On June 14, 2024 Syndax Pharmaceuticals (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported updated data from multiple combination trials of revumenib, the Company’s potent, selective, small molecule menin inhibitor, in patients with acute leukemias (Press release, Syndax, JUN 14, 2024, View Source [SID1234644341]). The updated data are being presented at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Congress, being held June 13-16 in Madrid, Spain and virtually.

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"The growing body of data supports the potential for revumenib to have a meaningful impact in combination with current standard of care therapies," said Joshua F. Zeidner, M.D., Chief, Leukemia Research at the University of North Carolina, Lineberger Comprehensive Cancer Center. "Based on the BEAT AML data in the newly diagnosed setting which showed a high rate of MRD-negative responses coupled with a safety profile that enables combination use, revumenib has the potential to become a cornerstone of treatment as front-line therapy for newly diagnosed KMT2Ar and mNPM1 AML."

"We are committed to advancing revumenib across a spectrum of acute leukemia patients. As we prepare for the expected near-term approval of revumenib in the relapsed or refractory setting, we look forward to providing additional clinical data as monotherapy and in combination to support treatment in various acute leukemia treatment settings where novel treatment options are urgently needed," said Neil Gallagher, M.D., Ph.D., President, Head of Research and Development at Syndax.

BEAT AML Trial

The Company announced updated data from the BEAT AML trial of revumenib in combination with venetoclax/azacitidine in newly diagnosed mutant nucleophosmin (mNPM1) or KMT2A-rearranged (KMT2Ar) acute myeloid leukemia (AML) patients aged 60 years or older in an oral presentation titled "Phase 1b Study of Azacitidine, Venetoclax and Revumenib in Newly Diagnosed Older Adults with NPM1 Mutated or KMT2A Rearranged AML: Interim Results of Dose Escalation from the BeatAML Consortium."

The dose escalation phase of the trial tested revumenib at doses of 113 mg and 163 mg q12h in combination with a strong CYP3A4 inhibitor beginning on day 1 of a 28-day cycle in combination with on label doses of venetoclax and azacitidine. As of the data cutoff date of May 1, 2024, 26 newly diagnosed mNPM1 (n=17) or KMT2Ar (n=9) AML patients were enrolled. In the efficacy evaluable population, the composite complete remission1 (CRc) rate was 96% (23/24) and 92% (22/24) of patients also attained minimal residual disease (MRD) negative status as determined by central flow cytometry. Three patients proceeded to hematopoietic stem cell transplant (HSCT). The first cohort of patients treated in the trial, at 113 mg, had extended follow-up and an estimated 12-month survival of 100%.

Revumenib was dosed safely at both the 113 mg and 163 mg q12h dose in combination with venetoclax and azacitidine. 15% (4/26) of patients experienced differentiation syndrome with one (4%) Grade 3 event. 46% (12/26) of patients experienced QTc prolongation with three (12%) Grade 3 events. All DS and QTc prolongations were self-limiting and resolved without complication or the need for revumenib dose reductions. Venetoclax was dosed in accordance with its label and an analysis of the onset and extent of hematologic toxicities suggest a similar experience to what has been reported for the venetoclax/azacytidine doublet. Overall, there were no new or increased safety signals observed when revumenib was added to this triplet combination.

An expansion cohort is ongoing at both dose levels to establish the recommended dose for future trials. The Company plans to initiate a pivotal trial with this combination in front-line newly diagnosed patients by year-end 2024.

AUGMENT-102 Trial

The Company also announced a poster presentation featuring updated data from the AUGMENT-102 trial of revumenib in combination with fludarabine/cytarabine in a predominantly pediatric population of patients with relapsed/refractory (R/R) mNPM1 (n=2), NUP98-rearranged (NUP98r) (n=1) or KMT2Ar (n=23) AML titled "Safety and Activity of Revumenib in Combination with Fludarabine/Cytarabine (FLA) in Patients with Relapsed/Refractory Acute Leukemias."

As of the data cutoff date of January 15, 2024, 27 patients received revumenib plus FLA, including 9 patients treated at 113 mg q12h and 18 treated at 163 mg q12h. The patients enrolled had a median age of 6 years and had received a median of 3 prior lines of therapy. Eighteen (67%) patients had prior FLA containing regimens while 11 (41%) patients had prior HSCT. Five (56%) patients treated at the 113 mg q12h dose and nine (50%) patients treated at the 163 mg q12h achieved a CRc. Most patients who achieved a CRc and had evaluable data achieved (MRD) negative status (10/14; 71%) and 7 patients underwent HSCT while in remission following treatment.

Overall, revumenib was tolerable in heavily pretreated patients with KMT2Ar, NUP98r, or NPM1m acute leukemias without increased frequency or severity of AEs compared with historic FLA data or revumenib monotherapy. One DLT occurred at the 163 mg q12h dose that was a Grade 4 decreased neutrophil count in a patient with multiple prior transplants.

Grade 3 and above adverse events in over 40% of patients included decreased platelet count (17/27; 63%), anemia (15/27; 56%) and febrile neutropenia (13/27; 48%). Lower rates of cytopenias were reported at the 163 mg q12h dose than the 113 mg q12h dose, consistent with faster remission at the higher dose. Lower rates of nonhematologic adverse events were also observed at the higher dose level, which further suggests that the adverse event profile was not driven by revumenib. There was one adverse event leading to death (sepsis at the 113 mg q12h dose level) not related to revumenib. There were no cases of differentiation syndrome in the trial.

This study supports the selection of revumenib 163 mg q12h (95 mg/m2 q12h if weight <40 kg) combined with FLA and a strong cytochrome P450 inhibitor as the RP2D, in line with the dose of revumenib under FDA review as a monotherapy agent.

Additional Presentations at EHA (Free EHA Whitepaper) 2024

In addition to updated results from the BEAT AML and AUGMENT-102 studies, an encore presentation of results from the pivotal AUGMENT-101 study of revumenib in R/R KMT2Ar acute leukemia were also featured at the Congress during an oral session titled "Revumenib Monotherapy in Patients with Relapsed/Refractory KMT2Ar Acute Leukemia: Topline Efficacy and Safety Results from the Pivotal AUGMENT-101 Phase 2 Study."

Results from an exploratory analysis of immunophenotypic changes in AML blasts following treatment with revumenib were also featured in a poster presentation titled "Characterization of Immunophenotypic Changes Following Menin Inhibition in Acute Myeloid Leukemia."

Copies of EHA (Free EHA Whitepaper) posters and presentations will be available in the Publications and Meeting Presentations section of Syndax’s website.

About Revumenib

Revumenib is a potent, selective, small molecule inhibitor of the menin-KMT2A binding interaction that is being developed for the treatment of KMT2A-rearranged (KMT2Ar), also known as mixed lineage leukemia rearranged or MLLr, acute leukemias including ALL and AML, and mutant nucleophosmin (mNPM1) AML. Positive topline results from the Phase 2 AUGMENT-101 trial in R/R KMT2Ar acute leukemia showing the trial met its primary endpoint were presented at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, and data from the Phase 1 portion of AUGMENT-101 in acute leukemia was published in Nature. Revumenib was granted Orphan Drug Designation by the FDA and European Commission for the treatment of patients with AML and Fast Track designation by the FDA for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation. Revumenib was granted Breakthrough Therapy Designation by the FDA for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement.

On June 14, 2024 Shattuck Labs, Inc. (Shattuck) (Nasdaq: STTK), a clinical-stage biotechnology company pioneering the development of bifunctional fusion proteins as a potential new class of biologic medicine for the treatment of patients with cancer and autoimmune disease, reported updated interim data from the Phase 1B dose expansion clinical trial of SL-172154 in combination with AZA in frontline HR-MDS and TP53m AML patients (Press release, Shattuck Labs, JUN 14, 2024, View Source [SID1234644339]). These data are to be featured in a poster presentation on June 14, 2024 at 18:00 CEST, during the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Congress.

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"We are pleased to present additional data from our Phase 1B dose expansion clinical trial, which further supports our differentiated mechanism of action and underscores SL-172154’s emergence as the leading CD47 inhibitor in hematologic malignancies," said Taylor Schreiber, M.D., Ph.D., Chief Executive Officer of Shattuck. "This update shows that the rate of complete remission has improved since our last data release in December, with additional patients in both cohorts who continue to improve on therapy. As a result of these encouraging data, and our expectation of rapid enrollment and progress in our ongoing randomized, controlled cohort in HR-MDS, we are focusing our efforts on our opportunity in HR-MDS and TP53m AML. These are indications with high unmet need, limited competition, and potential for accelerated paths to approval."

Dr. Lini Pandite, MBChB, M.B.A., Chief Medical Officer of Shattuck added, "We are encouraged by the maturing data that continues to underscore the therapeutic potential, and manageable safety profile, of SL-172154 for patients with previously untreated HR-MDS and TP53m AML. Accumulating clinical evidence now shows the pharmacodynamic contribution of CD40 activation in the peripheral blood, and an emerging correlation between clinical remission and CD40 mediated induction of certain cytokines. The TP53m AML and HR-MDS patients we have treated represent a high-risk group with short duration of complete remission and overall survival when treated with azacitidine alone. Median overall survival and duration of remission have not yet been achieved, and we look forward to sharing additional durability data later this year. Enrollment is now underway for our randomized, controlled expansion cohort in frontline HR-MDS patients, and we expect to engage in regulatory discussions later this year regarding the registrational strategy for SL-172154."

A copy of the EHA (Free EHA Whitepaper) poster, titled "Phase 1b Study of SL-172154, a Bi-functional Fusion Protein Targeting CD47 and CD40, in Combination with Azacitidine (AZA) in Previously Untreated Acute Myeloid Leukemia (AML) and Higher-Risk Myelodysplastic Syndromes/Neoplasms (HR- MDS) Patients (pts)," will be made available under posters in the Our Science section of Shattuck’s website.

Phase 1B Trial of SL-172154 in Frontline HR-MDS and TP53m AML

Key takeaways: Additional interim efficacy observed for SL-172154 in combination with AZA in frontline HR-MDS and TP53m AML.

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HR-MDS: As of the data cut-off date of April 23, 2024, in 24 treated patients (21 had TP53m, 16 had complex karyotype, and seven had therapy-related MDS), the ORR was 67%.

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Ten (42%) patients achieved a CR with 3.6 months as the median time to CR.

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Nine patients are continuing on treatment (five CR, two mCR+HI, one SD+HI, one SD).

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Three patients proceeded to allogeneic hematopoietic cell transplantation (HCT), all three patients achieved CR prior to HCT.

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TP53m AML: As of the data cut-off date of June 4, 2024, in 21 treated patients (all 21 had TP53 mutations or deletion, 19 had a complex karyotype, and 14 had secondary AML) the ORR was 43%.

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Six (29%) patients achieved a CR. One patient achieved a CRi and two patients achieved a partial remission (PR). The median time to CR was 3.8 months and none of the responders progressed as of the data cutoff.

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Five responders (three CR, one CRi, one PR) were taken to HCT and seven patients were still undergoing treatment, including two patients in CR. Additional patients may be bridged to transplant in the coming months.

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Preliminary analysis indicates clearance of TP53 mutation in four out of five TP53m HR-MDS patients and two out of four TP53m AML patients who achieved CR and were evaluated as of the data cutoff.

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Median duration of response for OR and CR and overall survival had not yet been reached in either HR-MDS or TP53m AML as of the respective data cutoff dates.

Safety Results: As of the data cutoff date of April 23, 2024, SL-172154 showed a manageable safety profile: Infusion-related reactions (IRRs) were the most common SL-172154 treatment-emergent adverse events (TEAEs). There have been no G3 or higher IRRs when patients have been premedicated with dexamethasone. There was no evidence of hemolytic (destructive) anemia.

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HR-MDS:

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Grade 3/4 AEs were reported in ten (42%) patients as related/possibly related to SL-172154: IRR (n=3), febrile neutropenia (n=2), anemia, alkaline phosphate increased, chondrocalcinosis, colitis, cytokine release syndrome, decreased appetite, fatigue, hypertension, left ventricular dysfunction, myocardial infarction (MI), neutropenia, pancytopenia, thrombocytopenia, troponin I increase, each in one patient.

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There was one death due to AE of sepsis, deemed unrelated to SL-172154, and three treatment discontinuations due to AEs, including MI (n=1), IRR (n=1) and sepsis (n=1)

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As already reported in the Company’s May 2024 EHA (Free EHA Whitepaper) abstract, a Grade 4 MI occurred in one patient who first developed sepsis on-study. This patient had a history of coronary artery disease and type II diabetes. The MI occurred eight days after the last dose of SL-172154. Although reported by the investigator as possibly related, Shattuck’s assessment is that this event was unlikely related to SL-172154.

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TP53m AML:

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Grade 3/4 AEs were reported in seven patients (33%), as related/possibly related to SL-172154, including neutropenia (n=3), thrombocytopenia (n=2), leukopenia (n=2), ALT increased (n=1), AST increased (n=1), enterococcal bacteremia (n=1), fatigue (n=1), hypoxia (n=1) and pneumonia (n=1)

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There were three deaths due to AEs deemed unrelated to SL-172154 including sepsis (n=1) and pneumonia (n=2)

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As already reported in the Company’s December 2023 update for the ASH (Free ASH Whitepaper) Annual Meeting, a Grade 5 cardiac arrest occurred in one patient with a history of significant cardiovascular disease, prior MI, prior stenting, prior arrhythmia, hypokalemia in the setting of amiodarone, additional adverse risk factors and other comorbidities. Although reported by the investigator as possibly related, Shattuck’s assessment is that this event was unlikely related to SL-172154.

Key Takeaways from Phase 1B Trial of SL-172154 in Platinum-Resistant Ovarian Cancer (PROC)

SL-172154 in combination with pegylated liposomal doxorubicin (PLD) or mirvetuximab soravtansine (Elahere)

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Interim efficacy results as of April 23, 2024, showed four of 21 (19%) treated patients in our Phase 1B study of SL-172154 in combination with PLD have achieved partial responses. The Javelin-200 study reported an ORR of 4% with PLD alone. Two additional patients with stable disease showed maximum tumor reductions of 17% and 27% and were continuing on study. The Company is continuing to follow patients for progression free survival and overall survival.

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In our cohort combining SL-172154 with Elahere, the Company has completed enrollment. As of the April 23, 2024 data cutoff, the Company has not observed an ORR benefit beyond Elahere alone, and the Company plans to further follow patients for progression free survival and overall survival.

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Both of these combinations, SL-172154 combined with PLD and SL-172154 combined with Elahere, have shown an acceptable safety profile with IRRs as the most common treatment emergent AE as of the data cutoff.

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The Company is not currently planning to conduct additional clinical development in PROC, in part due to the evolving competitive landscape in this indication. Should progression free survival or overall survival mature favorably in either PROC cohort, we would evaluate further development in PROC at that time. Shattuck will focus all current later-stage clinical development efforts in AML and HR-MDS due to the strength of the emerging efficacy results in those patient populations, the limited competition, and the potential for these indications to be the fastest path to registration.

Conference Call at 7:30 a.m. ET Today

Shattuck will host a conference call today at 7:30 a.m. ET featuring lead investigator Dr. Naval Daver, MD, (Professor and the Director of the Leukemia Research Alliance Program in the Department of Leukemia and MD Anderson Cancer Center in Houston, TX) to discuss the data from the poster presentation featured at the EHA (Free EHA Whitepaper) 2024 Congress, including an interim safety and efficacy update from the frontline expansion cohorts in HR-MDS and TP53m AML. To listen to the live webcast, please visit the Investor Relations page of the Shattuck Labs website here. Participants may register for the call here. While not required, interested participants are encouraged to join 10 minutes prior to the start of the event.

A replay of the webcast will be available following the conclusion of the live call and will be accessible on the Company’s website.

About SL-172154

SL-172154 (SIRPα-Fc-CD40L) is an investigational Agonist Redirected Checkpoint (ARC) fusion protein designed to simultaneously inhibit the CD47/SIRPα checkpoint interaction and activate the CD40 costimulatory receptor to bolster an anti-tumor immune response in patients with advanced cancer. Multiple Phase 1 clinical trials are ongoing for patients with platinum-resistant ovarian cancer (NCT04406623, NCT05483933) and patients with AML and HR-MDS (NCT05275439).

On June 14, 2024 Pfizer Inc. (NYSE: PFE) reported detailed overall survival (OS) results from the Phase 2 MagnetisMM-3 study of ELREXFIO (elranatamab-bcmm) in patients with heavily pretreated relapsed or refractory multiple myeloma (RRMM) (Press release, Seagen, JUN 14, 2024, View Source [SID1234644338]). The study demonstrated a median OS of 24.6 (95% CI, 13.4, NE) months in cohort A (n=123) of the pivotal single arm trial.

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These data from MagnetisMM-3 will be presented during a poster session (#932) at the European Hematology Association (EHA) (Free EHA Whitepaper) Hybrid Congress in Madrid, Spain, from June 13-16. Additional presentations at EHA (Free EHA Whitepaper) 2024 will highlight ELREXFIO data across the comprehensive MagnetisMM clinical trial program.

"These compelling overall survival data support the clinical benefit ELREXFIO has already demonstrated and its potential to be a transformative treatment option for people with multiple myeloma," said Roger Dansey, M.D., Chief Development Officer, Oncology, Pfizer. "The latest results from MagnetisMM-3 reinforce the very promising efficacy observed with ELREXFIO in a relapsed or refractory setting, with deep and durable responses and although definitive conclusions cannot be drawn across studies, the longest reported median progression-free survival among B-cell maturation antigen bispecific antibodies."

After more than two years of follow-up in the MagnetisMM-3 trial, the overall response rate (ORR) for patients on ELREXFIO was 61.0% (37.4% ≥complete response rate (CRR)), with responses deepening over time, and the median duration of response (DOR) was not reached. At two years, the estimated DOR rate was 66.9% (95% CI: 54.4, 76.7) for all responders, and 87.9% (95% CI: 73.1, 94.8) for patients with CR or better response. Median progression-free survival (PFS) was 17.2 months (95% CI: 9.8 months-NE). For patients with CR or better response, the median PFS was not reached, and at two years, the estimated PFS rate was 90.6% (95% CI: 76.9, 96.4).

"People with relapsed or refractory multiple myeloma often have limited therapeutic options as their disease progresses due to treatment resistance, resulting in increasingly shorter remission and duration of response," said MagnetisMM-3 clinical trial investigator Mohamad Mohty, M.D., Ph.D., Professor of Hematology and Head of the Hematology and Cellular Therapy Department at the Saint-Antoine Hospital and Sorbonne University, Paris, France. "These impactful overall survival data are particularly encouraging given the very advanced patient population with characteristics associated with poorer outcomes."

The safety and tolerability of ELREXFIO in MagnetisMM-3 were consistent with what have been previously observed. Five patients (4.1%) experienced secondary primary malignancies (SPMs), all cases being squamous cell carcinoma of the skin, consistent with SPMs often observed in patients with multiple myeloma (MM), while no hematological SPMs were reported. Due to the risk of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), patients should be monitored for signs and symptoms for 48 hours after administration of each of the two step-up doses within the ELREXFIO dosing schedule and instructed to remain in proximity of a healthcare facility. In the EU, precautionary hospitalization is not required. Patients are not required to stay near a healthcare facility for the 76 mg first treatment dose.

Based on results of the MagnetisMM-3 trial, ELREXFIO received accelerated approval in August 2023 from the U.S. Food and Drug Administration for the treatment of adult patients with RRMM who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody. Continued approval for this indication is contingent upon verification of clinical benefit in a confirmatory trial. In December 2023, the European Commission granted conditional marketing authorization for ELREXFIO for the treatment of adult patients with RRMM who have received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody, and have demonstrated disease progression on the last therapy. ELREXFIO has also received approval in Switzerland, Brazil and Canada under Project Orbis, a framework for the concurrent submission and review of oncology drugs among international partners to potentially expedite approvals. Two other countries (Australia and Singapore) are participating in Project Orbis. The Medicines and Healthcare products Regulatory Agency (MHRA) granted ELREXFIO authorization for Great Britain for RRMM.

Pfizer’s comprehensive ongoing MagnetisMM clinical development program is investigating the use of elranatamab across the entire spectrum of patients with MM, from RRMM to newly diagnosed MM. Ongoing registrational-intent trials are comparing elranatamab to current standards of care both as monotherapy and in combination with standard or novel therapies. These include MagnetisMM-4 investigating elranatamab treatment with other anti-cancer therapies, MagnetisMM-5 in the double-class exposed setting, MagnetisMM-6 in newly diagnosed patients who are ineligible for stem cell transplant, MagnetisMM-7 in newly diagnosed patients after transplant, and MagnetisMM-32 in patients with prior anti-CD38-directed therapy.

About MagnetisMM-3

MagnetisMM-3 is an open-label, multicenter, non-randomized Phase 2 study of ELREXFIO monotherapy in participants with multiple myeloma who are refractory to at least one proteasome inhibitor, one immunomodulatory drug, and one anti-cluster of differentiation 38 antibody. The study enrolled two cohorts of participants: one with and one without prior treatment with a B-cell maturation antigen-directed antibody-drug conjugate or chimeric antigen receptor T-cell therapy. Participants received subcutaneous ELREXFIO as two step-up priming doses followed by a weekly 76 mg injection. The primary endpoint is objective response rate as assessed by Blinded Independent Central Review (BICR). Key secondary endpoints include duration of response, progression-free survival, minimal residual disease negativity rate, overall survival, and safety. For more information about the trial, visit www.clinicaltrials.gov (NCT04649359).

About Multiple Myeloma

Multiple myeloma (MM) is an aggressive and currently incurable blood cancer that affects plasma cells made in the bone marrow. Healthy plasma cells make antibodies that help the body fight infection.1 MM is the second most common type of blood cancer, with over 50,000 new cases diagnosed annually in Europe and over 187,000 new cases diagnosed globally each year.2,3 About 40% of those diagnosed with MM won’t survive beyond five years,4 and most will receive 4 or more lines of therapy due to relapse.5 While disease trajectory varies for each person, relapses are nearly inevitable.6 The goal of therapy for people with relapsing or refractory MM is to achieve disease control with acceptable toxicity and improved quality of life.7

About ELREXFIO (elranatamab-bcmm)

ELREXFIO is a subcutaneously delivered B-cell maturation antigen (BCMA)-cluster of differentiation (CD)3-directed bispecific antibody immunotherapy that binds to BCMA on myeloma cells and CD3 on T cells, activating the T cells to kill myeloma cells.

U.S. INDICATION

ELREXFIO may cause side effects that are serious, life-threatening, or can lead to death, including cytokine release syndrome (CRS) and neurologic problems. CRS is common during treatment with ELREXFIO.

Tell your healthcare provider or get medical help right away if you develop any signs or symptoms of CRS or neurologic problems, including:

fever of 100.4°F (38°C) or higher
trouble breathing
chills
dizziness or light-headedness
fast heartbeat
headache
increased liver enzymes in your blood
agitation, trouble staying awake, confusion or disorientation, or seeing or hearing things that are not real (hallucinations)
trouble speaking, thinking, remembering things, paying attention, or understanding things
problems walking, muscle weakness, shaking (tremors), loss of balance, or muscle spasms
numbness and tingling (feeling like "pins and needles")
burning, throbbing, or stabbing pain
changes in your handwriting
Due to the risk of CRS, you will receive ELREXFIO on a "step-up" dosing schedule and should be hospitalized for 48 hours after the first "step-up" dose and for 24 hours after the second "step-up" dose of ELREXFIO.

For your first dose, you will receive a smaller "step-up" dose of ELREXFIO on day 1
For your second dose, you will receive a larger "step-up" dose of ELREXFIO, which is usually given on day 4 of treatment
For your third dose, you will receive the first "treatment" dose of ELREXFIO, which is usually given on day 8
If your dose of ELREXFIO is delayed for any reason, you may need to repeat step-up dosing. Before each dose of ELREXFIO you receive during the step-up dosing schedule, you will receive medicines to help reduce your risk of CRS. Your healthcare provider will decide if you need to receive medicines to help reduce your risk of CRS with future doses.

ELREXFIO is available only through the ELREXFIO Risk Evaluation and Mitigation Strategy (REMS) Program due to the risk of CRS and neurologic problems. You will receive an ELREXFIO Patient Wallet Card from your healthcare provider. Carry the ELREXFIO Patient Wallet Card with you at all times and show it to all of your healthcare providers. The ELREXFIO Patient Wallet Card lists signs and symptoms of CRS and neurologic problems. Get medical help right away if you develop any of the signs and symptoms listed on the ELREXFIO Patient Wallet Card. You may need to be treated in a hospital.

Before taking ELREXFIO, tell your healthcare provider about all of your medical conditions, including if you:

have an infection
are pregnant or plan to become pregnant. ELREXFIO may harm your unborn baby. Females who are able to become pregnant should do a pregnancy test before starting treatment with ELREXFIO and should use effective birth control during treatment and for four months after your last dose of ELREXFIO. Tell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment with ELREXFIO
are breastfeeding or plan to breastfeed. It is not known if ELREXFIO passes into your breast milk. Do not breastfeed during treatment and for four months after your last dose of ELREXFIO
Tell your healthcare provider about all of the medications you take, including prescription and over-the-counter medications, vitamins, and herbal supplements.

Do not drive, operate heavy or potentially dangerous machinery, or do other dangerous activities during treatment with ELREXFIO:

for 48 hours after completing each of the 2 doses of ELREXFIO that are part of the "step-up dosing schedule" and your first full treatment dose, and
at any time during treatment with ELREXFIO if you develop any new neurologic symptoms, such as dizziness, confusion, shaking (tremors), sleepiness, or any other symptom that impairs consciousness, until the symptoms go away
Infections: Upper respiratory tract infection and pneumonia are common during treatment with ELREXFIO. ELREXFIO can cause bacterial and viral infections that are severe, life-threatening, or that may lead to death.

Your healthcare provider may prescribe medications for you to help prevent infections and treat you as needed if you develop an infection during treatment with ELREXFIO
Tell your healthcare provider right away if you develop any signs or symptoms of an infection during treatment with ELREXFIO, including: fever of 100.4°F (38°C) or higher, chills, cough, shortness of breath, chest pain, sore throat, pain during urination, or feeling weak or generally unwell
People with active infections should not start ELREXFIO
Decreased white blood cell counts: Decreased white blood cell counts are common during treatment with ELREXFIO and can also be severe. A fever can occur with low white blood cell counts and may be a sign that you have an infection. Your healthcare provider will treat you as needed.

Liver problems: ELREXFIO can cause increased liver enzymes and bilirubin in your blood. These increases can happen with or without you also having CRS. Tell your healthcare provider if you develop any of the following signs or symptoms of a liver problem, including:

tiredness
loss of appetite
pain in your right upper stomach-area
dark urine
yellowing of your skin or the white part of your eyes
The most common side effects of ELREXFIO include:

tiredness
injection site reaction, such as redness, itching, pain, bruising, rash, swelling, and tenderness
diarrhea
muscle and bone pain
decreased appetite
rash
cough
nausea
fever
The most common severe abnormal lab test results with ELREXFIO include decreased white blood cells, red blood cells, and platelets.

Your healthcare provider may temporarily or permanently stop ELREXFIO if you have any of the side effects listed and they are severe. These are not all of the possible side effects of ELREXFIO.

Call your healthcare provider for medical advice about side effects. You may report side effects to the U.S. Food and Drug Administration (FDA) at 1-800-FDA-1088.

What is ELREXFIO?

ELREXFIO is a prescription medication used to treat adults with multiple myeloma who:

have already received at least 4 treatment regimens, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, to treat their multiple myeloma, and
their cancer has come back or did not respond to prior treatment
ELREXFIO was approved based on patient responses and durability of response. There are ongoing studies to confirm its clinical benefit. It is not known if ELREXFIO is safe and effective in children.

Please read full Prescribing Information , including BOXED WARNING, for ELREXFIO.

On June 14, 2024 Rezolute, Inc. (Nasdaq: RZLT) ("Rezolute" or the "Company"), a late-stage biopharmaceutical company committed to developing novel, transformative therapies for serious rare diseases, reported the pricing of its previously announced underwritten public offering of an aggregate of 11,250,000 shares of its common stock at an offering price of $4.00 per share, and, to certain investors in lieu of common stock, pre-funded warrants to purchase up to 3,750,000 shares of common stock at an offering price of $3.999 per pre-funded warrant, which represents the per share offering price for the common stock less the $0.001 per share exercise price for each pre-funded warrant (Press release, Rezolute, JUN 14, 2024, View Source [SID1234644337]). Gross proceeds from the underwritten public offering before deducting underwriting discounts and commissions and other offering expenses are expected to be approximately $60 million.

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All shares of common stock and pre-funded warrants to be sold in the offering will be offered by Rezolute. The closing of the offering is expected to occur on or about June 17, 2024, subject to the satisfaction of customary closing conditions.

Jefferies and Cantor are acting as the joint book-running managers for the offering. BTIG, Craig-Hallum, H.C. Wainwright & Co., Jones and Maxim Group LLC are acting as co-managers for the offering.

A shelf registration statement on Form S-3 (File No. 333-275562) relating to the securities to be offered in the public offering was filed with the Securities and Exchange Commission (the "SEC") and was declared effective on November 29, 2023. The public offering will be made only by means of a prospectus supplement and accompanying prospectus that form a part of the registration statement. A preliminary prospectus has been filed with the SEC and may be obtained on the SEC’s website at www.sec.gov. A final prospectus supplement and the accompanying prospectus relating to and describing the terms of the underwritten public offering will be filed with the SEC and, when available, may be obtained on the SEC’s website at www.sec.gov. Copies of the final prospectus supplement and accompanying prospectus relating to the public offering, when available, may be obtained by contacting: Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, New York, New York 10022, by telephone at 877-821-7388, or by email at [email protected] or Cantor Fitzgerald & Co., Attention: Capital Markets, 110 East 59th Street, 6th Floor, New York, New York 10022, or by email at [email protected]

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

On June 14, 2024 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting hard-to-treat tumors and viruses, reported additional efficacy findings from the Company’s ongoing Phase 1B/2 (MB-106) clinical trial evaluating Annamycin in combination with Cytarabine (also known as "Ara-C" and for which the combination of Annamycin and Ara-C is referred to as AnnAraC) for the treatment of subjects with acute myeloid leukemia (AML) (Press release, Moleculin, JUN 14, 2024, View Source [SID1234644335]). The preliminary data was presented at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Hybrid Congress. The Company also hosted a data presentation to leading AML experts as part of a KOL meeting held in conjunction with EHA (Free EHA Whitepaper) 2024 Congress.

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To date, a total of 22 subjects have been enrolled (the Intent-to-Treat population, ITT), 20 (Lines 1st-7th) of whom have completed efficacy evaluations with 9 subjects (45%) achieving a composite complete remission (CRc or CR/CRi), consisting of 8 (40%) subjects with complete remission (CR) and one subject with complete remission with an incomplete recovery of peripheral blood counts (CRi), following treatment with AnnAraC. Efficacy outcomes for 2 additional subjects (enrolled and treated) are pending.

Of the 10 ITT subjects for whom AnnAraC was administered in the 2nd line setting, 5 achieved a CR (50%) and 6 achieved a CRc (60%). Of the 13 subjects in the ITT evaluable population that were 1st or 2nd line treatment, 7 achieved a CR (54%) and 8 achieved a CRc (62%). The mDOR for the 9 subjects who achieved a CRc is approximately 6 months and climbing. Additionally, the median overall survival in the 2nd line subjects (n=10) is approximately 6 months and increasing.

Additionally, 89% of the subjects included in the CRc group (n=9) had cytogenetics and/or mutations generally considered to contribute to a poor prognosis. These include FLT3, IDH2, ASXL1, KMT2A and others. While not yet statistically relevant, the Company believes such cytogenetic and mutation data are informative to clinicians.

"We continue to be highly encouraged by the positive growing body of preliminary clinical data demonstrated by Annamycin in the treatment of patients with AML," commented Walter Klemp, Chairman and Chief Executive Officer of Moleculin. "While still preliminary, we believe the efficacy to date including the climbing durability of response demonstrated by AnnAraC in 2nd line patients continues to significantly exceed the performance reported by any drug currently approved for use in 2nd line AML. We are incredibly pleased with the progress of the trial and the data and continue to advance our preparations for an End of Phase 2 meeting with FDA."

"There remains a significant unmet need for safe and effective therapies for R/R AML. These data are exciting, and I believe further underscore the potential of Annamycin to provide patients and physicians with a promising treatment option in AML," concluded Mr. Klemp.

Currently, the median age of subjects in MB-106 is 69 years. Not including the two most recent subjects, a total of 17 subjects had relapsed/refractory AML and 3 subjects were first line treatment. Two subjects discontinued early due to allergic reactions. All subjects who completed treatment had undergone post-therapy bone marrow assessment (Day 15 or later). No clinically significant signs of cardiotoxicity were noted during or after treatment in any of the subjects enrolled. The combination was well tolerated with myelosuppression and infections being the main adverse events (AEs). All data from MB-106 is preliminary and subject to change.

Data presented at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Hybrid Congress:

As previously announced, the poster titled "LIPOSOMAL ANNAMYCIN (L-ANN) IN COMBINATION WITH CYTARABINE FOR TREATMENT OF PATIENTS WITH ACUTE MYELOID LEUKAEMIA (AML) REFRACTORY TO OR RELAPSED (R/R) AFTER INDUCTION THERAPY (MB-106 STUDY)," was presented as part of the "Acute myeloid leukemia – Clinical" session by Wolfram C. M. Dempke, MD, PhD, MBA, European Chief Medical Officer of Moleculin. The poster presentation mentioned above will be posted on the Company’s website and filed on Form 8-K with the Securities and Exchange Commission.

Annamycin currently has Fast Track Status and Orphan Drug Designation from the U.S. Food and Drug Administration for the treatment of relapsed or refractory acute myeloid leukemia, in addition to Orphan Drug Designation for the treatment of soft tissue sarcoma. Furthermore, Annamycin has Orphan Drug Designation for the treatment of relapsed or refractory acute myeloid leukemia from the European Medicines Agency (EMA). For more information about the ongoing MB-106 Phase 1B/2 trial, visit clinicaltrialsregister.eu and reference EudraCT 2020-005493-10 or clinicaltrials.gov and reference NCT05319587.