8-K: Keros Therapeutics Presents Promising Clinical Data for Elritercept in MDS and Myelofibrosis

Keros Therapeutics announced encouraging new data from Phase 2 trials of elritercept (KER-050) in myelodysplastic syndromes (MDS) and myelofibrosis (MF), showing durable transfusion independence and clinical benefits.

Summary

• Keros Therapeutics presented additional data from its Phase 2 clinical trials of elritercept (KER-050) in patients with myelodysplastic syndromes (MDS) and myelofibrosis (MF) at the European Hematology Association (EHA) Annual Congress.
• In the MDS trial, 55.6% of patients achieved an overall erythroid response, and 41.3% of transfusion-evaluable patients achieved transfusion independence (TI) for at least eight weeks.
• Notably, 61.5% of patients who achieved TI maintained it for at least 24 weeks, and 42.3% had responses lasting over one year.
• Patients achieving TI also showed clinically meaningful improvements in fatigue scores.
• In the MF trial, elritercept showed potential to address anemia, with 60.6% of patients showing reductions in transfusion burden.
• Specifically, 72.7% of patients receiving 3.0 mg/kg or higher of elritercept with ruxolitinib had a 50% or greater reduction in transfusions, and 45.5% achieved TI.
• Additionally, 52.9% of patients with enlarged spleens showed some reduction in spleen volume, and a majority of patients experienced a reduction in disease symptoms.
• Preclinical data in an animal model of MF showed that a research form of elritercept promoted erythropoiesis, mitigated anemia, and improved muscle mass and function.

Sentiment

Score: 8

Explanation: The document presents very positive clinical data for elritercept, with strong efficacy and safety profiles. The company is moving towards a Phase 3 trial, which is a significant milestone. The sentiment is very positive, with some caution due to the inherent risks in drug development.

Positives

• Elritercept showed a strong safety profile in both MDS and MF trials, with most adverse events being mild to moderate.
• The data supports the potential of elritercept to address ineffective hematopoiesis and cytopenias in both MDS and MF.
• The observed improvements in fatigue scores in MDS patients suggest a potential for improved quality of life.
• The reduction in spleen volume and symptom scores in MF patients indicates a broader clinical benefit.
• The company received positive feedback from the FDA regarding the design of a Phase 3 trial in MDS.

Negatives

• There were three fatal treatment-emergent adverse events in the MDS trial and four in the MF trial, though all were deemed unrelated to treatment.
• Some patients experienced treatment-related adverse events, including thrombocytopenia and diarrhea in the MF trial.
• The median duration of transfusion independence in the MDS trial was not reached, indicating the need for longer-term data.

Risks

• The company has a limited operating history and has incurred historical losses.
• Keros is dependent on the success of its product candidates, particularly elritercept.
• There is a risk of delays in initiating, enrolling, or completing clinical trials.
• The company faces competition from third parties developing similar products.
• There are risks associated with obtaining, maintaining, and protecting intellectual property.
• Keros is dependent on third parties for manufacturing, clinical trials, and preclinical studies.

Future Outlook

Keros plans to initiate a registrational Phase 3 clinical trial in MDS following positive feedback from the FDA and expects to complete enrollment in the Phase 2 TROPOS trial for cibotercept in Q4 2024. Initial data from the Phase 1 trial of KER-065 is expected in Q1 2025.

Management Comments

• Jasbir S. Seehra, Ph.D., President and Chief Executive Officer, stated that the data presented at EHA continues to show an encouraging broad profile of elritercept and supports its potential to treat not just the disease-associated cytopenias, but also impact the pathogenesis of MDS and MF.
• Management is excited by the results presented, including the durability of transfusion independence observed with elritercept, and are excited to progress towards initiating a registrational Phase 3 clinical trial in MDS following positive feedback from the U.S. Food and Drug Administration.

Industry Context

The results are significant in the context of current treatments for MDS and MF, where there is an unmet need for safe and durable treatments that address the underlying pathophysiology of these diseases. The data suggests elritercept could be a potential alternative to existing treatments such as erythroid stimulating agents and transfusions.

Comparison to Industry Standards

• In a third-party placebo-controlled clinical trial in second-line lower-risk MDS, luspatercept achieved 38% 8-week transfusion independence (TI) compared to 13% with placebo, and 20% 8-week TI in high transfusion burden (HTB) patients compared to 4% with placebo. Keros' elritercept achieved 41.3% 8-week TI in the overall population and 34.8% in HTB patients, suggesting comparable efficacy.
• The median duration of TI in the luspatercept trial was 30.6 weeks, while the median duration of TI for elritercept has not yet been reached, indicating potentially more durable responses.
• In the second-line setting, a medical reviewer of luspatercept noted patient reported outcome (PRO) data showed no improvement in quality of life for patients who received luspatercept or who responded to luspatercept, while Keros' elritercept showed clinically meaningful improvements in fatigue scores.
• RYTELOTM (imetelstat) is approved in 2nd line HTB MDS patients who have not responded to or have lost response to or are ineligible for ESAs. Keros' elritercept is being developed for a broader range of patients including those who are ESA naive, intolerant or experienced.

Stakeholder Impact

• Shareholders are likely to react positively to the promising clinical data and the progress towards a Phase 3 trial.
• Patients with MDS and MF may benefit from a new treatment option with the potential for durable transfusion independence and improved quality of life.
• Employees of Keros are likely to be motivated by the positive results and the company's progress.
• The results may attract potential partners and investors.

Next Steps

• Keros plans to initiate a Phase 3 registrational trial for elritercept in MDS.
• The company will continue enrollment in Part 2 of the RESTORE trial for elritercept in MF.
• Keros expects to complete enrollment in the Phase 2 TROPOS trial for cibotercept in Q4 2024.
• Initial data from the Phase 1 trial of KER-065 is expected in Q1 2025.

Key Dates

Keywords

elritercept, KER-050, myelodysplastic syndromes, MDS, myelofibrosis, MF, anemia, transfusion independence, hematopoiesis, cytopenias, clinical trial, TGF-beta, EHA, spleen volume, fatigue