Provention Bio, Inc.

Good morning. My name is Kaylee, and I will be your conference operator today. At this time, I would like to welcome everyone to Prevention Bio Call. This 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 hand the conference over to Mr. Robert Doody, Vice President of Investor Relations for Prevention Bio.

Thank you, Operator. and thank you all for joining us on PreventionBio's first quarter 2021 financial results conference call. Joining today's call from the PreventionBio team is Ashley Palmer, Chief Executive Officer and Co-Founder, Andrew Drexler, Chief Financial Officer, and the other members of the PreventionBio leadership team. 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 expectations, clinical results, regulatory, and other developments and timelines related to our product candidates, including for the teplizumab DLA, such as our plans to work with the FDA to resolve their PK comparability concerns and expectations for the upcoming advisory committee meeting. 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, financial projections, including our anticipated use of cash and our cash runway, and our business plans and prospects, including planned pre-commercial activities across the company in preparation for the potential approval of Proclizumab 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, which we filed with the SEC this morning, 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 prevention files with the SEC. These documents are available on prevention's website at www.preventionbio.com under the investor section. We encourage you to review these documents carefully. With that, I will now turn the call over to Ashley.

Thank you, Bob, and good morning to all of you joining us today. We greatly appreciate your support and attention as we continue our mission to develop and commercialize pioneering therapeutic options to intercept or prevent serious life-threatening and life-impacting autoimmune disease. In founding Prevention Bio just four years ago, our intention was to disrupt how the biopharma industry and healthcare systems around the world typically wait for patients with autoimmune disease to present to clinicians with symptoms. Often by this time, irreversible tissue damage has already taken place. Precious cells and organs have been damaged or destroyed. It's simply too late. It's not good enough. And we believe that patients and their families deserve better in this modern world of medicine. As with all pioneering endeavors, we recognize that our path to accomplishing our mission is not without its obstacles, hurdles, and resistance. As such, we've built our company from the ground up with like-minded professionals and industry experts capable of addressing those challenges head on. We have established a resilient and tenacious culture dedicated to improving the lives of patients and their loved ones. Ultimately, we believe we will prevail. I open our call this morning with these comments to put into context the current status of the ongoing review of our BLA for teplizumab for the delay of progression to stage 3 clinical type 1 diabetes in at-risk individuals. When we acquired teplizumab just three years ago, we took on the challenge of reviving a potential therapeutic option that had been long deprioritized by others. Our original strategic intent was to do so by focusing on the preservation of beta cells in newly diagnosed patients by way of our phase three PROTECT study. At the time of acquiring teplizumab in 2018, The TN10 trial conducted by the NIH-sponsored academic consortium TrialNet had already been fully enrolled and was waiting for the progression of a threshold number of patients to clinical stage disease before opening up the blind. The drug product administered in the TN10 study had been manufactured using drug substance produced by Eli Lilly more than seven years beforehand, now over a decade ago, and involving plant and certain processes that are no longer available. Importantly, when prevention acquired teplizumab, we also acquired the original cell lines used to manufacture the original Lilly drug substance. along with the original batch records, specifications, and other know-how necessary to transfer this process to our manufacturing partner and into the modern biotechnology era. We believe we have produced a quality and comparable teplizumab drug substance by way of an up-to-date, well-controlled, reproducible, and validated commercial scale manufacturing process. Additionally, throughout 2020, all the physicochemical testing and analyses required for our manufacturing partner, AGC Biologics, to release that drug substance for filling met all the requisite specifications and parameters, thereby enabling the completion and submission of our BLA's CMC module. Before introducing new drug product containing AGC drug substance into our phase three PROTECT trial in newly diagnosed T1D patients, we conducted a single low-dose PK-PD bridging study in healthy volunteers. And we observed a PK area under the curve, or AUC, level below the target comparability range, indicating that in this particular study, the new drug product might be clearing from the bloodstream faster than drug product manufactured from the old Lilly drug substance. Importantly, in this study, we believe that other relevant PKPD parameters, such as the peak concentration, or Cmax, the clinically relevant PD marker of transient lymphocyte drop, the immunogenicity, and the safety profile all fell within acceptable ranges of comparability. As we stated previously, based upon very extensive PK PD modeling and taking into account the totality of the information available to us at this time, It is our firm belief that the observed difference in PKAUC is not clinically relevant and should not impact clinical efficacy or safety since the predicted exposure for the intended commercial product remains above the requisite threshold for beta cell protection. Based on its review to date, the FDA is not comfortable with our conclusions. the agency has informed us that it does not yet consider the two drug products to be sufficiently comparable and cannot be certain that the PKAUC shortfall observed in our single low-dose PKPD bridging study in healthy volunteers might not translate into clinical relevance. Nevertheless, under our breakthrough therapy designation, the FDA continues to be very engaged, very helpful, and very cooperative, and has agreed to work closely with us to figure out our next steps and a path forward to a solution, which we anticipate will likely require our provision of additional data to support PK-PD comparability. One potential pathway may be to access PKPD data from patients in our ongoing PROTECT study, which has begun enrolling patients to receive either drug products using the original Lilly drug substance or drug product intended for commercialization using AGC drug substance. We have also stated that we expect the need to provide the agency with additional data will result in a delay of the expected timelines within which teplizumab has the potential to be approved and made available to patients. We are continuing to discuss next steps with the FDA and will keep you apprised and updated as to our progress. These comparability discussions are occurring in parallel with preparations for the upcoming advisory committee meeting in three weeks' time on May 27th. And the FDA notified us of its intention to mention the comparability considerations in its briefing materials, along with an affirmative statement that the agency is actively working with us to find a solution. We believe the FDA's intent is to focus the advisory committee meeting on an examination of type 1 diabetes unmet need and the safety and efficacy of teplizumab from the TN10 trial supported by data from other historic studies in newly diagnosed patients. Our understanding is that since the FDA's comparability considerations do not bear on the benefit-risk assessment of the TN10 study clinical data package, no comparability-related questions or discussion topics are planned for the meeting. We are also fully aligned with the FDA's recommendation to remove the term prevention from the wording of teplizumab's initial indication. and instead focus exclusively on delaying the progression of disease. We believe this will help to reinforce the fact that while pre-symptomatic, T1D patients with two autoantibodies and dysglycemia already have the disease and may benefit from therapeutic options targeting the preservation of functional beta cells. Our team has been working diligently for quite some time now preparing for this advisory committee meeting as we realize the pioneering importance of having an opportunity to present the first disease-modifying therapy for type 1 diabetes to be reviewed by this committee. We look forward to standing alongside scientific key opinion leaders, endocrinologists, immunologists, and other treating physicians, diabetes nurse educators, and other members of the T1D clinical community, as well as patient advocacy organizations, patients and their families, who for so very long have hoped and waited for a disruptive innovation that has the potential to delay clinical stage disease and the burden and risks of insulin dependence. such a therapeutic advance would be a critically important breakthrough, especially for younger patients, otherwise facing a lifetime of continuous blood sugar monitoring and insulin therapy. We understand that much of our investors' focus and attention this year has concentrated on the nearer-term regulatory pathway to the potential commercialization of teplizumab for the at-risk patient population. However, that is certainly not all that Prevention Bio is about, and I would now like to spend a few moments providing you with an update on the progress and momentum that is taking place throughout our organization with our impressive pipeline of other immunology therapeutic programs. Importantly, our previous guidance with respect to our programs remains on track. Beginning with our PROTECT phase three trial of teplizumab in newly diagnosed patients, as you know, randomization into this trial was paused for some time last year due to COVID-19. However, upon resuming randomization, enrollment has steadily increased as various sites and countries have come back online. And we are now on track to complete enrollment of this trial in the second half of this year. Importantly, this will position us to have top-line results available in mid-2023. Now turning to PRV3279. This is our humanized bispecific scaffold targeting both CD32B and CD79B receptors designed to inhibit B-cell function and suppress autoantibody production without causing B-cell or platelet depletion. In addition to the strategic collaboration agreement we announced in the first quarter of this year with Huadong Medicine for development and commercialization in Greater China, we continue to progress preparations towards the initiation of our prevailed Phase IIa lupus trial in the second half of this year. Also, with respect to PRV3279, we reported preclinical data and results from a model of Pompe disease, showing improved efficiency of transfection of a gene therapy product by reducing its immunogenicity with a PRV3279 surrogate. PRV015, our partnered fully human anti-IL-15 monoclonal antibody program, continues enrollment in the Phase IIb proactive trial, and we expect top-line results in 2022. As a reminder, after this Phase IIb trial is completed, Amgen has an option to take the asset back for Phase III development and commercialization. At which point, if exercised, we would receive a payment of $150 million, along with subsequent milestone and royalty payments. Lastly, we are excited to announce that we have completed enrollment in the first in human phase one healthy volunteer trial for PRV101, our vaccine against Coxsackievirus B. We expect to have a top line results for this trial in quarter four of this year. As discussed previously, it is believed that Coxsackievirus B is one of the main triggers of the immune cascade that results in pancreatic beta cell destruction in type 1 diabetes and gluten exposure driven gastrointestinal autoimmunity in celiac disease. we continue to make significant progress advancing all of our autoimmune disease therapeutic programs, whilst at the same time concentrating on the teplizumab regulatory pathway and potential commercialization preparation. I'm now going to turn the call over to Andy to provide you with details on our financial results for the first quarter before returning for closing remarks and questions. Andy.

Thanks, Ashley, and good morning, everyone. Before I begin, I would encourage you to read our 10-Q that was filed today. The 10-Q includes our financial statements, risk factors, as well as management's discussion and analysis of our financial condition. I would also like to call your attention to the earnings press release, which was issued prior to this call. Let me start with the P&L. We generated a net loss for the first quarter of 2021 of $32.4 million, or $0.52 per basic and diluted share. The increase in net loss compared to the first quarter of 2020 is the result of increases in research and development expenses of $10.6 million, driven primarily by costs for our Teplizumab program, including the Protect Phase III trial, manufacturing and regulatory activities, as well as the build-out of our medical affairs infrastructure to support suplizumab, which includes type 1 diabetes, disease state awareness, and screening education programs. The increase in net loss also resulted from an increase in general and administrative costs of $9 million, which includes $5.1 million in pre-commercial expenses. Shifting now to cash. As of March 31, 2021, our cash position was $207.2 million. Our net cash-based operating expenses were $29.5 million for the first quarter ended March 31, 2021. During the first quarter, we completed a follow-on offering, which generated approximately $102.3 million of net proceeds. In addition, during the quarter, We also received a $6 million upfront payment related to our strategic collaboration with Huadong to develop and commercialize PRB 3279 in Greater China. Please note that from an accounting perspective, we expect to recognize the upfront payment and other R&D funding from this agreement on a proportional performance basis over the next three years as we conduct the development activities contemplated by the agreement. Finally, we expect to use between $30 and $35 million of cash for operations in the second quarter of 2021. We expect our current cash, cash equivalents, and marketable securities will be sufficient to fund projected operating requirements for at least the next 12 months, and that will enable us to actively develop all four of our programs. Lizumab for type 1 diabetes, PRV-3279 for lupus, PRV015 for celiac, and PRV101, a Coxsackievirus B vaccine. We plan to provide additional cash guidance on each quarterly call as we continue to progress towards the potential regulatory approval and commercial launch of teplizumab. With that, let me turn the call over to Ashley for closing comments. Ashley?

Thank you, Andy. Before we open the call up to address any questions you may have, I want to share my deep appreciation for all our colleagues here at Prevention Bio for their hard work, expertise, and dedication. You demonstrate each and every day the highest levels of commitment, tenacity, and professionalism. as together we fulfill our mission of becoming the disruptive, catalytic, game-changing industry pioneer we set out to create four years ago. I am also thankful to the team of officers and reviewers at the FDA for their level of collaboration. They've shown our company as we strive to bring teplizumab closer to becoming a disease-modifying option for patients with stage 2 type 1 diabetes. There will always be challenges along the path of innovation and change. However, the cooperation we have witnessed to date provides us with optimism and confidence. I especially want to thank our shareholders, both new and those who have been with us from the very beginning. Your support enables us to continue to progress our mission and make the significant strides we have witnessed over the past 12 months. Sincerely, thank you. And finally, I want to acknowledge and thank the patient advocacy organizations, clinicians, patients, and their family members impacted by type 1 diabetes and other serious autoimmune diseases. We believe your cause goes beyond worthy and deserving. It's essential and has compelled us to create and found Prevention Bio four years ago. It is your needs and your courage that inspires and propels us forward each and every day. With that, operator, we'd like to take any questions.

We will now begin the question and answer session. To ask a question, you may press star then one on your telephone keypad. If you're using a speakerphone, please pick up the handset before pressing the keys. To withdraw your question, please press star then two. At this time, we will pause momentarily to assemble our roster. Your first question comes from Aletha Young with Kantor. Please go ahead.

Hey, guys. Thanks for taking my questions. Just a couple. So on like this kind of pre-specified 80% to 125% area under the curve range, I guess can you just kind of give us like background or walk us through how, you know, like obviously it was pre-specified so it was kind of known, just how did it become kind of, you know, a significant consideration for the FDA and, you know, kind of why did it happen now? And then maybe another question just on, you know, what's your hypothesis on like why the these comparability issues exist, you know, basically in the first place. And then maybe just a third one on the panel. Do you think that effectively this kind of now puts a little bit more significance on the panel? Because it seems like if you have a positive panel, you know, there will be a little bit more focus on trying to sort this out. Thanks for taking my questions.

Thank you for the questions, Alethea. Let me answer the last one. and then hand over to Francisco to answer the question regarding what I understand is a very typical comparability range and address the question as to why. Yes, the significance on this advisory committee meeting is now exceptionally important at this juncture. A very positive advisory committee and community support. will create a context in which the company and the agency will work together under a breakthrough therapy designation to find a solution as quickly as possible. And if the advisory committee is not positive, then essentially the comparability issue becomes a moot point. So you're exactly correct there. Francisco, could you speak to the 80-125 comparability range and any thoughts as to why?

Good morning, Alicia. 80-125% is the target that is typically required for bioequivalence. Even though we are not obviously biosimilar, we are an innovative product, It was used as a target as well in our study. As to why we were below that target, the honest answer is we still don't know. But this was a single low-dose study in healthy volunteers. And we do believe that it bears no clinical relevance, especially when you think of multiple higher doses in patients, which is our intended use. So we are working towards trying to understand it and also working towards providing additional data and analysis, pharmacodynamic inputs, et cetera, that might ameliorate FDA's questions and concerns.

Just as a follow-up, so effectively, I guess it's kind of like you know, maybe perhaps like you guys didn't think that the low dose would be something that the FDA would be so focused on? Or I guess just I'm trying to figure out how it kind of all came together that it was, you know, now this like new focus in the past couple months, you know, versus like maybe like eight months ago.

We conducted the PKPD study specifically to bridge to the inclusion of the AGC-originated drug product in our PROTECT study. All of the physicochemical analyses, and that includes assays, potency assays, and so on, conducted by AGC Biologics and ourselves that was submitted into the BLA showed comparability, as did many of the other parameters of the PKPD study itself. The reason that it has appeared at the same time as the BLA is being reviewed is because that PKPD study's results became available at the beginning of the year. And so the first time we had an opportunity to discuss this study, which has to be submitted to our IND and our BLA, we can't not disclose that to the agency, was at the mid-cycle review in February, and at that time, had indicated to us that they were evaluating the results and doing their own modeling. And as you know, it was only in last month, April, that we had meetings with the agency that indicated their conclusions that they were not comfortable with the comparability. And that's where we're at today.

Awesome. Great. Thank you for that follow-up.

Your next question comes from Gregory Renza with RBC Capital.

Good morning, Ashley and team. Thank you for the update and thanks for taking my questions. Ashley, maybe just to build on Alethea's question, I'm just curious if you could comment a little bit on some of the mention of the reliability of the analytical methods or one of the analytical methods to release teplizumab in your filing today, as well as just some commentary on the Form 483 that were issued to AGC, which sounds like they would be required to be resolved prior to any decision on teplizumab. Any additional color you have on those findings would be helpful. Thank you.

Yes, certainly. So the agency, as part of its priority review, has asked questions regarding an assay that's used to assess the stability of the product in order to establish expiration and shelf life. These are questions that we believe we can answer and will be able to answer in a satisfactory manner to them. And then, as you'll appreciate, the agency has done a pre-approval site inspection of AGC biologics it was part of an inspection for products for other sponsors as well and in the process of finalizing that inspection they reported some observations and 483s these appear to be relatively straightforward. We're working with AGC Biologics to answer those, and we believe that they will be able to do that.

Thank you. That's helpful. And maybe just one more. As you've spoken about the possibility of using data from the PROTECT trial to address the comparability question, I'm just curious, what would be the best protocol to conduct such an analysis without unblinding, maybe some of the more tactical steps in thinking about leveraging that study in order to fulfill some of the voids or the additional data would be great. Thank you very much again.

Thanks, Greg. Yes. So, we have not discussed the specifics of how we can make that data available. I can tell you that we are collecting PKPD data from the ProTech study in anticipation of its being able to assist the agency in its review. And we intend to have a discussion with them in parallel with the continuing preparations of the ADCOM to get their input to ensure that we do evaluate that data and present it to them in a way that's useful to them without undermining the integrity of the pro-tech study, and we believe we can do that.

That's great. I appreciate it. If I may, maybe I'll sneak one more in perhaps for Jason just on the commercial side. How should we think about some of these issues that are raised now at the 11th hour impacting potentially any commercial receptivity of Tiplizumab and how docs could sort of view the comparability issue, but just also some of the proceedings along what has been certainly a winding road for now. Thanks again, Ashley.

Yeah, thanks. I'm sorry, Andy, Ashley.

I was going to say, I'll let you answer that, but we don't think that the comparability issue has any impact on the market potential or, the clinical benefits, benefit risk assessment, or any considerations that would drive commercialization other than the timelines. But please carry on, Jason.

Yeah, thanks, Ashton. Thanks for the question, Greg. You know, I think, you know, under, you know, if the drug's approved, we don't see this being an issue for many physicians. And, you know, during recent advisory boards, we haven't heard it come up a single time yet. Obviously, we're tracking it, but under an approval, we don't see it being an issue.

Your next question comes from Ram Selvaraju with HC RainRide.

Thanks very much for taking my questions. So, firstly, I just wanted to clarify. There's no possibility that the ADCOM discussion will even touch at all on the comparability issue. or it's something that could come up in discussion, but it's not part of the official list of items that the adcom is supposed to render a vote on? Just wanted to clarify.

We can never guarantee what will come up in the discussion RAM, but the agency has informed us that they intend to include a brief mention of the comparability considerations in their briefing document, with an affirmative statement that the agency and the company are collaborating to find a solution. And the reason they're doing that is to compartmentalize it and allow the adcom to focus on the key considerations that adcoms typically focus on, the need, the efficacy, and the safety.

Have you asked the agency whether it would be possible to include a question for the adcom regarding whether they would consider it advisable to approve the drug, even though all the comparability questions have not been fully answered, simply because the efficacy profile in the at-risk study was so compelling and T1D is such a significant unmet need?

But we have not discussed questions specifically with the agency related to that. It would not make sense to me in so far as the comparability issue is a technicality. The agency is fully staffed and capable and qualified of addressing as it does with any comparability biosimilar change in manufacturing facility formulation, et cetera, and the members of the panel do not typically have that background or expertise and wouldn't be able to provide the agency with any additional advice.

Okay. With respect to Europe, as you look towards the filing of the MAA, Do you think that it might be advisable to discuss with the European regulators whether if they do consider the comparability data to be deficient or they need additional information along the same lines as the FDA does, you could conceivably apply for conditional marketing authorization instead until and unless the additional comparability data that the FDA is asking for and that European regulators may ask for has been furnished? Is that a viable option at this point?

We are in the middle of our scientific advice discussions with the EMA and with the NHRA. We have received non-binding advice and guidance on a number of subjects. We have not discussed yet the comparability, but I think it's reasonable to assume, given how closely regulatory agencies now interact throughout the world, that we will have to solve this comparability issue for them in the same way as we will have to solve it for the FDA but it's to be determined and we haven't yet had those discussions with regulatory authorities in the UK or Europe okay then just lastly to clarify on the timeline for reporting of top-line data from the protect study just wanted to be reminded what you're targeting now

And if you could also just provide us with some additional granularity on how that trial is progressing overall in terms of enrollment, in terms of any logistical challenges you're encountering, or there's been an absence of that and everything's going as smoothly as it might be expected to go.

Thanks, Ram. Yes. So our guidance is still the second half of this year for the completion of enrollment and then there is an 18 month follow up for the study to close and so the results, top line results we anticipate will be available in the middle of 2023. We've seen a steady increase in enrollment rates as a result of better management of the COVID pandemic in countries and sites and vaccination. And so we're encouraged by that as we go into the summer months and believe that we will in fact be on track to complete the targeted enrollment in the second half. I would just like to point out that we are having discussions with the agency regarding PKPD data. from the PROTEC study, and we do not yet know the details, but we shouldn't assume that we have to wait until the top line results to get that data. That data can be accessed much more quickly than waiting for the final results of the study.

Great. Thank you very much.

Your next question comes from Justin Kim with Oppenheimer & Co.

Good morning. This is Isabel on for Justin. Thanks for taking the question. Can you just remind us of what we can expect from the findings of the PREVENT-CVB study and the strategy to reach patients before exposure of the disease, just from a regulatory perspective?

Thank you very much for that question, Francisco. I think you're best to answer that, please.

Yes, I just want to clarify the question. Did you mention PreventCB? Yes, that's correct. Or do you mean the Proactive Celiac Study?

The PreventCB study.

So just want to clarify, are we talking about the vaccine, PRV101? Yes, the vaccine. Okay. So we are targeting eventually newborns and infants before exposure to their first encounter with Coxsackie B virus. It's a primary prevention vaccine because we believe based on all the literature that Coxsackie B virus is a key trigger in type 1 diabetes, celiac disease and other and diseases. So just attempting to prevent the first infection.

Great, thank you. Thank you.

Your next question comes from Thomas Smith with SVB LearLink.

Hey guys, good morning. Thanks for taking the questions. I guess first, now that we're about three weeks out from the adcom, can you just talk to your interactions with the agency regarding the TN10 clinical data? I guess, you know, what's your sense for the FDA's comfort or where their areas of concern might be around the clinical data set and where they plan on asking the panel for more input?

Thanks for the question, Tom. We're very encouraged by the fact that the agency is continuing with the advisory committee meeting. We believe that that's an indication that under breakthrough therapy designation, they find the TN10 study clinical data set in the context of the safety database from newly diagnosed and the supporting evidence of protection of beta cells as determined by C-peptide from historic studies as a data set that's worthy of this advisory panel evaluating it and the timing. And we believe that the focus of the committee will be on understanding the unmet need and the relevance of a delay. in the progression of the disease from stage two to stage three, then the efficacy and the strength of that signal from the TN10 study, which although a modest study has a very powerful p-value and statistical significance and a very significant delay with a median of two years and in follow-up published data indicating that that is now approximately three years delay. And then finally, the safety profile. A safety profile of an immunomodulatory therapy, potentially the first disease-modifying therapy for type 1 diabetes. And in the context of that, they'll be concentrating on the potential risks of immunomodulatory therapy. But again, we're very keen to point out that this is a discrete exposure. It is a resetting and a rebooting of the immune system. It is not chronic immunosuppression. And after the conversion of the autoreactive T cells, which destroy or attack the beta cells, and conversion to exhausted regulatory T cells, the course of therapy is over, and that therefore reduces the prospect or the risk of opportunistic infections and malignancies that might be associated with a chronic immunosuppression. So that's the discussion that we're expecting and we believe that we will also have a lot of support from key opinion leaders and from patients and patient advocacy groups. We're really looking forward to that coming up in three weeks' time.

Got it. Got it. Okay. Ashley, on the manufacturing and the Form 483s for AGC Biologics, were the issues cited specific to plizumab? I guess, can you describe what the issues are specifically related to plizumab, and what's your level of confidence that these issues could be resolved ahead of the current July 2nd to-do-for-date?

We believe that they will be satisfactorily addressed by AGC and its response to the 483s. The 483s were typical observations made from a pre-approval site inspection. Some of them pertained to general matters at the site. Some of them pertained to matters that were related to the products that were being manufactured. And a few pertained to the process or facility associated with But as I mentioned earlier, we're working with AGC and we believe that they will be able to satisfactorily address the 483s for the agency to not have those considered as an approval obstacle.

Okay. Okay. And then just on the PK PD comparability. Can you comment at this point as to how many patients within the PROTECT study have received the legacy Lilly manufactured product versus the new AGC Biologics product?

We've not disclosed that information yet.

Okay. Maybe can you just comment at a high level? Is your expectation that the majority of patients in the study would have received the legacy product or the new product?

Well, the issue isn't necessarily how many patients received the legacy product versus the new product. It's about bringing a PK-PD sub-study into a trial that was a Phase III trial simply looking at efficacy compared between active and placebo. And as you may appreciate, a PK-PD study is a different approach. protocol, it requires taking blood samples much more regularly immediately after the therapy has been administered in order to evaluate how it clears from the blood, for example, and early PD biomarkers. So what's important is whether we will be able to initiate and complete a sub-study before the clinical trial completes its enrollment, and we believe we will be able to do that and provide PKPD data to the agency to assist them in their ongoing considerations.

Okay, got it. That's very helpful. Thanks, Ashley. I appreciate you taking the questions.

Thanks, Tom.

Your next question comes from David Huang with SMBC.

Hi, guys. Thanks for the update and taking my questions. So I just had one on the one and then a follow-up. First one, on the PDUFA date, July 2nd, we know it still stands. If that should need to be revised or moved, is that something that you're going to wait for the agency to give you that guidance, or is that something you can have an active conversation around?

Well, we've indicated that there is likely to be a delay based on our understanding of the agency's position on comparability. We've not had discussions on how that delay will manifest itself, whether it will be within the current review cycle with some extension or after a formal response. But we certainly indicated the potential for that delay I think a lot will depend on the adcom and the outcome of the adcom, and I suspect that the agency will wait until the adcom has taken place, complete its clinical review, take into consideration the meetings that we hope to have with them concurrently in regards to additional data we can provide, and then we will obviously update you at the appropriate time when we have material information.

Okay. Got it. That's helpful. Thank you. And then just on the celiac disease asset, so I understand, you know, there is the option for Amgen to take that asset back and pay you a, you know, a milestone fee. If Amgen elects not to take it back,

um you know are they still involved are are you still kind of splitting the cost of development in phase three or would all that you know developmental costs come back to you uh the full control of that asset by way of um an arm's length license arrangement that would continue after their decision means that we would have the full benefit of the ongoing development and potential commercialization of that asset if merited, but it would also mean that we would have the full burden of development costs or we would have an opportunity to partner that with other parties interested in CILIA.

I see. Okay, great. Thanks so much for taking the questions. Thank you for the questions.

This concludes our question and answer session. I would like to turn the conference back over to Ashley Palmer for any closing remarks.

Thank you, Kaylee, and thank you, everybody. Thank you for the questions. We'd again like to thank you for your time, and we hope that you all have a great day and look forward to speaking to you again soon.

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.