ASXL1

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Cero Therapeutics Holdings, Inc., (NASDAQ:CERO) ("CERo") an innovative immunotherapy company seeking to advance the next generation of engineered T cell therapeutics that employ phagocytic mechanisms today announced the publication in Clinical Cancer Research, a journal of the American Association for Cancer Research, a paper titled “Therapeutic Targeting of TIM-4-L With Engineered T Cells for Acute Myeloid Leukemia.” The paper details preclinical studies by CERo analyzing its lead clinical candidate CER-1236 in targeting Acute Myelogenous Leukemia (AML) tumor cells from human patients, and the candidate’s killing effects on these tumor cells. The results in the paper found that the target for CER-1236 is found in the large majority (83%) of leukemic cells extracted from the bone marrow from patients, and that more importantly CER-1236 effectively eliminated leukemic cells in the company’s experiments. Finally, the target for CER-1236 was found by CERo to be highly expressed and detectable across common AML genetic classification subtypes, including patient samples with adverse risk mutations in TP53, ASXL1 and RUNX1. “This new publication provides support for our plans to test CER-1236 in AML patients in our planned Phase I clinical trial, and moreover extends the scientific data we have produced showing the target for CER-1236 is present on tumor cells from diverse cancers, including ovarian, non-small cell lung cancer (NSCLC), and B cell malignancies,” said Daniel Corey M.D, Ph.D, CERo’s Founder and Chief Technology Officer. “We’re very pleased with this publication in Clinical Cancer Research supporting our near term plans to advance CER-1236 into the clinic. As we have previously reported, CERo plans to Investigational New Drug (IND) application in the first half of 2024, and is targeting initial treatment of AML patients as well as B Cell lymphoma patients before the end of the year,” said Brian G Atwood, CERo’s Chairman and Chief Executive Officer. About CERo Therapeutics, Inc. CERo is an innovative immunotherapy company advancing the development of next generation engineered T cell therapeutics for the treatment of cancer. Its proprietary approach to T cell engineering, which enables it to integrate certain desirable characteristics of both innate and adaptive immunity into a single therapeutic construct, is designed to engage the body’s full immune repertoire to achieve optimized cancer therapy. This novel cellular immunotherapy platform is expected to redirect patient-derived T cells to eliminate tumors by building in engulfment pathways that employ phagocytic mechanisms to destroy cancer cells, creating what CERo refers to as Chimeric Engulfment Receptor T cells ("CER-T"). CERo believes the differentiated activity of CER-T cells will afford them greater therapeutic application than currently approved chimeric antigen receptor ("CAR-T") cell therapy, as the use of CER-T may potentially span both hematological malignancies and solid tumors. CERo anticipates initiating clinical trials for its lead product candidate, CER-1236, in 2024 for hematological malignancies. Forward-Looking Statements This communication contains statements that are forward-looking and as such are not historical facts. This includes, without limitation, statements regarding the financial position, business strategy and the plans and objectives of management for future operations of CERo. These statements constitute projections, forecasts and forward-looking statements, and are not guarantees of performance. Such statements can be identified by the fact that they do not relate strictly to historical or current facts. When used in this communication, words such as “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “possible,” “potential,” “predict,” “project,” “should,” “strive,” “would” and similar expressions may identify forward-looking statements, but the absence of these words does not mean that a statement is not forward-looking. When CERo discusses its strategies or plans, it is making projections, forecasts or forward-looking statements. Such statements are based on the beliefs of, as well as assumptions made by and information currently available to, CERo’s management. Actual results could differ from those implied by the forward-looking statements in this communication. Certain risks that could cause actual results to differ are set forth in CERo’s filings with the Securities and Exchange Commission, including its Current Report on Form 8-K, as amended, filed on February 27, 2024, and the documents incorporated by reference therein. The risks described in CERo’s filings with the Securities and Exchange Commission are not exhaustive. New risk factors emerge from time to time and it is not possible to predict all such risk factors, nor can CERo assess the impact of all such risk factors on its business, or the extent to which any factor or combination of factors may cause actual results to differ materially from those contained in any forward-looking statements. Forward-looking statements are not guarantees of performance. You should not put undue reliance on these statements, which speak only as of the date hereof. All forward-looking statements made by CERo or persons acting on its behalf are expressly qualified in their entirety by the foregoing cautionary statements. CERo undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

Subgroup analyses showed consistently higher transfusion independence (TI) response rates than placebo across different risk groups regardless of International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R) or IPSS molecular (IPSS-M) Robust TI rates with imetelstat treatment compared with placebo in patients with poor prognosis mutational profiles For the nearly 20% of imetelstat-treated patients who achieved greater than 1-year sustained TI, median duration of TI was more than two years and median hemoglobin increase was more than 5 g/dL Consistent with prior imetelstat clinical experience, the most common adverse events were thrombocytopenia and neutropenia that were manageable and of short duration Imetelstat is currently under regulatory review by the FDA and EMA for the treatment of transfusion-dependent anemia in adult patients with lower risk MDS FOSTER CITY, Calif.--(BUSINESS WIRE)--Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, today announced the publication of abstracts from the IMerge Phase 3 clinical trial evaluating its first-in-class investigational telomerase inhibitor imetelstat in patients with lower risk myelodysplastic syndromes (MDS). Four abstracts have been accepted for presentation at the 65th American Society of Hematology (ASH) Annual Meeting taking place from December 9-12 in San Diego, California and virtually. “The 2023 ASH abstracts present data and analyses from the IMerge Phase 3 clinical trial that reinforce the differentiated clinical pro imetelstat in lower risk MDS, and specifically highlight that patients achieve TI irrespective of risk status based on classification systems, or specific poor prognostic mutation pro Of particular importance, the nearly 20% of imetelstat-treated patients who achieved one year or greater transfusion independence with accompanying hemoglobin rises of 5 g/dl and reduction of MDS-associated mutations speak to the potential of this novel therapy to provide clinical benefits to patients that have not been observed before in transfusion-dependent lower risk MDS,” said Faye Feller, M.D., Geron’s Executive Vice President, Chief Medical Officer. Imetelstat is currently under regulatory review by the U.S. Food and Drug Administration (FDA) and by the European Medicines Agency (EMA) for the treatment of transfusion dependent anemia in adult patients with lower risk MDS who have failed to respond or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESAs). “The data from IMerge Phase 3 being presented at the ASH annual meeting provides important insight into the breadth of effect of TI achieved with imetelstat across different risk subgroups and across the various underlying mutations associated with MDS, suggesting a broad use for imetelstat in patients eligible for the study, including in difficult-to-treat subgroups. Imetelstat also demonstrated efficacy among patients who were reclassified as higher risk using molecular international prognostic scoring system (IPSS-M),” said Rami S. Komrokji, M.D., Vice Chair, Malignant Hematology Department, Moffitt Cancer Center, one of the principal investigators of IMerge Phase 3 and ASH presenter. “Additionally, our abstract showcasing a real-world data population level analysis of over 5,000 lower risk MDS patients adds to the significant literature suggesting a correlation between TI and improvement in survival. These data support the importance of TI to improve outcomes for patients with lower risk MDS.” Abstract #194: “Efficacy of Imetelstat in Achieving Red Blood Cell Transfusion Independence (RBC-TI) Across Different Risk Subgroups in Patients with Lower Risk Myelodysplastic Syndromes (LR MDS) Relapsed/Refractory (R/R) to Erythropoiesis Stimulating Agents (ESAs) in IMerge Phase 3 Study” Oral Presentation on December 9, 2023, at 2:15 p.m. PT This abstract evaluates TI rates in patients treated with imetelstat vs. placebo across different risk subgroups as defined by International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R) or IPSS molecular (IPSS-M) risk profiles and shows that patients treated with imetelstat consistently had higher TI response rates than placebo regardless of risk classification. Further, in patients re-classified as high or very high risk using IPSS-M, TI response rates with imetelstat (and not placebo) were similar to TI response rates in lower risk subgroups. This analysis suggests imetelstat has clinical activity in lower risk MDS patients independent of risk categories. Abstract #4603: “Impact of Mutational Status on Clinical Response to Imetelstat in Patients with Lower Risk Myelodysplastic Syndromes in the IMerge Phase 3 Study” Poster Presentation on December 11, 2023, from 6-8 p.m. PT This abstract evaluates the impact of MDS-associated mutations on clinical efficacy of imetelstat for the 165 of 178 patients for whom mutation data were available and shows that RBC-TI response rates in patients receiving imetelstat occurred regardless of the presence of baseline MDS associated mutations that have a poor prognosis (either specific mutations or multiple concurrent mutations). In patients with mutations associated with poor prognosis (TP53, ETV6, RUNX1, ASXL1, or EZH2), ≥8-week and ≥24-week, TI was observed in 31.8% and 9.1% of imetelstat-treated patients vs 0 on placebo. The 8-week TI rate for patients with 3 or more mutations was 55.6% with imetelstat compared to 14.3% with placebo. This analysis suggests clinical benefit of imetelstat across different molecularly defined subgroups and independent of the underlying molecular pattern. Abstract #4605: “Durable Continuous Transfusion Independence (TI) With Imetelstat in IMerge Phase 3 for Patients with Heavily Transfused Non-Del(5q) Lower Risk Myelodysplastic Syndromes (LR MDS) Relapsed/Refractory (R/R) to or Ineligible for Erythropoiesis-Stimulating Agents (ESAs)” Poster Presentation on December 11, 2023, from 6-8 p.m. PT This abstract evaluates the 1-year TI responders in IMerge Phase 3, including 17.8% of imetelstat-treated patients (21/118; 95% CI, 11.4-25.9) and 1.7% of patients on placebo (1/60; 95% CI, 0-8.9). The median duration of TI for imetelstat ≥1-year TI responders was 123 weeks (95% CI, 80.4 to not evaluable); the median increase in hemoglobin during the longest TI interval was 5.18 g/dL (range, 2.67-13.76 g/dL) for the imetelstat group vs 1.67 g/dL for the placebo patient. Of the 18/21 imetelstat-treated 1-year TI responders for whom mutation data were available, 72.2% achieved ≥50% SF3B1 variant allele frequency (VAF) reduction, including 7 patients in whom there was complete elimination of MDS associated mutations. The abstract concludes that the long-term durable TI, robust increases in hemoglobin and meaningful reductions in mutational burden suggest imetelstat may have disease-modifying activity. Grade 3-4 thrombocytopenia and neutropenia occurred in 14 (67%) and 20 (95%) patients with ≥1-year TI, respectively, and the mean duration of grade 3/4 thrombocytopenia and neutropenia events was 2.25 and 1.78 weeks, respectively. 89% of grade 3/4 thrombocytopenia and 81% of grade 3/4 neutropenia was reduced to grade 1/2 within 4 weeks. Abstract #2440: “Durable Transfusion Independence in Lower Risk Myelodysplastic Syndrome (LR MDS) Is Associated with Better Survival: A Population Level Analysis Based on a Large US Health Insurance Claims Database” Poster Presentation on December 11, 2023, from 6-8 p.m. PT This abstract describes a population level analysis of 5,662 lower risk MDS patients identified through Optum Clinformatics® between October 2015 and June 2022. Among these patients, 35% and 49% were transfusion-dependent before first and second lines of therapy, respectively. The median overall survival from start of second line therapy was 23.4 months overall, and 37.9 months vs 9.3 months among responders becoming transfusion independent vs non-responders, respectively (P < .0001). Despite the currently available therapies, transfusion dependence after any line of therapy is associated with poorer outcomes. Achievement of durable TI was associated with improved survival, supporting the clinical benefit of achieving transfusion independence in lower risk MDS. These abstracts are available on the ASH 2023 Meeting website at . About IMerge Phase 3 The Phase 3 portion of the IMerge Phase 2/3 study 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 HMA 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 TI). Key secondary endpoints include the rate of RBC-TI lasting at least 24 weeks (24-week TI), the duration of 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, Middle East and Asia. About Imetelstat Imetelstat is a novel, first-in-class investigational telomerase inhibitor exclusively owned by Geron and being developed 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 and potential disease-modifying activity. 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 associated 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 adult patients with lower risk myelodysplastic syndromes (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 United States Food and Drug Administration (FDA) with a Prescription Drug User Fee Act (PDUFA) target action date of June 16, 2024. In addition, an MAA is under review in the European Union for the same proposed indication. Furthermore, Geron currently has an ongoing pivotal Phase 3 clinical trial evaluating imetelstat in relapsed/refractory myelofibrosis (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: (i) that data from the IMerge Phase 3 clinical trial in the ASH abstracts reinforce the differentiated clinical pro imetelstat in lower risk MDS; (ii)that the nearly 20% of imetelstat-treated patients who achieved one year or greater transfusion independence with accompanying hemoglobin rises of 5 g/dl and reduction of MDS-associated mutations speak to the potential of imetelstat to provide clinical benefits to patients that have not been observed before in transfusion-dependent lower risk MDS; (iii) that data from IMerge Phase 3 associated with the ASH annual meeting suggests a broad use for imetelstat in patients eligible for the study, including in difficult-to-treat subgroups; (iv) that a real-world data population level analysis of over 5,000 lower risk MDS patients adds to the significant literature suggesting a correlation between transfusion independence and improvement in survival and support the importance of transfusion independence to improve outcomes for patients with lower risk MDS; and (v) 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 regulatory authorities permit the further development of imetelstat on a timely basis, or at all, without any clinical holds; (b) whether any future safety or efficacy results cause the benefit-risk pro imetelstat to become unacceptable; (c) whether imetelstat actually demonstrates that it alters the underlying drivers of disease and has disease-modifying activity in patients; and (d) whether the FDA and EMA will approve imetelstat for the treatment of transfusion-dependent anemia in patients with lower risk MDS. 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 quarterly report on Form 10-Q for the quarter ended September 30, 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.

FOSTER CITY, Calif.--( BUSINESS WIRE )--Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, today announced new data and analyses from IMerge Phase 3 reporting robust durability of transfusion independence (TI), evidence for disease-modifying activity and favorable fatigue patient-reported outcomes (PRO) in lower risk myelodysplastic syndromes (MDS) patients treated with the Company’s first-in-class telomerase inhibitor, imetelstat, vs. placebo. The data and analyses were presented at the European Hematology Association (EHA) Annual Meeting, which took place from June 8-11, 2023 in Frankfurt, Germany and virtually. “ The new IMerge Phase 3 data and analyses presented at EHA continue to support the unprecedented and differentiating attributes of imetelstat, including 24-week transfusion independence across key MDS subgroups, potential disease-modifying activity, as well as favorable patient-reported outcomes (PRO) data on meaningful improvement in fatigue,” said Faye Feller, M.D., Executive Vice President, Chief Medical Officer of Geron. “ Each of these qualities address important unmet needs for lower risk MDS patients due to the limitation of current treatment options. Submission of our New Drug Application later this month is a significant step to hopefully bring imetelstat to these transfusion burdened patients.” Presentation Title: Continuous Transfusion Independence with Imetelstat in Heavily Transfused Non-Del(5q) Lower Risk Myelodysplastic Syndromes Relapsed/Refractory to Erythropoiesis Stimulating Agents in IMerge Phase 3 Top-line results from the primary analysis of IMerge Phase 3 presented earlier this month at the 2023 American Society of Hematology (ASCO) Annual Meeting were also covered in the EHA presentation, including the primary endpoint of 8-week transfusion independence (TI) and key secondary endpoint of 24-week TI were met with high statistical significance (P<0.001) for imetelstat-treated patients vs. placebo. Further, mean hemoglobin levels in imetelstat-treated patients increased significantly (P<0.001) over time compared to placebo patients. In addition to these results, the EHA presentation also provided new data and analyses highlighting clinically meaningful and durable TI for imetelstat-treated patients vs. placebo. As of a January 2023 data cut-off, 17.8% (21/118) of imetelstat-treated patients vs. 1.7% (1/60) of placebo-treated patients achieved 1-year TI (P=0.002), representing 63.6% of 24-week TI imetelstat responders. Two new analyses presented at EHA on TI responses by subgroups underscored the breadth of potential effect of imetelstat vs. placebo. The first analysis reported higher durability of TI for imetelstat-treated patients vs. placebo across key MDS subgroups: Durability of RBC-TI for 8-Week TI Responders Across Key LR MDS Subgroups Imetelstat median, weeks (95% CI) Placebo median, weeks (95% CI) Hazard ratio (95% CI) P-value Overall 51.6 (26.9–83.9) 13.3 (8.0–24.9) 0.23 (0.09–0.57) <0.001 WHO category RS+ 46.9 (25.9–83.9) 16.9 (8.0–24.9) 0.32 (0.11–0.95) 0.035 RS- 51.6 (11.9–NE) 11.2 (10.1–NE) 0.11 (0.01–1.43) 0.062 Prior RBC transfusion burden per IWG 2006 4–6 units/8 weeks 51.9 (24.9–122.9) 16.9 (10.1–24.9) 0.35 (0.13–0.96) 0.035 6 units/8 weeks 39.9 (15.9–NE) 8.4 (8.0–NE) 0.04 (0.003–0.48) <0.001 IPSS risk category Low 43.9 (25.0–NE) 15.1 (8.0–24.9) 0.26 (0.10–0.68) 0.004 Intermediate-1 51.6 (11.9–NE) 10.1 (NE–NE) 0.15 (0.01–2.47) 0.128 Baseline sEPO ≤500 mU/mL 51.6 (26.9–83.9) 13.3 (8.0–24.9) 0.21 (0.075–0.61) 0.002 >500 mU/mL 122.9 (8.14–NE) 14.6 (12.3–NE) 0.34 (0.03–3.85) 0.364 Prior ESA use Yes 43.9 (26.9–80.0) 13.3 (8.0–24.9) 0.26 (0.10–0.72) 0.006 No 122.9 (8.14–NE) 14.6 (12.3–NE) 0.34 (0.03–3.85) 0.364 ____________________ Data cut-off: October 13, 2022. Hazard ratio (95% CI) from the Cox proportional hazard model, stratified by prior RBC transfusion burden (≥4 to ≤6 vs >6 RBC units/8 weeks during a 16-week period prior to randomization) and baseline IPSS risk category (low vs intermediate-1), with treatment as the only covariate. P -value (2-sided) for superiority of imetelstat vs placebo in hazard ratio based on stratified log-rank test. ESA, erythropoiesis-stimulating agent; IPSS, International Prognostic Scoring System; IWG, International Working Group; LR-MDS, lower-risk myelodysplastic syndromes; NE, not estimable; RBC, red blood cell; RS, ring sideroblast; sEPO, serum erythropoietin; TI, transfusion independence. The second analysis reported higher 24-week TI for imetelstat-treated patients vs. placebo across key MDS subgroups: Comparable 24-Week RBC-TI Rate Across Key LR MDS Subgroups Imetelstat n/N (%) Placebo, n/N (%) % Difference (95% CI) P-value Overall 33/118 (28.0) 2/60 (3.3) 24.6 (12.64–34.18) <0.001 WHO category RS+ 24/73 (32.9) 2/37 (5.4) 20.5 (−0.03–35.75) 0.003 RS- 9/44 (20.5) 0/23 (0.0) 0.11 (0.01–1.43) 0.019 Prior RBC transfusion burden per IWG 2006 4–6 units/8 weeks 19/62 (30.6) 2/33 (6.1) 24.6 (5.68–38.66) 0.006 6 units/8 weeks 39.9 (15.9–NE) 8.4 (8.0–NE) 0.04 (0.003–0.48) <0.001 IPSS risk category Low 23/80 (28.8) 2/39 (5.1) 23.6 (7.23–35.75) 0.003 Intermediate-1 10/38 (26.3) 0/21 (0) 26.3 (3.46–43.39) 0.009 Baseline sEPO ≤500 mU/mL 29/87 (33.3) 2/36 (5.6) 27.8 (10.46–39.71) 0.002 >500 mU/mL 4/26 (15.4) 0/22 (0) 15.4 (−5.81–35.73) 0.050 Prior ESA use Yes 31/108 (28.7) 2/52 (3.8) 24.9 (11.61–35.00) <0.001 No 2/10 (20) 0/8 20.0 (-23.47–55.78) 0.225 _____________ Data cut-off: October 13, 2022. 95% CI based on Wilson Score method. P -value determined by the Cochran-Mantel-Haenszel test, with stratification for prior RBC transfusion burden (≥4 to ≤6 vs >6 RBC units/8 weeks during a 16-week period prior to randomization) and baseline IPSS risk category (low vs intermediate-1) applied to randomization. ESA, erythropoiesis-stimulating agent; IPSS, International Prognostic Scoring System; IWG, International Working Group; LR-MDS, lower-risk myelodysplastic syndromes; RBC, red blood cell; RS, ring sideroblast; sEPO, serum erythropoietin; TI, transfusion independence. Additionally, the rate of 24-week TI was higher with imetelstat vs. placebo regardless of baseline mutation status, telomerase activity (TA), telomerase length (TL), and human telomerase reverse transcriptase (hTERT). “ For the first time at EHA, we see comparable 24-week TI across key MDS subgroups, which is especially meaningful for patients without ring sideroblasts (RS-) and very heavily transfusion burdened patients, who particularly have limited options today,” said Uwe Platzbecker, M.D., Department of Hematology, Cellular Therapy and Hemostaseology, Leipzig University Hospital, Leipzig, Germany, who presented the data at EHA and is an IMerge investigator. “ In addition to the durability of TI, imetelstat-treated patients also achieved significant increases in hemoglobin and reductions of transfusion units that could be life changing for lower risk MDS patients, who often present with symptomatic anemia and transfusion dependence.” As previously reported, the safety profile observed with imetelstat in IMerge Phase 3 was consistent with prior clinical experience with no new safety signals. The EHA presentation provided new data on the consequences of the grade 3-4 thrombocytopenia and neutropenia which were most often reported during Cycles 1-3 and led to dose modifications. While approximately 50% of patients treated with imetelstat had dose reductions due to treatment emergent adverse events (TEAE), less than 15% of patients discontinued treatment due to TEAE. Discontinuation of imetelstat treatment in these patients due to a TEAE generally occurred late in treatment, with a median time to treatment discontinuation of 21.1 weeks (range 2.3 to 44.0 weeks). Presentation Title: Disease-Modifying Activity of Imetelstat in Patients with Heavily Transfused Non-Del(5q) Lower Risk Myelodysplastic Syndromes Relapsed/Refractory to Erythropoiesis Stimulating Agents in IMerge Phase 3 “ In IMerge Phase 3, not only did we observe efficacy with imetelstat across the spectrum of genetic mutations associated with lower risk MDS, but we also saw a reduction in mutation burden, as measured by variant allele frequency (VAF). Furthermore, greater reduction of VAF in multiple genes correlated with the clinical endpoints of TI response, longer TI duration and increase in hemoglobin levels, suggesting the potential of imetelstat to modify the disease. This is the first therapy we know of that may alter the underlying biology of lower risk MDS by potentially reducing or eliminating malignant clones and improving ineffective erythropoiesis,” said Valeria Santini, M.D., MDS Unit, Azienda Ospedaliero Universitaria Careggi, University of Florence, Florence, Italy, who presented the data at EHA and is an IMerge investigator. In the EHA presentation, new data on cytogenetic responses and reductions in bone marrow RS supported the telomerase inhibition mechanism of action (MOA) of imetelstat. Among patients with cytogenetic abnormalities at baseline, the cytogenetic response rate was 35% (9/26) in imetelstat-treated patients and 15% (2/13) in the placebo group. Among cytogenetic responders, 89% (8/9) of patients in the imetelstat group and 50% (1/2) in the placebo group also achieved 8-week TI. A higher percentage of patients treated with imetelstat (40.8%) vs. placebo (9.7%) had a ≥50% reduction in central bone marrow RS. TI responses were enriched in patients achieving a ≥50% reduction in central bone marrow RS. Furthermore, the EHA presentation provided updated data on VAF reductions and new analyses on the correlation of such reductions with clinical responses which further support the potential disease-modifying activity of imetelstat. Reductions in variant allele frequency (VAF) of genes frequently mutated in MDS were greater for imetelstat-treated patients than placebo: SF3B1 (P< 0.001), TET2 (P= 0.032), DNMT3A (P= 0.019) and ASXL1 (P= 0.146). More patients treated with imetelstat vs. placebo had ≥50% VAF reduction in these mutations. For patients with the SF3B1 mutation, 29.5% (23/78) of those treated with imetelstat vs. 2.6% (1/38) on placebo (P=0.001) had a ≥50% VAF reduction. Imetelstat treatment resulted in sustained reduction of SF3B1 VAF over time. In the imetelstat group, 83% (19/23) of patients had 8-week TI among patients who achieved ≥50% maximum reduction from baseline in SF3B1 VAF vs. 38% (21/55) of those who did not. Similarly, TI responders were also enriched in imetelstat-treated patients achieving ≥50% reduction in TET2 VAF. In the imetelstat group, 83% (10/12) of patients had 8-week RBC-TI among patients who achieved ≥50% maximum reduction from baseline in TET2 VAF vs 43% (10/23) of those who did not. In imetelstat-treated patients, 24-week and 1-year TI responders were enriched in patients achieving ≥50% reduction in SF3B1 and TET2 VAF. VAF reduction in SF3B1, TET2 and DNMT3A correlated with longer TI duration and increases in hemoglobin levels in imetelstat-treated patients. Further, 8-week and 24-week TI correlated with reduction in RS+ cells, cytogenetic responses and VAF reduction. These correlations suggest the disease-modifying activity of imetelstat. Presentation Title: Analysis of Patient-Reported Fatigue in IMerge Phase 3 Trial of Imetelstat vs. Placebo in Heavily Transfused Non-Del(5q) Lower Risk Myelodysplastic Syndromes Relapsed/Refractory to Erythropoiesis Stimulating Agents (ESA) “ The patient-reported outcome data from IMerge Phase 3 is particularly important as fatigue is a concern for lower risk MDS patients, most of whom are elderly. Furthermore, many of the current treatments for these patients cause fatigue. It is therefore very welcome news that imetelstat-treated patients showed sustained meaningful improvement in patient-reported fatigue vs. placebo. This is the first Phase 3 trial we know of to show an improvement in fatigue in lower risk MDS patients,” stated Dr. Platzbecker. The EHA presentation described results from an exploratory analysis from IMerge Phase 3 of patient-reported fatigue conducted using Functional Assessment of Chronic Illness Therapy, or FACIT, a validated 13-item patient questionnaire. The analysis reported imetelstat-treated patients were more likely to have sustained meaningful improvement in fatigue, as well as experience such improvement more quickly. Patients treated with imetelstat reported a lower rate of sustained meaningful deterioration in fatigue than placebo (43.2% vs 45.6%), while also receiving fewer transfusion units over time. For patients treated with imetelstat, there was a numerically higher percentage of patients reporting any episode of sustained meaningful improvement in fatigue. Further, patients receiving imetelstat experienced a shorter median time to first sustained clinically meaningful improvement in fatigue vs placebo (28.3 vs 65.0 weeks). For patients treated with imetelstat, there were significant associations between sustained meaningful improvement in fatigue and 8- and 24-week TI and HI-E response rates, an association not seen in the placebo group. Additional analysis showed that patients experiencing grade 3 or 4 neutropenia or thrombocytopenia had the same rates of sustained meaningful improvement in fatigue (52.5% and 53.4%, respectively) as the total imetelstat population (50%). Additional Presentations at EHA In addition to these IMerge Phase 3 presentations, Geron collaborators presented a translational analysis from a subset of IMerge Phase 2 patients, as well as imetelstat myelofibrosis (MF) pre-clinical results. The presentation slides and posters are available on the Publications section of Geron’s website: https://www.geron.com/research-and-development/publications/ . About IMerge Phase 3 The Phase 3 portion of the IMerge Phase 2/3 study 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 HMA 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 TI). Key secondary endpoints include the rate of RBC-TI lasting at least 24 weeks (24-week TI), the duration of 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, Middle East and Asia. About Imetelstat Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed 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 and potential disease-modifying activity. 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 MF whose disease has relapsed after or is refractory to janus associated kinase (JAK) inhibitor treatment. Geron plans to submit a New Drug Application (NDA) in the U.S. in June 2023 and a Marketing Authorization Application (MAA) in the EU in the second half of 2023 in the lower risk MDS indication. About Geron Geron is a late-stage biopharmaceutical company pursuing therapies with the potential to extend and enrich the lives of patients living with hematologic malignancies. Our first-in-class telomerase inhibitor, imetelstat, harnesses Nobel Prize-winning science in a treatment that may alter the underlying drivers of disease. Geron currently has two Phase 3 pivotal clinical trials underway evaluating imetelstat in lower risk myelodysplastic syndromes (LR MDS), and in relapsed/refractory myelofibrosis (MF). To learn more, visit www.geron.com 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) that for IMerge Phase 3, Geron plans to submit a New Drug Application in the U.S. in June 2023 and a Marketing Authorization Application in the EU in the second half of 2023; (ii) a potential U.S. commercial launch of imetelstat for lower risk MDS in the first half of 2024; (iii) that imetelstat may alter the underlying biology of lower risk MDS and has the potential to demonstrate disease-modifying activity in patients; and (iv) 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 the current or evolving effects of the COVID-19 pandemic and/or geopolitical events and resulting global economic and financial disruptions will materially and adversely impact Geron’s business and business prospects, its financial condition and the future of imetelstat; (b) whether Geron overcomes all of the potential delays and other adverse impacts caused by the current or evolving effects of the COVID-19 pandemic and/or geopolitical events, as well as all the 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; (c) whether regulatory authorities permit the further development of imetelstat on a timely basis, or at all, without any clinical holds; (d) whether imetelstat has demonstrated sufficient safety, efficacy and clinical benefit in IMerge Phase 3 to enable regulatory approval; (e) whether any future safety or efficacy results cause the benefit-risk profile of imetelstat to become unacceptable; (f) whether imetelstat actually demonstrates that it alters the underlying biology of lower risk MDS and has disease-modifying activity in patients;; (g) 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; (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 lower risk MDS; (i) whether the follow-up period of 12 months for the IMerge Phase 3 primary analysis was sufficient to demonstrate safety and efficacy, including transfusion independence and clinical benefit, and obtain regulatory approval; and (j) for IMerge Phase 3, the FDA may require Geron to submit additional information or require advisory committee procedures that could cause a regulatory approval, if any, to be delayed. 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 quarterly report on Form 10-Q for the quarter ended March 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.