On November 12, 2024 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage biotechnology company developing first-in-classi targeted and immune-mediated therapeutics to fight cancer, reported financial results for the quarter ended September 30, 2024, and provided a corporate update (Press release, Tempest Therapeutics, NOV 12, 2024, View Source [SID1234648217]).

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"During the third quarter, the team continued to move amezalpat successfully towards the pivotal study, achieving important milestones on both the regulatory and business fronts," said Stephen Brady, president and chief executive officer of Tempest. "Based on the positive randomized Phase 2 data and a Phase 3 plan we believe is designed for success, we were thrilled to receive broad agreement with the FDA. Coupled with Roche’s support for the Phase 3 study, the third quarter further solidified the foundation of a pivotal study that we hope will result in a new and meaningful therapy for first-line HCC patients."

Recent Highlights

Amezalpat (TPST-1120) (clinical PPARα antagonist):
Received a "Study May Proceed" letter from the U.S. Food and Drug Administration (FDA) to evaluate amezalpat in combination with atezolizumab (Tecentriq) and bevacizumab (Avastin), the current standard of care for unresectable or metastatic hepatocellular carcinoma (HCC), in a pivotal Phase 3 trial for the first-line treatment of unresectable or metastatic hepatocellular carcinoma.
Announced an agreement with F. Hoffmann-La Roche Ltd. (Roche) to advance the evaluation of amezalpat in combination with atezolizumab and bevacizumab into a pivotal Phase 3 trial for the first-line treatment of unresectable or metastatic HCC, a form of liver cancer with high unmet need.
Under the agreement, Roche will supply atezolizumab globally and Tempest will sponsor and lead the pivotal study. The agreement builds on a clinical collaboration between the companies pursuant to which amezalpat was combined with atezolizumab and bevacizumab in first-line HCC patients and compared to atezolizumab and bevacizumab alone in a randomized Phase 1b/2 study. Tempest retains all development and commercial rights to amezalpat.
Announced positive feedback from the end-of-Phase 2 meeting with the FDA for amezalpat in combination with atezolizumab and bevacizumab to treat first-line unresectable or metastatic HCC. Key outcomes included:
Agreement on Phase 3 study design, including the standard-of-care control arm and the primary and secondary study endpoints.
Agreement on appropriateness of the current amezalpat dose and schedule for the Phase 3 study.
Agreement on the Phase 3 statistical plan, including a pre-specified early efficacy analysis that the company currently estimates could shorten the time to primary analysis by up to 8 months.
Corporate:
Expanded leadership team to strengthen global clinical expertise with the appointments of Troy M. Wagner as Vice President of Quality Assurance and Sheldon Mullins as Vice President of Regulatory Affairs.
Other Potential Future Milestones

TPST-1495 (clinical dual EP2/4 prostaglandin receptor antagonist)
Plan to advance TPST-1495 into a Phase 2 study in patients with Familial Adenomatous Polyposis (FAP) in 2024 or early 2025 under the auspices of the Cancer Prevention Clinical Trials Network and funded by the National Cancer Institute (NCI) Division of Cancer Prevention.
Expect to disclose data from the TPST-1495 Phase 1 combination arm in patients with advanced endometrial cancer in 2025.
Financial Results

Third Quarter 2024

Tempest ended the quarter with $22.1 million in cash and cash equivalents, compared to $39.2 million on December 31, 2023. Subsequent to September 30, 2024, Tempest raised an additional $19.9 million in net proceeds through the sale of 17 million shares of common stock under the Company’s at-the-market (ATM) program.
Net loss and net loss per share for the quarter ended September 30, 2024, were $10.6 million and $0.41, respectively, compared to $6.8 million and $0.48, respectively, for the same period in 2023.
Research and development expenses for the quarter were $7.6 million compared to $4.2 million for the same period in 2023. The $3.4 million increase was primarily due to an increase in costs incurred from contract research and manufacturing organizations.
General and administrative expenses for the quarter were $3.0 million compared to $2.4 million for the same period in 2023. The $0.6 million increase was primarily due to an increase in stock-based compensation, and consulting and professional services.
Year-to-Date

Cash used in operating activities for the nine months ended September 30, 2024 was $22.9 million.
Net loss and net loss per share for the nine months ended September 30, 2024 were $28.0 million and $1.19, respectively, compared to $22.0 million and $1.57, respectively, for the same period in 2023.
Research and development expenses for the nine months ended September 30, 2024 were $17.7 million compared to $13.3 million for the same period in 2023. The $4.4 million increase was primarily due to an increase in costs incurred from contract research and manufacturing organizations, as well as an increase in stock-based compensation.
General and administrative expenses for the nine months ended September 30, 2024 were $10.4 million compared to $8.3 million for the same period in 2023. The $2.1 million increase was primarily due to an increase in stock-based compensation as well as legal and consulting services.

On November 12, 2024 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage biotechnology company developing first-in-classi targeted and immune-mediated therapeutics to fight cancer, reported that the company received a "Study May Proceed" letter from the U.S. Food and Drug Administration (FDA) to evaluate amezalpat (TPST-1120) in combination with atezolizumab and bevacizumab, the current standard of care, versus the standard of care alone in a pivotal randomized Phase 3 trial for the first-line treatment of unresectable or metastatic hepatocellular carcinoma (HCC) (Press release, Tempest Therapeutics, NOV 12, 2024, View Source [SID1234648216]).

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"The clinical and regulatory team at Tempest are thrilled to receive this notice from FDA with respect to the planned pivotal Phase 3 trial to evaluate amezalpat as a potential treatment for first-line liver cancer," said Sam Whiting M.D., Ph.D., chief medical officer and head of R&D of Tempest. "Previously reported positive Phase 2 data underscore amezalpat’s potential to improve the survival of patients facing this life-threatening disease, and our team is dedicated to advancing the program and bringing amezalpat to patients."

About the TPST-1120-301 Study (NCT06680258)

The planned Phase 3 study is a global, blinded, 1:1 randomized study of amezalpat plus atezolizumab and bevacizumab versus placebo plus atezolizumab and bevacizumab, the standard of care, for the first-line treatment of patients with unresectable or metastatic HCC. In August 2024, the company received agreement from the FDA on its Phase 3 study design, dose of amezalpat, and the statistical plan, including a pre-specified efficacy analysis that could shorten the time to primary analysis. The company is working to enable a Phase 3 study to start in the first quarter of 2025.

About Amezalpat

Amezalpat is an oral, small molecule, selective PPAR⍺ antagonist. Data suggest that amezalpat treats cancer by targeting tumor cells directly and by modulating immune suppressive cells and angiogenesis in the tumor microenvironment. In an ongoing global randomized phase 1b/2 study of amezalpat in combination with atezolizumab and bevacizumab in first-line patients with advanced HCC, the amezalpat arm showed clinical superiority across multiple study endpoints, including overall survival in both the entire population and key subpopulations, when compared to atezolizumab and bevacizumab alone, the standard of care. These randomized data were supported by additional positive results observed in the Phase 1 clinical trial in patients with heavily pretreated advanced solid tumors, including renal cell carcinoma and cholangiocarcinoma.

On November 12, 2024 Syros Pharmaceuticals (NASDAQ:SYRS), a biopharmaceutical company committed to advancing new standards of care for the frontline treatment of hematologic malignancies, reported that the SELECT-MDS-1 Phase 3 trial evaluating tamibarotene in combination with azacitidine in newly diagnosed higher-risk myelodysplastic syndrome (HR-MDS) patients with RARA gene overexpression did not meet its primary endpoint of complete response (CR) rate (Press release, Syros Pharmaceuticals, NOV 12, 2024, View Source [SID1234648215]). Tamibarotene is Syros’ proprietary oral, selective, retinoic acid receptor alpha (RARα) agonist.

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In the first 190 enrolled patients, the CR rate by intent-to-treat (ITT) in the tamibarotene/azacitidine treatment arm was 23.8% (n=126; 95% CI: 16.7%-32.2%) compared to a CR rate of 18.8% (n=64; 95% CI: 10.1%-30.5%) in the placebo/azacitidine control arm and was not statistically significant (p-value = 0.2084). In the safety analysis of all enrolled patients (n=245), tamibarotene in combination with azacitidine (n=160) appeared to be generally well-tolerated, with an adverse event profile that was similar to that seen in earlier Syros-sponsored studies.

Syros also reported that, as previously disclosed in its filings with the SEC, the failure of the SELECT-MDS-1 trial to achieve its primary endpoint constitutes an event of default under its secured loan facility with Oxford Finance LLC.

"We are deeply disappointed by this outcome, particularly for the HR-MDS patients who are seeking a new treatment option for this challenging disease," said Conley Chee, Chief Executive Officer of Syros. "We plan to stop the study, review the clinical data more thoroughly, and evaluate the next steps. We want to express our sincere appreciation for the patients, caregivers and healthcare professionals who took part in the SELECT-MDS-1 trial and to all the employees of Syros for their exceptional work on the tamibarotene program."

About SELECT-MDS-1 Phase 3 Trial

SELECT-MDS-1 is a multinational Phase 3 randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of tamibarotene in combination with azacitidine compared to placebo and azacitidine in HR-MDS patients with RARA overexpression. The primary endpoint of the trial was the CR rate in the first 190 patients.

On November 12, 2024 Biohaven Ltd. (NYSE: BHVN) (Biohaven or the Company), a global clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of life-changing therapies to treat a broad range of rare and common diseases, reported financial results for the third quarter ended September 30, 2024, and provided a review of recent accomplishments and anticipated upcoming developments (Press release, Biohaven Pharmaceutical, NOV 12, 2024, View Source [SID1234648213]).

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Vlad Coric, M.D., Chairman and Chief Executive Officer of Biohaven, commented, "The team at Biohaven continues to advance multiple late and early stage assets that have the potential to change the current standard of care treatment paradigm across a number of diseases. Last quarter we announced positive topline results in our RWE trial assessing troriluzole for the treatment of spinocerebellar ataxia. Troriluzole (200 mg dosed orally) met the study’s primary endpoint on the change from baseline in the f-SARA at 3 years in all study population genotypes, showed statistically significant superiority after both 1 and 2 years of treatment, and achieved statistically significant superiority on 9 consecutive, prespecified primary and secondary endpoints. This was truly a watershed moment for the Company, given the implications of potentially bending the arc of one of the most intractable neurological diseases with no currently approved treatment options. SCA robs patients of their ability to speak, walk, and take care of themselves, and often shortens lifespans and has unfortunate intergenerational implications. We were encouraged by the robust dataset gathered to date and look forward to submitting an NDA to the FDA."

Dr. Coric continued, "We continue to execute across our broad pipeline including the recent initiation of our Phase 2 trial with BHV-2100 in acute migraine. Migraine burden and disability remain high despite advances in treatment; we believe our TRPM3 antagonistic approach has the potential to be a highly-effective, non-sedating, non-opioid treatment for pain and migraine. In the final months of 2024, we expect to report on a number of updates including SMA topline data and data across our MoDE platform including a SAD/MAD update and multiple INDs spanning β1AR for the potential treatment of dilated cardiomyopathy, galactose deficient IgA for IgA nephropathy and a further optimized IgG degrader for use in rare diseases."

Third Quarter 2024 and Recent Business Highlights

Achieved positive topline results in pivotal study of troriluzole in SCA – In September 2024, the Company announced positive topline results from pivotal Study BHV4157-206-RWE demonstrating the efficacy of troriluzole on the mean change from baseline in the f-SARA after 3 years of treatment. The study achieved the primary endpoint and showed statistically significant improvements on the f-SARA at years 1 and 2. Additionally, troriluzole achieved statistically significant superiority on 9 consecutive, prespecified primary and secondary endpoints. SCA patients treated with troriluzole showed a 50-70% slowing of disease progression, representing 1.5-2.2 years delay in disease progression over the 3-year study period. The Company intends to submit an NDA to the FDA for troriluzole in the treatment of all SCA genotypes in 4Q 2024. The development program for troriluzole has been granted orphan and fast track designations, and is eligible for priority review. European Medicines Agency marketing authorization remains under review and Biohaven completed a clarification meeting with CHMP Rapporteurs in 4Q 2024. MAA documents are being updated to include the new positive BHV4157-206-RWE study data with broader indication to include all SCA genotypes.

Initiated Phase 2 trial evaluating BHV-2100 in the acute treatment of migraine – In September 2024, the Company initiated a Phase 2 study of an orally administered TRPM3 antagonist, BHV-2100, in the acute treatment of migraine. The study is a randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of two doses (75 mg and 150 mg) of BHV-2100 in the acute treatment of migraine. The trial is designed to support registration with FDA-accepted co-primary endpoints of pain freedom and freedom from most bothersome symptom at 2 hours and is expected to enroll approximately 575 patients across 60 sites in the United States.

Public offering – On October 2, 2024, the Company closed its previously announced underwritten public offering of 6,052,631 of its common shares, which included the full exercise of the underwriters’ option to purchase additional shares, at the public offering price of $47.50 per share. The net proceeds raised in the offering, after deducting underwriting discounts and estimated expenses of the offering payable by the Company, were approximately $269.9M. As of November 8, 2024, we had 101,122,246 common shares outstanding.
Expected Upcoming Milestones:

We believe Biohaven is well positioned to achieve significant milestones in 2024 and 2025 across numerous programs:

Selective Kv7 Activator:

Continue 5 ongoing Phase 2/3 trials with BHV-7000 in focal epilepsy, idiopathic generalized epilepsy, MDD, and bipolar disorder
Troriluzole:

NDA submission to FDA on track for 4Q 2024, following release of pivotal topline results in SCA in September 2024
Two Phase 3 trials with troriluzole in OCD; expect to conduct interim analysis of the second Phase 3 OCD trial in 4Q 2024 and report topline data from first Phase 3 OCD trial in 1H 2025
Taldefgrobep alfa:

Report topline data from Phase 3 trial with taldefgrobep in SMA in 4Q 2024
Initiate Phase 2 trial with taldefgrobep in obesity in 4Q 2024 or early 2025
First-in-class TRPM3 Antagonist:

Continue advancing enrollment in Phase 2 trial with BHV-2100 in acute migraine and neuropathic pain (laser-evoked potential experimental pain paradigm)
TYK2/JAK1 Inhibitor:

Complete SAD/MAD studies with BHV-8000 and advance to Phase 2 in the coming months
MoDE Platform

Submit a total of 4 INDs in 2024
Continue to advance Phase 1 SAD and MAD studies with subcutaneous BHV-1300, with a further study update in 4Q 2024
Next Generation ADC Platform:

Advance Phase 1 Trop-2 directed program BHV-1510 in multiple tumor types
Capital Position:

Cash, cash equivalents, marketable securities and restricted cash as of October 2, 2024 totaled approximately $642 million, which includes net proceeds of $269.9 million from the public offering of 6,052,631 common shares completed on October 2, 2024.

Third Quarter 2024 Financial Highlights:

Research and Development (R&D) Expenses: R&D expenses, including non-cash share-based compensation costs, were $157.6 million for the three months ended September 30, 2024, compared to $95.5 million for the three months ended September 30, 2023. The increase of $62.1 million was due to additional and advancing clinical trials, including late Phase 3 and Phase 2/3 studies, and preclinical research programs in 2024, as compared to the same period in the prior year. Non-cash share-based compensation expense was $7.2 million for the three months ended September 30, 2024, an increase of $5.0 million as compared to the same period in 2023. Non-cash share-based compensation expense was higher in the third quarter of 2024, primarily due to our annual equity incentive awards granted in the fourth quarter of 2023 and the first quarter of 2024.

General and Administrative (G&A) Expenses: G&A expenses were $20.6 million for the three months ended September 30, 2024, compared to $15.0 million for the three months ended September 30, 2023. The increase of $5.5 million was partly due to increased non-cash share-based compensation expense, which was $5.0 million for the three months ended September 30, 2024, an increase of $2.7 million as compared to the same period in 2023. Non-cash share-based compensation expense was higher in the third quarter of 2024 primarily due to our annual equity incentive awards granted in the fourth quarter of 2023 and the first quarter of 2024.

Other Income, Net: Other income, net was $17.8 million for the three months ended September 30, 2024, compared to other income, net of $4.7 million for the three months ended September 30, 2023. The increase of $13.1 million was primarily due to non-cash changes in the fair value of our derivative liabilities recorded in connection with the amendment to our Membership Interest Purchase Agreement with Knopp Biosciences LLC in May 2024 (the Knopp Amendment), as well as increased investment income, partially offset by changes in the fair value of our forward contract liability recorded in connection with the Knopp Amendment.

Net Loss: Biohaven reported a net loss for the three months ended September 30, 2024 of $160.3 million, or $1.70 per share, compared to $102.6 million, or $1.50 per share, for the same period in 2023. Non-GAAP adjusted net loss for the three months ended September 30, 2024 was $164.1 million, or $1.74 per share, compared to $98.1 million, or $1.44 per share for the same period in 2023. These non-GAAP adjusted net loss and non-GAAP adjusted net loss per share measures, more fully described below under "Non-GAAP Financial Measures," exclude non-cash share-based compensation charges and losses from the change in fair value of derivatives. A reconciliation of the GAAP financial results to non-GAAP financial results is included in the tables below.

Non-GAAP Financial Measures
This press release includes financial results prepared in accordance with accounting principles generally accepted in the United States (GAAP), and certain non-GAAP financial measures. In particular, Biohaven has provided non-GAAP adjusted net loss and adjusted net loss per share, which are adjusted to exclude non-cash share-based compensation, which is substantially dependent on changes in the market price of common shares, and changes in the fair value of derivative liabilities, which do not correlate to actual cash payment obligations in the relevant periods. Non-GAAP financial measures are not an alternative for financial measures prepared in accordance with GAAP. However, Biohaven believes the presentation of non-GAAP adjusted net loss and adjusted net loss per share, when viewed in conjunction with GAAP results, provides investors with a more meaningful understanding of ongoing operating performance and can assist investors in comparing Biohaven’s performance between periods.

In addition, these non-GAAP financial measures are among those indicators Biohaven uses as a basis for evaluating performance, and planning and forecasting future periods. These non-GAAP financial measures are not intended to be considered in isolation or as a substitute for GAAP financial measures. A reconciliation between these non-GAAP measures and the most directly comparable GAAP measures is provided later in this news release.

On November 12, 2024 Syndax Pharmaceuticals (Nasdaq: SNDX), a commercial-stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported positive topline results from the relapsed or refractory (R/R) mutant NPM1 (mNPM1) acute myeloid leukemia (AML) cohort in the pivotal Phase 2 portion of the AUGMENT-101 trial of revumenib, an oral, small molecule menin inhibitor (Press release, Syndax, NOV 12, 2024, View Source [SID1234648212]).

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The primary endpoint was met with a complete remission (CR) plus CR with partial hematological recovery (CRh) rate of 23% (15/64; 95% confidence interval [CI]: 14%, 36%; one-sided p-value =0.0014) among the efficacy evaluable adults with R/R mNPM1 AML in the Phase 2 portion of the AUGMENT-101 trial. Among the patients who achieved CR/CRh, 12 patients had a CR and three had a CRh. The observed median duration of CR/CRh responses was 4.7 months (95% CI: 1.2, 8.2) at the time of the data cutoff with three patients remaining in response. Minimal residual disease (MRD) status was assessed in 14 of 15 patients who achieved CR/CRh, 64% (9/14) of whom were MRD negative. The overall response rate (ORR)1 was 47% (30/64; 95% CI: 34%, 60%). 17% (5/30) of patients who achieved an overall response underwent hematopoietic stem cell transplant (HSCT) following treatment with revumenib, with three resuming revumenib therapy post-transplant.

"We are thrilled to report positive pivotal data in R/R mNPM1 AML patients treated with revumenib, which has shown compelling and notably consistent results across treatment settings for both mNPM1 AML and KMT2A-rearranged acute leukemias," said Michael A. Metzger, Chief Executive Officer of Syndax. "With the anticipated FDA approval of revumenib for the treatment of R/R KMT2A-rearranged acute leukemias this quarter, and this second positive pivotal data readout, we are well-positioned to meaningfully impact the estimated 40% of AML patients with these two genetic alterations."

The AUGMENT-101 Phase 2 protocol-defined efficacy evaluable population included 64 adult patients with R/R mNPM1 AML. The median age was 65 (range: 19, 84). Patients were heavily pretreated, with 36% having received three or more prior lines of therapy (median prior lines: 2) and 75% of patients previously treated with venetoclax.

The safety population included 84 adult and pediatric patients with R/R mNPM1 AML in the Phase 2 portion of the AUGMENT-101 trial. The safety profile observed with revumenib in this population was consistent with previously reported data. Treatment-related adverse events (TRAEs) leading to treatment discontinuations were 5% (4/84). TRAEs of Grade ≥3 in more than 10% of patients included: QTc prolongation (21%), anemia (14%), febrile neutropenia (13%), differentiation syndrome (13%), and platelet count decreased (11%). Grade 3 treatment-related DS was observed in 11% (9/84) of patients while 2% (2/84) experienced Grade 4 DS and no patients experienced Grade 5. Grade 3 treatment-related QTc prolongation was observed in 19% (16/84) of patients while 2% (2/84) experienced Grade 4 QTc prolongation and no patients experienced Grade 5.

"Relapsed or refractory mNPM1 AML is a very challenging disease with a poor prognosis and an urgent need for new treatments," said Eytan M. Stein, M.D., Chief, Leukemia Service, Memorial Sloan Kettering Cancer Center. "The positive results for revumenib in this heavily pre-treated population, which included more than 75% who previously failed venetoclax, are very encouraging. In particular, the robust rates of overall response, including deep molecular remissions and low discontinuation rates, highlight the tremendous promise of revumenib in the treatment of R/R mNPM1 AML patients."

Revumenib Near-Term Milestones

The Company has several trials of revumenib ongoing across the treatment landscape in mNPM1 and KMT2A-rearranged (KMT2Ar) acute leukemias. In addition to the clinical trials that Syndax is conducting, the Company is working with cooperative groups and key investigators to further elucidate the potential clinical benefit of revumenib. Syndax expects to achieve the following upcoming revumenib milestones:

Receive FDA approval for treatment of R/R KMT2Ar acute leukemias in the fourth quarter of 2024.
Present data in KMT2Ar and mNPM1 acute leukemias at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2024.
Initiate a pivotal combination trial with venetoclax/azacitidine in newly diagnosed mNPM1 AML or KMT2Ar acute leukemias by year-end 2024.
Publish pivotal AUGMENT-101 results in R/R mNPM1 AML patients and present results at a medical conference in the first half of 2025.
Submit a supplemental NDA (sNDA) for treatment of R/R mNPM1 AML in the first half of 2025.
Conference Call and Webcast
Syndax will host a conference call and webcast to discuss the results of the AUGMENT-101 trial in R/R mNPM1 AML today, November 12, 2024, at 8:00 a.m. ET.

The live webcast 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: Syndax Conference Call 1
Domestic Dial-in Number: 800-590-8290
International Dial-in Number: 240-690-8800
Live webcast: https://www.veracast.com/webcasts/syndax/events/specialconf1.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 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.

About the Phase 1/2 AUGMENT-101 Trial
AUGMENT-101 an open-label, multi-center trial evaluating the safety, tolerability, pharmacokinetics, and efficacy of revumenib that consists of a dose escalation part and an expansion part. In the dose escalation part, a revumenib dose with and without a strong CYP3A4 inhibitor was identified. The expansion part was designed to evaluate revumenib in patients with relapsed or refractory (R/R) KMT2Ar AML, patients with KMT2Ar ALL, and patients with mutant NPM1 (mNPM1) AML. The primary endpoint for each of the cohorts is efficacy as measured by the rate of complete remission (CR) plus CR with partial hematologic recovery (CRh) and short- and long-term safety and tolerability, with secondary endpoints including duration of response (DOR) and overall survival (OS).

More information can be found on www.clinicaltrials.gov (NCT04065399).

Positive data from the KMT2Ar AML and ALL patients in the trial supported a New Drug Application (NDA) filing for revumenib in R/R KMT2Ar acute leukemia, which is currently under review by the U.S. FDA with a PDUFA action date of December 26, 2024. Positive data from the mNPM1 AML patients in the trial are expected to support an sNDA filing in the first half of 2025.

About Mutant NPM1 (mNPM1) Acute Myeloid Leukemia (AML)
Mutations in the NPM1 gene are the most common genetic alteration in adult AML and are observed in approximately 30% of cases. Patients with relapsed or refractory mNPM1 AML have a poor prognosis and high unmet need. Similar to KMT2A-rearranged acute leukemia, mNPM1 AML is highly dependent on the expression of specific developmental genes shown to be negatively impacted by inhibitors of the menin-KMT2A interaction. mNPM1 AML is routinely diagnosed through currently available screening techniques. There are currently no approved targeted therapies for mNPM1 AML.