Interest in therapies that remove senescent cells from the body, known as senolytics, has grown massively in the last year or so. There are now a number of companies actively developing senolytic therapies, including UNITY Biotechnology, Oisin Therapeutics, and Antoxerene.
Recently, another company, Cleara Biotech, has arrived on the scene. We anticipated this last year when we saw the original publication by Dr. Peter de Keizer, which showed that its drug candidate was effective at removing senescent cells while leaving healthy cells unharmed . This week, Fiercebiotech published a small article about this new company.
Its approach to the selective destruction of senescent cells is based on the interaction between FOXO4 and p53. This pathway encourages senescent cells to initiate a self-destruct program known as apoptosis, which destroys them. Cleara’s approach involves creating a modified, “broken” version of the FOXO4 protein, known as FOXO4-DRI, and then introducing it into the body. Senescent cells rely on FOXO4 to survive, and when they use the damaged FOXO4-DRI peptide instead, they are destroyed.
Dr. James Peyer, the managing partner at Apollo Ventures, is working with Dr. de Keizer and his team and has been instrumental in setting up Cleara Biotech. Thanks to the support of Apollo Ventures, work continues at a pace to refine the FOXO4-based approach to create a safe and effective senolytic therapy and bring it into human clinical trials.
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.
We believe that the more companies developing therapies that target the aging processes, the merrier. Senolytics is shaping up to be a crowded space in biotech, and that can only be a good thing from our point of view; more approaches and companies developing products means more competition and lower prices. Given the track record of pharma when one company has a monopoly, we welcome the news that yet another company has joined the fray to drive competition even harder.
 Baar, M. P., Brandt, R. M., Putavet, D. A., Klein, J. D., Derks, K. W., Bourgeois, B. R., … & van der Pluijm, I. (2017). Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging. Cell, 169(1), 132-147.