Regeneron Pharmaceuticals Inc at Jefferies Heathcare Conference Transcript

The following is excerpted from the question-and-answer section of the transcript.

Question: Akash Tewari - Jefferies LLC - Analyst : Awesome. Thanks so much, Mark. And you mentioned everyone's coming back from ASCO. I did as well. And I think the general view is we're hitting a wall of when it comes to oncology, right? We're seeing therapeutic window issues and limitations on efficacy whether it's durability, immune exhaustion across the board, whether it's in IO, whether it's even with some of these ADC targets. Let's start off -- and I think the other interesting thing is we're seeing oftentimes it's not different targets, right? The talk with PD-1 VEGF. It's sometimes the assets themselves that actually can end up having differences in a clinical profile. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. JUNE 05, 2024 / 12:30PM, REGN.OQ - Regeneron Pharmaceuticals Inc at Jefferies Heathcare Conference So I wanted to start off with your PD-1 LAG-3 program, and I think this is something top of mind for a lot of investors. You're going to have potentially first line data in NSCLC. That's going to be coming out soon. I'd hand it off to maybe your team. What did you see in terms of the development of agents in first-line and second-line NSCLC, and where do you think there's an opening for a high-efficacy PD-1 LAG-3 therapy to really differentiate here versus, let's say, using a Trop-2 ADC first line or some of these targeted therapies?

Question: Akash Tewari - Jefferies LLC - Analyst : Understood. And I definitely want to hit on melanoma, but maybe just to stay on NSCLC for a sec, Bristol has talked about they had a Phase 2 that I think they've verbally described. They found a signal in first line, and they talked about maybe 20% to 30% in first-line NSCLC where a PD-1 LAG-3 approach could possibly fit into the treatment paradigm. I don't know if necessarily your team shares that view where PD-1 LAG-3 is just a biomarker-driven subpopulation. Can you talk to us about for your program where you're seeing higher levels of receptor occupancy, do you think that PD-1 LAG-3 for NSCLC is a biomarker-driven approach or is something where maybe the population can be bigger than what Bristol has recently outlined?

Question: Akash Tewari - Jefferies LLC - Analyst : Understood. Now let's hit on melanoma. And to your point, I think if we saw the Bristol LAG-3, PD-1 APE first-line data that came out of melanoma, they had, I think, the same if not slightly lower response rate than even your PD-1 LAG-3 in first line. I think the pushback some investors have is, okay, it's an early study. Then number two, maybe Regeneron's early data, maybe there is a lower disease burden, maybe with slight differences in terms of patient population. And I think the second part is if we look at the multidisciplinary review for Opdualag, they tested higher doses of their LAG-3. We saw differences in terms of the response rate in that population, but I think one of the things the FDA noted is that didn't necessarily translate to PFS and OS. That's a data point, but you also have consistently shown higher responses across the board in melanoma. So when you think about your program and where you differentiate in melanoma, outside of ORR, where is your confidence that on PFS and OS, there's also going to be a clinically meaningful difference?

Question: Akash Tewari - Jefferies LLC - Analyst : Understood. And I think you mentioned something before, we were chatting ahead of this, LAG-3 and where is its ideal role in therapy in a lot of these solid tumors may be in that first line setting, not post PD-1. And I think that's really important here. Can you expand on that? And your point of, if we're really knocking down both of these targets in a way that's maybe different from these other agents, you're going to see efficacy with LAG-3 that maybe investors aren't really appreciating. So what is it about maybe in a first-line setting where LAG-3 really shines?

Question: Akash Tewari - Jefferies LLC - Analyst : No, that -- I mean, it's a good bridge because I think head and neck, obviously there's a lot of excitement with some of the bispecific approaches we saw, really encouraging data, I think, from Merus at ASCO, but I think something a lot of investors may not be paying attention to. So you actually have in late-line patients right now in head and neck PD-1, LAG-3 data that you showed very early. But if your point is really LAG-3 as a first-line REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. JUNE 05, 2024 / 12:30PM, REGN.OQ - Regeneron Pharmaceuticals Inc at Jefferies Heathcare Conference indication, you don't want to use it after patients have been treated with checkpoint inhibition. Help me contextualize the signal that you showed in late-line patients in head and neck at ASCO. How do you think that translates as we move up to a first-line setting?

Question: Akash Tewari - Jefferies LLC - Analyst : Understood. Actually, you mentioned adjuvant, and actually, it makes me think. You guys do have -- your team has with PD-1 LAG-3, I think we've seen with that regimen very strong disease-free survival with some of your peers. I know there's cancer vaccine approaches that Moderna and Merck have as well. When you think about PD-1 LAG-3 in an adjuvant setting, whether it's neoadjuvant or post resection, both for melanoma and NSCLC, do you feel like maybe investors are not appreciating the trials and your approaches in those settings right now?

Question: Akash Tewari - Jefferies LLC - Analyst : So right, you have data. We've seen competitor data from PD-1 LAG-3 where you can have disease-free survival in the 80%-plus range, which I think bodes well and stacks up well with some of the cancer vaccine data that we've seen from Moderna and Merck. I know you have approaches in adjuvant in both NSCLC and melanoma that you're you've talked about in the past. Is there -- can you talk to us about the potential of PD-1 LAG-3 in those indications in the adjuvant setting?

Question: Akash Tewari - Jefferies LLC - Analyst : Okay, understood. Maybe lastly, before we get into the heme program on CD28. And I remember two years ago, I think, Len and George, your team was really excited about CD28. It felt like there was going to be a breakthrough in solid tumors. And I think there was investor skepticism. You mentioned a lot of times, there's a wave of hysteria, then there's consolidation, and then we start understanding really the therapeutic window. I mean, your team had data, EGFR, CD28, at ASCO this year. You are taking approaches where you're dosing with IL-6. You're also taking approaches where you're dosing with other CD3s. Talk to me about where you stand with the CD28 program. Why should investors start paying attention to this given some of the early signals that we saw on the safety side last year? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. JUNE 05, 2024 / 12:30PM, REGN.OQ - Regeneron Pharmaceuticals Inc at Jefferies Heathcare Conference

Question: Akash Tewari - Jefferies LLC - Analyst : So you mentioned prostate, and actually, I'm going to ask a follow-up because I agree. I think in ASCO, it's now sequencing therapies together especially when it comes to IO. That might be more thoughtful and more may not always be better as well. We're seeing some signs signs of that. It's interesting because there are some SMID companies which are showing interesting data with the PSMA CD3 approach. We don't have the durability question. Regeneron, I mean, you have -- Probably, you know more about that target than a lot of companies. Why are you going with the PSMA CD3 with a PSMA CD28? What's special when you're hitting -- its same target, but you're hitting CD28 and CD3 separately. How can that maybe differentiate versus other therapies when it comes to not only response rate but, as you mentioned, the durability of response which is really critical in prostate.

Question: Akash Tewari - Jefferies LLC - Analyst : Interesting. Very helpful. Okay. On heme, I wanted to start off with GA. And I could tell you, I cover Apellis. I've kind of in the back of my mind said, okay, this is more of a problem for me in two years. I'm going to willingly ignore this question. So I'm facing my fears here as well. obviously, back of the eye therapies, there's issues in terms of getting chairs available, but obviously, retinal vasculitis and safety is really critical here. The question that I think we're all wondering is, with these kind of systemic approaches, how do you ensure you're not having so much immune suppression that there's some type of infection issue? But then number two, where is your confidence that you are going to be able to REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. JUNE 05, 2024 / 12:30PM, REGN.OQ - Regeneron Pharmaceuticals Inc at Jefferies Heathcare Conference get adequate exposure in the back of the eye? What work has your team done internally? You guys are famous on the translational side that maybe investors should be paying attention to here. Andres Sirulnik - Regeneron Pharmaceuticals Inc - Senior Vice President, Translational and Clinical Sciences, Hematology So first, thank you for having us here today. I think that, first of all, most of C5 which is the target of our approach in GA, our systemic approach approach in GA, most of C5 is made in the liver. And we believe that a systemic approach will pan out by understanding that the C5 is really activated in the vascular bed on the back of the eye. So the approach that we are taking is inhibiting or reducing the production of C5 in the liver using an siRNA and combining this with an antibody that will essentially capture whatever target there is left for activation with an antibody, therefore reducing the burden. So the siRNA reduces the target burden by inhibiting C5 production in the liver and whatever is left will be inhibited by the antibody. We think that this is a systemic issue and activation occurs in the vascular bed, rather than a purely local issue of production of C5 in the eye. So we think that this is a reasonable approach. The other issue is that GA is a bilateral disease. Injecting in the eye, you're treating one eye. Here, you're treating -- you have the opportunity to treat a bilateral disease with a systemic approach. So we think that that is an advantage. I think that the issue of the potential for infections, it begs to be answered in the context of a clinical trial. We are being very thoughtful and careful on the way we will be selecting patients for the trial and putting in place mitigation strategies that we think are reasonable in this setting. Mind you, there are major risks also with intravitreal injection. Remember, this is a slow progressing disease where complications of intravitreal injection could actually lead to blindness or losing an eye. So it's all about the risk benefit.