On May 14, 2025 Foghorn Therapeutics Inc. (Nasdaq: FHTX), a clinical-stage biotechnology company pioneering a new class of medicines that treat serious diseases by correcting abnormal gene expression, reported a financial and corporate update in conjunction with the Company’s 10-Q filing for the quarter ended March 31, 2025 (Press release, Foghorn Therapeutics, MAY 14, 2025, View Source [SID1234653058]). With an initial focus in oncology, Foghorn’s Gene Traffic Control Platform and resulting broad pipeline have the potential to transform the lives of people suffering from a wide spectrum of diseases.

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"In the first quarter, we continued to progress our novel partnered and proprietary programs, and we were pleased to share more details on the pipeline progress at this year’s AACR (Free AACR Whitepaper) annual meeting. The FHD-909 Phase 1 dose escalation trial is proceeding apace. Importantly, the FHD-909 combination data with chemotherapies, KRAS inhibitors and pembrolizumab, that was shared at AACR (Free AACR Whitepaper), reinforces the expansive potential of the selective SMARCA2 inhibitor program in non-small cell lung cancer," said Adrian Gottschalk, President and Chief Executive Officer of Foghorn. "Initial data defining potential combination opportunities in ER+ breast cancer for our Selective CBP degrader program are encouraging and support potential beyond EP300-mutant cancers. Our Selective EP300 degrader program continues to show anti-proliferative activity in a broad range of hematological malignancies. And lastly, as previously reported, we have achieved selective degradation for our Selective ARID1B program and look forward to providing a program update in 2025."

Mr. Gottschalk continued, "These advancements with FHD-909 and our pipeline programs underscore our track record and leadership in engineering promising selective therapeutics. With our robust balance sheet and cash runway into 2027, we are in a strong position to deliver significant value with differentiated, high-impact therapeutics in 2025 and beyond."

Recent Corporate Updates

Data presented at American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. In April 2025, Foghorn presented new preclinical data highlighting pipeline progress for potential first-in-class medicines including FHD-909, a SMARCA2 (BRM) selective inhibitor, and the Selective CBP degrader program and Selective EP300 degrader program.

Two Appointments to Board of Directors. In May, Foghorn announced the appointments of Neil Gallagher, M.D., Ph.D. and Stuart Duty, to its Board of Directors.
•Dr. Gallagher brings over 20 years of executive experience at pharmaceutical and biopharmaceutical organizations leading drug development programs across several therapeutic areas, including oncology. Currently he serves as the President, Head of Research and Development at Syndax Pharmaceuticals and held prior clinical development leadership roles at AbbVie, Amgen, Novartis, and AstraZeneca.
•Mr. Duty has over 30 years of executive experience in finance and investment banking in biotechnology and specialty pharmaceuticals. Most recently, he served as a Senior Managing Director at Guggenheim Securities, LLC where he advised senior executives and boards on a range of financing activities and strategic transactions. Previously, he held senior roles at Piper Jaffray and Montgomery Securities and operating roles at Oracle Partners and Curative Technologies.

Second Annual Chromatin Regulation Summit. In May 2025, Foghorn hosted its "Chromatin Regulation Summit: Targeted Protein Degradation and Induced Proximity," at their corporate headquarters in Cambridge, Massachusetts. The live event featured presentations and panel discussions with world-renowned industry and academic key opinion leaders on current and future applications of targeted protein degradation and induced proximity modalities for the treatment of disease.

Program Overview and Upcoming Milestones

FHD-909 (LY4050784). FHD-909 is a first-in-class oral SMARCA2 selective inhibitor that has demonstrated in preclinical studies to have high selectivity over its closely related paralog SMARCA4, two proteins that are the catalytic engines across all forms of the BAF complex. Selectively blocking SMARCA2 activity is a promising synthetic lethal strategy intended to induce tumor death while sparing healthy cells. SMARCA4 is mutated in up to 10% of NSCLC alone and implicated in a significant number of solid tumors.

•Advancing Phase 1 trial. Ongoing enrollment and dose escalation in the first-in-human Phase 1, multicenter trial for FHD-909 in SMARCA4 mutated cancers, with NSCLC as the primary target population following the dosing of the first patient in October 2024.

◦At the AACR (Free AACR Whitepaper) Annual Meeting in April 2025, Lilly presented, on behalf of the collaboration, the clinical study design poster for the Phase 1 trial evaluating FHD-909 in patients with SMARCA4 mutated locally advanced or metastatic solid tumors who have exhausted standard treatment options. The primary target population is NSCLC.

•Presented synergistic preclinical data of FHD-909 in combination with pembrolizumab and KRAS inhibitors. Also at the AACR (Free AACR Whitepaper) Annual Meeting in April 2025, Lilly, on behalf of the collaboration, made an oral presentation of new preclinical data demonstrating enhanced anti-tumor activity of FHD-909 in combination with standard-of-care chemotherapies, anti-PD-1 pembrolizumab and several novel KRAS inhibitors in NSCLC animal models. The combination data will inform further development plans of FHD-909.

Ongoing strategic collaboration with Lilly. Collaborating with Lilly to create novel oncology medicines that includes a U.S. 50/50 co-development and co-commercialization agreement for Foghorn’s selective SMARCA2 oncology program, including a selective inhibitor and a selective degrader, and an additional undisclosed oncology target. The collaboration also includes three discovery programs from Foghorn’s proprietary Gene Traffic Control platform.

Selective CBP degrader program. Selectively targets CBP in EP300-mutated cancer cells found in many types of cancer, including bladder, gastric, and endometrial cancers. CBP and EP300 are highly similar acetyltransferases that create a synthetic lethal relationship when EP300 is mutated. Attempts to selectively drug CBP have been challenging due to the high level of similarity between the two proteins, while dual inhibition of CBP/EP300 has been limited by dose-limiting toxicities.
•Presented preclinical combination data with Selective degrader CBP in ER+ breast cancer. In April 2025, preclinical data showing Selective CBP degraders have combinatorial benefit with approved chemotherapies and targeted agents in solid tumors beyond EP300-mutant cancers was presented as a poster at the AACR (Free AACR Whitepaper) Annual Meeting
•Synergistic combination activity demonstrated including with paclitaxel and CDK4/6 inhibitor abemaciclib in ER+ breast cancer
•Findings support combination opportunities for selective CBP degraders in solid tumors beyond EP300-mutant cancers

•On track for IND-enabling studies, targeting IND in 2026.
Selective EP300 degrader program. Selective degradation of EP300 for the treatment of hematopoietic malignancies and prostate cancer. Attempts to selectively drug EP300 have been challenging due to the high level of similarity between EP300 and CBP, while dual inhibition of CBP/EP300 has been limited by dose limiting toxicities. EP300 lineage dependencies are established in multiple myeloma and diffuse large B cell lymphoma.

•Presented preclinical data showing combination with diffuse large b-cell lymphoma (DLBCL) and multiple myeloma (MM) Standard-of-Care Treatment (SoC). In April 2025, preclinical data for the Selective EP300 degrader program demonstrating biological activity in hematological malignancies was presented at the AACR (Free AACR Whitepaper) Annual Meeting.
•Anti-proliferative activity in a broad range of hematological malignancies in vitro, including DLBCL, MM, and follicular lymphoma
•Combination of EP300 degrader with SoC in both DLBCL and MM are highly synergistic in vitro.
•Selective EP300 degradation is effective in IMiD-resistant MM cell lines.

•Program update expected in H2 2025.

Selective ARID1B degrader program. Selectively targets and degrades ARID1B in ARID1A-mutated cancers. ARID1A is the most mutated subunit in the BAF complex and amongst the most mutated proteins in cancer. These mutations lead to a dependency on ARID1B in several types of cancer, including ovarian, endometrial, colorectal and bladder. Attempts to selectively drug ARID1B have been challenging because of the high degree of similarity between ARID1A and ARID1B and the fact that ARID1B has no enzymatic activity to target.

•ARID1B is a major synthetic lethal target implicated in up to 5% of all solid tumors.
•Developed highly potent and selective binders. Preclinical data demonstrated potent and selective small molecule binders to ARID1B.
•Selective degradation of ARID1B achieved. Foghorn has successfully selectively degraded ARID1B and expects to provide an update on the Selective ARID1B degrader program in H2 2025.

Chromatin Biology and Degrader Platform. Foghorn continues to advance its chromatin biology and degrader platform with investments in novel ligases, long-acting injectables, oral delivery, and induced proximity.

First Quarter 2025 Financial Highlights

•Collaboration Revenue. Collaboration revenue was $6.0 million for the three months ended March 31, 2025, compared to $5.1 million for the three months ended March 31, 2024. The increase was driven by the continued advancement of programs under the Lilly Collaboration Agreement.

•Research and Development Expenses. Research and development expenses were $21.6 million for the three months ended March 31, 2025, compared to $25.5 million for the three months ended March 31, 2024. The decrease is attributed to a decrease in FHD-286 costs of $2.5 million, decreases in personnel-related costs, early development and other research external costs and facilities and IT-related expenses of $2.1 million, partially offset by an increase in Lilly-partnered programs of $0.7 million.

•General and Administrative Expenses. General and administrative expenses were $7.2 million for the three months ended March 31, 2025, compared to $7.7 million for the three months ended March 31, 2024. This decrease was primarily due to lower consulting costs.

•Net Loss. Net loss was $18.8 million for the three months ended March 31, 2025, compared to a net loss of $25.0 million for the three months ended March 31, 2024.

•Cash, Cash Equivalents, and Marketable Securities. As of March 31, 2025, the Company had $220.6 million in cash, cash equivalents, and marketable securities, providing expected cash runway into 2027.

About FHD-909
FHD-909 (LY4050784) is a potent, first-in-class, allosteric, and orally available small molecule that selectively inhibits the ATPase activity of SMARCA2 (BRM) over its closely related paralog SMARCA4 (BRG1), two proteins that are the catalytic engines across all forms of the BAF complex, one of the key regulators of the chromatin regulatory system. In preclinical studies, tumors with mutations in SMARCA4 rely on SMARCA2 for their survival. FHD-909 has shown significant anti-tumor activity across multiple SMARCA4 mutant lung tumor models.

On May 14, 2025 Citius Pharmaceuticals, Inc. ("Citius Pharma" or the "Company") (Nasdaq: CTXR), a biopharmaceutical company dedicated to the development and commercialization of first-in-class critical care products reported business and financial results for the fiscal quarter ended March 31, 2025 (Press release, Citius Pharmaceuticals, MAY 14, 2025, View Source [SID1234653057]).

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"As we continue to focus on the planned launch of our first FDA-approved product, LYMPHIR, through Citius Oncology, we are actively engaged in securing the necessary financing to advance our launch strategy in the coming months, as well as exploring strategic partners for Citius Oncology," said Leonard Mazur, Chairman and CEO of Citius Pharmaceuticals and Citius Oncology.

"We are also in the process of preparing a submission to the FDA that reflects the valuable feedback we received from the agency concerning clinical efficacy, safety data, and in-vitro data. This submission is a key step toward supporting a future New Drug Application (NDA) for our Mino-Lok program. As a reminder, our Phase 3 Trial, which was completed last year, met its primary endpoints," added Mazur.

"During the quarter, we took deliberate steps to strengthen our financial position, including completing a registered direct offering and leveraging our existing at-the-market sales agreement to ensure capital flexibility. We also amended our license agreement with Eisai to align our payment obligations with our commercialization timeline. With these efforts underway, we believe we are positioned to deliver long-term value to patients and shareholders alike," concluded Mazur.

FISCAL SECOND QUARTER 2025 Financial Results:

Liquidity

During the six months ended March 31, 2025, the Company received net proceeds of $6 million from the issuance of equity. On April 2, 2025, the Company closed on a registered direct offering to an institutional investor of our common stock and pre-funded warrants to purchase common stock. The net proceeds to the Company from the offering were approximately $1.735 million, after deducting placement agent fees and other offering expenses payable by the Company.

As of March 31, 2025, the Company had $26,410 in cash and cash equivalents and 8,760,649 common shares outstanding excluding the April 2, 2025 financing. Citius Pharma will need to secure additional capital to support operations beyond May 2025.

Until Citius Oncology raises adequate capital through equity financings from outside investors and/or generates revenue from the future sales of LYMPHIR, Citius Pharma plans to continue to fund Citius Oncology. Citius Oncology has also retained Jefferies LLC as its exclusive financial advisor to evaluate strategic alternatives aimed at maximizing stockholder value.

Research and Development (R&D) Expenses

R&D expenses were $3.8 million for the quarter ended March 31, 2025, as compared to $3.6 million for the quarter ended March 31, 2024. For the six months ended March 31, 2025, R&D expenses were $5.9 million, as compared to $6.3 million during the six months ended March 31, 2024. R&D expenses primarily reflect LYMPHIR-related costs.

Research and development costs for LYMPHIR were $5.3 during the six months ended March 31, 2025, as compared to $3.2 million for the six months ended March 31, 2024. The $2.1 million increase in expenses was primarily due to costs associated with the expense of a drug substance batch needed for the pre license inspection of the manufacturer.

R&D expenses related to Mino-Lok decreased due to completion of the Phase 3 trial. There were no Halo Lido R&D expenses during the quarter, and $11 thousand was recorded for the six months ended March 31, 2025.

We expect that research and development expenses will continue to decrease in fiscal 2025 as we continue to focus on the commercialization of LYMPHIR and because we have completed the Phase 3 trial for Mino-Lok.

General and Administrative (G&A) Expenses

G&A expenses were $4.8 million for the quarter ended March 31, 2025, as compared to $4.3 million for the quarter ended March 31, 2024. For the six months ended March 31, 2025, G&A expenses were $10.2 million, as compared to $7.9 million for the six months ended March 31, 2024. The increase was primarily due to higher costs for pre-launch commercial activities associated with LYMPHIR. General and administrative expenses consist primarily of compensation costs, professional fees for legal, regulatory, accounting, and corporate development services, and investor relations expenses.

Stock-based Compensation Expense

For the quarter ended March 31, 2025, stock-based compensation expense was $2.7 million, as compared to $3.1 million for the quarter ended March 31, 2024. For the six months ended March 31, 2025, stock-based compensation expense was $5.2 million, as compared to $6.1 million for the six months ended March 31, 2024. Stock-based compensation expense is primarily related to the Citius Oncology stock plans. The decrease compared to the prior year is due to lower costs associated with the Citius Pharma stock plans.

Net loss

Net loss was $11.5 million, or ($1.27) per share, for the quarter ended March 31, 2025, as compared to a net loss of $8.5 million, or ($1.34) per share, for the quarter ended March 31, 2024, as adjusted for the reverse stock split. The increase in net loss was due to a $2.6 million decrease in other income, offset by the increase in general and administrative expenses and research and development expenses.

For the six months ended March 31, 2025, we incurred a net loss of $21.8 million, as compared to a net loss of $17.8 million for the six months ended March 31, 2024. The $4.0 million increase in the net loss was primarily due to the increase of $2.2 million in general and administrative expenses and the decrease in other income of $2.9 million, partially offset by lower research and development expense and lower stock-based compensation expense.

On May 14, 2025 Celcuity Inc. (Nasdaq: CELC), a clinical-stage biotechnology company pursuing development of targeted therapies for oncology, reported financial results for the first quarter ended March 31, 2025 and other recent business developments (Press release, Celcuity, MAY 14, 2025, View Source [SID1234653056]).

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"We continue to make steady progress across our pipeline with several critical data catalysts anticipated this year," said Brian Sullivan, CEO and co-founder of Celcuity. "We now expect to report topline data for the PIK3CA wild-type cohort of the VIKTORIA-1 trial in the third quarter of this year and to report topline data for the PIK3CA mutant cohort in the fourth quarter of 2025. If our topline data from the WT cohort is positive, we expect the data will support the filing of our first new drug application and, if approved, our transition to a commercial stage company."

First Quarter 2025 Business Highlights and Other Recent Developments

● Based on evaluation of blinded event rates in the ongoing VIKTORIA-1 Phase 3 clinical trial, the primary completion date for the PIK3CA wild-type patient cohort is projected to occur in June 2025 with topline data now anticipated to be available in the third quarter of 2025.

○ Enrollment is ongoing in the PIK3CA mutant cohort of the VIKTORIA-1 trial and remains on track to report topline data in the fourth quarter of 2025.
○ VIKTORIA-1 is a global Phase 3 study evaluating gedatolisib in combination with fulvestrant with and without palbociclib in adults with HR+, HER2- advanced breast cancer who have received prior treatment with a CDK4/6 inhibitor.

● Site activation activities are underway globally for the VIKTORIA-2 Phase 3 clinical trial and dosing of the first patient is anticipated to occur in the second quarter of 2025.

○ VIKTORIA-2 is a global, Phase 3 open-label randomized study evaluating the efficacy and safety of gedatolisib in combination with fulvestrant plus a CDK4/6 inhibitor, either ribociclib or palbociclib, in comparison to fulvestrant plus a CDK4/6 inhibitor as a first-line treatment for patients with HR+/HER2- advanced breast cancer who are endocrine therapy resistant.
○ Prior to initiating the Phase 3 portion of the study, a safety run-in will be conducted in 12-36 participants to assess the safety of gedatolisib in combination with ribociclib and fulvestrant.

● The CELC-G-201 study is on track to report topline data for the Phase 1b portion of the trial late in the second quarter of 2025.

○ CELC-G-201 is a Phase 1b/2 evaluating gedatolisib in combination with darolutamide for the treatment of patients with metastatic castration resistant prostate cancer (mCRPC) whose disease progressed while on or after treatment with an androgen receptor signaling inhibitor.
○ The Phase 1b portion of the trial will assess the safety and tolerability of gedatolisib in combination with darolutamide and is expected to identify the recommended phase 2 dose regimen.

● Initiating a clinical trial collaboration with the Dana Farber Cancer Institute and Massachusetts General Hospital to evaluate gedatolisib in combination with abemaciclib and letrozole in patients with endometrial cancer

○ In a prior Phase 2 study, gedatolisib was evaluated as a monotherapy in patients with endometrial cancer.

First Quarter 2025 Financial Results

Unless otherwise stated, all comparisons are for the first quarter ended March 31, 2025, compared to the first quarter ended March 31, 2024.

Total operating expenses were $36.1 million for the first quarter of 2025, compared to $22.5 million for the first quarter of 2024.

Research and development ("R&D") expenses were $32.2 million for the first quarter of 2025, compared to $20.6 million for the prior-year period. Of the approximately $11.6 million increase in R&D expenses, $5.9 million primarily related to increased employee and consulting expenses. The remaining $5.7 million primarily related to activities supporting our ongoing clinical trials.

General and administrative ("G&A") expenses were $3.9 million for the first quarter of 2025, compared to $1.8 million for the prior-year period. Increased employee and consulting expenses accounted for $1.6 million of the increase. Professional fees, expanding infrastructure and other administrative expenses accounted for the remaining increase of approximately $0.5 million.

Net loss for the first quarter of 2025 was $37.0 million, or $0.86 loss per share, compared to a net loss of $21.6 million, or $0.64 loss per share, for the first quarter of 2024. Non-GAAP adjusted net loss for the first quarter of 2025 was $34.7 million, or $0.81 loss per share, compared to non-GAAP adjusted net loss of $19.9 million, or $0.59 loss per share, for the first quarter of 2024. Non-GAAP adjusted net loss excludes stock-based compensation expense, non-cash interest expense, and non-cash interest income. Because these items have no impact on Celcuity’s cash position, management believes non-GAAP adjusted net loss better enables Celcuity to focus on cash used in operations. For a reconciliation of financial measures calculated in accordance with generally accepted accounting principles in the United States ("GAAP") to non-GAAP financial measures, please see the financial tables at the end of this press release.

Net cash used in operating activities for the first quarter of 2025 was $35.9 million, compared to $17.1 million for the first quarter of 2024.

At March 31, 2025, Celcuity reported cash, cash equivalents and short-term investments of $205.7 million. We expect cash, cash equivalents, investments and drawdowns on our debt facility to fund current clinical development program activities through 2026.

Webcast and Conference Call Information

The Celcuity management team will host a webcast/conference call at 4:30 p.m. ET today to discuss the first quarter 2025 financial results and provide a corporate update. To participate in the teleconference, domestic callers should dial 1-800-717-1738 and international callers should dial 1-646-307-1865. A live webcast presentation can also be accessed using this weblink: View Source;tp_key=61a8c66165. A replay of the webcast will be available on the Celcuity website following the live event.

On May 14, 2025 bluebird bio, Inc. (NASDAQ: BLUE) ("bluebird"), Carlyle (NASDAQ: CG) ("Carlyle") and SK Capital Partners, LP ("SK Capital") reported they have amended their definitive agreement pursuant to which Carlyle and SK Capital will purchase all of the outstanding shares of bluebird (Press release, bluebird bio, MAY 14, 2025, View Source [SID1234653055]). Under the terms of the amended agreement bluebird stockholders can elect to receive either (x) the original offer of $3.00 per share in cash plus a contingent value right ("CVR") of $6.84 per share in cash payable upon achievement of a net sales milestone or (y) $5.00 per share in cash. The amended offer price provides an alternative for stockholders who would prefer greater upfront cash consideration instead of the potential upside of the CVR. Any shares tendered for which no election is made will receive the original consideration of $3.00 per share in cash and a contingent value right per share.

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The bluebird board of directors unanimously approved the amended agreement and recommends that all stockholders immediately tender their shares in support of the transaction. The bluebird board of directors continues to believe that the transaction with Carlyle and SK Capital, as amended, represents the only viable option for stockholders to receive consideration for their shares. Absent a majority of stockholders tendering, bluebird is at significant risk of defaulting on its loan agreements with Hercules Capital, and it is extremely unlikely that stockholders would receive any consideration for their shares in a bankruptcy or liquidation.

In connection with the amended agreement, the expiration date of the tender offer has been extended to expire at one minute after 11:59 p.m., New York City time, on May 29, 2025. Equiniti Trust Company, LLC, the depositary for the Offer, has advised that as of the close of business on May 13, 2025, approximately 2,281,724 shares of bluebird common stock have been validly tendered and not properly withdrawn pursuant to the Offer.

Instructions for Stockholders:

Stockholders that have previously tendered their shares and elect to receive the original offer of $3.00 per share plus a CVR do not need to re-tender their shares or take any other action in response to this extension
Stockholders that have previously tendered their shares and wish to elect to receive $5.00 per share in cash must withdraw and re-tender their shares and complete and sign the letter of election and transmittal attached to the Offer to Purchase. Detailed instructions are available in the Offer to Purchase.
Stockholders that hold shares of bluebird through a broker or other nominee may be subject to a processing cutoff that is prior to the tender deadline, so it is important to act now.
Stockholders who need assistance with tendering their shares of bluebird may contact the Information Agent, Innisfree M&A Incorporated, by calling toll-free at (877) 825-8793.
As previously announced on May 5, 2025, Carlyle and SK Capital have received all required regulatory approvals to complete the transaction, and all parties expect the transaction to be consummated promptly following the successful completion of the ongoing tender offer.

On May 15, 2025 Biomea Fusion, Inc. ("Biomea") (Nasdaq: BMEA), a clinical-stage diabetes and obesity medicines company, reported that preliminary clinical data from the Phase I COVALENT-103 trial of BMF-500 in adults with acute leukemia (AL) were selected for a poster presentation at the European Hematology Association (EHA) (Free EHA Whitepaper) 2025 Congress, taking place June 12–15 in Milan, Italy (Press release, Biomea Fusion, MAY 14, 2025, View Source [SID1234653054]).

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The presentation will highlight emerging safety, pharmacokinetics/pharmacodynamics (PK/PD), and clinical activity of BMF-500, a covalent FLT3 inhibitor, in patients with relapsed or refractory (R/R) AL, including those with FLT3 mutations (FLT3m) who have previously received FLT3 inhibitors such as gilteritinib (gilt).

"While we have strategically shifted our internal focus to metabolic disease, the preliminary results from the COVALENT-103 study underscore the strong potential of BMF-500 in relapsed or refractory acute leukemia. Despite having received and failed multiple prior lines of therapy, the majority of treated patients experienced reductions in bone marrow blasts. Early signs of overall survival already exceed historical benchmarks, even at non-optimized dose levels," said Mick Hitchcock, Ph.D., Interim Chief Executive Officer of Biomea Fusion. "We are actively advancing partnership discussions for this very selective and active covalent binding molecule which was developed in-house for patients with very limited treatment options."

Abstract and 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-Kashani, M.D., University of Texas MD Anderson Cancer Center
Background
R/R FLT3m AL post-failure with gilteritinib (gilt) has a poor prognosis. BMF-500 is a covalent FLT3 inhibitor, potent against ITD, TKD, and resistance mutations like the gatekeeper F691. BMF-500 lacks cKIT inhibition, exhibits cytotoxicity even after washout, and elicits improved survival in FLT3m AML xenografts.

Aims
Here we update the ongoing COVALENT-103 study, an open-label Phase I study evaluating escalating doses of BMF-500 in R/R AML with or without FLT3m.

Methods
Eligible pts are adults with R/R AL ineligible for standard of care. Pts with FLT3m AL must have failed gilt in the R/R setting. Up to 33% pts may have WT FLT3. BMF-500 is dosed BID in 28-day cycles until progression/intolerability in two arms: pts not taking (Arm A) or taking (Arm B) CYP3A4 inhibitors. Expansion cohorts will obtain further safety and efficacy data at the OBD/RP2D.

Results
As of 03Feb25, 24 R/R AL pts enrolled; 4 remain on treatment. Baseline features: 8 (33.3%) females, 5 (20.8%) non-whites, mean 57 yrs (23,80), median therapies 4 (1,10), HSCT 10 (41.7%), 24 (100%) with prior venetoclax (ven). Fifteen (62.5%) had FLT3m AL; all had prior FLT3 inhibitors including gilt.

BMF-500 was well tolerated with no DLTs or discontinuations due to treatment-related toxicities, and no related QTc prolongation or cytopenias. Twenty-three pts comprised the safety population. Common TEAEs (>20%): febrile neutropenia, nausea, peripheral edema, hypokalemia, hypocalcemia, dyspnea, pleural effusion, hypoxia, hypotension (range 5-7 pts). TRAEs were Gr 1-2: vomiting, hypotension, AST elevation, hypomagnesemia, hand cellulitis, oropharyngeal pain (each 4.3%) and Gr 3-4: leukocytosis, low WBC, ALT elevation (each 4.3%). Median treatment duration was 48 d (1,170). Eleven (45.8%) pts had at least one disease assessment and were efficacy evaluable. Nine (81.8%) pts showed clinical activity: decreased BM blasts (77.8%; 1 normalized blasts, 1 >50% reduction, 5 <50% reduction), decreased peripheral blasts (33.3%; 2 complete clearance, 1 >50% reduction), 4 decreased hydroxyurea use, 4 decreased transfusions. Objective response (ELN 2017) occurred as early as end of C1, and best response as CRi by end of C2. At 100 mg BID/DL2 (Arm A), 1 of 2 FLT3m pts achieved CRi and completed six cycles; the other achieved >60% reduced BM blasts. mOS for the 23 pts is 3.48 mos (3.25, NE; 95% CI; see figure) whereas mOS for the 7 efficacy evaluable FLT3m pts has not been reached (not shown); 9 pts continue in survival follow up. The historical mOS for pts R/R to gilt/ven is 2.1 mos.

The highest levels cleared are 100 mg BID (Arm A /DL2) and 50 mg BID (Arm B /DL2), with 3 of 3 (100%) in Arm A and 4 of 5 (80%) in Arm B showing reduced BM blasts. Escalation continues at 150 mg BID/DL3 (Arm A) and 75 mg BID (Arm B/DL3).

Based on exposures surpassing the preclinical target AUC, the study pivoted from single-patient cohorts to 3+3 at 100 mg BID (Arm A) and 25 mg BID (Arm B). Exposures were comparable at these two dose levels and Plasma Inhibitory Assay showed near complete FLT3 inhibition at steady state. PK/PD showed an EC90 of 500 ng/mL, with most pts at 100 mg BID and 25 mg BID surpassing it. BMF-500 and its metabolites had similar concentrations in BM and plasma.

Summary/Conclusion
BMF-500 was well-tolerated. The majority of efficacy-evaluable pts showed reduced BM blasts, with 1 pt achieving CRi. mOS of the efficacy-evaluable FLT3m pts has not yet been reached. Enrollment is ongoing
to identify the OBD/RP2D.

Following completion of the dose escalation phase in relapsed/refractory acute leukemia patients with FLT3 mutations, Biomea plans to conclude its internal development of BMF-500 in oncology and is actively exploring strategic partnerships to advance the program.

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 relapsed or refractory acute leukemia with FMS-like tyrosine kinase 3 (FLT3) wild-type and FLT3 mutations. 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. 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 and developed in-house at Biomea using the company’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.