Keros Therapeutics (KROS) Status Update summary

Pipeline and clinical program updates

• Elritercept phase 2 trials in lower-risk MDS showed 56% hematologic response and 41% transfusion independence, with durable responses and improved quality of life, supporting advancement to phase 3 registration trial.

• 55.6% of modified intent-to-treat MDS patients achieved an overall erythroid response over 24 weeks; 41.3% achieved transfusion independence for at least eight weeks, with median duration not met and 42.3% maintaining responses over one year.

• Elritercept was generally well-tolerated in MDS and myelofibrosis, with most adverse events mild to moderate, no treatment-related fatal events, and no AML progression observed.

• In myelofibrosis, elritercept, alone or with ruxolitinib, improved hemoglobin, reduced transfusion burden, spleen volume, and symptom scores; 45.5% of patients in combination therapy achieved transfusion independence.

• Cibotercept phase 2 TROPOS trial in pulmonary hypertension is on track for enrollment completion in Q4 2024, with initial phase 1 data showing safety and target engagement; KER-065 phase 1 trial in healthy volunteers is ongoing, with results expected in Q1 2025.

Regulatory and trial design updates

• Positive FDA feedback resulted in alignment on phase 3 trial design for elritercept in MDS, targeting a broad population including both RS and non-RS patients, with transfusion independence as the primary endpoint.

• Phase 3 trial will enroll high transfusion burden patients, with over 50% expected in this category, and will include quality of life measures such as FACIT-Fatigue.

• Approximately 60% of phase 2 MDS patients were uptitrated to the higher dose, and similar criteria will be used in phase 3.

• No ESA-experienced patients will be included in the phase 3 MDS trial.

• Enrollment for cibotercept TROPOS trial is progressing globally, with 75% of sites outside the US.

Competitive landscape and unmet needs

• Current MDS treatments like ESAs and Reblozyl have limited efficacy in high transfusion burden and non-RS patients, with no significant quality of life improvements.

• Elritercept aims to address these gaps by providing durable transfusion independence and quality of life benefits across a broad patient population.

• Investigator enthusiasm for cibotercept remains high despite recent sotatercept approval, with no observed slowdown in patient enrollment.