On December 6, 2025 Partner Therapeutics, Inc. (PTx), a private, fully-integrated biotechnology company, reported new data from a post hoc analysis of the Phase 2 eNRGy trial (NCT02912949) evaluating zenocutuzumab in patients with treatment-naïve non-small cell lung cancer (NSCLC) harboring a neuregulin 1 (NRG1) gene fusion. Results were presented in a late-breaking oral session at the IASLC-ASCO North America Conference on Lung Cancer (NACLC), in Chicago, Illinois.

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The new analysis evaluated the efficacy and safety of zenocutuzumab-zbco in treatment-naïve and previously treated NRG1+ NSCLC. Among 20 treatment-naïve and 121 previously treated patients, zenocutuzumab demonstrated an overall response rate (ORR) of 35% and 31%, respectively. The clinical benefit rate, defined as partial/complete response or stable disease for ≥24 weeks, was 65% in treatment-naïve and 58% in previously treated patients. Median duration of response was 17.1 months in treatment naïve patients, notably longer than in previously treated patients, 7.4 months. All treatment-related adverse events were grade 1 or 2. Zenocutuzumab safety profile was favorable and consistent with prior data.

"These data underscore the potential of zenocutuzumab as a first-line option for patients with NRG1-positive NSCLC, a patient population that typically responds poorly to standard first-line therapy," said Stephen Liu, MD, of Georgetown University. "Early and durable responses, coupled with a favorable safety profile are encouraging and highlight the importance of targeted therapy in this rare molecular subset."

"Consistent with other therapies targeting key oncogenic drivers, early intervention can lead to better outcomes — and we see the same with zenocutuzumab," said Pritesh J. Gandhi, Chief Development Officer at Partner Therapeutics. "These findings strengthen our conviction that early targeted inhibition of the NRG1 pathway with zenocutuzumab has the potential to meaningfully improve outcomes for patients with NRG1+ NSCLC."

"For patients and families facing NRG1+ lung cancer, these results mark meaningful progress," said Danielle Hicks, Chief Patient Officer of GO2 for Lung Cancer. "The durable responses and manageable safety profile of zenocutuzumab offer renewed hope and reinforce the need for continued innovation in biomarker-driven lung cancer care."

The abstract will be available on the Partner Therapeutics website under the research tab following the conference. Additional meeting information can be found on the IASLC-ASCO NACLC website.

In December 2024, zenocutuzumab-zbco (BIZENGRI) received U.S. Food and Drug Administration accelerated approval for the treatment of adults with advanced unresectable or metastatic non-small cell lung cancer (NSCLC) and pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy. The indications were approved under accelerated approval based on ORR and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

For more information on the eNRGy trial and zenocutuzumab-zbco, please visit www.partnertx.com.

About NRG1 Gene Fusions

NRG1 fusions are unique cancer drivers that create oncogenic chimeric ligands rather than the more widely described chimeric receptors (NTRK, RET, ROS1, ALK, and FGFR fusions). The chimeric ligands bind to HER3, triggering HER2/HER3 heterodimerization and activate downstream signaling pathways that cause cancer cells to grow and proliferate. Zenocutuzumab-zbco is a bispecific antibody that blocks HER2/HER3 dimerization and NRG1 fusion interactions with HER3, resulting in the suppression of these pathways. Comprehensive molecular testing, notably tissue-based RNA next generation sequencing, is essential to identify rare and actionable gene fusions like NRG1.

About BIZENGRI (zenocutuzumab-zbco)

INDICATIONS

BIZENGRI is indicated for the treatment of adults with advanced unresectable or metastatic non-small cell lung cancer (NSCLC) harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy.

BIZENGRI is indicated for the treatment of adults with advanced unresectable or metastatic pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy.

These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Important Safety Information

BOXED WARNING: EMBRYO-FETAL TOXICITY

Embryo-Fetal Toxicity: Exposure to BIZENGRI during pregnancy can cause embryo-fetal harm. Advise patients of this risk and the need for effective contraception.

WARNINGS AND PRECUATIONS

Infusion-Related Reactions/Hypersensitivity/Anaphylactic Reactions

BIZENGRI can cause serious and life-threatening infusion-related reactions (IRRs), hypersensitivity and anaphylactic reactions. Signs and symptoms of IRR may include chills, nausea, fever, and cough.

In the eNRGy study, 13% of patients experienced IRRs, all were Grade 1 or 2; 91% occurred during the first infusion.

Administer BIZENGRI in a setting with emergency resuscitation equipment and staff who are trained to monitor for IRRs and to administer emergency medications. Monitor patients closely for signs and symptoms of infusion reactions during infusion and for at least 1 hour following completion of first BIZENGRI infusion and as clinically indicated. Interrupt BIZENGRI infusion in patients with ≤ Grade 3 IRRs and administer symptomatic treatment as needed. Resume infusion at a reduced rate after resolution of symptoms. Immediately stop the infusion and permanently discontinue BIZENGRI for Grade 4 or life-threatening IRR or hypersensitivity/anaphylaxis reactions.

Interstitial Lung Disease/Pneumonitis

BIZENGRI can cause serious and life-threatening interstitial lung disease (ILD)/pneumonitis.

In the eNRGy study, ILD/pneumonitis occurred in 2 (1.1%) patients treated with BIZENGRI. Grade 2 ILD/pneumonitis (Grade 2) resulting in permanent discontinuation of BIZENGRI occurred in 1 (0.6%) patient. Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold BIZENGRI in patients with suspected ILD/pneumonitis and administer corticosteroids as clinically indicated.

Permanently discontinue BIZENGRI if ILD/pneumonitis ≥ Grade 2 is confirmed.

Left Ventricular Dysfunction

BIZENGRI can cause left ventricular dysfunction.

Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including BIZENGRI. Treatment with BIZENGRI has not been studied in patients with a history of clinically significant cardiac disease or LVEF less than 50% prior to initiation of treatment.

In the eNRGy study, Grade 2 LVEF decrease (40%-50%; 10 – 19% drop from baseline) occurred in 2% of evaluable patients. Cardiac failure without LVEF decrease occurred in 1.7% of patients, including 1 (0.6%) fatal event.

Before initiating BIZENGRI, evaluate LVEF and monitor at regular intervals during treatment as clinically indicated. For LVEF of less than 45% or less than 50% with absolute decrease from baseline of 10% or greater which is confirmed, or in patients with symptomatic congestive heart failure (CHF), permanently discontinue BIZENGRI.

Embryo-Fetal Toxicity

Based on its mechanism of action, BIZENGRI can cause fetal harm when administered to a pregnant woman. No animal reproduction studies were conducted with BIZENGRI. In post marketing reports, use of a HER2-directed antibody during pregnancy resulted in cases of oligohydramnios manifesting as fatal pulmonary hypoplasia, skeletal abnormalities, and neonatal death. In animal models, studies have demonstrated that inhibition of HER2 and/or HER3 results in impaired embryo-fetal development, including effects on cardiac, vascular and neuronal development, and embryolethality. Advise patients of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of BIZENGRI. Advise females of reproductive potential to use effective contraception during treatment with BIZENGRI and for 2 months after the last dose.

ADVERSE REACTIONS

NRG1 Gene Fusion Positive Unresectable or Metastatic NSCLC

Serious adverse reactions occurred in 25% of patients with NRG1 gene fusion positive NSCLC who received BIZENGRI. Serious adverse reactions in ≥ 2% of patients included pneumonia (n=4) dyspnea and fatigue (n=2 each). Fatal adverse reactions occurred in 3 (3%) patients and included respiratory failure (n=2), and cardiac failure (n=1). Permanent discontinuation of BIZENGRI due to an adverse reaction occurred in 3% of patients. Adverse reactions resulting in permanent discontinuation of BIZENGRI included dyspnea, pneumonitis and sepsis (n=1 each).

In patients with NRG1 gene fusion positive NSCLC who received BIZENGRI, the most common (>20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (35%), increased alanine aminotransferase (30%), decreased magnesium (28%), increased alkaline phosphatase (27), decreased phosphate (26%), diarrhea (25%), musculoskeletal pain (23%), increased gamma-glutamyl transpeptidase (23%), increased aspartate aminotransferase (22%), and decreased potassium (21%).

NRG1 Gene Fusion Positive Unresectable or Metastatic Pancreatic Adenocarcinoma

Serious adverse reactions occurred in 23% of patients with NRG1 gene fusion positive pancreatic adenocarcinoma who received BIZENGRI.

There were 2 fatal adverse reactions, one due to COVID-19 and one due to respiratory failure. In patients with NRG1 gene fusion positive pancreatic adenocarcinoma who received BIZENGRI the most common (≥20%) adverse reactions, including laboratory abnormalities, were increased alanine aminotransferase (51%), diarrhea (36%), increased aspartate aminotransferase (31%), increased bilirubin (31%), decreased phosphate (31%), increased alkaline phosphatase (28%), decreased sodium (28%), musculoskeletal pain (28%), decreased albumin (26%), decreased potassium (26%), decreased platelets (26%), decreased magnesium (24%), increased gamma-glutamyl transpeptidase (23%), decreased hemoglobin (23%), vomiting (23%), nausea (23%), decreased leukocytes (21%), and fatigue (21%).

Please see full Prescribing Information, including Boxed Warning

(Press release, Partner Therapeutics, DEC 6, 2025, View Source [SID1234661223])

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 6, 2025 Star Therapeutics, a late clinical-stage biotechnology company discovering and developing best-in-class antibodies for bleeding disorders and other diseases, reported interim data from its ongoing Phase 1/2 multidose study of VGA039 in von Willebrand disease (VWD). The data are being presented in an oral session at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in Orlando, Florida. VGA039 is a first-in-class monoclonal antibody therapy that targets Protein S, with dual actions promoting platelet attachment and enhancing fibrin deposition to restore hemostasis.

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In the Phase 1/2 multidose study, treatment with VGA039 administered subcutaneously once monthly resulted in a substantial reduction in annual bleeding rate (ABR) across all types of VWD and all types of bleeds, including meaningful improvement in bleed control for patients switching from prior von Willebrand factor (VWF)-containing intravenous (IV) prophylaxis. The study population includes patients with Types 1, 2, and 3 VWD who have high disease burden, including patients with serious gastrointestinal (GI) and hemophilia-like joint and muscle bleeds.

"The data presented at ASH (Free ASH Whitepaper) indicate that VGA039 could be transformative for people living with VWD, a condition with more than 130,000 diagnosed patients in the U.S. alone," said Allison Wheeler, M.D., MSCI, Associate Professor of Pediatrics at the University of Washington. "VWD can have a significant impact on quality of life, with patients experiencing frequent and severe bleeds that can require hospitalization. Current treatment options remain limited, with VWF-containing prophylaxis requiring multiple IV infusions per week. Data from the multidose trial support a once monthly subcutaneous dosing regimen for VGA039, which could meaningfully alleviate the current treatment burden with the potential for even better bleed control over the standard of care."

Key highlights from the presentation include:

As of November 14, 2025, interim data from all 16 patients enrolled in the Phase 1/2 multidose study were available, including safety data on all 16 patients and efficacy data on all 8 patients who had completed treatment with VGA039.
VGA039 once monthly subcutaneous prophylaxis was safe and well tolerated.
VGA039 demonstrated substantial reductions in ABR across all patients, with all types of VWD and all types of bleeds (including serious GI and hemophilia-like joint and muscle bleeds).
Bleed reductions were 73%-87% for all the participants enrolled who have the same ABR as the population being recruited into the Phase 3 trial (ABR ≥ 12, no prior IV prophylaxis).
In patients switching from prior VWF-containing prophylaxis (IV infusions multiple times per week), bleed reductions were 75%-100%, indicating potential efficacy and dosing improvement over standard-of-care.
All participants to date who have completed the multidose study have transitioned to the open-label extension (OLE) study.
"This dataset is compelling, encompassing a diverse patient population across multiple VWD types, a full spectrum of bleed profiles, and individuals transitioning from prior prophylaxis regimens. VGA039’s ability to consistently reduce bleeding across these groups along with its favorable safety and tolerability profile indicate that VGA039 has the potential to improve outcomes for all patients with VWD," said Steven Pipe, M.D., Professor of Pediatrics and Pathology at the University of Michigan. "Importantly, patients who transitioned from IV prophylaxis multiple times per week to once monthly subcutaneous VGA039 experienced marked improvements in bleed control, highlighting the potential to establish a new standard of care for people living with VWD."

"These interim data provide further validation of VGA039 as a potential once monthly subcutaneous treatment for multiple bleeding disorders, starting with VWD. All patients to date have opted to continue treatment as part of our open-label extension study after finishing the multidose trial," said Gary Patou, M.D., Chief Medical Officer of Star Therapeutics. "These data, along with the recent initiation of our pivotal Phase 3 study, VIVID-6, continue to add to the momentum surrounding this program, bringing us another step closer to achieving our mission of creating life-changing therapies for patients with bleeding disorders."
About VGA039
VGA039 is a monoclonal antibody therapy with a novel mechanism of action that targets Protein S, with dual actions promoting platelet attachment and enhancing fibrin deposition to restore hemostasis. VGA039 has potential to be a universal hemostatic therapy that can treat numerous bleeding disorders, starting with von Willebrand disease (VWD). As a subcutaneously self-administered antibody therapy with a convenient once monthly dosing regimen, VGA039 has the potential to dramatically reduce treatment burden for patients. VGA039 has received Fast Track and orphan drug designations from the U.S. Food and Drug Administration (FDA). VGA039 has advanced into a Phase 3 study (NCT07115004), VIVID-6, a global single arm cross-over study designed to investigate the safety and efficacy of subcutaneous administration of VGA039 as prophylaxis for bleeding in patients with every type of VWD. For additional information on our VIVID trials of VGA039, including how to enroll, please visit the website here.

About von Willebrand disease
Von Willebrand disease (VWD) is the most common inherited bleeding disorder in which the blood does not clot properly, caused by absent or defective von Willebrand factor (VWF). VWD patients may experience excessive bleeding with varying severity and frequency, negatively impacting their daily lives. Current therapies for VWD prophylaxis include factor replacement therapies requiring multiple intravenous (IV) infusions every week. More than 130,000 people in the U.S. are diagnosed with VWD.

(Press release, Star Therapeutics, DEC 6, 2025, View Source [SID1234661209])

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 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing highly differentiated targeted agents to treat hematologic malignancies, reported clinical data for its lead compound tuspetinib (TUS) combined with standard dosing of venetoclax (VEN) and azacitidine (AZA) in a poster presentation at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Orlando, FL. Updated data from patients in the TUSCANY trial across all three cohorts, 40 mg, 80 mg or 120 mg TUS dose in TUS+VEN+AZA, reveal promising clinical safety and antileukemic activity and support the use of TUS in combination with standard of care treatment across a broad range of AML populations, including those with adverse mutations regardless of FLT3 mutation status.

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Poster title: "TUSCANY study demonstrates safety and efficacy of tuspetinib plus standard of care venetoclax and azacitidine in patients with newly diagnosed AML ineligible for induction chemotherapy"

Key Findings and Messages:

In newly diagnosed AML patients, TUS+VEN+AZA shows promising safety, tolerability and resilient efficacy, including MRD-negative remissions across a broad mutational spectrum
High-quality clinical responses (CR/CRh):
90% across 40, 80 and 120 mg dose levels
100% at the higher 80 mg and 120 mg dose levels
Observed in FLT3-WT, FLT3-ITD, and NPM1c genetic subgroups
Observed in biallelic TP53/complex karyotype and RAS adverse genetic subgroups
Observed in AML with MDS-related mutations
MRD negativity: 78% by central flow cytometry in responding subjects
TUS targets VEN resistance mechanisms; inhibits kinase-driven abnormal signaling
Two subjects transitioned to stem cell transplantation and both returned for TUS maintenance
TUS+VEN+AZA triplet therapy was well tolerated with no dose-limiting toxicities (DLTs) across all evaluable TUS dose levels
No DLTs including no prolonged myelosuppression for subjects in remission in Cycle 1
No drug-related deaths, differentiation syndrome, QTc prolongation, or CPK elevation reported
8/10 evaluable subjects experienced red cell and platelet transfusion independence for > 8 weeks after their best response
Febrile neutropenia was reported in 2 subjects (16.7%), with 1 subject related to TUS
At the recently enrolled 160 mg dose level, preliminary findings show patients achieving early blast clearance with MRD-negativity and formal responses in the first few weeks of treatment (not included in poster data cut).

"Tuspetinib, as part of a triple drug therapy, continues to perform well, achieving 100% clinical response in the two higher doses we have evaluated to date," said Rafael Bejar, MD, PhD, Chief Medical Officer at Aptose. "We recently commenced treating patients at the highest dose level of 160 mg TUS and have already achieved early responses. With no dose-limiting toxicities and activity across diverse mutations, TUS+VEN+AZA targets AML’s greatest unmet needs and largest populations."

The ASH (Free ASH Whitepaper) poster presentation is available here.

About Tuspetinib

Aptose’s lead compound tuspetinib is a convenient once daily oral agent that potently targets SYK, mutated and wild type forms of FLT3, mutated KIT, JAK1/2, and RSK2 kinases, while avoiding many typical toxicity concerns observed with other agents. The ongoing TUSCANY triplet Phase 1/2 study is designed to test various doses and schedules of TUS in combination with standard dosing of azacitidine and venetoclax in newly diagnosed patients with AML who are ineligible to receive induction chemotherapy. Data from the first three dose cohorts demonstrate safety, CRs and minimal residual disease (MRD) negativity across patients with diverse mutations. The early data showed that 9 out of 10 patients responded to the TUS triplet therapy, with 100% complete remission (CR/CRh) achieved in the 80mg and 120mg cohorts. Notably, patients with difficult-to-treat mutations in TP53, RAS and FLT3 genes also achieved a 100% CR/CRh rate.

(Press release, Aptose Biosciences, DEC 6, 2025, View Source [SID1234661210])