Developing Therapies for Treatment Resistant Cancers: Q&A with Russell Hayward

Russell Hayward
CEO
Etira

Russell Hayward, CEO of Etira, recently spoke with Pharmaceutical Executive about recent developments with his company. Etira announced that Dr. Annalisa Jenkins and Dr. Justin Stebbing would be joining the company’s board, which provides insight into the direction that the company hopes to take its research into treatments for treatment-resistant cancers.

Pharmaceutical Executive: Can you describe recent advancements in developing therapies for treatment-resistant cancers?
Russell Hayward: Tumors evolve to adapt, mutate and evade the immune system, making it challenging for treatments to achieve long-term effects. There is a significant unmet need for therapies that provide durable responses to metastatic and some of the most aggressive cancers.

Metastatic tumors are not made up of single cell types, they are a complex conglomeration of different cell types. Many current targeted therapies are focused on specific genotypes, phenotypes or mutations which typically impact only one cell type. While these can be highly successful at treating that cell type inside a tumor, the heterogeneity of cells in tumors allows other cells to mutate around therapies and proliferate, causing tumor heterogeneity to be the single largest barrier to long term durable cancer therapy.

Our novel cancer treatment is the first of its kind to address tumor heterogeneity by exploiting a fundamental vulnerability present in a vast number of cancers, especially those that are resistant to current treatments.This is the high basal level of endoplasmic reticulum (ER) stress existing in cancer cells due to the voracious appetite they have for correctly folded proteins. Our first therapy, ERX-315, selectively targets lysosomal acid lipase (LIPA) in the ER to induce catastrophic levels of ER stress in cancer cells, leading to cell death through apoptosis. Importantly normal cells are left unharmed.

PE: What made Dr. Stebbing a good candidate for your board?
Hayward: When we set out to build our Board of Directors, we aimed to bring on an innovative key opinion leader with a strong background in oncology research and clinical trials. We were introduced to Dr. Stebbing in 2023, who had already reviewed our groundbreaking paper published in Nature Cancer. Intrigued by our innovative science and our unique approach to drug development, Dr. Stebbing was excited about joining us on this journey.

As Editor-in-Chief of Oncogene and a leading figure in oncology, Dr. Stebbing has extensive experience reviewing cutting-edge cancer research, giving him a unique ability to critically assess and opine on our science. His deep background in clinical trials has also been essential in supporting the design of our Phase 1 study. Dr. Stebbing’s insights and expertise make him a valuable addition to our team and has already provided great expert guidance insight to Etira since he joined our board.

PE: What made Dr. Jenkins a good candidate for your board?
Hayward: With Dr. Stebbing on the Board of Directors, we sought to add an expert with a deep background in drug development to help guide the company’s strategy as we move throughour next stage of development, clinical trials. Having served as a board member and advisor to numerous life science companies at similar stages to Etira,Dr. Jenkins understands where we are in our life cycle and the various forward paths available to us.

Furthermore, her experience as Global Head of Drug Development at Merck Serono and Bristol Myers Squibb, along with her role on the Science Board of the U.S. Food & Drug Administration, gives us invaluable insights as we plan, strategize and analyze current and future clinical trials.

As a former CEO who led a successful exit to a major pharmaceutical company, Dr. Jenkins offers critical guidance on positioning Etira for potential future partnerships. Her insights and role as a trusted advisor have been instrumental in shaping our strategic decisions as we enter this next phase of growth.

PE: How are therapies like ERX-315 advancing and changing the landscape for cancer care?
Hayward: ERX-315 represents a breakthrough approach as the first treatment specifically designed to address tumor heterogeneity. ERX-315 stands alone due it’s unique combination of a novel molecular target and mechanism of action making it highly specific and cytotoxic only to cancer cells, sparing normal cells. Traditional treatments such as chemotherapy attack healthy cells and cancer cells making it a highly toxic therapy which many patients cannot tolerate. Our new approach could represent a paradigm shift in cancer treatment.

ERX-315’s mechanism is effective across various cancer types. High basal levels of ER stress and elevated expression of our molecular target, LIPA, are found in the many different cancer types enabling ERX-315 to engage a new cancer cell death pathway. This novel approach does not interfere with healthy cells or existing cellular pathways enhancing its suitability for combination therapy, potentially increasing overall efficacy.

With promising preclinical efficacy shown in metastatic breast, pancreatic, liver, endometrial, and ovarian cancers, we also see opportunities for ERX-315 in many other indications.

We believe ERX-315’s ability to target a vast majority of cells within a tumor reduces the likelihood of a cell developing resistance to the therapy, offering renewed hope as a durable option for patients who have exhausted other treatments. If successful in clinical trials, ERX-315 has the potential to redefine outcomes for those battling even the most challenging cancers.