Welcome to the Regeneron Pharmaceuticals ASH 2022 Investor conference call. My name is Catherine, and I'll be your operator for today's call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session. Please note that this conference is being recorded. I will now turn the call over to Ryan Crowe, Vice President of Investor Relations. You may begin. Thank you, Catherine. Good morning, good afternoon, and good evening to everyone listening around the globe. Welcome to our ASH 2022 Investor Call. Slides for our presentation have been posted to the Investors section of the regeneron.com website. I would like to remind you today that today's remarks include forward-looking statements about 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 the 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 on Regeneron's SEC filings. Regeneron does not undertake any obligation to update publicly any forward-looking statements, whether as a result of new information, future events, or otherwise. Joining me today are Dr. David Weinreich, Executive Vice President, Global Clinical Development, and Dr. Andres Sirulnik, Senior Vice President, Hematology Clinical Development. After our prepared remarks, we'll open the call for Q&A. With that, I'll turn the call over to David. Thank you, Ryan, and thanks to everyone joining today's call. Before we focus specifically on the updates from ASH, I would like to first discuss Regeneron's progress towards becoming a global oncology leader over time. We're applying more than three decades of scientific innovation to develop therapies that have the potential to advance the standard of care for patients with cancer. Our oncology portfolio is built around two foundational approaches, our approved PD-1 inhibitor, Libtayo, and our investigational bispecific antibodies, many of which are being evaluated both as monotherapies and in combination with emerging therapeutic modalities. Together, they provide us with unique combinatorial flexibility to develop potentially synergistic treatments for a wide range of solid organ and blood cancers. With our acquisition of full global rights to Libtayo earlier this year, we are well-positioned to continue advancing our oncology pipeline with Libtayo as the foundation. Over the past several years, we have established Libtayo monotherapy as the standard of care in certain skin cancers. Libtayo was also approved in first-line advanced non-small cell lung cancer, both as monotherapy in high PD-L1 expressers and, more recently, in combination with chemotherapy, irrespective of PD-L1 expression or histology, a high bar achieved by only one other anti-PD-1 targeting agent. We are excited to continue building our presence in dermato-oncology and lung cancer while advancing other investigational agents and combinations highlighted by the recent data presented for fianlimab, our LAG-3 antibody, in combination with Libtayo in both metastatic melanoma at ESMO and advanced non-small cell lung cancer at ESMO IO. 2022 was a pivotal year for Regeneron's oncology development efforts as we advanced our broad pipeline in diverse indications and settings. Earlier this year, we shared early but encouraging top-line data for our PSMA by CD28 co-stimulatory bispecific in combination with Libtayo for advanced prostate cancer, providing the first evidence for this innovative combination approach. We also presented important data at ESMO, including updated and expanded data for fianlimab plus Libtayo in anti-PD-1 naive metastatic melanoma, first clinical data for ubamatamab, our MUC16 by CD3 bispecific in recurrent ovarian cancer, representing our first CD3 bispecific in a solid tumor, as well as initial clinical data for our novel biparatopic MET by MET bispecific in MET-altered lung cancer. We are excited to round out 2022 with data from the potentially pivotal studies of odronextamab and linvoseltamab, which Andres will discuss shortly. The continued advancement of these efforts in oncology is a key focus of Regeneron, and we are well-positioned to advance the pipeline in 2023 with additional data readouts and potential regulatory filings. Anti-PD-1 therapy has become a standard of care across multiple tumor types and settings. Despite this progress, there are many cancer patients whose tumors do not respond to PD-1 blockade and many other tumor types that have not responded to anti-PD-1 therapy in clinical trials, such as prostate cancer, most breast cancers, and ovarian cancer. Our broad oncology toolkit gives us a unique opportunity to mix and match approaches with the goal of broadening and deepening antitumor activity. On this slide, you can see our different categories of investigational medicines in our oncology pipeline today, all of which centers upon Libtayo, including our CD3 bispecifics, our CD28 or co-stim bispecifics, our tumor target biparatopic bispecific antibodies, and other immune-modulating agents. Today, Andres will discuss data presented at ASH for both odronextamab in follicular lymphoma and diffuse large B-cell lymphoma, as well as linvoseltamab in multiple myeloma. We will also discuss our first CD28 costimulatory bispecific in hematology, CD22 by CD28, in combination with odronextamab in non-Hodgkin's lymphoma, for which initial preclinical data was presented at SITC last month. I will turn the call over to Andres. Thank you, David. Thank you to everyone joining the call today. Regeneron had a large presence at ASH with over 15 accepted abstracts as we increase our footprint in hematology and hemonc. My presentation today will focus on data from two oral presentations of phase II data for odronextamab in follicular lymphoma and diffuse large B-cell lymphoma, and phase II data for linvoseltamab in multiple myeloma. I will begin with odronextamab, where we present the data from our phase II ELM-2 study in FL and DLBCL. Odronextamab is an off-the-shelf CD20 by CD3 bispecific effective in patients with both indolent and aggressive lymphomas. We have previously shared data from our phase I study in FL and DLBCL, which showed encouraging efficacy and a manageable safety profile. This year at ASH, we provided the first interim data from the phase II ELM-2 study, which were presented in two oral presentations. With over 550 patients dosed in the program today, we are preparing to initiate our OLYMPIA phase III program in early 2023, and plan to submit a BLA in both indications in the second half of next year. As I mentioned, we previously shared data from ELM-1. That study is ongoing and protocols have been updated to include subcutaneous administration arms. Today, we will primarily focus on data from ELM-2 study, specifically in DLBCL and FL. The primary endpoint of the ELM-2 study is overall response as measured by an independent central review. Secondary endpoints include complete response, progression-free survival, and safety. In 2021, we revised the step-up dosing regimen for the program, lowering the initial dose to 0.7 mgs from 1 mg and adding a 4-mg dose before moving to the 20-mg dose, and ultimately the final dose for each indication. With a modified regimen, patients are administered the full therapeutic dose on day 21, which is seven days later than the prior regimen. Over the next few slides, the data will demonstrate that the new regimen had consistent efficacy with the prior regimen, but resulted in an improvement in the safety profile for the overall, resulting in lower rates of treatment discontinuations, interruptions, dose reductions, and dose delays. This was consistent in both FL and DLBCL arms. Approximately half of the patients in the program are on each regimen across both indications. We also made other protocol changes to help better manage CRS in the step-up dosing cycles. Moving to the data presented at ASH and starting with FL. As of this data cut, 121 patients were available for efficacy. Overall response in these heavily pre-treated, highly refractory patients was 82%, with 92% of the responders having a complete response, the highest complete response rate seen in this patient population to date. Based on an assessment at week 12, we observed efficacy was similar for patients regardless of step-up regimen. Here we see the percentage change in tumor size for each patient. The majority of patients had substantial tumor shrinkage, highlighting the ability of odronextamab to provide significant benefit to these late-line patients. These deep responses also show encouraging durability. Median duration of response was 20.5 months, and complete responses also had a median duration of 20.5 months. The probability of maintaining a response for 18 months was 55%. Median PFA was also at 20.2 months, the probability of remaining progression free at 18 months was also 55%. Overall survival data continues to mature with a median not yet reached. Overall, odronextamab has a manageable safety profile in FL. All patients experienced at least one adverse event, grade 3 or higher adverse events were reported in 78% of the patients. The majority of adverse events were grade 1 or 2, the most common adverse events were CRS in 57% of the patients, neutropenia in 40%, and pyrexia in 31% of patients. Treatment discontinuations due to adverse events that were considered related to odronextamab occur infrequently in 7.6% of the patients. 3 Grade 5 adverse events were considered by the treating physician to be treatment-related. All were infections, including 1 case of pneumonia, 1 case of PML, and 1 of a systemic mycosis. The changes made to the step-up dosing regimen for odronextamab have led to improvements in the safety profile. As can be seen from the table, the optimized step-up regimen decreased the incidence of Grades 2 and Grades 3 CRS events. There were no Grade 4 or 5 events. CRS was mostly Grade 1 and generally occurred during cycle 1 step-up dosing. All CRS resolved. Median time to resolution was two days. With a revised regimen, there were no cases of ICANS or tumor lysis syndrome. Overall, in follicular lymphoma, odronextamab showed encouraging and durable efficacy with a manageable safety profile that improved with a modified step-up dose regimen. Moving now to DLBCL. As of this data cut, 130 patients were available for efficacy. Overall response in these heavily pretreated, highly refractory patients was 49%, with 63% of responders having a complete response. Based on an assessment at week 12, observed efficacy was consistent for patients regardless of the step-up dose regimen. As a supporting analysis, we evaluated interim efficacy in the phase I post-CAR expansion cohort of the N-1 study. Based on the analysis, observed overall response rate was similar for patients regardless of CAR T experience. Responses were durable. Neither immediate duration of response nor duration of complete response were reached in the post-CAR T phase I dose expansion cohorts. The deep responses seen in DLBCL patients also show encouraging durability. Duration of response was 10.2 months, and complete responses were particularly durable, with a median duration of 17.9 months. The probability of maintaining a response for 18 months was 39%, and the probability of maintaining SCR for 18 months was 48%. PFS was also durable, with a median duration of 4.4 months. The probability of remaining progression-free at 18 months was 26%. Durability data for responses continues to mature. Otoxmapimod has a manageable safety profile in DLBCL. 99% of the patients experienced at least one adverse event, and Grade three or higher adverse events were reported in 79% of the patients. The majority of adverse events were of low grade, and the most common events were CRS in 55% of the patients, anemia in 42%, and pyrexia in 39% of the patients. Treatment discontinuations due to adverse events that were considered related to Otro occur in 7.9% of the patients. There were 5 Grade 5 adverse events considered by the treating physician to be related to odronextamab, again, all were infections and include three cases of pneumonia, one case of COVID-19, and one case of Pseudomonas sepsis. Similar to what was demonstrated in FL, the changes made to the step-up dosing regimen for odronextamab have led to improvements in the safety profile in DLBCL. The majority of CRS events were Grade 1 and generally occurred during cycle 1 step-up dosing, all CRS events resolved within a median of two days. As can be seen from the table, the optimized step-up regimen decreased the incidence of Grade 2 and Grade 3 CRS events, there were no Grade 4 or 5 events observed with either regimen. CRS was mostly Grade 1 and generally occurred with the cycle 1 step-up doses. There was only one instance of ICANS with the optimized step-up regimen and no Grade 3+ ICANS. Beyond the data presented at ASH for Otro, we recently shared initial preclinical data at SITC for our first human costim CD22 by CD28 in combination with Otro in DLBCL. In preclinical studies, and shown on the right, this molecule showed limited activity, limited T-cell activation, and no toxicity as a single agent, but immense T-cell activation when combined with Otro. Similar to what we have seen and demonstrated with other costimulatory antibodies like PSMA by CD28 and EGFR by CD28 in solid tumors. Our first in-human phase I combination study will initiate in early 2023. We are rapidly advancing a broad development plan for the odronextamab in lymphoma. With the initiation of our phase III OLYMPIA program early next year, we will begin testing odronextamab in early lines of therapy for DLBCL and FL, both as monotherapy and in various combinations. We expect the confirmatory phase III studies to support our planned BLA filing in the second half of 2023. We will also be initiating studies in combination with our CD22 by CD28 bispecific, as mentioned earlier, and continue to advance studies combining odronextamab with our PD-1, Libtayo. In summary, this initial phase II data for odronextamab show encouraging and durable efficacy, observing heavily pre-treated patients in both FL and DLBCL, including in FL, the highest computed response rate observed in these late-stage patients to date. The safety profile of Otrexumab appears manageable. Improved safety was seen with revised step-up dosing, including reduced instances of grade 2 and grade 3 CRS. We are excited about the prospects of Otrexumab in these indications and plan to file a BLA in both indications in the second half of 2023, with confirmatory phase III studies expected to initiate in early 2023. Moving to Linvoseltamab, our BCMA by CD3 antibody in relapsed refractory multiple myeloma. Last year, we presented updated phase I dose escalation data at ASH, which show that Linvoseltamab induced early, deep, and durable responses with a manageable safety profile in patients with a relapsed refractory multiple myeloma. This year, we presented updated phase 1/2 safety and efficacy data from the dose escalation and dose expansion portion of the study. The phase II dose escalation part of the study is fully enrolled. Pending FDA discussions, we intend to file in 2023. Our phase 1/2 study began with dose escalation, with doses ranging from 3 mg to 800 mg. The dose expansion portion is evaluating doses of 50 mg and 200 mg. Our recommended phase II dose is 200 mg. To date, we have treated over 100 patients in each of the 50 mg and the 200 mg dose expansion cohorts. Importantly, in the 200 mg arm of the study, patients with a VGPR or better by week 24 can move to dosing every four weeks instead of every two weeks, offering additional dosing convenience for those patients that achieve a good response. The primary endpoint of this study is overall response, and secondary endpoints include duration of response, PFS, and safety. Early, deep, and durable responses were observed with linvoseltamab in heavily pre-treated relapsed refractory myeloma patients. These results are in a difficult to treat patient population, including 84% of the patients being penta-exposed, 37% with bone marrow plasmacytosis greater than or equal to 50%, and a median soluble BCMA of 0.443 mgs per liter. The latter two are representative of high tumor burden. Responses were seen across all dose levels with a trend toward higher responses at higher doses. At a recommended dose of 200 mgs, the ORR was 64% in these heavily pre-treated and highly refractory patients. Over two-thirds of the patients who responded achieved a VGPR or better. Importantly, we have seen a trend for responses to deepen over time. We have expected numbers of patients achieving VGPR or better to increase with further follow-up. Among patients with a CR or strict CR and available MRD data, 47% of phase I patients were MRD negative at 10 to the minus five, and 60% of phase II patients were MRD negative at 10 to the minus five. Consistent responses were seen in high-risk subgroups, including a similar ORR observed in patients with bone marrow plasmacytosis greater than or equal to 50%, which generally indicates a higher disease burden. Notably, some competitor trials have fewer patients with bone marrow plasmacytosis greater than or equal to 50%, and a lower median level of soluble BCMA compared to patients in our trial. linvoseltamab has demonstrated meaningful response rates in the severe advanced patient population that is associated with poor outcomes and is in an area of high unmet medical need. Observed responses in patients occur early, deepen with time, and have shown promising durability. Median time to response was less than a month for both the 50mg and the 200-mg cohorts. The probability of maintaining a response at six months was 85% and 79% respectively. As of this data cut, the longest responses were over 28 months and ongoing. As we continue to let data mature, we hope to continue to see responses deepen over time, as has been our experience throughout the study. Importantly, per a protocol amendment, eight patients who did not respond at the 50mg dose were escalated to 200 mg. Of these eight patients, six responded to treatment at higher doses, including four with a VGPR. Data from these cohorts were not presented at ASH, but will be shared at a later date. Our data suggests a manageable safety profile for linvoseltamab. A majority of patients did not develop CRS, with CRS reported in only 44% of patients, and importantly, only 37% at a 200 mg dose. In the 200 mg cohort, over two-thirds of the CRS cases were grade 1, with just one transient grade 3 CRS. Most CRS occurred during step-up dosing, with onset on the day of dosing and resolution within one day. No correlation between CRS and the full dose was observed. There were 14 grade 5 AEs. None were considered treatment-related per the treating physician. We are rapidly advancing our clinical development program with linvoseltamab. In the first half of 2023, we plan to initiate a confirmatory phase III study in the first half of 2023 to support this filing, evaluating linvo monotherapy against standard of care regimen against LOPD. We continue to enroll our phase I umbrella study evaluating linvo in combination with various standard of care regimens. Our phase II study is fully enrolled, and we expect data from this study to form the basis of a 2023 BLA submission. We also expect to initiate the study of linvo in combination with a CD28 costimulatory bispecific in late lines of therapy. Altogether, we are rapidly initiating confirmatory studies and advancing studies into early lines of therapy. In summary, linvoseltamab demonstrated compelling phase II efficacy and manageable safety profile in heavily pretreated multiple myeloma patients. Responses were early, deep, and durable, with an ORR of 64% at a recommended 200 mg dose. 60% of phase II patients with CR or strict CR were MRD negative at 10 to the minus five. 6 of 8 patients who dose escalated from 50 mg to 200 mg responded to treatment, including 4 VGPRs. Safety was manageable, with only 44% of the patients developing CRS and only 37% in the 200 mg cohort. Most CRS were grade 1, occurring during dosing step up and resolved within one day. The phase II study is fully enrolled, and we expect to file for approval in the second half of 2023. Our robust clinical development program is advancing rapidly with a confirmatory phase III study and a study in combination with a costim bispecific, both expected to initiate in the first half of 2023. I'd like to conclude by briefly highlighting our growing hematology pipeline. We have a robust and advancing pipeline across various blood disorders and hematology. In, both, sorry, in hematologic malignancies and benign hematology, including phase III studies for our C5 antibody in combination with siRNA in PNH and myasthenia gravis. A phase II data for this combination in PNH was presented at ASH. We are harnessing the power of our technology along with collaborators to develop potential treatments using antibodies, gene editing, and gene knockout technologies, and investigational RNA approaches focusing on depleting abnormal proteins or blocking disease-causing cellular signaling. We are excited to continue advancing these programs and expand Regeneron's presence in hematology. With that, I will pass it back to David. David? Thank you, Andres. We are excited about the continued positive data for odronextamab and linvoseltamab and the competitive safety and efficacy profile highlighted today. Looking ahead, we expect a continued flow of important data across our immuno-oncology programs, with several proof-of-concept data readouts expected in 2023, including our MET by MET ADC antibody, our EGFR by CD28 costim bispecific, and data from several MUC16 combinations in ovarian cancer. In conclusion, we are pleased with the progress for odronextamab and linvoseltamab and the encouraging data presented at ASH this year. We are rapidly advancing robust phase III programs to the clinic to support 2023 filings for odronextamab in follicular lymphoma and diffuse large B-cell lymphoma and linvoseltamab in multiple myeloma. We plan to initiate studies next year combining both bispecifics with CD28 costimulatory bispecifics, applying our differentiated CD28 approach for the first time in hemoc. We continue to advance our diversified hematology pipeline, applying our differentiated capabilities to address rare blood cancers. With that, I'll turn the call back to Ryan. Thank you, David and Andres. We will now open the call for Q&A, where David and Andres can address your questions. In order to address as many questions as possible, we ask that each caller limit themselves to one question, and please keep the scope of your question within today's subject matter. Catherine, please go ahead and read the instructions for calling for questions. Thank you. If you would like to ask a question, press star one one on your telephone. That's star one one to ask a question. Please stand by while we compile the Q&A roster. Our first question comes from Matthew Harrison with Morgan Stanley. Your line is open. Hi, this is Maxwell Skor on for Matthew Harrison. Yeah, just briefly, can you comment on the competitive profile of your BCMA approach compared to others? Potentially any feedback you've received from the FDA prior to filing in the second half of next year? Thank you. Yes. Thank you for your question. We think that we have a very competitive profile in terms of both the safety and the efficacy that is emerging from our study. First, I want to focus on safety. The rates of CRS that we have observed to date with our dose moving forward remains very competitive. As I mentioned to you, at a selected dose or RP2D to move forward, we have observed a 37% overall of CRS, two-thirds of those being grade one. We believe that this is favorable. We also think that linvo has the least amount of hospitalizations requirement in based on our current schedule. The efficacy that is emerging, I think, is first, well, these responses, as I mentioned to you, is early days. We expect the depth of these responses to deepen over time. We are waiting. We think that first very competitively vis-a-vis other assets in the same class. Thanks, Andres. Next question, please, Catherine. One moment. Our next question comes from Chris Schott with J.P. Morgan. Your line is open. Great. Thanks so much for the questions. On your CD22, CD28, how are you thinking about potential toxicity we need to watch as we move, I guess, this platform into hematology? I guess how does the early success you've seen with PSMA kind of increase or change your confidence, I guess, in, in applying CD28 to liquid tumor? Thanks so much. David? Sure. Thank you for the question. I'll take them in reverse order. The fact that we are now seeing activity of the bi CD28 costims from our PSMA experience, I think validates our approach that this particular costim target is a good one. We can also steal some information from that other trial that the safety during the lead-in period, this is before we add cemiplimab to the patients, looks incredibly incredibly clean. The toxicity that we previously reported out was after you introduced the combination. While we don't know what's gonna happen in a hematologic malignancy when we add a CD28, there are reasons to believe that the combination should be well-tolerated. Traditionally in immuno-oncology, getting things to work in the solid organ malignancies is a lot harder than working in the hematological ones. If I had to be a betting man, I would suggest the likelihood that this is gonna work on the basis of all of the preclinical data that we've generated to bring this asset forward, we're quite hopeful. Thank you, David. Next question, Catherine. Our next question comes from Evan Seigerman with BMO. Your line is open. Hi, guys. Thank you so much for taking my question, and congrats on the progress. I'd love for you to just talk about how you envision both odronextamab and linvoseltamab fitting in a rapidly evolving hemoc landscape. We saw a lot of bispecific CAR T data at ASH. I'd love for your perspective there. Would you consider a SubQ formulation for linvoseltumab? Thank you. Yeah. Yes. In terms of the, I'll start with the SubQ formulation. For both otro and linvoseltamab, we are in. Well, for otro, I can tell you that we have already initiated and as I mentioned, during the presentation, the ongoing study is ongoing and exploring a SubQ formulation. We are initiating at the beginning of next year, a SubQ formulation study with linvoseltamab. We will be exploring that as well. In terms, you ask as well on the landscape. It is very competitive. We agree. However, we think that, you know, I'll start with otro, odronextamab. In follicular lymphoma, we believe that we have set a new benchmark in terms of the level of efficacy that has emerged from our study. Just to remind you, we are observing an overall response rate in follicular lymphoma of 82% with a CR rate of 75%. That's 92% of the patients achieved a complete response when you look at those responses. This is what we think outstanding and setting a new benchmark for this class. We think we are very competitive there. In overall, we see, just looking at the field, we look at odronextamab and linvoseltamab as foundational for our for Regeneron. As we mentioned, for both compounds, we'll be moving forward with combinations with our costimulatory molecules in the same way that Libtayo is foundational in our solid tumors. We think that we have a great opportunity for Regeneron there to differentiate and bring to patients a potential for a chemo-free regimens in the future. Thanks, Andres. Next question, please, Catherine. Our next question comes from Tyler Van Buren with Cowen. Your line is open. Hey, guys, thanks very much for the presentation. For linvoseltamab, you talked about hoping to see responses deepen over time, and the median follow-up of the 200 mg dose is quite short, I believe, at around 3 months. Can you elaborate more on the potential for responses to deepen over time based upon what you saw in the earlier phases of the program? In other words, what% of patients convert from a PR to a CR at later scan intervals, and when do you think the data will be mature? Yeah. From what we have observed previously, particularly, as you probably know, you know, we had our patients on the phase I portion of the study. We also have patients on the initial cohorts, and we have presented the data from all our cohorts. We clearly have observed that over time, we achieved deeper responses. Even if you look at our prior presentations, our CR rates have increased on not only based on dose, but on the duration. Even after one year, we have observed patients deepening their response. All in all, we expect that over time, as our data mature, we will be seeing a higher number of patients achieving CRs and D, and S, and strict CRs. Thanks, Andres. Catherine, next question, please. Thank you. Our next question comes from Salveen Richter with Goldman Sachs. Your line is open. Good morning. Thanks for taking my question. I just wanted to follow up on a prior question on positioning here, specifically with BCMA. If the thought is to use it post CAR-Ts and given the GPRC5D data, I guess how are you thinking about the evolving positioning there? Thank you for your question. We believe that the level of efficacy that we have observed in late lines of therapy affords the opportunity for patients in the future to have what I would call chemo-free regimens. Our goal is to move to early lines of therapy, not only we are exploring in combination with the standard of care regimen, but we believe that we have an opportunity to bring to early lines of therapy monotherapy. As you will see, and I have mentioned that our complementary phase III study will be exploring monotherapy versus standard of care. We are confident again that the level of activity we have observed is such that this will be potentially a positive study. That's one aspect. You mentioned post CAR. I'm not sure that, you know, there will be a post pre-CAR. Remember, these are complementary therapies. Not every patient is amenable to CAR, not every patient can be mobilized, and CARs are not... Available to all patients. There are still issues with manufacturing. We see these as complementary. Remember, bispecifics are off the shelf. The responses that we are observing are getting better. The durability may be comparable, and we think that these are complementary. All in all. This is David. I'll add one other thing. As is very typical in, in oncology, you start in late line therapies, but that's not the end of all of this. The, the best combinations of the future to treat myeloma patients are unknown. Having multiple different mechanisms of action, available to patients provide doctors with flexibility because toxicity is going to be different across differing agents. For linvoseltamab, the principal toxicity that we're seeing is very low-grade CRS that we think can mostly be managed as an outpatient. You brought up one of the newer CD3s, targeting GPRC5D. That safety profile looks different. Providing options to physicians to fit with their patients, I think is actually a win-win in the grander scheme of things as we look for better combinations that can actually cure this disease. Thanks. Thank you. Next question, please, Catherine. One moment. Our next question comes from Brian Abrahams with RBC. Your line is open. Hi. Good morning. congrats on all the progress. Thanks for taking my question. How are you guys thinking about the optimal tumor-associated antigen combo partner with the coast in bispecific to pair with your CD3 bispecific? I guess I'm curious why CD22 for the odronextamab combo, and how you're thinking about it for the linvo combo. Is there a rationale for that to also be BCMA, or might you consider something like GPRC5D or CD38? Thanks. Thanks. I'll answer that question. We have an enormous repertoire of TAA or tumor-associated antigen by either signal one or signal two, so CD3, CD28, and amongst the signal twos, many different signal twos. We do a very robust preclinical screening in our VelocImmune mice to help us pick which of these assets and which combination of targets are gonna move forward faster than others. We've essentially got a library of, if you will, of many of these combinations that we can test preclinically and then decide what to move into the clinic. In each case, it's a little bit different. For instance, in ovarian cancer targeting MUC16, we've actually picked the CD3 and the CD28 to target the same thing. It's a MUC16 by CD3 and a MUC16 by CD28. In lymphoma, we've picked a different target, so it's a CD22. It doesn't preclude at some point in the future, we would want to do a CD20 by CD28, but it allows us to bring different things to bear. By mixing and matching the tumor-associated antigen, you could potentially, if you will, cross-target where maximal activity is occurring and help refine which cells we direct for killing in the case where one of the antigens is somewhat promiscuous, and it has potential for off-target toxicity. Another reason to pick two different targets is if one of the targets disappears because of escape mechanisms, you potentially would not lose activity of the entire combination. It's a fairly complicated calculus as to which ones we pick, but that isn't precluding that other ones won't follow into the clinic. We'll have more details on which antigen we've selected for combination with linvoseltamab when we begin dosing early next year, Brian. Next question, please, Catherine. Thank you. Our next question comes from David Risinger from SVB Securities. Your line is open. Yes, thanks very much. I have two questions, please. First, bispecifics are increasingly being evaluated with prophylactic anti-infective treatments to reduce the risk of infections. Could you please provide your perspective on that, including how Regeneron may evaluate appropriate duration of anti-infective use? Second, regarding your CD22 by CD28, is there any more color you can provide on the development plans, including the phase I study design and timing? Thank you. Yeah. In terms of the use of prophylactic antibiotics, we certainly are taking a lot of precautions and looking carefully into prophylaxis and have implemented and continue to evolve based on new emerging data, both for linvo and for the CD20 field. We have implemented prophylaxis across both. I think this is something that we are learning across the class, both the use of not only antibiotics but also IVIG, that will potentially become more prominent in the future. You also asked about the CD22 by CD20 in combination with odronextamab. We are hopefully dosing our first patient in the phase I study early next year, so first quarter. Thanks, Andres. Next question, please, Catherine. Thank you. Our next question comes from Olivia Breyer with Cantor. Your line is open. Hey, good morning, and thank you for the question. For the submissions next year in DLBCL and FL, is the plan to file both at the same time, or does it make sense to move forward with one indication first, you know, if it's a bigger priority, especially given the competitive dynamics at play? If you could just comment on how you're thinking about the commercial opportunity and market size for follicular, especially initially with those later line patients. Thank you. Sure. We're currently planning on filing both the follicular and the diffuse large B-cell indications simultaneously. Given the timing, I don't think any advantage could be had from trying to file one ahead of the other, and we're certainly capable of doing both at the same time. To answer your second question, we're not specifically commenting on our expectation of market size, but I would just remind you that we're looking at this as a long-term play. It's not just about the size of the relapse refractory market in non-Hodgkin's lymphoma, but it's a setup for both earlier lines of therapy, combination therapy, and potentially chemo-free regimens in NHL. Thanks so much. Next question, please, Catherine. Our next question comes from Hartaj Singh with Oppenheimer. Your line is open. Great, thank you, and thanks for the question. Great to see all the energy at ASH, especially with Regeneron. You know, quick question, just following up on some of the previous questions on CAR T versus bispecifics. You know, in some of our calls with KOLs, they have mentioned that sequencing, you know, is becoming more and more important for them, especially hematological malignancies, various therapies as they're being developed. Some multiple myeloma patients, for example, are fifth, sixth, seventh, eighth line, you know, in various clinical trials. When you look forward to the filing in the second half of 2023 with both these projects, can you just give us a sense for where do you see it exactly, you know, in that sequences? Will it be pre-CAR T, post-CAR T? What line of therapy? Just any sense there would really help us. Thank you. Absolutely. I think that, you know, your question was referring to linvoseltamab and ODRO for both. I'll say that the issue of sequencing hasn't fully been addressed in clinical trials. I will remind you that with ODRO, we and I mentioned before that the overall response rate and CR rate that we have observed in lymphoma patients, diffuse large B-cell lymphoma, are consistent both in CAR T-naive and CAR T-experienced patients. Just to remind you, we're seeing an overall response rate of 50% in both with a CR rate of approximately 30% in both. Very consistent whether they're naive or exposed to CAR T or CAR T experienced. That is very encouraging. That's 1 point I wanted to make. Talking about sequencing, I think that again, as I mentioned, not every patient will have access, and we see the advantage or the value on bispecifics being off the shelf and accessible to physicians, vis-a-vis the experience that is required to deliver CAR T to patients. I think that that is eventually going to be an issue of adoption. Thanks, Andres. Catherine, I think we have time for two more. Next up, please. Our next question comes from Geoff Meacham with Bank of America. Your line is open. Hi, this is Susan on for Geoff Meacham. Can you comment about the reformulation process for subQ ODRO, specifically speaking on the regulatory requirements and timing? All I can tell you at the moment is that we are moving forward, and we are exploring already in our phase I study odronextamab as a subcutaneous form, and so that study is moving along well. Thanks, Andres. Last question, please. Our last question comes from Michael King with EF Hutton. Your line is open. Good morning, guys. Thanks for taking the question, and let me add my congratulations on the progress you've been making. A multi-part question on DLBCL and ODRO. In the plenary talk on ELM-1, in the Q&A, the investigator was asked about the step up dosing and his comments, his words were that, you know, hospitalization was required and a quote, unquote, problem. I'm just wondering about that, and also if you could link that to the grade 5 events and how ODRO might compare to some of the other CD3, CD20s in terms of grade 5 events. Thanks. Absolutely. The first thing I wanna mention is about the grade 5 event. Patients deaths are inevitably when dealing with highly refractory patients with advanced disease, especially with a long follow-up, both in DLBCL and in SL. I think that, you know, we need to take that into consideration. Just to remind you that most were infections complications, which is expected for these patients. I think that, you know, I'm not gonna compare with, you know, other assets, but the question will have to be answered in the setting of a randomized trial. Yeah, these are single-arm studies. That is the first point. Sorry, you asked another question. About hospitalization. Hospitalization. The, yeah. Yeah. Hospitalization is primarily on the first cycle, and during the step up. Mike it's David. I'll add just a little more color. I think you have to separate out the safety procedure- This concludes today's conference call. Thank you for participating. You may now disconnect.