Fredric Abramson

As a field, we need to be much more precise about what can be called a "senolytic therapy" based on two key criteria: •      What percent of senescent cells are demonstrably and reliably eliminated by the candidate therapeutic in acceptable pre-clinical models •      How specific is the therapeutic in targeting senescent cells for elimination versus affecting other biologic processes important in all cells generally? We suggest the following "senolytic” criteria be adopted: •      Demonstrated ability to eliminate at minimum >50% of senescent cells in at least two organs of the body by assay of at least two senescent-cell biomarkers, e.g. SA-βgal, p16, p21, uPAR and/or Lamin B1 •      In addition, a candidate senolytic should have demonstrated specificity in targeting senescent cells over nonspecific effects on cellular pathways important in all cells, along with a reasonable Method of Action explaining that specificity.   Eos SENOLYTIX, Inc.'s (https://eossenolytix.com) lead MitoXcel™ (https://mitoxcel.com) clinical candidates, PTC-2105 and PTC-2107, eliminate ~60 to 80% of senescent cells in all organs of the body, including the brain, in over 20 well-controlled studies performed in naturally aged 75-week or 90-week-old mice, within 8 weeks of treatment as demonstrated and confirmed by all of the above-listed biomarkers of senescent cells. Furthermore, our proprietary MitoXcel™ Technology is highly specific at targeting the two types of cells that demonstrate a lower Mitochondrial Membrane Potential, aging senescent cells and cancer cells. Cancer indications of MitoXcel Technology are being developed by Perseus SENOLYTIX (https://lnkd.in/e4y8XAfM). Phoenix SENOLYTIX, Inc.’s (https://lnkd.in/ehA5ud4t) lead senolytic gene therapy clinical candidate, ApoptiCIDe-CE-GERO-002™ plus proprietary dimerizer activating agent PTC-2102, eliminated ~60 to 70% of senescent cells in the spleens of treated naturally aged 75-week-old mice as assayed by SA-β-gal and Lamin B1. Phoenix SENOLYTIX recently executed a cross license with MD Anderson Cancer Center to advance this technology (https://lnkd.in/ekdurZZM). Marco Quarta Marco Demaria Joao Pedro de Magalhaes Andrew Steele Andrea B. Maier Mark Hyman, MD Robin Mansukhani Alex Zhavoronkov Sebastian A. Brunemeier S. Jay Olshansky, Ph.D. Petr Sramek Peter Fedichev Dr Tamsin Lewis David Agus Yuxi Lin, Ph.D. Evelyne Bischof, MD, PhD Adam Stone Nathan LeBrasseur Roger Fielding Jamie Justice, Ph.D. Peter H. Diamandis Longevity Biotechnology Association Shane Shifflett Amy Dockser Marcus Alex Janin Peter Thiel Brian Armstrong Eric Schmidt "Joe Betts-LaCroix" Joe Lonsdale Yuri Milner Peter H. Diamandis Vinod Khosla ARCH Venture Partners Marc Benioff Naveen Jain Casey Means, MD #heathspan #lifespan #longevity #aging #longevityinvestors #aging #geroscience #gerotherapeutics

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