Company: KROS
Filing Date: 2025-02-26
Form Type: 10-K
Source: 0001664710-25-000018
Chunk: 96

Company: Keros Therapeutics, Inc.
Filing Date: 2025-02-26
Form: 10-K
Item: Item 1
Chunk 96
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 end-of-trial visits. We expect to present topline data from all treatment arms in this trial in the second quarter of 2025.

Completed Phase 1 Clinical Trial in Healthy Volunteers

In September 2022, we completed a randomized, double-blind, placebo-controlled, two-part Phase 1 clinical trial to evaluate single and multiple ascending doses of cibotercept in healthy volunteers. The primary objectives of this trial were safety, tolerability and pharmacokinetics. The trial design is summarized in the figure below.

Phase 1 Clinical Trial Design

Observed tolerability data 

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Cibotercept was generally well tolerated in Part 1 of this trial at dose levels up to 5 mg/kg, the highest dose level tested, when administered as a single dose, and multiple doses of 0.75 mg/kg, 1.5 mg/kg and 4.5 mg/kg. In Part 1 of this trial, one subject withdrew consent after receiving a single 1.5 mg/kg dose of cibotercept and did not complete the safety follow-up. In Part 2 of this trial, one subject discontinued after receiving two doses of placebo due to a serious adverse event unrelated to treatment and another subject withdrew consent after receiving two 1.5 mg/kg doses of cibotercept. None of the discontinuations in this trial were due to treatment-related adverse events. No serious adverse events were reported in Part 1 of this trial. Additionally, the majority of the adverse events that were observed in this trial were mild in severity and resolved. 

Trend for increased whole-body bone mineral density observed

Bone mineral density, or BMD, was assessed temporally by dual-energy x-ray absorptiometry in Part 2 of this trial at baseline and at Day 113 of the trial. A trend for increased whole-body BMD was observed after multiple doses of cibotercept.

Part 2 of the Trial: BMD Change from Baseline

Observed changes in pharmacodynamic markers were consistent with increased BMP signaling in the bone

We observed dose-dependent increases in serum bone specific alkaline phosphatase, or BSAP, a marker of osteoblast activity, with a maximal increase observed at the highest doses evaluated in this trial.

Cibotercept is designed to inhibit activins and growth differentiation factor ligands in bone, which potentially results in reduced SMAD 2/3 signaling and increased signaling of the BMP pathway (SMAD 1/5/9). The increased BMP signaling