Equity investment in MDI Therapeutics by Juvenescence will develop novel serpin-based therapies.

Juvenescence, a biopharmaceutical company focused on treating aging and age-related disease, has announced today its new equity investment in MDI Therapeutics, Inc, a Michigan-based company developing novel serpin-based therapies for the treatment of fibrosis and fibroproliferative disorders. Juvenescence will provide MDI with up to $9 million in Series A financing and collaborate with MDI to advance its lead program through Phase 1 clinical trials.

Longevity.Technology: Juvenescence develops therapies to modify aging and increase healthy human lifespan and is committed to inspiring and equipping the world to not just reimagine what it means to get older but to help people reimagine their lifetime. Juvenescence has a broad portfolio of products in development to which it is adding serpins, serine protease inhibitors.

Serine proteases have been described as the “workhorses of the human body” [1] and there are approximately 180 in humans; these play a role in diverse physiological processes, including blood coagulation, fibrinolysis and inflammation to immunity. Inhibitory serpins are single-use or ‘suicide’ inhibitors that change shape to do their job, but this ability also renders them vulnerable to mutations that promote misfolding or mis-timed changes, which can lead to conformational diseases or ‘serpinopathies’ including emphysema, thrombosis and angio-edema [2].

“MDI has developed deep proprietary expertise in the biology of serine protease inhibitors (“serpins”), a class of proteins associated with coronary heart disease, thrombosis and chronic fibrotic and inflammatory diseases,” said Juvenescence’s Chief Scientific Officer Dr Grazia Piizzi.

“Serpins have historically been a challenging target for pharmaceutical development, but MDI has shown that they can successfully use their proprietary high throughput screening platform to find novel drug candidates. Their lead program, a first-in-class orally available Plasminogen Activator Inhibitor (PAI-1) inhibitors, has demonstrated efficacy in multiple preclinical models of fibrosis and thrombosis, as well as a promising pharmacokinetic and safety profile. These data were particularly impressive compared to other small molecule inhibitors of PAI-1 that have been studied in humans.”

“Extensive scientific evidence points clearly to PAI-1’s involvement in fibrosis and thrombosis” said Dr Steve Felstead, Juvenescence’s Head of Development Projects. “By successfully targeting PAI-1, MDI may provide a powerful new tool for the treatment of these common and devastating diseases of aging.”

Stephen Benoit, MDI’s President & CEO, said: “MDI’s mission is to unlock the therapeutic potential of serpin biology for the benefit of patients diagnosed with chronic fibrotic and inflammatory diseases. Juvenescence’s broad drug development expertise and their deep commitment to, and expertise in, diseases of aging make them an ideal collaborator for us as we strive to rapidly advance our lead PAI-1 program into the clinic.

“Fibrosis and thrombosis represent enormous and devastating health burdens on an aging population,” said Dr Greg Bailey, co-founder and CEO of Juvenescence. “We are excited to add our new partnership with MDI to our robust and growing portfolio of investments that target age-related diseases via their fundamental causes.”

Longevity.Technology reached out to Alexander Pickett, Managing Director of Juvenescence who told us that PAI-1 has been on Juvenescence’s radar since the company began. “PA-1 is a very challenging target to drug properly – many groups have tried to drug it and failed,” Pickett told us.

“The gene was discovered through studying a rare subtype of hemophilia found in an Old Order Amish community. In 2017, a Science Advance paper was published showing that carriers of that gene, who have one functional copy of PAI-1, appeared to be healthier than non-carriers. They had lower rates of diabetes and obesity, longer leukocyte telomere length, and they even lived longer. A PAI-1 inhibitor clearly fit into the profile of a pro-longevity therapeutic. What was also exciting was that PAI-1 was clearly implicated in a range of diseases, including idiopathic pulmonary fibrosis and systemic sclerosis. There was both a link to aging and a tractable clinical development path – that got us really excited.”

Speaking about the equity investment, he said: “MDI succeeded because it was committed to deeply understanding its target and why previous efforts to drug it failed. A lot of patience and drug discovery expertise were required to produce their lead molecule, and we’re excited to develop it.”