The accumulation of senescent cells is thought to be one of the root causes of aging, and a growing body of evidence points to their direct contribution to numerous age-related conditions. Removing senescent cells is a narrow form of rejuvenation, capable of turning back measures of aging and age-related disease. Last year researchers published data on an approach to selective destruction of senescent cells based on interfering in the interaction between FOXO4 and p53. This pushes senescent cells into the form of programmed cell death known as apoptosis, while doing next to nothing to normal cells. The method of interference involves creating a safe but broken version of the FOXO4 protein, FOXO4-DRI, and introducing it into the body. A sizable fraction of senescent cells relying on the presence of working FOXO4 are destroyed as a result. The principal researcher involved in this work has now started a company with the assistance of Apollo Ventures to further develop this line of work into a viable senolytic therapy.
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.
James Peyer, Ph.D., managing partner at aging-focused fund Apollo Ventures 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 his collaborators. 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.