On December 6, 2025 Disc Medicine, Inc. (NASDAQ:IRON), a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of novel treatments for patients suffering from serious hematologic diseases, reported positive initial data from the RALLY-MF Phase 2 trial of DISC-0974 in anemia of MF at the ASH (Free ASH Whitepaper) Annual Meeting in Orlando, FL. The data demonstrated that treatment with DISC-0974 resulted in substantial reductions in hepcidin and increases in iron levels translating to positive impact on clinically meaningful measures of anemia across a broad range of patient types.

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"We are excited that we continue to see robust hematologic responses to DISC-0974 regardless of background JAK inhibitor therapy," said John Quisel, J.D., Ph.D., President and Chief Executive Officer of Disc Medicine. "It is also encouraging to see these hematologic improvements translating into reduced transfusion burden and fatigue. We look forward to advancing this program with the goal of addressing a significant unmet need as anemia is one of the key manifestations of MF and there is currently no therapy approved to treat anemia in this population."

This ongoing Phase 2 open-label study had enrolled 47 adult patients with MF and anemia as of the data cutoff date of October 16, including 34 patients with sufficient follow up to be included in the responder analysis (non-transfusion dependent receiving no transfusions (nTD, n=24), transfusion dependent with low transfusion burden (TD Low, n=7) and transfusion dependent with high transfusion burden (TD High, n=3)). The trial was comprised of both patients receiving concomitant JAK inhibitor therapy (n=18) and not receiving JAK inhibitor therapy (n=16). DISC-0974 was administered subcutaneously at 50 mg every 4 weeks for up to 6 treatments. Initial results demonstrated:

Consistent, substantial decreases in hepcidin reaching >75% reduction from baseline and corresponding increases in serum iron
63% of baseline nTD patients achieved a hemoglobin increase of ≥1 g/dL for ≥12 weeks (overall response) and 50% had an increase of ≥1.5 g/dL for ≥12 weeks (major response)
71% of TD Low patients achieved transfusion independence (TI, major response) over a 16-week period
67% of TD High patients with at least 85 days on study achieved a ≥50% reduction in transfusion requirement (overall response)
Initial data for additional n=3 TD High patients trending towards major response of TI >12 weeks
50% of patients receiving concomitant JAK inhibitor therapy achieved a major hematologic response
Dosing with DISC-0974 was associated with improvements in FACIT-Fatigue scores in nTD and TD Low participants
DISC-0974 was generally well-tolerated. Diarrhea and urinary tract infections, neither considered serious, were the only adverse events (AE) that were considered related to DISC-0974 and reported in two or more subjects. The majority of AEs were not considered related to DISC-0974.
Additional data to be shared in H2 2026
Disc also shared a poster overviewing the trial design for the ongoing Phase 2 study of the anti-TMPRSS6 antibody DISC-3405 in polycythemia vera requiring frequent phlebotomy.

Management will host a call during the ASH (Free ASH Whitepaper) meeting to review highlights of the presented data and plans for next steps in development on Sunday, December 7 at 7:30am EST. Please register for the event on the Events and Presentations page of Disc’s website (View Source).

(Press release, Disc Medicine, DEC 6, 2025, View Sourcenews-releases/news-release-details/disc-medicine-presents-positive-initial-data-rally-mf-phase-2 [SID1234661198])

On December 6, 2025 Cogent Biosciences, Inc. (NASDAQ: COGT) reported complete results from the registration-directed Part 2 of the SUMMIT clinical trial of bezuclastinib in patients with nonadvanced systemic mastocytosis (NonAdvSM). As previously reported, bezuclastinib demonstrated clinically meaningful and highly statistically significant improvements across the primary and all key secondary endpoints. New results further highlight the benefit of bezuclastinib on patient-reported symptoms and objective measures of mast cell burden and demonstrate significant correlation between improvement in disease pathology and patient-reported symptom severity.

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"We are excited to present additional data from the SUMMIT trial that support our conviction that bezuclastinib will be the best-in-class treatment option for patients with nonadvanced systemic mastocytosis," said Andrew Robbins, Cogent’s President and Chief Executive Officer. "We remain on track to submit our first New Drug Application for bezuclastinib in NonAdvSM with the FDA this month and are encouraged by the increased interest in our Expanded Access Program."

"Nonadvanced systemic mastocytosis patients currently have very limited treatment options, and the benefit bezuclastinib demonstrated in the SUMMIT trial across measures of disease pathology and symptomatic improvement is very exciting for this patient population," said Lindsay Rein, MD, Associate Professor of Medicine in the Division of Hematologic Malignancies and Cellular Therapy, Duke University. "The SUMMIT trial results match my clinical experience using bezuclastinib with NonAdvSM patients, delivering rapid and deep improvement in symptom control and objective measures of disease without tolerability challenges."

SUMMIT Trial Data

In the registration-directed Part 2 of the SUMMIT clinical trial, 118 patients received bezuclastinib once daily plus best supportive care (BSC) and 60 patients received placebo plus BSC. The study included adults with a NonAdvSM diagnosis confirmed by central pathology review, and moderate-to-severe symptom burden despite an optimized regimen of BSC.

Following completion of the 24-week treatment period, patients had the option to receive bezuclastinib in an open-label extension study. Baseline patient demographics were balanced between treatment arms and reflected significant disease burden. Disease symptoms were assessed using the Mastocytosis Symptom Severity Daily Diary (MS2D2).

Bezuclastinib delivered clinically meaningful and statistically significant symptomatic improvement

Outcome measure Bezuclastinib Placebo p-value
At 24 weeks of treatment (primary endpoint and key secondary endpoints)
Mean change TSS (%) -24.3 (-43%) -15.4 (-29%) p<0.001
Proportion of patients with ≥50% reduction in TSS 34.3% 18.1% p=0.01
Proportion of patients with ≥30% reduction in TSS 65.4% 38.6% p<0.001
For patients treated through 48 weeks (follow-up data cut off Nov 2025)
Mean change TSS (%) -32.0 (-54%) n/a n/a
Proportion of patients with ≥50% reduction in TSS 56.4% n/a n/a
Proportion of patients with ≥30% reduction in TSS 86.2% n/a n/a

Across several additional key secondary endpoints, bezuclastinib demonstrated rapid, deep and sustained improvement on objective disease markers of mast cell burden. At week 24, 87.4% of patients achieved ≥50% reduction in serum tryptase levels, 75.6% of patients demonstrated ≥50% reduction in bone marrow mast cells or clearance of aggregates and 85.7% of patients achieved ≥50% reduction in KIT D816V variant allele frequency or undetectable, each of which was statistically significant when compared to placebo. Additional pathobiology data from SUMMIT patients will be shared in an oral presentation on Monday, December 8th at ASH (Free ASH Whitepaper).

SUMMIT Subgroups

As part of the SUMMIT study, patients with Smoldering Systemic Mastocytosis (n=8 bezuclastinib arm, n=4 placebo arm) and patients who had previously been treated with avapritinib (n=11 bezuclastinib arm, n=3 placebo arm) were enrolled. Patients treated with bezuclastinib in these subgroups showed a mean change in TSS of -35.6 and -21.6, respectively. The response in objective measures of disease burden in these patients was consistent with results from the broader SUMMIT population, as were their related adverse events and overall tolerability.

Safety Data

As previously reported on July 7, 2025, the majority of treatment emergent adverse events (TEAEs) (98.3% in bezuclastinib arm vs. 88.3% in placebo arm) were of low grade. The most frequent TEAEs reported on bezuclastinib treatment were hair color change (69.5% bezuclastinib vs. 5.0% placebo), altered taste (23.7% bezuclastinib vs. 0% placebo), nausea (22.0% bezuclastinib vs. 13.3% placebo) and ALT/AST elevations (22.0% bezuclastinib vs. 6.6% placebo; ≥Gr 3, 5.9% vs. 0%). Serious AEs occurred in 4.2% of patients treated with bezuclastinib, compared to 5.0% of patients treated with placebo. Discontinuations due to treatment-related AEs occurred in 5.9% of patients treated with bezuclastinib, all due to ALT/AST elevations and all patients fully resolved. There were no hepatic AEs reported in any patient other than transient and manageable lab abnormalities.

SUMMIT Long Term Follow-up

Data from longer term follow-up in patients participating in the SUMMIT trial are expected to be presented at an upcoming scientific meeting in Q1 2026. Preliminary 48-week data will be shared during the investor call scheduled for Monday, December 8th.

(Press release, Cogent Biosciences, DEC 6, 2025, View Source [SID1234661197])

On December 6, 2025 BioNTech SE (Nasdaq: BNTX, "BioNTech") and OncoC4, Inc. ("OncoC4") reported data from the non-pivotal dose-confirmation stage of the global randomized Phase 3 trial PRESERVE-003 (NCT05671510) for gotistobart (also known as BNT316 or ONC-392), a tumor microenvironment-selective regulatory T cell ("Treg") depletion candidate, targeting CTLA-4 in patients with metastatic squamous non-small cell lung cancer (sqNSCLC). Gotistobart demonstrated a clinically meaningful overall survival ("OS") benefit compared to standard-of-care chemotherapy and a manageable safety profile in sqNSCLC patients whose disease had progressed following anti-PD-(L)1 therapy and platinum-based chemotherapy. Data from the non-pivotal stage of the trial are being presented today in an oral presentation at the IASLC ASCO (Free ASCO Whitepaper) 2025 North America Conference on Lung Cancer, hosted by the International Association for the Study of Lung Cancer in Chicago, Illinois, USA.

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"With a median survival of less than a year, advanced squamous NSCLC remains an aggressive and difficult-to-treat lung cancer1,2. Survival outcomes have improved in recent years due to advances in immunotherapy and combination regimens. However, patients who progress on anti-PD-(L)1 inhibitor treatment face a poor prognosis, leaving them only with the option of chemotherapy or palliative care," said Byoung Chul Cho, M.D., Ph.D., Lead Investigator and Professor at the Division of Medical Oncology, Yonsei Cancer Center, Seoul. "We are encouraged by the median overall survival still not being reached for patients treated with gotistobart at almost 15 months of follow-up, and we are excited to continue to investigate the candidate’s potential in the ongoing pivotal stage of the trial."

The analysis from the non-pivotal stage of the global Phase 3 trial included 45 metastatic sqNSCLC patients who received gotistobart as monotherapy, compared with 42 metastatic sqNSCLC patients who received chemotherapy (docetaxel) as second or later line of systemic therapy. At the data cut-off on August 8, 2025, 87 patients with sqNSCLC had been randomized to either gotistobart 6 mg/kg with two 10 mg/kg loading doses (N=45) or docetaxel 75 mg/m2 (N=42). The OS rate at 12 months was 63.1% for gotistobart compared to 30.3% for docetaxel. At a median follow-up of 14.5 months, patients in the gotistobart treatment arm had not yet reached the median OS, while the docetaxel treatment arm achieved a median OS of 10 months. The data showed that the gotistobart arm reduced the risk of death by 54% compared to the docetaxel treatment arm (HR=0.46, 95% CI: 0.25–0.84; nominal p-value 0.0102). The safety profile of gotistobart was consistent with previously established data and remained manageable. Grade ≥3 treatment-related adverse events ("AEs") were reported in 19/45 (42.2%) patients in the gotistobart treatment arm versus 20/41 (48.8%) patients in docetaxel treatment arm. The pivotal stage of the Phase 3 trial is ongoing in more than 160 sites globally.

"Gotistobart is designed to selectively deplete tumor-infiltrating regulatory T cells within the tumor microenvironment. The data presented today showed encouraging signals for our approach to translating our deep understanding of the immune system into meaningful survival benefits for patients with squamous NSCLC," said Prof. Özlem Türeci, M.D., Co-Founder and Chief Medical Officer at BioNTech. "With its unique mode of action, we are investigating gotistobart both as a monotherapy and in synergistic combinations with other modalities. Our goal is to deliver transformative treatment options that provide meaningful and durable benefits for patients."

"Gotistobart represents a step forward in our goal of offering a chemotherapy-free treatment option for patients with advanced squamous NSCLC, a population with limited therapeutic choices and a lack of actionable biomarkers to guide treatment," said Pan Zheng, M.D., Ph.D., Chief Medical Officer and Co-Founder at OncoC4. "The encouraging data presented today underscore the potential of gotistobart to address the unmet medical needs. We look forward to continuing to jointly explore the potential of the novel mechanism of action and advance clinical development for patients who have not benefited from currently approved immunotherapy."

About the PRESERVE-003 trial
PRESERVE-003 (NCT05671510) is a two-stage, open-label Phase 3 trial evaluating the efficacy and safety of gotistobart as monotherapy compared to the standard-of-care chemotherapy (docetaxel) in sqNSCLC patients, who have progressed on PD-(L)1 inhibitors and platinum-based chemotherapy. The non-pivotal stage of the trial originally included all NSCLC patients. The ongoing pivotal stage is currently enrolling patients with sqNSCLC. During the ongoing pivotal stage, approximately 500 patients are planned to be enrolled at clinical sites in various countries and regions, including Australia, Belgium, Canada, China, Germany, Italy, the Netherlands, Spain, South Korea, Türkiye, the United Kingdom and the United States. The primary endpoint is overall survival. Secondary endpoints include overall response rate, progression-free survival and safety profile.

About gotistobart (BNT316/ONC-392)
Gotistobart (BNT316/ONC-392) is a tumor microenvironment-selective Treg depletion candidate developed jointly by BioNTech and OncoC4. As a pH-sensitive monoclonal antibody, gotistobart is designed to enable CTLA-4 protein recycling. After binding to the CTLA-4 receptor on the cell surface, the complex is internalized, and the pH change causes the antibody to unbind, allowing CTLA-4 to return to the surface to preserve the immune checkpoint function at peripheral organs and to enhance anti-tumor immunity in the tumor microenvironment3. Gotistobart is currently in late-stage clinical development as monotherapy and as a component of combination therapy in various cancer indications. Gotistobart has received Fast Track Designation from the U.S. Food and Drug Administration ("FDA") in 2022 for the treatment of patients with metastatic NSCLC whose disease progressed on prior anti-PD-(L)1 therapy and Breakthrough Therapy Designation from China’s National Medical Products Administration ("NMPA") in 2025.

Multiple trials are ongoing, including a pivotal Phase 3 trial (PRESERVE-003; NCT05671510) in patients with metastatic squamous NSCLC, a Phase 2 trial (PRESERVE-004; NCT05446298) in patients with platinum-resistant ovarian cancer, a Phase 2 trial (PRESERVE-006; NCT05682443) in patients with metastatic castration-resistant prostate cancer, and a Phase 1/2 open-label dose escalation trial (PRESERVE-001; NCT04140526) in patients with advanced solid tumors. BioNTech also evaluates gotistobart in combination with its mRNA cancer immunotherapy candidate BNT116 in a signal seeking cohort of the ongoing Phase 1 trial (LuCa-MERIT-1; NCT05142189).

About NSCLC
Non-small cell lung cancer ("NSCLC") covers all epithelial lung cancers other than small cell lung cancer and includes squamous cell carcinoma, large cell carcinoma, and adenocarcinoma of the lung. It is the most common type of lung cancer, accounting for up to 85% of cases4, with risk factors ranging from smoking to asbestos exposure and pulmonary fibrosis5. Around 25% of all lung cancer cases are attributed to the subtype squamous cell carcinoma (SCC)6. With a 5-year relative survival rate of 15% and a median overall survival of 11 months in the United States (2000-2017), sqNSCLC is a devastating disease with limited treatment options7. Current standard-of-care includes surgery and radiotherapy in combination with chemotherapy8. Treatment options for second-line therapy after first-line immunotherapy and chemotherapy are limited to chemotherapy or palliative therapy in advanced/metastatic sqNSCLC, and remain more limited than for non-squamous NSCLC.

On December 6, 2025 Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company creating a new class of drugs based on targeted protein degradation, reported preclinical data for ARV-393, a PROTAC BCL6 degrader, in combination with glofitamab, a CD20×CD3 bispecific antibody, presented in a poster at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, held December 6–9, 2025, in Orlando, Florida. In a humanized high-grade B-cell lymphoma (HGBCL) cell line–derived xenograft (CDX) model, the combination of ARV-393 and glofitamab resulted in significantly enhanced tumor growth inhibition (TGI) and increased rates of tumor regression compared with either agent alone. These preclinical data suggest mechanistic synergies between BCL6 degradation with ARV-393 and T-cell engagement.

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"Despite advances in treatment options, many patients with diffuse large B-cell lymphoma continue to face limited options once standard therapies fail. By pursuing a chemotherapy-free combination approach, we aim to address this significant unmet need and potentially offer patients a more targeted, better-tolerated therapeutic alternative," said Noah Berkowitz, M.D., Ph.D., Chief Medical Officer, Arvinas. "The initiation of our Phase 1 combination clinical trial, planned for 2026, represents an important step toward defining the potential of ARV-393 in the treatment of this aggressive form of lymphoma."

Key highlights from the poster presentation include:

In a humanized HGBCL CDX model ARV-393 (3 mg/kg) combined with glofitamab (0.15 mg/kg) achieved 81% TGI with concomitant dosing and 91% TGI with sequential dosing (ARV-393 followed by glofitamab), versus 38% for single-agent ARV-393 and 36% for glofitamab alone.
At a higher ARV-393 dose (6 mg/kg) combined with glofitamab (0.15 mg/kg), an increase in tumor regressions was observed with concomitant (10/10 mice) and sequential dosing (7/8 mice) vs single-agent ARV-393 (5/11 mice) or glofitamab (0/11 mice).
RNA sequencing and biomarker analyses revealed that ARV-393 upregulated CD20 expression and genes that promote interferon signaling and antigen presentation, while downregulating proliferation-associated gene sets. These collective effects likely contributed to the observed synergistic antitumor activity.

"We believe these results underscore the potential for ARV-393 and provide a strong mechanistic rationale for exploring ARV-393 in combination with glofitamab as a chemotherapy-free treatment strategy for patients with diffuse large B-cell lymphoma," said Angela Cacace, Ph.D., Chief Scientific Officer, Arvinas. "These preclinical results support our belief in the clinical potential and combinability of ARV-393 and the possibility to provide real benefit to patients in need."

ARV-393 is currently being evaluated in a Phase 1 clinical trial in patients with relapsed/refractory non-Hodgkin lymphoma and Arvinas plans to share clinical data from this trial at a medical congress in 2026. Additionally, Arvinas plans to add a glofitamab combination cohort in patients with DLBCL in the ongoing Phase 1 clinical trial of ARV-393 in 2026.

About ARV-393

ARV-393 is an investigational, orally bioavailable PROTAC designed to specifically target and degrade B-cell lymphoma 6 protein (BCL6), a transcriptional repressor and major driver of B-cell lymphomas. During B-cell development, tightly controlled BCL6 protein expression regulates >600 genes to facilitate rapid B-cell proliferation and tolerance of somatic hypermutation and gene recombination for antibody generation. Deregulated BCL6 expression is common in B-cell lymphoma and promotes cancer cell survival, proliferation, and genomic instability. PROTAC-mediated degradation has the potential to address the historically undruggable nature of BCL6.

(Press release, Arvinas, DEC 6, 2025, View Source [SID1234661193])

On December 5, 2025 OTR Therapeutics, a biotechnology company dedicated to transforming early-stage innovations into globally impactful therapies, reported the successful completion of a $100 million Series A financing closed in June 2025. The round was backed by True Light Capital, a wholly-owned subsidiary of Temasek, LAV, Pfizer Ventures, and Sirona Capital.

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Founded in March 2025, OTR Therapeutics is establishing a novel, scalable, and capital-efficient model that synergizes internal R&D with strategic curation of high-potential external innovation. This integrated approach enables the company to focus on scientific rigor and operational agility, leveraging its deep regional insights and the development efficiency of the local ecosystem to accelerate innovative therapies to patients worldwide.

The proceeds of the financing will advance OTR’s pipeline of differentiated programs that target significant treatment gaps in immunology & inflammation, oncology, and other disease areas. The funds will also expand OTR’s R&D hub capability, which emphasizes both scientific excellence and strategic partnership agility to foster expedited development of high-impact therapies.

In line with its strategy, OTR also announced the acquisition of a preclinical program with best-in-class potential for neurological diseases with high unmet needs. This acquisition is part of the company’s strategic and ongoing efforts to identify and advance promising early-stage assets into global clinical development, alongside its internal proprietary discovery programs to address a broader range of critical patient needs.

"The rapidly evolving global pharmaceutical R&D landscape demands greater novelty, speed and efficiency," said Dr. Zhui Chen, Founder and CEO of OTR Therapeutics. "At OTR, we aim to build a next-generation biotech model that delivers unprecedented R&D and capital efficiency. It enables us to stay agile while remaining rigorously focused on propelling novel, differentiated drug candidates through global clinical translation in a disciplined and efficient manner. We are grateful for the strong support from our investors and their confidence in our vision and capability to deliver transformative therapies for patients."

Co-founded by Zhui Chen, Ph.D., Shannon Chuai, Ph.D., and Yuan Shi, Ph.D., OTR Therapeutics is led by a team of seasoned drug hunters and entrepreneurs in the biotech and pharmaceutical industries with a proven track record of delivering breakthrough innovation, operational excellence, and financial success.

Yi Shi, Managing Director, LAV: "We believe the biopharma industry is shifting towards more capital-efficient and specialized R&D models. OTR Therapeutics is at the forefront of this evolution, demonstrating how a focused, integrated framework can expedite the journey of translating early-stage innovation into global clinical development."

Michael Baran, Partner, Pfizer Ventures: "Pfizer Ventures identifies and invests in emerging companies who are developing innovative medicines and technologies that have the potential to shape the future of our industry. To this end, we’re pleased to be able to support OTR Therapeutics as it scales its R&D capabilities and builds a portfolio of potentially transformative therapies."

(Press release, OTR Therapeutics, DEC 5, 2025, View Source [SID1234661191])