On December 10, 2024 Immix Biopharma, Inc. ("ImmixBio", "Company", "We" or "Us" or "IMMX"), a clinical-stage biopharmaceutical company developing cell therapies for AL Amyloidosis and select immune-mediated diseases, reported that new NXC-201 NEXICART-1 clinical data in relapsed/refractory AL Amyloidosis has been presented at 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held in San Diego, California (Press release, Immix Biopharma, DEC 10, 2024, View Source [SID1234648983]). The updated results include follow-up and clinical data from 3 new NEXICART-1 patients.

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"We are encouraged by the updated NXC-201 results being presented by our academic collaborators at ASH (Free ASH Whitepaper) 2024. We believe the high percentage of complete responders, combined with the consistent, attractive tolerability profile is critically important in relapsed/refractory AL Amyloidosis. This expanded NXC-201 dataset continues to bolster our leadership in relapsed/refractory AL Amyloidosis, where no drugs are FDA approved today," said Ilya Rachman, M.D., Ph.D., Chief Executive Officer of Immix Biopharma. Gabriel Morris, Chief Financial Officer of Immix Biopharma, added, "We are looking forward to bringing this promising therapy to U.S. relapsed/refractory AL Amyloidosis patients."

At the NXC-201 ASH (Free ASH Whitepaper) 2024 oral presentation, data were presented from 16 relapsed/refractory AL amyloidosis patients (including 3 new patients) in the ongoing Phase 1b/2 NEXICART-1 study, with median 4 lines of therapy prior to NXC-201. Patients were infused with CAR+T cells at doses of 150 x 106 (n=1), 450 x 106 (n=2), and 800 x 106 (n=13).

Patient characteristics:

81% (13/16) had cardiac involvement
38% (6/16) had New York Heart Association (NYHA) stage 3 or 4 heart failure (3 stage 4, 3 stage 3)
31% (5/16) had Mayo stage 3 (1 stage 3b, 4 stage 3a) AL amyloidosis disease
44% (7/16) had t(11;14) translocation
Relapsed/refractory to a median 4 lines of prior therapy (range: 3-10)
Safety and efficacy data:

Overall response rate of 94% (15/16)
Complete response rate of 75% (12/16) (9 out of 16 were MRD- 10-5)
Organ response rate of 62% (8/13 evaluable)
Best responder had a duration of response of 31.5 months as of December 9, 2024, with complete response ongoing
There were no immune effector cell-associated neurotoxicity syndrome (ICANS) events
Median CRS duration was 2 days (range: 1-5):
No grade 4 cytokine release syndrome (CRS) events
2 experienced no CRS; 3 experienced grade 1 CRS; 8 Experienced grade 2 CRS; 3 experienced grade 3 CRS
The NXC-201 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting oral presentation video can be accessed on the ASH (Free ASH Whitepaper) website: View Source

The NXC-201 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting oral presentation can be accessed on the ImmixBio corporate website at this link: View Source

ASH Presentation Details (CAR-T NXC-201 in relapsed/refractory AL Amyloidosis).

Event 66th ASH (Free ASH Whitepaper) Annual Meeting and Exposition, San Diego, CA
Title "Efficacy and Safety of Anti-BCMA Chimeric Antigen Receptor T-Cell (CART) for the Treatment of Relapsed and Refractory AL Amyloidosis"
Presentation
Date/Time (Pacific Time)
Publication #894
Session Date: Monday, December 9, 2024
Session Name: 652. MGUS, Amyloidosis, and Other Non-Myeloma Plasma Cell Dyscrasias: Clinical and Epidemiological: Ignored no Longer-Progress in AL Amyloidosis
Session Time: 2:45 PM-4:15 PM
Presentation Time: 4:00PM PT
About NEXICART-1
NEXICART-1 (NCT04720313) is an open-label, ex-U.S. Phase 1b/2 clinical trial of NXC-201 (formerly HBI0101) in patients with relapsed/refractory multiple myeloma and relapsed/refractory AL amyloidosis (including AL Amyloidosis patients with impaired cardiac function and including AL Amyloidosis patients exposed to prior BCMA-targeted therapy). The primary objective of the study is to characterize the safety and efficacy of NXC-201. NEXICART-1 clinical results are available at View Source .

About NEXICART-2
NEXICART-2 (NCT06097832) is an open-label, single-arm, multi-site U.S. Phase 1b/2 dose expansion clinical trial of CAR-T NXC-201 in relapsed/refractory AL Amyloidosis. NEXICART-2 is expected to enroll 40 patients with adequate cardiac function who have not been exposed to prior BCMA-targeted therapy. The study is designed with a standard 6 patient safety-run in to evaluate two doses (three patients each at 150 million CAR+T cells and 450 million CAR+T cells) (both dose levels were evaluated in the NEXICART-1 study and have produced complete responses in relapsed/refractory AL Amyloidosis patients). The study aims to evaluate the safety and efficacy of NXC-201. Primary endpoints are complete response rate and overall response rate, according to consensus recommendations (Palladini et al. 2012).

About NXC-201
NXC-201 is a sterically-optimized BCMA-targeted chimeric antigen receptor T (CAR-T) cell therapy. Initial data from Phase 1b/2 ex-U.S. study NEXICART-1 has demonstrated high complete response rates and no neurotoxicity of any kind in AL Amyloidosis.

NXC-201 is being studied in a comprehensive clinical development program for the treatment of patients with relapsed/refractory AL amyloidosis in the U.S., with the potential to expand into select immune-mediated diseases. The NXC-201 NEXICART-2 (NCT06097832) U.S. clinical trial builds on a robust clinical dataset. NXC-201 has been awarded Orphan Drug Designation (ODD) in AL Amyloidosis by the US FDA and in the EU by the EMA.

About AL Amyloidosis
AL amyloidosis is caused by abnormal plasma cells in the bone marrow, which produce misfolded amyloid proteins that build-up in the heart, kidney, liver, and other organs. This build-up causes progressive and widespread damage to multiple organs, including heart failure, and leads to high mortality rates.

The U.S. observed prevalence of relapsed/refractory AL Amyloidosis is estimated to be growing at 12% per year according to Staron, et al Blood Cancer Journal, to approximately 33,277 patients in 2024.

The Amyloidosis market was $3.6 billion in 2017, and is expected to reach $6 billion in 2025, according to Grand View Research.

On December 10, 2024 Halia Therapeutics, a biopharmaceutical company at the forefront of developing treatments for chronic inflammation and related disorders, reported promising topline data resulting in the advancement to the second stage of its Phase 2 clinical trial evaluating HT-6184, a first-in-class allosteric NEK7/NLRP3 inflammasome inhibitor given orally, in patients with lower-risk myelodysplastic syndromes (LR-MDS) (Press release, Halia Therapeutics, DEC 10, 2024, View Source [SID1234648981]).

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The initial cohort of 18 patients with LR-MDS demonstrated a hematological improvement-erythroid (HI-E) response to HT-6184 treatment following 16 weeks of monotherapy, exceeding the preset requirement of at least three responders. Having achieved this critical milestone, the trial now advances to its second stage enrolling an additional 8-10 patients to further validate HT-6184’s potential.

"The high frequency of erythroid response following treatment with HT-6184 validates the key importance of the NLRP3 inflammasome and myddosome pathways as pathogenetic drivers of ineffective hematopoiesis in MDS, offering the prospect of a safe and effective oral therapeutic for LR-MDS patients," said Alan List, MD Halia SAB Member.

"This trial represents a significant step forward in addressing the unmet needs of patients with LR-MDS," said Dr. David J. Bearss, Ph.D., President and CEO of Halia Therapeutics. "By targeting the underlying inflammatory signaling driving this condition, HT-6184 aims to transform treatment outcomes and improve quality of life for patients who currently face limited options."

The Phase 2 trial utilizes a Simon’s minimax two-stage design to evaluate the safety and efficacy of HT-6184 in up to 40 patients across multiple clinical sites in India. Primary endpoints include hematologic improvements such as transfusion dependency and changes in hemoglobin levels. Secondary endpoints assess HT-6184’s impact on biomarkers of inflammasome activation in MDS and the size of somatic gene mutation clones, offering a comprehensive view of its therapeutic potential.

The trial is expected to conclude by the end of Q2 2025. The results of this study are anticipated to provide pivotal data to support HT-6184’s continued clinical development and eventual regulatory submission.

About Myelodysplastic Syndromes (MDS): An Urgent Unmet Need

MDS is a group of hematologic cancers characterized by bone marrow dysfunction, leading to abnormal and underdeveloped blood cells. These conditions result in complications such as anemia, increased infection risk, and, in some cases, progression to acute myeloid leukemia. Current treatments are limited in efficacy and durability for patients with LR-MDS, underscoring the need for innovative therapeutic solutions. Novel oral agents are needed for the treatment of this disease to alleviate the need to go into the office for treatment either with an injection or needed infusion.

About HT-6184

HT-6184 is a groundbreaking drug candidate that targets the protein NEK7 through an allosteric mechanism. NEK7 plays a crucial role in the NLRP3 inflammasome, which is essential for its assembly and activity. In preclinical models, Halia demonstrated that inhibiting NEK7’s binding ability to NLRP3 disrupts inflammasome signaling and reduces the inflammatory response. HT-6184 prevents the formation of the NLRP3 inflammasome and promotes its disassembly once activated.

On December 10, 2024 Geron Corporation (Nasdaq: GERN), a commercial-stage biopharmaceutical company aiming to change lives by changing the course of blood cancer, reported results from an oral presentation at the 66 th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, reporting Phase 1 findings from the two-part IMproveMF study (Press release, Geron, DEC 10, 2024, View Source [SID1234648980]). The safety results from the dose escalation Part 1 suggest the tolerability of RYTELO (imetelstat), a first-in-class telomerase inhibitor, in combination with ruxolitinib as frontline therapy in patients with intermediate-1 (INT-1), intermediate-2 (INT-2) or high-risk (HR) myelofibrosis (MF). Based on the dose escalation findings in Part 1, imetelstat 9.4 mg/kg dosed every four weeks with ruxolitinib was the selected dose for the dose expansion Part 2 of the study, which is currently enrolling patients.

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"As a telomerase inhibitor, the potential of imetelstat to affect the malignant clone differentiates it from any other drug currently approved or in development for myelofibrosis treatment. These early results also support the potential tolerability of imetelstat and ruxolitinib as a combination therapy and could have significant implications for future development efforts," said Faye Feller, M.D., Executive Vice President, Chief Medical Officer of Geron. "Given these early findings from the IMproveMF study presented at ASH (Free ASH Whitepaper), we are now enrolling Part 2 of the study for dose confirmation and expansion at the highest dose level, imetelstat 9.4 mg/kg every 4 weeks, to further explore and confirm this dosing and schedule in combination with ruxolitinib as a potential frontline therapy in MF."

"Upon diagnosis, intermediate-1 and -2 and high-risk myelofibrosis patients typically receive ruxolitinib as the primary therapy, which reduces enlarged spleens and alleviates symptoms. These early results showing the tolerability of ruxolitinib combined with imetelstat in this patient population are highly encouraging, because as a non-JAK inhibitor treatment option with a potentially novel mechanism of action, imetelstat could provide an additive benefit, affecting the underlying malignant clones implicated in MF progression, when combined with ruxolitinib alone," said John Mascarenhas, M.D., Professor of Medicine at the Icahn School of Medicine at Mount Sinai and a principal investigator on the IMproveMF study, who delivered the oral presentation at ASH (Free ASH Whitepaper).

IMproveMF is an ongoing, multicenter Phase 1/1b trial that aims to evaluate the safety, pharmacokinetics (PK), and clinical activity of imetelstat in combination with ruxolitinib in patients with INT-1/INT-2/HR MF. As of the November 4, 2024 cutoff date, at least three patients had received each imetelstat dose level: Dose Level 1, imetelstat 4.7 mg/kg (n=3); Dose Level 2, imetelstat 6.0 mg/kg (n=3); Dose Level 3, imetelstat 7.5 mg/kg (n=4); and Dose Level 4, imetelstat 9.4 mg/kg (n=7). Ruxolitinib doses were individualized per patient. The PK profiles of imetelstat and ruxolitinib were consistent with previous monotherapy studies of imetelstat and ruxolitinib. At the time of this analysis, the median duration of imetelstat treatment for the seven patients in the imetelstat 9.4 mg/kg cohort was 12.1 weeks (range: 4.1-20.9 weeks).

The combination of imetelstat with ruxolitinib was well-tolerated, and no dose-limiting toxicities were reported at any imetelstat dose level within the first 28 days of Cycle 1. Grade 3 treatment-emergent adverse events (TEAEs) were reported in 47% (8/17) of patients, with anemia reported in 24% (4/17), neutropenia in 18% (3/17), leukopenia in 12% (2/17), and abdominal pain, fatigue, pneumonia and epistaxis each reported in 6% (1/17) of patients. No Grade 4 or 5 TEAESs were reported.

For patients in the 9.4 mg/kg imetelstat dose level selected for dose expansion in Part 2 of the study, hematology values, including hemoglobin, leukocytes, neutrophils and platelets, were stable over time. Across all four dose cohorts, average absolute change from baseline total symptom score (TSS) over week 12 was a median of –5 and maximum absolute reduction from baseline TSS up to Week 24 was a median of –5. A trend for dose-dependent spleen volume reduction (SVR) at Week 24 was observed in the first three doses. Further evidence is needed in the 9.4 mg/mg dose where Week 24 data were not available at the time of this analysis. Preliminary results showed variant allele frequency (VAF) reductions in JAK2, CALR, MPL and high molecular risk driver mutations across the four dose cohorts.

IMproveMF is actively enrolling patients for dose confirmation and expansion (NCT05371964). In parallel, the separate IMpactMF Phase 3 trial is ongoing in MF patients who are relapsed/refractory to JAK inhibitors (NCT04576156). This Phase 3 trial is designed to confirm the results from the IMbark Phase 2 study, where single-agent imetelstat treatment resulted in multiple clinically meaningful benefits, including symptom response and potential improvement in overall survival.

The ASH (Free ASH Whitepaper) presentation, titled "Trial Update from IMproveMF, an Ongoing, Open-Label, Dose-Escalation and -Expansion, Phase 1/1B Trial to Evaluate the Safety, Pharmacokinetics, and Clinical Activity of the Novel Combination of Imetelstat with Ruxolitinib in Patients with Intermediate-1, Intermediate-2, or High-Risk Myelofibrosis (MF)," is available on Geron’s website in the investor section under publications.

About RYTELO (imetelstat)

RYTELO (imetelstat) is an FDA-approved oligonucleotide telomerase inhibitor for the treatment of adult patients with low-to-intermediate-1 risk myelodysplastic syndromes (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.

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.

IMPORTANT SAFETY INFORMATION

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 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

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.

Please see RYTELO (imetelstat) full Prescribing Information, including Medication Guide, available at View Source

On December 10, 2024 Geron Corporation (Nasdaq: GERN), a commercial-stage biopharmaceutical company aiming to change lives by changing the course of blood cancer, reported new analyses presented at the 66 th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting from the IMerge clinical trial in patients with lower-risk myelodysplastic syndromes (LR-MDS) with transfusion-dependent anemia suggesting clinical activity of first-in-class telomerase inhibitor RYTELO (imetelstat) regardless of type or number of prior therapies, as well as favorable patient-reported outcomes (PROs) (Press release, Geron, DEC 10, 2024, View Source [SID1234648979]).

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"These latest IMerge analyses presented at ASH (Free ASH Whitepaper) contribute to a growing body of clinical evidence that support RYTELO as a second-line option in red blood cell transfusion-dependent lower-risk MDS, regardless of prior treatments," said Faye Feller, M.D., Executive Vice President, Chief Medical Officer of Geron. "Additionally, the sustained improvement in fatigue observed in the IMerge Phase 3 patient-reported outcomes population is meaningful for this progressive disease that is characterized by fatigue."

"Patients with red blood cell transfusion-dependent lower-risk MDS often cycle through limited available therapies. The IMerge data presented at ASH (Free ASH Whitepaper) suggesting clinical activity of imetelstat regardless of prior therapies, offers physicians important clinical evidence while assessing sequencing of treatments," said Rami S. Komrokji, M.D., Vice Chair, Malignant Hematology Department, Moffitt Cancer Center, an investigator of the IMerge clinical trial, who presented IMerge results at ASH (Free ASH Whitepaper). "Further, anemia and fatigue remain two of the most burdensome symptoms of lower-risk MDS, and patient-reported outcomes such as improvement in fatigue and maintenance of quality of life and anemia symptoms may inform treatment choices as we aim to improve outcomes for our patients."

"Effect of Prior Treatments on the Clinical Activity of Imetelstat in Transfusion-Dependent Patients with Erythropoiesis-Stimulating Agent, Relapsed or Refractory/Ineligible Lower-Risk Myelodysplastic Syndromes"

This oral presentation reported findings from analyses investigating the effects of prior therapies on the clinical activity of imetelstat using pooled data from IMerge Phase 2, Phase 3, and the QTc substudy. Of the 226 total imetelstat-treated LR-MDS patients included in this analysis, 90% had prior treatment with an erythropoiesis-stimulating agent (ESA), 12% had prior treatment with lenalidomide, 16% had prior treatment with luspatercept and 10% had prior treatment with a hypomethylating agent (HMA). Across this pooled population, median imetelstat treatment duration was 33.6 weeks (range: 0.1-260.1 weeks).

Imetelstat clinical activity was observed in the pooled patient population consistent with that of the IMerge Phase 3 pivotal trial with regards to safety and critical efficacy measures that include ≥8-week red blood cell transfusion independence (RBC-TI), ≥24-week RBC-TI, RBC transfusion reduction ≥4 U/8 weeks and hemoglobin rise ≥1.5 g/dL/8 weeks.

The results suggest that patients who were ESA ineligible, patients who had prior treatment with luspatercept or lenalidomide, or patients who had prior treatment with ESAs followed by luspatercept or lenalidomide experienced clinical benefit from imetelstat treatment similar to that demonstrated in the IMerge Phase 3 pivotal trial. Patients who had prior treatment with HMAs, or with ESAs followed by HMAs, showed modest clinical activity with imetelstat. Overall, while these analyses were limited by the small number of patients in each group, imetelstat showed clinical activity regardless of prior ESA response status and regardless of the number of prior lines of therapy.

"Initial Results from the QTc Substudy of the IMerge Phase 3 Trial Demonstrate Clinically Meaningful Efficacy, Manageable Safety, and Absence of Proarrhythmic Risk in Patients with Lower-Risk Myelodysplastic Syndromes Who Received Prior Therapies Beyond Erythropoiesis Stimulating Agents"

This poster presentation reports initial results from the ventricular repolarization (QTc) substudy of IMerge conducted per FDA guidance. This substudy differed from the IMerge Phase 3 trial in its crossover design, the inclusion of patients with del(5q) MDS, and by allowing prior lenalidomide and HMA therapy besides ESAs. The QTc substudy population comprised 53 treated patients (n=35 imetelstat, n=18 placebo). As of the data cutoff on May 10, 2024, 16 of 18 placebo recipients crossed over to receive imetelstat. Median treatment duration on imetelstat, including crossover (n=51) was 29.3 weeks; median duration in the imetelstat group (n=35) was 37.0 weeks and median duration in the crossover group (n=16) was 27.9 weeks.

In the total imetelstat population (n=51), 41% of patients (n=21) achieved ≥8-week RBC-TI, 25% of patients (n=13) achieved ≥24-week RBC-TI, 41% of patients (n=21) achieved hematologic improvement-erythroid (HI-E) per IWG 2018 criteria, 35% of patients (n=18) had hemoglobin rises ≥1.5 g/dL lasting ≥8 weeks and 75% of patients (n=38) had RBC transfusion reductions ≥4 U/8 weeks.

In patients with prior luspatercept, lenalidomide or HMA (azacitidine or decitabine) treatment, 30% (7/23), 38% (5/13), and 21% (3/14) of patients achieved ≥8-week RBC-TI, and 22% (5/23) 15% (2/13), and 14% (2/14) achieved ≥24-week RBC-TI, respectively. Patients treated with imetelstat showed no treatment-related changes in absolute and change in QTcF nor clinically meaningful effects on cardiac repolarization compared with placebo.

The poster concludes that in this QTc substudy, imetelstat was associated with an absence of proarrhythmic risk, durable RBC-TI, transfusion reduction, clinically meaningful increases in hemoglobin, and a safety profile comparable to the overall population of the pivotal Phase 3 IMerge trial. RBC-TI was attained in imetelstat-treated patients who received prior therapies with HMA, luspatercept and lenalidomide, supporting the use of imetelstat in patients with relapsed or refractory LR-MDS regardless of prior therapies.

"Correlation of Patient-Reported Outcomes with Red Blood Cell Transfusion Reduction and Rise in Hemoglobin in Patients with Lower-Risk Myelodysplastic Syndromes in the IMerge Trial"

This poster reports on the exploratory PRO analysis from IMerge Phase 3, with a data cutoff of October 2022. PROs were assessed with validated using Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), Functional Assessment of Cancer Therapy-Anemia (FACT-An), and Quality of Life in Myelodysplasia Scale (QUALMS) questionnaires. Sustained meaningful improvement in fatigue was defined as a ≥3-point increase in FACIT-Fatigue score for ≥2 consecutive assessments. The PRO population (n=175) included all patients in the intent-to-treat population who had FACIT-Fatigue data at baseline and consisted of 118 imetelstat-treated patients and 57 patients who received placebo.

In the subgroup analysis, more patients treated with imetelstat than placebo reported sustained improvement in fatigue regardless of ring sideroblast (RS) status, prior transfusion burden and baseline serum EPO levels. Additionally, improvement in fatigue was seen in more patients who responded to imetelstat versus those who did not across measures of response including RBC-TI, hemoglobin rise and transfusion reduction. The QUALMS and FACT-An analyses suggested that imetelstat maintained QOL and anemia symptoms, while placebo recipients experienced worsening QOL and anemia symptoms.

The poster concludes that data from the pivotal IMerge phase 3 trial showed that improvement in fatigue with imetelstat was associated with reduced transfusion burden and a rise in hemoglobin and that imetelstat appears to offer the advantage of sustained RBC-TI benefit while maintaining QOL in patients with LR-MDS with TD anemia.

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

About RYTELO (imetelstat)

RYTELO (imetelstat) is an FDA-approved oligonucleotide telomerase inhibitor for the treatment of adult patients with low-to-intermediate-1 risk myelodysplastic syndromes (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.

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.

IMPORTANT SAFETY INFORMATION

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 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

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.

Please see RYTELO (imetelstat) full Prescribing Information, including Medication Guide, available at View Source

On December 10, 2024 Enterome, a clinical-stage company developing first-in-class immunomodulatory drugs for cancer based on its unique Mimicry platform, reported new clinical data from the ongoing Phase 1/2 ‘SIDNEY’ trial evaluating EO2463 in patients with indolent Non Hodgkin Lymphoma (Press release, Enterome, DEC 10, 2024, View Source [SID1234648978]).

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The data were presented in two posters at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Conference by Dr. Villasboas Bisneto, M.D., hematologist and oncologist at Mayo Clinic, and Dr. Stephen Smith, M.D., hematologist and oncologist at Fred Hutchinson Cancer Center.

Enterome is also holding a webinar on December 12, 2024 for external audiences in order to run through the data sets. See details at the end of this release.

The Phase 1/2 SIDNEY trial (EONHL1-20) investigates EO2463, an off-the-shelf immunotherapy targeting four B cell antigens and based on Enterome’s OncoMimic peptides, in patients with frequent forms of indolent Non-Hodgkin Lymphoma. In Cohort 2 of the SIDNEY trial, patients with newly diagnosed, asymptomatic follicular lymphoma, received EO2463 monotherapy as an alternative to the standard "watch-and-wait" approach. With most patients still on study treatment, an objective response rate of 46% has been observed in the first 13 patients, including 15% complete responses and 31% partial responses. Consistent with observations from the safety lead-in cohort, the treatment was well tolerated, with no severe adverse events, suggesting EO2463 may offer a safe treatment option for patients with early-stage disease.

A biomarker analysis was conducted in Cohort 1 (EO2463 in monotherapy and in combination with lenalidomide/rituximab, in patients with relapsed/refractory disease) to explore whether early CD8+ T cell expansion in response to EO2463 administration could serve as a predictor of later clinical benefit. The current assessment indicates that the biomarker as applied (measuring fast expansion of EO2463 specific CD8 T cells) can predict for clinical response, both for EO2463 monotherapy, and for EO2463 in combination with lenalidomide + rituximab.

Jan Fagerberg, Chief Medical Officer of Enterome, commented, "These new data provide encouraging indications that EO2463 can safely induce meaningful responses in patients with newly diagnosed follicular lymphoma typically managed with observation alone, addressing an important unmet need. Additionally, our biomarker findings open up possibilities for precision immunotherapy by identifying patients most likely to benefit early in their treatment course."

Pierre Bélichard, CEO of Enterome, added, "These promising results from Cohort 2 in the SIDNEY trial mark an important step in our commitment to providing early therapeutic options for patients who would usually not receive immediate treatment due to the absence of safe and effective therapies. We look forward to advancing EO2463 through the SIDNEY trial and to expanding our work with OncoMimics immunotherapies in other blood cancer types."

Details of the poster presentations:

Abstract #1616

Title: EO2463 Peptide Immunotherapy in Patients with Indolent NHL: A Phase 1 Exploration of a Response Biomarker for EO2463 Monotherapy and EO2463 in Combination with Lenalidomide/Rituximab
Presenting Author: Jose Caetano (JC) Villasboas, MD Mayo Clinic
Session: 622. Lymphomas: Translational – Non-Genetic: Poster I

Abstract #4395

Title: EO2463 Peptide Immunotherapy in Patients with Newly Diagnosed Asymptomatic Follicular Lymphoma Results in Monotherapy Objective Clinical Responses Linked with Anti-Peptide Specific CD8 Memory T Cell Responses: The EONHL1-20/SIDNEY Study
Presenting Author: Stephen Smith, M.D., UW Medicine, Fred Hutchinson Cancer Research Center
Session: 623. Mantle Cell, Follicular, Waldenstrom’s, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster III

About EONHL1-20/SIDNEY:

SIDNEY (EONHL1-20) is a Phase 1/2 multicenter, open-label, first-in-human study of EO2463 as a monotherapy and in combination with lenalidomide and/or rituximab for the treatment of patients with iNHL. The study aims to assess the safety, tolerability, immunogenicity, and preliminary efficacy of EO2463 monotherapy and combination therapy in approximately 60 patients with follicular lymphoma (FL) and marginal zone lymphoma (MZL).

For more information on the study, visit www.Clinicaltrials.gov, reference: NCT04669171.

About EO2463:

EO2463 is an innovative, off-the-shelf immunotherapy candidate that combines four synthetic OncoMimic peptides. These non-self, microbial-derived peptides correspond to CD8 HLA-A2 epitopes that exhibit molecular mimicry with the B lymphocyte-specific lineage markers CD20, CD22, CD37, and CD268 (BAFF receptor). EO2463 also includes the helper peptide (CD4+ epitope) universal cancer peptide 2 (UCP2).

The unique ability of EO2463 immunotherapy to selectively target multiple B cell markers enables the destruction of malignant B lymphocytes that are abundant in iNHL. By ensuring broad target coverage across malignant B cells, this novel approach aims to simultaneously improve safety and maximize efficacy, reducing the tumor cells’ capacity to develop immune-resistance mechanisms.

Details of the webinar, please register at [email protected] to attend.

Date: 12 December 2024

Time: 7.30am-8.30am PT / 9.30am-10.30am Central US time / 3.30pm-4.30pm UK / 4.30pm-5.30pm CET

Presenters:

Jose Caetano (JC) Villasboas, MD Mayo Clinic

Pierre Belichard PhD, CEO, Enterome

Laurent Chene PhD, Head of Drug Discovery, Enterome

Jan Fagerberg, MD, PhD, CMO Enterome