Venetoclax

In first line AML (ALICE-2 trial), iadademstat with azacitidine and venetoclax showed high levels of clinical activity, with 100% (18/18) ORR, 89% (16/18) CRc and 78% (14/18) CR, and continued to demonstrate a favorable safety profile All patients with TP53 or RAS pathway mutations achieved a complete response, showcasing the activity of the iadademstat combination across genomically defined adverse-risk subgroups and its potential in these populations In FLT3-mutated refractory-relapsed patients (FRIDA trial), iadademstat with gilteritinib continued to show a favorable safety pro a high CRc rate of 67% MADRID and CAMBRIDGE, Mass., June 11, 2026 (GLOBE NEWSWIRE) -- Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company and a global leader in epigenetics, today presented updated positive clinical data from two clinical trials of its selective LSD1 inhibitor iadademstat in acute myeloid leukemia (AML) at the 2026 European Hematology Association (EHA) Annual Congress. “We are encouraged by the sustained strength and consistency of the data from both the ALICE-2 and FRIDA trials,” said Carlos Buesa, Chief Executive Officer of Oryzon Genomics. “With over 80% of patients now enrolled in ALICE-2, the favorable safety pro strong efficacy signals of iadademstat in newly diagnosed, unfit AML patients reinforce our confidence in this combination approach, including within genomically defined adverse-risk populations such as TP53-mutated and RAS pathway–mutated AML. These results are consistent with prior findings in TP53-mutated patients in our ALICE trial, where the combination of iadademstat and azacitidine doubled median overall survival compared with historical rates. As enrollment continues, we anticipate reporting final data by year-end and advancing toward a potential registrational study in first-line AML by 2027, with a focus on adverse-risk populations.” Ana Limón, Senior Vice President of Clinical Development and Global Medical Affairs at Oryzon, added: “Historically, with azacitidine plus venetoclax, one third of first line AML patients do not respond, and the depth of response is variable, underscoring the need for novel triplet strategies, particularly for patients without targetable mutations. The maturing data from both trials continue to reinforce the strength of LSD1 inhibition as an add-on approach in AML. In addition to the high ORR and CR rates observed to date in the ALICE-2 trial, treatment with the iadademstat-azacitidine-venetoclax triplet has enabled a high proportion of patients to transition to allogeneic hematopoietic cell transplantation (HCT), potentially improving long-term survival. Overall, the safety and efficacy observed across both trials support further clinical development.” Data Summary ALICE-2 Phase Ib clinical trial (NCT06357182) investigating iadademstat in combination with azacitidine and venetoclax in newly diagnosed AML High rates of activity, with a 100% (18/18) overall response rate (ORR), 89% (16/18) composite complete remission (CRc) rate and 78% (14/18) complete response (CR) rate. CRs occur early, most of them in cycle 1. Efficacy was observed across different genomic risk groups, including TP53 and RAS pathway mutations and patients with complex karyotypes, all considered adverse risk. Patients with TP53-mutated disease (2/2) attained CR and showed a reduction in TP53 variant allele frequency (14% to undetected and 22% to 1%, respectively). All patients with RAS pathway mutations (3/3) achieved CR. After a median follow-up of 8 months, median overall survival (OS) and event-free survival (EFS) were not reached; estimated 12-month OS and EFS were 79% and 71%, respectively. 9 patients successfully transitioned to allogeneic HCT, with an estimated 12-month OS of 88%. The iadademstat-azacitidine-venetoclax combination continues to show a favorable safety profile. FRIDA Phase Ib clinical trial (NCT05546580) investigating iadademstat in combination with gilteritinib in FLT3 ‑ mutated relapsed/refractory AML The poster reports data from the expansion cohort at the selected pharmacological active dose (PAD, 75 ug iadademstat); 23 patients have been enrolled at this dose, with 18 being evaluable for response. High CRc rate of 67% (12/18) in a heavily pre-treated population. Iadademstat plus standard of care (SoC) treatment gilteritinib demonstrated a manageable safety profile, without adding toxicity to the SoC. About ALICE-2 ALICE-2 (NCT06357182) is a Phase Ib investigator-initiated study sponsored by Oregon Health & Science University (OHSU) in newly diagnosed AML. It is evaluating treatment with iadademstat in combination with azacitidine and venetoclax, the standard of care, in newly diagnosed unfit patients. The study’s primary endpoint is the incidence of dose-limiting toxicities (DLTs). Secondary endpoints include efficacy measurements such as composite complete remission (CRc: complete remission [CR] + CR with partial hematologic recovery [CRh] + CR with incomplete recovery [CRi]), and overall response rate (ORR: CRc + morphologic leukemia free state [MLFS] + partial remission [PR]). The trial plans to enrol 24 patients to achieve 21 evaluable patients. About FRIDA FRIDA (NCT05546580) is a Phase Ib clinical study sponsored by Oryzon. It is evaluating iadademstat in combination with gilteritinib for the treatment of FLT3-mutant relapsed/refractory AML. The primary endpoints are incidence of treatment emergent adverse events (TEAEs) and determination of the recommended Phase II dose (RP2D). Secondary endpoints include response rates (CR, CRh, CRi, MLFS, CRc), event-free survival (EFS), and overall survival (OS). About Oryzon Founded in 2000 and headquartered in Barcelona, Spain, Oryzon (ISIN: ES0167733015) is a clinical-stage biopharmaceutical company and a European leader in epigenetics, with a strong focus on personalized medicine for central nervous system (CNS) disorders and oncology. Oryzon’s team comprises highly experienced pharmaceutical professionals based in Barcelona, Boston, and New Jersey. The Company has an advanced clinical portfolio built around two LSD1 inhibitors: iadademstat, its oncology/hematology program, with several ongoing Phase I and II studies and which has demonstrated strong preliminary clinical activity in acute myeloid leukemia, including a 100% overall response rate (ORR) in first-line AML; and vafidemstat, its lead CNS program, which is Phase III–ready in Borderline Personality Disorder (BPD). In addition, Oryzon is advancing a broader epigenetics pipeline targeting other mechanisms, including HDAC6, for which the Company has nominated ORY-4001 as a clinical candidate for potential development in Charcot–Marie–Tooth disease (CMT), amyotrophic lateral sclerosis (ALS), and other neurological disorders. The Company also operates a robust platform for biomarker identification and target validation across malignant and neurological diseases. For more information, visit About Iadademstat Iadademstat (ORY-1001) is an oral, highly selective inhibitor of the epigenetic enzyme LSD1, with potent differentiating effect in hematologic cancers. Iadademstat has shown encouraging safety and strong clinical activity in combination with azacitidine in a Phase IIa trial in elder 1L acute myeloid leukemia (AML) patients (ALICE trial). Iadademstat is currently being evaluated in combination with azacitidine and venetoclax in 1L AML in the ALICE-2 trial, an investigator-initiated study (IIS) led by OHSU, and in combination with gilteritinib in the company-sponsored Phase Ib FRIDA trial in relapsed/refractory FLT3-mutant AML, with highly encouraging preliminary safety and efficacy data in both trials reported at EHA-2026: 100% overall response rate (ORR) and 89% composite complete remission rate (CRc), with 78% strict CR in 1L AML, and 67% CRc in R/R Flt3-mut AML. Additional studies in hematologic malignancies include an IIS in myelodysplastic syndrome (MDS) and National Cancer Institute (NCI)-sponsored trials in myeloproliferative neoplasms and 1L AML conducted under the Cooperative Research and Development Agreement (CRADA) between Oryzon and the NCI. Beyond hematological cancers, iadademstat is being evaluated in extensive stage small cell lung cancer (ED-SCLC) in a Phase I/II randomized trial in 1L in combination with immune checkpoint inhibition (ICI) sponsored by NCI and led by the Memorial Sloan Kettering Cancer Center, and an IIS trial in combination with ICI and radiotherapy. Oryzon has also expanded iadademstat into non-oncological hematology indications, with ongoing trials in sickle cell disease and essential thrombocythemia. Iadademstat has orphan drug designation for AML in the US and EU and for SCLC in the US. 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In addition, this document does not constitute an offer of purchase, sale or exchange, nor a request for an offer of purchase, sale or exchange of securities, nor a request for any vote or approval in any jurisdiction. The shares of Oryzon Genomics, S.A. may not be offered or sold in the United States of America except pursuant to an effective registration statement under the Securities Act of 1933 or pursuant to a valid exemption from registration. Spain Oryzon IR & Media, Europe & US Patricia Cobo/Mario Cordera Emili Torrell Sandya von der Weid Atrevia Chief BD Officer LifeSci Advisors, LLC +34 91 564 07 25 +34 673 33 97 65 +34 93 515 1313 +41 78 680 05 38 pcobo@atrevia.com mcordera@atrevia.com etorrell@oryzon.com svonderweid@lifesciadvisors.com

– High response rates observed with the all-oral combination in a heavily pretreated population, including 88% (37/42) ORR, 71% (30/42) CRc, and 60% CR/CRh (25/42) – – Strong activity across subgroups, including 70% (14/20) CR/CRh in venetoclax-naïve and 50% (11/22) CR/CRh in venetoclax-exposed patients – – Deep responses with 80% (24/30) MRD negativity among evaluable CRc responders – – Robust transplant rate with 45% (19/42) of patients proceeding to transplant and 63% (12/19) resuming revumenib post-transplant – – Encouraging durability with median overall survival after transplant not reached – – Combination was generally well-tolerated – NEW YORK, June 11, 2026 (GLOBE NEWSWIRE) -- Syndax Pharmaceuticals (Nasdaq: SNDX), a commercial-stage biopharmaceutical company advancing innovative cancer therapies, today announced that data from the Phase 1/2 SAVE trial of an all-oral regimen of Revuforj ® (revumenib), decitabine/cedazuridine, and venetoclax in relapsed or refractory (R/R) NPM1 mutated (NPM1m), KMT2A-rearranged (KMT2Ar), or NUP98-rearranged (NUP98r) acute myeloid leukemia (AML) were published in the Journal of Clinical Oncology and simultaneously presented at the European Hematology Association (EHA) 2026 Congress in Stockholm, Sweden. Revuforj is the first and only menin inhibitor that is FDA approved for patients one year and older with R/R AML with a susceptible NPM1 mutation who have no satisfactory alternative treatment options or R/R acute leukemia with a KMT2A translocation as determined by an FDA-authorized test. “The deep and durable remissions observed among patients with R/R NPM1m, KMT2Ar, or NUP98r AML who received an all-oral combination of revumenib, decitabine/cedazuridine, and venetoclax, highlight the potential for revumenib combinations to advance the standard of care treatment for menin-dependent acute leukemias,” said Nick Botwood, MBBS, Head of Research & Development and Chief Medical Officer at Syndax. “The SAVE data provide strong support for further studying revumenib with venetoclax and a hypomethylating agent in multiple settings, including among newly diagnosed patients who are unfit for intensive chemotherapy in the ongoing pivotal EVOLVE-2 trial and among fit patients in the RAVEN trial.” “The results observed with the all-oral SAVE regimen in heavily pretreated patients with R/R NPM1m, KMT2Ar, or NUP98r AML are very encouraging,” said Ghayas C. Issa, M.D., Associate Professor of Leukemia at The University of Texas MD Anderson Cancer Center and Principal Investigator of the SAVE trial. “Notably, 88% of patients achieved a response with the majority achieving MRD negativity, 45% proceeded to a potentially curative stem cell transplant, and we observed a 14-month median overall survival. We also saw an impressive 50% CR/CRh rate and approximately 12-month median overall survival in patients with prior venetoclax exposure, a population that has historically experienced poor outcomes with a median survival of less than three months.” Summary of Key Results from the SAVE Trial in R/R NPM1m, KMT2Ar, and NUP98r AML The publication entitled, “All-Oral Combination of Revumenib, Decitabine, and Venetoclax for Relapsed or Refractory AML (SAVE)” reports results from the R/R cohort of patients in the Phase 1/2, single-center, open-label SAVE trial. The primary endpoint of Phase 1 was the recommended Phase 2 dose of revumenib in combination therapy, which was identified as dose level 1 (the FDA-approved monotherapy dose of revumenib). The primary endpoint of Phase 2 was the composite complete remission 1 (CRc) rate. As of January 2026, 42 patients with R/R AML were enrolled in the SAVE trial, including five adolescents. 38% (16/42) had NPM1m, 40% (17/42) had KMT2Ar, and 21% (9/42) had NUP98r. The median age was 40 years (range: 12-82). Patients were heavily pretreated, with a median of two prior lines of therapy (range: 1-5); 52% (22/42) had received prior venetoclax and 33% (14/42) a prior hematopoietic stem cell transplant (HSCT). The overall response rate (ORR) was 88% (37/42), the CRc rate was 71% (30/42), and the complete remission plus complete remission with partial hematological recovery (CR/CRh) rate was 60% (25/42) for the entire population. Response rates were similar across genotypes, including patients with NPM1m, KMT2Ar, or NUP98r. Overall, 45% (19/42) of patients proceeded to HSCT following treatment with the regimen, including 38% (6/16) of NPM1m patients, 65% (11/17) of KMT2Ar patients, and 22% (2/9) of NUP98r patients. Of the 19 patients that proceeded to HSCT, 63% (12/19) resumed revumenib after HSCT. The rates of measurable residual disease (MRD) negativity by flow cytometry were 68% (25/37) among evaluable responders, 80% (24/30) among those with CRc, and 80% (20/25) among those with CR/CRh. Among evaluable patients with CRc, 67% (8/12) were MRD negative by NPM1 NGS ( 450 msec. If QTc interval prolongation occurs, interrupt, reduce, or permanently discontinue Revuforj. WARNINGS AND PRECAUTIONS Differentiation Syndrome: Revuforj can cause fatal or life-threatening differentiation syndrome (DS). Symptoms of DS, including those seen in patients treated with Revuforj, include fever, dyspnea, hypoxia, peripheral edema, pleuropericardial effusion, acute renal failure, rash, and/or hypotension. In clinical trials, DS occurred in 60 (25%) of 241 patients treated with Revuforj at the recommended dosage for relapsed or refractory acute leukemia. Among those with a KMT2A translocation, DS occurred in 33% of patients with acute myeloid leukemia (AML), 33% of patients with mixed-phenotype acute leukemia (MPAL), and 9% of patients with acute lymphoblastic leukemia (ALL); DS occurred in 18% of patients with NPM1m AML. DS was Grade 3 or 4 in 12% of patients and fatal in 2 patients. The median time to initial onset was 9 days (range 3-41 days). Some patients experienced more than 1 DS event. Treatment interruption was required for 7% of patients, and treatment was withdrawn for 1%. Reduce the white blood cell count to less than 25 Gi/L prior to starting Revuforj. If DS is suspected, immediately initiate treatment with systemic corticosteroids (e.g., dexamethasone 10 mg IV every 12 hours in adults or dexamethasone 0.25 mg/kg/dose IV every 12 hours in pediatric patients weighing less than 40 kg) for a minimum of 3 days and until resolution of signs and symptoms. Institute supportive measures and hemodynamic monitoring until improvement. Interrupt Revuforj if severe signs and/or symptoms persist for more than 48 hours after initiation of systemic corticosteroids, or earlier if life-threatening symptoms occur such as pulmonary symptoms requiring ventilator support. Restart steroids promptly if DS recurs after tapering corticosteroids . QTc Interval Prolongation and Torsades de Pointes: Revuforj can cause QT (QTc) interval prolongation and Torsades de Pointes. Of the 241 patients treated with Revuforj at the recommended dosage for relapsed or refractory acute leukemia in clinical trials, QTc interval prolongation was reported as an adverse reaction in 86 (36%) patients. QTc interval prolongation was Grade 3 in 15% and Grade 4 in 2%. The heart-rate corrected QT interval (using Fridericia’s method) (QTcF) was greater than 500 msec in 10%, and the increase from baseline QTcF was greater than 60 msec in 24%. Revuforj dose reduction was required for 7% due to QTc interval prolongation. QTc prolongation occurred in 21% of the 34 patients less than 17 years old, 35% of the 146 patients 17 years to less than 65 years old, and 46% of the 61 patients 65 years or older. One patient had a fatal outcome of cardiac arrest, and one patient had non-sustained Torsades de Pointes. Correct electrolyte abnormalities, including hypokalemia and hypomagnesemia, prior to and throughout treatment with Revuforj. Perform an electrocardiogram (ECG) prior to initiation of Revuforj, and do not initiate Revuforj in patients with QTcF >450 msec. Perform an ECG at least once weekly for the first 4 weeks and at least monthly thereafter. In patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval, more frequent ECG monitoring may be necessary. Concomitant use with drugs known to prolong the QTc interval may increase the risk of QTc interval prolongation. Interrupt Revuforj if QTcF increases >480 msec and 500 msec or by >60 msec from baseline, and restart Revuforj twice daily at the lower-dose level after the QTcF interval returns to ≤480 msec Permanently discontinue Revuforj in patients with ventricular arrhythmias and in those who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia Embryo-Fetal Toxicity: Revuforj can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with Revuforj and for 4 months after the last dose of Revuforj. ADVERSE REACTIONS Fatal adverse reactions occurred in 9 (4%) patients who received Revuforj, including 4 with sudden death, 2 with differentiation syndrome, 2 with hemorrhage, and 1 with cardiac arrest. Serious adverse reactions were reported in 184 (76%) patients. The most frequent serious adverse reactions (≥10%) were infection (29%), febrile neutropenia (20%), bacterial infection (15%), differentiation syndrome (13%), and hemorrhage (11%). The most common adverse reactions (≥20%) including laboratory abnormalities, were phosphate increased (51%), hemorrhage (48%), nausea (48%), infection without identified pathogen (46%), aspartate aminotransferase increased (44%), alanine aminotransferase increased (40%), creatinine increased (38%), musculoskeletal pain (37%), febrile neutropenia (37%), electrocardiogram QT prolonged (36%), potassium decreased (34%), parathyroid hormone intact increased (34%), alkaline phosphatase increased (33%), diarrhea (29%), bacterial infection (27%), triglycerides increased (27%), phosphate decreased (25%), differentiation syndrome (25%), fatigue (24%), edema (24%), viral infection (23%), decreased appetite (20%), and constipation (20%). DRUG INTERACTIONS Drug interactions can occur when Revuforj is concomitantly used with: Strong CYP3A4 inhibitors: reduce Revuforj dose Strong or moderate CYP3A4 inducers: avoid concomitant use with Revuforj QTc-prolonging drugs: avoid concomitant use with Revuforj. If concomitant use is unavoidable, obtain ECGs when initiating, during concomitant use, and as clinically indicated. Withhold Revuforj if the QTc interval is >480 msec. Restart Revuforj after the QTc interval returns to ≤480 msec SPECIFIC POPULATIONS Lactation: advise lactating women not to breastfeed during treatment with Revuforj and for 1 week after the last dose. Pregnancy and testing: Revuforj can cause fetal harm when administered to a pregnant woman. Verify pregnancy status in females of reproductive potential within 7 days prior to initiating Revuforj. Infertility: based on findings in animals, Revuforj may impair fertility. The effects on fertility were reversible. Pediatric: monitor bone growth and development in pediatric patients . Geriatric: no overall differences were observed in the effectiveness of Revuforj between patients who were 65 years and older, and younger patients. Compared to younger patients, the incidences of QTc prolongation and edema were higher in patients 65 years and older. To report SUSPECTED ADVERSE REACTIONS, contact Syndax Pharmaceuticals at 1-888-539-3REV or FDA at 1-800-FDA-1088 or . Please see Full Prescribing Information , including BOXED WARNINGS. About Syndax Syndax Pharmaceuticals is a commercial-stage biopharmaceutical company advancing innovative cancer therapies. Highlights of the Company's pipeline include Revuforj ®  (revumenib), an FDA-approved menin inhibitor, and Niktimvo™ (axatilimab-csfr), an FDA-approved monoclonal antibody that blocks the colony stimulating factor 1 (CSF-1) receptor. Fueled by our commitment to reimagining cancer care, Syndax is working to unlock the full potential of its pipeline and is conducting several clinical trials across the continuum of treatment. For more information, please visit  or follow the Company on  X  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, the acceptance of Syndax and its partners' products in the marketplace, sales, marketing, manufacturing and distribution requirements, 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 to Revuforj's or Niktimvo’s commercial availability; 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 Composite complete remission (CRc) includes CR, CRh, CRp, and CRi. Overall response rate (ORR) includes CR, CRh, CRp, CRi, MLFS, and PR. CR = Complete remission CRh = Complete remission with partial hematologic recovery CRp = Complete remission with incomplete platelet recovery CRi = Complete remission with incomplete count recovery MLFS = Morphologic leukemia-free state PR = Partial response Syndax Contact Sharon Klahre Syndax Pharmaceuticals, Inc. sklahre@syndax.com Tel 781.684.9827 SNDX-G