Is There a Relationship Between Aging Mechanisms and Lifespan?

Gene therapy screening to discover aging targets (Martin Borch Jensen -  Gordian Biotechnology)

Gordian Biotechnology is a San Francisco Bay Area biotech company that has created the first in vivo therapeutic screening platform aimed at drug development for complex diseases of aging. Co-founder and Chief Science Officer, Dr. Martin Borch Jensen joins the show today to discuss Gordian’s unique in vivo pooled screening in animals, as well as which indications they are targeting, their strategy to bring drugs to market, and how Gordian is currently tackling the challenges inherent to animal models. Martin also speaks about his passion from an early age to help fight age-related disease, and making the transition from academia to entrepreneurship, giving up a K99 fellowship at the Buck Institute for Research on Aging to make the jump into biotech.

You’ll also hear about Martin’s involvement in multiple efforts to promote longevity science and bring new people into the field, including his apprenticeship program, the newly announced Longevity Impetus Grants program, and recording his “Science of Aging” seminar. Next, Martin shares what’s next for Gordian as they get ready to scale to the next level, which areas of longevity science he is most interested in but not currently working on, and how he predicts the field will evolve over the next five to ten years. For more information on Martin’s apprenticeship program and Impetus Grants application process, please visit MartinBorchJensen.com or follow him on Twitter.

Episode Highlights:

• Dr. Martin Borch Jensen is the co-founder and CSO of Gordian Biotechnology
• Gordian Biotechnology created the first in vivo therapeutic screening platform to radically improve drug development for complex diseases of aging
• Martin is also involved with an apprenticeship program and a newly announced grant program to catalyze rapid progress in aging research
• How Gordian’s unique in vivo pooled screening in animals works
• They’re focused on removing the diseases of aging, beginning with their three lead indications, NASH (nonalcoholic steatohepatitis or fatty liver), osteoarthritis and idiopathic pulmonary fibrosis
• How Gordian compiles their gene libraries
• While other companies start with in vitro models and then figure out ways to test them in living animals, Gordian starts with the second step 
• They deliver hundreds of gene therapies at once to a single animal
• The drugs that they ultimately develop won't necessarily be gene therapy, but instead whatever is most appropriate to pursue the indication once they know the target (small molecule drugs, antibodies)
• What a cell needs depends on what a cell is
• Gene therapy has plenty of advantages, but the cost is very high
• How Gordian is overcoming challenges that are inherent to animal models
• Older mice are much more expensive and are rarely used in aging research
• Animal models can actually be useful if the animal has progressively developed a disease in the same way humans do, and has similar biology
• Example of studying osteoarthritis in horses, because the load-bearing structure of their joints is much more similar to humans, as is their cartilage thickness
• Gordian’s strategy to bring drugs to market
• Martin’s transition from academic to entrepreneur and what inspired him make the jump to biotech
• He gave up a K99 fellowship at the Buck Institute for Research on Aging
• He realized as a teenager that he wanted to try to fix aging
• Martin is good friends with Dr. Kristen Fortney, co-founder and CEO of BIOAGE; her journey showed him that it was possible to start his own company
• Martin is also involved in multiple efforts to promote longevity science, and to bring people into the field
• His apprenticeship program was developed as a way to bring people in, and train them to be able to work on direct projects
• Longevity Impetus Grants is a $21 million (update: $26 million as of the release of the podcast) program that provides funding for scientists to start working on what they consider the most important problems in aging biology without delay
• This was inspired by COVID-19 “Fast Grants,” created by Tyler Cowen, Patrick Collison, and Patrick Hsu
• Their goal is to take big bets on projects that could move the field forward, and recipients will be able to publish their findings regardless of what their results are
• Impetus Grants applications open on Monday, September 13, 2021
• Martin also recorded a comprehensive seminar about the science of aging
• What’s next for Gordian as they get ready to scale to the next level
• Martin predicts that in 5-10 years, we will have ways of measuring biomarkers for aging in humans

Quotes:

“It's phenotypic screening, but also because it's gene therapies we're putting in, we know the target immediately. So I call it ‘pheno-target screening,’ combining the best of both discovery modalities that are used.”

“At Gordian, we're focused on removing the diseases of aging. Right now we're doing that with three lead indications, and that number will grow, which are NASH and osteoarthritis and idiopathic pulmonary fibrosis.”

“We've created the platform in order to be able to do somewhat unbiased screens or entirely unbiased screens, and just explore a lot more of the biology of these diseases than has ever been explored in vivo so far, because we have this higher throughput.”

“The logistics of the other method simply don't allow you to test a wide range of things in the in vivo context.”

“I'm very excited about gene therapy in the long run to treat aging, diseases of aging, and just the physiological processes of aging. Because it turns out that what a cell needs depends on what a cell is. And so you probably don't want the same treatment in every type of cell in your body.”

“You need a targeted way to go in and give each type of cell and each tissue what it needs, if we're going to really exercise control over the aging process.”

“Maybe animal models aren't so bad for many diseases, if you find an animal that has continuously developed, progressively, a disease in the same way that humans develop this disease, and has biology that resembles human biology and the relevant organ.”

“We are a drug development company. We've developed this in vivo full screening platform in order to use it ourselves and discover the best drugs for each of the indications that we go into.”

“We are in conversations with a whole bunch of pharma companies about partnering at the clinical stage around the assets that we are discovering with our platform.”

“As a teenager, I came to the realization that I wanted to try to fix aging… The idea that everyone is going to get sick and be in pain, and then die, just seemed really bad.”

“I wanted, with Gordian, not only to have the successful outcome of treating age-related diseases, but I also wanted to feel for myself that I was doing absolutely everything that I could towards the goal that I had decided.”

“It's going to be really hard. There's going to be doubts and challenges… And so if you're doing it for reasons that won't compel you to push through all of that, it's probably not going to work out.”

“[This apprenticeship program] is needed, because there are more things that should happen, and apparently could happen, than I could possibly ever go and do myself.”

“The apprentices end up doing most of the legwork by far. And I'm kind of steering it.”

“This is the real test of success for this apprenticeship - if the people in it end up running important projects within the longevity field overall, then it's a success.”

“If there is something there, if the project does work out, that would actually be a really big push forward for the field, then we should try to fund those things. And many of them won't work out and that's okay. We can learn from that.”

“Any nonprofit can apply from anywhere in the world. Or any researcher at a nonprofit.”

“What you really have to explain to us is, How is what you're doing going to move the field forward, if it works, and why is the way that you're doing it, a good, robust, well thought-out experimental plan for doing it? Those are the main things that we look for.”

“In five to 10 years, I think we will have drawn studies for biomarkers of human aging. So I think that in five to 10 years -hopefully more like five - we will have ways of measuring in humans, something that we choose to call aging.” 

Links:

Email questions, comments and feedback to podcast@bioagelabs.com

Translating Aging on Twitter: @bioagepodcast

BIOAGE Labs Website BIOAGELabs.com

BIOAGE Labs Twitter @bioagelabs

BIOAGE Labs LinkedIn

Martin Borch Jensen Website MartinBorchJensen.com

Martin Borch Jensen on Twitter: @MartinBJensen

Longevity Impetus Grants Website ImpetusGrants.org

Gordian Biotechnology Website Gordian.bio