Longevity biotech exclusive Q&A with Cambrian Biopharma’s CEO – hallmarks of aging and classifying aging as a disease.
Dr James Peyer is Cambrian’s CEO and Co-Founder; he has spent his career actively finding ways of preventing people from getting diseases like cancer and Alzheimer’s, rather than waiting for disease to come calling, a philosophy he is continuing at Cambrian.
Longevity.Technology: Peyer co-founded Cambrian along with seasoned biotech investor and entrepreneur Christian Angermayer, who serves as Cambrian’s chairman. While in stealth mode, the company raised $60 million from a syndicate of long-term investors, and is setting about creating a longevity R&D company across its series of pipeline companies.
“Over the next decade, Cambrian aims to detect and prevent aging-related diseases before they take root,” said Peyer. “Much like scientists were able to prevent and reverse lethal diseases like smallpox and polio in the 20th century, we are inspired to lay the foundation for conquering today’s most devastating diseases at the onset of the 21st century.”
Cambrian scientists are targeting the nine hallmarks of aging, but there has been some discussion about a tenth hallmark of aging, whether extracellular matrix stiffening and crosslinking or controlling splicing regulation. Is this a debate Cambrian is keeping a close eye on?
“Absolutely – it’s an important question,” says Peyer. “ECM stiffening was, I think, unintentionally omitted from the 2013 Cell paper because it’s harder to measure and talk about in the context of aging. There was a very thoughtful paper that made this case that came out last fall from Alex Fedintsev and Alexiey Moskalev and Cambrian is thinking very carefully about how the ECM changes as we age.
“I believe that the entire discussion about whether aging should be considered a disease is actually little more than a distraction from the real, more technical issues standing in the way of getting a medicine that enhances healthspan from being approved for that use.”
“Splicing is a bit more difficult to quantify, I think the debate there is still in its infancy and more at the academic level. We’re watching the space very closely, but drugs targeting splicing factors are just beginning to enter development in oncology and other areas, adding to the degree of risk to develop such a drug first in the longevity space.
“More generally – I think it’s important to remember that the 9 Hallmarks of Aging are a guideline, not a hard and fast set of rules. They serve as a way of categorizing the pathways that contribute to aging, and have helped reinforce the very important view that there is not a single cause for the decline of our bodies. Pathways that become dysregulated as we age and contribute damage to our molecular, cellular, or organ systems as we age can be flexibly included into the Hallmarks of Aging thesis without much twisting and turning.
“Putting these pieces together as a small final point, the 9 Hallmarks we use to think through the geroscience space within Cambrian actually are slightly rearranged from the original 2013 categories – we included one for ‘Disrupted Tissue Architecture’ which includes ECM damage.
“One of the most valuable learnings from the pioneering work of Nir Barzilai on the TAME trial and other conversations with the FDA has been that building a composite chronic disease endpoint is already acceptable to the FDA”
Following on from that, we wondered what Dr Peyer’s views were on classifying aging itself as a disease?
“I have a somewhat controversial view on this amongst folks in our field,” says Dr Peyer. “I believe that the entire discussion about whether aging should be considered a disease is actually little more than a distraction from the real, more technical issues standing in the way of getting a medicine that enhances healthspan from being approved for that use.
“Many of my colleagues advocate in good faith that this would be a key inflection point for the field, and I used to believe the same. However, the more I have come to understand about the way that these drugs would be regulated in the future, the less concerned that I am with worrying about categorizing aging as a disease.
“I do absolutely think that it is appropriate and proper to classify the build-up of damage that accumulates during aging as a disease. There is already a gray area about when other conditions are labeled a pathology vs not a pathology. We have categorizations for pre-diabetes, mild cognitive impairment, benign tumors, and high cholesterol. Are these conditions diseases? I would argue that it’s not important what we call it. What is important is the following: (A) Can we run a clinical trial to address the condition and (B) would health insurance companies provide such a medicine to its patients?
“One of the most valuable learnings from the pioneering work of Nir Barzilai on the TAME trial and other conversations with the FDA has been that building a composite chronic disease endpoint is already acceptable to the FDA. Building a drug that reduces stroke and heart disease risk (what the statins were approved for) has been acceptable to the FDA for ~20 years. Building a drug that reduces heart disease, stroke, Alzheimer’s, cancer, and diabetes risk is also acceptable. What would change in this context if the regulators labeled aging a disease? Nothing. We just have to do the trial to show that such a drug is actually working. The path is already there for us. The real challenge is how we design and power these trials and whether we can use biomarker-based endpoints to make the iteration time of testing these medicines shorter.
“This is actually a very optimistic view, it means that there’s not a popular opinion or political barrier that we have to break down to get healthspan medicines onto the market.
“To borrow a now dated pop culture reference:
Skeptic: Not everyone believes as you believe.
Geroscience: My beliefs do not require them to.”
Catch our interview with Cambrian’s COO, Dr Juliette Han here.