On June 12, 2025 Syndax Pharmaceuticals (Nasdaq: SNDX), a commercial-stage biopharmaceutical company advancing innovative cancer therapies, reported new data from the pivotal AUGMENT-101 trial of Revuforj (revumenib), the Company’s first-in-class menin inhibitor, in patients with relapsed or refractory (R/R) mutant NPM1 (mNPM1) and NUP98-rearranged (NUP98r) acute myeloid leukemia (AML) (Press release, Syndax, JUN 12, 2025, View Source [SID1234653849]). The data are being presented in posters at the 30th European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress Meeting being held June 12-15, 2025, in Milan, Italy and virtually.

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"The new data from AUGMENT-101 continue to highlight Revuforj’s best-in-class profile and its potential to transform the treatment paradigm for acute leukemia patients with certain genetic alterations," said Nick Botwood, M.B.B.S., Head of Research & Development and Chief Medical Officer at Syndax. "The compelling AUGMENT-101 results led to the FDA approval of Revuforj for R/R acute leukemia with a KMT2A translocation and serve as the foundation for the supplemental NDA we submitted to the FDA for R/R mNPM1 AML, another area of high unmet need."

"Revumenib has shown a potential best-in-class efficacy profile and the latest data in R/R mNPM1 AML underscore the opportunity for revumenib to become a standard of care treatment for this patient population in addition to R/R KMT2Ar acute leukemia," said Ibrahim Aldoss, M.D., Associate Professor, Division of Leukemia, Department of Hematology & Hematopoietic Cell Transplantation at the City of Hope. "The revumenib data in R/R mNPM1 AML presented at EHA (Free EHA Whitepaper) are impressive, with 26% of patients achieving CR/CRh and nearly 50% achieving an overall response with a medicine that was generally well-tolerated. Furthermore, the 23-month median overall survival observed in responders in a subgroup analysis is very encouraging."

Additional Results from R/R mNPM1 AML Patients in the Pivotal Phase 2 Portion of the AUGMENT-101 Trial of Revumenib

The Phase 2 portion of the AUGMENT-101 trial of revumenib enrolled 84 patients with R/R mNPM1 AML. As previously reported, the primary endpoint was met in the protocol-defined primary analysis population which included the first 64 adults who met the efficacy evaluable criteria. At EHA (Free EHA Whitepaper) 2025, the Company will highlight consistent results from all the efficacy-evaluable R/R mNPM1 AML patients (n=77) in the Phase 2 portion of AUGMENT-101 (DCO: September 2024). In this population, the median age was 63 (11-84), 20% had received four or more prior lines of therapy (median prior lines: 2), and 74% had previously received venetoclax.

The complete remission plus complete remission with partial hematologic recovery (CR+CRh) rate was 26% (20/77; 95% CI: 17%-37%). The median duration of CR/CRh response was 4.7 months (95% CI: 2.1-8.2) and the median time to first CR/CRh was 2.8 months (range: 0.9-8.8). Minimal residual disease (MRD) status was assessed in 19 of 20 patients who achieved CR/CRh, 63% (12/19) of whom were MRD negative.

The overall response rate (ORR)1 was 48% (37/77; 95% CI: 37%-60%). Of the patients who achieved an overall response, five patients proceeded to hematopoietic stem cell transplant (HSCT) while in remission, with three patients resuming revumenib after HSCT. Four patients were in CR or CRh and one was in morphologic leukemia-free state (MLFS) when they proceeded to HSCT.

Newly shared data from this single-arm trial show that the median overall survival (OS) observed was 4.8 months (95% CI: 3.4-8.4) among all efficacy-evaluable Phase 2 R/R mNPM1 AML patients, based on the Kaplan-Meier estimate. A new subpopulation analysis that will be reported at a future medical meeting show that a median OS of 23.3 months (95% CI: 8.4-NR) was observed among the 37 patients who achieved an overall response, based on the Kaplan-Meier estimate.

Additionally, newly shared analyses from all efficacy-evaluable Phase 2 R/R mNPM1 AML patients show that CR+CRh responses were observed across subgroups, regardless of co-mutations, number of prior lines of therapy, or prior venetoclax exposure. The CR+CRh rate was 25%, 20%, and 33% among patients with one, two, or three or more prior lines of therapy, respectively. The CR+CRh rate was 45% (95% CI: 23%-69%) among patients without prior venetoclax exposure and 19% (95% CI: 10%-32%) among patients with prior venetoclax exposure.

The AUGMENT-101 Phase 2 safety population included 84 adult and pediatric patients with R/R mNPM1 AML. Detailed results from this safety population were previously published in the journal Blood and will be summarized in the EHA (Free EHA Whitepaper) presentation. The safety profile observed with revumenib in this population was consistent with previously reported data. Revumenib was generally well-tolerated with 4.8% (4/84) of patients discontinuing treatment due to treatment-related adverse events.

Results in R/R NUP98r AML in the Phase 1 Portion of AUGMENT-101 Trial of Revumenib

The Phase 1 portion of the AUGMENT-101 trial of revumenib enrolled R/R acute leukemia patients with KMT2Ar, mNPM1, and other genetic alterations associated with upregulation of HOX, including five patients with NUP98-rearranged (NUP98r) AML. NUP98r is among a growing list of genetic abnormalities associated with upregulation of HOX in leukemia that are susceptible to menin inhibition in preclinical studies.

Among the patients with R/R NUP98r AML, 60% (3/5) attained morphological remission, including one patient who proceeded to transplant, resumed revumenib post-transplant and was in maintenance cycle 10 as of the February 2024 data cutoff date. The safety profile of revumenib in patients with R/R NUP98r AML was consistent with previous reports observed in KMT2Ar or mNPM1 AML.

To further explore the potential for menin inhibition in other genetic populations, a Phase 2 investigator-sponsored study evaluating revumenib in R/R acute leukemia associated with HOX upregulation, including patients with NUP98r AML, has been initiated (NCT06229912). Patients with NUP98r are also included in several other ongoing clinical trials of revumenib, such as the Phase 1 trial of revumenib in combination with intensive chemotherapy in newly diagnosed AML patients and the Phase 1/2 SAVE trial of revumenib in combination with venetoclax and decitabine/cedazuridine in R/R and newly diagnosed patients with AML or mixed-lineage acute leukemia (MPAL). In the SAVE trial, a 100% (5/5) ORR was observed in patients with R/R NUP98r AML (DCO: November 2024).

Additional Revumenib Presentations at EHA (Free EHA Whitepaper) 2025

In addition to newly shared data from patients with R/R mNPM1 AML and NUP98r in the AUGMENT-101 trial, an encore presentation of data from patients with R/R KMT2Ar acute leukemia in the pivotal Phase 2 portion of the trial will also be presented. The data will be featured in a poster session titled "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." Results from the pivotal AUGMENT-101 trial led to the FDA approval in November 2024 of Revuforj (revumenib) for the treatment of R/R acute leukemia with a KMT2A translocation in adult and pediatric patients one year and older.

Two other abstracts were accepted for publication-only. One is a ‘trial in progress’ abstract which describes the design of the ongoing Phase 1 study of revumenib in combination with intensive chemotherapy in newly diagnosed AML patients with KMT2Ar, mNPM1, or NUP98r. The second abstract describes real-world treatment patterns in patients with R/R mNPM1 AML in the U.S. between January 2009 and June 2024.

The posters and publication-only abstracts have been published on the virtual EHA (Free EHA Whitepaper) congress platform. Copies of the posters will be made available in the ‘Publications & Meetings Presentations’ section of the Syndax website.

About Revuforj (revumenib)

Revuforj (revumenib) is an oral, first-in-class, selective menin inhibitor that is FDA approved for the treatment of relapsed or refractory (R/R) acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation in adult and pediatric patients one year and older.

Revumenib is in development for the treatment of R/R acute myeloid leukemia (AML) with a nucleophosmin 1 mutation (mNPM1). Positive pivotal data from the AUGMENT-101 trial in this population with revumenib as a monotherapy were recently published and the Company submitted a supplemental NDA for revumenib in R/R mNPM1 AML in April 2025. Additionally, multiple trials of revumenib in combination with standard-of-care agents in mNPM1 AML or KMT2A-rearranged acute leukemia are ongoing or planned across the treatment landscape, including in newly diagnosed patients.

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.

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME

Differentiation syndrome, which can be fatal, has occurred with Revuforj. Signs and symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, and renal dysfunction. If differentiation syndrome is suspected, immediately initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.

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, and/or hypotension. In clinical trials, DS occurred in 39 (29%) of 135 patients treated with Revuforj. DS was Grade 3 or 4 in 13% of patients and fatal in one. The median time to onset was 10 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: In the clinical trials, QTc interval prolongation was reported as an adverse reaction in 39 (29%) of 135 patients treated with Revuforj. QTc interval prolongation was Grade 3 in 12% of patients. The heart-rate corrected QT interval (using Fridericia’s method) (QTcF) was greater than 500 msec in 8%, and the increase from baseline QTcF was greater than 60 msec in 18%. Revuforj dose reduction was required for 5% of patients due to QTc interval prolongation. QTc prolongation occurred in 16% of the 31 patients less than 17 years old, 33% of the 88 patients 17 years to less than 65 years old, and in 50% of the 16 patients 65 years or older.

Correct electrolyte abnormalities, including hypokalemia and hypomagnesemia, prior to 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, and restart Revuforj at the same dose twice daily after the QTcF interval returns to ≤480 msec
Interrupt Revuforj if QTcF increases >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 4 (3%) patients who received Revuforj, including 2 with differentiation syndrome, 1 with hemorrhage, and 1 with sudden death.

Serious adverse reactions were reported in 99 (73%) patients. The most frequent serious adverse reactions (≥5%) were infection (24%), febrile neutropenia (19%), bacterial infection (17%), differentiation syndrome (12%), hemorrhage (9%), and thrombosis (5%).

The most common adverse reactions (≥20%) including laboratory abnormalities, were hemorrhage (53%), nausea (51%), phosphate increased (50%), musculoskeletal pain (42%), infection (41%), aspartate aminotransferase increased (37%), febrile neutropenia (35%), alanine aminotransferase increased (33%), parathyroid hormone intact increased (33%), bacterial infection (31%), diarrhea (30%), differentiation syndrome (29%), electrocardiogram QT prolonged (29%), phosphate decreased (25%), triglycerides increased (25%), potassium decreased (24%), decreased appetite (24%), constipation (23%), edema (23%), viral infection (23%), fatigue (22%), and alkaline phosphatase increased (21%).

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.

Pediatric: monitor bone growth and development in pediatric patients.

Geriatric: compared to younger patients, the incidences of QTc prolongation and edema were higher in patients 65 years and older.

Infertility: based on findings in animals, Revuforj may impair fertility. The effects on fertility were reversible.

To report SUSPECTED ADVERSE REACTIONS, contact Syndax Pharmaceuticals at 1-888-539-3REV or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see Full Prescribing Information, including BOXED WARNING.

On June 12, 2025 Syndax Pharmaceuticals (Nasdaq: SNDX), a commercial-stage biopharmaceutical company advancing innovative cancer therapies, reported that data from the BEAT AML trial of revumenib in combination with venetoclax and azacitidine (ven/aza) in newly diagnosed mutant NPM1 (mNPM1) and KMT2A-rearranged (KMT2Ar) acute myeloid leukemia (AML) patients were published in the Journal of Clinical Oncology and simultaneously presented in an oral session at the 30th European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress Meeting being held June 12-15, 2025, in Milan, Italy and virtually (Press release, Syndax, JUN 12, 2025, View Source [SID1234653848]).

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"The data observed in BEAT AML underscore the potential for revumenib with ven/aza to improve outcomes for newly diagnosed mNPM1 or KMT2Ar AML patients who are not eligible for intensive chemotherapy, a population that continues to face poor long-term outcomes despite recent advances," said Nick Botwood, M.B.B.S., Head of Research & Development and Chief Medical Officer at Syndax. "These data, along with the results from other trials of revumenib in different settings, highlight revumenib’s potential to become a cornerstone therapy for all menin-dependent acute leukemias across the treatment continuum."

"These data support the ability to combine revumenib with ven/aza in the frontline setting and the clinical activity observed highlights the potential for the triplet to provide high rates of complete remission and MRD-negativity, two treatment goals associated with improved clinical outcomes," said Joshua F. Zeidner, M.D., Chief, Leukemia Research at the University of North Carolina, Lineberger Comprehensive Cancer Center and Principal Investigator in the BEAT AML trial. "Overall, the data we observed in BEAT AML are very encouraging and suggest that the ongoing EVOLVE-2 pivotal frontline trial evaluating the triplet in unfit mNPM1 AML patients could deliver practice-changing results."

Summary of Results from BEAT AML Phase 1 Trial

The publication and EHA (Free EHA Whitepaper) presentation report updated results from the Phase 1b BEAT AML trial evaluating the safety and clinical activity of revumenib in combination with venetoclax/azacitidine in newly diagnosed older adults (≥60 years) with mNPM1 or KMT2Ar AML. The trial is being conducted as part of The Leukemia & Lymphoma Society’s Beat AML Master Clinical Trial (NCT03013998).

As of September 2024, 43 patients were enrolled and treated in BEAT AML across two dose levels of revumenib (113 mg q12 or 163 mg q12h with strong CYP3A4 inhibitor azoles) in combination with venetoclax and azacitidine. Overall, 79% (34/43) of patients had mNPM1 AML and 21% (9/43) had KMT2Ar AML. The median age was 70 years (range: 60-92) and 40% were ≥75 years.

Revumenib was generally well tolerated at both dose levels in combination with venetoclax and azacitidine without a maximal tolerated dose identified. The most common overall non-hematologic treatment-emergent adverse events (TEAEs) of any grade were nausea (60%), constipation (53%), QTc prolongation (44%), hypokalemia (44%), and vomiting (42%). Overall Grade ≥3 non-hematologic AEs were rare and similar between both dose levels.

In the intent-to-treat population, the observed rate of complete remission (CR) was 67% (29/43), composite complete remission (CRc) was 81% (35/43), and the overall response rate (ORR) was 88% (38/43). Among 37 patients with measurable residual disease (MRD) response assessment, 100% were MRD negative by centralized flow cytometry testing (sensitivity of 0.02%). The median duration of CRc was 12.0 months (95% CI: 7.8-not reached). 23% (10/43) of patients had proceeded to hematopoietic stem cell transplantation (HSCT) as of the February 2025 data cut off.

In an early analysis of survival from this single-arm trial (median follow-up of 6.9 months), the median overall survival (OS) observed was 15.5 months (95% CI: 9.5-19.5). Subset analysis showed a CRc rate of 77% and an observed median OS of 15.5 months in mNPM1 patients with intermediate risk by ELN 2024 (n=17), and a CRc rate of 89% and observed median OS of 18.0 months in KMT2Ar patients (n=9). In contrast, historical data from newly diagnosed mNPM1 patients with intermediate risk treated with venetoclax and azacitidine show a CRc of 57% and median OS of 9.9 months.1 In newly diagnosed KMT2Ar AML patients treated with venetoclax and hypomethylating agent therapy, a CRc rate of 43% and median OS of 2.5 months was observed in a retrospective analysis.2

About Revuforj (revumenib)

Revuforj (revumenib) is an oral, first-in-class, selective menin inhibitor that is FDA approved for the treatment of relapsed or refractory (R/R) acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation in adult and pediatric patients one year and older.

Revumenib is in development for the treatment of R/R acute myeloid leukemia (AML) with a nucleophosmin 1 mutation (mNPM1). Positive pivotal data from the AUGMENT-101 trial in this population with revumenib as a monotherapy were recently published and the Company completed the submission of a supplemental NDA for revumenib in R/R mNPM1 AML in April 2025. Additionally, multiple trials of revumenib in combination with standard-of-care agents in mNPM1 AML or KMT2A-rearranged acute leukemia are ongoing or planned across the treatment landscape, including in newly diagnosed patients.

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.

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME

Differentiation syndrome, which can be fatal, has occurred with Revuforj. Signs and symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, and renal dysfunction. If differentiation syndrome is suspected, immediately initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.

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, and/or hypotension. In clinical trials, DS occurred in 39 (29%) of 135 patients treated with Revuforj. DS was Grade 3 or 4 in 13% of patients and fatal in one. The median time to onset was 10 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: In the clinical trials, QTc interval prolongation was reported as an adverse reaction in 39 (29%) of 135 patients treated with Revuforj. QTc interval prolongation was Grade 3 in 12% of patients. The heart-rate corrected QT interval (using Fridericia’s method) (QTcF) was greater than 500 msec in 8%, and the increase from baseline QTcF was greater than 60 msec in 18%. Revuforj dose reduction was required for 5% of patients due to QTc interval prolongation. QTc prolongation occurred in 16% of the 31 patients less than 17 years old, 33% of the 88 patients 17 years to less than 65 years old, and in 50% of the 16 patients 65 years or older.

Correct electrolyte abnormalities, including hypokalemia and hypomagnesemia, prior to 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, and restart Revuforj at the same dose twice daily after the QTcF interval returns to ≤480 msec
Interrupt Revuforj if QTcF increases >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 4 (3%) patients who received Revuforj, including 2 with differentiation syndrome, 1 with hemorrhage, and 1 with sudden death.

Serious adverse reactions were reported in 99 (73%) patients. The most frequent serious adverse reactions (≥5%) were infection (24%), febrile neutropenia (19%), bacterial infection (17%), differentiation syndrome (12%), hemorrhage (9%), and thrombosis (5%).

The most common adverse reactions (≥20%) including laboratory abnormalities, were hemorrhage (53%), nausea (51%), phosphate increased (50%), musculoskeletal pain (42%), infection (41%), aspartate aminotransferase increased (37%), febrile neutropenia (35%), alanine aminotransferase increased (33%), parathyroid hormone intact increased (33%), bacterial infection (31%), diarrhea (30%), differentiation syndrome (29%), electrocardiogram QT prolonged (29%), phosphate decreased (25%), triglycerides increased (25%), potassium decreased (24%), decreased appetite (24%), constipation (23%), edema (23%), viral infection (23%), fatigue (22%), and alkaline phosphatase increased (21%).

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.

Pediatric: monitor bone growth and development in pediatric patients.

Geriatric: compared to younger patients, the incidences of QTc prolongation and edema were higher in patients 65 years and older.

Infertility: based on findings in animals, Revuforj may impair fertility. The effects on fertility were reversible.

To report SUSPECTED ADVERSE REACTIONS, contact Syndax Pharmaceuticals at 1-888-539-3REV or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see Full Prescribing Information, including BOXED WARNING.

On June 12, 2025 Quince Therapeutics, Inc. (Nasdaq: QNCX) ("Quince" or the "Company"), a late-stage biotechnology company dedicated to unlocking the power of a patient’s own biology for the treatment of rare diseases, reported that it has entered into a securities purchase agreement with certain institutional and accredited investors to purchase shares of its common stock (or pre-funded warrants in lieu thereof), and accompanying common warrants ("Warrants") that is expected to result in approximately $11.5 million in upfront proceeds and potential additional proceeds of up to $10.4 million if the accompanying common warrants are exercised in full for cash, before deducting placement agent fees and other private placement expenses (Press release, Quince Therapeutics, JUN 12, 2025, View Source [SID1234653847]).

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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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The private placement is being led by healthcare-focused institutional investor Nantahala Capital with participation from existing Quince stockholders including ADAR1 Capital Management, along with members of Quince’s senior management.

Quince intends to use the net proceeds of this offering for working capital and general corporate purposes, including funding the ongoing enrollment of the Company’s pivotal Phase 3 NEAT (Neurological Effects of eDSP on Subjects with A-T; NCT06193200/IEDAT-04-2022) clinical trial in Ataxia-Telangiectasia (A-T), research and development expenses, general and administrative expenses and capital expenditures. The net upfront proceeds from the private placement, combined with Quince’s current cash, cash equivalents, and short-term investments are expected to fund the Company’s operations into the second quarter of 2026, or the second half of 2026 if the Warrants are exercised in full for cash.

At the closing, the Company will issue to the investors an aggregate of 8,671,928 shares of common stock (or pre-funded warrants in lieu thereof), along with accompanying Warrants to purchase an aggregate of 8,671,928 shares of common stock (or pre-funded warrants in lieu thereof), at a combined purchase price of $1.325 per share (or $1.324 per pre-funded warrant) and accompanying Warrant (representing a 10% premium over the $1.20 closing price per share of the Company’s common stock). The accompanying Warrants have an exercise price of $1.20 per share and will become exercisable immediately. The Warrants will expire five years from the date of issuance. The private placement is expected to close during the week of June 16, 2025, subject to the satisfaction of customary closing conditions.

Citizens Capital Markets is acting as the lead placement agent for the private placement. Maxim Group LLC and Brookline Capital Markets, a division of Arcadia Securities, LLC, are acting as co-placement agents for the private placement.

The securities to be issued in connection with the private placement described above are being offered in a private placement and have not been registered under the Securities Act of 1933, as amended (the "Securities Act"), or any state or other applicable jurisdictions’ securities laws, and may not be offered or sold in the United States absent registration or an applicable exemption from the registration requirements of the Securities Act and applicable state or other jurisdictions’ securities laws.

This news release does not constitute an offer to sell or the solicitation of an offer to buy the securities described herein, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation, or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

On June 12, 2025 Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted protein degradation medicines, reported positive clinical data from the Company’s ongoing NX-5948-301 study, a Phase 1a/b clinical trial of bexobrutideg (NX-5948) in patients with relapsed or refractory B-cell malignancies (Press release, Nurix Therapeutics, JUN 12, 2025, View Source [SID1234653846]).

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The data include findings from the fully enrolled Phase 1a dose escalation study in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) and the ongoing Phase 1a/1b cohorts of patients with Waldenström macroglobulinemia (WM). Talha Munir, M.B. Ch.B, Ph.D., consultant hematologist at Leeds Teaching Hospitals NHS Trust, deputy chair of the United Kingdom National Cancer Research Institute CLL Study Group, and Dima El-Sharkawi, M.B., B.S., M.A., Ph.D., MRCP FRCPath, Consultant Haematologist, Royal Marsden NHS Foundation Trust, Sutton, U.K., will present these data at the 30th European Hematology Association (EHA) (Free EHA Whitepaper) Congress (EHA2025), taking place June 12–15, 2025, in Milan, Italy.

"These data demonstrate an impressive safety and efficacy profile for bexobrutideg with improvement in responses in patients over time, including the notable achievement of a complete response in a patient with CLL and a history of two lines of prior therapy who has been on bexobrutideg treatment for over two years," said Dr. Munir. "Patients with relapsed or refractory CLL and WM who have failed treatments with commonly prescribed BTK inhibitors and other agents due to intolerance or acquired resistance have few therapeutic options. Nurix’s bexobrutideg has the potential to address this unmet need and provide a life-changing treatment for patients with CLL and WM."

"With longer time on treatment, we are encouraged by the continued favorable safety profile and high ORR with deepening responses in CLL and WM, including those with clinical and genomic high risk features including CNS involvement," said Paula G. O’Connor, M.D., chief medical officer of Nurix. "We have further expanded our Phase 1b cohorts in select CLL populations and remain on track to initiate pivotal studies in 2025."

"Bexobrutideg offers a next-generation approach to BTK targeting with exquisite selectivity, superior preclinical potency, broad coverage of mutations and demonstrated clinical activity in areas of high unmet medical need," said Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix. "We are not only preparing to initiate pivotal studies in the coming months but are also laying the foundation for the commercialization of bexobrutideg as a differentiated treatment option for patients with B-cell malignancies."

Data presented at EHA (Free EHA Whitepaper)2025 include efficacy and safety findings for patients with CLL/SLL in the fully enrolled Phase 1a dose escalation study (n=48). This cohort of CLL patients was a heavily pretreated population that had received a median of four prior lines of therapy (range = 2–12) including prior covalent BTK inhibitors (97.9%), prior BCL2 inhibitors (83.3%), and prior non-covalent BTK inhibitors (27.1%). At baseline, many patients had mutations associated with BTK inhibitor resistance, including mutations in BTK (38.3%) and PLC2G (14.9%). Poor prognostic features were common, including TP53 mutations (44.7%), and five patients (10.4%) had central nervous system (CNS) involvement.

Patients were treated with bexobrutideg at doses ranging from 50 mg to 600 mg once daily by oral administration in the Phase 1a dose escalation study. As of the March 12, 2025 data cut, the median follow up was 9.0 months with most patients still on treatment. Bexobrutideg was well tolerated across all doses evaluated with the most common treatment emergent adverse events of purpura/contusion (45.8%), neutropenia (29.2%) and thrombocytopenia (22.9%), primarily low grade. No new onset atrial fibrillation was observed. Among the efficacy evaluable patients with CLL (n = 47), bexobrutideg treatment resulted in a robust objective response rate (ORR) of 80.9% across all doses tested with a median time to first response of 1.9 months. Many patients experienced deepening of their response with longer time, with multiple conversions from stable disease to partial responses and one patient, who has been on treatment for over two years, experienced a complete response. The median duration of response has not been reached, with 18 patients on treatment for more than a year. Responses were observed across all populations regardless of prior treatment, baseline mutations, or CNS involvement.

The data presented at EHA (Free EHA Whitepaper) included patients with WM (n=22) treated with bexobrutideg at doses ranging from 50 mg to 600 mg once daily by oral administration from both the Phase 1a dose escalation and Phase 1b cohort expansion. Among the 22 WM patients, the median age was 72.5 years (range 58-86 years) and the median number of prior lines of therapy was 3 (range 2-5). All 22 patients previously had been treated with a covalent BTK inhibitor (100%), 21 had received prior chemotherapy/chemo-immunotherapy (95.5%), four had received prior non-covalent BTK inhibitor (18.2%), and one patient (4.5%) had received prior treatment with a BCL2 inhibitor. Baseline mutation status in MYD88 and CXCR4 was captured from patient records. 15 patients (68.2%) had mutations in MYD88, and five patients (22.7%) had mutations in CXCR4. Bexobrutideg was well tolerated in patients with WM with a profile that was consistent with the overall study population and previous disclosures. Adverse events (AEs) were predominantly low grade; with the most common being petechiae (27.3%), diarrhea (22.7%), purpura/contusion (18.2%), neutropenia (18.2%), and thrombocytopenia (18.2%). There were no dose limiting toxicities observed and no grade 5 AEs. Two treatment emergent AEs led to drug discontinuation. No new onset atrial fibrillation was observed.​ As of the March 12, 2025 data cut, 19 patients were evaluable for responses. Objective response was observed in 16 patients (84.2%), including two patients (10.5%) with very good partial response (VGPR), 11 patients (57.9%) with partial response (PR), and three patients (15.8%) with minor response (MR). Three patients (15.9%) had a best response of stable disease (SD). Responses were observed in patients regardless of their baseline mutations in MYD88 and CXCR4. Steady reductions in IgM levels were observed starting from the first assessment at four weeks, which continued to deepen, and three patients achieved IgM reductions of greater than 90%.

Conference Call Details
On June 12, 2025, at 8:00 a.m., ET (2:00 p.m., CEST), Nurix will host a conference call and webcast to discuss data from the bexobrutideg clinical trial. The live webcast, with an accompanying presentation, will be accessible under the Events and Presentations page in the Investors section of the company’s website here. To participate in the live conference call, the dial-in number in the United States is 877-346-6112. For participants outside the United States, the dial-in number is 1-848-280-6350. A replay of the webcast and call will be archived on the Nurix website for approximately 30 days after the event.

About Bexobrutideg (NX-5948)
Bexobrutideg is an investigational, orally bioavailable, brain penetrant, small molecule degrader of BTK. Bexobrutideg is currently being evaluated in a Phase 1 clinical trial in patients with relapsed or refractory B cell malignancies. Additional information on the ongoing clinical trial can be accessed at clinicaltrials.gov (NCT05131022).

On June 12, 2025 Nona Biosciences, a global biotechnology company providing integrated solutions from "Idea to IND" (I to ITM), reported a license agreement with Visterra, Inc. to advance Visterra’s next-generation biotherapeutic pipeline for immune-mediated and autoimmune diseases, leveraging Nona’s proprietary HCAb Harbour Mice technology platform (Press release, Nona Biosciences, JUN 12, 2025, View Source [SID1234653845]).

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Nona’s HCAb Harbour Mice platform enables the generation of fully human heavy-chain-only antibodies (HCAbs), offering key advantages such as reduced immunogenicity and enhanced versatility for next-generation biotherapeutics. This innovative platform has been clinically validated and widely recognized by global partners.

"We are pleased to collaborate with Visterra and support the development of their biotherapeutic pipeline," said Jingsong Wang, MD, PhD, Chairman of Nona Biosciences. "This collaboration reflects our commitment to advancing biotherapeutic innovation. By leveraging our fully human HCAbs, we aim to unlock new therapeutic possibilities and accelerate the development of transformative medicines for patients worldwide."