Regeneron Pharmaceuticals, Inc. — 2024 Q1

Thanks. Great question. As when you block with other approaches like bimagrumab, you're blocking over a dozen members of the so-called BMP, GDF family and so forth. And that raises the concern because only a couple of those are actually involved in muscle preservation that you may end up doing more harm than good. What we have identified over the years is we identified 2 members of this very large family of almost 20 factors, which 2 are specifically involved in muscle preservation and we created antibodies to each of these 2 individually.

Well, just to remind you, if you look at our paper where we did the nonhuman primate studies and so forth, is the first thing we're going to be looking for is there is the very real possibility of increased weight loss. And that might be the simplest regulatory endpoint of all. After that, if we don't see that, but we see better quality of weight loss, that could be manifested in a variety of ways, though we, of course, recognize that those would perhaps create more complicated ways of being regulated. So obviously, if you increase the fat loss while preserving muscle you should have dramatic benefits in metabolic parameters, which are often used in the field, particularly in people with diabetes and so forth as well as ultimately in terms of function by having maintenance of function as opposed to losing function and maintaining those sort of functional endpoints.

Sure. So let me take the inventory item first, and then I'll come back to the overall marketplace. But this was in aggregate. As I mentioned, in the quarter, we saw a reduction in wholesaler inventory broadly of about $40 million. So that reflects market-wide. But that was a combination of 2 elements. It was a sequential drawdown of EYLEA inventory that was partially offset by a modest increase in EYLEA HD inventory ahead of the permanent J-Code on April 1. And then I would share on the overall market in all the categories where we participate, we're always very conscious of the segmentation of the market, targeting the market, what's occurring in terms of customer base and certainly, our strategies and our approach to the marketplace is reflective of that. And the range of customers we have, as you point out, in retina and how that market has evolved over time. And I think our commercialization approach has been very effective in addressing that market evolution.

Yes, Salveen, thanks for the question. You're right. From our perspective, we think the data broadly supports the entire BLA and as well as all these analyses, the approval of the drug in eosinophilic COPD. As you might imagine, the FDA went anticipating or looking at a new class of biologics is very interested in checking it up and down and down and up and making sure that there's no subpopulation of the study that might be driving the data. So they might -- if one saw that, one might think about labeling it differently, but none of that has occurred. We've looked at all these analyses. We're going to submit them a way ahead of the schedule that they've asked for, and all of the analyses show a consistent and clinically meaningful reduction in the COPD exacerbations across all of these subgroups that have been asked for.

These are great questions. We hope from the first few patients if the results are as dramatic as they are in the preclinical studies that we'll be seeing meaningful indicators that we are really reversing severe food allergy. Of course, the first thing and the most important biomarker, as I said, is this evil immunoglobulin IgE, which you can both measure, but they are also routinely tested using these skin prick tests, which are how people are actually evaluated for allergies.

George, can you comment? I think they also want to know how long you have to stay on IgG...

Yes. The interesting thing is the animal study suggests that the antibodies against the allergens come back as IgG, G for good antibodies. The whole point of -- if you guys are familiar with so-called immunotherapy or desensitization therapy, all of those therapies, what they're trying to do is induce production of IgG to overwhelm the IgE. That's a much harder thing to do because they're not really getting rid of the Ig. They just have to overwhelm with a lot more IgG. In the animal studies, it suggests that we get rid of the Ig and we replace it with IgG. We don't know, obviously, in the humans, it may be possible that short-term treatment, relatively short-term treatment, may allow patients who have replaced their IgE with IgG, and they will have long-term protection.

Right. That's a great question. Obviously, the thing that gets us excited about our program compare to the field is that we've seen levels of activity that haven't been seen in the other LAG-3 programs, particularly in melanoma. If that's true in melanoma, there would be hope that this would be seen broadly in other settings and indications. We are certainly excited to see the follow-up details on the BMS story with potential activity in a specific subpopulation that will certainly help point us in our own studies to see what we're seeing within that subpopulation that they are talking about as well as more broadly. But of course, the hope, as I said, is if it is indeed more active in one setting such as melanoma, the hope is it will be broadly more active across other cancer settings as well. So we are excited to see follow-up on their data. We're excited to see follow-up on our data, both in melanoma and in our lung studies.

Yes, these are all great questions. What we've already actually shown based on a variety of studies that we've done is that normal nonmalignant noncancerous plasma cells, the cells that are the immunoglobulin factory cells are the normal versions of the cells are much more susceptible to the bispecific than our malignant myeloma cells. So in discussions and communications with the FDA, we're actually starting at much lower doses than the doses that are used in the myeloma programs, though there is an intrapatient dose escalation process. So we're literally watching -- we're starting with low doses and we're going up in the doses until we actually hopefully see elimination of the IgE. That said, in terms of the safety, I'd just remind you that the much higher myeloma doses, we came up as Len briefly summarized in this program.

That's a phenomenal question. And first of all, let me remind you that with our long-term collaboration and recent acquisition of 2seventy. 2seventy had exactly the sort of CAR-T programs that you're referring to in lupus and other autoimmune settings, which we are now obviously pursuing together with them but that is one of the reasons why we were excited about turning the collaboration into a situation where we brought all the expertise and the scientists and leadership from 2seventy in-house because we're doing exactly what you suggested. We're hoping to actually literally look in side-by-side studies, how CAR-T approaches in these settings of autoimmune, severe autoimmune disease like lupus and so forth, compare directly head-to-head to our bispecifics. And as you are sort of suggesting, you would think that there would be really little reason to think that the CAR-T solutions would be preferable in this setting, both in terms of off-the-shelf mess and the ability to eliminate the normal cells.

So certainly, we look forward to the potential launch of Dupixent in COPD. There's such unmet need and such opportunity to help those patients with an eosinophilic COPD. Our team, as you know, is very experienced with launches in Dupixent. So work is very much underway at Regeneron and also with, obviously, under our collaboration with Sanofi to make sure that we apply the best practices and launch of new indications.

Well, there's always the possibility of disease modification. We actually believe, for example, Dupixent in asthma may be doing exactly that sort of benefit. One of the best ways of actually looking at that is looking at overall loss of lung function over time because, as you know, in these lung diseases as Marion said, in both asthma and COPD, these are diseases of the lungs followed largely by pulmonologists, the same sort of doctors and it is well known that in both of these diseases over time, patients start permanently losing lung capacity and lung function. We are and have been and have early data suggesting that Dupixent may prefer that in asthma, and we'll certainly be looking at those sorts of things for not only Dupixent but itepekimab in the COPD patients in terms of modifying disease and long-term preservation and prevention of this otherwise unstoppable lung function loss.

Mary can take the question on the launch and everything. I mean, obviously, the MRD negativity as endorsed by that panel gives an opportunity to get these kinds of drugs to patients earlier in a variety of settings. So we are looking forward to applying that approach in our future studies as we move towards earlier in different lines of therapy. Marion on the launch?

Sure. So we're certainly preparing for the potential launch with the August 22 PDUFA date. And we're really excited because as I've mentioned before, the recent data reinforces linvoseltamab as potentially a best-in-class product for late-stage myeloma patients. So it's a wonderful opportunity to extend our oncology franchise in the new disease area.

All right. Thanks, Len and Marion, and thanks to everyone who dialed in for your interest in Regeneron. We apologize to those remaining in the queue that we did not have a chance to hear from. As always, the IR team here at Regeneron is available to answer any remaining questions that you may have. Thank you once again, and have a great day.