Company: KROS
Filing Date: 2025-02-26
Form Type: 10-K
Source: 0001664710-25-000018
Chunk: 95

Company: Keros Therapeutics, Inc.
Filing Date: 2025-02-26
Form: 10-K
Item: Item 1
Chunk 95
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 in combination with other PAH therapies. We believe that potent therapies that do not exhibit tachyphylaxis, are orally bioavailable or do not require continuous infusion therapy would have advantages over the currently available treatments for PAH.

Therapies that delay or reverse the obliterative pulmonary vascular remodeling could have a long-term clinical stabilizing effect in PAH. We believe that cibotercept has the potential to increase the signaling of BMP pathways through the inhibition of activin A and activin B signaling, and consequently treat diseases such as PAH that are associated with reduced BMP signaling due to inactivating mutations in the BMP receptors.

Phase 2 Clinical Trial in Patients with Pulmonary Arterial Hypertension

We conducted a randomized, double-blind, placebo-controlled Phase 2 clinical trial to evaluate cibotercept in combination with background therapy in adult patients with PAH, which we refer to as the TROPOS trial. The primary objective of this trial 

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was to evaluate the effect of cibotercept on hemodynamics compared to placebo in patients on background PAH therapy, and the primary endpoint was change from baseline in pulmonary vascular resistance at Week 24. The key secondary objective of this trial was to evaluate the effect of cibotercept on exercise capacity compared to placebo in patients on background PAH therapy, and the key secondary endpoint was change from baseline in 6-minute walk distance at Week 24. Additionally secondary objectives of this trial included evaluating the safety and tolerability of cibotercept, the effects of cibotercept on N-terminal pro B-type natriuretic peptide, or NT-proBNP, a biomarker of myocardial stress, and the improvement in functional class of cibotercept compared to placebo.  The original trial design is summarized in the figure below.

In December 2024, we announced that we voluntarily halted dosing in the 3.0 mg/kg and 4.5 mg/kg treatment arms in the fully enrolled TROPOS trial based on a safety review due to the unanticipated observation of pericardial effusion adverse events at those dose levels. Subsequently, we announced in January 2025 that we voluntarily halted all dosing in the TROPOS trial, including the 1.5 mg/kg and placebo treatment arms, based on the ongoing safety review due to new observations of pericardial effusion adverse events. The TROPOS trial is being terminated early, and patients are expected to be monitored through the