For a post-Soliris world, Atlas-backed Q32 Bio outlines $46M next-gen complement play
Long before Alexion kindled a renaissance of complement therapeutics with the introduction of the first anti-C5 antibody, Mike Holers — a longtime professor at the University of Colorado School of Medicine — became fascinated with the host defense system as he completed his rheumatology training. As Soliris begins to fade and follow-on, rivals and even generics catch up to the standard bearer. Holers is debuting a next-generation approach he’s been refining with Atlas Venture over the last two years.
Funded with $46 million provided by Atlas as well as OrbiMed, Abingworth and Sanofi Ventures, Q32 wants to bring the first tissue-targeted complement drugs into the clinic by the end of 2021. The CU Healthcare Innovation Fund and Children’s Hospital Colorado are also investors.
Over his years of research and collaboration with colleague Joshua Thurman and Steven Tomlinson at the Medical University of South Carolina, Holers told Endpoints News, the complement field has evolved to reveal targets that can help scientists zero in on diseased tissue, rather than blocking complement activation systemically.
When you think through how the complement system functions, you see “a lot of high levels of systemic proteins, but its real tissue injury, its real damage is localized to cells and tissues on the surface of cells, in the interstitium,” he said.
Yet knowing how to direct drugs to the right places wasn’t enough, as his experience with a previous startup dubbed Taligen — which had an early tissue targeting technology that was acquired but ultimately retired by Alexion — showed. You also need deep knowledge in protein engineering to make sure you’re reining in the complement system properly.
That’s where Atlas and Shelia Violette, Q32’s co-founder, CSO and president of research, comes in.
Rather than antibodies, they are working on fusion proteins that grab the tissue-specific targets on one end and carries a naturally occurring protein that normally keeps the system in check.
“One of the things that is now better understood is that across pretty much any disease where complement activation becomes dysregulated, it’s because you’re losing the optimal function of those negative regulator proteins,” Violette, who left a lengthy career at Biogen to become Atlas’ entrepreneur-in-residence in 2016, said.
It’s so central to what they do that the startup renamed itself from Admirx to Q32, drawing inspiration from the region of the chromosome where these molecules reside, she added; the number 32 also is a shoutout to the importance of strategy, embodied by chess.
The lead candidate blocks both C3 and C5 convertases, Holers said, playing into multiple parts of the system. Their initial focus will be in kidney and skin diseases.
On top of the platform play, Q32 also in-licensed an unrelated antibody that blocks IL-7 receptors from Bristol Myers Squibb. The deal closed in October, as Bristol Myers Squibb was auctioning off assets on the back of its Celgene buyout. At that point, it was also close to nominating its first development candidate on the complement side.
“In the spirit of full transparency,” CEO Mike Broxson, a Takeda vet and former chief of Goldfinch Bio who officially came on board in February, said, “but for Covid we might have launched the company several months ago.”
While the compound, ADX-914, resides in the realm of adaptive immunity rather than innate immunity where its tech platform operates, it pursues a similar strategy not to completely knock out a problematic pathway but fine tune it. (Just don’t expect any more such deals; after this the 12-person team will focus entirely on the complement platform.)
“We’re really about restoring homeostasis,” Broxson said.