High Risk Myelodysplastic Syndrome

Geron’s blood disorder drug imetelstat is forecast to generate $1.2bn in sales in 2029, according to GlobalData. Credit: MacroEcon via Shutterstock. Advisers to the US Food and Drug Administration (FDA) on 14 March defended Geron ‘s blood disorder drug, saying the benefits outweighed the risks associated with the treatment, based on data from a Phase III trial. The FDA’s Oncologic Drugs Advisory Committee voted 12 to two in favour of the clinical benefit / risk profile of imetelstat based on results from the IMerge Phase III clinical trial (NCT02598661), to treat transfusion-dependent anaemia in patients with a group of blood cancers called myelodysplastic syndromes (MDS). The Phase III IMerge trial enrolled 178 patients across North America, Europe, the Middle East, and Asia. Imetelstat, a telomerase inhibitor, showed significantly higher red blood cell transfusion independence (RBC-TI) rates for at least eight consecutive weeks, compared to placebo, meeting its primary endpoint. Additionally, 28% of imetelstat-treated patients achieved a statistically significant improvement in the key secondary endpoint of RBC-TI at 24 weeks, compared to 3% on placebo. The concerns leading up to the FDA’s advisory panel meeting were surrounding the high rate of cytopenias (low red blood cell counts) in patients treated with the drug, but the committee ultimately backed the drug’s efficacy and safety. See Also: With FDA greenlight, BMS Breyanzi brings CAR-T cell therapy to CLL and SLL FDA approves Madrigal’s Rezdiffra as the first NASH therapy The regulatory agency will now provide a decision on the approval of the treatment by 16 June 2024 under the Prescription Drug User Fee Act. If approved, imetelstat will be competing with Bristol Myers Squibb ‘s Reblozyl (luspatercept). The drug generated $1bn last year, as per BMS’ annual report. GlobalData expects the drug to continue its upward sales trajectory and pull in $3.4bn in global sales in 2030. The FDA expanded Reblozyl’s label in August 2023 to treat the same indication. According to GlobalData’s Pharma Intelligence Center, imetelstat is forecast to generate $1.2bn in sales in 2029. GlobalData is the parent company of Pharmaceutical Technology. The drug is also being investigated in a Phase III IMpactMF (NCT04576156) open-label, controlled trial to treat patients with relapsed/refractory myelofibrosis (MF). Approximately 320 subjects with intermediate-2 or high-risk MF who are relapsed after or refractory to previous JAK inhibitor treatment will be randomised to receive either imetelstat or the best available therapy (BAT). In the announcement accompanying the backing, Geron CEO Faye Feller said: “We are pleased with the committee’s decision to recognise the positive clinical benefit/risk profile of imetelstat for the treatment of transfusion-dependent anaemia in adult patients with lower-risk MDS. “There are few treatment options and significant unmet medical need remains for these patients, particularly among those with difficult-to-treat subtypes of this blood cancer.”

FDA Oncologic Drugs Advisory Committee voted 12 to 2 in favor of the clinical benefit/risk pro imetelstat based on results from the IMerge Phase 3 clinical trial There are significant unmet needs across key TD LR-MDS patient populations, including difficult-to-treat subgroups that are underserved by currently available treatment options June 16, 2024 PDUFA target action date for imetelstat NDA for the treatment of TD anemia in adult patients with LR-MDS FOSTER CITY, Calif.--(BUSINESS WIRE)-- Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company developing investigational first-in-class telomerase inhibitor, imetelstat, to treat hematologic malignancies, today announced that the U.S. Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) voted 12 to 2 in favor of the clinical benefit/risk pro imetelstat for the treatment of transfusion-dependent (TD) anemia in adult patients with low-to-intermediate-1 risk myelodysplastic syndromes (LR-MDS) who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESAs). “We are pleased with the Committee’s decision to recognize the positive clinical benefit/risk pro imetelstat for the treatment of transfusion-dependent anemia in adult patients with lower-risk MDS. There are few treatment options and significant unmet medical need remains for these patients, particularly among those with difficult-to-treat subtypes of this blood cancer,” said Faye Feller, M.D., Geron’s Executive Vice President, Chief Medical Officer. “We believe that imetelstat has the potential to be an important new medicine for patients and look forward to continuing our collaboration with the FDA as they complete their review of our New Drug Application.” The ODAC reviewed the results from the IMerge Phase 3 clinical trial. The primary endpoint of red blood cell transfusion independence (RBC-TI) for at least eight consecutive weeks was significantly higher with imetelstat vs. placebo (p<0.001), with median RBC-TI duration approaching one year for imetelstat ≥8-week RBC-TI responders. In addition, 28% of imetelstat-treated patients compared to 3% on placebo obtained a statistically significant improvement in the key secondary endpoint of at least 24-week RBC-TI. For those patients achieving ≥24-week RBC-TI, the median duration was 80 weeks. Clinically meaningful RBC-TI was achieved across key MDS subgroups irrespective of ring sideroblast (RS) status, baseline transfusion burden and International Prognostic Scoring (IPSS) risk category. Additionally, a sustained increase in mean hemoglobin levels in imetelstat-treated patients was observed over time compared to placebo patients. Consistent with prior imetelstat clinical experience, the most common Grade 3-4 adverse events were thrombocytopenia (62%) and neutropenia (68%) that were generally manageable and of short duration. The FDA assigned a Prescription Drug User Fee Act (PDUFA) target action date of June 16, 2024 for Geron’s New Drug Application (NDA) for imetelstat for the treatment of TD anemia in adult patients with low- to intermediate-1 risk myelodysplastic syndromes, who have failed to respond, or have lost response to, or are ineligible for ESAs. The ODAC provides the FDA with independent opinions and recommendations from outside medical experts, patients and caregivers, though the recommendations are not binding. Geron plans to commercially launch imetelstat in the U.S. upon potential FDA approval. About IMerge Phase 3 The Phase 3 portion of the IMerge Phase 2/3 trial is a double-blind, 2:1 randomized, placebo-controlled clinical trial to evaluate imetelstat in patients with IPSS Low or Intermediate-1 risk (lower-risk) transfusion-dependent MDS who were relapsed after, refractory to, or ineligible for, erythropoiesis stimulating agent (ESA) treatment, had not received prior treatment with either a hypomethylating agent or lenalidomide and were non-del(5q). To be eligible for IMerge Phase 3, patients were required to be transfusion-dependent, defined as requiring at least four units of packed red blood cells (RBCs), over an eight-week period during the 16 weeks prior to entry into the trial. The primary efficacy endpoint of IMerge Phase 3 is the rate of red blood cell transfusion independence (RBC-TI) lasting at least eight weeks, defined as the proportion of patients without any RBC transfusion for at least eight consecutive weeks since entry to the trial (8-week RBC-TI). Key secondary endpoints include the rate of RBC-TI lasting at least 24 weeks (24-week RBC-TI), the duration of RBC-TI and the rate of hematologic improvement erythroid (HI-E), which is defined under 2006 IWG criteria as a rise in hemoglobin of at least 1.5 g/dL above the pretreatment level for at least eight weeks or a reduction of at least four units of RBC transfusions over eight weeks compared with the prior RBC transfusion burden. A total of 178 patients were enrolled in IMerge Phase 3 across North America, Europe, the Middle East and Asia. About Imetelstat Imetelstat is a novel, first-in-class investigational telomerase inhibitor exclusively owned by Geron and being developed by Geron in hematologic malignancies. Data from non-clinical studies and clinical trials of imetelstat provide strong evidence that imetelstat targets telomerase to inhibit the uncontrolled proliferation of malignant stem and progenitor cells in myeloid hematologic malignancies, resulting in malignant cell apoptosis. Imetelstat has been granted Fast Track designation by the U.S. Food and Drug Administration for both the treatment of adult patients with transfusion-dependent anemia due to Low or Intermediate-1 risk MDS that is not associated with del(5q) who are refractory or resistant to an erythropoiesis stimulating agent, and for adult patients with Intermediate-2 or High-risk myelofibrosis (MF) whose disease has relapsed after or is refractory to Janus kinase (JAK) inhibitor treatment. Imetelstat is currently not approved by any regulatory authority. About Geron Geron is a late-stage clinical biopharmaceutical company pursuing therapies with the potential to extend and enrich the lives of patients living with hematologic malignancies. Our first-in-class investigational telomerase inhibitor, imetelstat, harnesses Nobel Prize-winning science in a treatment that may alter the underlying drivers of disease. The New Drug Application (NDA) for imetelstat for the treatment of transfusion-dependent anemia in patients with lower-risk myelodysplastic syndromes (TD LR-MDS) who have failed to respond or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESAs), based on the results from the Phase 3 IMerge clinical trial, is currently under review by the U.S. Food and Drug Administration (FDA) with a Prescription Drug User Fee Act (PDUFA) target action date of June 16, 2024. In addition, the European Medicines Agency (EMA) validated the Marketing Authorization Application (MAA) for the same proposed indication and is under review. Furthermore, Geron currently has an ongoing pivotal Phase 3 clinical trial evaluating imetelstat in relapsed/refractory myelofibrosis (R/R MF). To learn more, visit or follow us on LinkedIn. Use of Forward-Looking Statements Except for the historical information contained herein, this press release contains forward-looking statements made pursuant to the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that such statements, include, without limitation, those regarding: (i) few treatment options and significant unmet needs across key TD LR-MDS patient populations, including difficult-to-treat subgroups that are underserved by currently available treatment; (ii) that imetelstat has the potential to be an important new medicine and Geron’s plans to work with the FDA as they complete their review of the NDA; (iii) plans to commercially launch in the U.S. upon potential approval by the FDA (PDUFA date June 16, 2024); (iv) that imetelstat has the potential to demonstrate disease-modifying activity in patients; (v) that IMpactMF has registrational intent; and (vi) other statements that are not historical facts, constitute forward-looking statements. These forward-looking statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. These risks and uncertainties, include, without limitation, risks and uncertainties related to: (a) whether Geron overcomes all of the potential delays and other adverse impacts caused by enrollment, clinical, safety, efficacy, technical, scientific, intellectual property, manufacturing and regulatory challenges in order to have the financial resources for, and to meet the expected timelines, planned milestones and expenses noted herein; (b) whether regulatory authorities permit the further development of imetelstat on a timely basis, or at all, without any clinical holds; (c) whether imetelstat has demonstrated sufficient safety, efficacy and clinical benefit in IMerge Phase 3 to enable regulatory approval; (d) whether any future safety or efficacy results of imetelstat treatment cause the benefit-risk pro imetelstat to become unacceptable; (e) whether imetelstat actually demonstrates disease-modifying activity in patients and the ability to target the malignant stem and progenitor cells of the underlying disease; (f) that Geron may seek to raise substantial additional capital in order to complete the development and commercialization of imetelstat to meet the expected timelines, planned milestones and expenses noted herein; (g) whether regulatory authorities require an additional clinical trial for approval of imetelstat in TD LR-MDS, or post-approval; (h) whether there are failures or delays in manufacturing or supplying sufficient quantities of imetelstat or other clinical trial materials that impact a commercial launch in TD LR-MDS or the continuation of the IMpactMF trial; (i) that the projected timing for the interim and final analyses of the IMpactMF trial may vary depending on actual enrollment and death rates in the trial; and (j) whether the FDA and EMA will approve imetelstat for the treatment of TD LR-MDS or other indications on the timelines expected, or at all. Additional information on the above risks and uncertainties and additional risks, uncertainties and factors that could cause actual results to differ materially from those in the forward-looking statements are contained in Geron’s filings and periodic reports filed with the Securities and Exchange Commission under the heading “Risk Factors” and elsewhere in such filings and reports, including Geron’s annual report on Form 10-K for the year ended December 31, 2023 and future filings and reports by Geron. Undue reliance should not be placed on forward-looking statements, which speak only as of the date they are made, and the facts and assumptions underlying the forward-looking statements may change. Except as required by law, Geron disclaims any obligation to update these forward-looking statements to reflect future information, events or circumstances. View source version on businesswire.com: Contacts Aron Feingold Vice President, Investor Relations and Corporate Communications Kristen Kelleher Associate Director, Investor Relations and Corporate Communications investor@geron.com media@geron.com Source: Geron Corporation View this news release online at:

LEXINGTON, Mass., March 14, 2024 (GLOBE NEWSWIRE) -- Keros Therapeutics, Inc. (“Keros”) (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 the U.S. Food and Drug Administration (“FDA”) has granted Fast Track designation for KER-050 (elritercept) for the treatment of anemia in adult patients with very low-, low-, or intermediate-risk myelodysplastic syndromes (“MDS”). “Receiving Fast Track designation for KER-050 underscores the need for novel treatment options to address the serious unmet medical needs of people living with lower-risk MDS,” said Jasbir S. Seehra, Ph.D., President and Chief Executive Officer. “We look forward to working closely with the FDA as we engage on the design of a Phase 3 clinical trial evaluating KER-050 in lower-risk MDS in the first half of this year.” Fast Track is a process designed by the FDA to facilitate the development and expedite the review of investigational treatments that demonstrate a potential to address unmet medical needs in serious or life-threatening conditions. Programs with Fast Track designation can benefit from early and more frequent interactions with the FDA to discuss the product candidate’s development plan in addition to a rolling submission of the marketing application. Product candidates with Fast Track designation may also be eligible for priority review and accelerated approval. About KER-050 Keros’ lead product candidate, KER-050, is an engineered ligand trap comprised of a modified ligand-binding domain of the TGF-ß receptor known as activin receptor type IIA that is fused to the portion of the human antibody known as the Fc domain. KER-050 is being developed for the treatment of low blood cell counts, or cytopenias, including anemia and thrombocytopenia, in patients with MDS and in patients with myelofibrosis. About Keros Therapeutics, Inc. Keros is 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 TGF-ß family of proteins. We are a leader in understanding the role of the TGF-ß family of proteins, which are master regulators of the growth, repair and maintenance of a number of tissues, including blood, bone, skeletal muscle, adipose and heart tissue. By leveraging this understanding, we have discovered and are developing protein therapeutics that have the potential to provide meaningful and potentially disease-modifying benefit to patients. Keros’ lead product candidate, KER-050 (elritercept), is being developed for the treatment of low blood cell counts, or cytopenias, including anemia and thrombocytopenia, in patients with MDS and in patients with myelofibrosis. Keros’ second product candidate, KER-012, is being developed for the treatment of pulmonary arterial hypertension and for the treatment of cardiovascular disorders. Keros’ third product candidate, KER-065, is being developed for the treatment of obesity and for the treatment of neuromuscular diseases. 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 “look forward,” “plan” and “potential” or similar expressions are intended to identify forward-looking statements. Examples of these forward-looking statements include statements concerning: Keros’ expectations regarding its growth, strategy, progress and the design, objectives and timing of its clinical trials for KER-050, including its regulatory plans. 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, KER-050, KER-012 and KER-065; that Keros may be delayed in initiating, enrolling or completing any clinical 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 Annual Report on Form 10-K, filed with the SEC on February 28, 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