Targeting Tau in Alzheimer's Disease With Voyager Therapeutics' Al Sandrock, M.D., Ph.D.

On this week's episode of the Business of Biotech, Al Sandrock, M.D., Ph.D., President and CEO at Voyager Therapeutics, talks about why tau is becoming a central target in Alzheimer’s drug development and how gene therapy delivery across the blood-brain barrier could change what treatment looks like at scale. Sandrock shares his current thinking on the amyloid vs. beta debate (it's likely both) in Alzheimer's disease treatment, the role of emerging tools like fluid biomarkers in diagnosis and prevention, and why small biotechs take bigger risks than big pharma.  

Access this and hundreds of episodes of the Business of Biotech videocast under the Business of Biotech tab at lifescienceleader.com.  

Subscribe to our monthly Business of Biotech newsletter.

Get in touch with guest and topic suggestions: ben.comer@lifescienceleader.com

Find Ben Comer on LinkedIn: https://www.linkedin.com/in/bencomer/

Transcript

Welcome And Guest Overview

Ben Comer 0:03

Welcome back to the Business of Biotech. I'm your host, Ben Comer, Chief Editor at Life Science Leader, and today I'm speaking with Al Sandrock, MD PhD, president and CEO at Voyager Therapeutics, a company developing treatments for neurological disorders. Voyager's wholly owned pipeline is targeting Alzheimer's disease through the Tau protein, one of the two primary culprits, along with amyloid beta associated with various dementias, including Alzheimer's. Voyager is targeting Tau with an antibody and a gene therapy in two early stage programs, in addition to other preclinical studies, as well as licensing and collaboration activities with other companies. Al is a Harvard-trained MD and PhD and has worked in academic medicine as a professor at Mass General, and he spent more than 20 years moving up the ranks at Biogen. Before joining Voyager as CEO in 2022, he was Biogen's executive vice president of RD and was there for the FDA approval of the anti-amyloid drug Aduhelm, the first disease-modifying drug approved for Alzheimer's. It was not a perfect drug, but it was an important stepping stone in a devastating disease, and I'm excited to speak with Al about the switch to Tao as a target, his professional journey in neurobiology and drug development, how a small biotech like Voyager competes in Alzheimer's disease against big pharma, and what the future holds for Alzheimer's patients. Thank you so much for being here, Al.

Al Sandrock, M.D., Ph.D. 1:35

Thank you for having me, Ben. Looking forward to the conversation.

Ben Comer 1:38

Me

Falling In Love With Neurobiology

Ben Comer 1:39

too. And I thought we could start off uh with your background and uh we'll we'll take it all the way back if you're willing. I'm curious about your initial interest in neurobiology. What attracted you to this area of research?

Al Sandrock, M.D., Ph.D. 1:53

Yeah, that I remember it well. I was uh a freshman in college, and uh we had a and I was taking my my major was human biology, and we had a guest speaker uh who happened to be a psychiatrist, and he talked about the biological basis of psychiatry. So this was in the mid-70s, it tells you how old I am. Um, but you know, psychiatry had been for many, many years more uh uh more psychoanalytical. Um, and so you know, the origin of psychiatric disease was felt to be how you were raised and you know, things that happened in your childhood, etc. But in the 70s, the the idea that that there's a biological basis for psychiatric disease, that it's a chemical imbalances, if you will, uh, that cause disease, and that they can be treated with simple chemicals like lithium from manic depressive disorder. I thought that was fascinating. And uh and and then we had another professor who talked about the beauty of the nervous system. He was studying actually the nervous system of invertebrates, which was very simple. But even there, the the nervous system is just so beautiful in the way it's organized and the way neurons talk to each other and how synapses, the connections work. It just blew me away and I had to do it. And right after that lecture, I went to the psychiatrist and said, Can I work in your lab? Um, and and I ended up working in a psychiatry lab for the rest of my uh college uh time. And and then when I went to Harvard Medical School, just continued on.

Ben Comer 3:35

That's really interesting. You were you were there kind of at the birth of um being able to develop drugs uh for psychiatry. You couldn't develop, you know, a drug for talk therapy, but you know, once there was a biological basis for for psychiatry, you know, uh we're off to the races. Um that so you I think have a an excellent uh view of how this field has evolved, you know, from then all the way up to 2026. We won't have time to talk about you know every every bit of that uh timeline. Um, but uh I'm glad to have you on uh for the perspective that you bring, Al.

Leaving Academia For Patient Impact

Ben Comer 4:15

You went to Biogen, but before that you were uh on the academic faculty uh at Mass General. I mentioned in the intro. Um why did you decide to uh move over into industry um after after working at uh as a professor at Mass General? And and did you ever regret leaving uh academia?

Al Sandrock, M.D., Ph.D. 4:36

Sometimes I do, you know, because uh academia is a wonderful environment to explore and to uh treat patients in in an academic setting, um, to do things that uh that you really think is right for patients. But I'll tell you the reason why I moved to biotech was that at the time that I was there, uh uh Dr. Robert Brown had just discovered the first genet gene that causes ALS, amiotrophic lateral sclerosis. And so we were getting a lot of patients coming from all around the world to Mass General to see Dr. Brown, and of course he couldn't see them all, so they had to see one of his associates, i.e. Al Sandra, sometimes. And and uh and in that setting, you know, ALS is such a horrendous disease. And uh I felt like I wasn't doing enough for my patients. I felt bad that I would diagnose them and I had very little to offer them. There was one drug that had been approved called Real Azole, but I would give the drug, prescribe it, and I didn't see and I didn't really notice any difference in my patients. They were still worsening right in front of my eyes. And then in the meantime, I had some friends who had ventured over across the Charles River to uh Cambridge to uh biotech. And they had just started working on multiple sclerosis, and the first drugs for multiple sclerosis had been approved, and biogen had one, and interferon beta approved for MS. And I thought, wow, we can actually make drugs that help patients with bad neurological diseases. And so that whole thing intrigued me so much that I had to I had to take a stab and and come over and and uh come to uh back then it was considered the dark side, yeah uh but I thought boy if I can make drugs that can help patients or take part in that, that that would be very fulfilling. And it turned out to be true.

Industry Lessons From MS Drug Development

Ben Comer 6:42

Well, I mentioned you had a long career at Biogen and were steadily promoted. Um could you talk a little bit about maybe what you learned after joining industry, um, maybe some of the the challenges that you faced while you were there?

Al Sandrock, M.D., Ph.D. 6:58

Yeah, you know, in industry it's much more of a team sport. You know, in academia, you have your own lab, you get grants for your own lab. You do collaborate sometimes, but really it's you know, you it's you you run your own lab, you see your patients. Whereas in industry, you can't make a drug by yourself. It's very much a team sport. And I really enjoyed that aspect of it and learning from all the other disciplines that that are that need to be involved. Um, the tricky part is that in academia you can work on whatever you want as long as you can get grant money and funding for it. But in industry, you have to kind of conform to what the company's strategic objectives are. Right. So uh now I had chosen Biodip because they had already started in neurology, as I said, for MS. And I thought maybe what I could do is influence the company to do even more in neurology. Uh, because initially it was more of an immunology company, and the first drugs for MS, even though it's a neurological disease, are approached by immunomodulators, so drugs that affect the immune system. But I thought, boy, there's a lot more we could do by studying the brain and actually making drugs for brain disorders. So that turned out to be true. You know, the more successful you are in industry, the more they listen to you, and the more that they you can influence the direction of the company. And then I was able to hire some unbelievably good colleagues who who joined me on this quest. And we ended up making multiple drugs for uh multiple sclerosis. And, you know, when I was a medical student, I had a classmate in my who got diagnosed with MS in our first year, and by the time the class graduated, four years later, she was in a wheelchair. That doesn't happen that often anymore. You know, there are treatments now, and the time to getting in a wheelchair has been delayed quite significantly. Some some patients never end up in a wheelchair, right? I saw that transformation with my own eyes and had a role in that. So that was really meaningful to me. And and uh it was a dream come true.

Aduhelm And The FDA Balancing Act

Ben Comer 9:10

What was it like uh, you know, working with the FDA? I think you left correct me if I'm wrong on this, Al, I think you left Biogen at the end of 2021. Aduhelm was approved by the FDA, I believe, in July of that year. Could you talk a little bit about, you know, uh it sure it must have been uh a challenging process to go through. Uh anytime you're seeking approval for a drug, you know, for something that's that's never existed, in this case a disease-modifying drug for Alzheimer's, it's a challenge. But I I wonder, you know, what you might say about your takeaways kind of in that process working with the FDA to get that uh get that drug approved.

Al Sandrock, M.D., Ph.D. 9:56

Yeah, no, it was uh it was quite an experience. Um, you know, the world didn't really believe that amyloid directed treatments would work. Right. Um, there have been so many failures, billions of dollars had been spent, and there were no drugs that that seemed to work. And then Aduhelm came along, and and look, it wasn't perfect. We had one trial that was positive and one trial that was negative, and then an earlier trial that was positive as well. So two trials that were positive, one that was clearly negative, and so FDA had to grapple with this. And I thought FDA did a fantastic job thinking about what's the best thing for patients. You know, here we have a disease that is universally fatal, and before you die, it's terrible for not only the patient and the but the family as well. Right. There are seven million people with Alzheimer's disease in the U.S. alone, but likely 14 million caregivers for those patients. You lose the ability to live independently, and you can't, you know, you can't even recognize your own family members uh in the later stages of disease. It's awful. So FDA knew that high, high unmet need. And and the fact that there was a drug, even though it was modest in efficacy, in some patients it could delay the worsening and give you some more time, living independently, recognizing and being with your family members. They thought that was important and that the benefits outweighed the risk. And I thought the c you know, look, frequently companies in FDA are kind of you know naturally they're they're they're not they're antagonistic. If you're not antagonistic, but but FDA is a watchdog, right? I mean, they have to uh scrutinize companies, and so we don't always agree. But in this case, I thought FTA did a really uh beautiful job balancing the uh uh things and making sure that the patients got what they needed, and and uh so I I have but but as you just pointed out, it wasn't perfect. Right. Yeah, and you know, I think I left before the commercial rollout kind of really happened, and that's where I think uh there was some missteps.

Ben Comer 12:18

Yeah, I I uh it's been a while since I I remember covering this at the time, but I I think CMS's decision not to cover the drug in Medicare was kind of a shock. You know, it was something that didn't typically happen after an FDA approval. Um, and I don't know that it's really happened since, and we don't need to get all the way into that, but um, yeah, so that that commercial rollout kind of happened after you left um after you left Biogen.

Joining Voyager For Better Brain Delivery

Ben Comer 12:49

You landed at Voyager as a CEO and I think in March of 2022. What what circumstances led to that switch over to uh to small and scrappy biotag?

Al Sandrock, M.D., Ph.D. 13:02

Yeah, well, so you know, Voyager had just so gene therapy I thought was a really important modality for to treat neurological diseases. You know, I had seen how transformative it can be for patients. Um and but there was one problem with gene therapy is the delivery. We had to inject the viral particles that contain the gene either directly into the brain or into the spinal fluid that surrounds the brain uh into various compartments. And that was not optimal. Um it not only were there safety issues associated with that, but but it just wouldn't work because you don't get broad distribution of the gene therapy into the brain. And most of the diseases that we're dealing with, you need to reach multiple parts of the brain, multiple regions. And so what I saw was that Vorger scientists had figured out a way to deliver the gene therapy across the blood-brain barrier into the brain and get broad distribution and you get and get the cells to really express the gene. And that was a big breakthrough, I thought. This all happened before I joined, but I saw it happening and I said, wow, um you know, this is this this is a breakthrough that it's another, you know, I I think of it as a drug developer who needs tools uh to help the patients. And this was a a tool that I that I thought could be very helpful to help treat patients with many terrible diseases, not just neurodegenerative, but neurodevelopmental as well. And so I just, you know, at first I joined the board and I said, well, this, you know, um, but as I was a board member, I got to meet the scientists, and the scientists here were so good that I felt like boy, I could really help this company maybe by being CEO. All my friends told me I would hate it, that I shouldn't do it. But it turned out that uh that I didn't hate it, and uh it turned out to be a really good decision, I think, in retrospect.

Learning The CEO Job Fast

Ben Comer 15:18

Well, what did you find uh to be the most challenging aspect of coming into that CEO role? I'm I'm curious about how you kind of got up to speed with the company, you know, how you spent your first couple of days and and weeks on on the job. Um, it was your first CEO role. You had worked primarily on the scientific side, I believe, for most, you know, maybe all of your career uh at Biogen up to this point. Um, so what what was challenging? How did you kind of uh figure out the lay of the land?

Al Sandrock, M.D., Ph.D. 15:50

Yeah, so uh this podcast is called The Business of Biotech. So it's the business side that that I wasn't really as familiar with. Uh yeah, you're right. I was an RD guy, you know, physician scientist. I knew that part reasonably well, although I'm still I'm always learning. But the business side was new, and I had to worry about money a lot more than I did. You know, at Baijan, we were making a lot of money and we had a budget, and of course I couldn't spend uh uh as much as I wanted uh there either. But here we had a cash runway. We we did not have revenue coming in from products that we were selling. So to I had to really learn about cash, cash runway, and how to get revenue, even though we don't have any products that we sell. And so that was, and so I must have been a complete disaster initially when I walked in, Ben. I I I I feel bad for my colleagues who had to deal with me. Uh the board had to deal with my you know lack of knowledge on the business side. And but I but I had to get up to speed quickly, right? I mean, I was the CEO. And so um so I had really good colleagues who helped me understand the business of biotech, uh, including the board member. And the chairman of the board happened to be his he was formerly the CFO uh at uh at uh his other companies before coming to the by uh to the Voyager board. So so he was very helpful. And in retrospect, you know, I thank him frequently and say, hey, Michael, his name's Michael Higgins, thanks so much for helping me out in those early days. I must have been a complete disaster. If it weren't for you, I don't think I could have done, you know, you know, I could have gotten this far. And so I I I was telling him recently that I really appreciated that that the role that he played.

Ben Comer 17:46

But you didn't hate it like your friend suspected you might. You you ended up liking the CEO role and uh and and learning all of these new pieces of uh of the business that you know are a big part of the CEO job.

Al Sandrock, M.D., Ph.D. 17:58

Yeah, I I I didn't hate it. And you know, one of the things I really uh enjoy also is to be able to create the culture I want in the company, you know, the CEO has to take ownership of the culture.

Building Culture With Transparency

Ben Comer 18:14

Yeah.

Al Sandrock, M.D., Ph.D. 18:15

And what I like is a strong science culture that which which I which I which I found when I came, as I said, you know, I met the scientists, I was very impressed. I wanted to be sure I maintained that strong science culture and to reduce politics uh as much as possible. How do you do that? How do you reduce politics inside of a company? I I rely a lot on transparency, empowerment, and accountability. To me, empowerment and accountability are are two sides of the same coin, you know, and so and uh but I think and then I I I do things at meeting, you know, if you have something to say, say it at the meeting. Don't come to me later and try to take the backdoor approach. If you don't like the decision, say it at the meeting. And and I like open debate, you know. I don't like people who just tell me things that they think I want to hear. I want I I I want I I make sure we have time to openly debate topics, do it in a transparent manner, and then and then yeah, after a period of debate though, we have to align and move forward. Otherwise, we can't execute. So there's a period to debate and a period when the debate ends, and we have to align and execute on that decision. But it's this openness and transparency that that I really rely on to reduce politics. And then when people try to come to my office, uh, you know, use the backdoor approach, I don't let it happen.

Ben Comer 19:54

That's great. That's really interesting. I I appreciate

Amyloid And Tau How They Interact

Ben Comer 19:57

that. Um, I I want to uh talk about Alzheimer's disease and and maybe we can start with uh the Holy Own Pipeline programs that that you're working on, Al. I mentioned you have an anti-monoclonal antibody and a uh a gene therapy uh which contains uh short interfering RNA, si RNA. Um what do you like, I guess, uh about the gene therapy modality uh for Alzheimer's disease? Uh maybe, maybe not versus uh the antibody, uh, because you're developing both. Um, but maybe you could compare and contrast those a little bit. Like uh what you know, what makes sense for each of those modalities to potentially treat this disease?

Al Sandrock, M.D., Ph.D. 20:44

Yeah, but Ben, that's a great question. But before I answer that, may I talk about why I think Tao is so important? And and you mentioned at the beginning the two kind of culprits, if you will, amyloid and tau.

Ben Comer 20:58

Let's talk about, let's do that first. Amyloid versus tau. Um, it yeah, where does the debate stand? Because when Ajuhelm was approved, this is when you know the amyloid conversation really blew up and and people had very divided opinions on is amyloid, you know, the key factor in the development of Alzheimer's? Is it not? Is it tau instead? Is it both? Where does that where does that debate stand?

Al Sandrock, M.D., Ph.D. 21:25

Yeah, so I don't think you have to choose camps. I think they're both important. And in fact, at Baijan, even while we had get we were getting uh educanumab approved, we had programs directed against Tau there too. In fact, one of them, Bib 80, has just read out, and we're gonna see the results at at the conference in July. But so I I'm in both camps, actually. And here's how I think the two culprits play kind of work with each other to cause damage. So it turns out that all of us have uh have a little bit of tau misfolding and Aggregation. So tau is a normal protein. But when it starts to clump together and when it gets modified, that clumping together causes problems in a ner in a nerve cell. It turns out that that clumping together and misfolding happens as part of normal aging. But we all get it if we uh uh but it's restricted to a very small part of the brain uh called the rhinal cortex. It's a the f the floor of the temporal lobe. And so if you don't have any amyloid, it stays there and it doesn't really cause too many problems, none that that I know of. But when you get amyloid accumulation, it triggers that tau to start to spread. So the pathological tau spreads and accumulates and goes to other parts of the brain. So they're synergenistic, is what you're saying. Yeah, so amyloid triggers the tau progression. So not the initial misfolding and clumping, but the progression and the worsening and the spread throughout the brain. And so that's how the the they they kind of work together to cause problems. And so it's like it's like you know, the it's like a forest fire. The tau is the forest fire, but the match might be amyloid. Um and and so if you if you if you reduce amyloid, you reduce that trigger. So you um and I always worried that maybe once the forest fires have started, you can't affect it. But it turns out you can. Um so so uh but but I do think that it that if you really want to treat Alzheimer's more effectively, you got to go after Tau. And as you pointed out, we have these two approaches. You asked why gene therapy is is uh is so important. Gene therapy could be a once-and-done therapy.

Gene Therapy Versus Antibody Approaches

Al Sandrock, M.D., Ph.D. 24:05

You could give it intravenously one time, and we have the cells in the brain express this small interfering RNA, which by the way, all cells have small interfering RNA. We're just putting one in that's an artificial one that reduces the expression of tau. So we we so we we deprive the cells of tau, which in the case of Alzheimer's patients is spreading and wreaking habit of havoc on the nervous system. So, so as opposed to other approaches, for example, Bib 80, the one I just mentioned that biogen has, requires intrathecal injections. So you need a needle into the lumbar into the back into get a lumbar puncture, and it needs to be given every six months, uh, which is cumbersome, uh to say the least, uncomfortable for the patient. But imagine trying to do that to to millions of patients. It's it would overwhelm the medical system. It's because you need, you know, you need lumbar puncture takes time, you need a doctor to do it, it's a procedure. It's very painful too, isn't it? Very painful as well. Yeah. Well, if you I used to do a lot of if you're really good at it, it's less painful. But no, but still it's it's yeah, it's invasive, it's painful. Um, and so um so being able to do an intravenous once and have the body, the the cells in the brain make that SIRNA uh and and to reduce the expression, that could be a game changer. Um so that's that's that approach. The antibody approach is a little different. It's in instead of decreasing the expression of tau, um we we're trying to use the antibody to block the spread from one cell to the other. Uh as it's trying to go from one cell to the other, the antibody captures that pathological tau and removes it. So that's all that's an that's another approach. And you know, who knows? One day maybe we'd we'd be using both.

Combination Therapy And Early Treatment Bets

Ben Comer 26:14

Well, that's what I was gonna ask is given what you've just described about the interaction between amyloid and tau, would you potentially need uh a combination therapy where you're tar targeting both both proteins? Yeah.

Al Sandrock, M.D., Ph.D. 26:30

So that's gonna depend a little bit on the results of two pretty exciting studies going on with the anti-amyloid uh treatment. One is a big study conducted by Lily, and the other one is a study conducted by Bijin and ASI. Um and what they're looking at is can the anti-amyloid treatments, if used earlier, even before you actually have cognitive impairment, could that actually make it so that uh uh you don't even need to worry about treating for tau? In other words, can you have a much bigger treatment effect if you start earlier? Those results are gonna read out within the next year or so, so that's pretty important. So if we can if we remove the trigger, maybe the tau stays in that little part of the brain and never spreads. And as I said, that's part of normal aging. We don't know the answer to that question, we have to wait for the results. But it's possible that even if you treat early, you may still need to treat the tau. And so I can imagine that one day we'll have look, there may be some patients who, if you treat the amyloid, you need nothing else. There may be other patients, particularly those who've been allowed to progress a little bit more before they get the anti-amyloid treatment. Maybe there you need to add the tau treatments to really address the disease more fully.

Partnering Choices And Non Dilutive Cash

Ben Comer 28:02

Excellent. Um, I want to uh ask a kind of business-y question here about your pipeline. I mentioned the the antibody, we've just been talking about the antibody of the gene therapy. Uh, there's a third candidate in preclinical uh in your wholly owned uh pipeline, but then you also have licensing and collaboration deals. Uh you have opt-in opportunities uh with other products that uh I assume have been discovered uh at Voyager. My question is, how do you decide which assets to bring into your wholly owned pipeline and develop internally versus what you want to collaborate on or potentially participate in some other way?

Al Sandrock, M.D., Ph.D. 28:47

Yeah, so business development turns out to be one of the key ways in which we can get cash. As I said, we don't have any products that we're selling yet. Yeah. So either we sell more shares of the company, which the current shareholders don't like because then they get diluted. They own less and less of the company as that goes on. But this is non-dilutive revenue that we can bring in. The downside, though, is that you give up a piece of the future. So in other words, we had these assets, they they were wholly owned, and so the Voyager, if they're successful, the Voyager shareholders then get a full benefit of those assets when they become commercial. But um, but you have to give up a piece of that, sometimes a lot of it. On the other hand, it's risky, right? All these, I mean, most programs fail, let's be honest. Yeah, right. And so the ability, uh the ability to get revenue up front, which helps our bottom line, but also uh to be able to uh spread that risk to other companies who are willing to share the risk with us. Oh, yeah, we share the we we have to share in the upside, but I'm willing to do that if we can bring in near-term cash and they and they take on some of the risk of drug development. Also, I look for companies that have the capabilities to do a good job with our assets. You know, if they have infrastructure, and you know, often these companies are much bigger, they have more resources, and if if they have expertise and resources, they can apply that. I can't in a small company, that that makes it even better. So that asset has a higher chance, actually, of getting uh to the across the finish line, if you will. Um, and so I look at all that, and uh so far we've done some some very nice deals with some very good partners, and I'm very proud of that. And by the way, in some of those situations, we have the ability to opt back in. So, in other words, they they pay for it, they take all the risk up until a certain uh until we get some clinical trial data, and then we have the ability to opt back in. In the case of one one program, 40% U.S. rights, uh, and in the other program 50%. So that's nice. So we see whether the programs are looking promising and we can opt back in to get economics, that helps the Voyager shareholder. And but at the end of the day, getting these programs partnered allows us to try more things, and I think the patients win at the end, because now we can prosecute more programs um and try new things that may not otherwise have seen the light of day. Uh, and so I think at the end of the day, the patient wins too.

Near Term Milestones And Tau PET Readouts

Ben Comer 31:33

Um, I want to just get us we've talked about the the antibody and the gene therapy targeting tau. Um, just for for the listeners, can you let us know where those are in terms of maybe what the next milestone is? I think um FDA granted an IND for VY 1706. That's the gene therapy. That was at the beginning of June. You received an IND there. Um, but do you have a sense of when that will enter the clinic? And then also on the antibody drug, uh, where that one currently stands.

Al Sandrock, M.D., Ph.D. 32:06

Yeah, so the gene therapy, we just got IND clearance a couple of weeks ago. We expect to enroll the first patient in our phase one trial in the second half of this year. Um, and so that's that's a pretty important uh uh thing for for for us at Voiger. The other program, the antibody, has already been in the clinic for a couple of years. Oh, okay. We're we're actually waiting for, so here we're gonna look at uh by by doing what's called tau pet imaging. So we're gonna actually be able to visualize whether we can impede that spread of pathological tau that I was talking about with the antibody treatment. And we'll we'll find that out at uh toward the uh in the second half of this year as well. So so uh two important milestones on tau for for Voyager this year.

Ben Comer 32:57

Now, for that Tau pet screening, um, is that something that has has been you know commonly used in the past, or maybe not commonly used, but in the past like say five or six years? Is that is that the tool that's used to assess you know this the amount of tau in the brain?

Al Sandrock, M.D., Ph.D. 33:15

Yes. Um it's only been around for uh uh certainly less than 10 years. Okay and but it has been used. I mean, it's been used in the amyloid trials. Remember, I said amyloid effects tau? That's how we know because we were able to do Tau pet imaging in some of the amyloid trials in the past. But yeah, and and these are all new tools, and and I love the fact that you use the word tools because you know uh a drug developer needs tools. Uh not only does it need the modalities like gene therapy and delivery tools, but we need the tools that can measure what's going on. And this has been a problem in neuro in neuroscience for a long time. You know, the brain is inside the skull. Um, we can't access the tissue. We can, but it's you don't want to. Right. Yeah. Uh and so how do you know that the drug is working in the brain? We need to so sometimes we take fluid out of the spinal, we take spinal fluid out and we see whether or not we see changes. But one of the very best ways is to actually image the brain. So all these new technologies that have come online just in the last couple of decades have really helped us not only take care of patients when they get diseased, but also measure what's going on in the disease. I can't tell you how important that is for us drug developers to have these tools.

Ben Comer 34:37

Oh, absolutely. Yeah.

De Risking Programs In Small Biotech

Ben Comer 34:39

Um I uh I wanted to ask, uh, you know, and you've kind of alluded to this, uh, just the the disparity of research or the differences in resources between, you know, a company like Ace or Biogen and uh and Voyager. Uh and it's expensive to develop drugs for for Alzheimer's disease. Uh and I'm wondering how you think about development costs as CEO, how you manage development costs, and how you think about risk um, you know, when you decide to green light and go forward on a new program.

Al Sandrock, M.D., Ph.D. 35:12

Yeah, the risk is the key thing. And what I what I all I always you know, for a small company, we we only choose programs where we feel we can mitigate de-risk rapidly and efficiently. So we chose Tau because of the availability of these imaging tools and these uh fluid measurements that allow us to know whether the drug is at least engaging the target and producing the biological effect in the brain, and then hopefully also be able to measure whether there's a clinical effect as well by using you know more modern uh ways of measuring the clinical changes, too. So so we choose programs that that have an efficient path to de-risking events. And uh because in a small company, we can't wait to do the 2,000 patient two-year trial to know whether or not the drug works. That's too risky for us. Maybe for a large company, they could take that risk. But even there, you don't, you know, so so that's why the availability of these tools is really, really important. You know, the conundrum here is that we're a small company, but we have to take, in some ways, even riskier moves. See, because nobody's gonna care about investing in a company that's doing a Me Too drug. And we're not gonna be able to compete in the Me Too space. We have a great point, right? So we have to be highly innovation is is is uh very important for us. Well, innovation is risky. Yeah. And and and so um so then so we have to do risky things, but how do you mitigate the risk? How do you deal with the risk, manage the risk? That's the key, I think, in a small company when you don't have enough cash to be able to do everything or to do me too things and to wait until you can't be spending huge amounts of money before you know whether or not your drug is on track.

Ben Comer 37:15

And uh the risk that you're talking about is is in some cases less likely to happen in a big pharma. You know, you talked about you know portfolio needs and and kind of a ruling from the top on you know what areas a company is going to explore. And if you have a you know, maybe a really promising uh asset or or idea for a development program, if it doesn't kind of fit into that slot that the company has, they're probably not gonna pursue it, particularly in a really risky disease area, which I think underscores you know what what you've been saying already. Uh, I did want to ask, you know, maybe one follow-up on how a smaller company like Voyager competes with uh with these big pharma companies.

Why Alzheimer’s Needs Big Partners

Ben Comer 38:03

And and I guess what I'm thinking about, it becomes more important maybe in the commercial realm than in the div on the development side. Have you thought about, and you're you know, Voyager is uh still a ways from market for these two products that we've been discussing or two development assets that we've been discussing, but have you thought about you know what as these candidates progress, um, you know, what you might do on the commercial side? Does does Voyager intend to potentially commercialize these drugs themselves? It seems like it'd be a Herculean effort given the size of the Alzheimer's population, uh both domestically and and globally, or or do you anticipate uh partnering in in the commercial space when the time comes?

Al Sandrock, M.D., Ph.D. 38:48

Yeah, we we're probably gonna we're definitely gonna need to partner it. It's uh Alzheimer's disease is too big. Yeah. And in fact, even before, I mean, I can't even imagine us doing a big phase three program by ourselves, you know. It's it's thousands of patients, yeah, very probably. And so we we will need to partner before phase three, even. Uh, but for smaller diseases, you know, we also are working on, for example, ALS. You know, we have something in our pipeline for ALS. That's a smaller disease. And in particular, if you have a subset of patients with ALS, um, for example, potentially we had a program for SOD1 ALS, a small subset of ALS, that we could potentially take all the way to the finish line and even commercialize. And then there's some rare diseases like the lysosomal storage diseases, where we could take it to the finish line. But um, but but I think for these large diseases, we need a partner.

Ben Comer 39:48

Got it.

Blood Tests And Prevention Like Cholesterol

Ben Comer 39:49

Okay. I want to uh maybe end our conversation, Al, with a discussion on the future uh for uh in the you know, in the context of patients, uh, you know, how new drugs and uh and and new discoveries might help them and maybe lifestyle modifications is as well. Uh there's been you know a lot of coverage in recent years. I've written some about you know new blood tests that have emerged to help diagnose patients. We've heard for a long time now that the earlier that you can uh initiate uh a treatment for a patient, uh the better off they're gonna be uh in terms of staving off uh the disease over time. But um, what what excites you, I guess, Al, you know, aside from your own activities that you're doing uh at Voyager in terms of these new tools, you know, whether it's uh diagnostics or or or other tools that you think are gonna help um you know alleviate this disease and and push the science forward?

Al Sandrock, M.D., Ph.D. 40:50

Yeah, I think that I I see a day where we will tr we will start treatment very early, even before people are sick. So so the analogy that I often use is the cholesterol analogy, right? So cholesterol, we know is a by it's basically a biomarker. Your primary care physician checks you for cholesterol. You don't wait till you get a heart attack uh or or a stroke. You treat the cholesterol, you lower it. I think we're gonna be doing the same thing with amyloid. We're gonna be checking for amyloid with some simple blood test that that, for example, that you've already mentioned that can tell us whether or not amyloid is building up in the brain. Why wait till you have cognitive impairment to treat? Why not treat the amyloid before you get sick? And in the nervous system, I think it's especially important because neurons don't divide, you know, as opposed to almost every other tissue in the body where the cells can regenerate by dividing. Neurons don't divide. So if you lose a neuron, it's gone forever and it doesn't get replaced. Um, and also new connections don't form very well in the adult. So I think it's imperative to treat as early as possible. You know, in many cases, we don't even recognize the diseases happening until the majority of neurons are lost. Um, and that's a shame.

Ben Comer 42:19

Because the symptoms don't show up right now.

Al Sandrock, M.D., Ph.D. 42:21

That's right, right. Or they uh they and and and so um why not prevent the disease? But and I see a day where we can maybe prevent all these neurodegenerative diseases long before they just by by using a blood test to know whether or not the disease is happening based on the buildup of amyloid or or any other in other diseases will be different proteins. I see this happening. Um you know, and this trial that we that I just mentioned, that these two trials on the early, you know, treating before people have cognitive impairment, that's also going to be very important. So getting data from clinical trials that you can treat earlier and get a bigger bang, if you will, uh for the drug. And the blood tests that we can use to screen the population, man, I I I'm just so excited about that possibility. Um, so I, you know, maybe I'm just ridiculously optimistic, but I but I see it all happening. I think it's all right there. It's it's gonna happen soon.

Ben Comer 43:24

Well, I mean, to stick with your cholesterol analogy, uh, we know that a lot of patients are not very adherent to their statins. It's a daily medication you have to take in perpetuity. Now there's like some really exciting, uh, really exciting programs editing, you know, gene editing the PCSK9 uh genes as potentially a one and done for cholesterol. Well, it seems like what you're trying to do is kind of similar to that, where uh a kind of one and if you can identify the patient early before symptoms and and treat it with a single therapy, uh that that's uh that's Really exciting too.

Al Sandrock, M.D., Ph.D. 44:01

Thank you for that, Ben. That's exactly right. Once and done, don't have to even worry about it anymore.

Lifestyle Factor Sleep And Amyloid Clearance

Ben Comer 44:08

Um, I I did want to ask you about lifestyle changes. Uh, the science has progressed uh every year, all the time it's progressing. Are there any lifestyle changes that have been proven to help uh prevent the onset of this disease that you know that people should should think about right now?

Al Sandrock, M.D., Ph.D. 44:27

Proven's a big word. Um but I think but I but uh certainly diet, exercise, but I would say that the one I focus on a lot is sleep. Um we know that sleep during sleep you actually remove amyloid. That there's a it's a naturally occurring way where amyloid is removed uh uh uh from the brain during sleep. So if you don't so I would r strongly recommend getting a good night's sleep. I do think that's one lifestyle change that we should all I think there's lots of other benefits to getting a good night's sleep, but one of them is removal of amyloid, and I think it I think it it is likely to prevent Alzheimer's disease or slow, you know, delay its its its progression. But I but to say that there's proof, I I I'm not sure I've seen absolute proof of it, but certainly the evidence that it can remove amyloid, that there's strong evidence for that.

Ben Comer 45:26

Well, the sleep issue, uh, some of the entrepreneurs and and young biotech leaders listening are probably not gonna want to hear that. But uh we we keep finding out more and more about the benefits of a good night's sleep. And a good night's sleep is what, seven hours, or does it is it need to be eight? I think it's I I'm hearing it's eight.

Al Sandrock, M.D., Ph.D. 45:45

It may depend on age, you know. If yeah, just that as you get older you need less. Uh and boy, when I was a teenager, I used to sleep 10 hours, you know, but at least on weekends. But anyway, um, yeah, I I'm not an expert enough to know, but I would say a good eight hours is is is and maybe nine, maybe even better for all I know.

Career Advice For Future Neuro Leaders

Ben Comer 46:07

Uh let me ask you one uh final question with uh the business of biotech's audience in mind. Um, what what advice would you give, Al, to someone who's maybe uh in in the midst of a neurobiology or neurology uh PhD program, wants to go into industry and and you know change the world. Uh what advice would you give uh to that individual? Uh if you, you know, maybe one or two ideas that you would share?

Al Sandrock, M.D., Ph.D. 46:37

Yeah, I I think you should do it. I mean, you know for me, uh I this is what I tell my kids too. First of all, you gotta love it. You know, and you and you know how I know whether I love it is if if I wake up in the morning and I'm thinking about it, and if it's the last thing you think about when you're going to sleep, you must love it. B, you have to be good at it. You know, if you're struggling with it, you're probably not good at it. If it comes easy for you, you're probably good at it. Um three, uh it has to be something that makes a living. Yeah. Um, and for me, the great thing about this industry is you get the fourth thing, is that you can have an impact on the world, a positive impact. And I can tell you, nothing pleases me more than when I meet a patient who's taking a drug that I had some hand in developing, and they say thank you. You know, then I feel like a doctor again, even though I'm I'm I'm a drug, I'm a drug company guy now. I feel like a doctor again when a patient comes and says, I've taken the medicine that you guys developed, and I appreciate it.

Ben Comer 47:49

Al, uh, thank you so much for coming on the show. It was a real pleasure speaking with you. Thank you very much, Ben.

Al Sandrock, M.D., Ph.D. 47:55

I enjoyed

Closing And Where To Follow

Al Sandrock, M.D., Ph.D. 47:56

it.

Ben Comer 47:56

We've been speaking with Al Sandrock, MD PhD, president and CEO at Voyager Therapeutics. I'm Ben Comer, and you've just listened to the Business of Biotech. Find us and subscribe anywhere you listen to podcasts, and be sure to check out our weekly video cast of these conversations every Monday under the Business of Biotech tab at life scienceleader.com. We'll see you next week, and thanks as always for listening.