Cytarabine

- Data continue to support revumenib's potential to enhance current standard of care agents - - 96% CRc (23 of 24 pts) observed in BEAT AML trial exploring revumenib in combination with venetoclax/azacitidine in newly diagnosed mNPM1 or KMT2Ar AML - - 52% CRc (14 of 27 pts) observed in AUGMENT-102 trial of revumenib in combination with fludarabine-cytarabine in acute leukemia patients with R/R mNPM1, NUP98r or KMT2Ar - WALTHAM, Mass., June 14, 2024 /PRNewswire/ -- Syndax Pharmaceuticals (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, today announced updated data from multiple combination trials of revumenib, the Company's potent, selective, small molecule menin inhibitor, in patients with acute leukemias. The updated data are being presented at the European Hematology Association (EHA) 2024 Congress, being held June 13-16 in Madrid, Spain and virtually. "The growing body of data supports the potential for revumenib to have a meaningful impact in combination with current standard of care therapies," said Joshua F. Zeidner, M.D., Chief, Leukemia Research at the University of North Carolina, Lineberger Comprehensive Cancer Center. "Based on the BEAT AML data in the newly diagnosed setting which showed a high rate of MRD-negative responses coupled with a safety profile that enables combination use, revumenib has the potential to become a cornerstone of treatment as front-line therapy for newly diagnosed KMT2Ar and mNPM1 AML." "We are committed to advancing revumenib across a spectrum of acute leukemia patients. As we prepare for the expected near-term approval of revumenib in the relapsed or refractory setting, we look forward to providing additional clinical data as monotherapy and in combination to support treatment in various acute leukemia treatment settings where novel treatment options are urgently needed," said Neil Gallagher, M.D., Ph.D., President, Head of Research and Development at Syndax. BEAT AML Trial The Company announced updated data from the BEAT AML trial of revumenib in combination with venetoclax/azacitidine in newly diagnosed mutant nucleophosmin (mNPM1) or KMT2A-rearranged (KMT2Ar) acute myeloid leukemia (AML) patients aged 60 years or older in an oral presentation titled "Phase 1b Study of Azacitidine, Venetoclax and Revumenib in Newly Diagnosed Older Adults with NPM1 Mutated or KMT2A Rearranged AML: Interim Results of Dose Escalation from the BeatAML Consortium." The dose escalation phase of the trial tested revumenib at doses of 113 mg and 163 mg q12h in combination with a strong CYP3A4 inhibitor beginning on day 1 of a 28-day cycle in combination with on label doses of venetoclax and azacitidine. As of the data cutoff date of May 1, 2024, 26 newly diagnosed mNPM1 (n=17) or KMT2Ar (n=9) AML patients were enrolled. In the efficacy evaluable population, the composite complete remission1 (CRc) rate was 96% (23/24) and 92% (22/24) of patients also attained minimal residual disease (MRD) negative status as determined by central flow cytometry. Three patients proceeded to hematopoietic stem cell transplant (HSCT). The first cohort of patients treated in the trial, at 113 mg, had extended follow-up and an estimated 12-month survival of 100%. Revumenib was dosed safely at both the 113 mg and 163 mg q12h dose in combination with venetoclax and azacitidine. 15% (4/26) of patients experienced differentiation syndrome with one (4%) Grade 3 event. 46% (12/26) of patients experienced QTc prolongation with three (12%) Grade 3 events. All DS and QTc prolongations were self-limiting and resolved without complication or the need for revumenib dose reductions. Venetoclax was dosed in accordance with its label and an analysis of the onset and extent of hematologic toxicities suggest a similar experience to what has been reported for the venetoclax/azacytidine doublet. Overall, there were no new or increased safety signals observed when revumenib was added to this triplet combination. An expansion cohort is ongoing at both dose levels to establish the recommended dose for future trials. The Company plans to initiate a pivotal trial with this combination in front-line newly diagnosed patients by year-end 2024. AUGMENT-102 Trial The Company also announced a poster presentation featuring updated data from the AUGMENT-102 trial of revumenib in combination with fludarabine/cytarabine in a predominantly pediatric population of patients with relapsed/refractory (R/R) mNPM1 (n=2), NUP98-rearranged (NUP98r) (n=1) or KMT2Ar (n=23) AML titled "Safety and Activity of Revumenib in Combination with Fludarabine/Cytarabine (FLA) in Patients with Relapsed/Refractory Acute Leukemias." As of the data cutoff date of January 15, 2024, 27 patients received revumenib plus FLA, including 9 patients treated at 113 mg q12h and 18 treated at 163 mg q12h. The patients enrolled had a median age of 6 years and had received a median of 3 prior lines of therapy. Eighteen (67%) patients had prior FLA containing regimens while 11 (41%) patients had prior HSCT. Five (56%) patients treated at the 113 mg q12h dose and nine (50%) patients treated at the 163 mg q12h achieved a CRc. Most patients who achieved a CRc and had evaluable data achieved (MRD) negative status (10/14; 71%) and 7 patients underwent HSCT while in remission following treatment. Overall, revumenib was tolerable in heavily pretreated patients with KMT2Ar, NUP98r, or NPM1m acute leukemias without increased frequency or severity of AEs compared with historic FLA data or revumenib monotherapy. One DLT occurred at the 163 mg q12h dose that was a Grade 4 decreased neutrophil count in a patient with multiple prior transplants. Grade 3 and above adverse events in over 40% of patients included decreased platelet count (17/27; 63%), anemia (15/27; 56%) and febrile neutropenia (13/27; 48%). Lower rates of cytopenias were reported at the 163 mg q12h dose than the 113 mg q12h dose, consistent with faster remission at the higher dose. Lower rates of nonhematologic adverse events were also observed at the higher dose level, which further suggests that the adverse event profile was not driven by revumenib. There was one adverse event leading to death (sepsis at the 113 mg q12h dose level) not related to revumenib. There were no cases of differentiation syndrome in the trial. This study supports the selection of revumenib 163 mg q12h (95 mg/m2 q12h if weight <40 kg) combined with FLA and a strong cytochrome P450 inhibitor as the RP2D, in line with the dose of revumenib under FDA review as a monotherapy agent. Additional Presentations at EHA 2024 In addition to updated results from the BEAT AML and AUGMENT-102 studies, an encore presentation of results from the pivotal AUGMENT-101 study of revumenib in R/R KMT2Ar acute leukemia were also featured at the Congress during an oral session titled "Revumenib Monotherapy in Patients with Relapsed/Refractory KMT2Ar Acute Leukemia: Topline Efficacy and Safety Results from the Pivotal AUGMENT-101 Phase 2 Study." Results from an exploratory analysis of immunophenotypic changes in AML blasts following treatment with revumenib were also featured in a poster presentation titled "Characterization of Immunophenotypic Changes Following Menin Inhibition in Acute Myeloid Leukemia." Copies of EHA posters and presentations will be available in the Publications and Meeting Presentations section of Syndax's website. About Revumenib Revumenib is a potent, selective, 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 ALL and AML, and mutant nucleophosmin (mNPM1) AML. Positive topline results from the Phase 2 AUGMENT-101 trial in R/R KMT2Ar acute leukemia showing the trial met its primary endpoint were presented at the 65th American Society of Hematology Annual Meeting, and data from the Phase 1 portion of AUGMENT-101 in acute leukemia was published in Nature. Revumenib was granted Orphan Drug Designation by the FDA and European Commission for the treatment of patients with AML and Fast Track designation by the FDA for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation. Revumenib was granted Breakthrough Therapy Designation by the FDA for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement. About Syndax Syndax Pharmaceuticals is a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies. Highlights of the Company's pipeline include revumenib, a highly selective menin inhibitor, and axatilimab, a monoclonal antibody that blocks the CSF-1 receptor. For more information, please visit or follow the Company on X (formerly Twitter) and LinkedIn. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "anticipate," "believe," "could," "estimate," "expects," "intend," "may," "plan," "potential," "predict," "project," "should," "will," "would" or the negative or plural of those terms, and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Syndax's expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties. Actual results may differ materially from these forward-looking statements. Forward-looking statements contained in this press release include, but are not limited to, statements about the progress, timing, clinical development and scope of clinical trials, the reporting of clinical data for Syndax's product candidates, and the potential use of its product candidates to treat various cancer indications and fibrotic diseases. Many factors may cause differences between current expectations and actual results, including: unexpected safety or efficacy data observed during preclinical or clinical trials; clinical trial site activation or enrollment rates that are lower than expected; changes in expected or existing competition; changes in the regulatory environment; failure of Syndax's collaborators to support or advance collaborations or product candidates; and unexpected litigation or other disputes. Other factors that may cause Syndax's actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in Syndax's filings with the U.S. Securities and Exchange Commission, including the "Risk Factors" sections contained therein. Except as required by law, Syndax assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available. References 1Composite complete remission (CRc) includes CR, CRh, CRp, and CRi CR = Complete remission CRh = Complete remission with partial hematologic recovery CRp = Complete remission with incomplete platelet recovery CRi = Complete remission with incomplete count recovery Syndax Contact Sharon Klahre Syndax Pharmaceuticals, Inc. [email protected] Tel 781.684.9827 SNDX-G SOURCE Syndax Pharmaceuticals, Inc.

- Novel targeted radiotherapy-based combination being studied as potential backbone therapy potential relapsed or refractory acute myeloid leukemia - Actimab-A + CLAG-M produced high rates of response, measurable residual disease negativity, bone marrow transplant access and improved survival outcomes in high-risk patients including TP53+ and venetoclax treated patients - SNMMI oral presentation highlighted dosimetry results and safety data supporting this novel radiotherapy combination NEW YORK, June 11, 2024 /PRNewswire/ --Actinium Pharmaceuticals, Inc., (NYSE AMERICAN: ATNM) (Actinium or the Company), a leader in the development of Antibody Radiation Conjugates (ARCs) and other targeted radiotherapies, today highlighted data from the completed Phase 1b combination trial of Actimab-A + CLAG-M in patients with relapsed or refractory acute myeloid leukemia (r/r AML) at the 2024 Society of Nuclear Medicine & Molecular Imaging (SNMMI) Annual Meeting held June 8 – 11, 2024, in Toronto, Canada. Actimab-A is an ARC comprised of a CD33 targeting monoclonal antibody conjugated with the alpha-particle emitter Actinium-225 isotope payload. Actimab-A has been studied as a single agent and in combination with chemotherapies and targeted therapies in Phase 1 and Phase 2 trials. Sandesh Seth, Actinium's Chairman and CEO, said, "These results demonstrate the immense potential of targeted radiotherapy via ARCs from both an efficacy and safety perspective. Through the use of dosimetry, we can estimate radiation doses to the target organ and non-targeted healthy organs and as observed in this trial, we saw no safety signals for the kidneys, liver or other major organs. Together with the potent efficacy, particularly in these high-risk relapse and refractory patients, we are highly excited by the building clinical pro We look forward to continuing to advance our Actimab-A program as a broad-based combination approach with targeted and non-targeted therapies in collaboration with the NCI for the benefit of AML patients who are eligible for targeted radiotherapy." The Phase 1b Actimab-A + CLAG-M combination trial enrolled patients with high-risk r/r AML with the following features: Median age of 62 with patients up to 73 years old 91% of patients had intermediate (n=3, 13%) or adverse cytogenetics (n=18, 78%) Over 50% of patients had a TP53 mutation Median of 2 lines of prior therapy (range:1-5) including: Prior bone marrow transplant: 57% Prior venetoclax treatment: 57% Despite the high-risk pro the patients on the study, the combination of Actimab-A + CLAG-M produced high rates of response and measurable residual disease negativity and improved survival outcomes across all patient subsets: 64% of eligible patients proceeded to bone marrow transplant with these patients having a median overall of 24 months. Dosimetry and Safety: A validated pharmacokinetic model was used to estimate the biodistribution of Actimab-A based on the distribution of CD33+ AML blast cells based on data derived from patients in the Phase 1b study Across all dose levels including 0.75 µCi/kg, which was determined to be the optimal dose, and 1.0 µCi/kg (the highest dose in the Phase 1b study) radiation doses for key organs were well below known tolerance levels with external beam radiation therapy (EBRT) No safety signals for major organs such as liver, heart, kidneys, lungs and intestines were observed and a safety pro with that expected in heavily pre-treated r/r AML patients given salvage therapy A single 30-minute administration of Actimab-A results in rapid radiation delivery and clearance with peak concentration reached around 0.6 hours and undetectable in the blood by 48 hours after administration The dose of 0.75 µCi/kg was identified as optimal for this combination therapy and will be further evaluated in the next stage of clinical development About the SNMMI Annual Meeting The SNMMI Annual Meeting is recognized as the premier educational, scientific, research, and networking event in nuclear medicine and molecular imaging. The four-day event, taking place each June, provides physicians, technologists, pharmacists, laboratory professionals, and scientists with an in-depth view of the latest research and development in the field as well as providing insights into practical applications for the clinic. About Actinium Pharmaceuticals, Inc. Actinium develops targeted radiotherapies to meaningfully improve survival for people who have failed existing oncology therapies. Advanced pipeline candidates Iomab-B (pre-BLA & MAA (EU)), an induction and conditioning agent prior to bone marrow transplant, and Actimab-A (National Cancer Institute CRADA pivotal development path), a therapeutic agent, have demonstrated potential to extend survival outcomes for people with relapsed and refractory acute myeloid leukemia. Actinium plans to advance Iomab-B for other blood cancers and next generation conditioning candidate Iomab-ACT to improve cell and gene therapy outcomes. Actinium holds more than 230 patents and patent applications including several patents related to the manufacture of the isotope Ac-225 in a cyclotron. For more information, please visit: Forward-Looking Statements This press release may contain projections or other "forward-looking statements" within the meaning of the "safe-harbor" provisions of the private securities litigation reform act of 1995 regarding future events or the future financial performance of the Company which the Company undertakes no obligation to update. These statements are based on management's current expectations and are subject to risks and uncertainties that may cause actual results to differ materially from the anticipated or estimated future results, including the risks and uncertainties associated with preliminary study results varying from final results, estimates of potential markets for drugs under development, clinical trials, actions by the FDA and other governmental agencies, regulatory clearances, responses to regulatory matters, the market demand for and acceptance of Actinium's products and services, performance of clinical research organizations and other risks detailed from time to time in Actinium's filings with the Securities and Exchange Commission (the "SEC"), including without limitation its most recent annual report on form 10-K, subsequent quarterly reports on Forms 10-Q and Forms 8-K, each as amended and supplemented from time to time. Investors: investorrelations@actiniumpharma.com Company Codes: AMEX:ATNM