In this exclusive interview with Dr. Jerome Boyd-Kirkup, Chief Scientific Officer of Hummingbird Bioscience, BioPharma APAC  delve into the recently initiated Phase Ib clinical trials of HMBD-001 in Australia. Discover the primary objectives, expected outcomes, and the groundbreaking potential of HMBD-001 as a differentiated HER3-targeting antibody in inhibiting HER3 oncogenic signaling. Explore the strategic partnership with Omico and its role in expediting patient recruitment, as well as the utilization of genetic signatures for patient selection and trial design.

Can you provide more details about the recently initiated Phase Ib clinical trials in Australia for HMBD-001? What are the primary objectives and expected outcomes of these trials?

We are excited to have initiated two HMBD-001 Phase Ib precision clinical trials in Australia for the first time. We have identified biomarker-defined populations in patients with squamous non-small cell lung cancer (sqNSCLC) and solid tumors with HER3 aberrations, and are confident that these populations will benefit from HMBD-001. The main objectives of both studies are to assess the safety and efficacy of various treatment regimens containing HMBD-001, following the completion of the Phase Ia monotherapy dose escalation in the United Kingdom. 

Could you elaborate on the significance of HMBD-001 as a differentiated HER3-targeting antibody in inhibiting HER3 oncogenic signaling? How does it stand out from other treatment approaches for patients with squamous non-small cell lung carcinoma (sqNSCLC) and genetic aberrations in HER3 signaling? 

HMBD-001 is a novel monoclonal antibody with a unique mechanism of action targeting the dimerization interface of the HER3 receptor. This prevents HER3 from binding to other receptors of the same family and activating cancer growth pathways. Significantly, given its unique binding site, HMBD-001 prevents all mechanisms of activation of HER3, whether or not they involve the HER3 ligand NRG1. Previous drugs against HER3 that bound to other regions of the receptor did not do this and in turn showed underwhelming performance in clinical trials.  

Common genetic alterations that increase HER3 and EGFR signaling are frequently observed in squamous cell carcinomas, such as sqNSCLC. Inhibiting EGFR often results in compensatory increases in HER3 activity and signaling through the PI3K growth pathway, leading to resistance to those monotherapy agents. Therefore, our approach to combine HMBD-001 with docetaxel (a second-line cytotoxic therapy approved for sqNSCLC) with or without cetuximab (EGFR inhibitor widely used in various indications) has the potential to greatly improve clinical outcomes following standard-of-care therapies. 

The partnership with Omico to accelerate clinical development through the PrOSPeCT initiative seems crucial. Could you explain how this collaboration will expedite patient recruitment and contribute to the success of the HMBD-001 trials? 

Australia was our choice location to conduct these clinical trials due to our partnership with Omico and the streamlined regulatory and institutional approval process in the country, which allows for short start-up timelines.

Omico’s landmark initiative, PrOSPeCT, provides access to world-class genomic profiling for advanced cancer patients, clinical assessment of the results by an expert team and matching to potential treatments available locally, including clinical trials. 

Effective drugs sometimes fail because they are not given to the right patients, or the development process can be long as it involves a lot of trial and error. By partnering with Omico, we are efficiently matching patients who are best suited for HMBD-001 treatment to our precision clinical trials. This increases the likelihood of clinical benefit and the advancement of our trials.   

Could you shed light on the genetic signatures that have been identified as predictive of a positive response to HMBD-001? How will these predictive markers be utilized in patient selection and trial design? 

Hummingbird Bioscience has built a team with accumulated experience in systems biology, computational biology, pharmacology and omics to achieve our focus of understanding the underlying disease biology of our drug targets. For one of the new trials, we are recruiting patients with aberrations in HER3 signaling (specifically NRG1 fusions, a rare cancer-causing mutation, and patients with selected mutations in the HER3 receptor). For the other trial, we are recruiting patients with a subtype of sqNSCLC that share the same genetic signature. This proprietary signature defines the presence or absence of mutations in specific genes involved in various cancer growth signaling pathways to predict those patients that are likely to benefit from HMBD-001 treatment. Patients with this signature can be identified by Omico and then have the option to enroll in the sqNSCLC trial. 

The trials are being led by Professor Nick Pavlakis at GenesisCare, with support from Omico's PrOSPeCT platform. Could you discuss the the role of Professor Pavlakis in advancing precision oncology through these trials? 

Professor Nick Pavlakis is a medical oncologist with a passion for clinical research and a Principal Investigator of both Phase Ib trials for HMBD-001. His extensive experience implementing genomic testing as an enabler for precision oncology in Australia, particularly in lung cancer and in collaboration with Omico, aligns well with our vision as a biotech company developing precision therapeutics.

Precision oncology holds great promise for improving cancer treatment outcomes. How does the initiation of these trials in Australia align with Hummingbird Bioscience's broader goals and vision for transforming biologic medicines in the context of hard-to-treat diseases? 

Hummingbird Bioscience is dedicated to ensuring that the right patients receive the right drugs and has invested significant resources over the years in discovering our therapies, understanding what types of cancer can be treated with our therapies, and identifying patients with those cancer types. We are glad to be advancing the trials of our flagship HMBD-001 therapy in Australia. By partnering with Omico, we are leveraging the PrOSPeCT platform to recruit patient populations precisely defined by novel biomarkers. By applying this approach with innovative clinical methodologies, we hope to efficiently deliver clinical proof-of-concept for HMBD-001, and eventually all our programs for hard-to-treat diseases.