Regeneron Pharmaceuticals, Inc. (REGN) Earnings Call Transcript & Summary

Good day, and thank you for standing by. Welcome to Regeneron's ASH 2021 Investor Event Conference Call. [Operator Instructions] Please note that this conference is being recorded. [Operator Instructions] And now, I'd like to hand the conference over to your first speaker today, Mark Hudson, from Investor Relations. Thank you. Please go ahead.

Thank you. Welcome, everyone, to Regeneron's Oncology/Hematology ASH 2021 Webcast. Joining me on the call today are Dr. George Yancopoulos, Co-Founder, President and Chief Scientific Officer; Dr. Andres Sirulnik, Senior Vice President, Translational and Clinical Science, Hematology; Dr. Izzy Lowy, Senior Vice President of Translational and Science in Oncology. After our prepared remarks, we'll open up the call for Q&A. Before handing the call over to George, I'd like to remind you that remarks made today include forward-looking statements about Regeneron, including those related to Regeneron's business and research and development programs, anticipated milestones and regulatory matters. Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement. A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission. Regeneron does not undertake any obligation to update publicly any forward-looking statement, whether as a result of new information, future events or otherwise. With that, let me turn the call over to Dr. George Yancopoulos.

Thank you, Mark. These continue to be very exciting times at Regeneron, and the oncology/hematology space is no exception to that. And today, you'll hear our updates that present data that we presented at -- or we are presenting at this year's annual ASH meeting, and you'll get a sense of where we are in our programs and where we're going and what our goals are on our way to hopefully making major contributions in the hem/onc space. So with the next slide, I just want to remind you all where our medicines and our potential therapeutics come from. They come from what we believe are some of the most powerful discovery and development technologies in the biotech industry, which create and power our pipeline. These allow us to create an incredibly diverse pipeline, often starting with our VelocImmune mouse that creates our antibodies and our VelociT biotechnology that utilizes this mouse to generate bispecifics, both more standard now that it's hard to believe that we are calling them standard CD3 bispecifics, but also things like our co-stimulatory bispecifics and even more science fiction versions of these bispecifics. And the important thing about our approach is that we turn almost all of our technologies eventually into turnkey plug-and-play ones that once we develop the platform, we can easily then modify them to, for example, change the specific targets, which we think give us a tremendous advantage in this space. And it's these capabilities to generate the new technologies that create different classes of platform opportunities and our abilities to then combine and mix them in unique ways that we think creates a very exciting portfolio of opportunities with breadth across essentially everything in the oncology space. And we're going to be focusing on today is the hem/onc space. But -- if you can go to the next slide. Before we get there, I just want to highlight and remind you one important thing that we hope to do is to get best-in-class types of agents that represent very important therapeutic targets throughout the oncology space and particularly the immuno-oncology space. We think that we've done that with Libtayo, which, as many of you know, is the leading player now in non-melanoma or dermato-oncology indications in terms of immuno-oncology. We're now also approved in first-line advanced non-small cell lung cancer, and we have submitted filing for a combination with chemo in first-line lung cancer. So we think that we are moving Libtayo to become a key best-in-class type player that can compete across these spaces. And there, among the checkpoint inhibitors, we're also combining it with LAG3 antibody, where we presented recently our combination data in first-line melanoma, which was very exciting and we're moving that into a Phase III program. So we think in that space, things are looking pretty exciting. You've heard previously recently when we were reviewing the data elsewhere, Izzy Lowy is on the call in case you need to ask him any more questions, but in terms of solid tumor bispecifics programs, they are moving along in different spaces from ovarian cancer to prostate cancer to lung cancer and so forth, all of them leaving us with these combination portfolio opportunities. And what we're going to speak mostly about today are our hem/onc bispecifics, and particularly, our BCMAxCD3 bispecifics. We'll touch on briefly our CD20xCD3 bispecific program as well as potential near-term combination opportunities in each of those with co-stimulatory bispecifics. And you'll also hear a little bit about our efforts in classical hematology. And all this is part of this compete, enhance and extend. As I said, we hope in classes where immuno-oncology is also a major player with checkpoint inhibitors like anti-PD-1s, we want to have our best-in-class data to be able to compete there. But more importantly, they create foundational partners for our more novel opportunities that we will be potentially combining, for example, with the first-generation immuno-oncology agents like the PD-1 antibodies so that we can enhance the ability to attack cancers, as we all know, despite the success of PD-1s. And even for PD-1 responsive tumors, the results are not yet what we would all hope they could be to ultimately help patients. And of course, we know that there are so many patients who don't respond and so many classes of tumors like prostate, pancreatic and others that don't respond to PD-1 inhibitors. And that's why we're enhancing them with these bispecific approaches and all these combination opportunities and enhancing both where the initial immuno-oncology agents are working but also extend them to cancers that do not respond to PD-1s at all. And it's really our toolkit that I've already touched upon that gives us this ability to create this unparalleled opportunity to mix and match for the right cancer, the right indication, the right set of approaches, whether it be a PD-1 and/or a CD3 bispecific and/or a co-stimulatory bispecific and/or new classes of bispecifics. And this doesn't even enter into the collaborations we have with many important players in, for example, the vaccine space and also the CAR-T space. So it's really this oncology tool kit that provides us unique combinatorial flexibility that we can adapt and mix and match to well position us, we think, to try these approaches in so many different types of cancers where there is major unmet need. And as I've already touched upon, our pipeline continues to advance. We have a really, I think, impressive collection of combination opportunities. Many of them are getting started. Like we said, our CD3 bispecifics are now also not only what you'll hear about today in the hem/onc space, but also in solid cancers. Our costims are also already entered in the clinic, and we're adding more of those in our clinical trials. We expect this year to be a big year in terms of readout for some of these. And of course, we'll be talking -- or touching just briefly upon even in our BCMA and our CD20 programs or combination approaches with costims there as well, which are really important. As I said, Libtayo continues to advance. It's becoming the leading player in non-melanoma dermato-oncology, but now we're moving into other indications as well and we think where we've delivered some of the most important non-small cell lung cancer data in the PD-1 field, which is suggesting that, along with Keytruda, we have the only one right now that has similar sorts of data across the space, across histologies and across the different PD-1 levels. And as I said, I mean, the importance to us is to establish the foundational pieces like a Libtayo, like an anti-PD-1 and to be adding in intelligent and logical fashions, of the important combination opportunities that we have there. We're doing it already in the solid tumor space. Some of our major areas of investigation where we're hoping to deliver some important data this year are continuing to deliver with combination in the lung cancer space. And more recently, particularly with our bispecifics, both our CD3 bispecifics, our CD20 costim bispecifics but also in combination with Libtayo in both the ovarian cancer space and the prostate cancer space. And we're pretty excited about those programs. And as I said, we're really hoping this is the year where we start delivering exciting data on this program. And I think with that introduction to the overview of everything that we're trying to do and briefly touching upon what we're doing in the solid tumor space, I'm going to turn it over to Andres and he's going to focus on our efforts in hem/onc using all of these technologies and all of these pipeline portfolio opportunities.

Thank you, George, and good afternoon, everyone. I am Andres Sirulnik. I'm Senior Vice President in Clinical Development and Hematology Therapeutic area here at Regeneron. We are establishing a broad hematology pipeline in the areas of hematologic malignancies and also classical hematology, including complement, coagulation, immune modulation and amyloid deposition disorders. And again, following on, on what George has mentioned, taking into consideration our biologic insights, our toolkit, our ability to mix and match technologies, our combinatorial flexibility, we are uniquely positioned to solve these most challenging problems across spectrum of diseases. I will begin with odronextamab, our CD3xCD20 bispecific program. While there was no data update presented this year at ASH, we are laser focused on accelerating enrollment and are pleased with the recruitment in our potential pivotal study following a partial clinical hold that was lifted earlier this year. We have now enrolled across the program over 450 patients. Odronextamab demonstrates efficacy across both aggressive and indolent lymphomas, including patients who failed CAR-T therapies in what we view as a potential best-in-class therapeutic. Our agent has a manageable safety profile with CRS observed mainly during cycle 1 step-up dosing. And furthermore, we are encouraged with the data that is emerging as it relates to CRS following adjustment of the step-up regimen. We have significant milestones ahead, and our development plan provides a tremendous opportunity to bring this therapeutic to many patients. We expect to complete enrollment in our potential pivotal Phase II study in follicular lymphoma and diffuse large-cell lymphoma, initiate dosing with subcutaneous formulation and initiate our Phase III program and additional combination studies. I want to move and review our ASH BCMAxCD3 data update, which was presented by Dr. Zonder in an oral presentation over this past weekend. We are very encouraged by the emerging data, which I will walk you through shortly. On Saturday, Dr. Zonder presented data from the dose escalation Phase I portion of the ongoing Phase I/II study. Shown here is the study design. Accrual to the dose escalation has completed in which we explore a range of doses from 3 milligrams up to 800 milligrams. Dosing is weekly through the first 16 weeks, after which it is biweekly and included in the regimen is a weekly step-up dosing for the first 2 weeks. Last year, we showed data from 6 dose cohorts to a total of 49 patients, and this year, we are showing [ all 9 ] cohorts to a total of 73 patients. Of note, patients around in our study are heavily pretreated with a median of 5 prior lines of therapy. 90% of these patients were refractory to the last line of therapy. And more than 95% of the patients were triple refractory, mainly refractory to immune modulators, proteasome inhibitors and anti-CD38-directed therapy. Furthermore, 40% of the patients in this study were penta-refractory. That means refractory to 2 immune modulators, 2 proteasome inhibitors and an anti-CD38-directed therapy. And while this is the Phase I portion, it is important to note that the potential registration of Phase II expansion is actively enrolling. We continue to see early, deep and durable responses across all dose levels, and these responses deepened over time. There is a trend for higher response rates at higher doses. These are very encouraging results, especially in these heavily pretreated and refractory patients. We observed a 75% overall response rate and 58% VGPR or better with the higher doses between 200 million and 800 milligrams. And as these higher dose patients were mostly recently dosed and there are -- there is a short follow-up, some of the responses observed are likely to continue to deepen with longer follow-up, similarly to what we observed across all dose levels. Now when we look among all responders across the study, 86% achieved a clinically meaningful response of VGPR or better with 43% of the patients achieving a CR or stringent CR. Among CRs or stringent CRs with available MRD data, 4 out of 10 patients achieved MRD negativity with an assay sensitive to 10^-5. The observed median duration of follow-up was 3 months with some patients followed for almost 2 years. When we look at the [ -- and seen across ], it's important that we are seeing responses, as I mentioned, deepening over time with a trend to progression all the way from PR to CRs. The median time response is fast, less than 1 month, meaning that most responders are already showing treatment benefit at the first follow-up visit. The median duration of response as estimated by Kaplan-Meier terms was not reached, which is another indicator that most patients continue to respond. And the probability of responders being event-free at 8 months is 90% with the longest responses still ongoing for more than 19 months at the data cutoff. Our bispecific continues to demonstrate an acceptable safety profile and a tolerability profile with more patients and with higher doses. Notably, there were no Grade 3 CRS or ICANS events. In fact, the minority of patients developed CRS with only 38% of the patients and the vast majority of which were Grade 1. That means fever with only 3 patients classified as having a Grade 2 CRS event across the entire dose escalation. These CRS events mostly occurred within 24 hours -- either -- within the first 24 hours either on the first or the second dose. The median time to CRS onset was 10 hours and the median duration of CRS was 15 hours. In summary, our team has incorporated important learnings from our odronextamab program that enabled us to dose escalate quickly and manage CRS effectively for this particular program. Taken together, we are encouraged by our progress and the data presented at ASH. We are confident that the REGN5458 can play an active role in the treatment of multiple myeloma given its efficacy and safety profile. And as a quick summary of the key takeaways, I wanted to, again, focus on the observed early, deep and durable responses with, at the highest doses, a 75% overall response rate, 58% VGPR or better at higher doses, its safety and tolerability profile that was manageable with no Grade 3 or higher CRS or ICAN events. Now when we look at the next steps, we expect to complete enrolling in the Phase II portion of the ongoing study and initiate a Phase I umbrella study of REGN5458 in combination with a variety of multiple myeloma agents, which is now publicly listed and will be enrolling soon. Building upon our success and progress with monotherapies, part of our overall strategy and development plan for hematology is also to specifically pair CD28 costimulatory bispecifics with our CD3 bispecifics to potentially turn nonresponders into responders and provide deeper and more sustained responses. This is similar to what we already started into the clinic in solid tumors. We anticipate that the B-cell-targeting CD28 costim will be paired and combined with odronextamab and this will enter the clinic shortly for lymphoma, and at a later time, a plasma cell targeting CD28 costim combined with REGN5458 will enter the clinic for multiple myeloma. Now I would like to direct our attention to our up and coming nonmalignant hematology programs. While our CD3 bispecifics are rapidly progressing, we want to share some of our ongoing efforts within our classical hematology pipeline. We are establishing a broad hematology pipeline in the areas of complement, coagulation, immunomodulation and amyloid deposition disorders. There is also a large ongoing effort from our scientists to push more novel targets and development therapeutics into the clinic over the next few years. Again, as I mentioned before, our biologic insights, the toolkit and the ability to mix and match technologies together with our combinatorial flexibility put us in a unique position to solve these challenging problems. One increasingly important differentiated program we have here is our C5 program in complement-mediated disorders. This is the first of its kind moving forward into pivotal studies combining an siRNA therapeutics with an antibody for a specific target. This combination program has a lot of potential, including complete and sustained C5 inhibition at lower doses for each of the components, resulting in optimal efficacy and better control of breakthrough hemolysis in the case of paroxysmal nocturnal hemoglobinuria, one of our target indications. This is achieved by inhibiting synthesis of C5 by cemdisiran, therefore, decreasing target burden amenable to pozelimab inhibition. We also expect to see an acceptable safety, including in patients who switch from prior therapies, efficacy in a broader range of patients also compared to current standard of care, all together in a highly convenient and prudent self-administered subcutaneous formulation. At ASH, the team presented a poster on the PK/PD results observed in a Phase I 30-volunteer study, and this data support dose and schedule selected for our pivotal studies of the first-of-its-kind combination of an antibody and siRNA therapeutics. We have an ongoing broad C5 program for the combination, and we are pleased that Phase III studies in myasthenia gravis and paroxysmal nocturnal hemoglobinuria have or are about to be initiated. Figures for the PNH Phase III studies are available on ClinicalTrials.gov. For the PNH starting next year, we are planning to test our combo in both naive and switch patients tested against standard-of-care therapies, including ravulizumab and eculizumab. Now I would like to highlight some of the recent ground-breaking progress with our Intellia collaboration. A few months back, Intellia and Regeneron announced positive clinical data for the first ever systemically delivered CRISPR-based cheap knockout in humans for the TTR program. It is in these first 6 patients with transthyretin amyloidosis, a single systemic treatment led to dose-dependent reduction of up to 95% in the disease-causing protein with no serious adverse events of cell through day 28. Phase I data update from the completed dose escalation in patients with hereditary amyloidosis with peripheral neuropathy are expected in the first quarter of '22 as well as the initiation of the dose expansion. Another collaborative program with Intellia is the Factor IX gene insertion program for hemophilia B, which is also progressing well. For this potentially first-to-clinic in vivo CRISPR-based gene insertion program, which is [indiscernible] with Regeneron, we have now selected the development candidate and the program has progressed to the IND-enabling studies. In summary, we remain very excited about these programs and are evaluating more than 20 preclinical programs under Intellia collaboration, and Regeneron has the rights to develop up to 15 in vivo gene-editing products with Intellia. I would also want to highlight an ongoing and exciting early-stage effort exploring our BCMA bispecifics in a variety of non-oncology indications with significant unmet medical need. The focus of this approach is to reduce the level of pathogenic antibodies by depleting antibody-producing plasma cells. In our proof-of-concept study, we believe BCMAxCD3, 5458 and 5459, has the potential to reduce the levels of anti-HLA antibodies present in chronic kidney disease patients who are awaiting a kidney transplant and are highly sensitized to human leukocyte antigen. Just to remind you that in addition to organ availability being a challenge to potential transplant recipients, the other major hurdle is the presence of anti-HLA antibodies in patients, which contributes to transplant rejection. Currently, there are no approved desensitization regimens in the U.S., and we are very excited that we anticipate our first patients to be dosed in this program in early 2022. So in closing, we have accomplished a great deal across our oncology/hematology pipeline to date. We have a robust development strategy and a clear path forward for Regeneron to be one of the leaders across this space. Our broad oncology and hematology portfolio is advancing rapidly with the potential to unlock numerous opportunities. In hematology, REGN5458 continues to show strong responses in heavily pretreated multiple myeloma patients. Enrollment continues in a potential pivotal Phase II study. Odronextamab and off-the-shelf bispecific effective in both indolent and aggressive lymphomas with a broad program and path to approval continues to advance rapidly. And we have an emerging non-oncology/hematology portfolio that is broad, including the C5 program I just mentioned for the complement program, the hereditary amyloidosis TTR program with Intellia and now our BCMAxCD3 being studied in non-oncology indications. I want to pass now to George. Thank you very much. George, will give some ideas on what's to come in the next 12 to 18 months. George?

Thank you, Andres. So I hope you all appreciate that at Regeneron, we have taken something -- undertaking something that's incredibly ambitious and challenging, that is to simultaneously invent and clinically develop in a parallel processing fashion several different classes of potential therapeutics that can all work and were designed to work in a mix-and-match fashion to be able to logically target and optimize the benefit/risk in various indications. And you heard how we're already progressing on this in oncology, where we believe we're delivering some of the best-in-class data with the leading checkpoint inhibitor approaches. But also, we've been leading, we believe, in terms of efficacy readouts in the field with the CD3 class of bispecifics while also leading the field with these post-inventory CD28 bispecs, giving us enormous mix-and-match opportunities, not even touching upon the new classes, for example, of bispecifics in other categories as well. So we think that, that in oncology will allow incredible flexibility and ability to tailor treatment and optimize benefit/risk in both the solid tumor setting as well as the hem/onc setting. But we're also taking the same sort of approach in terms of parallel processing multiple different approaches outside the oncology space. And you heard a little bit in hem/onc how in the setting of PNH we've brought forth to the world the first logical combination of an antibody approach with an siRNA approach. The siRNA approach to lower the target load to allow the antibody to work and deliver its complete blockade capability, which can't be delivered through the siRNA, but for longer extended dosing intervals to allow both longer-term complete control while also affording patients more convenient regimens than what are available today. And layering on top of that, a whole new set of approaches using CRISPR technologies and so forth where we've delivered to the world, in collaboration with our Intellia colleagues, the first human systemically delivered CRISPR approaches. So this is an incredibly ambitious approach. It requires a lot of maneuvering to be parallel processing all of these programs and trying to optimize them individually, but also collectively understanding how to mix and match them so as to afford maximum benefit in each tailored indication for patients. So we are very excited about this. We think that our teams have really been delivering from beginning to end from inventing these molecules to creatively understanding how to mix and match them in the clinic. And we're very excited about what we're going to be delivering for patients in the near term but also in the long term. And with that, I think I'll turn it over back to Mark.

Thank you, George and Andres. Now I'd like to open up the call for Q&A, where George, Andres and Izzy are available to answer your questions. To ensure we're able to address as many questions as possible, we'll answer one question from each caller before moving to the next. Operator, please go ahead.

[Operator Instructions] Your first question is from the line of Geoffrey Porges with SVB Leerink.

George, a nice setup overviewing your oncology development efforts. You didn't mention the CITYSCAPE data from Roche that came out on Friday, but I'm sure you paid close attention. You have a GITR or a CTLA-4 and a LAG3 but you don't have a TIGIT, and it doesn't appear that you're developing your LAG3 outside of melanoma. So in the past, you've suggested that the reason for not having a TIGIT is because it doesn't really add anything to a PD-1, but clearly your competitors believe it does. Do you have any interest in developing a TIGIT? Why wouldn't you be adding it on to those second mechanisms to provide a foundation for your I/O franchise?

Yes, it's a great question, Geoff. So as you know, the beauty of our technology is it allows us to have candidates in clinical stage or near-term clinical stage candidates for essentially any target of interest, such as TIGIT for example. So we have what we think are very exciting TIGIT clinical candidates. We have been thinking and deciding about how to move those forward in the clinic. And I think that we're going to be carefully evaluating data that's coming out and making a decision about whether we should be moving more quickly with our TIGIT development candidate, which, as I said, is essentially on the tipping point of deciding whether to go forward with it or not. So we're poised. We have a great antibody candidate and we're thinking about evaluating the data and where to go with that in the space of combining it, for example, with our PD-1. And LAG3, I think, just to add to that, yes, we are by no means limiting our thinking of LAG3 with melanoma. It's just that that's where we first delivered some of our own exciting combination data. We are initiating, as you know, a Phase III study in first-line melanoma. We're thinking about going to earlier lines of treatment there as well, such as adjuvant, but we're also thinking of moving on outside of the melanoma space as well.

Your next question is from the line of Mohit Bansal with Wells Fargo.

Great. And maybe a big picture question for you, George. So among the new readouts that you are expecting and anticipating for 2022, what you are most excited about and looking forward to see at this point?

Well, people have been asking me that question for 33 years and it's sort of like asking me which of my children I love more. I think that the thing that has historically really distinguished Regeneron and has served us well is, I think, what we have proven to be really an unprecedented and unparalleled ability to be parallel processing so many opportunities, simultaneously allowing us to rapidly also pivot as one thing becomes more or less exciting and so forth. I wouldn't be lying if I didn't tell you that we think that this is the year that we might be producing some of our first exciting co-stimulatory bispecific results. If we see those, I think that, that suggests that, that could really change the field where I think we're going to continue to produce and get, we hope, better and more convincing and advanced data from all of our CD3 programs not only in the hematology space, but in the solid organ space, which we're very excited about. And I think we're going to continue to be producing data from our checkpoint inhibitor approaches as well. But the thing that we really believe is going to be distinguishing us is the ability to, as we've been saying a lot, which is mix and matching these different portfolio assets in a logical and rational way to enhance efficacy without sacrificing safety for all these particular indications. So for sure, it's very exciting to see. I mean I think it's where we design these things to be and where we are that the first generation, essentially single approaches with our checkpoint inhibitors, are delivering best-in-class type of efficacy. Our single-agent approaches with our CD3 classes of bispecifics are delivering best-in-class efficacy individually. And we now have these CD28 programs that are in the clinic. And it's going to be, we think, starting this year is the time, as we've already seen with, for example, the LAG3 combination with the checkpoint inhibitors is the year we're going to see some of these combination activities showing what we're hoping is convincing data that shows enhancement. And once you have that, this ability to be adding more of the single agents, but then combining them in a logical and rational manner we think can really change the landscape in terms of treatment possibilities for all these different cancers and really change the practice of medicine, which is what we're hoping to do.

Your next question is from the line of Kennen MacKay with RBC Capital Markets.

On the BCMA bispecific that was presented here at ASH, I was wondering if you could just clarify the rate of pneumonia and especially whether or not this is a dose-limiting toxicity. It seems like some of that was largely at the higher doses. Is that -- and how that's managed moving forward?

I'll turn that over to Andres. Go ahead, Andres.

Yes. So thank you for your question. In terms of the pneumonia, we think that the cases that we have observed are very much in line with -- has been reported across the class. Of note is that this is a current event in multiple myeloma. And at this stage, I think across all programs with primarily single-arm studies will be very difficult to tease out what is the underlying disease vis-a-vis what it is truly an event related to drug. So I hope that this answers your question. Again, we have observed what we think is very much in line with the class. l

The next question is from the line of with Carter Gould with Barclays.

Great. Congrats on the data. I guess for George and team, relative to the other BCMA bispecifics in the field, just wanted to get your level of confidence you're still seeing a path to market on a competitive time frame. And to what extent you think that's important given the differentiation you've seen? I mean, to be frank, much of the milestones you highlighted at ASH last year still remain to be hit, and I recognize there's no shortage of external circumstances that may have impacted the dynamics, but I also feel like it's a highly competitive environment here. And would love to hear your view on competitiveness in terms of time lines.

Yes. I think that -- let me just back up, first, just a question in a moment just to add a little bit to that. I mean, as Andres said, I mean, clearly, this is a general problem for myeloma patients. I think that certainly there's various approaches to try to enhance immunity in these patients, particularly we know it's recommended trying to vaccinate patients with appropriate vaccines and so forth. But one thing that we are talking about initiating into our program is -- which I think the investigators are very excited about is actually protecting or prophylaxing in an investigative fashion these patients against COVID-19, which I think could be -- prove very important in terms of a way to protect these patients. But moving on to the next question. I think that we all know what we want to do. And I really do think that, as I said, we're seeing this as a long game, okay, in that the most important thing to us is to demonstrate how effective our agents are as single agents in their class because we believe that we can change the practice of medicine by providing these unique combinations. So of course, for both the CD20 program and the BCMA program, our first goal is to just complete our registrational studies. I mean as you know, for various reasons, from COVID to some initial FDA asking us to slow down or change our step-up regimens and so forth, it delayed things but we're still on track to get our registrational data by this coming year, 2022, in both of these programs. Then, of course, next is to be moving these programs into earlier lines of therapy, which we are on target to do. And simultaneously, as I said, I mean, this is sort of orchestrating a complicated symphony here, okay? Simultaneously not to be settling for these as single agents, but to be starting to seamlessly weave in the very interesting combinations that we think can really separate these from other agents. So we think that our goal, and we think we are on target, is to deliver the single agent best-in-class activity to show each of these single agents are delivering efficacy as good as anything else that's out there. And I think whether we're talking about PD-1s, whether we're talking about BCMAs or CD20s or so forth, I think we're doing that. And then we're going to be talking about the various interesting combinations that we have with this. And I think that we're on target.

I want to ask to George. Thank you, George. To your question of a competitive environment, we recognize this is a very competitive environment, both lymphoma, myeloma and wherever you look actually in hematology/oncology. But I want to remind you that the devils are in the details. We think that our antibodies have the potential to differentiate vis-a-vis the competition. We have shown already cemiplimab, for example. There are multiple PD-1s out there, one of the only 2 antibodies that actually demonstrated a significant benefit in first-line lung cancer. Similarly, we think that patterns of and difference will emerge across the class of antibodies on the CD3 engager group. And when we look at the BCMA data, I want to remind you, when we look at the level of efficacy that we have observing, which is very encouraging, I'm also going to focus on safety. I want to highlight we have seen 38% of the rate of CRS today that has been reported with other BCMAxCD3 bispecifics. There might be a multitude of reasons by which this might be the case, it could be dosing schedule and also one should consider our antibody, yes, or the affinity to CD3, the affinity to BCMA and so forth, we get our antibodies before we go into the clinic. And I think that the toolkit that we have allow us to truly develop some of the best antibodies out there and eventually think we will catch up and show that the differentiation exists -- is already showing.

Your next question is from the line of Tyler Van Buren with Cowen.

This is Brittany on for Tyler. Congratulations on all the progress. One for us on the BCMA program. So looking at the summary slide and median duration of follow-up was around 3 months. But for the 200- to 800-milligram dose cohorts, what was the approximate treatment duration there? And how does that compare to some of the lower doses where treatment was potentially ongoing for longer? And related to that, could you just remind us of what dose is being evaluated in the Phase II portion?

Thank you very much for your question. As you probably have gathered by looking at the summary plots, the overall median duration of response is approximately -- sorry, the median duration of follow-ups is about approximately 3 months. And as you can imagine, for those in the higher dose level cohorts it's significantly shorter than the rest of the population. That's why we made the point that the responses are expected to deepen over time. And we hopefully will continue to see that happening in the patients in the higher doses. That's one point. But all in all, as you heard, the median duration of response has not been reached. Now you asked the question on which doses we are expanding. We have not -- in the Phase II portion, we have not communicated that. But we are very encouraged by the speed at which the Phase II portion is occurring and expect to complete in this coming year 2022.

And just to emphasize, I mean, once again, the point about the responses continue to deepen, people who had an opportunity, it was just that, that was the time point where we had sort of the most data. Individuals who had the opportunity to be followed for 8 months who are responders had over 90% maintenance of being event-free at that point, which is showing the long duration of action. We hope -- we hope with continued follow-up that, that's going to just get longer and longer and longer. And I think that this is just showing how powerful this approach can be to getting impressive, deeper and deeper and long-term benefit for the patient.

We are already observing deep responses in very early on. As we mentioned, the overall response rate of 75% with VGPR or better of over 50% in spite of a very short duration of follow-up, I think, is very telling.

Your next question is from the line of Cory Kasimov with JPMorgan.

Wanted to ask if you can talk about how you think the current safety and tolerability profile for your BCMA asset sets up from a combination point of view with other standards of care. In particular, do you think the grade for hematologic AEs are problematic on this front? Or can you work around them when combining?

Go ahead, Andres.

Yes. Thank you for the question. All in all, I would say that the overall safety profile of the drug makes it amenable to combination with all classes of drug in the treatment of multiple myeloma. We do not see the neutropenia, anemia or thrombocytopenia being in any way rate limiting at this strength for the most part. And we -- I want to highlight, we only saw 25% of the patients having Grade 3 or 4 decreases in their ANC, which is actually very competitive when we look at what's happening in the class. So amenable to combinations and to monotherapy and to move it to early lines of therapy.

Your next question is from the line of Salveen Richter with Goldman Sachs.

This is Elizabeth on for Salveen. Just wondering if you could help us sort of frame expectations for the solid tumor data that's expected in 2022 from either the monotherapy or combination approaches?

So in which solid tumor programs, in particular, are you asking about?

Yes. So for ovarian and prostate specifically?

Okay. Izzy, do you want to take that on?

Sure. Thanks for the opportunity to contribute to this exciting update. So we have a lot of exciting data that we're expecting to be able to share by the end of the year. In our PSMA program, we have continued to dose escalate very comfortably on our costim together with cemiplimab and we have initiated our PSMAxCD3 program and we'll be dosing our first patient in that shortly. We're beginning to see some evidence of potential activity. And we believe that at some point at a conference during the coming year, we'll be in a position to share some data that will add some credence to the very strong preclinical data that we've previously published. I'd also like to add that, that preclinical data that was published also suggested that some of the benefit of the signaling that's obtained through these costimulatory bispecifics can provide similar types of signals that one would get with TIGIT, so that we may not -- while we're exploring TIGIT, and that question was raised earlier, it's possible that TIGIT may not even be necessary for us if our costim platform works well. In our MUC16xCD3 program, there, too, we are seeing evidence of clinical activity and we are planning to be able to at least share the data from our dose-escalation experience in that group in the coming year at an appropriate conference. We've also initiated our MUC16xCD28 program and we've already successfully dosed our first patients getting the combination of the CD28 and the CD3 bispecific. And if you recall from the preclinical data that was published, that was one of the combinations that showed really impressive activity. So I would say that for both of those programs, the MUC16 and the PSMA and the bispecifics, you -- we hope to share some exciting clinical data in the coming year. And that doesn't stop us from continuing on with our other programs, METxMET bispecific, our GITR, our EGFRxCD28, all those are progressing quite steadily.

Your next question is from the line of Geoff Meacham with Bank of America.

This is Alec on for Geoff. Just in regards to your BD strategy as it relates to your hem/onc portfolio. I guess how do you approach partnering versus developing things on your own? Would you say this is sort of driven by the science as it evolves? Or are there key additional technologies that you maybe want to gain greater exposure to? You highlighted the siRNAs and CRISPR. But anything on the oncology side as well? And how important does combos with standard of care sort of play into your development?

Yes. I mean, as you said, I mean, we're very scientifically driven. So as we already said, I mean, we established a major collaboration with Alnylam because we saw both the value of single-agent siRNA approaches, but also the combo opportunities, mostly in the non-oncology space, as Andres highlighted one of the programs there. Same sort of thing with Intellia. In the cancer space, as I think we had on the slide, one thing that we're really very actively addressing, mostly through collaborations, we think that our portfolio of biologics candidates are really second to none in terms of the breadth, the actual -- how good the individual reagents are and so forth. And so we're excited about all of our biologics combinations opportunity. But we also have to say that in the vaccine space, particularly the T cell vaccine space, this is somewhere where we're expecting or hoping to be able to find useful combination opportunities with various partners. And I think on the slide we mentioned whether it be, for example, a BioNTech or whether it's a Vyriad or whether it's a multitude of our other various collaborators, we are, once again, mixing and matching in hopefully logical and rational fashion when one of our biologics programs should or need to be combined with one of these vaccine approaches as necessary. So we can handle, we believe, the biologics, the bispecifics and those forth, but we're looking to report outside collaborations to combine in the oncology space in terms of particularly T cell and oncolytic vaccines. I don't know if, Izzy, you have something to add to that?

I think all I would say is that antibodies -- good antibodies are not commodities. And I think that's been demonstrated by the fact that, as already has been mentioned, Libtayo is only the second anti-PD-1 to have positive outcomes in first-line non-small cell lung cancer, either as a monotherapy or in combination with chemotherapy across all histologies. We're very proud of that despite all the years of other people putting things out there. Similarly, the bispecific platform was designed with a great deal of care and thought and elegance, I might add. And the first couple, the CD20xCD3 and the BCMAxCD3 gave us a great deal of confidence in the robustness of our platform approach and has basically encouraged us to run with it and develop additional CD3s and these novel constructs targeting CD28 for costim. And we're not done. We have other ligands that we're thinking of tying together with the tumor antigen-directed approach. So -- and we do have this really plug-and-play almost opportunities to really mix and match where we know if there's anything that the last 20 years have taught us, as well as the preceding 50 years, it's that combinations are what's required. And the greater the ability you have facilely provide combinations, the better off you're going to be. And the last thing was that not only internally, but one of the exciting things that happened when we started providing data that showed that our Libtayo was an absolutely outstanding antibody was other companies coming to us and wishing to partner with a company that not only had a strong asset, but also had the scientific enlightenment and open-mindedness to really look for what kind of combinations make sense. This was something we didn't really even anticipate so much at the beginning and it's been a fringe benefit of having developed some strong antibodies. So I think you're looking at a really diverse internal pipeline in both solid and hematologic malignancies. And by the way, the fact that I'm on this call with Andres and George, we all talk to each other. We learn from each other about what all of our experiences are with these agents of similar modalities. And we enjoy having the opportunity to collaborate with other companies that have complementary technologies.

So your next question is from the line of Robyn Karnauskas with Truist Securities.

This is Nicole on for Robyn. Robyn apologizes for not being on the call, but she did say that at ASH KOLs were telling her how much they like the safety profile of your BCMA bispecific. Our question is how much more can Regeneron push the bar here on efficacy in heavily pretreated multiple myeloma patients? Are there plans to dose higher given the safety profile thus far?

Well, I think like you heard, I mean, of course, we're going to continue to try to optimize the single agent, which already we believe is among best-in-class in terms of the efficacy data. But our abilities to further push efficacy will also hopefully come from the combination approaches that we've already been discussing, which we think can take things to a whole another level and provide further differentiation from competitors in this space. So we think, as I said, we wanted to be in a good position with the single agents, and in parallel processing, set single agents across a whole assortment of different cancer settings while simultaneously parallel processing so that we can be layering on in a thoughtful and intelligent manner of the right types of combinations to further enhance the benefit to patients. And we think we're on target on our plan. And I think with that, we'll have to call an end to today's conference. Thank you guys for all your interest and attention, and speak to you all soon.

Thanks, everyone. Really appreciate you joining today's call. There were a couple of callers in the queue that we didn't get to. So the IR team is around so we'll definitely reach out, and hope everyone has a good night. Thank you very much.

Ladies and gentlemen, this concludes today's conference call. Thank you for joining. You may now disconnect. Stay safe and well.