Keros Therapeutics Announces Additional Update on the Phase 2 TROPOS Trial

Rhea-AI Summary

Keros Therapeutics (NASDAQ: KROS) has announced the complete halt of dosing in its Phase 2 TROPOS trial of cibotercept (KER-012) for pulmonary arterial hypertension (PAH) due to new observations of pericardial effusion adverse events. This decision extends to all treatment arms, including the 1.5 mg/kg and placebo groups, following a previous halt of the 3.0 mg/kg and 4.5 mg/kg treatment arms announced on December 12, 2024.

The company has notified investigators and regulatory authorities, including the FDA, about the early termination of the trial. Patients will be monitored through end-of-trial visits. Despite the setback, Keros maintains its timeline to present topline data from all treatment arms in the second quarter of 2025.

Positive

• Company maintains timeline for topline data presentation in Q2 2025

Negative

• Complete halt of Phase 2 TROPOS trial due to safety concerns
• Early termination of all treatment arms including placebo group
• New observations of pericardial effusion adverse events
• Potential delay in drug development timeline

Insights

Clinical Trial Analyst

The voluntary halting of all dosing arms in the TROPOS Phase 2 trial represents a severe setback for Keros Therapeutics' PAH program. The extension of safety concerns from higher doses (3.0 and 4.5 mg/kg) to lower doses (1.5 mg/kg) suggests a dose-independent safety signal, which is particularly concerning for the therapeutic window of cibotercept. Pericardial effusion, the accumulation of fluid around the heart, is a serious adverse event that can be life-threatening.

The early termination of the trial will likely result in incomplete efficacy data, potentially compromising the statistical power of the study. While topline data is still expected in Q2 2025, the truncated treatment duration may affect the ability to demonstrate meaningful clinical benefits. This development could significantly delay or potentially derail the PAH program, requiring substantial protocol modifications or possibly a complete reassessment of the therapeutic approach.

In simple terms: Think of this like a car manufacturer discovering a serious safety issue - first in their luxury models, then finding the same problem in their economy cars too. They have to stop selling all models until they figure out what's wrong. This is similarly serious for Keros' drug development efforts.

Biotech Investment Analyst

This development represents a material negative catalyst for KROS. With a market cap of $505M, the company's valuation could face significant pressure as the PAH program was a key value driver. The complete suspension of the TROPOS trial introduces several critical concerns:

1. Potential pipeline reprioritization may be necessary, impacting resource allocation and development timelines
2. Regulatory scrutiny could intensify across Keros' entire platform, given the safety signal
3. Additional capital requirements may emerge if program modifications or alternative development paths are needed

For retail investors: This is comparable to a company's main product line being pulled from development due to safety concerns. The stock will likely experience increased volatility as the market reassesses the company's prospects. The risk profile of KROS has significantly increased, particularly given its clinical-stage status and dependence on pipeline success.

LEXINGTON, Mass., Jan. 15, 2025 (GLOBE NEWSWIRE) -- Keros Therapeutics, Inc. (“Keros” or the “Company”) (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 that it has voluntarily halted all dosing in the TROPOS trial, a Phase 2 clinical trial of cibotercept (KER-012) in combination with background therapy in patients with pulmonary arterial hypertension (“PAH”), 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. On December 12, 2024, the Company announced that it had voluntarily halted the 3.0 mg/kg and 4.5 mg/kg treatment based on the observation of pericardial effusions at those dose levels.

“While we are disappointed in this new development, patient safety is always our top priority. We continue to work with the investigators, the U.S. Food and Drug Administration (“FDA”) and other relevant regulatory authorities, and we look forward to analyzing and presenting TROPOS topline clinical data in the future,” said Jasbir S. Seehra, PhD., Chair and CEO.

The Company has notified investigators and certain regulatory authorities, including the FDA, about this decision, and is in the process of notifying other relevant regulatory authorities. The TROPOS trial is being terminated early, and patients are expected to be monitored through the end-of-trial visits. The Company continues to expect to present topline data from all treatment arms in this trial in the second quarter of 2025.

About TROPOS (NCT05975905)

TROPOS is a randomized, double-blind, placebo-controlled, global Phase 2 clinical trial to evaluate cibotercept in combination with background therapy in patients with PAH. The primary objective of this trial is to evaluate the effect of cibotercept on pulmonary hemodynamics compared to placebo in participants on background PAH therapy. The key secondary objective of this trial is to evaluate the effect of cibotercept on exercise capacity compared to placebo on participants on background PAH therapy.

About Cibotercept

Cibotercept is designed to bind to and inhibit the signaling of TGF-β ligands that stimulate smooth muscle hypertrophy and fibrosis, including activin A, activin B and myostatin. Keros believes that cibotercept has the potential to increase the signaling of bone morphogenic protein (“BMP”) pathways through this 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. Cibotercept is being developed for the treatment of PAH and for the treatment of cardiovascular disorders.

Cautionary Note Regarding Forward-Looking Statements

Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Words such as “continue,” “expect” and “forward,” or similar expressions are intended to identify forward-looking statements. Examples of these forward-looking statements include statements concerning: Keros’ expectations regarding its progress and the design, objectives and timing of its clinical trial for cibotercept, including expected timing for data readout for the TROPOS trial; the response of FDA or any regulatory authorities to our voluntary actions with respect to the TROPOS trial; and the potential of cibotercept to increase the signaling of BMP pathways to treat diseases such as PAH. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. These risks and uncertainties include, among others: Keros’ limited operating history and historical losses; Keros’ ability to raise additional funding to complete the development and any commercialization of its product candidates; Keros’ dependence on the success of its product candidates, cibotercept, elritercept and KER-065; that Keros may be delayed in initiating, enrolling or completing any clinical trials; the risk that initial or interim results from a clinical trial may not be predictive of the final results of the trial or the results of future trials; competition from third parties that are developing products for similar uses; Keros’ ability to obtain, maintain and protect its intellectual property; and Keros’ dependence on third parties in connection with manufacturing, clinical trials and preclinical studies.

These and other risks are described more fully in Keros’ filings with the Securities and Exchange Commission (“SEC”), including the “Risk Factors” section of the Company’s Quarterly Report on Form 10-Q, filed with the SEC on November 6, 2024, and its other documents subsequently filed with or furnished to the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. Except to the extent required by law, Keros undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

Investor Contact:
Justin Frantz
jfrantz@kerostx.com
617-221-6042

FAQ

Why did Keros Therapeutics (KROS) halt the TROPOS trial in January 2025?

Keros halted the TROPOS trial due to new observations of pericardial effusion adverse events across all treatment arms, including the 1.5 mg/kg and placebo groups.

When will Keros (KROS) release the TROPOS trial topline data?

Keros expects to present topline data from all treatment arms of the TROPOS trial in the second quarter of 2025.

What doses were affected in the KROS TROPOS trial suspension?

All doses were affected, including 1.5 mg/kg, 3.0 mg/kg, 4.5 mg/kg, and placebo treatment arms.

What was the initial December 2024 halt of the TROPOS trial by KROS?

On December 12, 2024, Keros initially halted only the 3.0 mg/kg and 4.5 mg/kg treatment arms due to pericardial effusions at those dose levels.

What happens to patients enrolled in the KROS TROPOS trial after the halt?

Patients in the TROPOS trial will be monitored through end-of-trial visits as the trial is being terminated early.