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Welcome to BIOTECH NATION !!! With understandable interviews requiring no background in science, BTN attracts a wide global audience. From everyday people looking for hope in treatments in development, to bioentrepreneurs interested in the experience of their fellow travelers, to venture capitalists looking for possibilities in cutting-edge breakthroughs, to scientists simply interested in the work of others, BioTech Nation is the voice of human endeavor, driving science to new realities for everyone. These interviews are drawn directly from the public radio program, "Tech Nation", which also can be heard in numerous global radio and podcasting venues.
The world we know is changing. I'm Moira Gunn, and welcome to Biotech Nation. Science is not only figured out when our genes are working at their best, it's also figured out which genes start not working so well. You know, under producing some proteins you need or overproducing others. What if you could keep your protein production right where it ought to be?
Dr. Moira Gunn:Doctor Noah Davidsohn is the cofounder and chief scientific officer of Rejuvenate Bio. Doctor Davidsohn, welcome to Tech Nation.
Dr. Noah Davidsohn:Thank you for having me.
Dr. Moira Gunn:Now one of the notes I wrote down when we spoke earlier was this, in general, everything gets worse as you age. No kidding. I know what you mean. Now now give us an example in humans. What gets worse as we age?
Dr. Noah Davidsohn:Generally, the body's ability to heal itself and to regulate protein expression. So this manifests itself in a number of different diseases like heart disease or liver disease or kidney disease because the proteins are becoming out of whack with each other.
Dr. Moira Gunn:So our cells are producing, proteins. Sometimes now they start generating too many, sometimes too little. I know I wrote down here that a, the number of proteins in a young liver cell is greater than the number of proteins in an older liver cell. So that means that those protein they're generating fewer than they did before.
Dr. Noah Davidsohn:It depends on the protein. Some proteins get more and some proteins become less than they should be. And what we try to do with our therapy is we try to take the proteins that have accumulated too much and turn them back to their ideal level and the proteins that are too little and make them more so that they're their ideal level. And so protein regulation, the balance of the different proteins is really key here.
Dr. Moira Gunn:Now some people inherit genes, for and they come from very long lived families. Is it fair to say that not everyone's genes are created equal?
Dr. Noah Davidsohn:That is fair to say. Some people definitely, quote, unquote, age slower than others, and you can see that when people are still running marathons well into their 80s, whereas other people are having a hard time getting around. And they're just able to maintain the proper balance of the different proteins in your body for a longer period of time to forestall a lot of the negative effects of aging.
Dr. Moira Gunn:Now I understand that that science has figured out that there are 3 primary genes that that drive health. And and let's talk about each of them. We're gonna call, the first one gene number 1, and I guess it's fgf21. What does that do?
Dr. Noah Davidsohn:Yeah. Gene 1 or fgf21 is involved in metabolic processes. And it increases when you exercise and everyone tells you that exercise is good for you. That's because FGF 21, gene 1, is being produced in larger quantities, and it has very beneficial effects throughout your body. And as you age, you generally have less of gene 1, and we're trying to return it to its better state in more quantities.
Dr. Moira Gunn:Okay. Now gene number 2, TGF Beta 1. I think everybody's figured out while we're naming this gene 1, 2, and 3 here. Okay. TGF beta 1.
Dr. Moira Gunn:What does that do?
Dr. Noah Davidsohn:TGF beta 1 is involved in inflammation and fibrosis. So if you have damage to any part of your body, this protein will be expressed and will be part of the healing process. But too much of it is bad. That's when you get scar tissue and fibrosis. And so what we try to do with gene 2 is actually decrease gene 2 over time and try to bring it back to a healthy level.
Dr. Moira Gunn:And now does exercise affect gene number 2?
Dr. Noah Davidsohn:Generally, exercise decreases inflammation in the body and will decrease gene 2, but we need something stronger to reduce gene 2 even more. And that's where our therapies come in. We can't really produce enough gene 1 and decrease enough gene 2 through with just exercise by itself.
Dr. Moira Gunn:Okay. So we're still rooting for exercise here. Still rooting for exercise.
Dr. Noah Davidsohn:It's still beneficial.
Dr. Moira Gunn:No beneficial. Okay. Now gene number 3 is called alpha clotho. Clotho is k l o t h o, alpha clotho. What does gene number 3 do?
Dr. Noah Davidsohn:Gene number 3 is generally cell protective. It is produced from the kidneys and is beneficial for other cells in your body. It will protect your your knee joints. It will protect your heart. It will protect your kidneys.
Dr. Noah Davidsohn:It's just a generally protective gene.
Dr. Moira Gunn:Oh, boy. This really is the 1, 2, 3. You you've said everything that seems to go wrong when you age. So I'm like, oh, yeah. All those three things corrected sounds good to me.
Dr. Moira Gunn:Now I know that before you founded REJUVENATE, you were a research scientist at George Church's lab at Harvard Medical School and the Wyss Institute. And George Church, if you don't know, very well known, very famous geneticist, is also a cofounder of REJUVENATE Bio. Just full disclosure full disclosure there. My question is is I know you were working in the lab doing a lot of science, and now we're creating these drugs. Are you specifically engineering these genes to do what we were just talking about, to restore this balance of either overproducing or underproducing, correctly producing the gene expression?
Dr. Noah Davidsohn:Yeah. We are using a technology called AAV, adeno associated virus. It is a way to deliver these genes into your body to bring them to the correct levels. So just think of them as a special mailman and a single one time injection can restore these levels to their store these genes to their appropriate level.
Dr. Moira Gunn:Permanently?
Dr. Noah Davidsohn:Hopefully. So far, we other people that use this technology have seen these genes work for greater than 12 years from a single injection.
Dr. Moira Gunn:Okay. Now let's talk about what, REJUVENATE is is doing. You have 2 drugs, the first two drugs in your pipeline, that you're developing right now. The first one is delivering a mod modified gene 1 and gene 2. We'll call it the gene 1, 2 combo.
Dr. Moira Gunn:And the second one is delivering a modified gene 2, gene 3 combo. Why the combination?
Dr. Noah Davidsohn:Aging is very complex. It is not a single gene problem, and the diseases of aging are similarly complex. And so what we try to do is simultaneously tackle a number of the problems at the same time. So the gene 1, 2 combo is functioning, the fibrosis and scar tissue and inflammation, as well as your metabolic health. Think type 2 diabetes and general obesity and overweight.
Dr. Noah Davidsohn:And so at the same, with one therapy, we can treat multiple different age related diseases.
Dr. Moira Gunn:So gene 12, I see is the cardiac, metabolic condition, kidney condition. But then when we go to gene 23, we're getting more into the inflammation and that those kind of conditions. Is that right?
Dr. Noah Davidsohn:Yeah. We, published a paper while I was in George's lab that showed that the gene 1, 2 combination can treat heart failure, kidney failure, diabetes, and obesity. And the gene 2, 3 combination can treat, heart failure, kidney failure, and osteoarthritis. And the osteoarthritis drivers of aging, that you actually can treat multiple different these drivers of aging that you actually can treat multiple different age related diseases with a single combination treatment.
Dr. Moira Gunn:Now these genes are additive. And by that, I mean, whatever you're producing, you're producing. So it's introducing an additional gene regulation, capability to your body. Otherwise, why don't you just give people every you know, the correct amount of gene 1, 2, and 3?
Dr. Noah Davidsohn:Yeah. The it's slightly more complex, but Darn. Darn. In general, your body, is constantly breaking these proteins down, and so we need to be constantly producing these proteins or getting rid of them depending on which if it's gene 1 or gene 2 or gene 3. Gene 1, we want more of, Gene 2, we want less of.
Dr. Noah Davidsohn:And so we wanna continually make more gene 1 and continually make less gene 2. And so our gene therapy delivers DNA to accomplish that task.
Dr. Moira Gunn:So if you have proteins that are already being delivered appropriately, then there's no reason to mess with that, to add any more gene expression to it.
Dr. Noah Davidsohn:True. If you're in the best health of your life, you will have the right amount of all these genes. But as you age, they become dysregulated, and you get the wrong amounts. And so we restore the correct amounts using these gene therapies.
Dr. Moira Gunn:Now these are all in preclinical, which means you're getting you're doing all this work to get them to be first in human. And so you have a big and fascinating road ahead of you. But I do wanna stop here because dogs have genes too and dogs age. And you're already in dogs. What are you doing in dogs?
Dr. Noah Davidsohn:Yeah. It's great that you mentioned that because dogs do have a lot of the same age related problems that humans do, and they also share our environment. They eat the same food a lot of the times. And so being able to treat the different diseases of aging in dogs is a real good indicator that we'll be able to treat similar human diseases. At Tufts University, we have a trial ongoing where people's pets that have mitral valve disease, came in and got the single one time injection of our therapy for gene 1, 2.
Dr. Noah Davidsohn:And we're seeing very promising results in those dogs for mitral valve disease. And we have the therapy in dogs now close to 3 years where we're seeing a benefit from a single injection.
Dr. Moira Gunn:From a single injection. And you're looking to expand that study, not by much, but by some. Let's tell people about that.
Dr. Noah Davidsohn:Yeah. That's correct. We're looking to expand the study. Another 10 dogs. It's run out of Tufts Veterinary School.
Dr. Noah Davidsohn:So you have to be in the Boston area to be part of this trial, and we're looking to enroll 10 more dogs.
Dr. Moira Gunn:Is there any overlap? Can we learn anything? What what's happening in the dog study for treating humans?
Dr. Noah Davidsohn:I think the dogs are a very good indication that this therapeutic will be beneficial to heart disease in humans. We're going into a different heart disease in humans than we did in dogs. But because they share similar paths to heart failure, they both have fibrosis, scar tissue in the heart. Their heart stops functioning as well. And even though the diseases are different, they share common pathways, similar to the way dogs and humans share similar aging problems and diseases of aging.
Dr. Noah Davidsohn:And so seeing a benefit in these dogs is a very good chance that we will see a benefit in humans.
Dr. Moira Gunn:Now you also now have a third drug you're working on, completely different genes than gene 1, 2, and 3. And and what is that, and what are you trying to do there?
Dr. Noah Davidsohn:Yeah. It is a more powerful therapy and that it can actually reverse the state of the cell. We had a preprint that we published in early January where we showed that we were able to reverse the age of the mice and make them live longer and healthier. And the goal for us for this therapy is to treat some of the harder diseases associated with aging that humans have, like Alzheimer's or frontal temporal dementia, where we haven't made many inroads into treating these diseases. But what we would like to do is actually reverse the disease altogether and bring your brain to a state that it was better than before it actually had that disease.
Dr. Noah Davidsohn:So get rid of the disease completely. Reverse.
Dr. Moira Gunn:What about the rest of my body? I'm always interested in me. What about the cells in the rest of my body? Could is there a chance you could reverse those?
Dr. Noah Davidsohn:Yes. The development path for this is, very long, but I think generally we, the goal is to apply it to every cell in your body. But, since science is very complex and we have to show incremental progress, we would first go after one disease in one, indicate in one tissue and organ, and then we'd go after another disease and another tissue and organ, and then we'd be able to, have many different tissues and organs and diseases that we can go after with a single therapy. So, our first therapy that has So, our first therapy that has gene 1 and 2, these proteins go around your whole body. So we don't need to slowly go from one tissue to the next, but the more powerful therapy for these new set of genes actually goes into every single individual cell.
Dr. Noah Davidsohn:And so we need to slowly build up that repertoire of tissues and organs that we're able to treat.
Dr. Moira Gunn:No. I haven't got that kind of time. Oh, no. I'm good.
Dr. Noah Davidsohn:I think it will be fairly quick. I think in the next 3 to 5 years, we'll be in humans.
Dr. Moira Gunn:Alright. I'm good. I'm good now. I feel much better. I wanna ask you a question I don't usually get to ask just because of timing.
Dr. Moira Gunn:You had a very successful academic and research and scientific career at the university. And now you're over in in in a biotech, in a real company, building new drugs, new treatments. What is it like for you? Have you changed how you think about science or do science? What what's different for you?
Dr. Noah Davidsohn:It's a little surreal to see something that I dreamed up in the lab be put into patients, people's pets that we care about, or hopefully humans next year. When I was just doing this research on the bench in an academic institution. I've definitely learned a whole lot about drug development. It's a very complicated path. But the way I think about science and what ideas and how we're going to come up with the next generation therapy, that still exists in its purest academic form where science leads me down the path, toward, coming up with novel therapies.
Dr. Moira Gunn:Noah, thank you so much, and and I hope you come back and and see us again.
Dr. Noah Davidsohn:Yeah. Thank you so much for having me. I would love to.
Dr. Moira Gunn:Doctor Noah Davidsohn is the cofounder and chief scientific officer of REJUVENATE Bio in San Diego on the web atrejuvenatebio.com. Listen to more biotech podcasts at biotechnology.com or subscribe on your favorite podcast provider. Biotech Nation is a regular feature of the weekly public radio program, Tech Nation. Listen to the full show via podcast or on your local public radio station. For Bio Tech Nation, I'm Moira Gunn.