that we now have in pleural most cancers, pancreatic most cancers, have a excessive chance of working as properly.”
Picture by Avenge Bio