On June 13, 2025 Biomea Fusion, Inc. ("Biomea" or the "Company") (Nasdaq: BMEA), a clinical-stage diabetes and obesity medicines company, reported updated preliminary clinical data from the ongoing Phase I COVALENT-103 trial of BMF-500 in adults with relapsed or refractory ("R/R") acute leukemia ("AL") (Press release, Biomea Fusion, JUN 13, 2025, View Source [SID1234653874]). The results will be presented in a poster presentation at the European Hematology Association (EHA) (Free EHA Whitepaper) ("EHA") 2025 Congress in Milan, Italy.

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The presentation by Dr. Farhad Ravandi of The University of Texas MD Anderson Cancer Center will highlight emerging safety, pharmacokinetics/pharmacodynamics, and early clinical activity data for BMF-500, a highly selective covalent FMS-like tyrosine kinase 3 ("FLT3") inhibitor, in heavily pretreated patients with R/R AL.

Key Results from the EHA (Free EHA Whitepaper) 2025 Poster Presentation
27 patients were enrolled across two study arms, Arm A (no CYP3A4 inhibitor; n=10) and Arm B (CYP3A4 inhibitor; n=17). All patients had R/R AL, with a median of 4 prior lines of therapy. 18 of the 27 patients were FLT3 mutations ("FLT3m") while the other 9 patients had FLT3 wild-type AL. Frequent co-mutations included WT1, TP53, IDH1/2, and NRAS. All 18 FLT3m patients had failed gilteritinib in the R/R setting and 9 of the 18 had received at least two FLT3 inhibitors prior to study entry. 26 of 27 (96%) enrolled patients had also received and failed the BCL2 inhibitor venetoclax. Key findings include:

Clinical Activity Observed:

9 of 11 efficacy-evaluable FLT3m patients, defined as all patients enrolled who received at least one dose and had at least one disease assessment, showed bone marrow (BM) blast reduction; 5 of 11 achieved >50% BM blast reduction.
1 FLT3m patient achieved complete remission with incomplete hematologic recovery (CRi), sustained for 6 cycles.
1 FLT3m patient achieved morphologic leukemia-free state (MLFS); response is ongoing.
1 FLT3m patient met all criteria for partial response (PR) except platelet recovery; categorized as near PR.
2 of 4 efficacy-evaluable FLT3 wild-type patients achieved durable disease control ≥120 days, with treatment ongoing for one patient.
Additional clinical improvements include reductions in peripheral blasts, transfusion dependency, and frequency of hydroxyurea use.
Pharmacokinetics/Pharmacodynamics:

FLT3 inhibition correlated with BMF-500 systemic exposures.
Bone marrow and plasma concentrations of BMF-500 and its metabolites were comparable, suggesting good compartmental penetration.
Survival:

Median overall survival (mOS) among all treated FLT3m patients (n=18) was 3.8 months (Arm A) and 3.5 months (Arm B) during dose escalation.
For the efficacy-evaluable FLT3m patients (n=12), the mOS for Arms A and B was 3.8 and 3.6 months, respectively during dose escalation.
These survival durations compare favorably to historical mOS of 2.1 months in patients with R/R FLT3m acute myeloid leukemia ("AML") post-failure with both gilteritinib and venetoclax. 1
Ongoing Dose Escalation:

Dose escalation continues at 200 mg BID (Arm A) and 75 mg BID (Arm B).
Based on observed activity and tolerability, further evaluation is underway to determine optimal biologic dose ("OBD") and recommended Phase II dose ("RP2D").
Safety and Tolerability

BMF-500 was generally well-tolerated across dose levels.
No dose-limiting toxicities (DLTs), QT prolongation, or discontinuations due to treatment-related adverse events were reported.
Escalation is ongoing without safety restrictions.
"The updated COVALENT-103 results continue to support the potential of BMF-500 as a selective, covalent FLT3 inhibitor," said Mick Hitchcock, Ph.D., Interim Chief Executive Officer of Biomea Fusion. "We are encouraged by the depth of bone marrow responses, the achievement of MLFS and CRi, and the early survival benefit in heavily pretreated patients with FLT3 mutations who had progressed following prior FLT3 inhibitor therapy. These data speak to BMF-500’s potential to meaningfully improve outcomes in a high-risk AML population with no currently available treatment options."

Following completion of the COVALENT-103 dose escalation phase in R/R AL patients with FLT3m, Biomea plans to conclude its internal development of BMF-500 in oncology and is actively exploring strategic partnerships to advance the program.

Poster Presentation Details

Date/Time: Saturday, June 14 (18:30-19:30 CEST)
Title: Covalent FLT3 Inhibitor BMF-500 in Relapsed or Refractory (R/R) Acute Leukemia (AL): Preliminary Phase 1 Data from the COVALENT-103 Study (NCT05918692)
Poster Number: PS1520
Presenter: Farhad Ravandi, M.D., University of Texas MD Anderson Cancer Center
About COVALENT-103
COVALENT-103 is a multicenter, open-label, non-randomized trial seeking to evaluate the safety and efficacy of BMF-500, a twice daily oral treatment, in adult patients with R/R AL with FLT3 wild-type or FLT3m. The Phase I COVALENT-103 study aims to evaluate the safety and tolerability of BMF-500, determine the optimal biologic dose and recommended Phase II dose, and identify initial efficacy signals. Additional information about the Phase I clinical trial of BMF-500 can be found at ClinicalTrials.gov using the identifier, NCT05918692.

About BMF-500
BMF-500 is an investigational, orally bioavailable, covalent small molecule inhibitor of FLT3, discovered in-house using Biomea’s proprietary FUSION System. Designed to be highly potent and selective, BMF-500 has demonstrated encouraging potential in extensive preclinical studies. Its kinase inhibitory profile indicates strong target selectivity, which may translate to a reduced risk of off-target effects.

On June 13, 2025 Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company working to develop a new class of drugs based on targeted protein degradation, reported data from preclinical studies of ARV-393, the company’s investigational PROteolysis TArgeting Chimera (PROTAC) B-cell lymphoma 6 protein (BCL6) degrader (Press release, Arvinas, JUN 13, 2025, View Source [SID1234653873]). BCL6 is a transcriptional repressor protein and a known driver of B-cell lymphomas. ARV-393 demonstrated significant single-agent activity in a patient derived xenograft (PDX) model of nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (nTFHL-AI also known as AITL) and PDX models of transformed follicular lymphoma (tFL). In combination with oral small molecule inhibitors (SMIs), ARV-393 demonstrated enhanced antitumor activity, including tumor regressions, in cell line-derived xenograft (CDX) models of high-grade B-cell lymphoma (HGBCL) and aggressive diffuse large B-cell lymphoma (DLBCL). The results from these preclinical studies were shared at the European Hematology Association (EHA) (Free EHA Whitepaper) 2025 Congress in Milan, Italy.

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Key findings from the preclinical studies included:

Single-agent ARV-393 significantly reduced tumor burden in peripheral blood, bone marrow and spleen in a systemic PDX model of nTFHL-AI derived from a patient who relapsed post chemotherapy. This is potentially the first preclinical evidence of anti-tumor activity with an efficacious BCL6-targeted small-molecule degrader in a human nTFHL-AI model.
ARV-393 monotherapy treatment resulted in robust (≥95%) tumor growth inhibition (TGI) in two PDX models of tFL.
ARV-393 in combination with 5 classes of SMIs targeting potentially cooperative oncogenic drivers (tazemetostat, palbociclib, everolimus, acalabrutinib, or venetoclax) demonstrated increased TGI in CDX models of HGBCL and aggressive DLBCL compared with the respective monotherapy treatments. Tumor regressions were observed when ARV-393 was combined with tazemetostat, palbociclib, acalabrutinib, or venetoclax.
RNA sequencing studies carried out to further characterize downstream mechanism of action suggested that ARV-393 inhibits tumor cell cycle progression and promotes differentiation, driving antitumor activity and broad combinability in preclinical models.
"We are encouraged by the marked single-agent activity of ARV-393 in PDX models of AITL and transformed follicular lymphoma and by the enhanced antitumor activity of ARV-393 in combination with five classes of small molecule inhibitors in models of aggressive DLBCL," said Noah Berkowitz, M.D., Ph.D., Chief Medical Officer at Arvinas. "We believe these preclinical data potentially suggest the broad utility of ARV-393 across non-Hodgkin lymphoma subtypes with unmet need beyond DLBCL and provide a compelling rationale for considering combination strategies including chemotherapy-free approaches as we work to bring forward new therapeutic options for adult patients with lymphoma."

A Phase 1 study of ARV-393 is enrolling adult patients with relapsed/refractory non-Hodgkin lymphoma, including DLBCL and nTFHL-Al (AITL) (NCT06393738).

Additional detail on the ARV-393 data presentation at the EHA (Free EHA Whitepaper) 2025 Congress:

Poster Title: ARV-393, a PROteolysis TArgeting Chimera (PROTAC) BCL6 Degrader, is Efficacious in Preclinical Models of Diffuse Large B-Cell Lymphoma, Nodal T-Follicular Helper Cell Lymphoma, and Transformed Follicular Lymphoma

Abstract: PF1000
Session Title: Lymphoma biology & translational research 
Date: Thursday, June 13, 2025
Time: 6:30-7:30 pm CEST

About ARV-393
ARV-393 is an investigational orally bioavailable PROteolysis TArgeting Chimera (PROTAC) designed to degrade B-cell lymphoma 6 protein (BCL6), a transcriptional repressor and major driver of B-cell lymphomas. The BCL6 protein facilitates B cell tolerance of rapid proliferation and somatic gene recombination via repressing cell cycle checkpoints, terminal differentiation, apoptosis, and the DNA damage response. PROTAC-mediated degradation has the potential to address the traditional undruggable nature of BCL6. ARV-393 is currently being evaluated in a Phase 1 clinical trial in patients with relapsed/refractory non-Hodgkin lymphoma.

On June 13, 2025 Ratio Therapeutics Inc. (Ratio), a pharmaceutical company employing innovative technologies to develop best-in-class radiopharmaceuticals for cancer treatment and monitoring, reported that it entered into an agreement granting Macrocyclics Inc. (Macrocyclics) exclusive manufacturing and distribution rights to Ratio’s proprietary chelator MacropaTM enabling broad access worldwide (Press release, Ratio Therapeutics, JUN 13, 2025, View Source [SID1234653872]).

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Macropa is a proprietary, best-in-class, bifunctional chelator for Actinium-225, known for its strong alpha-particle emissions and its use in targeted alpha therapy (TAT) for the treatment of cancer. Macropa can be tethered to small molecules, peptides, and large polypeptides such as proteins and antibodies to enable the development of targeted radiopharmaceuticals for alpha radiotherapy. By rapidly and quantitatively complexing Ac-225 at room temperature, Macropa’s unique selectivity and stability for Ac-225 enables simple "one-pot" manufacturing and improves in vivo stability of the resulting compound.

"Over the past year, we have been focused on building global scientific awareness and encouraging adoption of our chelator platform across the therapeutic radiopharmaceutical community," said Bill Cupelo, Chief Business Officer of Ratio. "We are proud to see our efforts realized through an expanding global ecosystem of collaborators who can now leverage Macropa to accelerate the development and adoption of radiopharmaceuticals worldwide. By enabling broader access to our platform, we are fostering a global community aligned in the mission to improve patient outcomes through targeted cancer therapies and diagnostics."

Incorporated in 1995, Macrocyclics is a CDMO specialized in chelating agents for radiopharmaceuticals and nuclear medicine. The company maintains a broad catalog of bifunctional chelating agents that are used in R&D and clinical programs across the globe. Under the terms of the agreement, researchers from academia and industry may purchase Macropa directly from Macrocyclics, enabling rapid access in many countries including Japan, Canada, Australia and majority of Europe.

"Ratio’s Macropa is a superior chelator for Ac-225," said Paul Jurek, Ph.D., CEO of Macrocyclics. "The ability to label quickly at room temperature provides a critical advantage, especially when working with proteins or vectors that degrade when heated. We are excited to be the exclusive manufacturer of Macropa and plan to add multiple derivatives to our catalog and provide it under GMP conditions for innovators engaged in clinical research."

Macrocyclics is an exhibitor at the 2025 SNMMI Annual Meeting, located in New Orleans, LA from June 21 to June 24. Ratio will also have representatives in attendance and will host a networking event for current and potential Macropa users.

On June 13, 2025 Syntara Limited (ASX:SNT), a clinical-stage drug development company, reported further positive interim data from its ongoing Phase 2 clinical trial evaluating SNT-5505 (200 mg BID) in combination with ruxolitinib (RUX) for the treatment of myelofibrosis (MF) (Press release, Syntara, JUN 13, 2025, View Source;v=04711220c3a57065317ba4efca4a3459a4e46882 [SID1234653852]). This data will be presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Conference on Sunday 15 June 2025 AEST, and builds upon the positive interim results announced at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2024.

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The latest interim results further highlight the safety and clinical benefits of SNT5505’s unique mechanism of action and competitive profile in treating MF patients who have had a suboptimal response to existing standard of care.

Patients in the trial had been treated with ruxolitinib (RUX) for an average of three years with symptom scores, spleen sizes and blood counts indicative of high disease burden.

Highlights:

73% (8/11) of evaluable patients achieved TSS50 at 24 weeks of treatment or beyond.

44% (4/9) of evaluable patients achieved a spleen volume reduction (SVR) of 25% at Week 24 or beyond. Notably there were no increases in dosage of concomitant RUX that might otherwise explain the impact of SNT-5505 on spleen volume.

The continued improvement in patient symptoms and spleen volume is a novel finding that differentiates SNT-5505 from MF drugs on market and in later stages of development. It highlights the potential of SNT-5505 to be used in combination with JAK inhibitors to change the long-term outcomes for MF patients.

SNT-5505 is safe and well tolerated, with no treatment related serious adverse events (SAEs) attributed to SNT-5505; providing additional and important differentiation to MF drugs on market and in development.

Syntara to engage with the FDA in Q3 on study results and trial design for a pivotal Phase 2c/3 study.

Syntara CEO Gary Phillips commented: "After very recently being awarded Fast Track designation, the positive interim data to be presented at EHA (Free EHA Whitepaper) 2025 further reinforces the promising profile of SNT5505 as an add-on therapy for myelofibrosis patients with a suboptimal response to existing standard of care. The sustained and increasing improvements in both symptom burden and spleen volume, coupled with its excellent safety and tolerability, continue to differentiate SNT-5505 from other drugs in this space. We are particularly encouraged by the durability of the responses observed and look forward to reporting final study results and engaging with the FDA and potential partners in the coming months."

On June 13, 2025 Alligator Bioscience (Nasdaq Stockholm: ATORX), a clinical-stage biotechnology company developing tumor-directed immunotherapies, reported that the U.S. Food and Drug Administration (FDA) has provided feedback supporting the selection of the 900 µg/kg dose of its CD40 agonist mitazalimab for the planned Phase 3 study in metastatic pancreatic ductal adenocarcinoma (mPDAC) (Press release, Alligator Bioscience, JUN 13, 2025, View Source [SID1234653851]).

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This positive regulatory feedback confirms Alligator’s dose selection and represents a key milestone in the late-stage development of mitazalimab.

"We are very pleased with the FDA’s timely and constructive response. This marks an important step forward as we finalize our Phase 3 program for mitazalimab in one of the most aggressive and underserved cancers. We are now in active partnering dialogues aiming to secure the right partner to take mitazalimab into Phase 3," said Søren Bregenholt, CEO of Alligator Bioscience.