SystImmune, Inc. and Bristol Myers Squibb Announce First Global Phase I Results of Iza-bren, an EGFR x HER3 Bispecific Antibody-Drug Conjugate, in Patients with Advanced Solid Tumors at ESMO 2025

Rhea-AI Summary

SystImmune and Bristol Myers Squibb (NYSE: BMY) presented first global Phase I results for iza-bren (EGFR x HER3 bispecific ADC) at ESMO 2025 on Oct 17, 2025.

At data cut-off July 23, 2025, 107 heavily pre-treated patients were treated. At 2.5 mg/kg (Days 1 & 8 q3w), confirmed response rate was 55% (11/20) with median progression-free survival 5.4 months. Confirmed responses occurred in EGFR-mutated (3/10) and EGFR wild-type (3/4) NSCLC subgroups. No interstitial lung disease observed; hematologic AEs (neutropenia) were manageable and prompted mandatory preventative measures in ongoing studies. Breakthrough Therapy designation granted Aug 2025.

Positive

• Confirmed ORR 55% at 2.5 mg/kg (11 of 20)
• Median PFS of 5.4 months at 2.5 mg/kg
• Responses in EGFR-mutated NSCLC: 3 of 10
• Responses in EGFR wild-type NSCLC: 3 of 4
• Breakthrough Therapy designation granted Aug 2025

Negative

• Hematologic toxicity (neutropenia) was common
• 107 patients treated—early Phase I dataset, limited follow-up

Insights

Clinical Oncology Strategist

Early global Phase I data show promising activity and a manageable safety profile for iza-bren in heavily pretreated solid tumors.

At the reported data cut-off (July 23, 2025), the global Phase I LUNG-101 program treated 107 patients and showed a notable confirmed response rate of 55% (11 of 20) at the 2.5 mg/kg schedule with a median progression-free survival of 5.4 months. Responses occurred in both EGFR-mutated (3 of 10) and EGFR wild-type (3 of 4) NSCLC subgroups. The program also received U.S. FDA Breakthrough Therapy designation in August 2025, which signals regulatory interest based on observed benefit in earlier data.

The safety signal described centers on hematologic events, principally neutropenia, which were said to be manageable with standard measures and rarely drove dose reductions; importantly, no interstitial lung disease was observed. Mandatory preventive measures for neutropenia are now incorporated into ongoing global studies. These facts point toward an acceptable tolerability profile for continued development, but the small subgroup sizes limit certainty about durability and breadth of activity.

Key dependencies include confirmation of these response rates and PFS in the ongoing registrational trials listed (e.g., IZABRIGHT-Lung01, NCT05983432) and the ability of mandatory neutropenia mitigation to prevent treatment-limiting toxicity at scale. Watch for complete response rate, duration-of-response, larger-cohort safety data, and interim registrational results over the next 6–24 months as the program advances through global registration pathways.

REDMOND, Wash. and PRINCETON, N.J., Oct. 17, 2025 /PRNewswire/ -- SystImmune Inc. (SystImmune), a clinical-stage biotechnology company, and Bristol Myers Squibb (NYSE: BMY) today announced the oral presentation of the first disclosure of the safety and efficacy data from the global phase I US-Lung-101 study (NCT05983432) of iza-bren (BL-B01D1), a potentially first-in-class EGFR x HER3 bispecific antibody-drug conjugate (ADC), at the European Society for Medical Oncology (ESMO) Congress 2025 in Berlin, Germany. Iza-bren is jointly developed by SystImmune and Bristol Myers Squibb under a collaboration and exclusive license agreement in territories outside of Mainland China. In August 2025, iza-bren was granted breakthrough therapy designation by U.S. FDA for patients with previously treated EGFR-mutated NSCLC based on the data from China studies and this global study.

This study evaluated the safety and efficacy of iza-bren in global patients with heavily pre-treated metastatic or unresectable advanced non-small cell lung cancer (NSCLC) and other solid tumors. At the data cut-off (DCO) of July 23, 2025, iza-bren has demonstrated:

• Promising antitumor activity in heavily pre-treated patients across multiple tumor types, including EGFR mutant and wildtype NSCLC
• Manageable safety profile, with hematologic adverse events effectively managed by standard medical measures, and no interstitial lung disease was observed

In the study, 107 patients with advanced solid tumors were treated, including non-small cell lung cancer (NSCLC) patients with and without EGFR mutations. Most had received several prior therapies. The most common side effects were blood-related, such as neutropenia. These were generally manageable and rarely led to dose reductions or serious complications. No new safety concerns were identified, and no cases of interstitial lung disease were seen. Mandatory preventive measures for neutropenia have been added in ongoing global studies.

For patients receiving 2.5 mg/kg (Days 1 and 8 every 3 weeks), 55% (11 of 20) showed a confirmed response, with a median progression-free survival of 5.4 months. Confirmed responses were also seen in both the subgroup with EGFR-mutated NSCLC (3 of 10 patients) and those without the mutation (3 of 4 patients).

Global registrational studies of first line metastatic TNBC (IZABRIGHT-Breast01, NCT06926868), second line metastatic EGFRmt NSCLC (IZABRIGHT-Lung01, NCT05983432) and second line metastatic Urothelial Cancer (IZABRIGHT-Bladder01, NCT07106762) are ongoing, with studies in other indications planned.

"The first global presentation of iza-bren builds on the compelling data initially observed in Chinese patients, showing consistent efficacy in a heavily pre-treated global population," said Jonathan Cheng, M.D., Chief Medical Officer, SystImmune. "These results support iza-bren's potential as a bispecific ADC treatment option across multiple tumor types, and we are excited to continue advancing this important program through our global collaboration with Bristol Myers Squibb."

"We are committed to developing first-in-class and best-in-class medicines that can meaningfully improve outcomes for patients with difficult-to-treat cancers," said Anne Kerber, Senior Vice President, Head of Development, Hematology, Oncology and Cell Therapy, Bristol Myers Squibb. "The encouraging activity observed with iza-bren in this early global study reinforce our confidence in its potential, and we look forward to the ongoing registrational studies across lung, breast, and urothelial cancers."

About the BL-B01D1-LUNG-101 Phase I clinical trial
BL-B01D1-LUNG-101 (NCT05983432) is a global, multi-center, Phase I study to evaluate the safety, tolerability, pharmacokinetics, and initial efficacy of iza-bren in participants with metastatic or unresectable NSCLC and other solid tumors. This study will be conducted in two different dosing schedules (Cohort A and Cohort B) and three parts (dose escalation, dose finding and dose expansion). Cohort A will be dosed on Day 1 and Day 8 of a continuous 21-day treatment cycle. Cohort B will be dosed on Day 1 of a continuous 21-day treatment cycle. The primary endpoint includes safety. Secondary endpoints include objective response rate (ORR) by RECIST 1.1 criteria, duration of response (DoR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OR) and PK analysis.

About EGFRmt NSCLC
Non-small cell lung cancer (NSCLC) accounts for approximately 80% of all lung cancer cases, which remains the leading cause of cancer-related death worldwide. Among patients with NSCLC, 10% to 15% in Western populations and up to 50% in Asian populations harbor activating EGFR mutations. These tumors, most commonly of non-squamous histology, initially respond to EGFR TKIs such as osimertinib. However, resistance is nearly universal, often occurring after about 18 months, and treatment options beyond TKIs and platinum-based chemotherapy provide limited clinical benefit with significant toxicities, highlighting the critical need for new, effective therapies.

About iza-bren
SystImmune, in collaboration with BMS outside of China, is developing iza-bren (BL-B01D1), a bispecific antibody-drug conjugate (ADC) that targets both EGFR and HER3, which are highly expressed in various epithelial cancers and are known to be associated with cancer cell proliferation and survival. Iza-bren's dual mechanism of action blocks EGFR and/or HER3 signals to cancer cells, reducing cancer cell proliferation and survival. In addition, upon antibody mediated internalization, iza-bren's therapeutic novel Topo1i payload is released causing cytotoxic stress that leads to cancer cell death.

About SystImmune
SystImmune is a clinical-stage biopharmaceutical company located in Redmond, WA and Princeton, NJ. It specializes in developing innovative cancer treatments using its established drug development platforms, focusing on bi-specific, multi-specific antibodies, and antibody-drug conjugates (ADCs). SystImmune has several assets in various stages of clinical trials for solid tumor and hematologic indications. Alongside ongoing clinical trials, SystImmune has a robust preclinical pipeline of potential cancer therapeutics in the discovery or IND-enabling stages, representing cutting-edge biologics development.

About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, X, YouTube, Facebook and Instagram.

SystImmune Forward-Looking Statements
Any research and development information provided by SystImmune is intended for general information purposes only. Such information is not intended to provide complete medical information. We do not offer patient-specific treatment advice and if you have medical conditions, please see your medical doctor or healthcare provider.

This press release may contain forward-looking statements with the meaning of Section 27A of the Securities Act of 1933, as amended, Section 21E of the Securities Exchange Act of 1934, and the Private Securities Litigation Reform Act of 1995, which reflects the expectations regarding the company's goals, strategies, results of operations, performance, business prospects, and opportunities, including but not limited to the ability to gain Investigational New Drug status for the resulting new product and the ability to develop a successful formulation. Terms such as "anticipates," "believes," "expects," "estimates," "could," "intends," "may," "plans," "potential," "projects," "will," "would" and other similar expressions, or the negative of these terms, are generally indicative of forward-looking statements.

While SystImmune, Inc. believes that expectations expressed in the forward-looking statements are based on the company's reasonable assumptions and beliefs in light of the information available to the company at the time such statements are made, it cannot give assurance that such forward-looking statements will prove to have been correct. Such forward-looking statements are not fact and are subject to uncertainties and other factors that could cause actual results to differ materially from such statements. We undertake no obligation to update any forward-looking statements contained in this press release to reflect events or circumstances occurring after its date or to reflect the occurrence of unanticipated events.

For additional information about the company, please visit https://systimmune.com/.

Bristol Myers Squibb Cautionary Statement Regarding Forward-Looking Statements
This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on current expectations and projections about Bristol Myers Squibb's future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, that the expected benefits of, and opportunities related to, the collaboration with SystImmune may not be realized by Bristol Myers Squibb or may take longer to realize than anticipated, that iza-bren (BL-B01D1) may not receive regulatory approval for the indications described in this release in the currently anticipated timeline or at all, any marketing approvals, if granted, may have significant limitations on their use and, if approved, whether such product candidates will be commercially successful.

No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol Myers Squibb's business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2024, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise.

View original content to download multimedia:https://www.prnewswire.com/news-releases/systimmune-inc-and-bristol-myers-squibb-announce-first-global-phase-i-results-of-iza-bren-an-egfr-x-her3-bispecific-antibody-drug-conjugate-in-patients-with-advanced-solid-tumors-at-esmo-2025-302586896.html

SOURCE SystImmune, Inc.

FAQ

What efficacy did BMY and SystImmune report for iza-bren at ESMO 2025?

At data cut-off July 23, 2025, confirmed ORR was 55% (11/20) at 2.5 mg/kg with median PFS 5.4 months.

Did the Phase I study of iza-bren report safety concerns for BMY (BMY) patients?

No new safety signals or interstitial lung disease were observed; hematologic AEs like neutropenia were common but generally manageable.

How many patients were treated in the global Phase I iza-bren study (NCT05983432)?

A total of 107 patients with advanced solid tumors were treated as of the July 23, 2025 data cut-off.

Did iza-bren show activity in EGFR-mutated NSCLC in the Phase I BMY study?

Yes; confirmed responses were reported in the EGFR-mutated subgroup (3 of 10 patients).

What regulatory milestone did iza-bren achieve before Oct 17, 2025?

Iza-bren received Breakthrough Therapy designation from the U.S. FDA in August 2025.