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])

On December 8, 2025 Autolus Therapeutics plc (Nasdaq: AUTL), an early commercial-stage biopharmaceutical company developing, manufacturing and delivering next-generation programmed T cell therapies, reported presentation of preliminary data from the CATULUS Phase 1 trial of obe-cel in pediatric relapsed or refractory (r/r) B-ALL patients, as well as further insights from the registrational FELIX study in adult r/r B-ALL, at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

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Dr. Matthias Will, Chief Development Officer of Autolus, said: "Pediatric patients with r/r B-ALL have a poor prognosis, particularly those who relapse early. We were pleased to share the first data from the Phase 1 CATULUS trial showing obe-cel can produce high remission rates in this pediatric patient population, including in patients with high-risk relapse and patients with primary CNS relapse. Consistent with our experience in the adult population, data show low rates of severe CRS and ICANS. We are now advancing into the Phase 2 portion of the study in line with our commitment to address the significant unmet need for new treatment options for pediatric patients with r/r ALL."

Dr. Will continued, "Insights from post-hoc analyses from our FELIX pivotal trial in r/r adult B-ALL explored various factors that may help to predict long-term patient outcomes. Specifically, investigators showed that detection of obe-cel in the blood three months post-treatment may be a predictor for long-term outcomes. They also identified characteristics of the product’s cell phenotype as additional factors for treatment outcomes."

He concluded, "In addition to Autolus’ presentations, we were highly encouraged by data from the real-world experience of the ROCCA consortium evaluating CAR T therapy for r/r adult ALL patients. These real world data mirror obe-cel’s safety profile observed in the pivotal FELIX trial with low single digits rates of CRS and ICANS as one of the differentiating characteristics of the therapy."

Abstract 740 – Poster presentation
Title: Treatment of pediatric patients (pts) with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) with obecabtagene autoleucel (obe-cel), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy: preliminary findings from the Phase Ib/II CATULUS trial
Session Name: Acute Lymphoblastic Leukemias: Therapies Excluding Allogeneic Transplantation: Poster II
Session Date and Time: December 7, 2025; 6:00 – 8:00pm ET
Session Room: Orange County Convention Center; West Halls B3-B4
Publication Number: 3337
Presenting Author: Sara Ghorashian, Consultant Haematologist at Great Ormand Street Hospital for Children (GOSH) and Honorary Associate Professor at UCL

Summary: CATULUS is a single-arm, open-label, multi-center study enrolling high-risk patients under age 18 with r/r B-ALL that is primary refractory, in high-risk first relapse, or in second or later relapse. The safety profile of obe-cel in pediatric patients was consistent with that previously reported in adults, with low rates of high-grade CRS and ICANS (both 8.7%). The ORR was high at 95.5% (n=21), with 90.9% (n=20) achieving complete response (CR). Twenty patients were in ongoing remission at data cut-off with a median follow-up of 8.8 months. These preliminary findings support further exploration of obe-cel in pediatric R/R B-ALL and planning for the Phase II expansion is underway.

Abstract 4060 – Poster presentation
Title: Chimeric antigen receptor (CAR) T-cell persistence at Month 3 predicts clinical outcomes in adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) treated with obecabtagene autoleucel (obe-cel)
Session Name: Acute Lymphoblastic Leukemias: Therapies Excluding Allogeneic Transplantation: Poster III
Session Date and Time: December 8, 2025; 6:00 – 8:00pm ET
Session Room: Orange County Convention Center; West Halls B3-B4
Publication Number: 5118
Presenting Author: Claire Roddie, MD, PhD, FRCPath, Associate Professor Haematology and Honorary Consultant Haematologist, Cancer Institute, University College London (UCL)

Summary: Of 99 patients who achieved remission (CR/CRi) in the FELIX study, 79 (79.8%) had ongoing remission at month three following obe-cel infusion and comprised the subgroup of interest for the analyses. At month three post infusion, 60/79 patients (75.9%) had ongoing CAR T-cell persistence, while 19/79 patients (24.1%) had loss of persistence. In patients who remained in remission beyond month three, including those with deep MRD-negative remission and no post obe-cel SCT, ongoing CAR T-cell persistence at month three, measured by droplet digital PCR (ddPCR), was associated with longer event-free survival (EFS) and overall survival (OS) compared with loss of persistence. These results suggest that persistence status at month three may be a marker for predicting long-term outcomes following obe-cel treatment in patients with r/r B-ALL.

Abstract 4031 – Poster presentation
Title: Evaluation of commercially available chimeric antigen receptor (CAR) detection reagents for monitoring of CAR T-cell (CAR T) expansion and persistence in patients (pts) treated with obecabtagene autoleucel (obe-cel)
Session Name: Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities: Poster I
Session Date and Time: December 6, 2025; 5:30 – 7:30pm ET
Session Room: Orange County Convention Center; West Halls B3-B4
Publication Number: 2367
Presenting Author: Rehan Hussain, Translational Medicine Senior Scientist

Summary: Measuring obe-cel expansion and persistence using flow cytometry (FC) is feasible with commercially available antibodies that directly target regions of the CAR construct, such as the G4S linker. These reagents show high correlation with anti-idiotype antibodies and provide a reliable method for tracking CAR expression in patients. Use of the G4S binder enabled tracking of CAR T expansion kinetics and phenotypic profiles in patients with different disease burdens. Reagents based on the CD19 protein, commonly used in other CAR T therapies, are unsuitable for obe-cel due to the unique features of the CAT19 binder, which limits effective detection.

Abstract 4429 – Oral presentation
Title: Impact of chimeric antigen receptor (CAR) product cell phenotypes on clinical outcomes following treatment with obecabtagene autoleucel (obe-cel)
Session Name: Acute Lymphoblastic Leukemias: Biomarkers, Molecular Markers, and Measurable Residual Disease in Diagnosis and Prognosis: Prognostic Genetic and Therapeutic Response Factors in Adult and Pediatric B-ALL
Session Date and Time: December 6, 2025; 10:00 – 10:15am ET
Session Room: Orange County Convention Center; W224CDGH
Publication Number: 33
Presenting Author: Benjamin Simpson, Ph.D., Bioinformatics & Data Management Principal Scientist, Autolus Therapeutics

Summary: Clinical data show the potential for obe-cel to produce long-term outcomes. This analysis details certain product features potentially affecting clinical outcomes, including how drug product phenotypes correlate with treatment outcomes following infusion with obe-cel. A higher percentage of central memory cells (Tcm) in the drug product samples was an independent predictor of positive clinical outcomes, including overall survival (OS), following obe-cel infusion. While the T-cell phenotype composition in the leukapheresis product (LP) was weakly correlated with that in the drug product, CD25+ HLADR+ CD4+ cells in the LP independently predicted less favorable clinical outcomes. However, other factors (e.g. tumor characteristics) are also likely to affect outcomes; therefore, further investigations are needed to better understand and predict favorable clinical outcomes, and to potentially guide studies of additional cell manipulations during CAR T-cell manufacturing.

(Press release, Autolus, DEC 8, 2025, View Source [SID1234661277])

On December 8, 2025 Opna Bio, a clinical-stage biopharmaceutical company focused on the discovery and development of novel oncology therapeutics, reported promising preclinical data from the company’s novel, multi-functional protein degrader program and positive updated data from an ongoing Phase 1 combination study with OPN-2853, a bromodomain and extra-terminal motif (BET) inhibitor, as an add-on to ruxolitinib in patients with advanced myelofibrosis.

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Data were shared in an oral and poster presentation this past weekend at the 67th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper), taking place December 6-9, 2025, in Orlando, FL.

Multi-Functional Degraders Designed to Block Key Oncogenic Pathways Using Single Chemical Entity

Opna’s novel protein degraders are designed to block multiple oncogenic targets – EP300, CBP, IKZF1 and IKZF3 – concurrently in the same cancer cell, achieving potent single agent anti-tumor activity. EP300, CBP, IKZF1 and IKZF3 are known to promote the progression of multiple myeloma, a type of blood cancer derived from malignant plasma cells in the bone marrow. In a proof-of-concept OPM-2 multiple myeloma model, OPN-5667 potently reduced the levels of key oncoproteins in vitro and caused tumor regression in all treated animals in vivo. Opna’s medicinal chemistry campaign has produced compounds with improved potency and pharmacological properties, advancing the program towards clinical candidate selection.

The degrader program is built on foundational studies presented at ASH (Free ASH Whitepaper) in 2024 with OPN-6602, an oral EP300/CBP inhibitor, in combination with immunomodulatory drugs (IMiDs). The combination resulted in strong synergy in vivo including complete regressions and improved response durability. A Phase 1 study of OPN-6602 is currently enrolling patients with relapsed or refractory multiple myeloma at multiple sites in the U.S.

"These promising data support our goal of developing a single agent ‘super drug’ for hematological malignancies, such as multiple myeloma and lymphoma," said Gideon Bollag, PhD, chief scientific officer of Opna Bio. "We anticipate identifying a lead candidate in mid-2026 and submitting an IND in 2027."

OPN-2853 Reduces Spleen Size in Patients with Advanced Myelofibrosis

OPN-2853, a potent, orally active small molecule BET inhibitor, is being evaluated as an add-on to ruxolitinib in the PROMise study in patients with myelofibrosis who are no longer responding to ruxolitinib. Myelofibrosis is a type of blood cancer that causes bone marrow fibrosis, anemia and an enlarged spleen, amongst other symptoms.

As of October 2025, 29 patients had been enrolled across multiple sites in the United Kingdom. Fourteen patients were treated with 40 mg of OPN-2853 and 15 patients were treated with 80 mg of OPN-2853 added to ruxolitinib. In 16 of 26 evaluable patients, there was a 50% or greater reduction of their palpable spleen length on treatment when compared to baseline.

The combination dose has been well tolerated, and the majority of patients have completed eight cycles of combination treatment.

The investigator-initiated study is led by Professor Adam Mead at the University of Oxford through a collaboration with Cancer Research UK (CRUK) and is run through the Cancer Research UK Clinical Trials Unit at the University of Birmingham.

"The emerging data from the PROMise study continue to be encouraging. We are now seeing consistent and clinically meaningful spleen size reductions, improvements in symptom burden, and durable benefit for patients who previously had limited options after an inadequate response to ruxolitinib alone," said Dr. Mead. "These findings strengthen our view that selective BET inhibition alongside JAK inhibition may offer a new therapeutic approach for patients with myelofibrosis."

(Press release, Opna Bio, DEC 8, 2025, View Source [SID1234661293])

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 Autolus Therapeutics plc (Nasdaq: AUTL), an early commercial-stage biopharmaceutical company developing, manufacturing and delivering next-generation programmed T cell therapies, reported presentation of preliminary data from the ongoing Phase 1 CARLYSLE trial in patients with severe refractory systemic lupus erythematosus (srSLE) in an oral presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

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Dr. Matthias Will, Chief Development Officer of Autolus, said: "Patients with srSLE have limited remaining treatment options and represent a difficult to treat population with a critical unmet need. Data reported from the CARLYSLE trial show an encouraging high rate of DORIS responses and a deep reset in the B cell compartment induced by obe-cel, suggesting the possibility for an immune reset. Based on this positive initial experience with obe-cel in the CARLSYLE trial we have initiated the LUMINA trial, a Phase 2 trial in lupus nephritis with registrational intent."

Abstract 302
Title: Obecabtagene autoleucel (obe-cel), a CD19-targeting chimeric antigen receptor (CAR) T-cell therapy, in patients with severe, refractory systemic lupus erythematosus (SLE) in the Phase I CARLYSLE study: initial safety, preliminary efficacy, pharmacokinetics, and biomarker results
Session Name: Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities: Emerging CAR-T Cell Therapies for Acute Leukemias and Autoimmune Diseases
Session Date and Time: December 8, 2025; 11:30 – 11:45am ET
Session Room: Orange County Convention Center; Valencia Room W415D
Publication Number: 815
Presenting Author: Claire Roddie, MD, PhD, FRCPath, Associate Professor Haematology and Honorary Consultant Haematologist, Cancer Institute, University College London (UCL)

Summary: Updated Phase 1 data with longer follow-up, and data in patients who received both 50×106 (50M) and 100×106 (100M) CAR T-cells were presented. Nine adult patients were infused with obe-cel, including six at the 50M dose and three at the 100M dose.

Obe-cel was well tolerated in all patients. No dose limiting toxicities (DLTs) or cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were observed at the 50M dose. Grade one cytokine release syndrome (CRS) was observed in three patients at the 50M dose and three patients at the 100M dose. Hypertension was observed in five patients at the 50M dose, with three of those patients having pre-existing history of hypertension. A case of transient Grade three liver toxicity was observed in one patient of the 100M cohort.

At the 50M dose, three patients (50%) achieved CRR and five patients (83%) achieved DORIS with a median onset of 5.1 months (range: 4.9–8.9), without evidence of new disease activity at a median of 12 months of follow up (range: 8.5–16.3). All non-renal manifestations of the disease resolved by month four. Urinary protein creatinine (UPC) ratio levels decreased over time, demonstrating significant decline or absence of disease activity. Data show high peak expansion and deep B cell aplasia consistent with known obe-cel characteristics in oncology indications. Peak expansion was reached at a median of 10 days (range: 9–13). The median time to loss of CAR T-cell persistence based on Kaplan-Meier analysis was 3.0 months. The B-cell reconstitution profiles suggest that obe-cel may induce a reset of pathologic autoimmunity.

Emerging data in the 100M cohort is consistent with the 50M adult cohort, and evaluation is ongoing.

Data support progressing obe-cel as a treatment for srSLE and 50M has been selected as the recommended Phase 2 dose. Autolus has aligned with U.S. Food and Drug Administration (FDA) on a Phase 2 trial design in LN and potential registrational path to approval. The LUMINA trial is now enrolling.

Dr. Christian Itin, Autolus Chief Executive Officer, said: "Obe-cel’s safety profile is based on a robust database spanning several clinical trials in B-ALL and B-NHL indications. Data presented today now also show the ability to induce deep depletion of B-cell lineages in patients with srSLE. Obe-cel successfully underwent the regulatory approval process with the FDA, EMA and MHRA in adult r/r B-ALL and launched commercially in the US and UK in 2025. Building on this strong foundation of clinical data, and demonstrated commercial and manufacturing capabilities, we believe Autolus is well positioned for a successful and efficient path into the autoimmune setting."

(Press release, Autolus, DEC 8, 2025, View Source [SID1234661278])