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4591 Hematologic Improvement and Fatigue Reduction with Elritercept (KER-050) in Participants with Lower-Risk (LR) Myelodysplastic Neoplasms (MDS) with Non-Transfusion Dependent Anemia: New Analyses from an Ongoing Phase 2 Trial

Program: Oral and Poster Abstracts
Session: 637. Myelodysplastic Syndromes: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
MDS, Adult, Clinical Practice (Health Services and Quality), Chronic Myeloid Malignancies, Diseases, Myeloid Malignancies, Human, Study Population
Monday, December 9, 2024, 6:00 PM-8:00 PM

Shuhying Tan, FRACP, FRCPA, MBBS1*, Montserrat Arnan, MD, PhD2*, Lynette C.Y. Chee, MBBS, PhD, FRACP, FRCPA3, Thomas Cluzeau, MD, PhD4, Maria Diez-Campelo, MD, PhD5*, Aristoteles Giagounidis, MD6, Devendra Hiwase, MD, MBBS, PhD, FRACP, FRCPA7, David M Ross, MD, PhD, FRACP, FRCPA8*, Mikkael A. Sekeres, MD9, David Valcarcel, MD, PhD10, Bhavna Patel-Shah11*, Ming Yang, PhD11*, Ying Jiang, PhD, MBA11*, Jiani Yin, PhD11*, Suresh Bobba11*, Montagu Hankin, MSc11*, Chris Materna, MSc11*, Christine Graham, PhD11*, Sanjay Thamake, PhD, MBA11*, Christopher Rovaldi, MSc11*, Dena Grayson, MD, PhD11* and Jen L. Salstrom, MD, PhD11

1St. Vincent's Institute of Medical Research, East Melbourne, Vic, AUS
2Hematology Department. Institut Català d’Oncologia, Hospital Duran i Reynals. Institut d’Investigació Biomèdica de Bellvitge (IDIBELL). Universitat de Barcelona, Hospitalet de Llobregat, Barcelona, Spain
3Department of Clinical Haematology and Bone Marrow Transplant Service, The Royal Melbourne Hospital, Parkville, Australia
4Department for Clinical Hematology, Nice University Hospital, Nice, Provence Alpes Cote d'Azur, France
5Hospital Clínico Universitario de Salamanca, Salamanca, Spain
6Clinic for Hematology, Oncology and Palliative Care Marien Hospital Düsseldorf, Dusseldorf, Germany
7Royal Adelaide Hospital, Adelaide, SA, Australia
8Royal Adelaide Hospital and SA Pathology, Adelaide, SA, Australia
9Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL
10Department of Hematology and Oncology, Hospital Universitario Vall d'Hebron, Barcelona, Spain
11Kero's Therapeutics, Lexington

Background: Roughly 80% of patients in the U.S. with MDS develop anemia, and half eventually require regular transfusions, which are associated with reduced overall survival and further decline in quality of life (QoL). Treating MDS-associated anemia early in the disease course may improve prognosis and QoL. Elritercept is an investigational, modified activin receptor type IIA ligand trap designed to inhibit activin A and other select TGF-β superfamily ligands (activin B, GDFs 8 & 11) to address ineffective hematopoiesis. Data from an ongoing Phase 2 trial (NCT04419649) in LR-MDS demonstrated potential for elritercept to provide durable transfusion independence, including in participants with high transfusion burden (≥4 RBC U/8 wks). Here, in new analyses, we evaluated the effects of elritercept in non-transfusion-dependent (NT) participants with MDS-associated anemia.

Methods: Data are presented as of a data cutoff (DCO) date of 03Apr24 from an ongoing Phase 2 study in LR-MDS for the subgroup of 15 NT participants (0 RBC U/8 wks prior to treatment) out of 87 participants treated with elritercept at the recommended Part 2 dose (RP2D; 3.75–5mg/kg, Q4W). Analyses included the rate of Hematological Improvement-Erythroid (HI-E; IWG 2006; mean hemoglobin [Hgb] increase ≥1.5g/dL over ≥8 wks), change from baseline (CFB) in hematologic and iron homeostasis parameters, and QoL scores assessed using the Functional Assessment of Cancer Therapy-Anemia (FACT-An; 47 items, includes 13-item FACIT-Fatigue subscale) at baseline and after approximately 4, 8, 12, 16, and 24 wks. Minimally clinically important difference (MCID) for FACIT-Fatigue was defined as improvement of ≥3 points.

Results: Eleven participants in the NT subgroup were RS (Ring Sideroblast) positive and 4 were non-RS. Median (range) baseline levels of Hgb, ferritin and hepcidin were 9.2g/dL (8.1-10.5), 417ng/mL (190-1632), and 9.8ng/mL (0-47.4), respectively. Median (range) duration of elritercept exposure was 66 wks (13-145). Elritercept was generally well tolerated, in NT participants with a safety profile consistent with the broader population, as previously reported.

Thirteen (86.7%; RS+ = 90.9%; non-RS = 75%) NT participants achieved HI-E response over the entire treatment period and 11 (73.3%) participants maintained mean Hgb levels ≥11g/dL over at least 8 wks. Responses were durable as supported by observed sustained increases in Hgb (mean increase of 1.5 and 1.7g/dL at wks 24 and 48, respectively). Increased Hgb was also the most common reason for dose modification in NT participants (delay or reduction based on Hgb ≥12g/dL or change >2g/dL in 1 cycle). Five NT participants reduced their dose from 3.75 to 2.5mg/kg and 2 reduced again to 1.5mg/kg, 1 due to a TEAE of neutropenia. HI-E responses were maintained or regained despite dose delay or reduction; one participant maintained HI-E >72 wks despite 2 dose reductions and multiple consecutive dose delays. No NT participants had become transfusion-dependent (>3 RBC U/16 wks) as of the DCO.

Clinically significant improvements in QoL were observed in multiple domains of FACT-An, with 60% and 54.5% achieving a MCID in FACIT-Fatigue by wk 12 and wk 24, respectively. Rapid decreases in ferritin and hepcidin following the first dose were observed that were maintained at 24 wks

Summary: In this first in-depth evaluation of NT participants in the ongoing Phase 2 study of elritercept in LR-MDS, elritercept was generally well tolerated, and robust Hgb responses were observed in most participants. None of the participants were transfusion-dependent as of the DCO. Dose delay and/or reduction occurred in some responders with no compromise in hematologic responses. Clinically meaningful improvements in fatigue, as well as rapid and sustained decreases in ferritin and hepcidin, were observed. Together, these data suggest potential for elritercept to provide durable and sustained benefits to NT participants with LR-MDS by improving anemia, QoL, and iron homeostasis and/or inflammation.

Disclosures: Chee: Keros Therapeutics: Consultancy, Honoraria; Otsuka: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cluzeau: Takeda: Speakers Bureau; Amgen: Speakers Bureau; Syros: Speakers Bureau; Servier: Consultancy, Speakers Bureau; Jazz Pharma: Consultancy, Research Funding, Speakers Bureau; Abbvie: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau; Keros: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Speakers Bureau; Pfizer: Other: International Congress. Diez-Campelo: ASTEX/OTSUKA: Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL TO MEETINGS; CURIS: Membership on an entity's Board of Directors or advisory committees; SYROS: Membership on an entity's Board of Directors or advisory committees; HEMAVAN: Membership on an entity's Board of Directors or advisory committees; BLUEPRINT MEDICINES: Consultancy, Membership on an entity's Board of Directors or advisory committees; AGIOS: Consultancy, Membership on an entity's Board of Directors or advisory committees; KEROS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Other: Travel reimbursement; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Advisory board fees. Giagounidis: BMS: Consultancy; Amgen: Consultancy. Hiwase: Abbvie: Honoraria; Astella Pharma: Honoraria; Otsuka: Honoraria. Ross: Menarini: Membership on an entity's Board of Directors or advisory committees; Keros: Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Sekeres: Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kurome: Membership on an entity's Board of Directors or advisory committees; Schroedinger: Membership on an entity's Board of Directors or advisory committees. Valcarcel: MSD: Consultancy, Honoraria, Speakers Bureau; Astellas: Consultancy, Honoraria; TAKEDA: Consultancy, Honoraria, Speakers Bureau; Kite/Gilead: Consultancy, Honoraria, Speakers Bureau; Jazz Pharmaceuticials: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Meeting and travel accommodation, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Grifols: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Meeting and travel accommodation, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Meeting and travel accommodation, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Gebro: Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Meeting and travel accommodation, Speakers Bureau; Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Meeting and travel accommodation, Research Funding, Speakers Bureau; Agios: Honoraria, Other: Meeting and travel accommodation, Speakers Bureau; AbbVie: Consultancy, Other: Meeting and travel accommodation; SOBI: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Meeting and travel accommodation, Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Other: Meeting and travel accommodation, Speakers Bureau. Patel-Shah: Keros: Current Employment. Yang: Keros: Current Employment. Jiang: Keros: Current Employment. Yin: Keros: Current Employment. Bobba: Keros: Current Employment. Hankin: Keros: Current Employment. Materna: Keros: Current Employment. Graham: Keros: Current Employment. Thamake: Keros: Current Employment. Rovaldi: Keros: Current Employment. Grayson: Keros: Current Employment. Salstrom: Keros: Current Employment.

*signifies non-member of ASH