After breathing new life into old mice, senescence startup Cleara bags cash to move toward the clinic

The mouse on the left was treated with a FOXO4 peptide, resulting in its denser fur. (Peter L.J. de Keizer)

Cleara Biotech has raised seed funding to advance a program that reversed aspects of aging in mice. The modified FOXO4-p53 interfering peptide program made headlines last year when it restored the physical fitness, hair growth and kidney function of mice.

Peter de Keizer, Ph.D., and his collaborators achieved the improvements by targeting cells that had entered senescence, a state in which they stop dividing and start secreting different factors. Studies have linked these cells to an array of big diseases, attracting multiple research groups and powering Unity Biotech to an $85 million IPO. 

Among all these activities, Keizer’s peptide stood out because it eliminated senescent cells without harming healthy tissues. By disturbing interactions between FOXO4 and p53, Keizer’s peptide killed senescent cells and enabled elderly mice to run longer, grow hair and regain kidney function.

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“We were just floored because it was this brand new mechanism specific to senescent cells, not present in other cells,” said James Peyer, Ph.D., managing partner at aging-focused fund Apollo Ventures. 

Peyer and his team had been looking for a marker specific to senescent cells without success. Such specificity is vital if a drug is to treat chronic, age-related conditions such as kidney disease without causing intolerable side effects. When Peyer’s fund saw Keizer’s preliminary data, he teamed up with the senescence scientist and two of his collaborators, Marco Demaria, Ph.D., and Tobias Madl, Ph.D. 

The result is Cleara. Cleara will spend the next year optimizing the peptide Keizer tested in mice in anticipation of moving into the clinic. This will entail designing multiple candidates with strengths, pharmacokinetic profiles and other characteristics tailored to indications that Cleara may target. 

Cleara is still zeroing in on indications, with Peyer noting that this is “one of the core challenges for a number of different drugs in this space, where you're presented with a cornucopia of options.” But it has a broad idea of the areas it is going to target.

One lead optimization strand will develop a candidate against a chronic condition, such as kidney disease, osteoarthritis or COPD. The second strand will target an acute, life-threatening “rare or rare-ish” disease. This second strand will likely get into the clinic first—reflecting the higher tolerance for risk among patients with life-threatening diseases—and may ultimately target a type of cancer.   

“Treatment-resistant primary tumors are highly-susceptible to inhibition of this interaction,” Peyer said. The finding reflects the similarities between senescent cells and certain treatment-resistant cancer cells.

While this program is advancing through lead optimization, Cleara will also perform basic research to expand its understanding of senescence. The research will seek to identify new senescence targets, moving the promising field beyond the fairly paltry list of options available to it today.

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