Keros Therapeutics (KROS) TD Cowen 46th Annual Health Care Conference summary

Pipeline and clinical development

• Lead asset rinvatercept (KER-065) advancing to phase II trials in DMD and ALS, with phase III trials for a partnered asset ongoing with Takeda as of late 2024.

• Rinvatercept targets neuromuscular and neurodegenerative diseases, bone, fibrosis, frailty, and obesity.

• KER-065 is designed to inhibit myostatin and activin, improving muscle regeneration, bone health, and reducing fat, inflammation, and fibrosis.

• Phase I studies showed KER-065 was well-tolerated, with no dose-limiting toxicities or bleeding events, and demonstrated increases in muscle mass, bone density, and reductions in fat mass.

• Elritercept, the most advanced program, is partnered with Takeda, with significant upfront and milestone payments and ongoing phase II/III trials.

Mechanism of action and preclinical/clinical data

• Rinvatercept acts as an activin receptor ligand trap, designed to avoid bleeding risks seen in first-generation molecules.

• Demonstrated efficacy in preclinical and phase I studies for increasing muscle and bone, reducing fat, and improving metabolic markers in DMD.

• In ALS models, KER-065 preserved muscle strength and function, with potential to slow atrophy and indirectly support neuromuscular junctions.

• Preclinical data in ALS mouse models showed improved grip strength and muscle contractility compared to placebo.

Clinical trial design and strategy

• Phase II DMD trial will focus on two cohorts: late ambulatory and early non-ambulatory boys, primarily those on glucocorticoids.

• Initial studies will combine rinvatercept with glucocorticoids, as removing standard of care is considered unethical.

• Early endpoints will include imaging-based changes in lean mass, fat mass, muscle volume, and bone mineral density, with functional stabilization expected at six months and beyond.

• ALS phase II trial design will target slow-progressing patients, likely in combination with standard of care, with endpoints focused on muscle preservation and function.