Joe Coletti
Welcome back to Pathfinders, a podcast series from RBC Capital Markets where we uncover key trends and catalysts, shaping the fast moving world of biopharma and healthcare. I'm your host, Joe Coletti. In today's episode, we're joined by three of our biotechnology analysts, Brian Abrahams, Luca Issi and Gregory Renza. And we'll discuss and we'll explore their key insights and takeaways from RBC’s annual Dr. Day series, covering various therapeutic fields and treatment approaches. Brian Luca, Greg, thanks for being here.
Brian Abrahams
It's great to be here.
Luca Issi
Great to be here.
Gregory Renza
Great to be here. Thanks, Joe.
Joe Coletti
So just to kick off and give our audience a little bit more background, Brian, maybe you can explain a little bit more about what exactly our Doctor Days are, and why they're so valuable.
Brian Abrahams
Our Doctor Days are in person science oriented forums that RBC hosts in major cities across the country. This year we hosted in San Francisco, Baltimore, New York, and Boston throughout the month of March and April. These are closed sessions each attended by up to 40 institutional investors. At our annual Doctor Day sessions, we bring together key opinion leader clinicians and researchers from various therapeutic fields. Their purpose is to share insights around disease mechanisms, treatment options, and emerging trends. These discussions help us stay informed about novel drugs, clinical trials, as well as breakthroughs in medical research. For instance, this year, we had the privilege of hosting several thought leading ophthalmologists, oncologists and psychiatrists. These sessions provide a valuable opportunity to validate scientific hypotheses. And the insights gained can significantly impact investment decisions and drive market adoption.
Joe Coletti
I'd like to pivot now and start to look at some of the key themes from your KOL discussions. Greg let's start with you. There's been a clear uptick in strategic activity in targeted oncology modalities. What are those treating cancer on the front lines saying about these new waves of innovation?
Greg Renza
Yeah, that's right, Joe. There are more precise and personalized approaches to treating an array of cancer today that are grabbing the headlines. And it's very timely and informative to sit with doctors to review these new datasets and to look at these new commercial successes across precision oncology. Now, key therapeutic modalities that have dominated or emerged this year and over the past include antibody drug conjugates, as well as targeted radio pharmaceutical therapies, which do correspond in our view to their broader clinical and commercial validation, as well as large pharmas effort to expand their pipeline and to conduct some M&A activities. Now additionally, we have noted a resurgence in targeted therapies among other areas, such as protein degradation, and synthetic lethality, and this has been evidenced by several debuts of novel targets and newer players. The doctors that we and our investors have engaged with appreciate adding new tools in their toolbox. Now radioligand therapy was indicated as a significant area of interest. And this is driven by the real world experience and the improving experience with Pluvicto and that in turn drives treatment centers and patients to want to participate in more clinical trials. We are seeing several stakeholders now solving for some of those usual complexities and making targeted radiotherapy more user friendly and more accessible. And this can all help address some of those stigmas that we have traditionally seen at the bedside here. Also, we're keeping an eye on some of the combination potential using next gen IO therapies, adding this and making a more precise approach even better; utilizing new dosing approaches, understanding how drugs can work alone, as well as putting them together to maximize effects. That said, we are still in the early innings here. datasets are immature, and it does command patience. However, we do believe that there are several blockbusters on the horizon across several of these modalities. And I think biopharma is matching this enthusiasm that we are seeing and hearing on the front lines. The strategic activities over the last year on radioligand therapies have been unprecedented. And also rather validating. Acquisitions, but also some key collaborations. So these are companies working together, in addition to larger players, just simply beefing up their resources. And we believe this can only accelerate that ability to reach patients.
Joe Coletti
Greg, we know that immunology and inflammation continues to be a compelling area for investors. But the markets and opportunities are vast. How is the time over the Doctor Days help to break down the new wave of treatments for these larger, chronic but also complex patient populations?
Greg Renza
So in a specialized area, such as with nephrology, or with kidney diseases, we do focus on these new areas of novel antibodies that have disease modifying effect. So we have a sound rationale of mechanism of action with an ability to actually address the root cause of something like IgA nephropathy, our kidney specialists particularly noted BAFF inhibition mechanisms as most compelling, again addressing the root cause of IgA again, and that potential to treat patients early. And with again, this is a condition where severity and chronicity are really underappreciated.
The doc simply views this as practice changing. When a percent of the US population is essentially affected by immunologic diseases, we do believe a staged approach to drug development is critical and finding the next asset that can have broad applicability. There are meaningful opportunities in lupus, autoimmune kidney disease, as well as cytopenias. The potential of over an estimated $165 billion in sales is potentially achievable once these programs work, but it starts in clinical trials. And a trial is comfort to see a development candidate succeed locally, contribute to data generation and then have that ability to reach more patients is critical. Also when it comes to a field like allergy and dermatology, another key inflammation and immunology area; indications like chronic urticaria, asthma, and COPD also rise to the top. We estimate about 5 million patients have an addressable market and a market potential of over $100 billion. So a great deal of improvement when it comes to effective and easier to manage therapeutics. Practicality was a big theme across all cities, for indications large and small. And when speaking with a medical oncologist, for example, someone who's treating ocular cancer, the advent of radiation surgery and IV infusions have revolutionized the field. They've helped patients on several efficacy measures, but these treatments are still inadequate, they do warrant new options. So solving for some of those challenges of the way things are currently done is also a prompt for development. IV inconvenience, safety issues, a limited population, this can all be solved with new oral options in addition to having multi filled response improvements. There are several attributes of these new drugs are programs that have practical features that deserve attention and are part of their own benefit risk calculus and should be part of ours.
Joe Coletti
So in the cardiology space, you guys have been telling me how much there's been so much ongoing research and treatment options for Transthyretin Amyloid Cardiomyopathy (TTR-CM). For our listeners, TTR-CM refers to a heart condition caused by abnormal protein deposits in the heart muscle. Luca, would you mind just talking us through some of the approaches researchers have taken to study and treating this conditions and the debate the medical community is currently having around treatment options?
Luca Issi
I mean, I'll make two comments, maybe a bigger picture comment on cardiology more broadly. I do believe that Cardiology is the new oncology. In other words, I think, you know, oncology really has, we've seen a lot of success in oncology because we have a much better approach in slicing and dicing patients’ populations and finding the right therapy for the right subtype of cancer that you have. And, you know, I think probably breast cancer is the perfect example of that, like, you know, what kind of breast cancer? Is it HER2-positive positive or HER2-negative is it ER-positive or ER-negative is PR positive or PR-negative is triple negative breast cancers... and for each of the different subtypes, we now have drugs that are really tailored to all of these subtypes. And I think this tailoring, the slicing and dicing the patients and find the right drug for the right patients is really allowed the field to make a lot of progress. And, and I think Cardiology is next. I think Cardiology is the new oncology because we have, I think, a much better sophistication in really slicing and dicing patient populations in cardiology, and I think TTR cardiomyopathy, to your point, is the perfect example of this. Because, you know, yes, you have cardiomyopathy, but your cardiomyopathy is actually caused by this protein called TTR. And so I think having the ability of having therapies that tackle this specific protein and prevent this protein from accumulating in the heart can really go a long way for patients. And so, you know, there's a lot of innovations in that space. And TTR cardiomyopathy is commonly referred as the Alzheimer diseases of the heart, because you have these plaques that accumulates in your heart. And there is a current therapy from Pfizer that generates $4 billion in revenues, and has been transformational for some patients, but now we have a lot more coming down the pike Alnylam. And there is in particular, this phase three trial this upcoming from a company called. And this is a highly anticipated trial that may show us that a new class of therapy called the silencers therapies, which actually turned off this protein in deliver may make an impact for patients. So lots of debate during doc days on, you know, expectations for this trial, it was very, very healthy debate between kind of bulls and bears on whether this trial is going to work or not, it's gonna be very, very important catalysts for the biotech sector more broadly. And that data is coming in late June, early July.
Joe Coletti
Sticking with cardiovascular. How have genetic medicines been impacting the space. Why is this area so ripe for disruption by genetic medicines in particular, Luca?
Luca Issi
Yeah, great question, Joe. I mean, I again, I'll make maybe a bigger picture comment, which is, you know, I'm obviously biased because I'm putting my career behind genetic medicine. But I do believe that we have a much better way to understand the genetic root cause of the diseases. And for a very long period of time, all we had was just an understanding of the genetic root cause of diseases, but we did not really have tools for tackling those diseases. And now we do. And you know, if you think about bigger picture, if a disease is caused by a lack of a gene, you can actually deliver that gene with either mRNA or gene therapy. Or if you're want to turn off a gene, you can use siRNA or antisense oligonucleotide. And now we can even edit, you know, the genome using gene editing and CRISPR cas9. So I think this is a technology that will that will have an impact on cardiovascular diseases and many other diseases. And I think maybe one, one target that was really highlighted during our conversation during doc days, is actually this target called LP(a), and LP(a) could basically be the next cholesterol, just as we talk about cholesterol today. And maybe in the future, we're going to talk about L P(a). And you know, there's a lot of companies developing therapies for LP(), they're, you know, trying to knock down LP(a). And, you know, companies are essentially testing the hypothesis that knocking down LP(a) can actually drive a cardiovascular benefit for patients. And so the jury's still out. But one highlight from these dark days that I'm still reflecting on it, is that one doc actually made a pretty bold statement, suggesting that he thinks that the correlation between LP(a) reduction and cardiovascular benefit could actually be better than what we're seeing for LDL and cholesterol. So we know the lowering cholesterol drives a cardiovascular benefit. And he was arguing that maybe lowering LP(a) could have a cardiovascular benefit is even better than what we've seen for cholesterol. So that obviously will go a long way for patients’, investors, and other stakeholders. So the jury's still out the data from Novartis Amgen and Eli Lilly is going to come next year and the next few years. So again, the jury's still out, but I thought it was super, super interesting comments from that Doc. So I wanna share with you as well.
Joe Coletti
Let's stay with you, Luca but let's turn to ophthalmology where the dynamics around gene therapy approaches for common ocular diseases is really picked up. Can you tell us a little bit more about that?
Luca Issi
Yeah, happy to. I mean, look, um, you know, in ophthalmology, the current standard of care has made a lot of progress. And when you think about disease is like a wet AMD, we have very, very effective therapies that are dosed very infrequently. And so I think the analyst community and the investment community, I think is pretty cautious about gene therapy for wet AMD. Again, given the progress this the standard of care has made. So a lot of people even question whether we need gene therapy or not because patients are relatively well managed today with the current standard of care. And I think one of the surprises for me during doc days is that Doc's are actually pretty excited about it. You know, this says the potential promise of a one and done approach. So you know, this is as close as it gets to potentially functional cure, and I think it was one doc did mention, not only is he excited about gene therapy, most Doc's are excited about gene therapy conceptually for wet AMD. But then when it comes down to like a commercial adoption, many of them are a little bit more cautious. But we have had one doc in particular who was pretty enthusiastic not only about the science around gene therapy for wet MD but also the potential of using gene therapy commercially. I think one doc actually argued that he can see 30% of his patients with wet AMD, ultimately be on this therapy. So again, an area where it's interesting to reflect on the dichotomy between kind of the investment community and the KOL community, the investment community, probably relatively cautious in this space. But the medical community was actually pretty, pretty excited about it. So I thought it was one of the key highlights from our doc days here.
Joe Coletti
Shifting back over to Brian, let's look at pulmonology. Can you elaborate a bit more on what's new and cutting edge in the treatment of lung disease that's driving some of the excitement in the space right now.
Brian Abrahams
So an estimated 14 million people in the US suffer from COPD, or chronic obstructive pulmonary disease that's 6.5% of our adult population. But treatments really haven't changed all that much from what's been given for years. bronchodilators and steroids. Long doctors that are doctors were really excited about some cutting edge development in the space, a different approach altogether, using biologics to tamp down some of the inflammatory pathways underlying the disease in certain patients. It's a concept that's really transformed the asthma treatment space, but hadn't really been used before and COPD. And they sounded really excited to integrate these new drugs into their practice once they become available. So that's something we're keeping a close eye on because we could see the first one approved as early as later this year. Another disease that pulmonologist have been struggling to treat is idiopathic pulmonary fibrosis or IPF. It's rarer, but it's severe and fatal. And our sense from our doctor discussions was that the treatments out there right now just aren't working all that well, for patients, they need more effective and safer options. Our Doc's did note some of the historical challenges running studies in this disease in that animal models, unfortunately, aren't very predictive. And patients can sometimes regress at different rates, which can make it hard to detect the signal. But they sounded really excited about some of the next generation targets being explored, including integrants, LPA, and PDE, where they see a lot of promise in the human trial data that's been shown so far. And there's several biopharma companies exploring these novel approaches.
Joe Coletti
I want to close and maybe stay with you, Brian, and talk a little bit about pain and Alzheimer's, which we've discussed on the podcast before. These are two disease areas of neurology that have been very challenging, but which biopharma companies have really tried to tackle including with some very recent efforts. What did you learn from the KOL physicians about some of the hope as well as some of the challenges within those areas right now?
Brian Abrahams
So as you may know, there really has never been a treatment for Alzheimer's disease that got at the root of the illness, the few treatments we have now, really just treat symptoms like band aids. But recently, we had the first approval of a drug that actually targets the underlying cause of the disease. And there's other drugs like this on the horizon as well. It hasn't been smooth sailing, though. And our sense from our doc days is that there's a lot of initial hurdles here, you need a PET scan to confirm the diagnosis, then you have to go in for an IV infusion every few weeks. And you also need to get regular MRIs to monitor for side effects. So not all the docs were completely convinced yet that the benefit risk equation made these drugs worth using — there is a big hassle factor involved. That said, it does sound like they're getting more on board with the idea and are starting to operationalize their administration at their respective centers. And between that, and prospects of easier delivered options like self injections, we think there's a lot of long term potential here.
Joe Coletti
And what about pain relief?
Brian Abrahams
Well, pain is another area in neurology that's been really challenging. One of the best options for pain relief we have is opioids. But obviously, those have side effects as well as addictive potential. So there's a big societal need to replace those. In acute pain, our doc feedback, though, was that the bar is really high. There's a lot of generic therapies out there in opioids and non-opioids, and for them to get behind a new acute pain relief drug, it's got to work quickly, and it's got to work well or they're just not going to be willing to fight insurance companies about it. On the flip side, there's a much larger opportunity potentially for drugs in chronic pain, since what's out there now isn't really that effective, but the bar there is high as well. And clinical trials in those settings can be tough to run to. Still, a lot of enthusiasm over how an effective chronic pain drug could be used, which continues to make it an attractive area for bio companies to invest in development for.
Joe Coletti
Brian, Luca Greg. Thanks for coming back to the podcast. I look forward to seeing you again soon. Well that's it for our conversation today.
Greg Renza
Thanks, Joe. Thanks for having us.
Joe Coletti
Thanks again for listening to Pathfinders and biopharma brought to you by RBC Capital Markets. Remember to subscribe to get more great content and be alerted about future episodes. This episode was recorded on May 3, 2024. If you'd like to learn more or continue the conversation, please visit rbccm.com/biopharma. See you all next time.