Iambic Therapeutics and Jazz Pharmaceuticals Announce Research Collaboration to Evaluate IAM1363 and Zanidatamab Combination in HER2-Positive Breast Cancer
SAN DIEGO, Calif., October 22, 2025 – Iambic Therapeutics, a clinical-stage life science and technology company pioneering the use of artificial intelligence (AI) in drug discovery and development, today announced a research collaboration and drug supply agreement with Jazz Pharmaceuticals plc (Nasdaq: JAZZ). The collaboration will evaluate the combination of IAM1363, Iambic’s brain-penetrant HER2-selective small-molecule tyrosine kinase inhibitor (TKI), with zanidatamab (Ziihera®), Jazz’s HER2-targeted bispecific antibody, in patients with HER2-positive breast cancer who have progressed following prior treatment with trastuzumab deruxtecan (T-DXd; Enhertu®).
Under the terms of the agreement, Jazz Pharmaceuticals will provide zanidatamab at no cost to Iambic for use in the clinical study. This collaboration builds upon Iambic’s growing clinical development program for IAM1363, which is currently being evaluated as both a monotherapy and in combination regimens for patients with HER2-altered cancers.
We are enthusiastic to pair our potential best-in-class HER2 TKI, IAM1363, with zanidatamab, the leading HER2-targeted bispecific antibody,” said Neil Josephson, M.D., Chief Medical Officer of Iambic Therapeutics. “Together, these agents represent a powerful new strategy with the potential to transform treatment for patients with advanced HER2-positive breast cancer whose disease has progressed following first- or second-line treatment.
Advancing the Treatment Landscape in HER2-Positive Breast Cancer
HER2-positive breast cancer represents a biologically aggressive subtype of the disease that has benefited from successive generations of HER2-directed therapies, including monoclonal antibodies, antibody-drug conjugates (ADCs), and TKIs. Despite these advances, patients whose disease progresses after treatment with T-DXd—a standard second-line therapy—have limited options. Resistance mechanisms, disease recurrence in the central nervous system (CNS), and cross-reactivity with EGFR remain major clinical challenges.
Iambic’s IAM1363 was specifically designed to address these unmet needs. Leveraging Iambic’s proprietary AI-driven discovery platform, IAM1363 was engineered for exceptional HER2 selectivity, CNS penetration, and broad activity against both wild-type and mutant forms of HER2. Preclinical studies demonstrated that IAM1363 achieves over 5,000-fold selectivity for HER2 over EGFR, thereby minimizing dose-limiting toxicities often seen with less selective TKIs. Additionally, the molecule exhibits ten-fold greater CNS exposure compared to currently approved HER2 TKIs, supporting its potential utility in treating or preventing brain metastases—a common site of progression in HER2-positive breast cancer.
The combination of IAM1363 and zanidatamab represents a rationally designed dual blockade approach that targets HER2 through complementary mechanisms of action. Zanidatamab binds two distinct epitopes on the HER2 receptor, promoting receptor clustering, internalization, and immune-mediated cytotoxicity, while IAM1363 inhibits downstream signaling through selective kinase blockade. This synergistic combination may enhance anti-tumor efficacy and overcome acquired resistance to prior HER2-directed therapies.
Clinical Evaluation: IAM1363-01 Phase 1/1b Study
As part of its ongoing Phase 1/1b IAM1363-01 trial (NCT06253871), Iambic will initiate a new study cohort evaluating the combination of IAM1363, zanidatamab, and capecitabine in patients with advanced or metastatic HER2-positive breast cancer who have received prior therapy, including T-DXd. The open-label, multi-center, dose escalation and dose optimization study is designed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of IAM1363 both alone and in combination with other HER2-targeted agents.
The trial is currently enrolling patients across multiple sites in the United States and has recently expanded into the European Union. Iambic plans to further broaden the study’s global footprint, adding clinical sites in the United Kingdom and Asia-Pacific (APAC) regions during the fourth quarter of 2025.
The initiation of the combination cohort marks a significant milestone in the IAM1363 development program and reflects Iambic’s commitment to advancing innovative HER2-targeted strategies for patients with limited treatment options.
Encouraging Early Clinical Data Presented at ESMO 2025
In parallel with the collaboration announcement, Iambic presented new clinical data for IAM1363 monotherapy at the European Society for Medical Oncology (ESMO) Annual Meeting 2025 in Berlin, Germany. The data demonstrated promising anti-tumor activity, a favorable safety profile, and broad tolerability across a diverse range of HER2-driven malignancies.
IAM1363 has shown early signs of clinical benefit in patients with HER2-mutant non-small cell lung cancer (NSCLC), HER2-positive breast and gastric cancers, and HER2-altered tumors lacking approved targeted therapies, including renal cell carcinoma, HER2-amplified NSCLC, and ovarian cancer. These findings reinforce IAM1363’s potential as a next-generation HER2-directed therapy capable of addressing both solid tumors traditionally associated with HER2 activation and emerging indications characterized by novel HER2 alterations.
Dr. Josephson emphasized the significance of these results:
The early clinical data underscore IAM1363’s differentiated profile as a highly selective, brain-penetrant HER2 TKI. Our AI-enabled design process has produced a molecule with a balance of potency, selectivity, and CNS activity that could set a new benchmark for targeted therapy in HER2-driven cancers.
Harnessing AI to Redefine Drug Discovery and Development
Iambic Therapeutics applies machine learning and physics-based modeling throughout its discovery pipeline to accelerate the identification and optimization of clinical candidates. The company’s proprietary AI-accelerated design loop integrates massive computational screening, predictive modeling of molecular interactions, and rapid medicinal chemistry cycles to generate and refine compounds with unprecedented precision.
This approach enabled the rapid discovery and optimization of IAM1363, which advanced from initial concept to clinical testing in record time. By uniting state-of-the-art AI tools with deep expertise in oncology and structural biology, Iambic aims to redefine the paradigm of precision medicine development.
Looking Ahead
The collaboration with Jazz Pharmaceuticals reflects a shared vision to develop innovative, rationally designed therapies that deliver meaningful benefits for patients with difficult-to-treat cancers. The planned IAM1363 and zanidatamab combination study represents a key step toward exploring synergistic HER2 inhibition strategies that could redefine treatment standards for patients who have exhausted current options.
We look forward to working with Jazz to evaluate this promising combination,” said Thomas Miller, Ph.D., Chief Executive Officer of Iambic Therapeutics. “Our shared commitment to scientific innovation and patient-centered development underscores the potential of this collaboration to advance the field of HER2-targeted therapy.
About Iambic Therapeutics
Iambic Therapeutics is a clinical-stage biotechnology company developing next-generation precision medicines using its proprietary AI-driven discovery and development platform. Iambic integrates computational innovation with world-class drug discovery to create novel therapeutics for patients with cancer and other serious diseases. The company’s lead program, IAM1363, is in Phase 1/1b clinical development for HER2-driven solid tumors.
