Keros Therapeutics Presents Preclinical Data From Its KER-065 Program At The 28th International Annual Congress Of The World Muscle Society

Author: Benzinga Newsdesk | October 04, 2023 08:20am

Keros Therapeutics, Inc. ("Keros") (NASDAQ:KROS), a clinical-stage biopharmaceutical company focused on developing and commercializing novel therapeutics to treat a wide range of patients with disorders that are linked to dysfunctional signaling of the transforming growth factor-beta ("TGF-ß") family of proteins, today announced results from preclinical studies evaluating the treatment effect of a research form of KER-065 ("RKER-065") in a mouse model of Duchenne muscular dystrophy ("DMD") and in prednisolone-treated mice, which were presented at the 28th International Annual Congress of the World Muscle Society ("WMS") on Wednesday, October 4, 2023.

 

"We are pleased to present promising preclinical data from our KER-065 program at WMS this year, showing that treatment with RKER-065 led to a robust increase in muscle mass, muscle function and bone mass in a mouse model of DMD and in prednisolone-treated mice," said Jasbir S. Seehra, Ph.D., President and Chief Executive Officer of Keros. "We believe these data support the potential of KER-065 to treat multiple pathophysiologies of DMD and other neuromuscular diseases, and we look forward to commencing a Phase 1 clinical trial of KER-065 in healthy volunteers in the first quarter of 2024."

RKER-065 treatment led to a robust increase in muscle mass, functional strength, and bone formation in a DMD mouse model

• RKER-065 ameliorated muscle and bone loss in a progressive murine model of Duchenne muscular dystrophy
  
   

Keros studied the effect of RKER-065 in a progressive and phenotypically severe DMD mouse model. DMD mice were dosed with vehicle or 10 mg/kg of RKER-065 once weekly for four or six weeks. A cohort of healthy mice received only vehicle.

In DMD mice, treatment with RKER-065 led to significant increases in body weight and lean mass by four weeks compared to vehicle-treated DMD mice. Additionally, an increase in forelimb grip strength was observed, which is supportive of improved muscle function. DMD mice treated with RKER-065 demonstrated significant increases in muscle mass in the pectoralis and tibialis anterior ("TA") as compared to vehicle-treated DMD mice. In addition, expression of utrophin, a functional analog of dystrophin, was higher in the TA of DMD mice treated with RKER-065 compared to vehicle-treated DMD mice.

Concomitant with neuromuscular decline, vehicle-treated DMD mice had significant decreases in bone mineral density ("BMD"), while DMD mice treated with RKER-065 showed no significant difference compared to healthy adult mice. RKER-065 treatment led to a significant increase in trabecular bone volume fraction by six weeks as compared to vehicle-treated DMD mice and a significant increase in trabecular thickness as compared to healthy mice. The RKER-065-treated DMD mice also had a significant decrease in trabecular spacing and a significant increase in trabecular number compared to both healthy mice and vehicle-treated DMD mice.

Overall, treatment with RKER-065 led to a robust increase in muscle mass, functional strength and bone formation in the DMD mouse model. These studies suggest that KER-065 has the potential to benefit DMD patients who suffer from severe muscle loss and impaired muscle function and are at higher risk of fractures.

RKER-065 increased muscle mass, improved muscle function and prevented bone loss in prednisolone-treated mice

• RKER-065, a novel ActRII ligand trap, counteracted the negative impact of glucocorticoid treatment on bone and muscle in mice
  
   

In order to evaluate if RKER-065 can prevent the negative effect of glucocorticoids, the standard of care for DMD, on bone and muscle mass function, Keros treated healthy mice, divided into two groups matched by body weight, with 5.0 mg/kg prednisolone daily ("Pred") and 10.0 mg/kg of RKER-065 weekly ("Pred-RKER-065") or Pred daily and vehicle weekly ("Pred-vehicle") for 9 weeks. A cohort of vehicle-treated mice were fed daily with cherry syrup.

The Pred-vehicle mice exhibited reduced weight gain relative to vehicle – which is consistent with the use of glucocorticoid treatment – while weight gain was maintained in Pred-RKER-065-treated mice. The Pred-vehicle mice also exhibited reduced lean mass gain relative to vehicle, while Pred-RKER-065-treated mice had a robust increase in lean mass compared to Pred-vehicle mice. The observed increase in lean mass in the Pred-RKER-065 mice was associated with an increase in forelimb grip strength compared to Pred-vehicle and vehicle, which was apparent by day 34.

At day 32, both right femoral and whole-body BMD in the Pred-vehicle mice were lower than vehicle. No difference in BMD reduction was observed between the Pred-RKER-065 and vehicle cohorts, suggesting that RKER-065 treatment prevented prednisolone-associated BMD reduction. A similar trend was observed at day 52. Additionally, Pred-RKER-065-treated mice showed increases in trabecular bone parameters relative to both vehicle and Pred-vehicle cohorts.

These data demonstrate that RKER-065 can increase muscle mass, improve muscle function, and prevent bone loss in prednisolone-treated mice. These data further support that targeting activin and myostatin can potentially increase muscle and bone strength in muscular dystrophic patients under glucocorticoid therapy.

About KER-065

KER-065, Keros' fourth product candidate, is designed to bind to and inhibit select TGF-ß ligands, including myostatin and activin A, which are negative regulators of muscle and bone mass and strength. Through inhibition of these TGF-ß ligands, we believe that KER-065 has the potential to induce muscle and bone anabolic effects, increase fat metabolism and reduce fibrosis. KER-065 is being developed for the treatment of neuromuscular diseases, with an initial focus on DMD.

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