Newly unveiled startup Morphic Therapeutic hopes that it’s solved some of the technical challenges that have hindered integrin-targeting therapeutics. It’s got more insight into their mechanism of action--as well as a novel structural approach that could enable a small molecule, oral version of what has previously only been injectable biologics.
A trio of strategic investors is buying into the next-gen oral integrin startup in a big way with a new $51.5 million Series A financing. GlaxoSmithKline’s ($GSK) SR One and Pfizer Venture Investments co-led the round, in addition to Omega Funds and AbbVie Ventures. Founding investors Polaris Partners and TA Springer also participated alongside Schrödinger and ShangPharma Investment Group.
The company is based on science from the lab of Tim Springer, a professor at Harvard Medical School and Boston Children’s Hospital. He initially discovered the integrins in the 1980s--spawning the first generation integrins, which now include 6 approved injectable therapies to treat multiple sclerosis, ulcerative colitis, Crohn’s disease, plaque psoriasis, acute coronary syndrome and complications during percutaneous coronary intervention.
“The integrins were actually discovered by Tim in the late '80s. That spawned six different drugs, some of them very big,” Morphic President and CEO Dr. Praveen Tipirneni told FierceBiotech in an interview. “But there were problems and a lot of the pharmas subsided and some left the field.”
“The integrin receptor has three different confirmations. One of these is actually an agonist, so instead of blocking signaling it triggered it. That’s what led to all the problems. He figured out the chemistry to lock it into the closed form to antagonize. That’s when Tim raised his hand to create next-gen integrins; then he and Kevin Bitterman of Polaris put the company together,” he added.
Springer is the scientific founder of Morphic, while Bitterman was the founding CEO. The company has now brought in as its head Tipirneni, who is the former SVP of corporate development and global strategy at Cubist Pharmaceuticals. Cubist was acquired by Merck ($MRK) early last year for $9.5 billion.
Morphic expects this financing will be sufficient to get it into the clinic in multiple programs; the initial areas of focus include fibrosis, autoimmune diseases and immuno-oncology. The goal with this round is to get to early proof of concept data.
The company will simultaneously advance on small molecules for already validated targets with biologic drugs, as well as novel targets--each of these projects are of interest to particular strategic investors, Tipirneni said.
Interestingly, this is the first time that computational chemistry company Schrödinger has invested cash into a company, Tipirneni said. Morphic hopes to follow in the footsteps of Nimbus Therapeutics, which is also partnered with Schrödinger. This spring, Nimbus sold an acetyl-CoA carboxylase (ACC) inhibitor program to Gilead Sciences ($GILD) for $400 million upfront with an additional up to $800 million in development milestones.
Morphic uses ultrahigh-resolution integrin crystal structures, which are said to be unique to Springer’s lab, and is working with Schrödinger to quickly work through design iterations of its development candidates via computational chemistry.
Integrins are a family of receptors that are on the surface of most human cells; they are involved in cellular processes such as cell survival, cell cycle progression, cell differentiation and cell migration.
“We had perfect small molecule drugs from a physical chemistry perspective, but they never worked as well as biologics. Now we know why. One of the confirmations of the integrins is an agonist, enhancing the signaling rather than blocking it. Biologics are so physically large that it blocks them from attaching,” summed up Tipirneni.
“But no one has ever been able to create small molecules for integrins. Now, we can lock them into a closed form. The idea is to create the first-ever small molecule to go after integrins. These are all in chronic diseases. So, the convenience of a pill would be a huge advantage,” he added.
- here's the release
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