Empty clinical research laboratory.
Empty clinical research laboratory.

A new biotech company gears up to target GPCRs with antibodies

The company plans to develop more specialized, antibody-based GPCR drugs to treat a myriad of diseases. They recruited a leader in overseeing successful clinical trials to get the job done.

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Marcella Ruddy, the newly appointed chief medical officer of the biotech start-up Tectonic Therapeutic Inc., has been busy for the past two decades. She oversaw nearly a dozen clinical trials at leading pharma companies, including Merck and Regeneron, before she was wooed to the shiny, new, start-up side of the industry.

Tectonic Therapeutic interested Ruddy enough to make the jump. The company develops antibody-based therapeutics targeting G-protein-coupled receptors (GPCRs), the largest and most diverse family of membrane bound receptors. As of 2017, approximately 475 drugs on the market or in clinical trials target GPCRs. Dysregulation of these receptors is connected to diseases including diabetes, Alzheimer’s disease, and cancer. 

Marcella Ruddy recently became the chief medical officer of the biotech start-up Tectonic Therapeutic where she will help develop clinical trials to test antibody-based drugs targeting GPCRs.
Marcella Ruddy recently became the chief medical officer of the biotech start-up Tectonic Therapeutic where she will help develop clinical trials to test antibody-based drugs targeting GPCRs.

There are an estimated 1,000 unique GPCRs in humans, so many drugs have off-target effects. Isolating individual GPCRs to characterize them is challenging though. Tectonic Therapeutic is developing methods to isolate GPCRs and develop more specific therapies. Ruddy wants to use the knowledge she gained in her former roles at pharma behemoths to lead Tectonic Therapeutic’s drug discovery program to success. 

How did you start working in the pharma industry?

I really loved taking care of patients as a pulmonologist and understanding how they deal with their medical problems in their daily lives. As I tried to prescribe my patients’ medications, I realized that there were limits to what is available therapeutically. I really appreciated this limit after I developed a cystic fibrosis translational research program at Massachusetts General Hospital while I was on staff. Working with the Cystic Fibrosis Foundation, I realized the need for therapeutics and got excited about being involved in clinical trials. Around that time, a friend asked if I would be interested in joining Merck. I was trying to do translational research at an academic center, but I knew I could do even more at pharma and biotech companies. I made that transition in 2004, and I’ve never looked back. It was the right fit.

What drew you to Tectonic Therapeutic?

I spent ten years at Merck and five years at Regeneron, which were both phenomenal experiences. At Regeneron, I ran one of the most exciting drug development programs in the respiratory immunology area, the dupixent program, which focused on developing a treatment for the inflammatory disorder chronic sinusitis with nasal polyps. 

Through that experience, I built a team that I was proud of; it felt like we accomplished an awful lot. I struggled to decide what the next stage of my career would be and determined that it was time to jump into the early biotech space. I was drawn to the idea of developing GPCR-targeted therapies. In a world of gene editing and cell therapies, it may not sound sexy, but it’s so important. The idea that we can target some of these GPCRs using an antibody approach was exciting. 

Since small molecules don’t effectively target GPCRs, the focus of the company is to build an antibody discovery platform. Researchers at Tectonic Therapeutic enhanced expression and purification of GPCRs in membranes, which was a huge stumbling block for drug development. They are making protocols to develop agonists and antagonists for GPCRs, isolate them, and pull antibodies from display libraries to find potent, functional GPCR modulators. They made a lot of progress in a tough business over a few years. 

Alise Reicin, the president of Tectonic Therapeutic, is an inspiring leader who I worked with at Merck. She really put a fun and successful team together to tackle these problems. I thought that this was the right team and the right science.

What did you learn from the dupixent trial that you will use at Tectonic Therapeutic?

Chronic sinusitis with nasal polyps is a disease driven by T Helper 2 (TH2) cell mediated inflammation that lasts longer than 12 weeks. Dupixent affects inflammation significantly. There were no other drugs approved for this disease that targeted both nasal polyps and the sinus disease associated with the polyps. The FDA wouldn’t approve us to test dupixent’s efficacy for both, but we had clinical data showing that we cleared up the sinus disease and the polyps. Even without approval, we ensured that our clinical program had the right endpoints to show that the sinuses improved in addition to the polyps.  

At the end of the day, even though the FDA initially said that they wouldn’t give that indication for the drug, they agreed. A lot of times in the past, I adapted the program to what the FDA told me. But if I know the disease and the drugs, build a solid argument, and develop the endpoints required, I can make better drugs. No one knows a program better than the team working on it.

What are you most excited to work on at Tectonic Therapeutic?

It’s amazing to join an organization this young. Sometimes people take things for granted when they inherit a department or a program where all of the processes are already in place. I can design the most streamlined, efficient processes. It challenges me to understand previous assumptions about why things are done a certain way at more established companies. How can I build — if not the best — a very efficient organization? It will be challenging to attract people to join our team since we’re so young. But we have an exciting idea, and we have experienced people already. It will be exciting to build that team and step up to that success. 

This interview has been condensed and edited for clarity.

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Tectonic Therapeutic is a new start-up searching for drugs that target a subset of receptors immune to small molecules: GPCRs.
Top Image:
Tectonic Therapeutic is a new start-up searching for drugs that target a subset of receptors immune to small molecules: GPCRs.
Credit: iStock/alvarez
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