IAM1363 / Iambic Therap - LARVOL DELTA

A phase I/Ib study of IAM1363, a selective and brain penetrant HER2 inhibitor in participants (pts) with advanced cancers harboring HER2 alterations (ESMO 2025) - P1 | "Three of the 4 pts with PRs had received prior T-DXd. The pt with breast cancer had also received prior tucatinib...Most AEs were low grade and manageable in the outpatient setting. Antitumor activity was observed across disease types and HER2 alterations and was evident both systemically and intracranially in heavily pretreated pts."

Clinical • Metastases • P1 data • Breast Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • EGFR

AIambic Shares Clinical Data from Ph1/1B Study of IAM1363, a Highly Selective Type-2 HER2 Inhibitor, Demonstrating Monotherapy Activity in Heavily Pretreated Patients with HER2 Alterations, at the 2025 ESMO Congress (Businesswire) - "Initial clinical data show activity in patients with HER2-mutant NSCLC and HER2-positive breast and gastric cancers, as well as indications lacking approved HER2-directed TKIs or antibodies, such as HER2-mutant renal cell cancer and HER2-amplified NSCLC and ovarian cancer. Best overall response (BOR) data in participants with HER2-targetable alterations dosed at ≥960 mg qd, as assessed by RECIST 1.1 and RANO-BM, showed partial responses in 28% (N=18) with measurable systemic disease and in 33% (N=3) with measurable intracranial tumors....The study...will continue to expand into additional sites across the U.S. and EU and into the UK and APAC in Q4 2025."

P1 data • Trial status • Gastric Cancer • HER2 Positive Breast Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Renal Cell Carcinoma

Iambic Announces Research Collaboration with Jazz Pharmaceuticals for IAM1363 and Zanidatamab Combination Cohort in HER2-Positive Breast Cancer (Businesswire) - "Under the agreement, Jazz will provide zanidatamab (Ziihera), a HER2-targeted bispecific antibody, at no cost to Iambic for evaluation in combination with IAM1363....The combination will be studied in patients with HER2-positive breast cancer....As part of the Phase 1/1b IAM1363-01 study, Iambic will initiate a cohort in patients with HER2-positive breast cancer to evaluate IAM1363 in combination with zanidatamab and capecitabine."

Commercial • Trial status • HER2 Positive Breast Cancer

IAM1363 Is a Potent, Selective, and Irreversible HER2 and Pan-HER2 Mutant Small Molecule Inhibitor for the Treatment of HER2-Driven NSCLC (IASLC-WCLC 2025) - P1 | "Trastuzumab deruxtecan (T-DXd), a HER2-specific antibody-drug conjugate, is an approved therapy for relapsed NSCLC with HER2-activating mutations or protein overexpression (IHC3+). Conclusions : Based on its high selectivity, broad anti-tumor activity across biomarker-positive nonclinical models, and brain penetrance, IAM1363 is anticipated to be an effective treatment for HER2 amplified or mutant NSCLC patients, including for patients with CNS metastases. IAM1363 is currently being evaluated in a phase 1/1b clinical trial (NCT06253871)."

Interstitial Lung Disease • Lung Cancer • Non Small Cell Lung Cancer • Pulmonary Disease • Respiratory Diseases • Solid Tumor • EGFR • HER-2

Iambic to Present New Pre-Clinical NSCLC Data for IAM1363, a Selective Type II Inhibitor for HER2 Cancers, at the 2025 World Conference on Lung Cancer (Businesswire) - "IAM1363 demonstrated robust anti-tumor activity with prolonged survival in an intracranial model of brain metastasis. Finally, treatment with IAM1363 resulted in striking tumor enrichment in a HER2 exon 20-mutant NSCLC model with strong tumor regression."

Preclinical • Non Small Cell Lung Cancer

Iambic Completes Dose Escalation in Ongoing Phase 1/1B Study of Lead Program IAM1363, a Small Molecule Inhibitor of Wild-Type and Oncogenic HER2 Mutant Proteins (Businesswire) - "Iambic Therapeutics...announced today that it has completed dose escalation in IAM1363-01, its Phase 1/1b clinical trial evaluating IAM1363, a selective and brain-penetrant small molecule inhibitor of wild-type and oncogenic mutant HER2. With completion of dose escalation, Iambic is advancing two well-tolerated doses into the dose optimization phase of the study. Patients enrolling into dose optimization include those with HER2-altered cancers and brain metastases, any advanced cancer harboring a HER2 TKD (tyrosine kinase domain) mutation, and advanced HER2-amplified non-small cell lung cancer....The Phase 1/1b trial, NCT06253871, is an open-label, multi-center, dose escalation and dose optimization study, designed to evaluate tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of IAM1363 in patients with advanced HER2 cancers....Iambic intends to present data from the study at the European Society for Medical Oncology Congress (ESMO) in October 2025."

P1 data • Trial status • Gastric Cancer • HER2 Positive Breast Cancer • Non Small Cell Lung Cancer

Screening or Early Detection of Brain Metastases and the Treatment in the Era of New Agents (GBCC 2025) - "Advances in systemic therapy have been greatest in HER2-positive breast cancer, where the current NCCN guidelines include a growing list of CNS-active regimens, such as tucatinib-capecitabine-trastuzumab, T-DXd, T-DM1, high dose trastuzumab and pertuzumab, neratinib-capecitabine, and lapatinib-capecitabine...There are a number of novel blood-brain-barrier (BBB) penetrant HER2-targeted tyrosine kinase inhibitors (e.g. ZN1041, IAM1363) in early-phase clinical trials. For patients with HER2-negative tumors, the data are more sparse; however, activity of chemotherapy drugs such as capecitabine, anthracyclines, platinums, and eribulin has been reported...Ongoing clinical trials are testing a wide variety of ADCs, such as patritumab deruxtecan, datopotamab deruxtecan, ARX788, and others...For example, the ELECTRA trial is testing the combination of elacestrant and abemaciclib. Overall, the expanding array of systemic options with clinically meaningful intracranial activity, as..."

Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2

Iambic Therapeutics to Present at the 43rd Annual JP Morgan Healthcare Conference (Businesswire) - "Dr. Miller will detail progress and anticipated milestones for Iambic’s emerging pipeline of development candidates, as well as advances to its AI drug discovery platform. The Company’s pipeline currently includes IAM1363, a highly selective, brain penetrant small molecule inhibitor of both wild-type and oncogenic HER2 mutants currently in a Phase 1/1b study, as well as a potential first-in-class selective dual CDK2/4 inhibitor for multiple cancer indications, an allosteric inhibitor for KIF18A, and additional new programs."

Clinical • Oncology • Solid Tumor

Iambic Therapeutics Appoints Michael Secora, Ph.D. as Chief Corporate Development Officer and Chief Financial Officer (Businesswire) - "Iambic’s pipeline includes IAM1363, a potential best-in-class, highly selective and brain penetrant small molecule inhibitor of both wild-type and oncogenic HER2 mutants currently in a Phase 1 study with data anticipated in 2025..."

P1 data • Bladder Cancer • Colorectal Cancer • Gastroesophageal Cancer • HER2 Positive Breast Cancer • Non Small Cell Lung Cancer • Solid Tumor • HER-2

IAM1363-01: A Phase 1/1b Study of IAM1363 in HER2 Cancers (clinicaltrials.gov) - P1 | N=243 | Recruiting | Sponsor: Iambic Therapeutics, Inc | Trial primary completion date: Apr 2028 ➔ Mar 2027

Trial primary completion date • Bladder Cancer • Brain Cancer • Breast Cancer • CNS Tumor • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Genito-urinary Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Iambic Therapeutics Closes $50 million Series B Extension to Broaden its Pipeline of AI-Discovered Clinical Oncology Programs (Businesswire) - "Iambic Therapeutics, a clinical-stage biotechnology company developing novel therapeutics using its unique AI-driven discovery platform, today announced the closing of an oversubscribed $50 million extension to its Series B financing....Proceeds from the latest financing will be used to further Iambic’s pipeline of clinical and pre-clinical programs. These include IAM1363, a highly selective, brain penetrant small molecule inhibitor of both wild-type and oncogenic HER2 mutants currently in a Phase 1/1b study, as well as a potential first-in-class selective dual CDK2/4 inhibitor designed to expand the therapeutic window and address treatment resistance in solid tumors in diseases such as breast cancer."

Financing • Oncology • Solid Tumor

IAM1363-01: A phase 1/1b study of a selective and brain-penetrant HER2 inhibitor for HER2-driven solid tumors. (ASCO 2024) - P1 | "Up to 287 patients will be enrolled at approximately 20 sites and treated until disease progression or unacceptable toxicity. The trial is designed to establish the safety profile of IAM1363 as a single agent and in combination with trastuzumab and to provide initial proof of antitumor activity in malignancies with HER2 overexpression, gene amplification, or tyrosine kinase mutations, including in patients with brain metastases."

P1 data • Bladder Cancer • Breast Cancer • Genito-urinary Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Iambic Therapeutics Announces Poster Presentation for IAM1363, a Clinical Stage Type II HER2 Inhibitor, at the 2024 ASCO Annual Meeting (Businesswire) - "Iambic Therapeutics...today announced a poster presentation highlighting the ongoing Phase 1 study of IAM1363, a selective and brain-penetrant inhibitor of HER2 signaling for the treatment of HER2-driven cancers. The TIP (trials in progress) poster will be shared at the American Society for Clinical Oncology (ASCO) Annual Meeting, taking place May 31-June 4 in Chicago."

Trial status • Oncology • Solid Tumor

Validation of a novel Type II HER2 inhibitor through preclinical studies across various cancer models (AACR 2024) - "For example, in a p95HER2 xenograft model, IAM1363 caused significant TR, including complete responses, at 100 mg/kg dose, whereas tucatinib achieved at best tumor stasis at MTD and T-DXd showed marginal effect. Additionally, IAM1363 was found to be consistently enriched in xenograft tumors that had moderate to high HER2 expression levels, and those with HER2 activating mutations. This distinctive pharmacokinetic property facilitates optimal target engagement in tumors, including those occurring in the brain, while minimizing potential systemic side effects."

Preclinical • Esophageal Cancer • Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • KRAS • MET

IAM1363-01: A Phase 1/1b Study of IAM1363 in HER2 Cancers (clinicaltrials.gov) - P1 | N=287 | Recruiting | Sponsor: Iambic Therapeutics, Inc | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology

Iambic Therapeutics Announces First Patient Dosed in Phase 1 Clinical Study of IAM1363, a Highly Selective HER2 Inhibitor for the Treatment of Solid Tumors - "'For the patients I see in clinic there remains a significant need to improve therapies for HER2-driven cancers....Because of its selective targeting, I see great potential for it to be developed across the entire spectrum of HER2 altered cancers, both as a single agent and in combination with other standard of care therapies,' said Dr. Alexander Spira..."

Media quote

Iambic Therapeutics to Present New Pre-Clinical Data for IAM1363, a Selective and Brain-Penetrant Inhibitor of Both HER2 Wild-Type and Oncogenic Mutants, at the 2024 AACR Annual Meeting (Businesswire) - "Iambic Therapeutics today announced it will highlight new preclinical data for IAM1363, a selective and brain-penetrant inhibitor of HER2 signaling for the treatment of HER2-driven cancers, in a poster presentation at the American Association for Cancer Research (AACR) Annual Meeting, taking place April 5-10 in San Diego...The poster presentation will showcase preclinical data illustrating how the unique binding mechanism and potent HER2 activity of IAM1363 overcomes multiple resistance mechanisms and how its strong EGFR avoidance widens the safety margin."

Preclinical • Oncology • Solid Tumor

Iambic Therapeutics Announces First Patient Dosed in Phase 1 Clinical Study of IAM1363, a Highly Selective HER2 Inhibitor for the Treatment of Solid Tumors (Businesswire) - "Iambic Therapeutics...announced that the first patient has been dosed in its Phase 1 clinical study evaluating IAM1363, a selective and brain-penetrant inhibitor of HER2 signaling for the treatment of HER2-driven cancers....The Phase 1/1b trial, NCT06253871, is an open-label, multi-center, dose escalation and dose optimization study, designed to evaluate tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of IAM1363 as monotherapy and in combination with trastuzumab in patients with advanced HER2 cancers."

Trial status • Oncology • Solid Tumor

A Phase 1/1b Study of IAM1363 in HER2 Cancers (clinicaltrials.gov) - P1 | N=287 | Not yet recruiting | Sponsor: Iambic Therapeutics, Inc

New P1 trial • Oncology

Iambic Therapeutics Announces New Research Published in Nature Machine Intelligence Demonstrating the Capabilities of Its Generative AI NeuralPLexer Technology to Predict Protein-Ligand Complex Structures (Businesswire) - "Iambic Therapeutics uses NeuralPLexer in building its own pipeline, including the discovery of IAM1363, a selective and brain-penetrant small molecule inhibitor of HER2 wildtype and oncogenic mutant proteins, designed to expand therapeutic index compared to available HER2 inhibitors and to avoid toxicities from off-target inhibition of EGFR, a related receptor tyrosine kinase. In preclinical studies, IAM1363 has demonstrated over 1000-fold selectivity for HER2 compared to EGFR. An IND for IAM1363 was recently accepted by FDA and clinical trials are planned to commence in early 2024 – a timeline that has the drug candidate moving from program start to clinical studies in under two years."

IND • New trial • Oncology

Iambic Therapeutics Announces Close of Oversubscribed $100 Million Series B Financing to Advance AI-Discovered Therapeutics into Clinical Development and Enters Collaboration with NVIDIA (Businesswire) - "Funding will Support Continued AI Platform Innovations and Advancement of Multiple Candidates into Clinical Development, Including IAM-H1, a Selective Brain-Penetrant HER2 Inhibitor, and IAM-C1, a Selective Dual CDK2/4 Inhibitor."

Commercial • Oncology • Solid Tumor