On December 11, 2023 Sutro Biopharma, Inc. (Sutro or the Company) (NASDAQ: STRO), a clinical-stage oncology company pioneering site-specific and novel-format antibody drug conjugates (ADCs), reported that its research collaborators presented data on anti-leukemic activity from the compassionate use of luveltamab tazevibulin (luvelta), a novel folate receptor-α (FR-α) targeting ADC, in pediatric patients with relapsed/refractory CBFA2T3-GLIS2 (CBF/GLIS) acute myeloid leukemia (AML), commonly known as RAM phenotype AML (Press release, Sutro Biopharma, DEC 11, 2023, View Source [SID1234638443]). Data demonstrated that treatment with luvelta produced meaningful clinical responses, including complete remission (CR); and prolongs overall survival (OS) enabling some patients to receive potentially curative therapies such as hematopoietic stem cell transplant. These patients were treated under the single patient IND mechanism. These data were featured in a poster presentation at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (ASH 2023) in San Diego, CA.

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"Treatment with luvelta led to notable response in a significant subset of patients who had exhausted all therapeutic options," said Soheil Meshinchi, M.D., Ph.D., presenter and primary author. "Response varied from deep remissions to disease stabilization with minimal toxicity – mostly in outpatient setting. Luvelta was well tolerated as long-term maintenance therapy with little to no hematopoietic toxicity."

CBF/GLIS subtype AML is a rare and highly lethal form of leukemia found exclusively in infants and young children, with the average age of onset at 18 months 1. There are no therapies specifically approved to target this form of leukemia and it is resistant to conventional chemotherapy, with an induction failure rate of over 80%2. Due to a lack of effective treatment, children diagnosed with the disease have a dismal two-year survival rate of 15%3. Recent studies have shown that FOLR1, which encodes for FolRα, is silent in normal hematopoiesis, but is uniquely induced by the CBF/GLIS fusion4.

Under compassionate use, 25 pediatric patients with relapsed/refractory CBF/GLIS subtype AML were treated with luvelta at doses up to 4.3 or 5.2mg/kg every two to four weeks for a median duration of 15.9 weeks (3-73.1), with the majority of patients receiving at least five doses (68%). Of the 25 treated patients, 19 had ≥5% blasts (morphologic disease, or MD) and 8 had <5% blasts (sub-morphologic disease, or SMD)5. Collective results show that treatment with luvelta produced clinically meaningful and durable responses across a broad range of patients in various settings including in patients with or without prior stem cell transplant and in monotherapy or in combination with cytotoxic therapy. These data were generated by the treating physicians and collected and enabled for presentation by Sutro.

"It is clear from these data that luvelta is providing an ongoing and promising impact on the lives of infants and young children with this rare leukemia," said Bill Newell, Sutro’s Chief Executive Officer. "These results add to the growing body of research supporting the development of luvelta, which has now seen positive clinical results across three different tumor types, including those with potentially low or variable folate receptor-α expression."

ASH Presentation Highlights:

Overall, anti-leukemic activity was seen with luvelta either as a single agent or in combination.
19 patients had ≥5% blasts and 8 patients had <5% blasts5.
A CR/CRh was observed in 8 out of 19 (42%) patients with ≥5% blasts treated with luvelta, with 5 out of 8 CR/CRh patients reaching a minimal residual disease (MRD)-negative CR (63%).
6 out of 8 patients with <5% blasts experienced an MRD-negative CR (75%).
Patients whose leukemia experienced an MRD-negative CR had an improved outcome over those who did not experience an MRD-negative CR.
Treatment with luvelta also enabled some children to bridge to stem cell transplant, which is potentially curative therapy.
Luvelta was well-tolerated as a monotherapy agent and in combination with standard of care therapies with minimal hematopoietic toxicity and can be delivered as outpatient therapy.
As of September 17, 2023, 8 patients remain on treatment, with 5 of the 8 (63%) in continued remission and on luvelta maintenance.
The poster titled, "Anti-leukemic Activity of Luveltamab Tazevibulin (LT, STRO-002), a Novel Folate Receptor-α (FR-α)-targeting Antibody Drug Conjugate (ADC) in Relapsed/Refractory CBFA2T3::GLIS2 AML," will be accessible through the News & Events page of the Investor Relations section of the company’s website at www.sutrobio.com.

About Luveltamab Tazevibulin
Luveltamab tazevibulin, abbreviated as "luvelta" and formerly known as STRO-002, is a FolRα-targeting antibody-drug conjugate (ADC) designed to treat a broad range of patients with ovarian cancer, including those with lower FolRα-expression who are not eligible for approved treatment options targeting FolRα. Developed and manufactured with Sutro’s cell-free XpressCF platform, luvelta is a homogeneous ADC with four hemiasterlin cytotoxins per antibody, precisely positioned to efficiently deliver to the tumor while ensuring systemic stability after dosing. Sutro recently initiated REFRaME, a Phase 2/3 registration-directed study for patients with platinum-resistant ovarian cancer. The company has ongoing trials in patients with endometrial cancer and in combination with bevacizumab in patients with ovarian cancer. The company is also assessing the clinical path forward for CBF/GLIS2 acute myeloid leukemia, a rare subtype of pediatric cancer, as well as non-small cell lung cancer. The U.S. Food and Drug Administration (FDA) has granted luvelta a Fast Track designation for Ovarian Cancer, as well as Orphan and Rare Pediatric Disease designations for CBF/GLIS2 Pediatric AML.

On December 11, 2023 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a leader in the development of targeted radiotherapies, reported four presentations at the 65th Annual American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition (ASH) (Free ASH Whitepaper) detailing results from the Phase 3 SIERRA trial of Iomab-B and Phase 1 trial of Actimab-A in combination with Venetoclax in patients with relapsed or refractory acute myeloid leukemia (r/r AML) (Press release, Actinium Pharmaceuticals, DEC 11, 2023, View Source [SID1234638442]). Iomab-B and Actimab-A are the only two clinical stage targeted radiotherapies in development for patients with AML, which is known to be highly sensitive to radiation.

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Sandesh Seth, Actinium’s Chairman and CEO, said, "Earlier in 2023 we presented data from both Iomab-B and Actimab-A highlighting positive outcomes in patients with relapsed or refractory AML. We are particularly excited by these results as our trials enrolled patients with difficult to treat disease as they were heavily pre-treated, elderly in age, or had adverse cytogenetic or molecular mutations. As evidenced by the data presented at ASH (Free ASH Whitepaper) in the oral presentation of the Phase 3 SIERRA trial results, Iomab-B produced improved outcomes in patients with a TP53 mutation, which is associated with dismal outcomes. We are proud to have showcased Iomab-B and Actimab-A at ASH (Free ASH Whitepaper) and excited by the enthusiasm for which the data were received. We look forward to progressing both programs with key BLA and MAA filings for Iomab-B next year and advanced development for Actimab-A."

ASH Presentations and Highlights:

131I-Apamistamab-Led Allogeneic Hematopoietic Cell Transplant Significantly Improves Overall Survival in Patients with TP53 Mutated R/R AML

Patients receiving Iomab-B had significantly greater median overall survival of 5.49 months compared to 1.66 months in patients on the control arm that received conventional care
24% of patients (37/153) enrolled on the SIERRA trial had a TP53 mutation, which is associated with the worst outcomes
Iomab-B produced response rates and overall survival in these very high-risk patients similar to those observed in patients without a TP53 mutation
131I-Apamistamab Effectively Achieved Durable Responses in Patients with R/R AML Irrespective of the Presence of Multiple High-Risk Factors

Patients receiving Iomab-B were able to receive a BMT and achieve durable Complete Remission (dCR), the primary endpoint in the SIERRA trial, irrespective of having multiple high-risk factors
Iomab-B met the dCR rate primary endpoint with high statistical significance (p<0.0001) with 22% dCR rate in the Iomab-B arm vs. 0% dCR rate in the control arm
53% of patients had 2-3 high-risk factors and 29% had 4-5 high-risk factors that included adverse-risk cytogenetics, age >65, prior treatment failure with Venetoclax, BMT comorbidity index > 3, and Karnofsky Performance Status < 90
There was no statistical difference in the rate of dCR in patients receiving Iomab-B across the high risk-factor categories (0-1, 2-3 & 4-5)
High-Dose Targeted Radiation with 131I-Apamistamab Prior to HCT Demonstrated a Dose-Response for Durable Complete Remission in Patients with R/R AML

Patients with higher bone marrow/liver absorbed dose ratios experienced considerably higher rates of dCR demonstrating a dose dependent response
27% of patients achieving dCR when receiving > 22 Gy to the liver vs 13.5% dCR rate in patients receiving < 22 Gy to the liver; maximum tolerable dose in SIERRA was 24 Gy administered to the liver
Rates of Grade 3 > treatment emergent events were similar between patients receiving < 22 Gy to the liver and those receiving > 22 Gy to the liver
Iomab-B led BMT produced to significantly higher rates of dCR with patients achieving dCR having a 92% 1-year overall survival and 60% 2-year overall survival
These results demonstrate the importance of maximizing the dose to target tissues within the established dose tolerances
Updated Results from Phase 1 Study of Targeted Radiotherapy with Lintuzumab-Ac225 in Combination with Venetoclax in Relapsed/Refractory AML

Actimab-A dosed up to 2.0 μCi/kg with Venetoclax in patients with relapsed/refractory AML was well-tolerated, with a manageable adverse event profile
Maximum tolerated dose was not reached with no dose-limiting toxicities observed at the 3 highest dose levels (1.0, 1.5 & 2.0 μCi/kg)
Complete responses were achieved including a complete response in a patients with prior Venetoclax treatment and a TP53 mutation
These results support the continued evaluation of Actimab-A in combination with Venetoclax-based treatment

On December 11, 2023 Affimed N.V. (Nasdaq: AFMD) ("Affimed" or the "Company"), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported updated data on its lead innate cell engager (ICE) acimtamig. Data from the investigator-initiated trial is being presented today at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2023 Annual Meeting by Yago Nieto, M.D., Ph.D., Professor of Stem Cell Transplantation and Cellular Therapy at The University of Texas MD Anderson Cancer Center and principal investigator of the study (Press release, Affimed, DEC 11, 2023, View Source [SID1234638441]). Affimed will host a webcast following the presentation to review the data and provide a strategic update on acimtamig’s future development.

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A total of 42 patients were enrolled in the study with 36 patients treated at the RP2D. 32 of the 36 patients treated at the RP2D were HL patients. All 32 HL patients were heavily pretreated with multiple lines of chemotherapy, all had previously received CPIs and BV, and were refractory to their most recent line of therapy with active progressive disease at the time of enrollment. Across all dose levels, the treatment regimen achieved an ORR of 93% with a CR rate of 67%; among the 32 HL patients treated at the RP2D the treatment regimen achieved an ORR of 97% and a CR rate of 78%. In addition, the treatment regimen demonstrated a good safety and tolerability profile with no cases of CRS, ICANS or GvHD of any grade. Mild to moderate infusion related reactions (IRRs) were seen in 7.7% of the acimtamig infusions.

Across all dose levels, median event free survival (EFS) was 8.8 months and median overall survival (OS) was not reached. For the HL patients treated at the RP2D, median EFS was 9.8 months – with 84% patients alive at 12 months. The median DoR was 8.8 months and 72% CR assessed at 6 months for HL patients treated at the RP2D; 30% of patients with complete response remained in CR beyond 12 months.

"When we conduct studies in a patient population that has failed their previous line of therapy, demonstrating even a modest response is encouraging. To see this magnitude of responses in terms of ORR (97%) and CR (78%) is remarkable and fuels our commitment to bring this therapy to more patients," said Dr. Andreas Harstrick, Chief Medical Officer at Affimed. "Building on these results, we are well underway with our Phase 2 LuminICE-203 study. We have enrolled and dosed patients in the first two cohorts and we look forward to sharing data in the first half of 2024."

The Company will host a call today at 1:30 p.m. PST / 4:30 p.m. EST / 22:30 CET to discuss the data presented at ASH (Free ASH Whitepaper) and provide a strategic update. The conference call will be available via phone and webcast. The live audio webcast of the call will be available in the "Webcasts" section on the "Investors" page of the Affimed website at View Source To access the call by phone, please use the link: https://register.vevent.com/register/BIb2258d6c5f5a474cad74869a7b7b1bb5, and you will be provided with dial-in details and a pin number.

Note: To avoid delays, we encourage participants to dial into the conference call 15 minutes ahead of the scheduled start time. A replay of the webcast will be accessible at the same link for 30 days following the call.

About the AFM13-104 Phase 1/2 Study

The University of Texas MD Anderson Cancer Center is studying acimtamig (AFM13) in an investigator-sponsored phase 1/2 trial in combination with cord blood-derived allogeneic NK cells in patients with recurrent or refractory CD30-positive lymphomas. The study is a dose-escalation trial of precomplexed NK cells, followed by an expansion phase that recruited 36 patients with r/r CD30 positive lymphomas, treated with the RP2D of 1×108 NK cells/kg followed by three weekly doses of 200 mg acimtamig monotherapy. Each treatment cycle consists of lymphodepleting chemotherapy with fludarabine (30 mg/m² per day) and cyclophosphamide (300 mg/m² per day) followed two days later by a single infusion of cytokine-preactivated and expanded cord blood-derived NK cells that are pre-complexed with acimtamig. Three weekly infusions of acimtamig (200 mg) monotherapy are subsequently administered and responses are assessed by the investigator on day 28 by FDG-PET.

MD Anderson has an institutional financial conflict of interest with Affimed related to this research and has therefore implemented an Institutional Conflict of Interest Management and Monitoring Plan. Additional information about the study can be found at www.clinicaltrials.gov (NCT04074746).

About Acimtamig

Acimtamig (AFM13) is a first-in-class innate cell engager (ICE) that uniquely activates the innate immune system to destroy CD30-positive hematologic tumors. Acimtamig induces specific and selective killing of CD30-positive tumor cells, leveraging the power of the innate immune system by engaging and activating natural killer (NK) cells and macrophages. Acimtamig is a tetravalent bispecific innate cell engager designed to act as a bridge between the innate immune cells and the tumor creating the necessary proximity for the innate immune cells to specifically destroy the tumor cells.

On December 11, 2023 Wugen, Inc., a clinical-stage biotechnology company developing allogeneic, off-the-shelf cell therapies for the treatment of hematological and solid tumor malignancies, reported the latest data from its ongoing Phase 1/2 dose escalation study of WU-CART-007 (Press release, Wugen, DEC 11, 2023, View Source [SID1234638440]). An investigational allogeneic CAR-T cell therapy, WU-CART-007 is being studied for the treatment of patients with relapsed or refractory T-cell Acute Lymphoblastic Leukemia (T ALL)/Lymphoblastic Lymphoma (LBL).

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Patients with relapsing or refractory (R/R) T-ALL face grim prognoses, with around 30% of patients failing to respond to first-line standard of care treatments, and for those who do respond, approximately 50% relapse.

"For a disease that disproportionately affects younger individuals, the need to find better treatments feels especially urgent," said Armin Ghobadi, M.D, associate professor of medicine and clinical director of Center for Gene and Cellular Immunotherapy (CGCI) in the Division of Medical Oncology at the Washington University School of Medicine in St. Louis. "It’s encouraging to see positive momentum — with favorable tolerability and efficacy data continuing to be reported as the study has expanded to include more patients with such difficult-to-treat blood cancers."

"As we at Wugen work diligently to reshape the treatment landscape for patients suffering from diseases with limited treatment options, we believe early results from this study speak to the larger potential of innovative allogeneic cell therapies to enhance the quality of life for patients with more effective and accessible treatments," said Chief Medical Officer Jan Davidson-Moncada, M.D., Ph.D. "We look forward to reporting topline Phase 2 results in the coming year, which will mark a pivotal milestone in our commitment to redefining the standard of care for these cancers."

Initial data presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress in June 2023 showed that treatment with WU-CART-007 resulted in overall favorable efficacy and tolerability profiles compared to the baseline standard of care. In the latest update, an additional 13 patients were treated with WU-CART-007, which showed clinically acceptable safety profiles and preliminary evidence of anti-leukemic activity, demonstrating a notable clinical improvement. WU-CART-007 remains on track to complete enrollment by the end of this year.

Positive and consistent data from the WU-CART-007 Phase 1/2 trial collectively underscore its potential to address unmet medical needs for difficult-to-treat blood cancers as it advances to the next crucial phase of development. These early results suggest that WU-CART-007 may offer a novel and effective therapeutic avenue, providing hope for improved outcomes in a patient population where viable alternatives are scarce.

In a presentation titled "Phase 1/2 Dose-Escalation/Dose-Expansion Study of Anti-CD7 Allogeneic CAR-T Cells (WU-CART-007) in Relapsed or Refractory (R/R) T-Cell Acute Lymphoblastic Leukemia/ Lymphoblastic Lymphoma (T-ALL/LBL)," Wugen shared these updated data:

As of Nov. 28, 2023, 25 patients have been dosed with WU-CART-007. Disease burden at baseline consisted of extramedullary only disease (EMD) in 28% (7/25) of patients, and a median bone marrow (BM) blast count of 63.2% (range 5%-95%) in patients with BM disease.
Overall, WU-CART-007 demonstrated a manageable safety profile:
No cases of Graft versus Host Disease (GvHD), prolonged T-cell aplasia, or prolonged pancytopenia in the absence of disease were observed. The majority of deaths were due to disease progression. Of three Grade 5 events observed, two were due to fungal infection and were not attributed to WU-CART-007. One event temporally related to WU-CART-007 occurred in the setting of CRS and progressive disease.
Most reports of cytokine release syndrome (CRS) were low-grade (84%; 21/25), with the exception of five Grade ≥ 3 report, which were manageable with supportive care.
One instance of Grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS), which resolved spontaneously, was reported in a patient at DL3.
WU-CART-007 showed dose-dependent anti-tumor activity with no responses seen at DL1. In evaluable patients at DL≥ 2 (18/22), the Composite Complete Remission Rate (CRc) in patients was 67%. At the recommended Phase 2 dose (RP2D), the CRc rate was 73%.
No patients developed novel anti-HLA antibodies against the donor, and of the 18 patients who were tested, no anti-drug antibodies against the CAR-construct were detected.
Phenotypic analysis revealed in vivo WU-CART-007 cells expressed activation markers (KI67, CD38, HLA-DR) and were largely an effector memory CD45RA+ (EMRA) CM phenotype (CD45RA+, CD197+).
ASH meeting information can be found here: View Source

The presentation can be found here: WU-CART-007

About WU-CART-007

WU-CART-007 is an allogeneic, off-the-shelf, fratricide-resistant CD7-targeted CAR-T cell therapy engineered to overcome the technological challenges of harnessing CAR-T cells to treat CD7+ hematological malignancies. Wugen is deploying CRISPR/Cas9 gene editing technology to delete CD7 and the T-cell receptor alpha constant (TRAC), preventing CAR-T cell fratricide and mitigating the risk of graft-versus-host-disease (GvHD). WU-CART-007 is manufactured using healthy donor-derived T-cells to eliminate the risk of malignant cell contamination historically observed in the autologous CAR-T setting. WU-CART-007 is currently being evaluated in a global Phase 1/2 clinical trial for the treatment of relapsed or refractory (R/R) T-cell acute lymphoblastic leukemia (T-ALL)/lymphoblastic lymphoma (LBL). Additional information is available on clinicaltrials.gov, identifier NCT# 04984356. WU-CART-007 has received Orphan Drug, Fast Track, and Rare Pediatric Disease Designations from the U.S. Food and Drug Administration for the treatment of R/R T-ALL/LBL.

On December 11, 2023 Syndax Pharmaceuticals (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported data from multiple trials of revumenib in combination with standard of care agents in patients with nucleophosmin mutant (mNPM1) and KMT2A-rearranged (KMT2r) relapsed/refractory (R/R) acute leukemias (Press release, Syndax, DEC 11, 2023, View Source [SID1234638437]). Revumenib is the Company’s highly selective, oral menin inhibitor.

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Data to date demonstrate that revumenib has been well tolerated and demonstrated clinical activity in combination with venetoclax/hypomethylating agents in both the frontline and R/R acute myeloid leukemia (AML) settings, as well as in combination with fludarabine/cytarabine (FLA) chemotherapy in a heavily pretreated R/R pediatric AML population, including in patients who relapsed on FLA. In all three trials, patients are now receiving the full monotherapy recommended Phase 2 dose in combination with the standard of care agents. The new combination data collectively highlight revumenib’s potential to safely combine with current standard of care agents across the acute leukemia treatment landscape, and support expansion of ongoing trials and advancement into additional combination trials currently in planning.

"Given the urgent need for novel, effective solutions for acute leukemia patients, we’re excited to show clinical data demonstrating tolerability and compelling clinical responses when revumenib is added to current treatment regimens," said Michael A. Metzger, Chief Executive Officer. "The potential to safely combine with standard of care positions revumenib to become a cornerstone of treatment across a range of acute leukemia populations. In addition, current response rates seen across all three trials strengthen revumenib’s already robust clinical profile as a monotherapy and furthers our conviction that revumenib could be a first- and best-in-class treatment for both KMT2Ar and mNPM1 acute leukemias."

SAVE AML Trial

Results from the SAVE AML trial of revumenib in combination with venetoclax-decitabine/cedazuridine in R/R AML were featured during an oral session at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. The dose escalation phase of the trial tested revumenib at doses of 113 mg and 163 mg every 12 hours (q12h) in combination with azole antifungals known to strongly inhibit CYP3A4 enzymes. As of a data cutoff date of November 1, 2023, nine patients with KMT2Ar, mNPM1 or NUP98r AML or mixed phenotypic acute leukemia (MPAL) were enrolled and response evaluable at the time of the data cut. Patients received a median of three prior lines of therapy, including 56% who received prior venetoclax and 67% who received prior hypomethylating agents (HMA) or underwent prior stem cell transplant or both.

All nine patients attained a morphologic remission for an overall response rate of 100%, 78% of whom achieved a CRc1 including 44% who achieved a CR/CRh. 67% (6/9) of patients in the trial attained minimal residual disease (MRD) negative status. Five patients transitioned to hematopoietic stem-cell transplantation (HSCT) following response. Two patients initiated post-transplant maintenance with revumenib and continue in remission for over 11 months.

The combination was well tolerated in this relapsed and refractory population, with no new safety signals observed beyond those reported for venetoclax-HMA. Grade ≥3 treatment related adverse events (TRAEs) included febrile neutropenia (56%), decreased platelets count (22%), decreased neutrophil count (22%) and lung infection (22%). There was one dose-limiting toxicity (DLT) at each dose level, Grade 4 thrombocytopenia that resolved after a dosing hold. There were no deaths due to TRAEs and no Grade 3 or higher QTc prolongation occurred.

BEAT AML Trial

The Company also announced data from the BEAT AML trial of revumenib in combination with venetoclax/azacitidine in newly diagnosed mNPM1 or KMT2Ar AML patients. The dose escalation phase of the trial tested revumenib at doses of 113 mg and 163 mg q12h in combination with azole antifungals known to strongly inhibit CYP3A4 enzymes. As of the data cutoff date of December 1, 2023, 13 newly diagnosed mNPM1 (n=8) or KMT2Ar (n=5) AML patients were efficacy evaluable. In the efficacy evaluable population, the CRc was 100% (13/13) after 1 – 2 cycles of induction. Eleven (85%) of 13 patients attained a CR/CRh and 92% (12/13) attained MRD negative status. Two patients proceeded to transplant.

No new safety signals were identified when revumenib was added to the standard venetoclax/azacitidine doublet in newly diagnosed AML patients. One patient at the lowest dose level, 113 mg q12h, experienced a DLT of decreased platelet counts; no DLTs were observed in the 163 mg q12h dose cohort. 31% of patients experienced differentiation syndrome or QTc prolongation, each included one (8%) Grade 3 event. All were managed without dose reductions. Cytopenias were manageable across the treatment experience with continuous dosing of venetoclax and revumenib. There were no increased safety issues outside of known adverse events reported for venetoclax/azacitidine toxicities.

An expansion cohort is planned to further evaluate safety and activity of this combination, and the full BEAT AML data will be presented at a future medical conference.

AUGMENT-102 Trial

The Company announced data from the AUGMENT-102 trial of revumenib in combination with fludarabine/cytarabine in a predominantly pediatric relapsed/refractory mNPM1 (n=1), NUP98r (n=1) and KMT2Ar (n=13) AML population. The dose-escalation phase of the trial tested revumenib at doses of 113 mg and 163 mg every 12 hours in combination with azole antifungals known to strongly inhibit CYP3A4 enzymes. As of the data cutoff date of September 20, 2023, 15 AML patients were efficacy evaluable, including three patients treated at 113 mg q12h and 12 patients treated at 163 mg q12h. The 163 mg q12hr cohort was comprised of primarily pediatric patients (median age of four), who had received a median of four prior lines of therapy. Across both dose groups, 50% of patients had failed prior treatment with fludarabine/cytarabine. Among the 12 patients treated at 163 mg q12h, four (33%) patients achieved a CRc including three (25%) patients that achieved a CR; four (33%) proceeded to transplant, including one mNPM1 patient who received a five-day course of decitabine prior to transplant.

The triplet of revumenib-fludarabine-cytarabine had an adverse event profile consistent with that observed with fludarabine-cytarabine alone, and no new safety signals were identified in the trial. Grade ≥3 TRAEs in over 30% of patients included decreased platelets (53%), decreased white blood cells (40%) and anemia (33%).

Copies of the ASH (Free ASH Whitepaper) presentations are available in the Publications and Meeting Presentations section of Syndax’s website.

Syndax Corporate Event

The above combination data, along with other data presented through today at the 65th ASH (Free ASH Whitepaper) Annual Meeting being held in San Diego, CA for both the revumenib and axatilimab clinical programs, will be highlighted at the Company’s investor event on Monday, December 11, 2023 at 7:00 a.m. PT/10:00 a.m. ET. The live audio webcast and accompanying slides for the event may be accessed through the Events & Presentations page in the Investors section of the Company’s website or directly through the meeting link here.

For those unable to participate in the conference call or webcast for the event, a replay will be available on the Investors section of the Company’s website at www.syndax.com for a limited time.

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, also known as mixed lineage leukemia rearranged or MLLr, acute leukemias including ALL and AML, and NPM1-mutant AML. 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 BTD by the FDA for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement. Syndax expects to complete an NDA submission for KMT2Ar acute leukemia under the Oncology Center of Excellence Review RTOR Program by year-end 2023.

About KMT2A (MLL) Rearranged Acute Leukemia

Rearrangements of the KMT2A (mixed lineage leukemia or MLL) gene give rise to KMT2Ar acute leukemia that is known to have a poor prognosis. KMT2A genes produce fusion proteins that require interaction with the protein called menin to drive leukemic cancer growth. Disruption of the menin-KMT2Ar interaction has been shown to halt the growth of KMT2Ar leukemic cells. KMT2Ar acute leukemia can phenotypically appear as AML, ALL, or mixed phenotype acute leukemia (MPAL) and is routinely diagnosed through currently available cytogenetic or molecular diagnostic techniques. The median overall survival (OS) after standard of care first-line treatment, including intensive chemotherapy and transplant, is less than one year and the majority of patients suffer relapse within five years. With third line treatment or beyond, less than 5% of patients achieve complete remission (CR), and the median OS is less than three months. There are currently no approved therapies indicated for KMT2A-rearranged acute leukemia.

About NPM1-Mutant Acute Myeloid Leukemia

NPM1-mutant AML, which is distinguished by mutations in the NPM1 gene that drive the leukemic phenotype, is the most common type of cytogenetically normal adult AML and represents approximately 30% of all adult AML cases. This subtype of AML has a five-year overall survival rate of approximately 50%. Similar to KMT2A- rearranged acute leukemia, NPM1-mutant AML is highly dependent on the expression of specific developmental genes shown to be negatively impacted by inhibitors of the menin-KMT2A interaction. NPM1-mutant AML is routinely diagnosed through currently available screening techniques. There are currently no approved therapies indicated for NPM1-mutant AML.