2023-03-13 14:49:10 ET
Regeneron Pharmaceuticals, Inc. (REGN)
Oppenheimer 33rd Annual Healthcare Conference
March 13, 2023 9:20 AM ET
Company Participants
Ryan Crowe - Vice President, Investor Relations
Neil Stahl - Executive Vice President, Research and Development
Jamie Orengo - Vice President, Allergy and Immunity Research
Conference Call Participants
Hartaj Singh - Oppenheimer
Presentation
Hartaj Singh
Great. For joining us, I always have to remember to give that pause. Always thank -- a little thankful to the operators for making this so smooth.
Our early morning on a busy and a little bit interesting week here on Wall Street. We've got Regeneron one of our favorite companies joining us. We have Neil Stahl and Jamie from there, and Ryan also joining the three of them.
We'll do a modified sort of fireside chat, we'll talk about the company's pipeline and some of the thoughts as to how the company is pursuing current projects and future projects also. One other Regeneron folk was not able to join us, John, but hopefully later on today, sending him our very best thoughts.
So, Ryan, please take it away and then we'll go the fireside chat.
Ryan Crowe
Thanks, Hartaj. I'll try and keep this brief, and thanks for hosting us here at the Oppenheimer Healthcare Conference just wanted to remind folks that remarks made today may include forward-looking statements about Regeneron and each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in such statements.
A description of material risks and uncertainties can be found in Regeneron’s SEC filings. Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.
Okay, Hartaj, back to you.
Question-and-Answer Session
Q - Hartaj Singh
Thank you. Thanks, Ryan. I really, really appreciate it. Neil and Jamie, maybe just start off very, very broadly, whenever I have kind of heard some of Regeneron’s thoughts behind the pipeline, George has spent a lot of time explain the company's approach. We've also had one of the heads of IO last year.
Maybe we can just start Neil with you, as to what are the fundamental underpinnings of how Regeneron use its pipeline, both R&D, and then maybe Jamie, can give us a perspective from the immunology and allergy side.
Neil Stahl
Sure. First, it's great to be here this morning. I hope everybody's getting used to daylight savings time. I'm not quite used to yet myself, but I've been with Regeneron for 32 years now, and it's really amazing that we've had really the same perspective and approach that entire time and that we couple, deep biological pursuit that sometimes can last decades on a single problem along with technology development that is provides us with cutting edge tools to rapidly get new candidates based on the discoveries that we made, and so, I think one example that, Jamie can touch on is Dupixent where I worked on that for 25 years, just taking the long view before we actually got it turned into to a drug. And then the VelociSuite technologies, which we worked on for two decades at least, those allowed us to do things like make Ebola drug, MERS drug and COVID cocktail very rapidly, like in four months, which is really unheard of.
We also invested heavily in the Regeneron Genetics Center, which really is the world's largest database of genetics, human genetics linked to anonymous medical records, that allows us to discover potential targets in biology that wasn't known before right in human beings. So it's a huge, huge tool. Beyond what I think is one of the best, if not the best antibody technologies in the world, we've also created collaborations to explore some of the new modalities that I think are going to be critical for the future of biology, and that's with CRISPR who we've partnered with Intellia and also siRNA with Alnylam. And we have a lot of really interesting programs that maybe we'll touch on here in this meeting, certainly in the day.
Hartaj Singh
To that point, Jamie, just sort of going over to you, Dupixent has, you know for lack of a better word, taken the world by storm change the course of the disease and patients atopic dermatitis especially. Just what are your thoughts on next stages for Dupixent, and I'm actually kind of asking this question because we'll have to ask about COPD somewhere down the line, but maybe if you can just set the stage for us before we go there.
Jamie Orengo
Right. So, thank you, and it's great to be here. I can echo a little bit of what Neil said and relate that to Dupixent. I've been at the company for 15 years, also super excited about the work that we're doing at Regeneron and really believe, and see that we're a technology based company, right? And we're constantly thinking of new ways to tackle complex biological questions, right? COPD would be one of those really complicated diseases that we're thinking about. And Dupixent, as you know, it started in our Regeneron research laboratories, and we've been working on this for a really long time and constantly trying to understand what are the key drivers of type 2 inflammation?
We believe that IL-4 and IL-13, play a key role. And then constantly on packaging the roles of IL-4 and IL-13 in different diseases, we've been able to identify areas that we believe we could benefit patients, right?
COPD being one of them, obviously asthma, all of the other indications which Dupixent is approved for. It continues to perform well in all of the approved indications and we have new indications coming down the road in the near future.
So, you know, I think the future is bright for Dupixent, right? I think we're just, at the beginning.
Hartaj Singh
And, Jamie, before going back to Neil, I mean, I just want to, kind of drill down a little bit there, with Dupixent, the focus on various types of inflammatory mediated conditions, you went from atopic dermatitis to asthma, specific portions within asthma, other indications also, how has the signs translated into these clinical advances? Like, what's been the stepwise process you've taken? And then again, I'll ask about, you know, we'll talk about COPD after this?
Jamie Orengo
So, I mean, this is something that I love talking about, right? As a basic science researcher, I think one of the views as the company is to understand the science and use the science to pick indications, right? There are no other deciding factors. It's really what's the biology of the disease. And then once we can understand that, we can apply medications that we also know the biology of and match the two together, right? And so we believe that we're making these thoughtful decisions where we understand, what are the key drivers of such disease, and in knowing that then we can take a medication and bring it there.
So something like Dupixent, you know, to Neil's point, we've all been working on this for a really, really long time and really trying to understand how this molecule is behaving in patients and in understanding how it behaves mechanistically in patients, we can understand the diseases that we can apply for future indications.
Hartaj Singh
Yes. And last question, just on COPD specifically, Jamie. We'll probably come back to this a little bit before the end. But I remember a few years ago, it didn't seem like Regeneron or partner Sanofi wasn't as excited about COPD. It's a different sort of a disease from like an asthma, as a lung disorder, more of a smoker disease, I guess. What's changed in the last two, three years to give it seems, your partner Sanofi and Regeneron, more confidence as you approach the COPD readout.
Jamie Orengo
So, you bring up a good question, right? And we all know for COPD, there's been no innovation in this space, right? There are no biologics. Patients, there's a huge unmet need for these patients, right? And as I mentioned, we've been learning more about how Dupixent works in patients, where it can improve, specific impacts in airway diseases, right, improvements to lung function, improvements to exacerbations, applying that knowledge to mechanisms that drive COPD, and the two married, right? So that we can then, hopefully we'll see an impact as these trials read out.
Hartaj Singh
Yes. That helps a lot, Jamie. Neil, kind of going back to you, we'll talk about EYLEA and maybe a little bit later, but maybe just about oncology where we've really focused the last few years. And I know if you can maybe just talked a little bit about what we're going to ask, John, which is that how is the company sort of doing its mix and match approach. It's been going on for about two, three years now. It seems every ASH or EHA, the company is getting more thoughtful and smarter about these. As ASH (ph) was definitely, I would imagine, the [odro] (ph) bispecifics, I mean, the energy I saw around bispecific is phenomenal. Just maybe, if you can just answer that question, a high level senses how are your combinations working out? How are you thinking about them going forward?
Neil Stahl
Sure. I mean, we have a really good foundational drug which is Libtayo, which is as good as any PD-1 blocker out there. And we call it foundational because, you know, as good as it is. There's still a lot of indications and a lot of patients, that are not treated well with it. And so, we firmly believe that adding in some of these other molecules, especially bispecifics, is a way to enhance the activity or increase the indication spread or increase a number of patients that respond. And so far, we've focused on both the CD3 bispecific pathway as well as now a CD28 bispecific pathway.
CD28 is the signal two of T-cell that by activating it in the presence of signal one, which is CD3 activation that you get more activity in cases. And the beauty of the CD28 is so they have, they have a really safe profile. There are maybe one or two that kind of molecules that do have a bit of activity.
So you're right, that the hardest thing is figuring out what combinations to use. And so, we really are expanding our reach to look at patients and biomarkers and things like that, try to understand which molecules might be the most effective.
The other thing is that, I do believe that we have the best mouse models of these diseases in the world that we've made humanized immune systems and humanized mouse and put in human tumors, that I think give us a better readout on which molecules to combine together than perhaps other companies or individuals had been able to have access.
Hartaj Singh
Yes. And to that point, I guess, as we see the updates from Regeneron, it seems you're also very fast follower, for example, in the PD-1 and the LAG-3, dual antibody approach, right? And then you've also got Libtayo combined with bispecifics. Has there been any sort of, I guess, learnings that Regeneron's having that some tumors might be more amenable to two antibodies versus an antibody plus a bispecifics out there. Any such thoughts coming to Regeneron when you're thinking of different tumors you're going after? Or is it still, you're using the best science to go after every tumor?
Neil Stahl
I think that we try to pick tumors that we think might have the best bet. But before we do that, we actually have to come up with the best molecule to treat them with, and so, we can compare our LAG-3 antibody to other people's LAG-3 antibodies, and evaluate whether or not we think ours has an advantage. And in every single case, our antibodies are either as good or have superior properties to what others have come up with. And I think you can see that in our LAG-3 data where we have some really interesting activity that although not directly compared to head-to-head looks really interesting compared to what others have shown.
Hartaj Singh
Yes. No. Absolutely. I mean, even Libtayo, we're doing some work there, especially in chemo combo, and it's really fascinating how much, further Regeneron has been able to push that antibody even though I think pembro is a fantastic, agent also.
Jamie, just kind of going back to you, IL-33 comes up from time-to-time in COPD, it seems a couple of years ago, Regeneron seemed a little bit less excited, now it seems its back in play. Just how to think about IL-33 assuming, Dupixent and COPD works out?
Jamie Orengo
Yes. So, we've always been excited about IL-33, right? This is another molecule that came from Regeneron research laboratories. As you recall, we tested it in asthma, and we also have some really exciting proof of concept data in COPD. In asthma, we also achieved proof of concept, so it's telling us that IL-33 is very active in the airway.
With respect to COPD, and that Phase II study, which brought a lot of excitement to the industry, is looking at our pre-specified subgroup analysis where we found that in patients that were former smokers, there was a 42% reduction in exacerbation. This was really incredible, right? So, we were really excited about these data. We kicked off two parallel Phase III studies to see if we can replicate these findings and eventually bring something like this to patients in need.
As I mentioned previously, there’s really limited options for patients with COPD, so we think this could be really beneficial.
Hartaj Singh
And I apologize, Jamie, if I indicated that maybe Regeneron's “love” for IL-33 had waned a little bit, it seems not. Maybe you can just talk to us a little bit about the COPD population that you're going after in this Phase III trial and where that population stands within the overall COPD sort of patient population?
Jamie Orengo
Right. So, for itepekimab there is no eosinophil requirement for these patients, right? So regardless of your eosinophil levels, we think that itepekimab could have benefit. But where we see this huge reduction in exacerbation is really limited to the former smokers. So, that's where we're looking to position this and where we're seeing the clinical benefit for those patients.
Hartaj Singh
The other question I have is just on the overall, I know this is more of a commercial question, but I just want to ask you this because I imagine it's important for you also when you look at the signs, but biologics are still underpenetrated in various, sort of lung associated conditions, asthma, probably better than most when you look at COPD. When you're running these trials, what's the level of comfort physicians have, using biologics to treat COPD for example?
Jamie Orengo
I mean, I can start off and then pass it over to Ryan, after. But from my point of view, I think with respect to COPD, it's going to come down to what the data say in the end, right? And if there's a meaningful reduction in exacerbation, together with improvements in lung function, there's reason to believe that physicians will use it. I mean, these patients are really looking for a therapy. I think clinicians are looking for a therapy that can meaningfully impact their disease.
Ryan Crowe
Yes. I just add to that, I think, per to a variety of opinions on what clinically meaningful is, and I think each KOL sort of has their own view on that. But for Regeneron, I think really to Jamie's point, a statistically significant result in this population would be very important. We haven't had one of those in the past. This is a disease that is the third leading cause of death globally. And hasn't had any innovation for decades. So, I think the low end for us would probably be in the mid to high teens percentage and reduction in exacerbations. But certainly, we're going to aim for hire and hope that because of the enriched population, we're able to achieve that.
Hartaj Singh
Yes. And Ryan, when you're talking about the low to mid, this is for to see the Dupixent's COPD trial, right?
Ryan Crowe
Yes.
Hartaj Singh
Itepekimab [Indiscernible]
Ryan Crowe
Yes. And for at the itepekimab, I think, again, there hasn't been any innovation in COPD, so I wouldn't say that my opinion on that is all that different.
Hartaj Singh
Yes. Yes.
Neil Stahl
I also think that there's beginning to be a greater understanding that biologics antibodies in particular their specificity is just so high that the off target toxicity is really low or nonexistent in many cases. And so I think that gives a lot -- and just look at the safety of Dupixent, which is exemplary. So, I think it gives them a lot of comfort that they had a tool that will actually treat the disease easily.
Hartaj Singh
Yes. No, absolutely, Neil. I mean, it was a little bit of question, I kind of already knew the answer too when I asked Jamie because, rheumatoid arthritis, you already got penetration of biologics in the high 40s and 50s. But again, you've got six, seven, eight companies marketing there. So, I imagine Marion's probably licking her chops, assuming a Dupixent approval and COPD positive Phase III trial, then approval. I imagine her staff would be very happy with.
Neil, maybe just coming back to you, if you can just kind of give us an idea as to where odronextamab is in terms of a potential filing this year. And then PSMA, both the CD3 and the CD28, it seems that's where the greatest excitement for Regeneron is right now for those two bispecifics?
Neil Stahl
Yes. So, I mean the PSMA results were really spectacular. In a situation where you don't have any responses, there we are getting 90% decreases in the target biomarkers, which is unbelievable. There was some toxicity accompanying it that we're working on ameliorating, and we had some I think strong ideas about how to do that.
So we're really, really excited by that. And I have to say that that data exceeded my own personal ideas of what would actually be achievable. So that was really heartbreaking, really good. Our BCMAxCD3 is also a really good model, [technical difficulty] that has shown really strong activity, shows a lot of activity, and then odronextamab, will I think file this year, right? Ryan?
Ryan Crowe
Yes. I think our goal for both the BCMAxCD3 bispecific known as Linvoseltamab, as well as CD20xCD3 bispecific odronextamab, both on track to submit for accelerated approval later this year. And certainly, we're excited about both. And I think you know, our whole goal here is to lay the foundation for potentially introducing costim to the hem-onc space and later in the year, we're going to co-administer a CD22xCD28 with odronextamab to help -- to hope leapfrog kind of the levels that we've seen in that category. And with BCMA, we also have a costim in the works to work in combination with linvoseltamab. So, there's some exciting things even beyond just these initial opportunities in the hem-onc space for Regeneron.
Hartaj Singh
Thanks, Ryan. That’s very helpful. I did not realize that, BCMA and PSMA -- BCMA would be under the accelerate approval potentially. Neil, just one last question, which is that you know, Libtayo seems to be a foundational medicine for Regeneron. Could odronextamab also be like that? I mean, when we've talked to physicians using bispecifics, they're getting comfortable with the Roche CD20 bispecific, could odronextamab sort of be similar in that vein or not really live higher the PD-1 is sort of the foundational medicine that you want to build on that? Or just how to think about that?
Neil Stahl
Well, I think that with odronextamab, there will be other combinations that we can use. So, in that sense that, we can add another molecule that might increase the activity or the number of indications, to that extent I do think that there is a foundational aspect to it. You know, the beauty of Regeneron's bispecific technology is that it's universal, so we can mix any of the two arms together, which gives us a huge library in different molecules that we can reach into.
So we have CD28, we have a lot of other co-stimulatory molecules that we really haven't talked about yet as well. So I think there is a very broad range of things that we can reach into for the future as well. But, yes, I do think many of them have a chance to become, I think, BCMA as well.
Hartaj Singh
No. I mean, it's the data that you're rolling out is fascinating, just for going over to Jamie, Neil, can you just mention what are the next sort of level after BCMA, BCMA or bispecific you get excited about that, year or two years from now we could be talking about on a call like this?
Neil Stahl
Yes. So, you did mention that the CD22xCD28, which I think is an interesting molecule as well. And just being able to combine different CD28 stimulators together in the same cancer, and I mean, we could put in pre-molecules together, and they all have different cell type specificity potentially or target binding molecules, but together they could really act to increase the activity of the immune system against the tumors. So I think, it's really exciting just to see how these combinations are going to play out and increase the activity.
Hartaj Singh
Yes. And, Jamie, I was going to go to you now, Dupixent in atopic dermatitis, asthma, the other indications which we don't remember as well on Wall Street actually I apologize, but what other areas do you get excited about an allergy and immunology, aside from Dupixent and IL-33?
Jamie Orengo
Yes. So, I mean, I think as a company the future is bright, right? So, we’re a research focused company just as I was talking before. So, we're really working hard to understand disease mechanisms, disease drivers, and then apply that knowledge to actually make our therapeutics, right? How do you make a drug for something when you don't even understand the disease, right? So we need to understand the disease and then take things forward. So coming up, we kind of touched upon it already outside of Dupixent. I think the next big thing, best big thing is itepekimab in COPD, right? And we're really looking forward to seeing those data come out because this is an additional population outside of Dupixent, right, that we could see some clinical benefit. We know, for example, the former smokers are 70% of COPD patients. So this would really be complementary and it allows for additional potential therapy for patients with COPD.
Hartaj Singh
Yes. And Jamie, I mean, if you were to think sort of a little bit what I'll call and maybe, Ryan might not want you to do this, but I going to ask anyway, a little bit outside the box, in the central Wall Street folks where something that you look in the pipeline when you sit down and with your team and you're like, you know, nobody's really paying attention to this, but this, personally excites me a lot. Is there anything from that perspective?
Jamie Orengo
I mean, I could just touch upon, very generally. Obviously, we don't go into the details at this kind of forum. But what excites me is that we're doing precisely that. We're really trying to understand autoimmune diseases, for example, deeper mechanisms of allergy so that we can then just not bring forward another vanilla antibody but really be creative, think about combinations, think about what exactly is doing this. Autoimmune diseases are very complex. They're heterogeneous. You can't just throw something in the air and hope for the best.
So we're trying to make scientific decisions about where we can see benefit and bring things forward to patients.
Hartaj Singh
No, it's really fantastic. I mean, I think just the stepwise approach you know, in ANI, it's really, really something else. So, honestly makes our life easier a little bit at this also. Neil, maybe just we can kind of, we're getting to the last three, four minutes here. So kind of like analogous to final jeopardy. John isn’t here. I know we've a lot about IO. You talked about some of, Ryan actually I think mentioned some of the other partnerships that I think are interesting.
Could you maybe just touch upon what you think about aside of cancer, that you really get excited about, especially in the partnership area, because honestly I don't think we've you know, as an analyst for our team, I don't think we've spent enough time there. We'll probably need to this year, but just any thoughts there.
Neil Stahl
Well, this is one of the most exciting things for the future, I think is these alternative modalities, as I call them, either siRNA or CRISPR and you've undoubtedly seen the data with TTR amyloidosis where we can get along with Intellia who's running the clinical trials get a much greater than 90% to 95% drop in the amyloid circulation levels, which is unprecedented, really. And this is after a single treatment in these patients. And so far, the safety has looked good from that systemic CRISPR approach.
We're also very excited about the opportunity to do siRNA, both systemically and especially in the nervous system, though you may remember that Regeneron was founded as a neurobiology company 35 years ago. Regeneron means regenerate neurons back in the day, and so now I think we have an opportunity in the tools and the animal models to actually attack some of the most insidious neurodegeneration debilitating diseases that faced mankind.
And so I'm very excited about doing that, we actually have a trial already and trying to knock down amyloid precursor protein. And we have biomarkers that we're looking at to gauge our success in doing that. And there's a lot of other really interesting targets in the nervous system that are -- that we've discovered and others have discovered.
And once again, we have the most unbelievably good mouse models that are humanized mice that share the exact features of the neurological diseases with humans in an unprecedented way. And so again I think that gives us a really strong toolbox to try to figure out which pathways we should be blocking and which molecules we should be taking into people since we're using human specific drugs in these human eyes to mice.
Hartaj Singh
Neil, not to put you on the spot here and maybe Ryan, might jump in. But, the company has really good partnerships and tell you the truth, as an analyst I've talked to smaller companies, and they really quite a few companies have told me they'd like that, Regeneron is their partner of choice now in large cap biotech, because of the attention to detail and the collaborative approach Regeneron has. But, Neil, how do you think as a scientist between wanting to partner and between wanting to internalize. I mean, I don't want to make this into a capital of this buy versus etcetera. But just how do you think -- how do you approach that when you look at a potential technology partnering versus maybe internalizing?
Neil Stahl
Yes. I think, we've always had the same attitude. If we find potential partners that are like minded to us that really like to dive deep into the science and work incredibly collaboratively and have breakthrough technologies, then we're really happy to work together with them. And sometimes that does just doesn't work out, and we actually take it in and develop it all internally.
Hartaj Singh
Yes. No. That helps a lot. So it's actually good to be collaborative, yes, and better chance of getting little a bit more money out of Regeneron. Jamie, I would just maybe end with you, the eye area has been really big for Regeneron and important commercially, cancer is becoming more important. But Dupixent is sort of carrying the load from a growth perspective. How do you think of the pipeline kind of helping Dupixent, not just from geography or ages, I know you talked about IL-33, which other areas could really add to the ANI profile going forward?
Jamie Orengo
Yes. So, as you mentioned, we're still invested in type 2 inflammation and allergy and immunity, right? We're still looking earlier in the pipeline, what's next after Dupixent, right? Can we bring other things forward in the T-2 space? Dupixent has allowed us to understand biology of some of these indications, right? We're learning from our translational studies. We're learning from our clinical studies outside of allergy and type 2 inflammation.
We're looking into autoimmune diseases, as I mentioned previously, and relying on some of our tools that we have internally. For example, mouse models the ability to humanize mice and actually study human disease in a very complicated system that can help hopefully we can translate that into additional therapies to bring forward to help patients.
Hartaj Singh
Yes. I think we're actually on the time or just beyond the time. Jamie, Neil, Ryan thank you so very much. Again, give John our best regards. Thank you for participating. We really, really do appreciate you here at Oppenheimer.
Ryan Crowe
Thank you, Hartaj.
Neil Stahl
Thank you very much.
Jamie Orengo
Thank you so much.
Hartaj Singh
Everyone take care. Have a good day. Alright. Take care.
Jamie Orengo
Bye.
Neil Stahl
Bye.
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Regeneron Pharmaceuticals, Inc. (REGN) Oppenheimer 33rd Annual Healthcare Conference