On June 4, 2025 Iambic Therapeutics, a clinical-stage life science and technology company developing novel medicines using its AI-driven discovery and development platform, reported 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 (Press release, Iambic Therapeutics, JUN 4, 2025, View Source [SID1234653730]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

"We are very encouraged by the progress of the study and the pace at which we arrived at what we believe are potentially efficacious dose levels," said Neil Josephson, M.D, Iambic’s Chief Medical Officer. "IAM1363 provides us considerable flexibility to evaluate the treatment as a monotherapy and in combination with other targeted therapies as we look to address a broad range of HER2-altered 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 in patients with advanced HER2 cancers. The study, which has multiple sites in the US, will expand to the EU, UK and APAC.

"Patients entering this study, particularly those with brain metastases, have few available treatment options," said Andrae Vandross, M.D., who leads the Phase 1 clinical trial group at NEXT Oncology in Austin, TX, a IAM1363 study site. "Our focus is on identifying important potential advances for these individuals and to look at novel approaches that may provide a therapeutic benefit."

In preclinical studies, IAM1363 has demonstrated over 1000-fold selectivity for HER2 compared to EGFR, a promising pharmacokinetic and safety profile, preferential tumor enrichment, and penetrance of the central nervous system. In HER2 tumor models, including intracranial tumor models, IAM1363 has demonstrated favorable efficacy and tolerability compared to benchmark tyrosine kinase inhibitors and HER2-targeted antibodies, and antibody-drug conjugates.

Iambic intends to present data from the study at the European Society for Medical Oncology Congress (ESMO) (Free ESMO Whitepaper) in October 2025.

About Iambic’s AI-Driven Discovery Platform

The Iambic AI-driven platform was created to address the most challenging design problems in drug discovery, leveraging technology innovations such as Enchant (multimodal transformer model that predicts clinical and preclinical endpoints) and NeuralPLexer (best-in-class predictor of protein and protein-ligand structures). The integration of physics principles into the platform’s AI architectures improves data efficiency and allows molecular models to venture widely across the space of possible chemical structures. The platform enables identification of novel chemical modalities for engaging difficult-to-address biological targets, discovery of defined product profiles that optimize therapeutic window, and multiparameter optimization for highly differentiated development candidates. Through close integration of AI-generated molecular designs with automated chemical synthesis and experimental execution, Iambic completes design-make-test cycles on a weekly cadence.

On June 4, 2025 MEDSIR reported the positive results of the TUXEDO-3 trial at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2025 (Press release, MedSIR, JUN 4, 2025, View Source [SID1234653729]). This phase II study funded by Daiichi Sankyo and Merck, known as MSD outside of the United States and Canada, evaluates the efficacy and safety of patritumab deruxtecan (HER3-DXd) in patients with active brain metastases and leptomeningeal disease, serious complications associated with advanced stages of the cancer.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The study was carried out to evaluate HER3-DXd in patients with metastatic breast cancer (mBC) and advanced non-small cell lung cancer (aNSCLC) with active brain metastases, and patients with leptomeningeal disease from solid tumors. This is an antibody-drug conjugate to target HER3, a protein receptor found on the surface of cancer cells in brain metastases. HER3-DXd is an investigational agent consisting of a fully human anti-HER3 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADC Technology payload causes tumor DNA damage, killing cancer cells within and surrounding the tumor microenvironment

The study showed promising results, which were presented today in an oral session. Results from the leptomeningeal cohort have been simultaneously published in the renowned journal Nature Medicine due to its potential benefit in patients with a high unmet medical need. In patients with breast cancer and brain metastases, intracranial responses were observed across all breast cancer subtypes, including luminal, HER2-positive, and triple-negative.

A NEW HOPE FOR DIFFICULT-TO-TREAT METASTASES

"This study represents a significant advancement in our understanding of how to treat brain metastases and leptomeningeal disease, and we are hopeful that our findings will pave the way for new, effective therapies for these patients," stated Dr. Matthias Preusser, MD, Medical Oncologist and Head of the Clinical Division of Oncology, Medical University of Vienna and Principal Investigator of TUXEDO-3. Dr. Rupert Bartsch, MD, PhD, Consultant Hematology and Medical Oncology, Medical University of Vienna, added: "Brain metastases and leptomeningeal disease represent severe complications in cancer, leading to increased morbidity and mortality, and HER3-DXd could be a promising therapeutic alternative for these patients."

Read more about TUXEDO-3 here: View Source

SHOWCASING PROMISING COLLABORATIVE TRIALS AT ASCO (Free ASCO Whitepaper)

MEDSIR’s trial DEMETHER, an international, phase II trial exploring the maintenance of trastuzumab and pertuzumab following trastuzumab deruxtecan as induction treatment for HER2-positive recurrent metastatic breast cancer patients, was mentioned during today’s Discussion of LBA1008. DEMETHER’s strategy is to optimize the sequence to increase patients’ progression free survival (PFS) while improving their quality of life.

The relevance of this mention highlighted the ability of MEDSIR for anticipating patients’ needs and designing strategical trials to keep on pushing the barriers of clinical research. MEDSIR active presence at the ASCO (Free ASCO Whitepaper) Annual Meeting 2025 reinforces its leadership in excellence-driven oncology research and highlights its focus on addressing unmet needs in cancer treatment, with the aim of not leaving any patient left behind.

On June 4, 2025 Acerand Therapeutics, a clinical-stage biotech company focusing on the discovery and development of innovative small-molecule therapies in oncology, reported the dosing of the first patient in its first-in-human Phase I clinical trial (NCT06801236) of ACE-232, a novel oral inhibitor of CYP11A1 (Press release, Acerand Therapeutics, JUN 4, 2025, View Source [SID1234653728]). The trial is being conducted in patients with metastatic castration-resistant prostate cancer (mCRPC).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This multicenter Phase I study is being conducted in both the United States and China. The study comprises two parts: a dose-escalation phase (Phase IA) and a dose-optimization phase (Phase IB). The primary objectives are to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), as well as preliminary clinical activity of ACE-232, and to determine the recommended Phase II dose (RP2D). Professor Emmanuel Antonarakis, Director of Genitourinary Oncology at Masonic Cancer Center, University of Minnesota, is serving as the global coordinating Principal Investigator for the study. "I would like to congratulate the Acerand team, the research staff, and the first patient for helping us to reach this important milestone," says Dr. Antonarakis.

Preclinical data demonstrated that ACE-232 possesses superior potency, efficacy, and pharmacokinetic properties (flat PK curve and long half-life profile) compared to other investigational CYP11A1 inhibitors, including MK-5684 (Opevesostat, formerly known as ODM-208). ACE-232 showed excellent tolerability in preclinical models, presenting a wide therapeutic window for clinical development.

The initiation of this trial marks a significant milestone for Acerand, representing its first clinical study in the United States and highlighting its strategic commitment to the global development of innovative cancer therapies that address major unmet medical needs.

About ACE-232

ACE-232 is a highly potent and selective small-molecule inhibitor of CYP11A1, a key adrenal enzyme involved in the first and rate-limiting step of steroid hormone biosynthesis. By targeting CYP11A1, ACE-232 aims to suppress the production of androgens and other steroid hormones, offering a novel therapeutic mechanism for the treatment of androgen-dependent (including enzalutamide or abiraterone-resistant) prostate cancer.

On June 4, 2025 Rakuten Medical, Inc., a global biotechnology company developing and commercializing Alluminox platform-based photoimmunotherapy, reported that its third drug candidate, RM-0256, has been selected for funding by the Japan Agency for Medical Research and Development (AMED) under its Support Program for Orphan Drug prior to the Designation (Press release, Rakuten Medical, JUN 4, 2025, View Source [SID1234653727]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

RM-0256 is a novel antibody conjugate composed of IRDye700DX (IR700)—a light-activatable dye for which Rakuten Medical holds exclusive global manufacturing and supply rights—and a proprietary anti-PD-L1 monoclonal antibody. The AMED funding will support the clinical development of RM-0256 photoimmunotherapy for unresectable, advanced, or recurrent malignant epithelial tumors.

In Japan, malignant epithelial tumors affect approximately 22,000 individuals annually1. While systemic therapies, including chemotherapy and immune checkpoint inhibitors, are currently the mainstay of treatment for unresectable advanced or recurrent cases, patients who develop resistance to these treatments face limited treatment options, which underscores the urgent need for novel therapeutic approaches.

RM-0256 targets Programmed Cell Death Ligand 1 (PD-L1), a key immune checkpoint protein that allows tumors to evade immune detection by binding to PD-1 receptors on activated T cells. PD-L1 is widely expressed in various solid tumors—including melanoma, ocular melanoma, lung, urothelial, gastrointestinal, gynecological, breast, and head and neck cancers2—as well as on immunosuppressive cells within the tumor microenvironment.

Pre-clinical studies of PD-L1-targeted photoimmunotherapy have suggested three complementary mechanisms of action3:

1) Direct depletion (necrosis) of PD-L1-expressing tumor cells;
2) Activation of anti-tumor immunity through the elimination of PD-L1–expressing immunosuppressive cells;
3) Checkpoint blockade, by inhibiting PD-L1/PD-1 interaction, potentially enhancing systemic immune responses.

With the support of AMED funding, Rakuten Medical is accelerating the development of RM-0256 photoimmunotherapy as a novel, multimodal cancer therapy that may induce both local and systemic anti-tumor effects.

On June 4, 2025 Duality Bio (HKEX: 9606.HK) reported the preliminary data of two clinical trials, HER3 ADC candidate DB-1310 and B7H3 ADC candidate DB-1311/BNT324, which is being jointly developed with BioNTech, in Oral/Rapid Oral presentations at the 2025 ASCO (Free ASCO Whitepaper) Annual Meeting taking place in Chicago, US, from May 30 to June 3 (Press release, DualityBio, JUN 4, 2025, View Source [SID1234653726]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

B7H3 ADC candidate DB-1311/BNT324:

Data from the ongoing Phase 1/2 clinical trial (NCT05914116) in patients with heavily pre-treated castration-resistant prostate cancer (CRPC) were presented during an oral session on BNT324/DB-1311, an B7H3-targeted ADC candidate.

The data indicated early clinical activity and a manageable safety profile with low discontinuation rates. Most common adverse events were gastrointestinal and hematologic toxicities. In the 52 efficacy evaluable patients with heavily pretreated CRPC based on RCIST v1.1, the confirmed objective response rate (cORR) was 30.8%, DCR was 90.4%. Among 68 evaluable patients, the 6-month rPFS rate was 69.8%. Similar outcomes were observed across both dose levels (6 mg/kg or 9 mg/kg). Outcomes appeared better in earlier treatment lines and in patients who received one prior NHT, while antitumor activity was also observed in later lines and regardless of type of prior treatment or metastatic site.

The clinical trial is currently enrolling post Lu-177 CRPC (Cohort 11) and taxane-naïve CRPC (Cohort 12).

As the incidence rate of prostate cancer is increasing[1],1 there is a high unmet need for new effective therapies for patients with heavily pretreated CRPC[1]. The DB-1311/BNT324 program received Fast Track Designation by the U.S. Food & Drug Administration ("FDA") for the treatment of patients with advanced/unresectable or metastatic CRPC that has progressed on or after standard systemic regimens in 2024.

HER3 ADC DB-1310：

Data from the first-in-human Phase I/IIa study (NCT05785741) presented by Professor Aaron E. Lisberg of the University of California, Los Angeles (UCLA), demonstrated that DB-1310 showed encouraging efficacy and a manageable safety profile in patients with advanced solid tumors who had failed standard treatments.

Among 123 efficacy evaluable patients, the unconfirmed objective response rate (uORR) was 31%, and the disease control rate (DCR) reached 84%. Notably, efficacy was particularly striking in the key subgroup of patients with EGFR-mutated non-small cell lung cancer (NSCLC) (n=46) where uORR reached 44%, DCR was 91%, median progression-free survival (mPFS) was 7.0 months, and median overall survival (mOS) was 18.9 months. The uORR reached an impressive 66.7% at the 5.5 mg/kg Q3W dose level (n=12).

In addition, DB-1310 was well-tolerated with a manageable safety profile. The most common treatment-related adverse events (TRAEs) were Grade 1-2 hematological and gastrointestinal events with a low treatment-related discontinuation rate of 3.5%.

These positive results support the continued development of DB-1310 in advanced solid tumors, particularly in patients with EGFR-mutated NSCLC. The company is advancing its global development program, including exploring DB-1310 as a monotherapy in additional tumor types, as well as exploring DB-1310 in combination with EGFR TKIs and HER2-targeted therapies.