On December 8, 2025 Kura Oncology, Inc. (Nasdaq: KURA, "Kura") and Kyowa Kirin Co., Ltd. (TSE: 4151, "Kyowa Kirin") reported new data demonstrating a favorable safety profile and encouraging antileukemic activity for KOMZIFTI (ziftomenib) in combination with venetoclax and azacitidine (ven/aza) for the treatment of acute myeloid leukemia (AML) harboring NPM1 mutations (NPM1-m) or KMT2A rearrangements (KMT2A-r). The ongoing KOMET-007 Phase 1a/1b trial evaluated patients in cohorts with newly diagnosed chemotherapy-ineligible AML and relapsed/refractory (R/R) AML. The new data are being reported today in two oral presentations at the 67th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) (ASH 2025).

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"The addition of ziftomenib to venetoclax and azacitidine has shown promising clinical activity, with 86% of newly diagnosed NPM1-mutated AML patients achieving composite complete remission and 68% attaining deep molecular MRD negativity, though median duration of response and overall survival remain immature," said Gail J. Roboz, M.D., the William S. Paley Professor in Clinical Medicine and Director of the Clinical and Translational Leukemia Program at Weill Cornell Medicine and a hematologist/oncologist at NewYork-Presbyterian/Weill Cornell Medical Center. "In relapsed/refractory NPM1-m and KMT2A-r AML, overall response rates of 65% and 41% were observed, rising to 83% and 70% in venetoclax-naïve patients, underscoring ziftomenib’s potential benefit even in challenging settings. Importantly, inclusion of ziftomenib was generally well tolerated, paving the way for its integration into front-line and relapsed/refractory regimens through ongoing registrational trials."

KOMZIFTI (ziftomenib), the first and only once-daily oral menin inhibitor for adult patients with R/R AML with a susceptible NPM1 mutation who have no satisfactory alternative treatment options, has been approved by the U.S. Food and Drug Administration (FDA) and is commercially available in the United States.

Ziftomenib + Venetoclax/Azacitidine in Newly Diagnosed NPM1-m AML

The ongoing KOMET 007 Phase 1a/b trial (NCT05735184) evaluated 40 patients with newly diagnosed NPM1-m AML as of the September 24, 2025 data cutoff date. Of these, 58% (23/40) had an ECOG performance status of 2 and 37 were response evaluable.

Robust activity was observed in newly diagnosed NPM1-m AML, including high rates of durable morphologic complete responses (CRc 86%; CR 73%).

68% of CRc responders achieved molecular MRD negativity by central next-generation sequencing (NGS).
Median duration of CR and OS were not reached at median follow-up of 26.1 weeks (range 1.6–54.1) as of the data cutoff.
68% of patients remained alive and on treatment or in long-term follow-up as of the data cutoff.
Five chemotherapy-ineligible patients received HSCT; three received ziftomenib maintenance therapy thereafter.
The triplet combination was generally well tolerated in newly diagnosed NPM1-m AML, with a safety profile consistent with that reported for ven/aza alone. Rates of ziftomenib-related myelosuppression were low, and the median times to neutrophil and platelet recovery were also consistent with those expected for ven/aza alone. One case each of grade 2 differentiation syndrome and grade 3 investigator-assessed QTc prolongation were successfully managed without treatment discontinuation.

Ziftomenib + Venetoclax/Azacitidine in R/R AML

The ongoing KOMET 007 Phase 1a/b trial (NCT05735184) evaluated 83 patients with R/R NPM1-m or KMT2A-r AML as of the September 24, 2025 data cutoff date. Of these, 58% (48/83) had received prior venetoclax and 80 were response evaluable.

Robust activity was observed in patients with R/R NPM1-m AML, including among those previously treated with venetoclax.

ORR was 65% and CRc rate was 48%, with CRc median duration of 39.9 weeks.
In venetoclax-naïve patients, ORR was 83% and CRc rate was 70%, compared with 48% and 28%, respectively, in venetoclax-exposed patients.
Median OS was 54.9 weeks (95% CI 32.0–NE).
14 patients received HSCT, five proceeded to ziftomenib maintenance therapy, and five were pending maintenance at time of data cutoff.
In patients with R/R KMT2A-r AML, encouraging activity was also observed.

ORR was 41% and CRc rate was 28%, with CRc median duration of 12.4 weeks.
In venetoclax-naïve patients, ORR was 70% and CRc rate was 60%.
Median OS was 21.1 weeks (95% CI 12.4–64.9).
Two patients received HSCT and both proceeded to ziftomenib maintenance therapy.
The combination was generally well tolerated in both R/R NPM1-m and R/R KMT2A-r AML. Rates of ziftomenib-related myelosuppression were low, with neutrophil and platelet recovery consistent with expectations for ven/aza alone. No ziftomenib-related QTc prolongation was reported. One grade 3 differentiation syndrome case (in an NPM1-m patient) was successfully resolved with protocol-specified measures, and the patient resumed treatment with ziftomenib.

"We’re truly encouraged by the consistent safety profile and the depth of responses observed with ziftomenib in combination with venetoclax and azacitidine across both newly diagnosed and relapsed/refractory NPM1-mutated and KMT2A-rearranged AML patients," said Mollie Leoni, M.D., Chief Medical Officer at Kura Oncology. "These compelling data reinforce our conviction that ziftomenib has the potential to become a foundational, best-in-class menin inhibitor for patients with AML. Importantly, we continue to activate sites in our pivotal KOMET-017 trials. The combination of a well-considered trial design and a compelling benefit-risk profile for ziftomenib gives us confidence in the pace and quality of enrollment of newly diagnosed and relapsed/refractory patients."

Presentations
Slides from the oral presentations will be available on Kura’s website at www.kuraoncology.com under the Posters and Presentations tab in the Ziftomenib section, and in the ASH (Free ASH Whitepaper) 2025 online program.

Virtual Investor Event
Kura will host a webcast and conference call today, December 8, 2025, at 12:30 p.m. ET / 9:30 a.m. PT featuring Kura management, Eunice Wang, M.D., Chief of Leukemia Service and Professor of Oncology at Roswell Park Comprehensive Center, and Amer Zeidan, M.B.B.S., M.H.S., Chief, Division of Hematologic Malignancies and Professor of Medicine at Yale School of Medicine. The live webcast and replay will be available on the on the Company’s website at www.kuraoncology.com under the Investors tab in the Events and Presentations section.

About KOMZIFTI (ziftomenib)
KOMZIFTI (ziftomenib) is an oral menin inhibitor approved for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible NPM1 mutation who have no satisfactory alternative treatment options.

Ziftomenib is in development for the front-line treatment of AML harboring NPM1 mutations, KMT2A translocations and FLT3 mutations, with the potential to be combined with approved therapies and benefit a broad spectrum of patients earlier in their disease course.

IMPORTANT SAFETY INFORMATION FOR KOMZIFTI FROM THE U.S. PRESCRIBING INFORMATION

Boxed WARNING: DIFFERENTIATION SYNDROME

Differentiation syndrome, which can be fatal, has occurred with KOMZIFTI. Signs and symptoms may include fever, joint pain, hypotension, hypoxia, dyspnea, rapid weight gain or peripheral edema, pleural or pericardial effusions, pulmonary infiltrates, acute kidney injury, and rashes. If differentiation syndrome is suspected, interrupt KOMZIFTI, and initiate oral or intravenous corticosteroids with hemodynamic and laboratory monitoring until symptom resolution; resume KOMZIFTI upon symptom improvement.

WARNINGS AND PRECAUTIONS

Differentiation Syndrome

KOMZIFTI can cause fatal or life-threatening differentiation syndrome (DS). DS is associated with rapid proliferation and differentiation of myeloid cells. Symptoms of DS, including those seen in patients treated with KOMZIFTI, may include fever, hypoxia, joint pain, hypotension, dyspnea, rapid weight gain or peripheral edema, pleural or pericardial effusions, acute kidney injury, and rashes.

In the clinical trial, DS occurred in 29 (26%) of 112 patients with R/R AML with an NPM1 mutation who were treated with KOMZIFTI at the recommended dosage. DS was Grade 3 in 13% and fatal in two patients. In broader evaluation of all patients with any genetic form of AML treated with KOMZIFTI monotherapy in clinical trials, DS occurred in 25% of patients. Four fatal cases of DS occurred out of 39 patients with KMT2A-rearranged AML treated with KOMZIFTI. KOMZIFTI is not approved for use in patients with KMT2A-rearranged AML.

In the 112 patients with an NPM1 mutation, DS was observed with and without concomitant hyperleukocytosis, in as early as 3 days and up to 46 days after KOMZIFTI initiation. The median time to onset was 15 days. Two patients experienced more than one DS event. Treatment was interrupted and resumed in 15 (13%) patients, while it was permanently discontinued in 2 (2%) patients.

Prior to starting treatment with KOMZIFTI, reduce the WBC counts to less than 25 x 10⁹/L. If DS is suspected, interrupt KOMZIFTI, initiate oral or intravenous corticosteroids (e.g., dexamethasone 10 mg every 12 hours) for a minimum of 3 days with hemodynamic and laboratory monitoring. Resume treatment with KOMZIFTI at the same dose level when signs and symptoms improve and are Grade 2 or lower. Taper corticosteroids over a minimum of 3 days after adequate control or resolution of symptoms. Symptoms of DS may recur with premature discontinuation of corticosteroid treatment.

QTc Interval Prolongation

KOMZIFTI can cause QTc interval prolongation. In the clinical trial, QTc interval prolongation was reported as an adverse reaction in 12% of 112 patients treated with KOMZIFTI at the recommended dosage for R/R AML with an NPM1 mutation. QTc interval prolongation was Grade 3 in 8% of patients. The heart-rate corrected QT interval (using Fridericia’s method) (QTcF) was greater than 500 msec in 9% of patients, and the increase from baseline QTcF was greater than 60 msec in 12% of patients. KOMZIFTI dose reduction was required for 1% of patients due to QTc interval prolongation. QTc prolongation occurred in 14% of the 42 patients less than 65 years of age and in 10% of the 70 patients 65 years of age or older.

Correct electrolyte abnormalities, including hypokalemia and hypomagnesemia, prior to treatment with KOMZIFTI. Perform an ECG prior to initiation of treatment with KOMZIFTI, and do not initiate KOMZIFTI in patients with QTcF > 480 msec. Perform an ECG at least once weekly for the first four weeks on treatment, and at least monthly thereafter. Interrupt KOMZIFTI if the QTc interval is > 500 ms or the change from baseline is > 60 ms (Grade 3). In patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval, more frequent ECG monitoring may be necessary. Concomitant use of KOMZIFTI with drugs known to prolong the QTc interval may increase the risk of QTc interval prolongation, result in a greater increase in the QTc interval and adverse reactions associated with QTc interval prolongation, including Torsades de Pointes, other serious arrhythmias, and sudden death.

Embryo-Fetal Toxicity

Based on findings in animals and its mechanism of action, KOMZIFTI can cause embryo-fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with KOMZIFTI and for 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with KOMZIFTI and for 3 months after the last dose.

ADVERSE REACTIONS

Fatal adverse reactions occurred in 4 (4%) patients who received KOMZIFTI, including 2 with differentiation syndrome, 1 with infection, and 1 with sudden death. Serious adverse reactions were reported in 79% of patients who received KOMZIFTI. Serious adverse reactions occurring in ≥ 5% of patients included infection without an identified pathogen (29%), febrile neutropenia (18%), bacterial infection (16%), differentiation syndrome (16%), and dyspnea (6%).

Dosage interruption of KOMZIFTI due to an adverse reaction occurred in 54% of patients. Adverse reactions that required dose interruption in ≥ 2% of patients included infection without an identified pathogen (15%), differentiation syndrome (13%), febrile neutropenia (5%), pyrexia (4%), electrocardiogram QT prolonged (4%), leukocytosis (4%), bacterial infection (3%), cardiac failure (2%), cholecystitis (2%), diarrhea (2%), pruritus (2%), and thrombosis (2%). Dose reduction of KOMZIFTI due to an adverse reaction occurred in 4% of patients. Permanent discontinuation of KOMZIFTI due to an adverse reaction occurred in 21% of patients. Adverse reactions that required permanent discontinuation of KOMZIFTI in ≥ 2% of patients were infection without an identified pathogen (8%), bacterial infection (4%), cardiac arrest (2%), and differentiation syndrome (2%).

Most common (≥ 20%) adverse reactions, including laboratory abnormalities, were aspartate aminotransferase increased (53%), infection without an identified pathogen (52%), potassium decreased (52%), albumin decreased (51%), alanine aminotransferase increased (50%), sodium decreased (49%), creatinine increased (45%), alkaline phosphatase increased (41%), hemorrhage (38%), diarrhea (36%), nausea (35%), fatigue (34%), edema (30%), bacterial infection (28%), musculoskeletal pain (28%), bilirubin increased (27%), potassium increased (26%), differentiation syndrome (26%), pruritus (23%), febrile neutropenia (22%), and transaminases increased (21%).

DRUG INTERACTIONS

Drug interactions may occur when KOMZIFTI is concomitantly used with:

Strong or Moderate CYP3A4 Inhibitors: Monitor patients more frequently for KOMZIFTI-associated adverse reactions.
Strong or Moderate CYP3A4 Inducers: Avoid concomitant use of KOMZIFTI.
Gastric Acid Reducing Agents: Avoid concomitant use of KOMZIFTI with proton pump inhibitors (PPIs), H2 receptor antagonists (H2RAs), or locally acting antacids. If concomitant use with H2RAs or locally acting antacids cannot be avoided, modify KOMZIFTI administration time.
Take KOMZIFTI 2 hours before or 10 hours after administration of an H2 receptor antagonist.
Take KOMZIFTI 2 hours before or 2 hours after administration of a locally acting antacid.
Drugs that Prolong the QTc Interval: Avoid concomitant use of KOMZIFTI. If concomitant use cannot be avoided, obtain ECGs when initiating, during concomitant use, and as clinically indicated. Interrupt KOMZIFTI if the QTc interval is > 500 ms or the change from baseline is > 60 ms.
USE IN SPECIFIC POPULATIONS

Pregnancy: Based on findings in animals and its mechanism of action, KOMZIFTI can cause embryo-fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Verify pregnancy status in females of reproductive potential prior to starting KOMZIFTI.

Lactation: Because of the potential for adverse reactions in the breastfed child, advise women not to breastfeed during treatment with KOMZIFTI and for 2 weeks after the last dose.

Infertility: Based on findings in animals, KOMZIFTI may impair fertility in females and males of reproductive potential.

Please see full Prescribing Information, including Boxed WARNING.

(Press release, Kura Oncology, DEC 8, 2025, https://ir.kuraoncology.com/news-releases/news-release-details/kura-oncology-and-kyowa-kirin-report-combination-data-komziftitm [SID1234661264])

On December 8, 2025 Kian Immune Cell, a knowledge-based biotechnology company specializing in cellular cancer therapies, in collaboration with the Barekat Comprehensive Cancer Hospital, reported it is honored to host the scientific seminar titled "Innovations in Cancer Treatment Using Immune Cells."
This seminar aims to bring together leading oncologists in Tehran, offering a valuable platform to review and discuss the latest advancements in cancer treatment through immune cell–based approaches.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Featured Speakers and Presentation Topics
A distinguished panel of experts will deliver talks covering emerging scientific and clinical developments:

Dr. Payam Azadeh: Overview of the seminar’s objectives
Dr. Abolhassan Shahzadeh Fazeli: The role of next-generation sequencing (NGS) in cancer detection and molecular identification
Dr. Mohammad Faranoush: Recent advancements in cancer immunotherapy and evolving therapeutic strategies
Dr. Mohammad Sadegh Najafi: Presentation by the esteemed representative of Behestan Darou
Dr. Reza Nakooeian: Examination of tumor growth mechanisms with a focus on genetics and epigenetics
Dr. Marzieh Ebrahimi: Insights into tumor immunology and immune cell–based therapeutic approaches for malignant solid tumors
Dr. Delbar Daneshjoo / Dr. Mobina Ghasemi: Case-based review of NK cell therapies, presenting clinical findings and long-term follow-up outcomes
These presentations collectively offer a comprehensive overview of cutting-edge scientific progress in cellular and immune-based cancer treatment.

Seminar Details
Date: Thursday, December 10, 2025 (20 Azar 1404)
Time: 08:00 to 14:00
Venue: Conference Hall, Barekat Comprehensive Cancer Hospital
Capacity: Limited; early registration is strongly recommended
Contact: For coordination, please call +98-21-92001360, extension 508

(Press release, Kian Immune Cell, DEC 8, 2025, View Source [SID1234661263])

On December 8, 2025 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported that the Company’s senior management team and Dr. Claire Harrison will participate in a virtual fireside chat as part of Baird’s Biotech Discovery Series on Wednesday, December 10, 2025 at 12:00 p.m. ET. Dr. Harrison is Professor of Myeloproliferative Neoplasms, Clinical Director at Guy’s and St. Thomas’ NHS Foundation Trust and a leading international expert in myelofibrosis.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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A live webcast of the event can be accessed under "Events & Presentations" in the Investor section of the Company’s website, View Source, and will be available for replay following the event.

(Press release, Karyopharm, DEC 8, 2025, View Source [SID1234661262])

On December 8, 2025 Greenwich LifeSciences, Inc. (Nasdaq: GLSI) (the "Company"), a clinical-stage biopharmaceutical company focused on its Phase III clinical trial, FLAMINGO-01, which is evaluating GLSI-100, an immunotherapy to prevent breast cancer recurrences, reported the completion of enrollment in the open label non-HLA-A*02 arm of FLAMINGO-01.

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In the double-blinded arms of the Phase III trial, approximately 500 HLA-A*02 patients are currently planned to be randomized to GLSI-100 or placebo, and up to 250 patients of other HLA types (non-HLA-A*02) are planned to be treated with GLSI-100 in a third open label arm. The non-HLA-A*02 patients do not have the HLA-A*02 allele from either parent and represent about 55% of the patient population in FLAMINGO-01.

FLAMINGO-01 has achieved a major milestone by completing enrollment in the 250 patient open label non-HLA-A*02 arm of the Phase III trial, which is a result of the high screen rate and ensuing enrollment rate. The Company is continuing its review of the most recent data of this arm, including recurrence rates, which can be updated and/or published at any time.
The Company stopped enrolling in this arm earlier this year and is now approaching regulatory agencies to seek approval to continue enrollment of new non-HLA-A*02 patients in a randomized manner with a control arm. The Company has continued to screen a large number of these patients so that rapid enrollment of these screened patients can commence if regulatory approval is received.
The Company previously reported promising observations earlier this year showing that the immune response at baseline prior to any GLSI-100 treatment, the increasing immune response during the primary immunization series, and the safety profile of non-HLA-A*02 patients is trending similarly to the HLA-A*02 arms of FLAMINGO-01 and to the Phase IIb study, where breast cancer recurrences were reduced up to 80% or more and no metastatic breast cancer recurrences were reported. A preliminary analysis suggests that these promising trends are continuing.

CEO Snehal Patel commented, "As we continue to analyze the immune response, safety, and recurrence rate data of the 250 patient non-HLA-A*02 data set, it is important to remember that all 250 patients received GLSI-100, which is 5 times more than the approximately 50 patients treated in the Phase IIb trial. We can compare the open label recurrence rate data of these 250 treated patients to the expected historical recurrence rate for this population, which is well known and recently reported, to the HLA-A*02 arms of FLAMINGO-01, and to the Phase IIb study. In addition, we may be able to compare the recurrence rate during the first 6 months of vaccination, also called the primary immunization series or PIS, to the recurrence rate after the PIS is completed and after peak immunity is achieved. We look forward to providing updates on this analysis at any time, including publications at conferences as we have previously done for the Phase IIb trial from 2020-2022."

Mr. Patel added, "The use of GLSI-100 in the non-HLA-A*02 patient population is an invention by the Company, and the Company believes that any patent claims related to this invention are not subject to any license, royalties, or milestone payments. These patent claims should complement other patent claims that the Company has recently filed to potentially extend patent protection of GLSI-100 beyond 2040. The Company believes that this patient population could double the number of US and European patients eligible for GLSI-100 treatment to approximately 88,000 new patients per year with a market potential using the drug prices per year of Kadcyla or Enhertu in the range of $8-10 billion per year."

Additional updates:

The non-HLA-A*02 types that are most commonly being enrolled in FLAMINGO-01 continue to be HLA-A*03, HLA-A*24, HLA-A*01, HLA-A*11, HLA-A*68, HLA-A*29, HLA-A*30, HLA-A*23, and HLA-A*33.
The enrollment of HLA-A*02 patients in the 500 patient randomized arms continues, unaffected by the end of enrollment in the non-HLA-A*02 arm, while the Company also seeks to increase the size of these HLA-A*02 arms such that enrollment is not stopped prior to any interim analyses.
Enhertu (trastuzumab Deruxtecan [T-DXd]) treated patients continue to be eligible for enrollment in FLAMINGO-01. The Company believes that GLSI-100 will synergize with any trastuzumab based treatment in the neoadjuvant or adjuvant settings, including Enhertu.

About FLAMINGO-01 and GLSI-100

FLAMINGO-01 (NCT05232916) is a Phase III clinical trial designed to evaluate the safety and efficacy of GLSI-100 (GP2 + GM-CSF) in HER2 positive breast cancer patients who had residual disease or high-risk pathologic complete response at surgery and who have completed both neoadjuvant and postoperative adjuvant trastuzumab based treatment. The trial is led by Baylor College of Medicine and currently includes US and European clinical sites from university-based hospitals and academic and cooperative networks with plans to open up to 150 sites globally. In the double-blinded arms of the Phase III trial, approximately 500 HLA-A*02 patients are planned to be randomized to GLSI-100 or placebo, and up to 250 patients of other HLA types are planned to be treated with GLSI-100 in a third arm. The trial has been designed to detect a hazard ratio of 0.3 in invasive breast cancer-free survival, where 28 events will be required. An interim analysis for superiority and futility will be conducted when at least half of those events, 14, have occurred. This sample size provides 80% power if the annual rate of events in placebo-treated subjects is 2.4% or greater.

For more information on FLAMINGO-01, please visit the Company’s website here and clinicaltrials.gov here. Contact information and an interactive map of the majority of participating clinical sites can be viewed under the "Contacts and Locations" section. Please note that the interactive map is not viewable on mobile screens. Related questions and participation interest can be emailed to: [email protected]

About Breast Cancer and HER2/neu Positivity

One in eight U.S. women will develop invasive breast cancer over her lifetime, with approximately 300,000 new breast cancer patients and 4 million breast cancer survivors. HER2 (human epidermal growth factor receptor 2) protein is a cell surface receptor protein that is expressed in a variety of common cancers, including in 75% of breast cancers at low (1+), intermediate (2+), and high (3+ or over-expressor) levels.

(Press release, Greenwich LifeSciences, DEC 8, 2025, View Source [SID1234661261])

On December 8, 2025 Geron Corporation (Nasdaq: GERN), a commercial-stage biopharmaceutical company aiming to change lives by changing the course of blood cancer, reported new data presented at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) 2025 Annual Meeting being held in Orlando, FL. Collectively, the oral and poster presentations reinforce the growing body of evidence supporting the potential of RYTELO (imetelstat), Geron’s first-in-class telomerase inhibitor, across lower-risk myelodysplastic syndromes/neoplasms (LR-MDS) and myelofibrosis (MF).

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"These new data confirm our understanding of how imetelstat works and highlight the potential long-term benefit in appropriate patients," said Joseph E. Eid, M.D., Executive Vice President, Research and Development and Chief Medical Officer of Geron. "The data suggesting the association between early treatment-emergent cytopenias and subsequent hemoglobin and transfusion independence response with imetelstat, together with the long-term outcomes from IMerge presented at ASH (Free ASH Whitepaper), continue to reinforce imetelstat as a differentiated treatment option for eligible patients with lower-risk MDS."

The oral presentation by Amer Zeidan, MBBS, MHS, Yale School of Medicine, and a principal investigator of the IMerge trial, featured pooled analyses of the IMerge population suggesting that early treatment-emergent neutropenia and thrombocytopenia may be associated with greater hemoglobin increases, which emerged as a main driver for achieving red blood cell transfusion independence (RBC-TI).

"What stands out in these analyses is the consistency between the clinical response we see in patients and the early treatment patterns observed in their blood counts when we use imetelstat in non-del5q lower-risk MDS patients with transfusion dependent anemia. This is reminiscent of similar trends we see with lenalidomide, which is a disease-modifying agent in del5q lower-risk MDS patients," said Amer Zeidan, Chief of the Division of Hematologic Malignancies and Professor of Medicine at Yale Cancer Center. "For patients with lower-risk MDS, transfusion dependence places a considerable physical and logistical burden on daily life, and treatment options beyond ESAs remain limited. The association we observed between early blood count changes and later improvements in hemoglobin provides valuable insight for clinicians and underscores the meaningful benefit imetelstat may offer to this population."

Additional poster presentations provided long-term outcomes data, including survival data in LR-MDS, exploratory biomarker analyses in MF, and ongoing combination and investigator-sponsored studies across the myeloid malignancy spectrum.

Highlights from the ASH (Free ASH Whitepaper) 2025 Presentations

Correlation between Treatment-Emergent Cytopenias and Clinical Response with Imetelstat in Patients with Lower-Risk Myelodysplastic Syndromes: Analysis from the IMerge Trial (Zeidan et al., Oral #490)

This oral presentation reported findings from post-hoc analyses examining the potential relationship between treatment-emergent cytopenias within the first two cycles of imetelstat treatment and key clinical outcomes in the pooled IMerge patient population. These analyses evaluated reductions in platelets and neutrophils alongside hemoglobin (Hb) rise, achievement of ≥8- or ≥24-week RBC-TI, and achievement of Hb rise ≥1.5 g/dL lasting ≥8 weeks.

Across analyses looking at single clinical factors, patients who experienced ≥75% reductions in neutrophils or ≥50% reductions in platelets during the first two cycles of imetelstat had greater maximum Hb increases compared with those who did not experience such reductions. Numerically higher rates of ≥8- or ≥24-week RBC-TI were also observed in these groups. When the analyses accounted for multiple clinical factors at the same time, the associations between early cytopenias and Hb improvements remained consistent: ≥75% neutrophil reduction was associated with greater Hb increase, whereas maximum ≥50% platelet reduction was associated with achieving Hb rise ≥1.5 g/dL lasting ≥8 weeks. Further, Hb rise emerged as a main driver of achieving transfusion independence. A strong association between platelet and neutrophil reductions was also observed.

These findings offer deeper context for interpreting patient responses and provide insight into how imetelstat’s biological effects may translate into meaningful clinical outcomes.

Long-Term Outcomes and Overall Survival from the Randomized, Double-Blind, Placebo-Controlled, Phase 3 IMerge Trial of Imetelstat for Lower-Risk Myelodysplastic Syndromes (Santini et al., Poster #2074)

This poster reported updated long-term outcomes data from the double-blind, placebo-controlled IMerge Phase 3 trial assessing overall survival (OS), progression-free survival (PFS), and time to progression to acute myeloid leukemia (AML) in patients with transfusion-dependent LR-MDS treated with imetelstat.

At a median follow-up of 45 months, the analysis showed a favorable trend toward improved secondary endpoints of OS, PFS, and time to AML progression for imetelstat-treated patients compared with placebo recipients in the overall population. OS favored imetelstat versus placebo in most predefined subgroups, regardless of transfusion burden, serum EPO (erythropoietin) level, and ring sideroblast positive or negative status. Additionally, OS outcomes were numerically improved in patients who achieved RBC-TI or hemoglobin improvement.

These results suggest that imetelstat may provide meaningful long-term benefit for patients with lower-risk MDS who are transfusion independent, although the trial was not powered to detect statistical significance for OS. The data support continued clinical exploration of telomerase inhibition as a potential disease-modifying approach for LR-MDS.

Correlation between IL-8 and TNF-Alpha Levels and Overall Survival in Patients with Myelofibrosis Relapsed or Refractory to a JAKi Treated with Imetelstat in the IMbark Trial​ (Mascarenhas et al., Poster #5585)

This poster reported results from a post hoc analysis of inflammatory cytokines in the Phase 2 IMbark trial of patients with JAK inhibitor relapsed/refractory myelofibrosis treated with imetelstat. The analysis evaluated how cytokine changes corresponded with clinical endpoints, including symptom improvement, spleen volume reduction, and survival trends.

The findings showed that patients treated with imetelstat experienced dose-dependent reductions in IL-8 and TNF-a (proinflammatory cytokines), with the 8.9 mg/kg dose showing more pronounced effects compared to the 4.4 mg/kg dose. Reductions in these cytokines corresponded with reductions in total symptom score or spleen volume, consistent with previously reported clinical activity. A longer survival trend was observed in patients receiving the higher dose, particularly among patients with elevated baseline IL-8 and TNF-a levels, although subgroup sizes were small.

These results suggest that cytokine modulation may contribute to the clinical activity of imetelstat and provide further support for its potential disease-modifying properties in myelofibrosis. These findings build on prior biomarker work demonstrating imetelstat’s impact on malignant progenitor cells in myelofibrosis.

IMproveMF: Phase 1b Trial of Imetelstat Plus Ruxolitinib in Patients with Intermediate-1/2 or High-Risk Myelofibrosis (Mascarenhas, et al., Poster #2052)

This poster reported enrollment progress and emerging observations from the Phase 1b IMproveMF trial evaluating imetelstat in combination with ruxolitinib for patients with intermediate-2 or high-risk myelofibrosis. The study is designed to determine safety, tolerability, and recommended dosing for future development.

As of the July 2025 cutoff, the trial had enrolled three patients in part 2 of the study, with the first patient treated in January 2025. The part 1 dose escalation phase of the study is complete, with 8.9 mg/kg imetelstat IV every 4 weeks identified as the recommended dose to be combined with ruxolitinib.

Advanced Myelodysplastic Neoplasms or AML Failing HMA-based Therapy – Preliminary Results of the IMpress Study​ (Ades, et al, Poster #5115)

This poster reported interim results from an investigator-sponsored Phase 2 study evaluating imetelstat in patients with advanced myelodysplastic neoplasms or acute myeloid leukemia who were refractory to, relapsed after, or intolerant to hypomethylating agent, or HMA, therapy.

The results showed that imetelstat administered at 7.1 mg/kg IV every 2 weeks in this patient population did not appear to be associated with additional toxicity, and that treatment-emergent adverse events were manageable in this heavily pre-treated population. While limited single-agent clinical activity was observed – consistent with the aggressive disease biology and prior treatment history – several patients were able to complete protocol-specified visits, and one remained on treatment at the time of the analysis.

These findings suggest that single agent imetelstat has a predictable and manageable safety profile at this exposure in these advanced diseases and provides important insights for potential combination strategies in high-risk populations, where unmet needs remain substantial.

The ASH (Free ASH Whitepaper) presentations are available on Geron’s website in the Investor section under publications.

Dr. Zeidan has served as a consultant for Geron and has received honoraria. The views expressed in this press release and in the presentation are his own and do not necessarily reflect those of his employer.

About RYTELO (imetelstat)
RYTELO is an oligonucleotide telomerase inhibitor approved in the U.S. for the treatment of adult patients with LR-MDS with transfusion-dependent anemia requiring four or more red blood cell units over eight weeks who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESAs). It is indicated to be administered as an intravenous infusion over two hours every four weeks.
In addition, RYTELO is approved in the European Union as a monotherapy for the treatment of adult patients with transfusion-dependent anemia due to very low, low or intermediate risk myelodysplastic syndromes without an isolated deletion 5q cytogenetic (non-del 5q) abnormality and who had an unsatisfactory response to or are ineligible for erythropoietin-based therapy.

RYTELO is a first-in-class treatment that works by inhibiting telomerase enzymatic activity. Telomeres are protective caps at the end of chromosomes that naturally shorten each time a cell divides. In LR-MDS, abnormal bone marrow cells often express the enzyme telomerase, which rebuilds those telomeres, allowing for uncontrolled cell division. Developed and exclusively owned by Geron, RYTELO is the first and only telomerase inhibitor approved by the U.S. Food and Drug Administration and the European Commission.

US IMPORTANT SAFETY INFORMATION ABOUT RYTELO

WARNINGS AND PRECAUTIONS

Thrombocytopenia

RYTELO can cause thrombocytopenia based on laboratory values. In the clinical trial, new or worsening Grade 3 or 4 decreased platelets occurred in 65% of patients with MDS treated with RYTELO.
Monitor patients with thrombocytopenia for bleeding. Monitor complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated. Administer platelet transfusions as appropriate. Delay the next cycle and resume at the same or reduced dose, or discontinue as recommended.

Neutropenia

RYTELO can cause neutropenia based on laboratory values. In the clinical trial, new or worsening Grade 3 or 4 decreased neutrophils occurred in 72% of patients with MDS treated with RYTELO.
Monitor patients with Grade 3 or 4 neutropenia for infections, including sepsis. Monitor complete blood cell counts prior to initiation of RYTELO, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated. Administer growth factors and anti-infective therapies for treatment or prophylaxis as appropriate. Delay the next cycle and resume at the same or reduced dose, or discontinue as recommended.

Infusion-Related Reactions

RYTELO can cause infusion-related reactions. In the clinical trial, infusion-related reactions occurred in 8% of patients with MDS treated with RYTELO; Grade 3 or 4 infusion-related reactions occurred in 1.7%, including hypertensive crisis (0.8%). The most common infusion-related reaction was headache (4.2%). Infusion-related reactions usually occur during or shortly after the end of the infusion.
Premedicate patients at least 30 minutes prior to infusion with diphenhydramine and hydrocortisone as recommended and monitor patients for at least one hour following the infusion as recommended. Manage symptoms of infusion-related reactions with supportive care and infusion interruptions, decrease infusion rate, or permanently discontinue as recommended.

Embryo-Fetal Toxicity

Based on animal findings, RYTELO can cause embryo-fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with RYTELO and for 1 week after the last dose.

ADVERSE REACTIONS

Serious adverse reactions occurred in 32% of patients who received RYTELO. Serious adverse reactions in >2% of patients included sepsis (4.2%) and fracture (3.4%), cardiac failure (2.5%), and hemorrhage (2.5%). Fatal adverse reactions occurred in 0.8% of patients who received RYTELO, including sepsis (0.8%).
Most common adverse reactions (≥10% with a difference between arms of >5% compared to placebo), including laboratory abnormalities, were decreased platelets, decreased white blood cells, decreased neutrophils, increased AST, increased alkaline phosphatase, increased ALT, fatigue, prolonged partial thromboplastin time, arthralgia/myalgia, COVID-19 infections, and headache.

(Press release, Geron, DEC 8, 2025, View Source [SID1234661260])