On November 5, 2024 Poseida Therapeutics, Inc. (Nasdaq: PSTX), a clinical-stage allogeneic cell therapy and genetic medicines company advancing differentiated non-viral treatments for patients with cancer, autoimmune and rare diseases, reported new preclinical data on allogeneic CAR+TCR-T cells rich in stem cell memory T cells (TSCM), along with platform enhancements aimed at enhancing potency and improving targeting of solid tumors, will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 39th Annual Meeting in Houston, November 6-10 (Press release, Poseida Therapeutics, NOV 5, 2024, View Source [SID1234647748]).

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Additionally, the Company announced presentations at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, which will be held December 7-10 in San Diego. To further characterize compelling emerging P-BCMA-ALLO1 clinical data, additional profiling of patient responses from the optimized lymphodepletion arm (Arm C) of the P-BCMA-ALLO1 Phase 1 study, along with data first presented at the 21st International Myeloma Society (IMS) Annual Meeting will be highlighted as a poster presentation. In addition, preclinical data from the ongoing Phase 1 trial of P-CD19CD20-ALLO1 in patients with B-cell malignancies will be delivered as a poster presentation.

P-BCMA-ALLO1 is an investigational non-viral TSCM-rich allogeneic CAR-T therapy in Phase 1/1b clinical development. This investigational off-the-shelf allogeneic CAR-T cell therapy targeting BCMA has received Regenerative Medicine Advanced Therapy (RMAT) designation for adult patients with relapsed/refractory multiple myeloma after three or more prior lines of therapies. P-CD19CD20-ALLO1, the Company’s first allogeneic dual CAR-T cell product candidate, targets both CD19 and CD20 antigens for the treatment of relapsed or refractory B-cell malignancies. The Company is developing P-BCMA-ALLO1 and P-CD19CD20-ALLO1 as part of a broader collaboration with Roche focused on addressing hematologic malignancies with Poseida’s TSCM-rich CAR-T platform.

SITC 2024 Poster Presentation

Title: Multi-antigen Targeting with CAR and TCR Co-expression in Allogeneic Cell Therapy for Solid Tumors

Presenting Author: Sergio M. Quinones-Parra, Ph.D., Poseida Therapeutics
Presentation Date/Time: Saturday, November 9, 2024, at 8:00 a.m. CT (9:00 a.m. ET / 6:00 a.m. PT)
Room: Exhibit Halls A and B, George R. Brown Convention Center
Abstract Number: 301
ASH 2024 Poster Presentations

Title: Late Polyclonal P-BCMA-101 CAR-T Cell Re-expansion and Rapid Complete Response in a Patient with Relapsed Multiple Myeloma Treated with One Cycle of Talquetamab, More Than 3 Years After CAR-T Infusion

Presenting Author: Anupama Kumar, M.D., Assistant Professor, Hematology, Blood & Marrow Transplant, and Cellular Therapy (HBC) Program, University of California, San Francisco (UCSF)
Session: 704. Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities: Poster I
Presentation Date/Time: Saturday, December 7, 2024, 5:30-7:30 p.m. PT (8:30-10:30 p.m. ET)
Room: Halls G-H, San Diego Convention Center
Abstract Number: 2083
Title: P-CD19CD20-ALLO1: Potent Fully Allogeneic CAR-T Therapy Targeting CD19 and CD20 with Superior Efficacy Over Single-Target Products

Presenting Author: Samy Jambon, Ph.D., Poseida Therapeutics
Session: 702. CAR-T Cell Therapies: Basic and Translational: Poster III
Presentation Date/Time: Monday, December 9, 2024, 6:00-8:00 p.m. PT (9:00-11:00 p.m. ET)
Room: Halls G-H, San Diego Convention Center
Abstract Number: 4805
Title: A Phase 1 Study of P-BCMA-ALLO1, a Non-viral, Allogeneic BCMA Directed CAR-T in Relapsed/Refractory Multiple Myeloma (RRMM): Results from Optimized Lymphodepletion Cohort

Presenting Author: Caitlin Costello, M.D., Professor of Medicine, Director of Multiple Myeloma Program, Division of Blood and Marrow Transplant, Moores Cancer Center, University of California, San Diego (UCSD)
Session: 704. Cellular Immunotherapies: Early Phase Clinical Trials and Toxicities: Poster III
Presentation Date/Time: Monday, December 9, 2024, 6:00-8:00 p.m. PT (9:00-11:00 p.m. ET)
Room: Halls G-H, San Diego Convention Center
Abstract Number: 4828
About P-BCMA-ALLO1
P-BCMA-ALLO1 is an allogeneic CAR-T product candidate licensed to Roche targeting B-cell maturation antigen (BCMA) for the treatment of relapsed/refractory multiple myeloma. This allogeneic program includes a VH-based binder that targets BCMA, and interim clinical data presented at IMS in September 2024 support the Company’s belief that T stem cell (TSCM)-rich allogeneic CAR-Ts have the potential to offer effective, safe and reliable treatment addressing unmet needs in multiple myeloma. The U.S. Food and Drug Administration (FDA) has granted P-BCMA-ALLO1 Orphan Drug designation for multiple myeloma and Regenerative Medicine Advanced Therapy (RMAT) designation for adult patients with relapsed/refractory multiple myeloma after three or more prior lines of therapies including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody.

P-BCMA-ALLO1 is currently being evaluated in a Phase 1/1b trial in patients with multiple myeloma. Additional information about the trial is available at www.clinicaltrials.gov using identifier: NCT04960579.

About P-CD19CD20-ALLO1
P-CD19CD20-ALLO1 is an allogeneic CAR-T cell therapy product candidate being developed for relapsed or refractory B-cell malignancies in partnership with Roche. P-CD19CD20-ALLO1 expresses two fully functional CAR molecules to target cells that express either CD19 or CD20. The dual targeting approach employed in P-CD19CD20-ALLO1 aims to overcome the antigen escape limitations of CD19-only targeted CAR-T therapies by simultaneously targeting both CD19 and CD20. In addition to the dual targeting, P-CD19CD20-ALLO1 uses a novel CD19 binder that showed greater potency in in vivo preclinical models when compared to the canonical FMC63 Single-chain variable fragment (scFv) binder. P-CD19CD20-ALLO1 is an off-the-shelf CAR-T therapy for which patients do not have to undergo apheresis and wait for cells to be manufactured, which can potentially overcome the limitation of autologous CAR-T therapies associated with significant manufacturing times. P-CD19CD20-ALLO1 is being studied in a Phase 1 study in B-cell malignancies. Additional information about the trial is available at www.clinicaltrials.gov using identifier: NCT06014762.

On November 5, 2024 Vaccinex, Inc. (Nasdaq: VCNX), a clinical-stage biotechnology company pioneering a differentiated approach to treating cancer and neurodegenerative disease (NDD) through the inhibition of SEMA4D, reported that it will present new biomarker data that neoadjuvant treatment with pepinemab enhanced the clinical activity of immune checkpoint inhibitors in poorly immunogenic, HPV-negative, head and neck cancer (HNSCC) (Press release, Vaccinex, NOV 5, 2024, View Source [SID1234647747]). In a presentation at Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s Annual Meeting (SITC) (Free SITC Whitepaper) on November 8th, Vaccinex will present data from the Phase 2 KEYNOTE-B84 study (NCT04815720) for treatment of recurrent and metastatic disease as well as an independent study evaluating neoadjuvant treatment of resectable HNSCC (NCT03690986) showing that pepinemab combination treatments appear to induce mature lymphoid aggregates correlating with clinical benefit within immunotherapy resistant tumor populations, including HPV-negative and PD-L1 low HNSCC.

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"Major advances beyond immune checkpoint therapies to expand and extend treatment benefits are needed for cancers whose activity may be limited by other resistance mechanisms, including expression of semaphorin 4D (SEMA4D), which binds receptors on myeloid cells to inhibit the migration and maturation of dendritic cells (DC) that are crucial for priming and expanding T cells in adaptive immune responses." said Maurice Zauderer, CEO at Vaccinex. "We are very excited to see that pepinemab treatment induced the formation of productive lymphoid structures within treated tumors and that this is associated with enhanced immune interactions and durable responses. We believe that novel modalities such as pepinemab can overcome limitations of ICI, particularly in patients who would not typically benefit from immune checkpoint monotherapy. We look forward to ongoing development of pepinemab combination therapies in metastatic and neoadjuvant settings."

Meeting: SITC 39th Annual Meeting
Date:
November 8, 2024
Poster Number: 747
Poster Title: Pepinemab a Semaphorin 4D blockade antibody in combination with immune checkpoint therapies induces mature lymphoid aggregates correlating with clinical outcomes
Presenter Crystal Mallow, Vaccinex, Rochester, NY, USA

About Pepinemab
Pepinemab is a humanized IgG4 monoclonal antibody designed to block SEMA4D, which can trigger collapse of the actin cytoskeleton and loss of homeostatic functions of astrocytes and glial cells in the brain and dendritic cells in immune tissue. Over 600 patients have been enrolled in clinical trials of pepinemab in different indications and pepinemab appears to be well-tolerated and to have a favorable safety profile.

On November 5, 2024 UroGen Pharma Ltd. (Nasdaq:URGN), a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, reported that management will participate in a fireside chat at the Guggenheim Securities Healthcare Innovation Conference to take place November 11-13, 2024 (Press release, UroGen Pharma, NOV 5, 2024, View Source [SID1234647746]).

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Guggenheim Securities Healthcare Innovation Conference

Date / Time:

November 12, 2024 at 3:00 PM ET

Format:

Fireside Chat and 1×1 investor meetings

Location:

Boston, MA

Webcast Link:

here

A live public webcast from the conference will also be available on UroGen’s Investor Relations website. A replay will be available on the site for approximately 90 days.

On November 5, 2024 Syndax Pharmaceuticals (Nasdaq: SNDX), a commercial-stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported its financial results for the quarter ended September 30, 2024, and provided a business update (Press release, Syndax, NOV 5, 2024, View Source [SID1234647745]).

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"This has been a historic period for Syndax as we transitioned to a commercial-stage company with the approval of Niktimvo. With the recently completed royalty financing, we expect to be funded through profitability and we are well positioned to maximize the potential of our pipeline," said Michael A. Metzger, Chief Executive Officer. "We have a very exciting quarter ahead with the anticipated FDA approval and U.S. launch of revumenib for adults and pediatrics with R/R KMT2Ar acute leukemia, as well as the expected readout of topline pivotal data from patients with R/R mNPM1 AML. Our commercial organization is well-prepared to launch revumenib and leverage our first-to-market position to drive long-term value creation."

Recent Pipeline Progress and Anticipated Milestones

Revumenib

The New Drug Application (NDA) for revumenib, an oral menin inhibitor, for the treatment of adult and pediatric relapsed or refractory (R/R) KMT2A-rearranged (KMT2Ar) acute leukemia was granted Priority Review and is being reviewed under the U.S. FDA’s Real-Time Oncology Review (RTOR) Program with a Prescription Drug User Fee Act (PDUFA) target action date of December 26, 2024.
The Company expects to report topline data from the AUGMENT-101 pivotal trial cohort of patients with R/R mutant nucleophosmin (mNPM1) acute myeloid leukemia (AML) in the fourth quarter of 2024. Positive data could support a supplemental NDA (sNDA) filing for revumenib in R/R mNPM1 AML in the first half of 2025.
The Company announced that data from 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) have been published in the Journal of Clinical Oncology.
The Company announced that a larger data set and longer follow-up from the pivotal Phase 2 portion of the AUGMENT-101 trial of revumenib in R/R KMT2Ar acute leukemia will be presented at the upcoming 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. The larger efficacy population (n=97) includes the 57 patients from the previously reported interim efficacy analysis plus an additional 40 patients. Consistent with previously reported data, the updated analysis shows that revumenib provides durable responses and robust rates of overall response, minimal residual disease (MRD) negativity, and hematopoietic stem cell transplantation (HSTC). With seven months of additional follow-up, the median duration of CR/CRh extended to 13 months among the 13 CR/CRh responders included in the interim analysis presented at ASH (Free ASH Whitepaper) 2023.
Multiple trials evaluating the potential to expand revumenib use across the mNPM1 and KMT2Ar acute leukemia treatment landscape are ongoing. These trials include:
BEAT AML: A Phase 1 trial evaluating the combination of revumenib with venetoclax and azacitidine in front-line AML patients. The trial is being conducted as part of the Leukemia & Lymphoma Society’s Beat AML Master Clinical Trial. The Company presented updated positive data from the trial at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Congress, showing a 96% (23 of 24 pts) composite complete remission (CRc) rate in patients with newly diagnosed mNPM1 or KMT2Ar AML. The BEAT AML trial is expanding to validate the recommended Phase 2 dose of the combination of revumenib with venetoclax and azacitidine. The company anticipates that an update on the trial will be available in the fourth quarter of 2024.
SAVE: A Phase 1 trial evaluating the all-oral combination of revumenib with venetoclax and decitabine/cedazuridine in R/R AML or mixed phenotype acute leukemias. The trial is being conducted by investigators from MD Anderson Cancer Center. The Company announced that updated data showing an 88% ORR (23 of 26 pts) in R/R patients with KMT2Ar, mNPM1, or NUP98r leukemias will be presented at the upcoming 66th ASH (Free ASH Whitepaper) Annual Meeting. In addition to the R/R cohort, a frontline cohort is now enrolling patients.
INTERCEPT: A Phase 1 trial evaluating the use of novel therapies, including revumenib, to target MRD and early relapse in AML. The trial is being conducted by the Australasian Leukaemia and Lymphoma Group as part of the INTERCEPT AML master clinical trial. Preliminary results from the first eight mNPM1 patients treated with revumenib will be presented at the upcoming 66th ASH (Free ASH Whitepaper) Annual Meeting.
Intensive chemotherapy: A Phase 1 trial evaluating the combination of revumenib with intensive chemotherapy (7+3) followed by revumenib maintenance treatment in newly diagnosed patients with mNPM1 or KMT2Ar acute leukemias. The trial is designed to identify the recommended Phase 2 dose for this combination to support further development.
Break Through Cancer: A Phase 2 trial studying whether the combination of revumenib and venetoclax can eliminate MRD in patients with AML and extend progression-free survival. The trial is being conducted by Break Through Cancer, a collaboration between leading U.S. cancer research centers.
The Company plans to initiate a pivotal trial of revumenib in combination with venetoclax and azacitidine in newly diagnosed mNPM1 or KMT2Ar acute leukemia patients unfit to receive intensive chemotherapy by year-end 2024.
The Company is evaluating revumenib in patients with R/R metastatic microsatellite stable (MSS) colorectal cancer (CRC). The trial is currently enrolling patients in the Phase 1b portion of its Phase 1/2 proof-of-concept trial.

Niktimvo (axatilimab-csfr)

Niktimvo received U.S. Food and Drug Administration (FDA) approval 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). The Company anticipates that Niktimvo will be launched in the U.S. no later than early first quarter 2025. In the U.S., Niktimvo will be co-commercialized by Syndax and Incyte.
The Company announced Niktimvo was added to the latest NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) as a category 2A recommendation for the treatment of GVHD after the failure of at least two prior lines of systemic therapy in adult and pediatric patients weighing at least 40 kg. Treatments are classified as category 2A when there is uniform NCCN consensus that the intervention is appropriate, based on lower level evidence.
The Company announced that results from the pivotal Phase 2 AGAVE-201 trial of Niktimvo in adult and pediatric patients with recurrent/refractory active chronic GVHD who had received at least two prior lines of systemic therapy were published in the New England Journal of Medicine.
The Company announced a secondary analysis of overall and organ-specific responses from the pivotal Phase 2 AGAVE-201 trial of Niktimvo in adult and pediatric patients with recurrent/refractory active chronic GVHD who had received at least two prior lines of systemic therapy will be presented at the 66th ASH (Free ASH Whitepaper) Annual Meeting. The data demonstrated rapid responses and symptom improvement in inflammatory and fibrotic manifestations of chronic GVHD in heavily pretreated patients.
Enrollment is ongoing in a 26-week randomized, double-blinded, placebo-controlled Phase 2 trial of axatilimab on top of standard of care in patients with idiopathic pulmonary fibrosis (IPF), now referred to as the MAXPIRe trial (NCT06132256). The Company expects to report topline data from the trial in 2026.
The Company’s partner, Incyte, is now recruiting patients for a Phase 2, open-label, randomized, multicenter trial of axatilimab in combination with ruxolitinib in patients ≥12 years of age with newly diagnosed chronic GVHD (NCT06388564). A Phase 3 trial of axatilimab in combination with steroids for the treatment of chronic GVHD is currently in preparation.
Corporate Update

The Company announced a $350 million royalty funding agreement with Royalty Pharma based on U.S. net sales of Niktimvo. Under the agreement, Syndax received $350 million in exchange for a 13.8% royalty on U.S. net sales of Niktimvo. Royalty payments to Royalty Pharma will cease upon reaching a multiple of 2.35x.

Third Quarter 2024 Financial Results

As of September 30, 2024, Syndax had cash, cash equivalents, and short- and long-term investments of $399.6 million and 85.6 million common shares and prefunded warrants outstanding.

Third quarter 2024 research and development expenses increased to $71.0 million from $39.1 million for the comparable prior year period. The increase was primarily due to greater clinical development expenses, higher pre-commercial manufacturing costs, and increased employee-related expenses and professional fees.

Third quarter 2024 selling, general and administrative expenses increased to $31.1 million from $17.3 million for the comparable prior year period. The increase was driven by a greater level of commercial readiness activities for revumenib and axatilimab as well as higher employee-related expenses and professional fees.

For the three months ended September 30, 2024, Syndax reported a net loss attributable to common stockholders of $84.1 million, or $0.98 per share, compared to a net loss attributable to common stockholders of $51.1 million, or $0.73 per share, for the comparable prior year period.

Financial Guidance

For the full year of 2024, the Company expects research and development expenses to be $245 to $250 million (prior guidance $240 million to $260 million) and total operating expenses to be $365 to $370 million (prior guidance $355 million to $375 million), which includes milestone payments that the Company expects to become due as well as an estimated $41 million (prior guidance $43 million) in non-cash stock compensation expense.

Syndax expects that its cash, cash equivalents and marketable securities, together with the $350 million from the sale of a portion of the Niktimvo royalty and anticipated product revenue and interest income, enables the company to reach profitability.

Conference Call and Webcast

In connection with the earnings release, Syndax’s management team will host a conference call and live audio webcast at 4:30 p.m. ET today, Tuesday, November 5, 2024.

The live audio webcast and accompanying slides may be accessed through the Events & Presentations page in the Investors section of the Company’s website. Alternatively, the conference call may be accessed through the following:

Conference ID: Syndax3Q24
Domestic Dial-in Number: 800-590-8290
International Dial-in Number: 240-690-8800
Live webcast: https://www.veracast.com/webcasts/syndax/events/SNDX3Q24.cfm

For those unable to participate in the conference call or webcast, a replay will be available on the Investors section of the Company’s website at www.syndax.com approximately 24 hours after the conference call and will be available for 90 days following the call.

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 mNPM1 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.

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).

About the Real-Time Oncology Review Program (RTOR)

RTOR provides a more efficient review process for oncology drugs to ensure that safe and effective treatments are available to patients as early as possible, while improving review quality and engaging in early iterative communication with the applicant. Specifically, it allows for close engagement between the sponsor and the FDA throughout the submission process and it enables the FDA to review individual sections of modules of a drug application rather than requiring the submission of complete modules or a complete application prior to initiating review. Additional information about RTOR can be found at: View Source

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.