DUBLIN – Beta cell regeneration has been a holy grail for type 1 diabetes (T1D) researchers for several decades. Despite some promising results in animal models, progress in patients has remained frustratingly elusive, however. Although the therapeutic concept has been widely explored, definitive clinical evidence that it will actually work is still wanting.

“What has been lacking is translation of what is found in animal models to humans,” Patrick Collombat told BioWorld. Collombat heads up a diabetes genetics group in the Valrose Biology Institute, which is affiliated with the University of Nice Sophia Antipolis. He is also scientific founder of a new startup, Diogenx SA, which has just raised €4.5 million (US$5.1 million) in seed funding from AFB Advent France, the Boehringer Ingelheim Venture Fund (BIVF) and the JDRF T1D Fund, a venture philanthropy fund associated with the New-York-based not-for-profit patient advocates JDRF.

Marseille, France-based Diogenx is embarking on a drug development program instigated by a chance discovery in Collombat’s lab. His group has demonstrated that a naturally occurring protein can regenerate beta cells, the insulin-producing cells found in the islet of Langerhans in the pancreas. A recombinant version of that protein is the basis for the program. “We have been testing it, mostly in the mouse system, and have shown it can induce generation of new beta cells,” Collombat said. “We are extremely enthusiastic, because it does pan out.”

Further details should emerge once the company completes the associated patent filings. “We have not disclosed the nature of the target we’re focusing on,” company co-founder and CEO Benjamin Charles told BioWorld. “It’s a novel approach.”

But Collombat has form in this area, having already licensed a previous discovery to an unnamed company. That involved a finding that the inhibitory neurotransmitter gamma amino butyric acid (GABA) activates a signal pathway involving the transcription factor, PAX4, which can reprogram alpha cells – which ordinarily secrete the hormone glucagon, which elevates blood glucose levels – to become functional beta cells. That deal is “completely independent” of Diogenx, Charles said.

The amount of cash it has raised may be small for now, but its backers have deep pockets, and are unlikely to be found wanting should the new company make real progress. Its immediate priorities are to undertake further work on the biology associated with Collombat’s finding and to conduct further studies on the feasibility of the approach, in terms of safety and tolerability, bioavailability and manufacturability. The aim, Charles said, is to have a candidate drug finalized in two years and to start clinical trials about two years after that.

Charles has a background in science, corporate strategy and business development. He is a co-founder and former chief business officer of another Marseille-based firm, Imcheck Therapeutics SAS, which is developing antibodies targeting gamma delta T cells for cancer indications. The third member of Diogenx’s trio of founders is Jean Pascal Tranié, who is an investor and entrepreneur.

The company is, of course, some ways behind its competitors. The most advanced efforts to regenerate beta cells involve stem cell reprogramming, Collombat said, although the results so far have been “a bit mixed.” Pace-setters include Semma Therapeutics, which is now part of Vertex Pharmaceuticals Inc., of Cambridge, Mass., following the latter firm’s eye-catching $950 million move into the field last year. Privately held Viacyte Inc., of San Diego, topped up its series D round last month with an additional raise of $27 million, and Sigilon Pharmaceuticals Inc., of Cambridge, Mass., raised $80 million in a series B round to progress its pipeline of “shielded living therapeutics” across a variety of indication areas. In T1D, it has been collaborating with Eli Lilly and Co., of Indianapolis, since 2018.

Following the present financing, Matthieu Coutet of AFB Advent, Johannes Zanzinger of BIVF and Katie Ellias of JDRF T1D Fund have joined the Diogenx board.

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