Gray Matter working with Insilico Medicine to identify peptide targets and accelerate development timeline for age-related disease therapies.

Earlier this month, we brought you the news from the Aging Research and Drug Discovery Meeting that Insilico Medicine had engaged in a strategic R&D collaboration with longevity startup Gray Matter to fight age-related cognitive decline.

Longevity.Technology: Gray Matter is developing peptide therapeutics for chronic conditions such as mild cognitive impairment (MCI), in the belief that the approach presents “a more favourable risk-benefit profile in the eyes of regulators as compared to interventions based on gene therapy, cell therapy and other novel approaches.” After ARDD, we caught up with the company’s co-founder and CEO Alexey Strygin to learn more.

Strygin has been fascinated by longevity since his early teens and, despite having worked in other areas of biotech, says that he is “more motivated” by working on aging than any other field.

“It just makes sense to me and, if you’re successful, the impact on the world will be huge,” he says. “Even improving health span for just two or three years, the impact is immense. And I think we as a society need to put much more effort than we currently do in this area.”

Seeking peptide therapies for aging

Gray Matter’s parent company is Lactocore, a company developing novel peptide therapeutics from mammalian milk and other natural sources, predominantly focused on psychiatric and metabolic disorders. Therapies developed from peptides are generally seen as being relatively safe and well-tolerated as they can be metabolised by the body.

“I had known the guys at Lactocore for about eight years or so, but I got interested in working with them when they told me they had developed several computational tools that could become a platform for developing even more peptides,” says Strygin.

The idea behind Gray Matter was to leverage the discovery platform to develop therapies for chronic age-related diseases. Many of these conditions, such as MCI, are now able to be diagnosed earlier and earlier, but there are very few therapeutics available for such diseases in their early stages.

“There is a really great market opportunity for extremely safe molecules, which are at the same time effective in targeting early stage age-related diseases,” says Strygin. “So we saw the opportunity to target that niche.”

Mechanism-agnostic discovery

Strygin claims that Gray Matter’s platform technology allows the company to quickly develop a peptide-based intervention whenever a novel aging mechanism is identified.

“We decided to build a aging mechanism-agnostic drug discovery company,” he says, pointing to the impact of clinical trial failures on companies focused on single mechanisms.

“We believe that if there was one universal mechanism of aging, we would have discovered it 10 or 15 years ago. We also we believe there will be many aging phenotypes, depending on age, gender, state of health and other factors. That is why we think our approach, which adapts to newly discovered mechanisms, is very interesting.”

Having only started this year, Strygin stresses that the company is still “very young” but has already set up a testing lab with several fish models including two from the Nothobranchius family. He says the short-lived fish is a faster and more cost-effective way to test potential aging interventions.

“In a single mouse lifespan you can test nine generations of fish. Flies and invertebrates have shorter lifespans but, because we’re developing indications focusing on the central nervous system, their CNS is very far from what we have as humans. Whereas the fish are vertebrates, and they have much more transferable and translatable data for humans.”

Collaboration with Insilico Medicine

Of course, Gray Matter’s in silico work is still its primary focus, and the company is heavily focused on ramping up its capabilities in this area.

“Our discovery platform works great for short peptides, but if we want to predict binding for longer peptides, we encounter a computational bottleneck,” explains Strygin. “Of course, we don’t want to be limited by the length of peptides, so we’re developing a tool that will help us solve this bottleneck. It’s a completely novel approach, and the first MVP version of the tool is now undergoing its first test runs.”

In addition to ramping up its own platform’s peptide capabilities, the new partnership with Insilico Medicine is designed to expand Gray Matter’s ability to find targets.

“We’ve got the expertise to build a molecule that hits a specific target, but what target to choose is a very important decision in drug development,” says Strygin. “Insilico has been doing this so well and for such a long time already, that it makes much more sense to collaborate with them on this – it’s a great synergy.”

“We are pleased to be collaborating with Gray Matter on its target identification efforts,” said Alex Zhavoronkov, CEO of Insilico Medicine in a press release. “Searching for peptide targets is an important modality of the target discovery in general, and we are happy to apply our technology in this challenging area.”

If everything goes to plan, Gray Matter hopes to generate its first candidates in the first half of 2022.

“If all goes extremely well, we will also squeeze in several tests and start to measure the effectiveness of the first generation of candidates,” says Strygin. “So in 2022 we should be able to show some efficacy data and proof of concept.”

Images courtesy of Gray Matter