Tackling Fibrosis and Cancer: A Conversation with John Hood, Co-Founder and Chief Executive Officer of Endeavor BioMedicines

In celebration of Healthy Aging Month this September, we are pleased to feature an exclusive interview with John Hood, CEO of Endeavor Biomedicines. A successful serial entrepreneur and accomplished drug hunter, John brings decades of experience and a deep passion for advancing new medicines for patients. Fresh off the heels of their recent $132 million Series C financing, Endeavor Biomedicines is at the forefront of developing innovative therapies for idiopathic pulmonary fibrosis (IPF) and cancer, diseases that disproportionally impact the aging population. 

John, congratulations on your recent $132M series C financing. Can you start by sharing with our audience why IPF and cancer are particularly relevant to the theme of healthy aging?

John Hood: Thank you for having me. As you said, we just completed a $132 million Series C financing, led by a syndicate of top-tier investors. The new funding will help us advance our pipeline in idiopathic pulmonary fibrosis and cancer. Both IPF and cancer disproportionately affect older adults. IPF primarily affects individuals between 50 and 70 years old, and its progression is influenced by age-related changes like telomere shortening and cellular senescence, which compromise lung repair. Similarly, the risk of developing cancer increases with age due to accumulated genetic mutations and a decline in immune surveillance. We are developing medicines designed to target the underlying causes of these diseases. We are excited about their potential to address significant health challenges. 

Let's talk about your lead program ENV-101. How does it work, and what makes it a promising treatment for IPF?

John Hood: ENV-101 targets the Hedgehog signaling pathway. We believe that it has the potential to improve lung function and reverse the fibrotic process in the lungs of individuals with idiopathic pulmonary fibrosis.

Our recent Phase 2a study showed the first evidence of any agent in IPF to potentially reverse the disease. That hasn't been seen before, and it was seen in multiple endpoints, lung function, as well as the lung architecture itself. We believe that this is a big step forward for patients with IPF and potentially any deadly fibrotic disease. IPF was our first foray into fibrotic diseases, because it’s a horrible disease with a five-year survival that’s worse than many cancers. There are limited treatment options for patients with IPF. The treatment options that are available may incrementally slow the rate of lung fibrosis; however, none have been shown to halt or reverse IPF disease progression. 

We’re initiating a global Phase 2b study with ENV-101 in IPF. As a company, we are focused on getting ENV-101 through the clinic and in the hands of patients as quickly as possible. 

What are some unique challenges you are facing?

John Hood: For IPF, it's interesting because it's one of the more prevalent rare diseases, with roughly 150,000 individuals in the United States affected. Nonetheless, recruiting those patients is quite difficult. These patients tend to be very sick. There's a lot of issues you have to address in terms of comorbidities and concomitant medications to make sure that any benefit or adverse events seen in your clinical trials are due to your drug and not background therapies or background disease.

How are you going to address this clinical trial challenge? 

John Hood: We plan to conduct the Phase 2b trial of ENV-101 globally in at least a half a dozen countries. We work closely with our clinical CRO to open trial sites and enroll and treat patients. We have a team of in-house Clinical Research Associates (CRAs) that support the trial sites. Any site can reach out to someone in-house at any time to discuss their experiences or address any issues they may encounter. We're building out this capability because I believe it's crucial for sites to have direct access to our in-house support to guide them through the patient recruitment and treatment process.

It takes a global village to develop a drug. 

John Hood: Yes. A good partner brings strengths and capabilities that we don’t have internally. We're a small company. The majority of our employees are focused on clinical development. It would be cost prohibitive for us to build a manufacturing and chemistry site internally. Why do that when you can partner with a company like WuXi AppTec? They have been a trusted partner for me going on two decades now. Time is often the biggest asset and I’m confident in WuXi AppTec to deliver drug product on time and at a high quality. Beyond that, as I mentioned earlier, we partner with clinical CROs who bring boots on the ground in other countries, which is super important. We try to build out the clinical side as much as we can, but we can't have an office in every country.

Your other program is ENV-501 for cancer indication. How does it fit into your ambition?

John Hood: Cancer is very much a disease of aging. It's driven by an accumulation of mutations that tend to occur much more often in the aging population. At Endeavor, we're developing ENV-501, a next generation antibody drug conjugate or ADC. We’re focused on a target called HER3, which is more commonly expressed on tumors than HER2. Clinically, ADCs have been successful in targeting multiple tumor types, but not without significant treatment-emergent side effects. We see this as an opportunity to target tumors in a different way by leveraging the effectiveness of ADCs while limiting the off-target toxicity seen in first generation ADCs. We’ve engineered ENV-501 to minimize the potential for off-target toxicity of the drug. In doing so, we believe that ENV-501 may have an improved safety and tolerability profile, which will give us an opportunity to go after cancers that are common in aging patients.

Thank you, John, for sharing your insights and the exciting work at Endeavor BioMedicines. It's encouraging to see innovative approaches like yours to tackling age-related diseases.

John Hood: Thank you. There are few enterprises you could get into that are more challenging than developing new drugs for patients. It's incredibly rewarding, because you see people live longer and feel better if you develop a novel medicine that treats the underlying causes of these diseases. The amount of work you must do is massive. It takes a village of dedicated people who really want to help patients live longer, more productive lives.