A coming ‘renaissance in endocrinology’: A conversation with R. Scott Struthers, PhD
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CHICAGO — R. Scott Struthers, PhD, had a lab job synthesizing peptide hormones as a college freshman. That experience launched a career featuring discovery of novel agents for endocrine diseases, women’s health conditions and cancers.
“I would say the theme throughout my career, and our main interest, is around peptide hormones, which regulate on the order of 130 different receptors that we know about,” Struthers, co-founder and CEO of Crinetics Pharmaceuticals, told Healio. “Already a few of these became important drug classes ... but there are 100 others that have never been drugged yet control important parts of physiology and pathophysiology.”
Crinetics specializes in discovery and development of new drugs for rare endocrine disorders, such as acromegaly, Cushing’s disease and congenital adrenal hyperplasia. The company is also pursuing new therapies for obesity, diabetes and thyroid diseases, among others.
“You’ll see kind of a renaissance in endocrinology in the next 10 years,” Struthers said.
Struthers also served in leadership at Neurocrine Biosciences and co-founded and serves as chairman of Radionetics Oncology.
For his contributions to drug discovery and development, Struthers is the most recent recipient of the John D. Baxter Prize for Entrepreneurship from the Endocrine Society, presented at ENDO 2023.
Healio spoke with Struthers about his career, advice to medical students and his predictions for where the field of endocrinology will be in 10 years.
Healio: What was the defining moment that led you to your field?
Struthers: It was a convergence of a couple of things when I was a freshman at University of California, San Diego. I already liked chemistry, and I got a job in a lab doing synthesis of peptide hormones, which taught me about peptides and a little of endocrinology and the fact that scientists could contribute to human health. My grandmother was dying of cancer at the time, and it anchored the two things together for me. I’ve been working on that for the last 40-some years since.
Healio: What area of research in endocrinology most interests you right now and why?
Struthers: One of the great things about endocrinology is it controls almost every cell in the human body in one way or another. You don’t have to be too focused on one piece or get pigeonholed into one thing. But I would say the theme throughout my career, and our main interest, is around peptide hormones, which regulate on the order of 130 different receptors that we know about. Already a few of these became important drug classes — most recently, the ones around diabetes and obesity that are making the news every day are part of this family — but there are 100 others that have never been drugged yet control important parts of physiology and pathophysiology. From a scientific point of view, that’s my main area.
The thing that’s newer, now that I’m in this role at Crinetics and getting involved in patients and clinical outcomes, is trying to understand more about how we translate this science not just to hard outcomes in clinical trials, but to things that patients care about. One of our leading indications is a disease called acromegaly, which is characterized by too much growth hormone, and then another hormone it produces called insulin-like growth factor I. We manage the disease by looking at these IGF-I numbers, but from a patient point of view, it’s important that they’re more than just a number. It has to do with the symptoms they face, the burden of care they face, and these things are hard to measure and translate into drug development and regulatory outcomes. That’s a big challenge for the whole field.
Healio: What advice would you offer a student entering your field today?
Struthers: I get asked that quite a bit. I’ve done a number of trainee meetings and seminars at different universities, and I’m frequently asked what they can do to make sure they get a good job or get their career started. It’s the wrong question because they’re trying to succeed, they’re not trying to figure out what they want.
The real advice would be to figure out what they enjoy and love doing and care about. Passion is overused, but it’s true in this case. Then they can go figure out how to make a career out of it. There’s almost always an answer, especially in endocrinology, because endocrinology is everything. You could be a clinician, you could be a basic researcher, you can even study fruit flies and understand more about endocrinology. You can find a career that pays well and allows you to live in any of those areas, but go after what you like, what is important to you, and then figure out how to make it a career. Don’t put the career ahead of what you love.
Healio: What do you think will have the greatest influence on your field in the next 10 years?
Struthers: I’m a little biased, but drug discovery in endocrinology is starting to take off.
We’ll see a bunch of new therapeutic agents that can provide new or better treatments for endocrine and endocrine-related diseases. It’s going to affect how we practice medicine and patients’ lives. There’s going to be a whole wave of those over the next decade. I hope a lot of them come from Crinetics, and that’s certainly our goal, but the other thing is that it’s going to allow us to ask questions about human physiology and pathophysiology.
For example, one of our molecules is an antagonist of the stress hormone ACTH, or adrenocorticotropic hormone, and this is the central hormone in the stress response pathway. We’ve known about it for more than 100 years. I did a PubMed search this morning on ACTH, and there were 65,000 hits — just to give you a sense of the scope of the intellectual effort there. We’ve never had an antagonist to this hormone before that we can investigate in humans, and now this molecule that we’re looking at in phase 2 is allowing us to ask some questions about how this works. It’ll be important for patients with Cushing’s disease or congenital adrenal hyperplasia. What would be interesting is to see what the clinical researchers do with it in those other indications that we didn’t understand fully. You’ll see kind of a renaissance in endocrinology in the next 10 years.
Healio: What’s up next for you?
Struthers: I’m excited to take the things we’re good at and expand them into more and more areas. In discovery, we’re working on thyroid disease, diabetes and obesity, even polycystic kidney with an endocrine approach. Last year, we launched a new radiotherapeutics company using peptide hormone ligands to target radionucleotides to almost all different types of solid tumors. We’ll be getting clinical data from that and then next from several of those molecules in the next year and a half. There are almost more things to do than there is time in the day, and it’s hard to choose between them.
Obesity and diabetes are linked. There’s some interesting science going on there apart from these new agents. What I’ve said publicly is that it’s a space that we should be playing in, and we’ve started an initiative to make small molecule oral drugs for diabetes and obesity that have so far been well served with these peptide hormones. The news and publicity around these peptides, and just the shortages of the ability to make enough of them, is huge.
I don’t think that peptide hormone as a peptide drug that needs to be injected is an ideal solution for a large percentage of the population. It’s not meant for millions of people. I do think that small molecule oral drugs are the solution for not just some of the rare endocrine disorders that we’ve worked on so far, but some of the prevalent endocrine disorders that we’re starting to work on now.
In thyroid and thyroid eye disease, there hasn’t been a new drug for Graves’ disease itself since 1946. There’s been a lot of excitement about the new drug Tepezza (teprotumumab-trbw, Horizon Therapeutics) for thyroid eye disease. There’s still just a fraction of patients with Graves’ disease, so we’ve got a project to go after both Graves’ and Graves’ ophthalmopathy. There are opportunities in oncology where these tumors have co-opted peptide receptors to help them grow or survive. If we can use our drugs strategies to treat these tumors, it’s a whole new set of targets that most of the oncology field is ignored.
Reference:
- Endocrine Society awards Baxter Prize to innovator in endocrine drug discovery. www.endocrine.org/news-and-advocacy/news-room/2023/endocrine-society-awards-baxter-prize-to-innovator-in-endocrine-drug-discovery#:~:text=Scott%20Struthers%2C%20Ph.,diseases%2C%20the%20Society%20announced%20today. Published Jan. 25, 2023. Accessed Jan. 26, 2023.
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