People-Focused Drug Development: Meeting the Challenge

By Heike Blockus, Ph.D., Senior Scientist, Verge Genomics

Challenges – personal and professional – exert a strong pull over me. As a teenager, I lost my mother to cancer. Her physicians lacked targeted medicines and a deep molecular understanding of her disease. This drove me to pursue a scientific education and career, and I was especially drawn to neuroscience, a field that often seems too complex for humans to fully understand.   

I joined Verge Genomics after spending many years in academia studying the mechanisms of memory in the mammalian brain. I wanted to change from this kind of basic research in animal models to something that had a greater positive impact on people dealing with illnesses with high unmet need such as amyotrophic lateral sclerosis (ALS). Working at Verge means being closer to people who need therapies to slow, halt or even reverse their disease. It also comes with a profound responsibility to put people at the center of all we do.

For us this is more than lip service. First, it’s the core of our scientific foundation: an all-in-human platform built on patient tissues and patient-derived cell cultures. Second, we listen to patients, caregivers, advocates and physicians about what matters most to them and what they need. What have they told us?

From people with ALS, we’ve learned they aren’t looking only for a therapeutic “home run” or cure: given how aggressively ALS moves – it’s usually fatal in 3-5 years – patients and their caregivers would be grateful for a treatment that prolonged survival and quality of life.

A key challenge in discovering new medicines is that we still lack a critical understanding of the mechanisms underlying neurodegenerative diseases.

As my academic work revealed, the human brain has evolved uniquely in the animal kingdom. Yet traditional preclinical research relies heavily on animal models that do not always faithfully represent the features or mechanisms of the disease in humans, especially in the brain. Verge aims to change all of that with our all-in-human platform.

The Verge platform begins with patient tissue samples that we analyze with machine learning techniques to identify dysregulated networks of genes. These networks enable us to find biological “master regulators” that traditional target discovery approaches may have missed. We then validate these master regulators as drug targets in patient-derived brain cell cultures. We believe this approach may bear the potential to avoid many of the clinical failures of the past, which have resulted from an over reliance on animal models.

Patients also inform our approach to clinical studies through discussion forums with people with ALS and their caregivers. Hearing their stories is eye-opening. For example, in the ALS community today, there isn’t much optimism about clinical trial design and access. These insights will help us be patient-centric as we plan to enter clinical trials later this year with Verge’s lead program targeting ALS.

Another example? When we procure patient tissue from brain banks, we often talk to physicians and neurosurgeons who know the patients personally and are eager to learn the results of our studies. It is both humbling and inspiring to see the excitement that patients, caregivers, and advocates have around our approach, and the hope it gives people who are so deeply affected by diseases like ALS. When you get this kind of feedback, you know you’re doing something truly important, and I think about this every day in my work.

This is an exciting time and place to work in neurodegenerative diseases, not only because our challenging work of unraveling the complexities of these diseases is beginning to bear fruit, but also because Verge’s commitment to patients is reflected in every aspect of what we do. This boldness, this commitment – this is exactly why I came to Verge. If you'd like to learn more about what Verge has to offer, check out our job openings https://bit.ly/3Ky4QiU.