On July 2, 2026 Treos Bio, a clinical-stage biotechnology company developing off-the-shelf and personalized active cancer immunotherapies based on its proprietary PEPI Technology, reported new translational data from the Phase Ib/II OBERTO-301 study (NCT05243862), presented at the ESMO (Free ESMO Whitepaper) Gastrointestinal Cancers Congress 2026.

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Conducted in collaboration with Mayo Clinic, the retrospective translational analysis demonstrates that PolyPEPI1018 treatment in combination with anti-PD-L1 immunotherapy induced measurable immune remodeling in patients with microsatellite-stable metastatic colorectal cancer (MSS mCRC), a tumor type generally considered resistant to checkpoint inhibition.

The retrospective analysis evaluated paired baseline and on-treatment tumor biopsies and peripheral blood samples from OBERTO-301 patients treated with PolyPEPI1018 plus atezolizumab. Post-treatment tumor samples showed increased CD8+ T-cell density and PD-L1 expression, indicating conversion toward a more inflamed tumor microenvironment.
T-cell receptor (TCR) sequencing demonstrated selective expansion of tumor-reactive T-cell clonotypes, including TCRs directed against PolyPEPI1018 antigens, additional tumor-associated antigens and neoantigens. The analysis also suggested treatment-induced antigen spreading beyond the PolyPEPI1018-targeted epitopes.

Importantly, higher numbers of tumor-reactive TCR clonotypes and higher post-treatment CD8+ TIL density were associated with improved clinical outcomes, including longer overall survival and progression-free survival. Together, these findings provide mechanistic evidence that therapeutic vaccination targeting shared tumor-associated antigens can remodel the immune microenvironment of MSS colorectal cancer converting immunologically "cold" tumors into a more immunologically active, potentially checkpoint-responsive tumor microenvironment.

"MSS colorectal cancer has long been one of the most difficult settings for immunotherapy because these tumors typically lack the immune activity needed for checkpoint inhibitors to work," said Dr. Eniko Toke, Co-founder and Chief Scientific Officer of Treos Bio. "What is encouraging in this analysis is not only that we observed immune activation in the tumor microenvironment, but that the depth of that response was associated with patient outcomes. Together with our recent clinical and platform data, these findings strengthen the rationale for advancing PolyPEPI1018 combinations in MSS colorectal cancer and applying PEPI Technology across other difficult-to-treat tumors."

Poster number: 115P
Presentation: 02 July 2026
Congress: ESMO (Free ESMO Whitepaper) Gastrointestinal Cancers Congress 2026

(Press release, Treos Bio, JUL 2, 2026, View Source [SID1234669059])

On July 2, 2026 VERAXA Biotech AG (NASDAQ: VRXA; "VERAXA"), an emerging leader in designing novel cancer therapies, reported the initiation of cell line development for its lead BiTAC T-cell engager (BiTAC-TCE) program. VERAXA has engaged ATUM, a global leader in bioengineering and cell line development, to apply the proprietary Leap-In Transposase technology to support stable clonal cell line generation. The collaboration marks a key step in progressing VERAXA’s most advanced T-cell engager candidate toward IND/CTA-enabling activities and supports future clinical development.

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"Today’s news underscores our commitment to accelerate the development path of our growing BiTAC-TCE portfolio. Initiating cell line development with ATUM is an important next step for our lead BiTAC-TCE program following the encouraging preclinical data we presented at AACR (Free AACR Whitepaper)," said Christoph Erkel, Ph.D., Vice President Research & Development of VERAXA. "Working with a recognized cell line development partner like ATUM allows us to pair our differentiated molecular design with expertise and workflows built for exactly this kind of advanced multi-chain formats."

Cell line development is an important milestone in translating a therapeutic candidate into a manufacturable product. The collaboration with ATUM is intended to support the generation of stable and high-producing clonal cell lines that will be used throughout CMC development, including early process, analytical, and formulation development, as well as the supply of material for nonclinical studies. ATUM’s Leap-In Transposase technology is designed to support efficient stable cell line generation and is particularly relevant for multi-chain antibody formats where balanced expression of multiple components is important, such as VERAXA’s BiTAC-TCEs. ATUM‘s Leap-In Transposase technology has supported the generation of stable cell lines used in over 50 IND submissions, providing VERAXA with an established cell line development approach for advanced biologic formats.

A new generation of T-cell engagers

T-cell-engaging bispecific molecules redirect cytotoxic T-cells to eliminate cancer cells, typically by binding the CD3 receptor on T-cells while simultaneously engaging a target protein on the tumor. While effective in select indications, conventional TCEs remain limited by toxicity; because their tumor target is often also present on healthy tissue, on-target but off-tumor T-cell activation can drive serious side effects and narrow the therapeutic window. A large proportion of conventional bispecific TCEs fail in development for this reason.

VERAXA’s BiTAC-TCE approach is designed to address this challenge at its source. Rather than delivering a single, fully active molecule, the BiTAC strategy splits the T-cell engager into two complementary precursors. In their isolated form, each precursor retains its tumor-binding capability while the CD3-binding function remains inactivated. Only when both precursors bind their respective targets on the same cell is the CD3-binding domain reconstituted and activated. This "AND"-gated mechanism restricts T-cell activity to cells displaying both tumor markers, sparing healthy cells that carry only one.

A dual-target, conditional-activation design distinguishes BiTAC-TCEs from both traditional TCEs and from masked-TCE approaches that rely on a single antibody whose effector function is shielded until cleaved in the tumor microenvironment. By requiring the simultaneous engagement of two distinct antigens to assemble the active engager, BiTAC-TCEs are engineered for greater tumor selectivity, with the goal of enabling higher dosing and a meaningfully wider therapeutic window.

Initial data from VERAXA’s most advanced BiTAC-TCE program were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2026, in April. In those studies, VERAXA’s BiTAC-TCE candidate performed as intended in vitro and in vivo, attacking cancer cells displaying both target molecules while sparing cells expressing only one of the two targets. The data demonstrated a superior safety profile with matching efficacy compared with a more traditional TCE, pointing to the possibility of a meaningfully improved therapeutic index. The related posters are available on the VERAXA website at www.veraxa.com.

(Press release, Veraxa Biotech, JUL 2, 2026, View Source [SID1234669058])

On July 2, 2026 Revolution Medicines, Inc. (Nasdaq: RVMD), a late-stage clinical oncology company developing targeted therapies for patients with RAS-addicted cancers, reported results from two Phase 1/2 clinical trials evaluating zoldonrasib, its oral RAS(ON) G12D-selective covalent inhibitor, in combination regimens for patients with RAS G12D metastatic pancreatic ductal adenocarcinoma (PDAC). The results, which will be presented today in a proffered paper session at the 2026 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Gastrointestinal Cancers Congress, include zoldonrasib in combination with standard of care chemotherapy in previously untreated patients and zoldonrasib in combination with daraxonrasib, the company’s oral RAS(ON) multi-selective inhibitor, in previously treated patients.

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"The Phase 3 RASolute 302 results provided clinical validation of RAS(ON) inhibition with daraxonrasib in second line metastatic pancreatic cancer and established a strong foundation for evaluating this therapeutic approach across additional RAS genotypes, treatment settings and combination strategies. The results presented at ESMO (Free ESMO Whitepaper) GI demonstrate compelling proof-of-concept for two zoldonrasib-based regimens in RAS G12D disease: combination with standard of care chemotherapy in previously untreated patients and a RAS(ON) inhibitor doublet with daraxonrasib in previously treated patients. Together, these findings are the foundation of two distinct Phase 3 strategies we are pursuing in previously untreated metastatic RAS G12D pancreatic cancer: the ongoing RASolute 305 trial evaluating zoldonrasib plus standard of care chemotherapy, and the planned RASolute 309 trial evaluating the combination of zoldonrasib plus daraxonrasib," said Alan Sandler, M.D., chief development officer of Revolution Medicines.

Safety and Efficacy of Zoldonrasib Plus Chemotherapy in Patients with First Line RAS G12D Metastatic Pancreatic Cancer (Abstract #340O)

RMC-GI-102 (NCT06445062) is an ongoing Phase 1/2 trial evaluating zoldonrasib 1200 mg once daily in combination with investigator’s choice of standard of care chemotherapy in patients with previously untreated metastatic RAS G12D PDAC. Investigator’s choice of chemotherapy includes modified FOLFIRINOX (mFFX) or gemcitabine plus nab-paclitaxel (GnP). As of the February 8, 2026 data cutoff, the trial enrolled 41 patients in the zoldonrasib plus mFFX arm and 40 patients in the zoldonrasib plus GnP arm.

Zoldonrasib demonstrated a manageable safety and tolerability profile in combination with standard chemotherapy. The safety profile of zoldonrasib in combination with chemotherapy was broadly consistent with the established profiles of each respective chemotherapy regimen. Grade 3 or greater treatment-related adverse events (TRAEs) occurred in 61% of patients who received the zoldonrasib plus mFFX and 80% of patients who received zoldonrasib plus GnP. The most common Grade 3 or greater TRAEs with zoldonrasib plus mFFX were decreased neutrophil count (37%), anemia (12%), and platelet count decreased (7%). The most common Grade 3 or greater TRAEs with zoldonrasib plus GnP were decreased neutrophil count (35%), anemia (28%), and fatigue (25%). No Grade 5 TRAEs were reported in either arm. The mean dose intensity was 86% with zoldonrasib plus mFFX and 90% with the zoldonrasib plus GnP.

In the trial, zoldonrasib with chemotherapy showed compelling antitumor activity, with an objective response rate (ORR) of 82% (95% confidence interval [CI]: 60, 95) and disease control rate (DCR) of 96% (95% CI: 77, 100) in the mFFX population, and an ORR of 61% (95% CI: 42, 78) and DCR of 90% (95% CI: 74, 98) in the GnP population.

These preliminary safety and clinical activity data support the ongoing RASolute 305 pivotal trial (NCT07621718), a global, randomized, double-blind placebo-controlled Phase 3 clinical trial evaluating zoldonrasib plus investigator’s choice of standard of care chemotherapy compared with placebo plus investigator’s choice of chemotherapy in patients with previously untreated metastatic RAS G12D PDAC.

Safety and Efficacy of Zoldonrasib Plus Daraxonrasib in Patients with Second Line-Plus RAS G12D Metastatic Pancreatic Cancer (Abstract #341O)

RMC-9805-001 (NCT06040541) is a Phase 1 trial evaluating zoldonrasib 1200 mg once daily plus daraxonrasib 300 mg once daily in advanced solid tumors with RAS G12D mutations. As of the February 9, 2026 data cutoff, 60 patients with RAS G12D metastatic PDAC who had previously received one or more prior lines of therapy were treated with the combination.

Zoldonrasib plus daraxonrasib demonstrated a manageable safety and tolerability profile that was broadly consistent with the established profile of daraxonrasib monotherapy. Grade 3 or greater TRAEs occurred in 35% of patients who received the combination. Among TRAEs occurring in 10% or more of all patients, the most common Grade 3 or greater events were rash (12%), anemia (10%), and stomatitis/mucositis (7%). Few patients discontinued due to TRAES; 2% discontinued zoldonrasib and 5% discontinued daraxonrasib. The mean dose intensity was 88% for zoldonrasib and 76% for daraxonrasib.

The zoldonrasib plus daraxonrasib combination demonstrated compelling antitumor activity in patients with previously treated metastatic PDAC. In the second line cohort (2L) (N=30), the ORR was 50% (95% CI: 31–69) and DCR was 97% (95% CI: 83–100). Median progression-free survival (PFS) in the 2L cohort was 9.6 months (95% CI: 7.1–NE), with a 6-month PFS rate of 71%. Median overall survival (OS) in the 2L cohort was not yet estimable, with a 6-month OS rate of 89%. In the third line and beyond (3L+) cohort (N=30), the ORR was 47% (95% CI: 28–66) and DCR was 90% (95% CI: 74–98). Median PFS in the 3L+ cohort was 7.6 months (95% CI: 4.6–10.5), with a 6-month PFS rate of 59%. Median OS in the 3L+ cohort was 10.5 months (95% CI: 6.7–NE), with a 6-month OS rate of 82%.

These safety and clinical activity data support the planned pivotal global, Phase 3 RASolute 309 clinical trial of zoldonrasib plus daraxonrasib versus GnP in patients with previously untreated RAS G12D metastatic PDAC.

About Pancreatic Cancer and Pancreatic Ductal Adenocarcinoma
Pancreatic cancer is one of the most lethal malignancies, characterized by its typically late-stage diagnosis, resistance to standard chemotherapy, and high mortality rate. Pancreatic ductal adenocarcinoma, or PDAC, is the most common form of pancreatic cancer. Due to the lack of early symptoms and effective detection methods, approximately 80% of patients are diagnosed with advanced or metastatic disease. PDAC is the most commonly RAS-driven malignancy of all major cancers, with more than 90% of patients having tumors that harbor RAS mutations.1 RAS G12D is the most prevalent RAS mutation subtype in PDAC, occurring in 40% of patients, and has been associated with poorer outcomes than RAS wild-type disease and certain other RAS-mutant subgroups.1-4

About Zoldonrasib
Zoldonrasib is an investigational, oral RAS(ON) G12D-selective covalent tri-complex inhibitor. RAS G12D is the most prevalent RAS mutation, accounting for 29% of all RAS cancers.1 Across tumor types, approximately 61,000 new patients with RAS G12D cancers are estimated each year in the U.S., and no targeted therapy is currently approved for these patients.5 Zoldonrasib is currently being evaluated as a monotherapy and in combination with other therapies, including with Revolution Medicines’ RAS(ON) multi-selective inhibitor daraxonrasib (RMC-6236), as well as standard of care regimens in lung and gastrointestinal cancers.

About Daraxonrasib
Daraxonrasib is an investigational, oral RAS(ON) multi-selective, non-covalent tri-complex inhibitor. The U.S. Food and Drug Administration (FDA) granted daraxonrasib Breakthrough Therapy Designation and Orphan Drug Designation for the treatment of patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC) harboring G12 mutations. In addition, daraxonrasib was selected for the FDA Commissioner’s National Priority Voucher pilot program, which is intended to accelerate the development and review of therapies aligned with U.S. national health priorities.

Daraxonrasib is designed to target cancers driven by a broad range of common RAS genotypes, including PDAC, non-small cell lung cancer (NSCLC), and colorectal cancer. Daraxonrasib is being advanced through a global Phase 3 registrational program comprising four trials, including the completed RASolute 302 trial and three additional trials in patients with PDAC and metastatic RAS mutant NSCLC.

(Press release, Revolution Medicines, JUL 2, 2026, View Source [SID1234669057])

On July 2, 2026 OnKure Therapeutics, Inc. (Nasdaq: OKUR), a clinical-stage biopharmaceutical company focused on developing novel precision medicines, reported that it will host a virtual key opinion leader (KOL) event on Wednesday, July 15, 2026 at 11:00 AM ET featuring Benjamin F. Cravatt, PhD (The Scripps Research Institute) and Robert Abraham, PhD (Engine Biosciences). They will join company management to discuss the significance of PI3Kα selectivity and the Company’s structure-based drug design approach for discovering allosteric pan-mutant PI3Kα inhibitors. To register, click here.

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Management will provide an overview of OnKure’s strategy for designing its portfolio of next-generation pan-mutant PI3Kα inhibitors.

A live question and answer session will follow the formal presentations.

About Benjamin F. Cravatt, PhD
Benjamin F. Cravatt, PhD, is Professor and Norton B. Gilula Chair of Chemical Biology in the Department of Chemistry at The Scripps Research Institute. His research group has developed several innovative chemical technologies that enable and expand protein and drug discovery on a global scale. Further application of these methods has offered insights to biological pathways that play important roles in human physiology and disease. Dr. Cravatt obtained his undergraduate education at Stanford University, receiving a B.S. in the Biological Sciences and a B.A. in History. He then received a Ph.D. from The Scripps Research Institute (TSRI) in 1996. Professor Cravatt joined the faculty at TSRI in 1997. Dr. Cravatt is co-founder of several biotechnology companies, including Activx Biosciences, Abide Therapeutics, Vividion Therapeutics, and Belharra Therapeutics. Dr. Cravatt’s honors include a Searle Scholar Award, the Eli Lilly Award in Biological Chemistry, the ASBMB Merck Award, the Wolf Prize in Chemistry, the Heinrich Wieland Prize, the Tetrahedron Award for Creativity in Bioorganic and Medicinal Chemistry, The NAS Award in Chemical Science, and memberships in the National Academies of Inventors, Medicine, and Sciences.

About Robert Abraham, PhD
Robert Abraham, PhD, currently serves as the Chief Scientific Officer at Engine Biosciences. He has previously held leadership roles in several successful biotechnology companies, including Odyssey Therapeutics and Vividion Therapeutics. Prior to entering the biotech sector, Bob was Chief Scientific Officer of the Oncology R&D Group at Pfizer, where he led teams that delivered multiple clinical candidates and 11 FDA-approved oncology drugs. One of those clinical candidates, gedatolisib, is a pan-PI3K/mTOR inhibitor, which has recently delivered highly promising clinical data in ER+ HER2- breast cancer patients. Before joining the pharmaceutical industry, Bob was a prolific immunology and pharmacology researcher with over 230 scientific publications while at Sanford-Burnham-Prebys Medical Research Institute, Duke University Medical Center, and the Mayo Clinic. His research accomplishments included the molecular cloning and functional characterization of the key PI3K pathway component, mTOR. He is also a member of the scientific advisory boards of several public and private companies, and a retained scientific advisor for Google Ventures.

About Next-Generation PI3Kα Pan-Mutant Programs

OnKure is advancing a portfolio that includes two next-generation PI3Kα pan-mutant inhibitor programs, OKI-345 for breast cancer and OKI-355 for vascular anomalies. These candidates are designed to selectively inhibit mutant PI3Kα while sparing wildtype PI3Kα, with the potential to deliver a wider therapeutic index while avoiding class-limiting toxicities associated with first-generation PI3Kα inhibitors. By providing high and sustained target coverage across all hotspot PI3Kα mutations, these programs are designed to support the potential for deep and durable responses as both monotherapy and in combination regimens. In addition, the Company’s pan-mutant candidates are designed to have minimal drug-drug interaction potential, supporting broad combinability with current standards of care. Together with a commanding intellectual property estate, OnKure believes it is well positioned to address a significant unmet need across various PI3Kα-driven indications.

PI3Kα mutations represent the most common driver alterations in key subtypes of vascular anomalies, where PIK3CA variants lead to dysregulated signaling that promotes abnormal cell growth, proliferation, and survival. OnKure believes that OKI-355 has significant potential to address this large and underserved patient population as a differentiated systemic chronic therapy.

OnKure plans to submit an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for each of OKI‑345 and OKI‑355 in the first half of 2027.

(Press release, OnKure Therapeutics, JUL 2, 2026, View Source [SID1234669056])

On July 2, 2026 Partner Therapeutics, Inc. (PTx), a private, fully integrated biotechnology company, reported that results from the cholangiocarcinoma cohort of the eNRGy trial (NCT02912949) have been published in the Journal of Clinical Oncology (JCO).1 These data supported the recent U.S. Food and Drug Administration (FDA) approval of BIZENGRI (zenocutuzumab-zbco) for the treatment of adults with advanced unresectable or metastatic cholangiocarcinoma harboring an NRG1 gene fusion with disease progression on or after prior systemic therapy. The approval was expedited by PTx’s receipt of a Commissioner’s National Priority Voucher (CNPV) underscoring the urgent unmet need in this patient population.

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"The FDA approval of BIZENGRI and the publication of these data in the Journal of Clinical Oncology highlight the clinical relevance of the eNRGy trial and reinforces our commitment to advancing therapies for patients with unmet medical needs, including those with NRG1 fusion-positive cholangiocarcinoma. The JCO publication further supports the therapeutic potential of zenocutuzumab in this rare population, which has historically experienced limited treatment options and poor outcomes with chemotherapy."

— Fiona Garner, Executive Director, Clinical Development, Partner Therapeutics

Data in NRG1+ Cholangiocarcinoma

The eNRGy trial is a multicenter, open-label, phase 2 study evaluating zenocutuzumab in adults with advanced solid tumors harboring NRG1 gene fusions. Data published in JCO include 22 patients with unresectable or metastatic NRG1 fusion-positive cholangiocarcinoma, of whom 19 were evaluable for efficacy. Most patients were pre-treated, with a median of one prior line of therapy (range up to 6). Notably, RNA-based next-generation sequencing (NGS) identified 100% of NRG1 fusions, compared with 29% detected by DNA-based testing.

The investigator-assessed overall response rate (ORR), defined as the proportion of patients with tumor shrinkage or disappearance, was 36.8%. Median duration of response was 7.4 months, and median progression-free survival was 9.2 months. The clinical benefit rate was 57.9%, defined as the percentage of patients achieving a complete or partial response or stable disease lasting longer than 6 months.

Zenocutuzumab was generally well tolerated. Most treatment-related adverse events were grade 1-2, with diarrhea (27.3%), fatigue (18.2%), and nausea (13.6%) being reported most frequently. No patients discontinued treatment due to treatment-related adverse events.

"The FDA approval of zenocutuzumab and the publication of these data represent important progress for patients with NRG1 fusion–positive cholangiocarcinoma. Limited efficacy and poor tolerability of second-line chemotherapy remain a significant clinical challenge in the treatment of patients with advanced cholangiocarcinoma. Zenocutuzumab provided meaningful tumor responses, durable clinical benefit, and a favorable tolerability profile. These findings also underscore the critical importance of comprehensive molecular testing—particularly tissue-based RNA sequencing—to reliably identify NRG1 gene fusions and ensure patients are matched with appropriate targeted therapy."

— James M. Cleary, MD, PhD, Director, Clinical Research, Division of Gastrointestinal Oncology, Dana-Farber Cancer Institute; and senior author.

FDA Approval in Three NRG1+ Solid Tumors

BIZENGRI was first FDA approved under accelerated approval in 2024 for advanced, unresectable or metastatic non-small cell lung cancer and pancreatic adenocarcinoma for patients harboring an NRG1 gene fusion on or after systemic therapy. In May 2026, BIZENGRI received FDA approval for advanced, unresectable or metastatic cholangiocarcinoma for patients harboring an NRG1 gene fusion on or after systemic therapy. Additionally, zenocutuzumab is included in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines) for non-small cell lung cancer, pancreatic adenocarcinoma, and cholangiocarcinoma.

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

About NRG1+ Cholangiocarcinoma

Cholangiocarcinoma is a rare, aggressive malignancy of the bile ducts with an all-stage 5-year overall survival of less than 15%. NRG1 gene fusions occur in fewer than 1% of cholangiocarcinoma cases. NRG1 fusions typically occur in patients who are otherwise driver negative, leaving affected patients, many of whom are younger adults, without approved targeted therapy. Standard cytotoxic regimens carry substantial toxicity, and second-line options such as FOLFOX produce objective responses in only approximately 5% of patients.

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 activating 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 the combination of tissue-based DNA and 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.*

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

*This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication 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 PRECAUTIONS

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 (n=99). 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 transferase (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 (n=39).

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 transferase (23%), decreased hemoglobin (23%), vomiting (23%), nausea (23%), decreased leukocytes (21%), and fatigue (21%).

NRG1 Gene Fusion Positive Advanced, Unresectable or Metastatic Cholangiocarcinoma

Serious adverse reactions occurred in 23% of patients with NRG1 gene fusion positive cholangiocarcinoma who received BIZENGRI (n=22).

In patients with NRG1 gene fusion positive cholangiocarcinoma who received BIZENGRI the most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased magnesium (59%), increased alanine aminotransferase (50%), fatigue (46%), decreased platelets (46%), decreased hemoglobin (41%), increased aspartate aminotransferase (41%), increased alkaline phosphatase (41%), decreased phosphate (41%), diarrhea (41%), abdominal pain (36%), musculoskeletal pain (36%), increased gamma-glutamyl transferase (36%), increased bilirubin (32%), decreased potassium (32%), decreased sodium (32%), nausea (27%), cough (27%), increased activated partial thromboplastin time (aPTT) (27%), dyspnea (23%), decreased appetite (23%), and decreased albumin (23%).

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(Press release, Partner Therapeutics, JUL 2, 2026, View Source [SID1234669055])