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spk14: Good day and welcome to the Ibericbio third quarter 2022 earnings conference call. All participants will be in listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star then one on your touchtone phone. To withdraw your question, please press star then two. Please note, today's event is being recorded. I would now like to turn the conference over to Kathy Galante, Senior Vice President, Investor Relations. Please go ahead.
spk03: Good morning and welcome to Ivericbio's conference call. Representing Ivericbio today are Glenn Splendorio, Chief Executive Officer, Dr. Praveen Dougal, President, Keith Westby, Chief Operating Officer, David Carroll, Chief Financial Officer, Dr. Double Desai, Chief Development Officer, Chris Sims, Chief Commercial Officer, and Tony Gibney, Chief Business and Strategy Officer. I would like to remind you that today we will be making statements relating to Iverett Biles' future expectations regarding operational, financial, and research and development matters. These statements constitute forward-looking statements for the purposes of the Safe Harbor provision under the Private Securities Litigation Reform Act of 1995. These statements cover many events and matters that are subject to various risks that could cause actual results to differ materially from those expressed or implied by any forward-looking statement. I refer you to our SEC filings, and in particular to the risk factors included in our quarterly report on Form 10Q, filed on July 26, 2022, for a detailed description of the risk factors affecting our business that could cause actual results or events to differ materially from the forward-looking statements that we make. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements at some point in the future, we disclaim any obligation to do so as except required by law. I would now like to turn the call over to Glenn.
spk12: Well, thank you, Kathy, and good morning, everyone, and thank you for joining us for our third quarter conference call. During the third quarter, we were thrilled to announce positive efficacy and favorable safety results from GATHER-2, our second phase three clinical trial of Avacyncaptad Pegol, or ACP, also known as Amora, for the treatment of geographic atrophy. We're proud to have achieved something that has never been done before in GA, deliver two phase three studies that met their pre-specified primary endpoint at 12 months of slowing GA progression. Our key focus now is to make ACP commercially available to physicians and their patients with GA as expeditiously as possible, subject to regulatory review and approval. The positive results from GATHER-1, our Phase III clinical trial of ACP for the treatment of GA, and GATHER-2, as well as our Special Protocol Assessment, or SPA, with the FDA provide the basis for our new drug application. As a reminder, we received written agreement from the FDA under an SPA for the overall design of Gather 2 in July of 2021. The SPA process is a procedure by which the FDA provides a clinical trial sponsor with an official evaluation and written guidance on the design of a proposed protocol intended to form the basis for an NDA. The earlier completed Gather 1 clinical trial allowed us to get a head start on assembling the NDA prior to receiving the Gather 2 results. Importantly, we are ahead of schedule in preparing our NDA for ACP for the treatment of GA and therefore are moving up our submission timeline to the end of this year. We look forward to continuing to engage with the FDA throughout the review process We're also planning to submit a marketing authorization application, or an MAA, to the European Medicines Agency in 2023, subject to feedback from planned interactions with regulatory authorities in Europe. We're also delighted that Gather 2 efficacy and safety results for ACP were presented in two oral presentations as part of the Retina Subspecialty Day at the American Academy of Ophthalmology annual meeting on September 30, 2022, in Chicago. We appreciated the opportunity to share the results of GATHER2 with eye care specialists from around the world at this highly respected medical meeting. Additionally, this week, GATHER1 and GATHER2 data will be presented at the Retina Society in Pasadena, California, and we will highlight the observed efficacy data from both studies. Praveen's going to talk about this in more detail in just a moment. Looking ahead, we're excited about the possibility to expand ACP into earlier stages of AMD. We received favorable feedback from the FDA on our development plans for intermediate AMD. We are more determined than ever to evaluate ACP for this important patient population. We look forward to continuing our productive and collaborative discussions with the FDA and updating you further as we clarify our strategy. We continue to invest in additional lifecycle initiatives for ACP to expand the patient population and to continue to evaluate multiple technologies for ACP. During the third quarter, we secured a term loan credit facility, providing us with access to $250 million in debt financing with Hercules and Silicon Valley Bank. This financing further strengthens our balance sheet and provides financial flexibility as we continue to build our U.S. launch readiness plan and prepare for the potential commercialization of ACP. In July, we borrowed $50 million at closing. With the positive Gather 2 results, we believe we have satisfied the first performance milestone under the facility, which allows us access to an additional $50 million tranche from the facility, which we plan to borrow before the end of the year. Well, again, thank you for your support, and I will now turn the call over to Praveen.
spk01: Thank you, Glenn, and good morning, everyone. As Glenn stated, ACP, our complement C5 inhibitor, is the only investigational therapy to have two positive Phase III studies in GAs. with high statistical significance at the 12-month primary endpoint and a favorable safety profile. We believe that the reduction in GA progression that we have seen in GATHER1 and GATHER2 is clinically meaningful. We look forward to submitting a package to the FDA by the end of this year with GATHER1 and GATHER2 that provides consistent efficacy and safety profiles. In Gather 1, a post hoc analysis showed that the reduction in the mean rate of GA growth or slope analysis over 12 months was 27.7% with a descriptive p-value of 0.0063 for the ACP 2 milligram group as compared to the corresponding sham group using the square root transformation. and 35.4% with a descriptive p-value of 0.0050 without using square root transformation, which we refer to as the observed GA area. In Gather 2, ACP also met its pre-specified primary efficacy endpoint of reducing the mean rate of growth slope analysis in GA area over 12 months compared to SHAM. The reduction in the mean rate of GA growth over 12 months was statistically significant at 14.3% with a p-value of 0.0064 for ACP 2 milligram group compared to the sham group using the square root transformation and 17.7% with a p-value of 0.0039 using the observed GA area. In addition to the slope analysis in Gather 2, we also performed a point analysis on the mean rate of change in GA area, which you may recall was the pre-specified primary endpoint analysis in Gather 1. The results for the 12-month point analysis were consistent with the slope analysis across both trials. This data was also presented during AAO. Importantly, In Gather 1 and Gather 2, we observed a reduction in the change in GA area for the ACP group as compared to sham early in the trial, which continued to increase over 12 months. This observation suggests that therapeutic benefit of ACP may occur early and continue to increase over time. We are thrilled with a consistency throughout Gather 1 and Gather 2 efficacy results. ACP's favorable safety profile, another potential key differentiating factor, was also maintained throughout the Gather 1 and Gather 2 clinical trials. In both Gather 1 and Gather 2 through month 12, there were zero ACP-related events of endophthalmitis. ACP-related intraocular inflammation events, zero vasculitis, and zero ACP-related ischemic optic neuropathy events. The most frequently reported ocular adverse events were related to the injection procedure, including transient intraocular pressure. In Gather 1, the incidence of choroidal neovascularization or CMV rates through month 12 were 6 or 9% in the ACP 2 milligram group and 3 or 2.7% in the corresponding sham group. Exudative macular neovascularization or EMNV rates were 4 or 6% in the non-exudative and non-exudative macular neovascularization, or NEMNV, were 2 or 3 percent in the ACP group. In Gather 2, the incidence of core neovascularization, or CMV, rates through month 12 were 15 or 6.7 percent in the ACP 2 milligram group and 9 or 4.1 percent in the sham group. EMNV rates were 11 or 4.9% in the ACP 2mg group and 7 or 3.2% in the sham group. There was 1 or 0.5% case of non-exudative MNV and 3 or 1.3% cases of peripapillary CMV in the ACP 2mg group and no cases of non-exudative MNV. and two or 0.9% cases of peripapillary CMV in the sham group. While the FDA has not requested that CMV cases be reported using a non-traditional, recently defined terms of exudative versus non-exudative, we provide this distinction of cases for both Gather 1 and Gather 2. The definition of exudation has been detailed by CORE. the reading center at the Cleveland Clinic, and can be found in our current report on form 8K filed with the SEC on April 4th, 2022. Additionally, we're encouraged that we saw a positive trend in mean change in best corrected visual acuity, one of the pre-specified supportive endpoints consistent in both Gather 1 and Gather 2. Remember, in GA, we consider BCVA to be primarily a measure of safety. For mean change in low luminance best corrected visual acuity, we did not see the same trend in GATHER2. We believe we have a solid, complete filing package with two clinical trials, GATHER1 and GATHER2, that each separately and independently met their pre-specified primary endpoint with a high degree of statistical significance, and a favorable safety profile. We believe this clinical data package meets the requirements for an NDA submission. We recently initiated an Open Label Extension, or OLE, trial for patients who completed their month 24 visit in the Gather 2 trial with the aim of providing patients access to ACP and collecting additional safety data. We plan to treat patients with ACP for 18 months or until potential regulatory approval of ACP in the applicable region, whichever is earlier. GA is a debilitating disease for which there are currently no approved treatments. We believe ACP has the potential to be life-changing for patients with GA. Returning to our HTRA1 inhibitor, we plan to conduct additional preclinical studies to optimize formulation, dosage, and delivery of IC500. As a result, we do not expect to submit an investigational new drug application for IC500 mid-next year, as we had previously planned. We remain committed to this program and will provide additional information as it becomes available. We thank you for your time and support and look forward to updating you on our progress going forward. I will now turn the call over to Dave.
spk13: Thank you, Praveen, and good morning, everyone. I would like to highlight a few items from our press release of this morning and provide some guidance on our expected year-end cash balance and our expected cash runway. For the quarter, our net loss totaled $42.4 million, or 35 cents per share. compared to a net loss of $24.6 million, or $0.23 per share, for Q3 2021. This increase in net loss was driven by increases in both R&D and G&A expenses. R&D expenses increased primarily due to the continued progress of the Gather 2 trial, increased manufacturing activities for ACP, and increases in personnel costs, including stock-based compensation associated with additional R&D staffing. G&A expenses increased primarily due to increases in personnel costs, including stock-based compensation, associated with staffing for commercial launch preparation for ACP. Turning to our expected year-end cash balance and cash runway, as of September 30th, we had cash of approximately $321 million, which reflects the initial $50 million borrowing from our term loan facility with Hercules and SVB. We estimate that our year-end cash will range between $265 million and $275 million. This estimate does not include any new borrowings from our debt facility, including the $50 million we plan to borrow during the fourth quarter of this year. We estimate that our cash and committed loan facilities will be sufficient to fund our planned capital expenditures, debt service obligations, and operating expenses through at least mid-2024. These estimates are based on our current business plan. which includes the continuation of our ongoing clinical development programs for ACP in GA and Stargardt's, including the recently initiated open label extension trial, evaluating ACP for intermediate AMD, preparation and submission of an NDA and NAA for ACP in GA, continuing preparations for potential commercialization of ACP in GA in the U.S., pursuing Delcitec sustained release delivery technology, and exploring additional sustained delivery technologies for ACP, and the advancement of our IC500 development program as currently planned. These estimates do not include any potential new borrowings under the term loan facility with Hercules and SVB, including the $50 million that we plan to borrow in the fourth quarter this year. Also excluded from these estimates are any potential approval or sales milestones payable to the Archimex Corporation, any potential expenses for the actual commercial launch of ACP, such as Salesforce expenses, and any additional expenditures related to potentially studying ACP in indications outside of GA, Stargardt's, or intermediate AMD, or resulting from the potential in-licensing or acquisition of additional product candidates or technologies, or any associated development that we may pursue. Thank you for your time, and I'll turn the call back over to Glenn.
spk12: Well, thanks, Dave. And just to summarize a few key takeaways for the quarter, First, the positive results from GATHER-2 provides us with two phase three trials that met their primary endpoint as a basis to file the NDA. Second, we've moved up the NDA submission date to the end of this year. Third, we received favorable feedback from the FDA on intermediate AMD development and as we talk about more to come as we continue our discussions with the FDA. Fourth, we will continue to present the Gather 1 and Gather 2 data at major medical meetings with the next presentation at Retina Society this week where we will highlight the observed data for G1 or Gather 1 and Gather 2 as for being just discussed. And finally, as Dave talked about, we secured access to up to $250 million of non-dilutive debt to strengthen our balance sheet. So quite a good quarter for us. And at this point, I'd like to turn the call over to the operators so that we can open up the line for questions. Thank you.
spk14: As a reminder, if you'd like to ask a question, please press star then one on your touch-tone phone. If your question has been addressed and you'd like to remove yourself from queue, please press star then two. Today's first question comes from Ken Cacciatore with Cowan & Company. Please go ahead.
spk10: Congratulations, team, on all the progress. Great to hear about the accelerated filing. I was just wondering on Gather 2 results, Praveen, you went through great details about that really nice safety profile. Can you just talk about why we may be seeing a differentiation in your formulation in terms of safety? And then also on Gather 1 and Gather 2, you touched briefly on the, we're starting to see a little bit of a separation on BCVA. And I know Dr. Chambers talked more about lesion growth than needing a functional endpoint, which maybe you could comment on as well, coming out of AAO. But are you able, if you had more time, to maybe identify any subgroup of patients or anything new as you analyze that data that you might want to discuss in more detail? And then lastly, and I'll get back into the queue, just on your extended release formulation, can you discuss maybe when we might hear any of the earliest data or decisions on what we might be moving forward? Thanks so much.
spk12: Praveen, go ahead. I think there's three questions there, and I'll jump in as... as appropriate, but I think Ken wants to hear from you at least on one and two.
spk01: Great. Thank you. And, Ken, good morning and thank you so much for being here and thank you for your question. So the first part regarding the safety and, you know, what I would say is it's not just the safety, it's also the efficacy. I think what we're seeing is the consistency of results that we see in both Gather 1 and Gather 2. I just want to highlight that. Regardless of how we look at the safety, how we look at the efficacy, how we look at the subgroup analyses in Gather 1, you'll see this remarkable consistency both in Gather 1 and Gather 2. And you asked specifically about the safety profile. Yes, we're very, very happy with the safety profile. Again, very consistent in Gather 1 and Gather 2 as I highlighted zeros for any drug-related adverse events both in Gather 1 and Gather 2. The reason for that, Ken, I believe, and this is my opinion, is really two. One is the biologic part and the other is the CMC part. From a biologic point of view, we have always maintained that inhibiting C5 and keeping the C3 loop alive is very important in terms of downregulating inflammation and potential infection from pathogens. And we believe we see that in both GATHER1 and GATHER2. So that's the biologic explanation, and there's good preclinical science to support that. From a manufacturing point of view, remember what we have is an RNA aptamer. So that means that the entire process of scaling up is synthetic. There is no biologic intermediary. There is no E. coli or CHO. So as you know, in a lot of the assets that we've seen, These biologic intermediaries are where foreign antigens are introduced and we bypass that entirely by having a purely synthetic process. So I believe that it's really both reasons that accounts for this consistent safety profile. Your question regarding visual acuity, we've looked at the trends in visual acuity in GATHER-1 at month 12 as well as month 18 and we've looked at the visual acuity trend and gather two at month 12. And the trends are positive, meaning that the visual acuity trend is positive in all three. So it's three out of three. And we want to remind everyone that visual acuity really is a safety measure. And we're very happy, again, consistent with your previous question regarding safety, that the visual acuity trends are in the proper direction. Regarding the extended release, as you know, we have a collaboration that's ongoing with Delsatech. We're very happy with the progress of that. We have not detailed any further guidance as to when milestones may be reached. We continue to report that we're very pleased with the progress. We've also stated that we are investing heavily in terms of sustained delivery because we believe that this asset is perfectly suited for sustained delivery. And we've also publicly announced that we will be looking at multiple sustained delivery opportunities and we continue to do so.
spk06: Thank you, Glenn. Upward to the next question.
spk14: Thank you. And our next question today comes from Greg Harris in the Bank of America. Please go ahead.
spk08: Hey, good morning. Thanks for taking the question. Definitely great to see the The filing timeline moved up. So the question is, what remains to be done in preparation of the MAA filing? And maybe you could talk about your expectations for the EMA's requirements for endpoint relative to what the FDA has asked for, especially in terms of functional benefit or any other stuff.
spk12: Yeah, Greg, thank you. It's Glenn, and good morning. Thanks for the question. So, with EMEA, and we've been consistent on this, I think the first step in that discussion will be to complete the NDA. I mean, once we have the NDA done, we believe we have the data set that would form the same information that goes into the MA. The next step, which is an important one, and we have not yet met with them, is to meet with the regulators in Europe talk about the package. This will be, and I think that one of the key points that Praveen raised today, this is the first time that the EMEA will see two phase three trial that have met their primary endpoint. So we think there's a discussion to be had there. We also believe, and I think it's been a discussion point that there's a need for functional data by the European regulators We think we have a data package that could satisfy them, but we can't confirm that until we meet with them. But we're very excited about talking to them about our data, what our data means, the safety profile. Once we have that discussion, that will define the timeline for an MAA. So that's our current plans.
spk08: Got it. That's helpful. And if I can sneak one more in. Sure. Could you characterize The feedback that you received from FDA on the intermediate AMD program, I think the prior guidance was that the trial would start this quarter. So is that not the case anymore?
spk12: So that's why we put out there that we've had very favorable interactions with them. And the second part of that is that we continue those discussions with them really to further define the strategy. But What we have discussed with them thus far has been very favorable. That's the reason we're mentioning it. To go beyond that at this point, we don't have all the details. We could be that specific. We need further conversation with them, but we believe there's a path forward on intermediate AMD. So as we said in the conversation before, more to come on that.
spk08: Great. Thanks for taking the questions, and congrats again on all the progress. Thanks, Greg.
spk14: And our next question today comes from Colleen Cussey with Baird. Please go ahead.
spk02: Hi, good morning. Congrats on the progress and thanks for taking our questions. So can you just talk to what were some of the factors that contributed to shortening of the timelines for the NDA and what are the remaining gating factors before filing? And then can you just clarify your expected timelines to approval?
spk12: Yes, so thank you for the question. Great question. So we originally, as we had the data, we had to put a stake in the ground for the NDA. And we saw it before the end of the first quarter. And as we always said, the team was working on Gather 1 data populating the NDA. As we continue to go through Gather 2 and look at the data, it's quite good. The team has been very, because it's good and because we believe it's straightforward, the team has been able to accelerate their timeline. So it's really that as we go through the data, it's cooperating. Gather One, clearly having Gather One definitely helped. As we also said, you know, coming off the data, you're kind of, you know, overwhelmed when you first turn the data card. as to what's there. We now understand it. We know how it needs to be put into the package. We put tremendous resource behind coming out of the data. I said the number one priority was to get the NDA filed. So all those factors have contributed to us revising our guidance to get this NDA in before the end of the year. So I hope that's helpful, and the team continues to work real hard on it. So the second part as to when, let's get the NDA in. Everybody knows the timelines. We do have fast track. You know, there's defined timelines for fast track approval. But I think the first thing is to get a date in the fourth quarter where the NDA is complete, which will start the clock, and then we can update the timing.
spk02: Okay, great. That's helpful. Thank you. And then I know it might be early for the open label extension study, but Any comment on the rate of patients converting from Gather 2 to the open label extension? And then can you just clarify, I think on clinicaltrials.gov, it only shows the monthly dosing for Xaviera in the open label extension. Can you just clarify what the dosing in that study is?
spk12: Sure. Praveen, you want to take that one?
spk01: Sure. Colleen, we haven't detailed the open label extension publicly as yet. That has just started, and yes, we, as you recall, we will be dosing monthly.
spk02: Okay. And any reason so that every other month patients will be converted to monthly?
spk01: Is that right? They will continue as is. Yes, that is correct.
spk02: Okay. Thank you. Thanks for taking our questions.
spk14: Thank you. And our next question today comes from Annabelle Samumi with Stiefel. Please go ahead.
spk04: Hi, thanks for taking my question. Congratulations on the progress. So I know this question has been asked many times, but given the results that you've seen now in G2 and maybe some of the observations you made about large lesion sizes versus smaller lesion sizes, do you think you still have a strong argument for a broad label? What's the rationale that you can give FDA to argue for that? I guess that's the first question. The second question I have is that I know the messaging for patients to convince them of treatment will be that if you go on treatment, you'll be able to drive for another five years or work for another 10 years. I know that's still somewhat intangible for them given it's so far out. Does the physician community have more objective tools yet to monitor how these patients are improving? within a standard vision to keep them, I guess, motivated to continue on treatment. And then I guess the third question I have is in intermediate AMD, I guess, given that there's a debate around how to convince patients to treat already here at the GA stage, what type of opportunity do you expect for intermediate AMD versus just straight GA? Thanks.
spk12: Annabelle, good morning, and thank you for the three questions. Praveen, I'll turn this one to you.
spk01: Yeah, thank you, Glenn. Annabelle, good morning. Three very important questions. Regarding labeling, Annabelle, as you know, it's premature at this point to have had any labeling discussions with the FDA, so I want to make sure I mention that we have not entered any labeling discussions. Our expectations and hope are that we will have a broad label that is required, that is consistent with monthly injections. Let me take each one of them individually. As we have seen in Gather 1, and we have not done this in Gather 2 as yet, the vast majority of the patients were within what is really defined as the clinical fovea, which is within 500 microns of the center point. We've presented that in several meetings. In fact, if patients were one micron, literally one micron away from the center point, those patients would be eligible. There are many patients in clinical practice who have parafovial fixation, and their center point may be involved, but there's a little island of photoreceptor cells that allows them to navigate, not bump into chairs, not burn their hands on stoves, et cetera. So we believe that we would be eligible for a broad label and that those patients wouldn't be denied access to a safe and effective drug because of 1 micron. Now, as far as monthly application is concerned, we want to have monthly injections on our label. As you know, my colleagues don't really treat according to the label. You can see this from the anti-VEGF experience, for instance. Most of us treat with a treat and extend regimen. And there is no anti-VEGF that has treat and extend on the label. So the label is really there for reimbursement purposes. So logically, it makes sense that you would want to have the maximal usage on the label so that any less would still be reimbursed. So again, our expectation is that we'll have a broad label that says monthly application. And again, I want to say that we have not entered into any formal labeling discussions with the FDA. As far as your second question in terms of function is concerned, you've identified a very important topic there, Annabelle, which is that we really don't have a good measure of function at all. In fact, as we may have discussed earlier, visual acuity is not a good measure of visual function. At the end of the day, rarely are we in a dark tunnel with a bright light at the end. Our day consists of contrast sensitivity changes, color changes, metamorphopsia, things like that. So there really is no great function test. We see this as an opportunity to expand the patient experience into an entirely new dimension. This has been done, for instance, in glaucoma with visual acuity tests and so forth. And we are investing heavily in terms of expanding the patient experience. For now, what I can tell you is that patients know. There are lots of patients out there who may have a visual acuity of 20-20, but will not be able to work, will not be able to live a normal life because visual function changes. And you can imagine that if you had a spot on the side of your vision and you couldn't finish reading a sentence, it'd be very difficult for anybody to work and have a normal functional life. So regardless of the visual acuity results, there is a visual function deficit which will allow patients to come in. This happens all the time in other diseases as well, such as diabetes, for instance, such as macular degeneration, where visual acuity may be 20-20, but because of the visual function deficit, patients are in desperate need of help. In regards to intermediate AMD, I think your question was, what are our plans going forward? As Glenn said, we've had very favorable discussions with the FDA. There's science to back up the fact that intermediate AMD is driven by complement activation. And again, I go back to what I said regarding the functional benefits that one can potentially have, even with intermediate macular degeneration. Intermediate macular degeneration is a very broad range. There are patients with intermediate macular degeneration that have large drusen, that have serous fluid, where patients experience metamorphopsia, changes in color vision, et cetera. And those patients, I believe, would benefit greatly from Zamora, as is with version 1. The last thing that I would say is, remember, what we have here is a safe and effective drug for the first time with two positive phase three results. This is version one of Zamora. We're investing heavily in version two, which is the sustained delivery opportunities that we see. And we believe that this is just the very beginning of opening up a new door in the treatment of the largest cause of blindness in this country. Back to you, Glenn.
spk14: Thank you. Thank you. And our next question today comes from Mike Alls with Morgan Stanley. Please go ahead.
spk09: Good morning, and thanks for taking the question. Maybe I can just ask a follow-up on intermediate AMD. I know you're planning to have further discussions with the FDA to sort of fine-tune the potential trial design here, but just curious if you can share some of the primary endpoints you might be considering and, you know, what maybe some of the secondary endpoints are as well. Thanks.
spk12: Yeah, Mike, thanks for the question. And, you know, as we said before, you know, these discussions are at a critical point, and we do need to have further discussions with them to come back to you with some specificity. So I apologize for not being more specific today, but that's as far as we could go. I do just want to emphasize that we believe there's a path forward based on our discussions thus far. and more to come on that. But we can't be that specific at this point, but we hope to be specific in the near future. So sorry for punting that one, but in order to get an adequate answer, we do need to continue the collaboration and dialogue with FDA.
spk09: No problem. Thank you.
spk14: Okay, ladies and gentlemen, our next question today comes from Ellie Merle with UBS. Please go ahead.
spk05: Hey, guys. Thanks so much for taking the question. Just curious your thoughts in terms of the recent MGM data, just any key learnings in terms of, you know, the biology of complement or any read-throughs in terms of how you can, you know, compare the different modalities for GA. And then just in terms of thinking about labeling, I know a lot of discussion around monthly versus every other month, but into the Apellas, PDUSA, and a potential label. Are there certain things that – and also – in your discussions and your filings, are there certain considerations that we could see in the label, such as potential for perhaps even multiple, like, or only every other month or just monthly? And then in yours, do you see a potential to have every other month, just given it's studied, even though I know there's a preference for only monthly? And anything you're thinking about to keep an eye out for in terms of safety as well, in terms of the labels? Thanks.
spk12: Ellie, good morning, and thank you for the questions. I think there were three there, but I'll let Praveen start.
spk01: Ellie, good morning, and thank you. I think the questions are coming in triplets now. So, I guess what I would say regarding the competitors' data, Ellie, is that it's our preference really not to comment on competitors' data. I think there's more data to be presented by by NGM in the Retina Society Conference, which is going on right now. In fact, I believe their talks are today. So, in general, we'd prefer, as you will understand, not to comment on competitors' data. In terms of the labeling, again, I go back to what I said early to Annabel's question, which is that our preference really is to have every month on the label. We expect every month in a broad label. You know, what I will tell you is if you look at what my colleagues do, they will find what is appropriate for patients, you know, given the biomarkers for response. And what I mean by that is my expectation personally is that the treatment of macular degeneration, dry macular degeneration is really going to be the ultimate in personalized medicine. I think what you'll find is that we will have some information regarding baseline biomarkers that will determine response. Some patients, as you might imagine, will respond better. Some may not respond as well. Some patients may be prone to develop neovascularizations. Others may not. And I think we'll see some biomarkers that will suggest those kind of responses. And I think what my colleagues will do is treat accordingly based on those biomarkers. The next step would obviously be genetic biomarkers, and then perhaps layered on top of that would be AI. So I think what you'll see really in the next five years or so is the ultimate in personalized medicine in the treatment of dry macular degeneration. This is just the beginning, but ultimately, going back to your question, what we would want for obvious reasons, for logistic reimbursement reasons, is the flexibility. So we really would want every month on the label. Again, I I want to say one more time that we have not entered into any formal discussions regarding labeling with the FDA. Back to you, Glenn.
spk14: Thank you. Ladies and gentlemen, our next question today comes from Eddie Hickman at Guggenheim Securities. Please go ahead.
spk11: Thanks. Good morning, guys, and congrats on all the progress. Just a few from me. Do you anticipate sharing any additional Gather 2 data, whether it's slope or functional visual measures or even additional safety data over time, like at 18 months or longer? And would that plan change if your EMA interactions end up requiring functional endpoints? Would it be worth reporting 18-month data? And then, Regarding the SPA agreement, can you just provide some additional details on those discussions that you had with the agency on the design and statistical plan? Did any of those assumptions change over the course of Gather 2 before you read out the data, or was that the plan that sort of you agreed with with the FDA? Thanks.
spk12: Good morning, Eddie, and thank you. As for additional data, We continue to emphasize the data from Gather 1 and Gather 2 in the medical meetings. I think you see it in the Pasadena meeting, the Retinal Society. We will present observed data that has been presented before, but I think as we further get an understanding of what we have here, these presentations will highlight the full data set that we actually presented in the in the press release on the initial date. So I think it's emphasis on the data set that we've put out there so far. We put quite a lot of safety data out there. We reinforced that again. So I think you'll continue to see presentations that reinforce the full data set that we outlined when we first disclosed the data. The important thing is now that I think we've had good discussions around GATHER2 is to really present both trials together. And I think you'll see that in future presentations, including the one at Retina Society, you're going to see both Gather 1 and Gather 2. I think it's very important that we talk about the totality of the two trials, where the focus over the last 30 plus days has really been on Gather 2. So you'll see the totality. And I think that will provide further insights on the favorable safety profile, as well as the efficacy. Second question, Praveen, do you want to take that?
spk01: Sure, I'll be happy to. Eddie, good morning, and thank you for the question. So remember, we have a pre-specified statistical analysis plan, which was reviewed by the FDA as part of our SPAR agreement. And that plan had an endpoint at month 12 and month 24. Now, we have absolutely no plans at all to look at the month 18 data. And I realize that others have done that after missing their primary endpoint at month 12. Remember, we hit our primary endpoint with two studies, so there's really no reason whatsoever to compromise the integrity of the study by opening it up at month 18, so we have no plans to do so. Our SPAR agreement is as clear as can be, and I'll refer you back to a press release in July of a couple of years ago, and you'll see that the SPAR agreement very transparently and nothing has changed at all. In regards to further analysis of GATHER-2, I'm not sure what more there is to show with safety. There are zeros all over. As I said earlier on, zero plus zero plus zero is zero, so we'll continue to show safety analyses, but nothing is going to change other than the zeros. The efficacy analyses you will also see, but unfortunately, you're not going to see it at the pace that you or I want because, remember, we're really focused entirely on the NDA submission at this time. All our resources are geared towards submitting the NDA as efficiently and with the highest quality possible. Thank you.
spk11: Just a quick follow-up. Do you plan, what about blinded safety data from like the open label extension or the second year of GATHER-2 or even the ongoing SARS-CoV-2 trial? Is that something that you're seeing and can confirm that the safety continues in further treatment?
spk01: So we're masked, as you know, in the Stargardt trial. Eddie, we have not, you know, we remain masked. And we certainly don't want to compromise the integrity of that trial. But as you know, in these large trials, there is a data safety monitoring committee that meets on a regular basis. And if there are any safety concerns, it is the responsibility of the data safety monitoring committee to alert the sponsor. That has not happened historically at all with Zamora in any of the trials, and there's been no change whatsoever in the Stargardt trial.
spk11: Great.
spk06: Thanks, and congrats again.
spk14: Thank you. And our next question today comes from Chris Howerton at Jefferies. Please go ahead.
spk07: Good morning. This is Combies on for Chris. A couple questions for me. What is the main difference between BCVA and LLBCVA, and what could have accounted for the differences and trends seen between those measures at 12 months and Gather 2? And I guess my third question would be, for year two of Gather 2, you have both monthly and every other month arms. If every other month is successful, would you want to submit an SNDA to get that on the label? Or could you provide some sort of literature to help in their prescribing practices? Thank you very much.
spk12: Praveen, go ahead, please.
spk01: Good morning and thank you for the question. So it's a great question regarding best corrective visual acuity and low luminance best corrective visual acuity. There is some preliminary evidence that in low luminance visual acuity may be more sensitive in terms of photoreceptor cell dysfunction than in bright light and thus there have been some data suggesting that the sensitivity in low luminance visual acuity for photoreceptor cells that are not healthy may be greater. However, it's very difficult to do those tests. The luminance has to be completely controlled. It's not something that we're used to doing regularly. There's a great deal of variability. So quite honestly, it's not surprising to see a great deal of variability in these functional tests that we're not used to doing on a regular basis. We do a regular visual acuity on every patient that comes in, but low luminance visual acuity is really very rarely done. I don't know that it's ever done in clinical practice as a routine, but it is done in some clinical trials and thus the variability. In terms of GATHER-2, year two, it really would be premature to discuss the results and the potential impact on the labeling. As I said earlier on, our desire at this point is to have a broad label that has monthly on the label. Thanks for the question.
spk14: Thank you very much. Thank you. And our next question comes from David Nearinggarten with Wedwood Securities. Please go ahead.
spk00: Hey, thanks for taking that question. I just had one on commercial preparations. Just, you know, how are you thinking about – you know, discussing, you know, capacity with ophthalmologists, you know, do you think they have the ability to accommodate, you know, adding more shots to their schedule, you know, things like that. And then a follow up to that, do you plan or, you know, how are you thinking about strategies to get new patients versus, you know, maybe patients who switch from, you know, another therapy that might be approved shortly onto Zamora. Thanks.
spk12: David, thank you for the question. And we do have Chris on today, but I think I'll take it. If I miss anything, Chris can add to it. On the capacity issue, I know that's been a theme that's been discussed recently in the investment community. And Chris is doing a lot of market research. And also, as you know, we're engaging customers now in an appropriate way. talking about things like capacity, you know, new therapies, et cetera. And I think the community will be ready for this. I think they're excited to have a treatment. They will adapt accordingly. We've seen something, and I was very fortunate to experience when the first anti-VEGFs were launched, and, you know, people talked about capacities then, and the retinal doctors adapted very well. There's different data points that have come out that says, you know, they may struggle with capacity. Our data and the contingent market research and part of our job in getting the market ready is to be sure that these offices can meet the patient flow. A big part of the issue for doctors seeing GA patients is they have no treatments. So now with the treatment, we believe they'll adapt accordingly and we don't see that as an issue. And we will share as we generate it market research that supports that. On the second question, just remind me, David, second question.
spk00: If you have differing strategies or thoughts on the proportions of patients who might switch from approved therapy or, yeah.
spk12: And also, I think you also asked about, you know, how do we get these patients? We're also looking at not only the retinal practices, but where these patients may be. Are they seeing optometrists and haven't been referred? Are they seeing ophthalmologists and haven't been referred? I think that's going to be a key part of the commercial plan is, you know, unlock where these patients are and get them in to see their retinal specialist. As Praveen said, another part of the strategy here is education, not only for the docs, but also for the patients to get them in earlier. We believe that earlier treatment will have better outcomes. More to come on that, and we need to put more data behind that, but that's our belief. And so that's where we are. And just a word about where Chris is. You know, he's built his organization out. We have not yet hired the field force. I think those type of discussions will come, you know, when the NDA is filed. We'll have a better timeline on potential approval dates. But we think we're in a very good position with our commercial team. And I will tell you, just like the leadership team, the people that we're hiring on the commercial team have extensive written experience. So looking forward to discussing this more as time goes on.
spk14: Thank you. And ladies and gentlemen, this concludes our question and answer session. I'd like to turn the call back over to Glenn Spondorio for any closing remarks.
spk12: Well, thank you. And thank you to everybody for listening today. A lot has happened in the third quarter, as I summarized before, and expect the same execution intensity in the fourth quarter. We look forward to continued dialogue. I appreciate the interest and continued support from all on this call today. Bye-bye.
spk14: Thank you, sir. This concludes today's conference call. We thank you all for attending today's presentation. You may now disconnect your lines and have a wonderful day.
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