On November 5, 2024 Syndax Pharmaceuticals (Nasdaq:SNDX) reported that multiple abstracts evaluating revumenib, an oral small molecule menin inhibitor, have been accepted for oral presentation at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held in San Diego, California, December 7-10, 2024 (Press release, Syndax, NOV 5, 2024, View Source [SID1234647743]). The oral presentations will highlight data evaluating the safety and efficacy of revumenib as monotherapy or in combination for the treatment of patients with acute leukemias.

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Copies of the abstracts are now available online on the ASH (Free ASH Whitepaper) website.

"The data being presented this year at ASH (Free ASH Whitepaper) demonstrate Syndax’s commitment to develop revumenib as a practice-changing therapy for adult and pediatric patients with acute leukemias," said Neil Gallagher, M.D., Ph.D., President, Head of Research and Development at Syndax. "We look forward to presenting these data and continuing to rapidly advance the development of revumenib for adult and pediatric acute leukemia patients who may respond to menin inhibition, such as patients with KMT2Ar or mNPM1 alterations."

The FDA has granted Priority Review for the New Drug Application (NDA) for revumenib for the treatment of adult and pediatric patients with relapsed or refractory (R/R) KMT2A-rearranged (KMT2Ar) acute leukemia. The NDA is being reviewed under the FDA’s Real-Time Oncology Review Program (RTOR) and has a Prescription Drug User Fee Act (PDUFA) target action date of December 26, 2024.

In March 2024, the Company announced the completion of enrollment in the final AUGMENT-101 pivotal trial cohort in patients with R/R mutant nucleophosmin (mNPM1) acute myeloid leukemia (AML). Topline data is expected in the fourth quarter of 2024 and could support a supplemental NDA filing for revumenib in R/R mNPM1 AML in the first half of 2025.

The Company will host an in-person investor event, along with a live webcast, to discuss the latest data supporting the Company’s pipeline on Monday, December 9, 2024 at 7:00 a.m. PT/ 10:00 a.m. ET during the ASH (Free ASH Whitepaper) Annual Meeting. The live webcast will be available on the Investor section of the Company’s website at www.syndax.com, where a replay of the event will also be available for a limited time.

Overview of Abstracts Accepted for Presentation at 66th ASH (Free ASH Whitepaper) Annual Meeting

New Data from Phase 2 Portion of the AUGMENT-101 Trial of Revumenib in R/R KMT2Ar Acute Leukemia

Syndax previously presented positive data from the protocol-defined interim analysis of the pivotal Phase 2 portion of the AUGMENT-101 trial of revumenib in adult and pediatric patients with R/R KMT2Ar AML and acute lymphoid leukemia (ALL). The trial met its primary endpoint at the protocol-defined interim analysis with a complete remission (CR) or a CR with partial hematological recovery (CRh) rate of 23% (13/57; 95% CI: 12.7-35.8; one-sided p-value = 0.0036) among the 57 efficacy evaluable patients in the KMT2Ar cohort as of the July 2023 data cutoff (DCO) date.

This updated analysis (DCO: February 2024) includes 116 patients in the Phase 2 safety population (an increase of 22 patients who were enrolled and treated with revumenib after the previous July 2023 DCO), and 97 patients in the Phase 2 efficacy population (an increase of 40 patients who were newly enrolled or who reached sufficient follow-up after the previous July 2023 DCO).

Within this larger efficacy population of patients with R/R KTM2Ar acute leukemia from the Phase 2 portion of the AUGMENT-101 trial (n=97), 23% (22/97) of patients achieved CR/CRh (95% CI: 15%-32%). The CRc rate was 42% (95% CI: 32%-53%) and the ORR was 64% (95% CI: 54%-73%). Among patients with measurable residual disease (MRD) results available, 61% (11/18) of CR/CRh responders and 58% (21/36) of CRc responders achieved MRD negativity. Of the 62 patients who achieved ORR, 34% (21/62) proceeded to hematopoietic stem cell transplantation (HSCT). Nine patients resumed revumenib post-HSCT.

The median duration of response among the 22 CR/CRh responders was 6.4 months (95% CI: 1.9 mo-NR). Of note, among the 13 CR/CRh responders from the interim analysis, the median duration of CR/CRh extended to 13.0 months (95% CI: 3.4 mo–NR) after seven additional months of follow-up (DCO: February 2024). Five of these patients remained in follow-up with no relapse or death as of the data cutoff.

Within the larger safety population of patients with R/R KTM2Ar acute leukemia from the Phase 2 portion of the AUGMENT-101 trial (n=116), revumenib was generally well tolerated and the safety profile was consistent with the Company’s previously reported data. Treatment-emergent adverse events (TEAEs) and treatment-related adverse events (TRAEs) leading to treatment discontinuation were low at 14% (16/116) and 5% (6/116), respectively. The most common Grade ≥3 TEAEs were consistent with previously reported data. Grade 3 treatment-emergent differentiation syndrome (DS) was observed in 14% (16/116) of patients and one patient (1%) experienced a Grade 4 DS. Grade 3 treatment-emergent QTc prolongation was observed in 13% (15/116) of patients, with no Grade 4 or Grade 5 events.

Details for the oral presentation are as follows:

Abstract Number: 211
Title: Updated Results and Longer Follow-up from the AUGMENT-101 Phase 2 Study of Revumenib in All Patients with Relapsed or Refractory (R/R) KMT2Ar Acute Leukemia
Presenter: Ibrahim Aldoss, M.D.
Session Name: 616. Acute Myeloid Leukemias: Investigational Drug and Cellular Therapies: Menin Inhibitors in AML
Session Date: Saturday, December 7, 2024
Session Time: 2:00 PM – 3:30 PM
Presentation Time: 2:00 PM

New Results from Phase 1/2 SAVE Trial of Revumenib in Combination with Venetoclax and Decitabine/Cedazuridine in R/R AML

The Phase 1/2 SAVE trial is an investigator-sponsored trial testing an all-oral regimen of revumenib, venetoclax and the hypomethylating agent (HMA) ASTX727 (decitabine/cedazuridine) in children and adults with R/R AML or mixed-lineage acute leukemia (MPAL) harboring either KMT2Ar, NUP98r or mNPM1 alterations.

As of the latest data cutoff (July 2024), 26 patients were enrolled in the trial. The median age was 35 years (range: 12-79). At baseline, 11 patients (42%) had KMT2Ar, 10 patients (38%) had mNPM1, and five patients (20%) had NUP98r. The median prior lines of therapy was three (range: 1-5); 17 patients (65%) had prior venetoclax, 11 (42%) had prior HSCT, and two had received a prior menin inhibitor.

The all-oral combination resulted in high rates of remission in patients with R/R KMT2Ar, mNPM1, or NUP98r AML. The ORR was 88% (23/26), with a CR/CRh rate of 58% (15/26). MRD status was available in 14 of the 15 patients who achieved a CR/CRh, 93% (13/14) of whom were MRD negative. In patients with MRD status available who achieved a response, 74% (17/23) were MRD negative. Twelve patients (46%) received HSCT following this combination, with three patients resuming revumenib post-HSCT.

With a median follow-up of 6.6 months, the 6-month relapse-free survival was 59% (95% CI: 26%-81%) and overall survival was 74% (95% CI: 39%-83%). The median duration of response in those with CR/CRh was not reached. Two patients had completed maintenance post-HSCT and remained in remission at the time of the data cutoff.

The combination was generally well tolerated. The most common (>20%) Grade ≥3 TEAEs were febrile neutropenia (46%) and lung infection (42%), while Grade ≥3 TRAEs (any agent) were thrombocytopenia (12%), neutropenia (8%), QT prolongation (8%), and DS (4%). No patient experienced Grade 4 or 5 DS, and all DS events were resolved with steroids.

In addition to the R/R cohort, a frontline cohort is now enrolling patients.

Details for the oral presentation are as follows:

Abstract Number: 216
Title: Phase I/II Study of the All-Oral Combination of Revumenib (SNDX-5613) with Decitabine/Cedazuridine (ASTX727) and Venetoclax (SAVE) in R/R AML
Presenter: Ghayas C. Issa, M.D.
Session Name: 616. Acute Myeloid Leukemias: Investigational Drug and Cellular Therapies: Menin Inhibitors in AML
Session Date: Saturday, December 7, 2024
Session Time: 2:00 PM – 3:30 PM
Presentation Time: 3:15 PM

Initial Results from INTERCEPT Trial of Revumenib as Pre-Emptive Therapy for MRD Positive AML

INTERCEPT is an investigator-sponsored platform trial evaluating the use of novel therapies, including revumenib, to target MRD and early relapse in AML. This proof-of-concept trial is exploring whether targeting MRD in patients with progressive AML may be an effective approach to maintaining patients in first (CR1) or second remission (CR2).

As of the July 2024 data cut off, nine patients with MRD relapse (eight with mNPM1 and one with KMT2Ar) were enrolled in the safety cohort and received revumenib. The median age was 62 years; seven were in CR1, two in CR2; three had prior venetoclax exposure and six had prior intensive therapy.

In a preliminary analysis of the eight mNPM1 patients who received revumenib, five of the eight patients had MRD reduction, including three who achieved MRD negativity within six cycles. In the nine-patient safety cohort, dose-limiting toxicities included reversible Grade 3 QTc prolongation in two patients; neither de-escalation nor elimination were mandated and 276 mg of revumenib BID was therefore considered safe for further expansion. These data support revumenib’s safety profile and activity in patients with mNPM1 MRD relapse.

Details for the oral presentation are as follows:

Abstract Number: 223
Title: Revumenib as Pre-emptive Therapy for Measurable Residual Disease in NPM1 mutated or KMT2A-rearranged Acute Myeloid Leukemia: A Domain of the Multi-Arm ALLG AMLM26 Intercept Platform trial
Presenter: Sun Loo, M.B.B.S.
Session Name: 619. Acute Myeloid Leukemias: Disease Burden and Minimal Residual Disease in Prognosis and Treatment: Measurable Residual Disease in AML in 2024 and Beyond
Session Date: Saturday, December 7, 2024
Session Time: 2:00 PM – 3:30 PM
Presentation Time: 2:00 PM

About Revumenib
Revumenib is an oral, small molecule inhibitor of the menin-KMT2A binding interaction that is being developed for the treatment of KMT2A-rearranged (KMT2Ar), also known as mixed lineage leukemia rearranged or MLLr, acute leukemias including acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML), and mutant NPM1 AML. The Journal of Clinical Oncology published results from the Phase 2 AUGMENT-101 trial of revumenib in R/R KMT2Ar acute leukemia showing the trial met its primary endpoint.

Revumenib was previously granted Orphan Drug Designation for the treatment of AML, ALL and acute leukemias of ambiguous lineage (ALAL) by the U.S. FDA and for the treatment of AML by the European Commission. The U.S. FDA also granted Fast Track designation to revumenib for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation and Breakthrough Therapy Designation for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement.

On November 5, 2024 Syndax Pharmaceuticals (Nasdaq:SNDX), reported that multiple abstracts evaluating Niktimvo (axatilimab-csfr), an anti-CSF-1R antibody for the treatment of chronic graft-versus-host disease (GVHD), have been accepted for presentation at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting being held in San Diego, California, December 7-10, 2024 (Press release, Syndax, NOV 5, 2024, View Source [SID1234647742]). The presentations will highlight a secondary analysis of overall and organ-specific responses and findings from an exposure-response analysis in patients with chronic GVHD from the pivotal Phase 2 AGAVE-201 trial of Niktimvo, as well as preclinical data further characterizing the Niktimvo mechanism of action.

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Copies of the abstracts are now available on the ASH (Free ASH Whitepaper) website.

"Further analyses of data from the pivotal AGAVE-201 trial continue to reinforce our confidence in Niktimvo’s ability to meaningfully advance the chronic GVHD treatment paradigm," said Neil Gallagher, M.D., Ph.D., President, Head of Research and Development at Syndax. "In collaboration with our partner Incyte, we look forward to providing clinicians and patients with a new approach to treating chronic GVHD and continuing to advance our clinical development programs investigating the potential use of Niktimvo earlier in the treatment of chronic GVHD as well as in other inflammatory and fibrotic diseases including idiopathic pulmonary fibrosis."

The Company will host an in-person investor event, along with a live webcast, to discuss the latest data supporting the Company’s pipeline on Monday, December 9, 2024 at 7:00 a.m. PT/ 10:00 a.m. ET during the ASH (Free ASH Whitepaper) Annual Meeting. The live webcast will be available on the Investor section of the Company’s website at www.syndax.com, where a replay of the event will also be available for a limited time.

Overview of Presentations

AGAVE-201 Secondary Analysis

Incyte and Syndax previously announced positive topline data from the pivotal AGAVE-201 trial of Niktimvo in adult and pediatric patients with refractory chronic GVHD who received at least two prior lines of systemic therapy. The trial met the primary endpoint across all dose cohorts. Among patients who received Niktimvo at the approved dose of 0.3 mg/kg every two weeks (N=79), the overall response rate (ORR) was 75% within the first six months of treatment. Of the patients who had a response, an estimated 60% of patients maintained a response at 12 months (measured from first response until new systemic therapy or death, based on the Kaplan Meier estimate). Results from the pivotal AGAVE-201 trial were recently published in the New England Journal of Medicine.

The abstract published today highlights new data from the secondary analysis of patients in the 0.3 mg/kg dose cohort which show that more than half of responders had an overall clinical response by day 56 of treatment and more than half of those with at least a seven-point improvement in their modified Lee Symptom Scale (mLSS) score had improvement by day 56 of treatment. In the 0.3 mg/kg dose cohort, the median time to organ-specific responses ranged from 1.2 to 3.7 months across organs. Lower gastrointestinal (GI), upper GI, esophagus, liver, and joints/fascia were typically the fastest organs to respond, whereas lung, mouth, eye, and skin responses were slower due to the highly fibrotic nature of these organ manifestations. Previously reported results from the AGAVE-201 trial showed that Niktimvo was generally well tolerated.

Details for the oral presentation are as follows:

Abstract Number: 98
Title: Dynamics of Overall and Organ-Specific Responses to Axatilimab in Chronic Graft-Versus-Host Disease: Analysis From the AGAVE-201 Study
Presenter: Hannah Choe, M.D.
Session Name: 722. Allogeneic Transplantation: Acute and Chronic GVHD and Immune Reconstitution: Predicting and Treating Acute and Chronic GVHD
Session Date: Saturday, December 7, 2024
Session Time: 9:30 AM – 11:00 AM
Presentation Time: 9:45 AM

Pooled Exposure-Response Analysis

The abstract published today describes the exposure-efficacy and exposure-safety relationships in patients with chronic GVHD treated with distinct doses of axatilimab in the pivotal Phase 2 AGAVE-201 trial and the prior Phase 1/2 trial. For the exposure-efficacy analysis (n=239), ORR and mLSS responses were associated with axatilimab exposure, with lower axatilimab exposure increasing the odds of response. For the exposure-safety analysis (n=278), all safety endpoints except infections of unspecified etiology were associated with axatilimab exposure, with higher axatilimab exposure increasing the odds of treatment-emergent adverse events. These results provide rationale for the 0.3 mg/kg every two weeks regimen, which is the FDA approved dose of axatilimab (Niktimvo).

Details for the poster presentation are as follows:

Abstract Number: 2140
Title: Exposure-Response Relationships for Axatilimab, a Humanized Monoclonal Antibody Targeting CSF-1R, in Patients With Chronic Graft-Versus-Host Disease
Presenter: Yan-ou Yang, Ph.D.
Session Name: 722. Allogeneic Transplantation: Acute and Chronic GVHD and Immune Reconstitution: Poster I
Session Date: Saturday, December 7, 2024
Presentation Time: 5:30 PM – 7:30 PM

Preclinical Mechanism of Action Data

Preclinical data detailing the anti-inflammatory and anti-fibrotic mechanism through which axatilimab is thought to impact the disease process in chronic GVHD will be presented.

Details for the poster presentation are as follows:

Abstract Number: 1147
Title: Axatilimab Abrogates Inflammatory Cytokines and Chemokines and Interrupts the Differentiation of Monocytes to Macrophages, a Pathogenic Driver of Inflammation and Fibrosis in cGVHD
Presenter: Anamika Bajpai, Ph.D.
Session Name: 201. Granulocytes, Monocytes, and Macrophages: Poster I
Session Date: Saturday, December 7, 2024
Presentation Time: 5:30 PM – 7:30 PM

About AGAVE-201

The global AGAVE-201 dose-ranging trial evaluated the efficacy, safety, and tolerability of axatilimab in 241 adult and pediatric patients with recurrent or refractory active chronic GVHD whose disease had progressed after two or more prior therapies. Patients were randomized to one of three treatment groups that investigated a distinct dose of axatilimab administered at 0.3 mg/kg every two weeks, 1.0 mg/kg every two weeks or 3.0 mg/kg every four weeks. The trial’s primary endpoint was the proportion of patients in each dose group who achieved an objective response as defined by 2014 NIH Consensus Criteria for chronic GVHD by cycle 7 day 1. Secondary endpoints included duration of response, percent reduction in daily steroid dose, organ specific response rates and validated quality-of-life assessments using the Modified Lee Symptom Scale.

For more information about AGAVE-201, visit View Source

About Niktimvo (axatilimab-csfr)

Niktimvo (axatilimab-csfr) is a first-in-class anti-CSF-1R antibody approved for use in the U.S. for the treatment of chronic graft-versus-host disease (GVHD) after failure of at least two prior lines of systemic therapy in adult and pediatric patients weighing at least 40 kg (88.2 lbs).

In the U.S., Niktimvo will be co-commercialized by Syndax and Incyte. Incyte has exclusive commercialization rights for Niktimvo outside of the U.S.

In 2016, Syndax licensed exclusive worldwide rights to develop and commercialize axatilimab from UCB. In September 2021, Syndax and Incyte entered into an exclusive worldwide co-development and co-commercialization license agreement for axatilimab in chronic GVHD and any future indications.

Axatilimab is being studied in frontline combination trials in chronic GVHD – a Phase 2 combination trial with ruxolitinib (NCT06388564) is underway and a Phase 3 combination trial with steroids is in preparation. Axatilimab is also being studied in an ongoing Phase 2 trial in patients with idiopathic pulmonary fibrosis (NCT06132256).

Niktimvo is a trademark of Incyte.
All other trademarks are the property of their respective owners.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS
Infusion-Related Reactions
Niktimvo (axatilimab-csfr) can cause infusion-related reactions. Infusion-related reactions, including hypersensitivity reactions, occurred in 18% of patients who received Niktimvo in the clinical trial (AGAVE-201), with Grade 3 or 4 reactions in 1.3%.

Premedicate with an antihistamine and an antipyretic for patients who have previously experienced an infusion-related reaction to Niktimvo. Monitor patients for signs and symptoms of infusion-related reactions, including fever, chills, rash, flushing, dyspnea, and hypertension. Interrupt or slow the rate of infusion or permanently discontinue Niktimvo based on severity of the reaction.

Embryo-Fetal Toxicity
Based on its mechanism of action, Niktimvo may cause 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 Niktimvo and for 30 days after the last dose.

ADVERSE REACTIONS
Serious adverse reactions occurred in 44% of patients who received Niktimvo (N=79). Serious adverse reactions in >2 patients included infection (pathogen unspecified) (14%), viral infection (14%) and respiratory failure (5.1%). Permanent discontinuation of Niktimvo due to an adverse reaction occurred in 10% of patients and dose reduction due to adverse reaction occurred in 8% of patients. Dose interruptions due to an adverse reaction occurred in 44% of patients. The adverse reactions leading to dose interruption in >2 patients were viral infection, infection (pathogen unspecified), bacterial infection, musculoskeletal pain, and pyrexia.

The most common (≥15%) adverse reactions, including laboratory abnormalities, were increased aspartate aminotransferase (AST), infection (pathogen unspecified), increased alanine aminotransferase (ALT), decreased phosphate, decreased hemoglobin, viral infection, increased gamma glutamyl transferase (GGT), musculoskeletal pain, increased lipase, fatigue, increased amylase, increased calcium, increased creatine phosphokinase (CPK), increased alkaline phosphatase (ALP), nausea, headache, diarrhea, cough, bacterial infection, pyrexia, and dyspnea.

Clinically relevant adverse reactions in <10% of patients who received Niktimvo included:

Eye disorders: periorbital edema
Skin and subcutaneous skin disorders: pruritus
Vascular disorders: hypertension
Immunogenicity: Anti-Drug Antibody–Associated Adverse Reactions
Across treatment arms in patients with cGVHD who received Niktimvo in clinical trials, among the patients who developed anti-drug antibodies (ADAs), hypersensitivity reactions occurred in 26% (13/50) of patients with neutralizing antibodies (NAb) and in 4% (2/45) of those without NAb.

USE IN SPECIFIC POPULATIONS
Lactation
Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment and for 30 days after the last dose of Niktimvo.

Females and Males of Reproductive Potential
Pregnancy Testing
Verify pregnancy status in females of reproductive potential prior to initiating Niktimvo.

Contraception
Females
Advise females of reproductive potential to use effective contraception during treatment with Niktimvo and for 30 days after the last dose of Niktimvo.

DOSAGE AND ADMINISTRATION
Dosage Modifications for Adverse Reactions
Monitor aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatine phosphokinase (CPK), amylase, and lipase prior to the start of Niktimvo therapy, every 2 weeks for the first month, and every 1 to 2 months thereafter until abnormalities are resolved. See Table 1 in the Prescribing Information for more recommendations.

On November 5, 2024 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS’’ or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported that data from its Phase 2a trial of SLS009, a highly selective CDK9 inhibitor, in relapsed/refractory acute myeloid leukemia (r/r AML) will be presented at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, which is being held on December 7 –10, 2024, in San Diego, California (Press release, Sellas Life Sciences, NOV 5, 2024, View Source;Exposition-2024/default.aspx [SID1234647741]).

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"We are excited to have SLS009 featured at the 2024 ASH (Free ASH Whitepaper) meeting and are pleased with the very promising safety and efficacy results from the Phase 2a trial in r/r AML," said Angelos Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "Treatment with SLS009 in combination with azacitidine and venetoclax was well tolerated and led to a 50% response rate in the selected optimal dose. Clinical activity was even higher in patients with AML-myelodysplasia-related changes (AML-MRC) and in particular those with ASXL1 mutations, suggesting that this subset of patients may exhibit preferential sensitivity to SLS009. These findings contribute to the growing evidence supporting the potential of SLS009 to address unmet needs in difficult-to-treat populations, and future development efforts will focus on further exploring its impact in patients with AML-MRC."

Poster presentation details:

Title: Phase 2a Study of SLS009, a Highly Selective CDK9 Inhibitor, In Combination with Azacitidine and Venetoclax for Relapsed/Refractory Acute Myeloid Leukemia After Prior Venetoclax Treatment

Session Date and Time: Sunday, December 8, 2024, 6:00 PM – 8:00 PM PST

Session Title: Acute Myeloid Leukemias: Investigational Drug and Cellular Therapies: Poster II

Location: San Diego Convention Center, Halls G-H

Lead Author: Joshua F. Zeidner, MD, University of North Carolina, Lineberger Comprehensive Cancer Center, Chapel Hill, NC

Abstract Number: 2877

The study enrolled 30 patients across three dosing levels (DLs) of SLS009:45 mg IV QW, DL2: 60 mg IV QW, and DL3: 30 mg IV BIW. SLS009 was well-tolerated across the DLs tested with no dose-limiting toxicities (DLTs) observed. Among 29 evaluable pts, 16 (55%) had ≥50% reduction in bone marrow (BM) blasts compared to baseline (DL1: 60%; DL2: 33%; DL3: 80%). Nine (31%) patients achieved an overall response (i.e., CR+CRi+MLFS), including 5 (17%) who achieved CR/CRi. The response rates per dose level were 10% in DL1, 33% in DL2, and 50% in DL3. All 9 responders had AML- Myelodysplasia Related (AML-MR) (9/23 of AMLMR pts responded) and 8/15 pts (53%) with somatic MR mutations responded. Among those with ASXL1 mutations, 5/9 (56%) achieved an overall response. 2/9 (22%) with TP53 mutations achieved a response including one patient with concomitant TP53 and ASXL1 mutation who had an ongoing response at data cut-off. Fifteen patients were still alive at the time of the data cutoff and the median OS for the trial has not been reached.

For more information on the study, visit clinicaltrials.gov identifier NCT04588922.

On November 5, 2024 Cartesian Therapeutics, Inc. (NASDAQ: RNAC) (the "Company"), a clinical-stage biotechnology company pioneering mRNA cell therapy for autoimmune diseases, reported that safety and tolerability data from patients treated with Descartes-08 will be featured during a poster presentation at the upcoming 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, being held December 7-10, 2024 in San Diego (Press release, Cartesian Therapeutics, NOV 5, 2024, View Source [SID1234647740]). A copy of the abstract is available on the ASH (Free ASH Whitepaper) website at www.hematology.org.

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Descartes-08, Cartesian’s lead mRNA cell therapy candidate, is an autologous mRNA-engineered chimeric antigen receptor T-cell therapy (mRNA CAR-T) product candidate targeting B-cell maturation antigen (BCMA).

Details of the poster presentation are as follows:

Publication Number: 2080
Title: Safety and Tolerability of BCMA-Directed mRNA CAR T-Cell Therapy in Multiple Myeloma and Autoimmune Diseases
Presenter: Miloš Miljković, M.D., M.Sc., Chief Medical Officer, Cartesian Therapeutics
Session Name: 704. Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities: Poster I
Session Date/Time: Saturday, December 7, 2024, 5:30-7:30 p.m. PT
Location: San Diego Convention Center, Halls G-H
In addition, the poster was selected for inclusion in the ASH (Free ASH Whitepaper) Poster Walk on Blood Immunology & Cellular Therapy: Advancing Innovations and Translational Insights. The Poster Walk, which aims to highlight cutting-edge emerging science featured at the meeting, will take place on Monday, December 9, 2024, at 7:30 a.m. PT in the Blood Journal Studio located in the Poster Hall.

About Descartes-08
Descartes-08, Cartesian’s lead mRNA cell therapy candidate, is an autologous mRNA-engineered chimeric antigen receptor T-cell therapy (mRNA CAR-T) product targeting B-cell maturation antigen (BCMA) in clinical development for generalized myasthenia gravis (MG) and systemic lupus erythematosus. In contrast to conventional DNA-based CAR T-cell therapies, mRNA CAR-T administration is designed so that it does not require preconditioning chemotherapy, can be administered in the outpatient setting, and does not carry the risk of genomic integration associated with cancerous transformation. Descartes-08 has been granted Orphan Drug Designation and Regenerative Medicine Advanced Therapy Designation by the U.S. Food and Drug Administration for the treatment of MG.

On November 5, 2024 Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL), a commercial stage biotechnology company focused on hematologic disorders and cancer, reported upcoming presentations of six posters highlighting data from their commercial and clinical-stage hematology-oncology portfolio at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition being held December 7-10, 2024, in San Diego, California and virtually (Press release, Rigel, NOV 5, 2024, View Source [SID1234647739]).

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Rigel’s presentations will include data from the ongoing Phase 1b dose escalation/expansion study evaluating R2891, a potent and selective dual inhibitor of IRAK1 and IRAK4, in patients with lower-risk myelodysplastic syndrome (LR-MDS) who are relapsed or refractory (R/R) to prior therapies; REZLIDHIA (olutasidenib) for the treatment of R/R mutated isocitrate dehydrogenase-1 (mIDH1) acute myeloid leukemia (AML); and TAVALISSE (fostamatinib disodium hexahydrate) for the treatment of chronic immune thrombocytopenia (ITP).

"We look forward to the presentation of posters at ASH (Free ASH Whitepaper) from across our product portfolio. We are very encouraged by the preliminary safety and efficacy data from our ongoing Phase 1b study of R289 in lower risk MDS. R289 was generally well tolerated and demonstrated responses in heavily pretreated LR-MDS patients, a population with a critical unmet need," said Raul Rodriguez, Rigel’s president and CEO. "In addition, data from olutasidenib will be presented that adds to the growing body of evidence showing the benefits of its use in patients with mIDH1 AML."

ASH Annual Meeting abstracts may be accessed online at www.hematology.org. Details of the poster presentations and publications, which will be available in the poster hall and via the virtual event platform, are as follows:

Abstract #: 4595
Title: R289, a Dual IRAK 1/4 Inhibitor, in Patients with Relapsed/Refractory (R/R) Lower-Risk Myelodysplastic Syndrome (LR-MDS): Initial Results from a Phase 1b Study
Presenter: Guillermo Garcia-Manero, M.D.
Time: Monday, December 9, 2024, 6:00pm to 8:00pm PT

Initial data from the dose escalation phase using a July 15, 2024 data cutoff date indicate that R289 was generally well tolerated in a heavily pretreated LR-MDS patient population (median number of prior therapies was 4; 79% had received an hypomethylating agent), the majority of whom were high transfusion burden (received ≥8 units red blood cells in 16 weeks prior to enrollment) at study entry.
Fourteen of 19 patients were evaluable for efficacy (received ≥1 dose of study drug with ≥1 efficacy assessment). Per International Working Group (IWG) 2018, RBC-transfusion independence (RBC-TI)/hematologic improvement (HI-E) occurred in 36% of patients receiving R289 doses ≥500 mg QD, with a median duration of RBC-TI of 29 weeks (range 12.4-35.9 weeks). RBC-TI >24 weeks was achieved in 2 high transfusion burden patients following 3 and 5 prior therapies, including a hypomethylating agent.
Updated data as of October 25, 2024 data cutoff will be presented during the poster session.
Abstract #: 1514
Title: Time to Response and Overall Survival in Patients with mIDH1 Relapsed/Refractory Acute Myeloid Leukemia Treated with Olutasidenib
Presenter: Stéphane de Botton, M.D., Ph.D.
Time: Saturday, December 7, 2024, 5:30pm to 7:30pm PT

Results show that while some patients with mIDH1 R/R AML achieve response to olutasidenib very quickly, within 1-2 months of treatment, other patients responded after 6 months of treatment for complete remission (CR) plus CR with partial hematologic recovery (CRh) and up to 10 months for overall response.
These results support the prescribing information that suggests treating for at least 6 months to allow time for clinical response in patients without disease progression or unacceptable toxicity.
A Cox regression model showed no significant association between time to response and overall survival in the overall responders and those with a CR/CRh response.
Abstract #: 2886
Title: Combination of Olutasidenib and Azacitidine Induces Durable Complete Remissions in mIDH1 Acute Myeloid Leukemia: A Multicohort Open-Label Phase 1/2 Trial
Presenter: Jorge E. Cortes, M.D.
Time: Sunday, December 8, 2024, 6:00pm to 8:00pm PT

Olutasidenib plus azacitidine induced high response rates and durable remissions with a tolerable side effect profile in patients with R/R mIDH1 AML, in the first reported analysis of a combination therapy with an mIDH1 inhibitor and a hypomethylating agent focused on the R/R AML setting.
CR/CRh was achieved in 31% (21/67) of patients and median duration of CR/CRh was 15 months.
Abstract #: 4600
Title: Olutasidenib Alone or in Combination with Azacitidine in Patients with mIDH1 Myelodysplastic Syndromes/Neoplasms: Final 5-Year Data
Presenter: Jorge E. Cortes, M.D.
Time: Monday, December 9, 2024, 6:00pm to 8:00pm PT

Olutasidenib demonstrated encouraging response rates with durable remissions and an acceptable and manageable safety profile in patients with intermediate to very high-risk mIDH1 MDS treated with olutasidenib monotherapy or in combination with azacitidine.
In a sub analysis of the 19 efficacy evaluable patients, 79% (11/14) of patients responded to combination therapy and 40% (2/5) responded to monotherapy, which included both patients (2/2) using the approved dose of 150 mg BID olutasidenib.
Abstract #: 1525
Title: Effectiveness of Olutasidenib Versus Ivosidenib in Patients with Mutated Isocitrate Dehydrogenase 1 Acute Myeloid Leukemia Who Are Relapsed or Refractory to Venetoclax: The 2102-HEM-101 Trial Versus a US Electronic Health Record-Based External Control Arm
Presenter: Catherine E. Lai, M.D.
Time: Sunday, December 8, 2024, 6:00pm to 8:00pm PT

This study provides the first evidence suggesting favorable effectiveness of olutasidenib versus ivosidenib in patients with mIDH1 AML who were R/R to a venetoclax-based regimen.
As with any real-world experience study, limitations include risk of unmeasured confounding and differential outcome reporting.
Abstract #: 5080
Title: Real-World Experience with Combination Therapy of Fostamatinib and Thrombopoetin Receptor Agonists (TPO-RAs) for Treatment of Immune Thrombocytopenia (ITP): Patient-Reported Outcomes
Presenter: Elizabeth Bowhay-Carnes, M.D.
Time: Monday, December 9, 2024, 6:00pm to 8:00pm PT

This real-world study treating patients with fostamatinib and a thrombopoetin receptor agonist (TPO-RA) demonstrated that the combination led to a clinically meaningful response in a majority of patients with ITP.
ASH Publication

Abstract #: 7908
Title: Treatment Patterns and Outcomes of Olutasidenib in Patients with Relapsed/Refractory (R/R) mutated IDH1 Acute Myeloid Leukemia (AML) in the Real World
Authors: Aaron Sheppard, Ph.D.; Lixia Wang, Ph.D.; Ravi Potluri, MBA; Eros Papademetriou, MA

About R289
R289 is a prodrug of R835, an IRAK1/4 dual inhibitor, which has been shown in preclinical studies to block inflammatory cytokine production in response to toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) family signaling. TLRs and IL-1Rs play a critical role in the innate immune response and dysregulation of these pathways can lead to various inflammatory conditions. Chronic stimulation of both these receptor systems is thought to cause the pro-inflammatory environment in the bone marrow responsible for persistent cytopenias in lower-risk MDS patients.2

About AML
Acute myeloid leukemia (AML) is a rapidly progressing cancer of the blood and bone marrow that affects myeloid cells, which normally develop into various types of mature blood cells. AML occurs primarily in adults and accounts for about 1 percent of all adult cancers. The American Cancer Society estimates that there will be about 20,800 new cases in the United States, most in adults, in 2024.3

Relapsed AML affects about half of all patients who, following treatment and remission, experience a return of leukemia cells in the bone marrow.4 Refractory AML, which affects between 10 and 40 percent of newly diagnosed patients, occurs when a patient fails to achieve remission even after intensive treatment.5 Quality of life declines for patients with each successive line of treatment for AML, and well-tolerated treatments in relapsed or refractory disease remain an unmet need.

About ITP
In patients with ITP (immune thrombocytopenia), the immune system attacks and destroys the body’s own blood platelets, which play an active role in blood clotting and healing. Common symptoms of ITP are excessive bruising and bleeding. People suffering with chronic ITP may live with an increased risk of severe bleeding events that can result in serious medical complications or even death. Current therapies for ITP include steroids, blood platelet production boosters (TPO-RAs), and splenectomy. However, not all patients respond to existing therapies. As a result, there remains a significant medical need for additional treatment options for patients with ITP.

About REZLIDHIA

INDICATION
REZLIDHIA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME

Differentiation syndrome, which can be fatal, can occur with REZLIDHIA treatment. Symptoms
may include dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury,
hypotension, fever, and weight gain. If differentiation syndrome is suspected, withhold
REZLIDHIA and initiate treatment with corticosteroids and hemodynamic monitoring until
symptom resolution.

WARNINGS AND PRECAUTIONS

Differentiation Syndrome
REZLIDHIA can cause differentiation syndrome. In the clinical trial of REZLIDHIA in patients with relapsed or refractory AML, differentiation syndrome occurred in 16% of patients, with grade 3 or 4 differentiation syndrome occurring in 8% of patients treated, and fatalities in 1% of patients. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal. Symptoms of differentiation syndrome in patients treated with REZLIDHIA included leukocytosis, dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, fever, edema, pyrexia, and weight gain. Of the 25 patients who experienced differentiation syndrome, 19 (76%) recovered after treatment or after dose interruption of REZLIDHIA. Differentiation syndrome occurred as early as 1 day and up to 18 months after REZLIDHIA initiation and has been observed with or without concomitant leukocytosis.

If differentiation syndrome is suspected, temporarily withhold REZLIDHIA and initiate systemic corticosteroids (e.g., dexamethasone 10 mg IV every 12 hours) for a minimum of 3 days and until resolution of signs and symptoms. If concomitant leukocytosis is observed, initiate treatment with hydroxyurea, as clinically indicated. Taper corticosteroids and hydroxyurea after resolution of symptoms. Differentiation syndrome may recur with premature discontinuation of corticosteroids and/or hydroxyurea treatment. Institute supportive measures and hemodynamic monitoring until improvement; withhold dose of REZLIDHIA and consider dose reduction based on recurrence.

Hepatotoxicity
REZLIDHIA can cause hepatotoxicity, presenting as increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased blood alkaline phosphatase, and/or elevated bilirubin. Of 153 patients with relapsed or refractory AML who received REZLIDHIA, hepatotoxicity occurred in 23% of patients; 13% experienced grade 3 or 4 hepatotoxicity. One patient treated with REZLIDHIA in combination with azacitidine in the clinical trial, a combination for which REZLIDHIA is not indicated, died from complications of drug-induced liver injury. The median time to onset of hepatotoxicity in patients with relapsed or refractory AML treated with REZLIDHIA was 1.2 months (range: 1 day to 17.5 months) after REZLIDHIA initiation, and the median time to resolution was 12 days (range: 1 day to 17 months). The most common hepatotoxicities were elevations of ALT, AST, blood alkaline phosphatase, and blood bilirubin.

Monitor patients frequently for clinical symptoms of hepatic dysfunction such as fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. Obtain baseline liver function tests prior to initiation of REZLIDHIA, at least once weekly for the first two months, once every other week for the third month, once in the fourth month, and once every other month for the duration of therapy. If hepatic dysfunction occurs, withhold, reduce, or permanently discontinue REZLIDHIA based on recurrence/severity.

ADVERSE REACTIONS
The most common (≥20%) adverse reactions, including laboratory abnormalities, were aspartate aminotransferase increased, alanine aminotransferase increased, potassium decreased, sodium decreased, alkaline phosphatase increased, nausea, creatinine increased, fatigue/malaise, arthralgia, constipation, lymphocytes increased, bilirubin increased, leukocytosis, uric acid increased, dyspnea, pyrexia, rash, lipase increased, mucositis, diarrhea and transaminitis.

DRUG INTERACTIONS

Avoid concomitant use of REZLIDHIA with strong or moderate CYP3A inducers.
Avoid concomitant use of REZLIDHIA with sensitive CYP3A substrates unless otherwise instructed in the substrates prescribing information. If concomitant use is unavoidable, monitor patients for loss of therapeutic effect of these drugs.
LACTATION
Advise women not to breastfeed during treatment with REZLIDHIA and for 2 weeks after the last dose.

GERIATRIC USE
No overall differences in effectiveness were observed between patients 65 years and older and younger patients. Compared to patients younger than 65 years of age, an increase in incidence of hepatotoxicity and hypertension was observed in patients ≥65 years of age.

HEPATIC IMPAIRMENT
In patients with mild or moderate hepatic impairment, closely monitor for increased probability of differentiation syndrome.

Click here for Full Prescribing Information, including Boxed WARNING.

To report side effects of prescription drugs to the FDA, visit www.fda.gov/medwatch or call 1-800-FDA-1088 (800-332-1088).

About TAVALISSE
Indication
TAVALISSE (fostamatinib disodium hexahydrate) tablets is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.

Important Safety Information
Warnings and Precautions

Hypertension can occur with TAVALISSE treatment. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects. Monitor blood pressure every 2 weeks until stable, then monthly, and adjust or initiate antihypertensive therapy for blood pressure control maintenance during therapy. If increased blood pressure persists, TAVALISSE interruption, reduction, or discontinuation may be required.
Elevated liver function tests (LFTs), mainly ALT and AST, can occur with TAVALISSE. Monitor LFTs monthly during treatment. If ALT or AST increase to ≥3 x upper limit of normal, manage hepatotoxicity using TAVALISSE interruption, reduction, or discontinuation.
Diarrhea occurred in 31% of patients and severe diarrhea occurred in 1% of patients treated with TAVALISSE. Monitor patients for the development of diarrhea and manage using supportive care measures early after the onset of symptoms. If diarrhea becomes severe (≥Grade 3), interrupt, reduce dose or discontinue TAVALISSE.
Neutropenia occurred in 6% of patients treated with TAVALISSE; febrile neutropenia occurred in 1% of patients. Monitor the ANC monthly and for infection during treatment. Manage toxicity with TAVALISSE interruption, reduction, or discontinuation.
TAVALISSE can cause fetal harm when administered to pregnant women. Advise pregnant women the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. Verify pregnancy status prior to initiating TAVALISSE. It is unknown if TAVALISSE or its metabolite is present in human milk. Because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during TAVALISSE treatment and for at least 1 month after the last dose.
Drug Interactions

Concomitant use of TAVALISSE with strong CYP3A4 inhibitors increases exposure to the major active metabolite of TAVALISSE (R406), which may increase the risk of adverse reactions. Monitor for toxicities that may require a reduction in TAVALISSE dose.
It is not recommended to use TAVALISSE with strong CYP3A4 inducers, as concomitant use reduces exposure to R406.
Concomitant use of TAVALISSE may increase concentrations of some CYP3A4 substrate drugs and may require a dose reduction of the CYP3A4 substrate drug.
Concomitant use of TAVALISSE may increase concentrations of BCRP substrate drugs (eg, rosuvastatin) and P-Glycoprotein (P-gp) substrate drugs (eg, digoxin), which may require a dose reduction of the BCRP and P-gp substrate drug.
Adverse Reactions

Serious adverse drug reactions in the ITP double-blind studies were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis, which occurred in 1% of TAVALISSE patients. In addition, severe adverse reactions occurred including dyspnea and hypertension (both 2%), neutropenia, arthralgia, chest pain, diarrhea, dizziness, nephrolithiasis, pain in extremity, toothache, syncope, and hypoxia (all 1%).
Common adverse reactions (≥5% and more common than placebo) from FIT-1 and FIT-2 included: diarrhea, hypertension, nausea, dizziness, ALT and AST increased, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia.
Please see www.TAVALISSEUSPI.com for Full Prescribing Information.

To report side effects of prescription drugs to the FDA, visit www.fda.gov/medwatch or call 1-800-FDA-1088 (800-332-1088).

REZLIDHIA and TAVALISSE are registered trademarks of Rigel Pharmaceuticals, Inc.