Semma steps toward the clinic after demonstrating effect of potential diabetes cure in landmark animal studies
The research team at the well-funded Semma Therapeutics has cleared one of the last remaining hurdles to getting a potential cure for diabetes into human studies. And if they’re right, it marks a major preclinical milestone for a resurgent regenerative medicine field focused on a new generation of stem cell therapies.
Felicia Pagliuca, VP of cell biology research and development at the Cambridge, MA-based biotech, told the 2019 International Society for Stem Cell Research meeting in LA Saturday that their stem cell-derived islets performed as hoped for — producing insulin — in a study involving non-human primates whose immune systems had been flattened to prevent a rejection. In a separate study involving two pigs, a package of these engineered islets contained in a specially designed package were used successfully to generate insulin without needing an immunosuppressant to protect against a reaction.
“For the first time ever the device protects the cell,” Pagliuca told me in a preview of today’s session, offering evidence from a large animal model that the technology functions with blood glucose levels, spurring insulin secretion as needed. “They really show quite consistent responsiveness.”
And that’s without fibrosis, without cell suffocation, while watching the integration of cell therapy into host tissue.
It’s exciting, says Semma CEO Bastiano Sanna, to see the “curative potential” of this cell therapy.
Really? A cure? For a mass market disease like diabetes?
If that all seems a bit too wonderful to be believed, think about where Pagliuca is coming from. Stem cell therapies had their heyday well over a decade ago as the next big thing in medicine — an overnight sensation which sputtered out in failure as the survivors went back into the lab to do the hard work necessary to make it a reality. That long period of quiet bred considerable skepticism, especially after the first wave of promised cures failed to materialize. And she’s watched it play out as regenerative medicine made its comeback.
One of those pioneering scientists who stayed in the lab was Semma scientific founder and Harvard professor Doug Melton, who published a landmark study 5 years ago outlining how he had successfully used stem cells to create insulin-producing pancreatic beta cells that were inserted in bulk into mice and successfully protected from an immune response — a breakthrough in regenerative medicine. And he’d been working on the cure for more than 20 years, which he started following his son’s diagnosis of Type 1 diabetes.
They’ve raised $158 million over 4 years at Semma to get to this stage, standing on the threshold of a pair of small human studies set to launch next year. They’ll now see if they can reproduce in humans what they did in the non-human primates and pigs: first by running a small study with an immunosuppressant, followed by the use of their device in another study later next year that will avoid immunosuppressants.
CAR-T and gene therapies have come along to demonstrate curative potential, but the CEO says it’s been frustrating to see the first wave of these therapies targeted at tiny patient populations. “We’re very excited about bringing the curative potential of cell therapies into a large indication.”
They’re taking it step by step.
Nobody is rolling out a mass trial for Type 2 diabetes. The first goal is to go after some of the Type 1 diabetes patients who are the hardest to treat, with nowhere left to turn to rein in the autoimmune disease. After that, they can turn to the broader Type 1 population before moving on, perhaps into particular subgroups of Type 2.
Initially, the goal will be to get the islets to do the work needed to safely produce insulin for these patients at a reliable level. These stem cell-derived islets will have to be able to be manufactured at scale. And there’s work underway to see if there’s a universal cell design that can be used to avoid the need for the device they use — something Melton compares to a tea bag.