Organization Description
SENOTHERAPEUTIX, Inc. (apparently also known as GEROTHERAPEUTIX) is a holding company for several interrelated subsidiary longevity therapeutics companies, mostly sharing a common technological platform. Eos SENOLYTIX, Perseus SENOLYTIX, and Ponce Aurora are all working to develop MitoXcel Technology for different indications. The company sometimes uses “MitoXcel” to refer to an additional subsidiary, at other times to refer to the drug discovery platform that this subsidiary is developing, and at still other times the candidates (“geropeptides”) that the platform has generated and that the other subsidiaries are advancing. These peptides are 18 to 30 amino acids long and cross the blood-brain barrier.
The company was founded by Kevin Slawin, a biomedical entrepreneur and Director of Urology at Memorial Hermann Hospital.
An additional subsidiary, Phoenix SENOLYTIX, is developing novel gene therapies using ApoptiCIDe, a separate proprietary technology or platform for cell elimination. This appears to be an inducible caspase polypeptide system, similar to the one used to destroy senescent cells in the INK-ATTAC mice, for which Slawin has a patent assigned to one of his prior companies.
The company states that its lead candidates, PTC-2105 and PTC-2107, reverse the age-related decline in mitochondrial membrane potential (MMP, ΔΨm), which is further exacerbated in senescent versus non-senescent cells. Their graphs, in fact, show that PTC2105 increases MMP in nonsenescent cells in vitro but has no obvious effect on MMP in senescent cells. They state that through this mechanism, their candidates exert two pro-longevity effects.
First, the company reports that MitoXcel peptides increase mitochondrial ATP production, leading to increased lipolysis without loss of lean mass and increased exercise endurance in obesogenic high-fat diet-fed mice, whether alone or in combination with the GLP-1 receptor agonist semaglutide.
Second, the company states that its candidates destroy senescent cells via programmed cell death (apoptosis), though it is not clear why increasing mitochondrial activity should do so. However, their graph of PTC2105’s selectivity for apoptotic cell death in senescent versus nonsenescent cells in vitro exhibits difficult-to-interpret changes in its dose-response dynamics. They state that these peptides therefore lower the SASP and systemic inflammation, increase the less inflammatory M2 macrophage phenotype, improve muscle mass, retard age-related cognitive decline, and “eliminat[e] cancer.”
The company also reports that PTC-2105 significantly reduces death from the late effects of gamma irradiation treatment in mice (i.e., treatment after the effects of acute radiation syndrome, which kills a substantial number of mice before treatment is initiated).
In all these preclinical experiments, the company states it has not observed any adverse effects and that the animals’ liver enzyme levels have remained normal. The company emphasizes that all of its effects are due to its core mechanism of action and are not specific to muscle, bone, or fat.
It is notable that the company’s animal studies described above are uniformly executed in relatively young mice (60-75 weeks old) and involve 18-20 weeks of continuous treatment.
Ponce Aurora is developing a cosmetic application of MitoXcel peptides called Yuuth.
In addition, the company reports that PTC-2107 and an additional “oncopeptide” candidate, PTC-2110, increase overall survival in an aggressive tail vein injection model of B-cell acute lymphoblastic leukemia, either alone or in combination with venetoclax.