Biotech 2050 Podcast

Redefining Dementia Care: CervoMed's Bold Journey with CEO John Alam

Synopsis:

Get ready for an insightful conversation as host Rahul Chaturvedi connects with John Alam, CEO of CervoMed, to uncover the revolutionary advancements transforming dementia treatment, with a spotlight on Dementia with Lewy Bodies (DLB). John shares his remarkable journey from practicing medicine to leading cutting-edge biotech innovations, shedding light on the bold breakthroughs in neurodegenerative research and the intense, high-stakes world of clinical trials. This episode reveals how CervoMed is not just advancing dementia care but redefining it, proving that resilience and bold thinking are the keys to success in biotech.

Biography:

John Alam serves as the Chief Executive Officer at CervoMed, co-founding the company (formerly known as EIP Pharma) in 2014. John is an industry leader in translational medicine with over 30 years of experience creating value to help build companies through clinical development success.

Until May 2014, he was therapeutic area head for diseases of aging at Sanofi, where he led all discovery and development activities directed at Alzheimer’s disease, as well as a number of other age-related diseases including sarcopenia/frailty, osteoarthritis, chronic pain and many others. From 1997 to 2008, he held positions of increasing responsibility at Vertex Pharmaceuticals, including Chief Medical Officer and Executive Vice President, Medicines Development. At Vertex, he played major roles in the development of novel innovative medicines for HIV, Hepatitis C and Cystic Fibrosis. Prior to Vertex, Alam led clinical development of Avonex (interferon beta-1a) for multiple sclerosis at Biogen from 1991 to 1997.

John is a member of the board of directors of the Alliance for Aging Research (AAR), a Washington, D.C. based non-profit organization dedicated to promoting innovation to address the healthcare needs of older Americans. He received a MD from Northwestern University School of Medicine and a BS in Chemical Engineering from the Massachusetts Institute of Technology. In addition, he completed an internal medicine residency at Brigham and Women’s Hospital and a post-doctoral fellowship at Dana-Farber Cancer Institute.

Duration:: 24m
Broadcast on:: 15 Aug 2024
Audio Format:: mp3

[MUSIC PLAYING] Hello, and welcome to the BioTech 2050 podcast. BioTech 2050 is a think tank, chronicling the disruptions changing the biotech industry over the next several decades. Check out our website at biotech2050.com on your favorite podcast listening platform. I'm Rahul Chutteraydi, co-founder of this podcast, and today's host. I'm also the founder and CEO of Chlora. Chlora is a platform that enables biotechs to build on-demand fractional teams. Check us out at Chlora.com. I'm excited to welcome John Allen, who's the CEO of ServoMed. Thanks for joining us today, John. Looking forward to the conversation. Thank you, Rahul, for having me. I'm really looking forward to the conversation myself. Great. So John, to kick us off, walk us back to your background, what initially drew your interest to biotech and then the arc of your career up to now. I'm trained in internal medicine, a doc by background, that a residency at Brigham Women's. And then went into the lab, Dana Farber, working with somebody named David Livingston, who's a very prominent tumor biologist, and was in the process of launching an academic oncology career. While I was there, where I really came to, where I wanted to be is what today would be called translational medicine, which in the time did not exist in academia. The way I voiced it to one of my mentors within Brigham Women's was to say, I want to be at the intersection of science and early drug development and helping accelerate development of novel therapeutics down novel pathway. And his common back to me was, you should go into industry. Because those are the only people who were really doing that work at the time. And so I did. He actually happened to know someone who was then the head of clinical at Biogen. So in 1991, May of 1991, I started at Biogen and had the good fortune, I would say, of being the clinical lead on their first multiple sclerosis drug, Avin-X, 4MS, and took work on that drug, took that through to marketing authorization, both in the US and Europe. And at that point, was looking to do something different, was approached by Vicki Sato, who is then the head of R&D at Vertex Pharmaceuticals. And that gave me an opportunity to go back to a little bit of oncology, but also to work on HIV, which out of during medical school was one of the areas that, because it was profoundly impacted by some of the patients I'd interacted with in the mid 80s, I wanted to be in HIV at some point in my career. So had that opportunity and that morph then into a whole range of therapeutic areas in Vertex, then there was a great grounding ground, and perhaps in many ways in biotech, the singular place to learn small molecule drug development, which I did for 11 years, and went from head of clinical to chief medical officer and EVP of medicines development, which was more broadly development, including non-clinical regulatory, et cetera. Left there in 2008 for a variety of different reasons, and it was just to pursue maybe a different track, is also having gone through the full launch process, and et cetera, that at Biogen and knowing the toll, and I felt uncertain levels were my expertise and what I really wanted to focus on at that time was done, it was time to take a break, did some advising for a couple years, eventually I actually ended up at Sanofi in France, in their core R&D group, heading what was perhaps remains the only R&D group in a large pharmaceutical company that was focused on aging, and diseases are aging per se, rather than being therapeutically area aligned. But within that group was where I had otherwise decided where I really wanted to be, which is in neurodegenerative diseases and dementia research in particular. More than half of, it's a 275 per person group, so big R&D group, but more than half the activity was towards Alzheimer's and Parkinson's and some activity and stroke. That was also great training ground in some ways. Sanofi was, rather within their research group, they singularly had built some really interesting translational platforms, multiple animal models, et cetera, really got to learn, learn underlying what the state of art and AD was at that time, also had access to pretty much every policymaker in Europe and US, many of the art research leaders and just ended up being a great opportunity to connect and build the network that has served me well since then. Eventually, there was a separate opportunity that, of taking out the drug we're working on now, licensing out of vertex, there was some really interesting science starting to come out on the mechanism, and this component had some unique properties that we can talk about that made sense to form a company around it, and I stepped out of Sanofi and launched that in 2014, and that has progressed to where we've ended up at. The arc is actually somewhat consistent. It's about that original vision of connecting science to early drug development, but then through it, it's been about clinical drug development. I am a drug developer in underlying it, but really using every single tool at your disposal. And the other thing I would say is that, and maybe this is just your last comment, what one thing I would advise is that every step along the way in each of these companies, in each therapeutic areas, they form very close relationships with some very one or two key leaders in the academic community, and that's part of what I fundamentally enjoy in what I do. - Yeah, great, John. And so now we went on to found EIP Pharma, walk us through those early days, what led you to go down the entrepreneurial route, and then quick follow on to that is I'm sure you had many wonderful lessons learned from your days at Sanofi, Vertex, et cetera, but what was something non-obvious when you first stepped into that founder CEO role that perhaps you hadn't imagined and that you would advise folks to think about if they're thinking about that entrepreneurial route? - I'd say that the launch of the company and everything that was all about, at the core of it was a science, and there's drive to do something disruptive originally in the Alzheimer's field, and taking a tack that was somewhat distinct from what the field was otherwise doing, and that being entrepreneurial actually gave you much more flexibility to take the science where you wanted to take it. This actually came out of during my time between Vertex and Sanofi. I was briefly an entrepreneur in residence for a venture capital firm in Boston, and they had me on one of their off-site meetings, and there was a talk by a consultant from BCG, which was all about this concept of being in smaller groups, setting up companies around, as in the film industry, around specific ideas that allows you to bring in completely different talent that's aligned and having that flexibility. That was the original business model concept, and to stay virtual in order to be able to go where you want it to go, where the science would take you. What I would say surprised me is how much the Sanofi experience, how relevant it was. The Sanofi is actually given that it's multi-trans, Germany, US, multiple different areas, and there's a lot of how you succeed is through, you can't allow anyone to do anything. It is about influence, making relationships and networks. That experience actually ended up being the best experience to be an entrepreneur and working in a network sort of way. How you can make connections, develop relationships, and get in some sort of what you want in a dispersed ecosystem. The Sanofi experience was actually great. Countering too. - If you're an HR or hiring manager in biotech, you know all too well that the pool of experts seeking full-time employment is shrinking. Filling key full-time positions can be a long, drawn out ordeal. It can slow the pace of execution and growth. Throw away the old hiring playbook. Now you can build a biotech dream team in a fraction of that time. Find out how. Visit chlora.com. Chlora. Talent optimized. - And John now with all of that background that you then brought to EFU Farman. Now, shrivel mad. You've been in the dementia space for quite some time now. I believe since 2011. Talk to us about how the field has progressed, as well as for our listeners, some of the inherent challenges with drug development in this field. - Within in the time that I was at Sanofi, I'd say the two things that I learned to very high level points of what had to change in order to be successful and they're actually linked. So one was that had to find a way to get better understanding what's happening inside the skull. There's too much of a black box. And short of actually opening up the skull and doing biopsy and gathering tissue, how could you get an understanding of both the physiology, the pathology, patient subsets, et cetera? We think of Alzheimer's as a single disease, but it's not. And there are different parts of the brain that are impacted, et cetera. And how do you differentiate all those? - This has been in the intervening, let's say, from when I joined Sanofi in 2011 to now, in the last 13 years, huge advances into that, respect it. That's imaging, that's CSF, and then really the correlation between imaging, both PET and MRI, structural MRI with plasma biomarkers, is I think just a radical change and fundamentally shifting that part of it. And then the second one was very clear. There's a point in there that how do you get to do clinical proof of concept in phase two, that your drug works? Not on biomarkers, but on a clinical endpoint, that you do what you do in most other fields. You go into phase three, it's truly a confirmatory trial. You know your drug works, you just need to do it in maybe a little longer duration, in a larger number of patients, just to know what the full range of efficacy is in a more heterogeneous patient population. The problem in this area has been that we don't know whether the drug works until phase three is done. And sometimes we don't know even then whether drug works. And so that is, I think we, and we'll talk about it some more, I think we know the path of how we can get there in many of these diseases. And DOB, it actually turns out to be a great place to be before to be able to demonstrate for concept. And John, during that time, has investor sentiment changed as it relates to this field along with improvements in efficiency of drug development? I think it's gone through cycles. When I came into the field, for one thing, that more generally CNS in the industry everywhere, part of the group that I was leading and they were set up as a neurodegenerative diseases group rather than a CNS therapeutics group. And the distinction is that CNS therapeutics is about neurotransmitter directed therapies, whether it's SSRIs for depression, all the various dopaminergic drugs, anti-psychotics, et cetera. They're really neuros, and which had a golden age. It is 70s, 80s, into the 90s and hit a wall. People moved away from it, moved towards nerdy generation and slowing in kind of disease progression drugs away from what were then termed symptomatic drugs. You've certainly seen a huge swing back to that. In the pharmaceutical industry, that's what Ceravel acquisition was about, that's what Karuna was about. And that in early stage funding, that in the public markets, that in what Bandang is going to. So that's certainly been a huge swing. But I think with that, you're starting to see success. You're certainly seeing more success in what we would be called neurodegenerative diseases. But what you're really seeing in our program, what we're doing is actually merging those two and bringing neurodegenerative diseases therapy and not just talk about the end stage and disease progression, but how do you bring it in the way where Cera therapeutics have always worked, which is that you actually get improvement. You make a patient feel better and see tangible results that you can pick up in a clinical trial in phase two. How do you do that? That's called a symptomatic effect, but being able to see a symptomatic effect with disease modifying approaches. What are the patients? What are the mechanisms that can do? I think we're there. We're starting to be there in certain fields, certainly in DLB with our program. And that merging back, I think we'll bring back investor interest into the dementia field and not just for drugs put towards disease modifying drugs for dementia. As evidence of that was the pipe we completed just in spring on April 1st, where we were taken out by one of the major banks and we had a major investment firm hedge fund, RA Capital be the lead investor. And it was that discussion and certainly I'm hopeful we're going to see more of that. Great, John, now with that pipe and congratulations on completing the transaction and certainly a very challenging market here in the middle of 2024. Talk to us about where you are from a development perspective and some of the exciting programs you have running right now. Sure. Our lead indication is dementia with Lewy bodies, which is the third most common chronic age related degenerative disease of the brain. So there's Alzheimer's, there's Parkinson's and right behind Parkinson's is D.L.B. High-end medical need, a lot of functional impact on patient, high caregiver burden, high medical costs, no proof therapy. It's also neurologist managed. So it's a specialty disease. So from a medical need and a commercial opportunity or a business opportunity, it's a great place to be. We are the one with a single drug that has shown efficacy or evidence of efficacy in phase two A in an exploratory study that we've published in high impact factor journals, Nature Communications, Neurology and now are in a phase two B confirmatory trial, hypothesis testing trial to what we hope we will be able to show is and believe we will show definitively show proof of concept. Like the phase two B study, as was the phase two A study, is a 16 week placebo controlled study, which is the reason we can see an effect in 16 weeks is that we are seeing, we're in a patient population that using a blood-based biomarker are in the early stages of their disease. They have limited frank neuronal death and loss. So fixed deficit. They have reversible disease that shows up as early as four weeks after starting treatment in our phase two A data. And that trial is nearing completion of enrollment. Our public, what we've said is that we will complete an enrollment within the second quarter. So in June, and we are on track for that. And with that, we will have a data readout by the end of the year in perhaps one of the most important clinical trials in the field. But what's important from an investor or a business standpoint is that because of this improvement, the phase three trial duration will be 24 weeks. And which is what you need for chronic treatment if you can show an effect there. And we know this from the FDA. This would apply in DLB. If you see significant, meaningful difference from placebo, you can get to prove on that. What that means is that phase two B trial of 16 week duration will do what it's supposed to do. Which is D risks substantially phase three. And that's what definitive proof of concept mean. That phase three is truly confirmatory. And not asking a whole new question as often it has been in AD. John, it seems like you and the ServoMed team have been quite efficient and productive and continue to stay quite lean. What advice would you provide folks that are listening, particularly in this environment in terms of how to accelerate your path to value creation but still continue to operate in a lean fashion which in my opinion, this environment mandates? It's about prioritizing and certainly through a certain point. And this is where I think in our industry, proof of concept in many, many different ways is a critical point. It's certainly the major value inflection point. But it's also a tipping point inherently in terms of development program. If you know your drug works, then you don't hold back. You do need to be fully staffed and that's our plan with phase two B result. And I mean, ahead of that, we're laying plans for that. We will grow. We will build the infrastructure to take this drug to the market. And that simply requires that. But ahead of that, one has to be thoughtful, my mind, of what are the questions you need to answer to know that your drug works and that you have a clear path to approval beyond that. Now, that may require, in some instances, more CMC work than you would in other contexts. It may require you do one, make sure that you have your handle on toxicology. But most of that is really focused on the clinical part and what are the key points in there. And most of that is now, it is through to a certain stage. You don't need to do that in terms. I think you're often better off doing it virtually. And I think it's, and the way you can succeed in that, if you're in a novel therapeutic area, is build very close relationships with a small number of key institutions, academic institutions, who have a lot of expertise to bring to you. In our case, the VU Medical Center in Amsterdam has served as well from 2014 onwards. Continue to have a very close relationship with them on the biomarker side, on MRI. More recently in DLB, we're very close with Mass General and with the Mayo Clinic. And there are groups of people there who give different insight in all sorts of different aspects of the disease. But it's really to find thought leaders that think broadly in terms of concepts, ideas, and build relationships that where they are advocates for you and the drug. They're doing an end for patient. And those people do exist. - And John, you founded EIP several years ago. And now you've been working at the Combined Entity for quite some time. I'm sure there's many impactful decisions that you've had to make and challenging decisions that you've had to make along the way. Was Kirsten, if you'd be willing to share one of those decisions, whether it be around indication, selection, or how to structure the team or anything like that comes to mind, where in retrospect, that was quite an important decision that you made, but obviously it was really challenging to make when you were making that decision. - I would say just probably the best one would be going into DLB. Because when we did so, it was in the first decision was in an SAB meeting we had in September of 2018. And at the point, there was most of what we know about the drug and how it's acting in DLB, we actually didn't know. We had animal data that was relevant to Alzheimer's and inflammation and its effect on the hippocampus, which is the memory forming part of the brain, where we're acting ultimately and where we're having real impact is on a different part of the brain called the basal forebrain and the colonergic system within the basal forebrain. We didn't know any of that. In going towards that, we had to raise money as well. It wasn't obvious, but I will say that the SAB and one of the advisors we brought in to present to the SAB on DLB, someone at UCSD, was really helpful towards that this was a good idea and gave us some confidence. But again, it wasn't an obvious choice to go there. - Thanks for walking us through memory lane there. Before we let you go, one last question and you would hint at a response here, but I'll come back to it. Given all that you've seen now and all that you've experienced throughout many years of your career, what's one piece of advice you wish you could provide your younger self knowing all that you now know? - I think it's less so on the science and medicine, but actually, which is obvious that in clinical development, you have to have patience and stick with the program because it just takes time. What I would say to my younger self is to the business and the business model and company, et cetera, patients there as well. I am very much science focused, but I think in retrospect, in a lot of different settings, having straight out, let's say, biogen or vertex, a longer period of time could have been that much more productive for me professionally. It's part of the reason now, and I think I can stay as I am now 10 years in to the program now. It is actually paying, I think my younger self may have given up on this two or three years ago. My older self with the learning is we're committed in being now a public company. It's great. I grew up at Biogen and vertex, talking to investors, being in a public company, setting and operating in those principles. It's more natural to me now, but there was a point in the private company context that was ready to give up on that. I'm glad and it's really paying off. - Well, John, thank you so much for joining us today, for walking us through the important work that you and your colleagues are pursuing at ServoMed and look forward to having you back on as your programs progress to later stage. - Yeah, thank you for having me. It was a great conversation. Thank you. - Thank you for listening to this episode of Biotech 2050. This episode is hosted by me, Rahul Chaturvedi and Alok Taiyi. If you enjoyed this episode of Biotech 2050, please subscribe to our podcast and leave us a review. Also follow us on Twitter and Instagram and Biotech 2050 pod. Again, that's Biotech 2050 pod. Until next time. (upbeat music) (upbeat music) [BLANK_AUDIO]