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.

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

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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.