Good morning. My name is Jason, and I will be your conference operator today. At this time, I would like to welcome everyone to the Provention Bio call. There will be a question and answer session to follow. Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Mr. Robert Doody, Vice President of Investor Relations for Provention Bio. Please go ahead. Thank you operator, and thank you all for joining us on Provention Bio's conference call. Joining today's call from the Provention Bio team is Ashleigh Palmer, Chief Executive Officer and Co-Founder; Francisco Leon, Chief Scientific Officer and Co-Founder; Chief Commercial Officer Jason Hoitt; and Thierry Chauche, Chief Financial Officer. Before we begin, let me remind you that the various remarks we will make today constitute forward-looking statements. These include statements about our future plans and expectations, clinical results, regulatory and other developments and timelines related to our product candidates, including our plan to resubmit our teplizumab BLA for the at-risk indication and address deficiencies identified in its CRL, as well as the planned delivery of significant catalysts over the next 24 months. The potential safety, efficacy and commercial success of teplizumab and our other product candidates, the potential COVID-19 impact on our clinical studies and business plans, and our business plans and prospects, including with respect to any potential BLA resubmission for teplizumab and projected timing for the same. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our most recent quarterly report on Form 10-Q and in other filings that we may make with the SEC in the future. Any forward-looking statements represent our views as of today only. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so, even if our views change, except as required by law. Therefore, you should not rely on these forward-looking statements as representing our views as of any date subsequent to today. There is more complete information regarding forward-looking statements, risks, and uncertainties in the reports Provention files with the SEC. These documents are available on Provention's website at www.proventionbio.com under the Investors section. We encourage you to read these documents carefully. With that, I will now turn the call over to Ashleigh. Thank you, Bob, and good morning to everyone joining us on the call today. As many of you will have seen from the press release we issued yesterday afternoon, our Type B pre-BLA resubmission meeting with the FDA took place earlier this week. The purpose of this meeting was to discuss and obtain agreement on our proposed clinical pharmacology data package, including data and analysis from the pharmacokinetic and pharmacodynamic, or PK/PD, sub-study completed by the company to address the FDA's PK comparability considerations contained in the complete response letter, or CRL, issued last July. In the agency's preliminary comments following our meeting request, the FDA noted that the data package presented did not adequately support PK comparability because predictive primary PK parameters were indicative of a lower exposure. However, to address this concern, the FDA proposed, and we agreed, to use the PK model developed with FDA input and guidance and approved at our Type A meeting in November to simulate PK parameters so as to adjust the 14-day dosage regimen for the planned commercial product to match the exposure of material used in prior clinical trials. The purpose of doing so is to ensure that the 90% confidence intervals for relevant PK parameters fall within the target 80%-125% range. I'm very, very pleased to confirm that on this basis, the FDA agreed that Provention Bio can proceed to resubmit the teplizumab BLA for the delay of clinical type 1 diabetes in at-risk individuals. Taking into account both our and the FDA's PK modeling, as well as our experience with various dosing regimens tested in our prior clinical trials, we believe that we will be able to satisfy the FDA's exposure matching request in the BLA resubmission with an appropriately modified 14-day course of therapy. As we agreed with the agency at our Type A meeting in August of last year, the BLA resubmission will also include responses to address the CRL considerations related to CMC and product quality. We believe that we will be in a position to resubmit the BLA this quarter. Under FDA guidelines, the agency will have 30 days to review the BLA resubmission, determine whether it is complete and acceptable for review, and will then provide an action date. Under our existing Breakthrough Therapy and priority review designations, the FDA's guidance for a Class 2 CRL response is within six months from the date of resubmission. Importantly, you will recall that the complete response letter did not cite any issues or deficiencies with respect to the clinical efficacy or safety of teplizumab in the target at-risk indication. Last year, Provention Bio and the FDA each had an opportunity to present their case for teplizumab in at-risk individuals to the FDA's Endocrinologic and Metabolic Drugs Advisory Committee. This committee voted in favor of the benefits of teplizumab outweighing the risks in support of approval. As we now prepare to resubmit the BLA, we continue to acknowledge the commitment and collaboration of our counterparts at the FDA and thank them very sincerely for their ongoing expertise and guidance. The team of reviewers we are working with could not be more dedicated, and it is patently clear to us that they recognize the magnitude of the unmet need that exists for individuals at risk of type 1 diabetes in accordance with teplizumab's Breakthrough Therapy Designation. We are very excited to now have taken another step towards our goal of delivering teplizumab to patients and their families, and we will keep you apprised of our planned BLA resubmission and our preparations for potential approval and launch. It is our view that the approval of teplizumab in this first indication would represent a significant advancement for patients affected by type 1 diabetes. However, we also believe it represents a substantial validation for the company we founded and continue to build. There are over 23 million patients living with autoimmune diseases just in the United States alone. Autoimmune diseases have no cure and remain one of the leading causes of death and disability with rising prevalence. These patients deserve more. They deserve better. We founded Provention on the principle that early intervention and immunotherapy can intercept and prevent autoimmune diseases before irreversible tissue damage and end organ failure takes place, before it's too late. Both teplizumab and PRV-3279 represent perfect examples of our conceptual platform, interception. We believe both therapeutic candidates have potential applicability across a broad spectrum of autoimmune disorders, both as monotherapy and in combination with other emerging approaches such as cell therapy, gene therapy, and tolerization. We are now even more committed to unlocking that potential, whether it be through independent development programs or strategic partnerships. Following a potential approval and U.S. launch of teplizumab for at-risk patients, we next look forward to the top-line results of our phase III PROTECT trial of teplizumab in newly diagnosed T1D patients. As reported last quarter, we had met our target enrollment of 300 patients and out of an abundance of caution, given the challenges to clinical trial follow-up presented by COVID, we proceeded to over-enroll this study by about 10%. We remain on track to deliver top-line results from the trial after completing the protocol's 18-month follow-up next year, opening up the prospect for expanding teplizumab's label to include an ever-growing 64,000 newly diagnosed patients presenting with T1D for the first time each year in the United States. Let's not get ahead of ourselves. If first approved for at-risk patients, our immediate future clinical development plans aim to broaden teplizumab's initial labeling and market potential by exploring younger age groups below eight years and evaluating the impact of repeat dosing to extend a single course of therapy's three-year median delay in progression to clinical stage insulin-dependent disease. Our longer-term plans include the evaluation of subcutaneous formulations, as well as the exploration of potential combinations of teplizumab with other rapidly advancing approaches such as pancreatic islet and beta cell transplantation, targeting the growing market potential of 1.6 million established insulin-dependent type 1 diabetics in the United States alone. In prior studies, the addition of teplizumab to islet transplantation induction regimens has been successful in extending the durability of the post-transplantation insulin-free period. With published studies reporting 75% of transplanted patients remaining free from the burden of insulin dependency for more than fiive years. Outside of T1D, we plan to begin exploring the potential use of teplizumab across other autoimmune related disorders such as celiac and Crohn's disease, early arthritis and autoimmune hepatitis. It is our intention to hold an investor R&D event later this year to dive more deeply into our expansion plan. In closing, we look forward to the important milestones ahead for teplizumab as we continue to work towards becoming the leader in interception and prevention of autoimmune diseases. At the same time, expect us to continue to draw your attention to the depth and breadth of our pipeline of development candidates across the autoimmune disease landscape, with significant catalysts expected over the course of the next 12-24 months. We thank you for your time today, and now would like to address your questions. Operator. Thank you. We will now begin the question and answer session. To ask a question, you may press star then one on your touch tone phone. If you're using a speaker phone, please pick up your handset before pressing the keys. To withdraw your question, please press star then two. At this time, we will pause momentarily to assemble a roster. Our first question is from Alethia Young from Cantor Fitzgerald. Please go ahead. Guys, thanks for taking the question and congrats on this progress and milestone. The first one is just it's sort of a clarifying question, but I just wanna make sure. It seems like you know this is kind of the final stone in the coffin as far as you know being prepared and having the buy-in for the FDA. I just you know just want you to you know double confirm that for us. You know it seems like you've done everything you need to do to move forward and you know now what the FDA wants from you. That's the first question. Just clarify that, maybe talk to it a little bit more. Second question is a commercial one where, you know, look, you've got some extra time to think about the market and, you know, invest in it. I just want, you know, you guys to talk about kinda commercial readiness, you know, if an approval does come perhaps maybe late this year. You know, kinda how you're now thinking about the market, some of the work that you've done in addition to figure it out. We still get a lot of questions about, you know, just, you know, kinda, you know, how open physicians will be to a very new treatment in this market, but you've obviously a lot of time to think about this now. Thank you. Thank you, Alethia, for the question. We definitely believe that we can proceed to file the BLA. We have obviously benefited from a CRL in the middle of last year that laid out the FDA's concerns, considerations and deficiencies. We've obviously met with the FDA to discuss our belief that we can address those. The remaining consideration was the PK comparability and the fact that certain parameters had a confidence interval falling below the 80-125% range. The agency has worked with us and recommended that we address this by a dosing regimen adjustment and has agreed that we can proceed to submit or resubmit our BLA on that basis. I think that is as clear a path to potential successful review and approval, but that remains to be determined. I think the second question about commercial readiness, I can hand over to Jason. Jason? Yeah, absolutely. Thanks for the question, Alethia. You know, as you can imagine, over the course of the past year, we've done a tremendous amount of work on the commercial front to better understand our key customers and key stakeholders, frankly, across the board. We've now conducted market research with over 1,200 individuals. Excuse me. That includes healthcare providers, adult and pediatric endocrinologists, certified diabetes educators, patients, caregivers, advocacy groups. With that, we have a really well thought through launch plan that we're ready to implement. With that being said, you know, I'm looking forward to sharing a lot more details on some of the key insights, our targeting and deployment model, the commercial model, pricing and our tactical plan as we get into a potential investor day later this year after we resubmit the BLA. To the first point in your question, our goal is to launch teplizumab as close as we practically can to the time of an approval. As we've stated before, we've been gating our spend and our hiring prudently so to regulatory confidence and regulatory milestones, and we'll continue to do that. Our goal will be to get the drug into the hands of patients as fast as we possibly can after a potential approval. A follow-up on that, though. I mean, it feels like you guys have the green light. So are you guys gonna kinda, you know, go full throttle making those investments, you know, kinda now? 'Cause it feels like you have the visibility. We're going to continue our gated approach. I think that even through the review period, there are indicators that will be associated with a lower risk. If, for example, we are beginning active labeling negotiations, that would be a really good indicator to us that the agency's review of the clinical pharmacology section and our resubmission is advancing nicely. Perhaps at that point, we would then see the gating open up. All right. Well, congrats, guys. It's been a long road, but congrats on your perseverance for bringing this important medicine to the market. Our next question comes from Ram Selvaraju from H.C. Wainwright. Please go ahead. Hi. Thanks very much for taking my questions. So just three quick ones. Firstly, I just wanted to clarify that the dosing schedule itself is effectively unchanged from the dosing schedule that was used in the at-risk study, and that whatever changes are being made based on the PK model are, for all intents and purposes, not likely to be considered material by the FDA itself when it comes to the question of evaluating the resubmitted BLA. In other words, the FDA has already given you some kind of clarity indicating that even though the dosing regimen is being driven now by this PK model, they're not going to regard it as a completely different and distinct dosing regimen relative to what was used in the at-risk study and force you to conduct a new clinical efficacy trial because of that. Secondly, I wanted to understand better if you need to conduct any additional work with respect to the manufactured material that is intended for commercial use in order to satisfy any further CMC requirements by the FDA, or if all of those have been satisfied. Lastly, if you could perhaps comment on what implications the interactions with the FDA may have for your discussions with European regulators. Thank you. Thank you, Ram. I think I have those three questions. By dosing schedule, I assume you mean the 14-day regimen, and that is correct. We believe that the adjustments will be made to a 14-day regimen, as used in the TN-10 study. In terms of what those would look like, we believe that modestly adjusting to have a faster ramp-up, and then modestly adjusting to have a higher maintenance period across those 14 days, is the way to go. That will obviously have to be to the FDA's satisfaction and generate the appropriate output from the agreed-upon model that we have built and it was designed, built, and agreed upon by the FDA at our November Type A meeting. The ramp-up would be no faster than the PROTECT study, and as you know, that had a slightly faster ramp-up over the TN-10 study because we compressed the total cumulative dosage from previous 14-day regimens into a 12-day regimen for PROTECT. So we have really good, you know, experience, in addition to studies that have taken place over many years, in terms of the impact of different dosing regimens. We even have psoriatic arthritis and transplantation studies that have much higher doses than used in T1D that we can reference to satisfy the modeling and its output with respect to safety. We do not anticipate the need to do another clinical trial to show efficacy at this adjusted dose. That is not the objective of the company, nor do I believe or understand it's the objective of the FDA. This is an adjustment to address the CRL consideration and move forward with a review and potential approval of this breakthrough therapy designated drug. We do not anticipate that there will need to be any new work process development to satisfy CMC issues coming out of this dosage adjustment with respect to the considerations that were in the CRL. As we reported back in August, from the Type A meeting we had to discuss those, we believe that they had either already been addressed in submissions made to the agency that had not been reviewed prior to the CRL being issued or were addressable. That Type A meeting was specifically to review our intentions with respect to a BLA resubmission, and those will be contained in the BLA we will be submitting along with the clinical pharmacology submission. With respect to the EU, yes, for certain, our assumption has been that the European and the U.K. regulatory authorities would have the same considerations with respect to PK comparability as the U.S. has and published in its CRL. With this approach going forward, we're looking forward to interacting with those international regulatory agencies to ensure that this approach also addresses their potential concerns. Okay. Just to clarify, once discussions with the FDA have been concluded, and I presume once the FDA has approved the BLA, it is your view that this can be used as an effective template with other regulators, notably those in Europe, to address whatever concerns they could conceivably have regarding this PK issue, correct? We believe our discussions with the FDA have already taken place with respect to this approach, and now we're going to submit the solution in the BLA. There is no reason in my mind why we can't begin discussing this approach and this solution with the other agencies now and not have to wait until the review has been completed by the FDA. Thank you for that. The next question comes from Thomas Smith from SVB Leerink. Please go ahead. Hey, guys. Good morning. Thanks for taking the questions, and congrats on the progress. Can you maybe just add some context and color to your conversations with FDA, and I guess how they became comfortable with you moving forward with a proposed dosing regimen that's based on PK modeling rather than explicit clinical experience? Sure. Thanks for the question, Tom. The PK modeling is based on clinical experience, obviously. The data collected from the PK sub-study in PROTECT enabled us to design, build, and agree upon a population PK model specifically for the purposes of simulating and modeling the primary PK parameters. As we reported in November, that modeling substantially supported our view that the original PK/PD bridging study, single fractional low dose trial or study in healthy volunteers predicting a very significant difference in clearance. When teplizumab is administered to patients at therapeutic dosing, that predicted gap closes very considerably. However, as we also reported in November, the lower confidence interval of some of the PK parameters fell below the 80%-125% range that is typically used to assess PK comparability. Remember, we're just talking about PK comparability. That is a measure of exposure. The agency said, "Look, to address our concerns about exposure, please come back to us with an adjusted dose to bring these primary PK parameters within the 80%-125% range." We believe we can do that. Okay, got it. Just on the remaining steps and the gating factors here to BLA resubmission, can you clarify, have you gathered and analyzed the comprehensive safety update that the agency requested be included in the resubmission, or is that something that's still in process? The safety update referenced in the CRL is basically ensuring that all of the patients from the time the BLA was originally submitted, the patients we've enrolled into the PROTECT study, for example, or the TN-10 extension study and so on, that all of those are captured in the database. We do that, you know, on an ongoing basis and believe that when the BLA is ready to be submitted from the pharmacology perspective, that the database will not be on the critical path and will be submitted alongside. Okay, great. Yeah, very helpful. Thanks, guys, for taking the questions, and congrats again on the progress. Thanks, Tom. The next question comes from Gregory Renza from RBC Capital Markets. Please go ahead. Congratulations on the development here, and thanks for taking my question. Actually just following up on the previous question. With respect to steps that are remaining before you submit the BLA, could you just comment just a little further what expectations are around any additional interactions with the agency before submission? I know you mentioned preliminary commentary that drove this. Are we waiting for minutes or have an expectation for another meeting with FDA prior to that first quarter refile? Thank you. Thanks, Greg. Yeah, we do not anticipate the requirement for another formal meeting with the FDA before the BLA resubmission. As I mentioned in my opening remarks, we could not be more grateful for the agency's collaboration throughout this entire Breakthrough Therapy Designation process all through last year prior to the AdCom and so on. As we reported throughout last year, we have the opportunity to meet informally and to discuss with the agency our questions or their questions including during the review period. We see no reason why that wouldn't continue to take place, and it's positive. In terms of a potential delay to a resubmission as a result of having to request a formal meeting to proceed with anything before the BLA resubmission, that is not the case. That's helpful. Thank you. Just with respect to the timeline being certainly on short time, you mentioned the six months, which is fantastic. I'm just curious if you have any early views on your look on the potential for a post-marketing requirement that could be instituted by FDA. Certainly cases where that makes a great deal of sense, and others where sponsors find that to be, you know, less acceptable and sort of walking away from programs and proceeding. Do you have views on what a post-marketing commitment from you would entail or how you would approach that with the agency? We've not recently had any discussions regarding post-marketing requirements. We think that the therapy has a very substantial historic database now over 800 patients with 300 patients enrolled into the PROTECT study. We are eager and welcome having an opportunity in the review period to discuss with the agency what it might deem to be appropriate for, you know, for post-marketing commitments and certainly would embrace those. We ourselves want to do a number of post-marketing studies to expand the label, some of which could address the agency's concerns as well. We very much want to study teplizumab in at-risk individuals below the age of 8 because as we all know, this is predominantly a pediatric age autoimmune disease, and there are a good many of the at-risk individuals below the age of 8 that could potentially benefit from a therapy that might delay the onset of the disease, the clinical stage disease. That's a high priority for us. Secondly, we really want to get involved in programs to assess redosing because the amazing clinical outcome reported in the TN-10 study in the publication in the New England Journal back in June of 2019, subsequently updated with a three-year median delay in onset, came from a single course of therapy. I think Francisco has indicated in some of the past calls we've had, there's the prospect of certain biomarkers, the exhausted T cells, for example, that could tell us when a patient is going to be sort of well satisfied from the impact of teplizumab from a single course of therapy and might not require redosing versus those patients that might require redosing and give us some information as to when to do that. We're excited to get into the review period with the FDA having resubmitted the BLA and then have these discussions. That's helpful. Maybe last question for me, actually maybe more for Francisco. Do you have any prior examples that you are leaning on where sponsors and regulators have used the PK modeling to achieve comparability to adjust dosing at this stage in order to gain approval for a program? There are precedents and we are compiling a list and, if we have a good comprehensive list, we'll share that with you in the coming period. Fantastic. Thanks again, Ash, and congratulations. Thanks, Greg. The next question comes from Justin Kim from Oppenheimer & Company. Please go ahead. Hi, good morning, and thanks for the positive update and taking the questions today. Just to clarify one point on the recent interaction with the agency, could you just provide any additional color on whether there's any feedback on the pop PK model results? In particular, just the sort of lower limit of the confidence intervals observed from the top-line results on AUC infinity and day 13 and, you know, what gives you confidence on the resubmission, you know, with respect to those metrics. The model that we have worked on with the FDA and its output is the result of this interaction with the FDA and their recommendation and proposal that we make the adjustment. There's concurrence between the company and the FDA that certain PK parameters have a confidence interval that falls below the 80% lower limit. The purpose of the FDA's recommendation is to make an adjustment to the 14-day dosage regimen in order to bring that lower confidence interval within the 80%-125% range. Okay. Got it. Great. Just maybe a final question from me. I mean, does the team have any updated thinking on you know, how to move infusion to sort of at home? I know we've sort of had talked about this previously. I'm just wondering, you know, whether that's sort of any updates there given sort of the time to sort of think about those processes and how to, you know, have patients infused at home, you know, for potentially some of the treatment regimen. Absolutely. Jason, could you answer that? Thanks, Justin. Yeah. Thanks for the question, Justin. You know, as we've said in the past, our intent with our distribution model is to allow for the site of care, the site of infusion to be a decision that's made by the healthcare provider, the patient and/or the caregiver, depending on the age of the patient. With that as a backdrop, we have a limited distribution network. We've got a selected specialty distributor from whom a hospital or infusion center can directly acquire the product and bill. We also have a network of two specialty pharmacies, both of which have home infusion capabilities in all 50 states. We're preparing for the eventuality of patients starting and completing in an infusion center, the potential for patients to start in an infusion center, under direct observation of a physician and then transition to home infusion. Over time, as patients and clinicians and caregivers become more comfortable having used teplizumab, the possibility of infusing at home right out of the start through one of the specialty pharmacies is certainly a consideration. Got it. Great. Thanks so much. The next question comes from David Hoang from SMBC. Please go ahead. Hey, everyone. Thanks for this great update this morning and congrats on this positive path forward. I think a lot of my questions have been covered already, but maybe, you know, just a couple from me to additionally clarify. I understand the agency, FDA itself, proposed the path forward here, you know, with the adjustment to the dosages based on PK modeling. I just want to get a sense of your level of confidence that, you know, during the review period, do you think there is any possibility that another clinical study, whether, you know, it's PK bridging or some other type of study, may still come up? You know, was that something that was discussed at all with FDA, you know, as a consideration in any, you know, shape or manner? Yeah, just trying to get a sense of is that something that, you know, may still be out there during the re-review period? Thanks, David. The study itself, the TN-10 study, there were no safety or efficacy considerations included in the CRL that we received in July. We have not had any conversations with the FDA regarding any deficiencies in that study since then. This is all about exposure matching. I think that I believe that the work we've been doing with the modeling and the PK/PD sub-study that we did in PROTECT has brought the FDA and Provention together to recognize that the commercial product and the product that the material that was used in past clinical trials are sufficiently similar to enable us to make a PK modeling based adjustment to the 14-day dosage regimen to simply ensure that with the commercial product individuals are going to get enough exposure to teplizumab to have the same benefits in the TN-10 study. Because it's exposure matching that also means that they should have the same risks and the same safety profile. We don't believe at this point in time that there is any suggestion that we would have to go back and do another study in order to show safety or efficacy with an adjusted dosage regimen. Got it. Okay, great. Thank you. Really appreciate you going into that detail. Then just in terms of, you know, milestones and communicating that to the market, do you plan to signal when you actually have done the resubmission and then when FDA has, I guess, formally accepted that application for re-review, would you also communicate that? I think that can be assumed. Of course, there will be a 2021 year-end results and update towards the end of this quarter, which will be timely. We believe that there will be ample opportunities for us to update the market. Okay. Thanks so much for taking the question. This concludes our question and answer session. I'd like to turn the conference back over to Ashleigh Palmer for any closing remarks. Well, thank you very much for joining us today. We really appreciate your time and attention this morning. We appreciate your patience throughout the period since we received the CRL. We hope that you're as optimistic and excited as we are regarding these latest updates, and we look forward to continuing to keep you updated on our progress going forward. Thank you. The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.