Q4 2022 IVERIC bio Inc Earnings Call

Speaker 1: And.

Speaker 2: Good morning and welcome to the Iverac Bio fourth quarter 2022 earnings conference call. All participants will be in listen only mode. If you need assistance, please signal a conference specialist by pressing star and zero on your telephone keypad. If you need assistance, please call the Iverac Bio fourth quarter 2022 earnings conference call. Please signal a conference specialist by pressing star and zero on your telephone keypad.

Speaker 2: After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star then 1 on your telephone keypad. To withdraw your question, please press star then 2. Please note this event is being recorded. I would now like to turn the conference over to Kathy Galante.

Speaker 3: investor relations. Please go ahead. Good morning and welcome to the Iverac Bio conference call. Representing Iverac Bio today are Glenn Splendorio, Chief Executive Officer, Dr. Praveen Dougal, President, Keith Westby, Chief Operating Officer, David Carroll, Chief Financial Officer, Dr. Devil Desai, Chief Development Officer,

Speaker 3: Chris Simms, Chief Commercial Officer, and Tony Gibney, Chief Business and Strategy Officer.

Speaker 3: I would like to remind you that today we will be making statements relating to Iverac Bio's 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.

Speaker 3: These statements cover many events and materials 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 10-Q .

Speaker 3: filed on November 4, 2022, for a detailed description of the risk factor 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.

Speaker 3: While we may elect to update these forward-looking statements at some point in the future, we disclaim any obligation to do so except as required by law. I would now like to turn the call over to Glenn.

Speaker 4: Well thanks Kathy and good morning everybody.

Speaker 4: In 2022, we continue to deliver on our goal to deliver, to provide potential treatments to patients suffering from retinal diseases with Avicend-Captive PEGL, or ACP, achieving a statistically significant reduction in the rate of geographic atrophy progression at the 12-month prespecified primary endpoint across 10-minimumiquities across 21 basic beats And around 15,000

Speaker 4: to phase 3 clinical trials. We begin 2023 with the FDA's acceptance of the filing of our new drug application for ACP for the treatment of geographic atrophy, or GA, secondary to age-related macular degeneration.

Speaker 4: With the achievement of this important milestone, we move closer to our goal of providing patients with a treatment for GA, a devastating disease that leads to irreversible blindness.

Speaker 4: Additionally, our NDA has been granted priority review by the FDA and given a prescription drug user fee act or PDUFA date of August 19, 2023.

Speaker 4: We were also informed that at the time of the FDA acceptance letter,

Speaker 4: The FDA had not identified any potential review issues, and the FDA was not currently planning to hold an advisory committee meeting for ACB.

Speaker 4: This morning we announced results of a post-hoc analysis on the data from the ACP Gather1 and Gather2 clinical trials, signaling an up to 59% risk reduction in the rate of vision loss for the ACP 2 mg groups compared to sham at 12 months of treatment.

Speaker 4: For vegan, we'll discuss this new data in more details in a few moments.

Speaker 4: As we move closer to potential approval,

Speaker 4: Our key focus in 2023 is to make ACP commercially available to physicians and their patients suffering with GA as quickly as possible.

Speaker 4: About a year ago, we started to build a world-class commercial team that includes sales leadership, reimbursement, marketing, and market access.

Speaker 4: Our commercial leadership team brings extensive experience in launching drugs for retinal diseases in large markets. We continue to accelerate our launch plans and expect to have a full US team, including a field-based sales team hired by early April of this year.

Speaker 4: Our commercial team which is led by Chris Sims expects to have a feel force of approximately 50 to 70 sales representatives in an organization of about 120 in total.

Speaker 4: Since this is our year-end call, I wanted to reflect back on some of the significant accomplishments of 2022. We received top-line data from Gather2 in early September .

Speaker 4: and finished our rolling submission of the NDEA for ACP.

Speaker 4: in late December . This was done in just over a little, just over three months.

Speaker 4: In November 2022, we announced the FDA-granted Breakthrough Therapy designation for ACP for the treatment of GA secondary to AMD.

Speaker 4: To date, ACP is the first and only investigational drug to receive breakthrough therapy status for this indication. ACP is the first and only investigational drug to receive breakthrough therapy status

Speaker 4: which was granted based on the 12-month results from both Gather 1 and Gather 2.

Speaker 4: We also intend to pursue further discussions with the FDA about utilizing the Gather 1 and Gather 2 clinical trial data included in the current NDA submission to support treatment of GA associated with earlier stage disease, including patients with intermediate AMD. We do not plan to conduct a new clinical trial of ACP in patients with intermediate AMD.

Speaker 4: for ACP to expand the patient population and evaluate multiple sustained delivery technologies for ACP.

Speaker 4: On the financial front, in December of 2022, we raised approximately $324.3 million in proceeds in an underwritten public offering of our common sock.

Speaker 4: Also in 2022, we secured a term loan credit facility, providing us with up to $250 million in non-dilutive debt financing under which we have drawn down $100 million to date.

Speaker 4: These financing further strengthen our balance sheet and provide financial flexibility as we continue to build our U.S. launch readiness plan and prepare for the potential commercialization of ACG. Dave's going to provide some more details on our cash position in the moment.

Speaker 4: I also want to acknowledge Praveen's election to the Board of Directors at the beginning of this year.

Speaker 4: Praveen has been instrumental in helping to shape the company's business strategy.

Speaker 4: and in overseeing the development and regulatory strategy for ACP. Praveen, it's truly a pleasure to work with you, and I look forward to our continued work together.

Speaker 4: Before I turn the call over to Pervene, on behalf of Iberic Bio, we want to take a moment to congratulate a Pellis for the approval of Cypheri, which finally provides patients with the first treatment for GA.

Speaker 4: We also want to commend the FDA for their ongoing commitment to finding treatments for patients suffering from AMD.

Speaker 4: I want to thank all of you for your continued support of iveric Bio, and I will now turn the call over to Prabir.

Speaker 5: Thank you, Glenn, and good morning, everyone. I could not agree more with you, Glenn. It would be congratulations to our friends at Appellus.

Speaker 5: Our plans to drive ACP to a potential approval in GA has been clear and consistent throughout this journey. We believe our special protocol assessment for Gather2, fast track and rolling review of our NDA, breakthrough therapy designation and now priority review further strengthens the

Speaker 5: our position as we get closer to a potential near-term launch of ACP for GA patients. We look forward to collaborating with the FDA throughout the remaining NDA review process.

Speaker 5: We are excited to announce a post hoc time to event analysis of the data from the Gather One and Gather Two trials that signaled a reduction in the rate of vision loss.

Speaker 5: for the ACP 2 milligram groups compared to sham after 12 months of treatment.

Speaker 5: In this analysis, we define vision loss as greater than or equal to 15 letter loss in best corrected visual acuity or BCVA from baseline measured at any two consecutive visits.

Speaker 5: These results were consistent in the Gather 1 and Gather 2 clinical trials when analyzed independently, which signaled a 44% reduction with a hazard ratio of 0.56 and a 59% reduction with a hazard ratio of 0.41, respectively.

Speaker 5: in the rate of vision loss for the ACP 2 milligram groups compared to sham after 12 months of treatment. In the combined analysis of Gather 1 and Gather 2, patients in the ACP 2 milligram groups experienced a 56% reduction with a hazard ratio of 0.44 in the total number of patients in the ACP 2 milligram group.

Speaker 5: through 12 months of treatment and is an exploratory analysis in nature.

Speaker 5: On average, it takes only 2.5 years for GA lesions to start impacting central vision.

Speaker 5: It is encouraging to see vision loss reduction data at early time intervals in the first 12 months, which further supports the statistically significant Gather 1 and Gather 2 primary end point.

Speaker 5: This time to event analysis will be presented at ARVO in April . We believe this is the first time a reduction in the risk of vision loss will be presented for a potential treatment being investigated for GA. With the completion of our NDA submission in December of last year, we are going to

Speaker 5: Additionally, this timing provides us the opportunity to have the data presented at a major scientific meeting, ARVO, in April .

Speaker 5: Cross gather one and gather two combined. The most common adverse reactions experienced by 5% or more of patients over 12 months in patients who received PCP2 milligrams was conjunctival hemorrhage, 13%.

Speaker 5: Increased IOP, 9%, most of which were transient and resolved within 30 minutes of injection. And CNV, 7%. In both Gather 1 and Gather 2 in the ACP 2 mg groups, the IOP is a

Speaker 5: there were no cases of endophthalmitis.

Speaker 5: cases of endophthalmitis. No serious

Speaker 5: intraocular inflammation events, no vasculitis,

Speaker 5: and no ischemic optic neuropathy events reported through month 12. We look forward to our PDUFA goal date of August 19, 2023.

Speaker 5: In the meantime, we will continue to work collaboratively with the FDA on review of our NDA.

Speaker 5: We believe we are well positioned to become a leader in the development and commercialization of safe and effective treatments for retinal diseases and to create long-term value for our shareholders.

Speaker 5: We thank you for your time and support and look forward to updating you on our progress going forward.

Speaker 5: I will now turn the call over to Dave. Thank you, Praveen, and good morning, everyone. I'd like to highlight a few items from our press release of this morning and provide some guidance on our expected cash runway.

Speaker 6: For the quarter, our net loss totaled $59.1 million, or $0.47 per share, compared to a net loss of $33 million, or $0.29 per share, per Q421.

Speaker 6: For the full year, our net loss totaled $185.2 million, or $1.53 per share, compared to a net loss of $114.5 million, or $1.12 per share for 2021. This increased net loss was driven by increases in both R&D and G&A expenses.

Speaker 6: R&D expenses increased primarily due to the continued progress of the Gather 2 trial, and increased manufacturing activities for ACP.

Speaker 6: and increases in personnel costs associated with additional R&D staffing, including share-based compensation.

Speaker 6: G&A expenses increased primarily due to increases in commercial launch preparation expenses for ACP and increases in personnel costs associated with additional staffing, including share-based compensation. For more information, visit www.acp.com.

Speaker 6: Turning to our cash balance and expected cash runway, at December 31st we had approximately $646.8 million in cash, cash equivalents and available for sale securities.

Speaker 6: With our successful equity financing and the flexibility provided by our term loan facility with Hercules Capital and Silicon Valley Bank, we believe we have the financial resources required to launch ACP for GA in the U.S., if approved, and to meet our planned capital expenditures, debt service obligations, and operating expenses for at least the next 12 months.

Speaker 6: This estimate does not include any potential new borrowings under our term loan facility beyond the $25 million that we plan to borrow in 2023 based on the FDA's acceptance for filing of our NDA.

Speaker 6: Upon the FDA's approval of ACP, we may borrow an additional $75 million from our term loan facility. Thank you for your time, and I'll turn the call back over to Glenn.

Speaker 4: Well, thank you, Dave, and thank you, Praveen. Thank you, Dave, and thank you, Dave, for your time.

Speaker 2: To ask a question, you may press star then 1 on your telephone keypad. If you are using a speakerphone, please pick up your handset before pressing the keys.

Speaker 2: If at any time your question has been addressed and you would like to withdraw your question,

Speaker 2: If at any time your question has been addressed and you would like to withdraw your question, please press star then 2.

Speaker 2: At this time we will pause momentarily to assemble our roster. The first question comes from Annabelle Cimini with Stevehole.

Speaker 7: Please go ahead. Hi everyone, thanks for taking my questions.

Speaker 7: Congratulations on the progress. Getting to be really exciting and heated. So the vision loss benefit.

Speaker 7: I guess is really interesting. I guess the way it's been phrases that nobody really expected it this early on. So should we view this as a possible functional benefit that you can put in the label today? Will they put post hoc data exploratory endpoints in the label?

Speaker 7: is just like the ultimate functional benefit that you can measure here.

Speaker 5: Annabelle, this is Praveen. Good morning and thank you for your question. In regards to our labeling discussions, look, we are under review currently by the FDA and we obviously don't want to be talking about our discussions with the FDA, so I really have no comment on that whatsoever.

Speaker 5: The message that I think this post-hoc analysis gives us, and again, I want to emphasize that this is a post-hoc analysis of a pre-specified safety endpoint. And we should look upon this as exploratory data. However, having said that, we also believe that it's quite impactful. The message here really is that vision matters and time matters.

Speaker 5: and let me take each one of them separately. The regulatory agencies have said that, ultimately, function will follow anatomy, and we've looked at an endpoint that involves a slope analysis. And I think what we've been able to show here with this post-hoc analysis is that that loop may be closed. This is the first time that we've really demonstrated a

Speaker 5: vision delta, vision benefit based on the anatomy. So function did actually follow anatomy. In terms of time, time does matter. This is not like treating a wet AMD for instance.

Speaker 5: In wet AMD, you can have fluid there. The fluid may be resolved with anti-VEGF usage and function may come back. Here, once the photoreceptor cells die, they don't come back. So the time of onset really does matter. We were very pleased to see that the time of onset was early in this retrospective analysis. So I think...

Speaker 5: At the end of the day, this we consider supportive of our primary endpoint, which is the slope analysis. This is supportive data of the primary endpoint. And again, I think the message here is that vision matters and time matters. And yes, there will be data coming out that will be additive to this.

Speaker 5: And we will be talking about this in major meetings, and you will see other supportive data coming out as well.

Speaker 7: Thank you for your question. Okay, great. And if I can ask one more question. You know, a lot of people are talking about target populations, who is the low-hanging fruit and I think you've even stated in the past, bilateral patients lose vision in one eye and have risk of loss in another eye. As well as...

Speaker 7: possibly patients with J&I and wet AMD and another because they're already in the practices.

Speaker 7: So I guess I'm curious about the latter target population. You had not... Well I just did, because I've been watching the stream and I don't remember.

Speaker 7: study patients with wet AMD in the other eye? Just want to make sure I understand it correctly. You would exclude a patient with wet AMD in the other eye, I think, just to reduce the risk of conversion. So how do we square that with the target population?

Speaker 5: these patients would effectively have it having to come in for up to two years every other week to be injected in one eye at a time and we felt that that was an excessive burden to be placed on these patients in clinical trials and that's why those patients were excluded that was the only reason no other. In terms of the target patient population I don't think the fellow eye exclusion has any bearing on the target population whatsoever.

Speaker 5: So I think, again, what we provided here today, the postdoc analysis, is a basis for that conversation, which is that there is potential here. Again, this is an exploratory retrospective analysis, but there's potential here to prevent catastrophic vision loss. And I think that is quite impactful.

Speaker 5: So I think, again, what we provided here today, the postdoc analysis, is a basis for that conversation, which is that there is potential here. Again, this is an exploratory retrospective analysis, but there's potential here to prevent catastrophic vision loss. And I think that is quite impactful. Okay, great. Thank you so much.

Speaker 2: The next question comes from Ken Katchatore with D.D. Cowan. Please go ahead.

Speaker 2: Hey team, congratulations on all the progress. I'm wondering if maybe you just step back and take a little bit of a crack at talking about the market in itself, the size and maybe how we should be thinking about the evolution of it. And then Praveen, you get to be, you're someone who's sat in front of real patients with this real issue. I'll just talk about

Speaker 2: their motivation to treat. I know there's a lot of discussion about the frequency of treatment, but would really like to get your perspective on it. And then maybe within that, how the real world use on dosing may play out. And then just lastly,

Speaker 2: You keep on highlighting intermediate and it makes a lot of sense. You just talk about what the implications of that would be on utilization and how would it differentiate the label if you were able to get it. Thanks so much.

Speaker 5: Ken, thank you and good morning. Thank you for your questions. Let me first ask Chris Sims, who is our Chief Commercial Officer, to answer the first part of the question that you asked and I'll handle the rest. Chris?

Speaker 8: I think the first part of your question is related to market size, and I think you'll share what we've shared previously. We believe it's a significant market. As we've said publicly, best measures is that we believe there's about a million and a half of accumulated patients in the US.

Speaker 8: we believe is important for this market is the education, notably upstream, where we believe a lot of these patients are not sitting with retina practices today. We believe the majority are under the care of a upstream ophthalmologist or an optometrist. So therefore the need, I think, to educate and engage with that community.

Speaker 8: it's critical to help facilitate awareness and ultimately diagnosis and referral for treatment. So our modeling on the market has not changed. We still believe it's quite a significant market. However, the need for that education remains pretty high. I hope it helps. Bad enough to turn attention.

Speaker 5: Thank you, Chris. The other questions, Ken, so the conversations with the patient and what this means to me as a clinician, this retrospective data, and as I mentioned to Annabelle, this allows me a language that I can have with the patient, which is to say, when you have a loss of vision of 15 letters or more, you have a loss of vision

well, what kind of patient? And I know there's been a lot of discussion regarding center involving or non-center involving patient. And I just want to clarify that as a clinician. Look, I believe all patients with geographic atrophy, center involving and non-center involving early and advanced, all of these patients are eligible.

A patient who has center-involving geographic atrophy may not progress as quickly as a patient that doesn't have center-involving geographic atrophy. However, a lot of these patients, when I was in practice, would come in, you know, their head may be a little bit tilted.

They would be looking from an island of periphovial photoreceptor cells that they've preserved, and that's what would allow them from tripping over furniture and burning their hands on stoves and et cetera. So this drug will be very valuable for those patients. I would argue that those patients would benefit directly from this drug. Now would I enroll a patient like that in a clinical trial?

probably less likely because it's less measurable, the delta would be, but that doesn't mean that the patient wouldn't have a great deal of benefit from this drug. So the bottom line to my answer is that yes, I think all patients regardless of how big the geographic atrophy is and where it is unless of course that's completely burnt out.

would be eligible for a safe and efficacious drug. In terms of dosing, look, I... You know that we will have every other month data in our second half of the year, and the second half of the study, of course. And our first year, a cart turn was on September 7th. So you can do the mathematics there.

However, dosing is, in my opinion, is really not going, dosing frequency is not going to be determined by what's in the label. It's really going to be determined by what the patient can do. The conversation is going to go something like this.

I'd say, Mrs. Smith, we have a drug that will help you and reduce your chance of having catastrophic vision loss potentially. And to get the best results, you would come in every month, as close to every month as you can. And Mr. or Mrs. Smith would then come in as close to every month as he or she can.

And that will determine the frequency of treatment, not necessarily what's written in a label. As far as your question on intermediate macular generation goes, look, there's a very broad range here. Intermediate macular generation can be anywhere from one druza to severe intermediate macular degeneration where patients have metamorphopsia.

that having a safe and efficacious drug as we believe ACP has the potential to be will allow us to target that patient population as well. Thank you for your question, Kim.

The next question comes from Ellie Merle with UBS. Please go ahead. Hey, guys. Thanks so much for taking the question and exciting data on vision loss. Maybe can you just comment a little bit in terms of the vision loss definition of 15 letters of vision loss?

or greater and I guess why 15 and whether you looked at other thresholds as well. Thanks. Good morning and thank you for your question. The 15 letter

milestone or landmark is really traditionally accepted as one that is a devastating amount of vision loss or a significant amount of vision gain and that's the doubling of the vision angle and that's traditionally accepted by regulatory agencies as a important landmark.

That's the reason that we chose to show that and do the analysis in this particular press release. Now, having said that, yes, we've done sensitivity analyses on several other landmarks as well. And we're convinced, because of the sensitivity analysis that we've done exhaustively, that this trend is a real trend. And again, I want to emphasize that this is a pre-specified safety endpoint.

It is a post hoc analysis, but yes, we've done numerous and exhaustive sensitivity analyses on this and are convinced that this trend is real and that it is impactful. Great, thanks. Maybe just in terms of those sensitivity analyses, is that data that we'll see at the presentation? If you can comment if there were any...

subgroup where you saw perhaps an even greater effect. Thanks. Yeah, Ellie, we have not yet put together that presentation as yet. So I can't comment on that. We will certainly be showing the data that we've released today. And what I can tell you is that we will, we are doing extensive studies based on providing you additional information regarding this functional benefit or potential functional benefit, which will be presented in other major meetings as well. Thank you for your question. The next question comes from Mike Ults with Morgan Stanley .

Please go ahead. Good morning. Congratulations on all the progress as well. And thanks for taking the question. Maybe just to follow up on the promising vision loss data, you provided this morning. Just curious if you're considering maybe exploring that further and maybe a prospective lead.

go ahead. Good morning, congratulations on all the progress as well and thanks for taking the question. Maybe just a follow-up on the promising vision loss data you provided this morning. Just curious if you're considering maybe exploring that further and maybe a prospectively designed study. Thanks.

for future studies. Having said that, however, remember our expectation and our goal per our agreements that we've outlined with the regulatory agencies are submission and potential acceptance of our NDA filing based on the 12-month primary endpoint, and that hasn't changed. I just want to make sure that we don't confuse those two things. Our expectation is that the NDA will be reviewed based on our pre-specified agreements that we've had with the FDA based on the...

and without going into your discussion, maybe just if there's any implications that, you know, for your label as a result of what we've seen with them. Greg, good morning and thank you for your question again. It really would be inappropriate for any of us to comment about a palace other than to say what, and after this maybe Glenn wants to say a few words as well, other than to say we are very happy that patients are getting a treatment. It's long overdue and a palace and the entire team deserves a great deal of credit for coming across the line here in terms of having a medicine that will help patients. We look forward to seeing how their launch is. We wish them very, very well.

but it really would not be appropriate for us to comment on a competitor's label. Maybe I can pass it to Glenn and see if Glenn has a few words to say as well. Yeah, Greg. And thank you for the question. And I go back to what we just said in the script. I congratulate them. It's really exciting to see a company finally be able to have a drug that patients could use. I think that's just outstanding. As Pervene said, we wish them luck. We will learn a lot from them. We just throw that patients and the patients have a drug available to them. And we throw it for a pill. Okay, great. And then as you're in the review process here and preparing for US commercialization, where are you in the process of potentially finding our NXUF commercialization partner? And what are you looking for? I'm looking for such a partner. Yes, so Pervene, I want to take that. Yeah, sure. Thanks. And thanks for the question, Greg. I think, you know, with today's data, we continue to build on the data set. And I think all of this is very important in defining a future partner.

You know, as we said in the past, we do have a number of meetings in the first half of the year with European regulators, which will give us more guidance. Having data like we presented today, we believe may be helpful in those discussions. So that will continue to move forward. Our objective, as we have said in the past, is to focus on the U.S. market and to find help overseas. So that's just another point of reference or data that will be helpful in that XUS discussion. So that all continues and we'll keep you posted on our ongoing discussions with European regulators. Great. Thanks again for taking the question. The next question comes from Eddie Hickman with Guggenheim Securities. Please go ahead. Hi, good morning. Grats on the progress. Just a few from me. Throughout Gather 2, you were able to provide updates on the injection fidelity, which gave you confidence on meeting at primary endpoint. Are you able to give any color on how that's tracking so far in the second year?

Eddie, good morning, and thanks for your question again. What I can tell you is, as of now, we haven't guided the numbers as yet, but I can tell you that we're very, very pleased with the way that that's tracking. We've got a fantastic clinical operations team, and they're very, very hard at work to make sure that all these patients are retained and that the injection fidelity is as high as possible. So we haven't given guidance as to the numbers as yet, but I can tell you that we're doing very well and are very pleased with the ongoing process. Great. And then really interesting visual acuity data that you presented. I'm curious if that's something you can share with the FDA as part of your back and forth that you get with your breakthrough designation without needing to file any additional amendments, just to sort of show them the confidence that you're seeing on that functional endpoint throughout the early part of the review. Thanks. Yeah, Eddie, as you know, we're under review at this time. We've said publicly that we're very pleased with our interactions with the FDA. We found them as expected to be extraordinarily collaborative.

And we feel that the questions that are going back and forth are exactly the right questions that we would like and that we are doing, we believe, everything that the FDA would like us to. So we're very, very happy with the interactions, but other than that, we certainly don't want to be publicly commenting on any details regarding the discussions that we're having with the FDA. But thank you for your question. The next question comes from Kombi's Yazdi with Jeffries. Please go ahead. Morning, team. Can you provide us any more color on your interactions with the FDA on intermediate Ambi? And then may have a few more thoughts. Thank you. Kombi's good morning and thanks for the question. What we said publicly is that with the interactions that we've had, we will not be doing an intermediate AMD study. As we had, as, as we've announced, I think some time ago, we feel that we'll be able to target intermediate AMD without doing a specific study for interoperability.

positive from year two of Gather Two. Would you pursue every other month dosing for ACP? Would this have to come as a SNBA? Appreciate all the answers today. Thank you.

Yeah, we have not guided us to that. We obviously want to see the data. We want to see what the situation is like at that time. That's the decision to be made down the road. But we really don't believe that having every other month dosing really provides any kind of a competitive advantage because we believe that physicians will treat according to what's best for the patient. And what's best for the patient is going to be dependent also on how often the patient can come in. And that's going to be the primary determinant of the frequency of treatment, not what's written in the label. And just to kind of put a emphasis on this, if you look at the anti-vegethe experience, for instance.

the vast majority of us treat and extend, and that's not in any label. So there is a history of my colleagues, really doing what's right for the patient given the particular situation, regardless of what the label says. So the answer to your question is, look, I'm not really sure what we will do with the 24 month data, whether it be on the label or not, that's yet to be determined. Thank you so much. This concludes our question and answer session. I would like to turn the conference back over to Glenn Splendorio for any closing remarks. Thank you, Andrew, and thanks everyone for listening this morning, and we're very happy and pleased with our progress. And we look forward to our continued work with the FDA and our NDA filing, and hopefully a potential approval in late August of this year. We're also committed, as we talked about today, to building a world-class commercial team to be ready to engage physicians, healthcare providers, and patients if ACP is approved. And finally, we look forward to having our vision loss data presented at ARVO. So you can expect continued execution from us. We always enjoy speaking to all of you, and have a great day. Bye-bye. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.

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Good morning and welcome to the Iveric Bio-Worth Quarter 2022 earnings conference call. All participants will be in listen only mode. Should you need assistance, please signify a conference specialist by pressing star and zero on your telephone keypad. After today's presentation, there will be an opportunity to ask questions.

To ask a question, you may press star than one on your telephone keypad. To withdraw your question, please press star than two. Please note, this event is being recorded. I would now like to turn the conference over to Kathy Galante. Invest relations, please go ahead. Good morning and welcome to the Iveric Bio conference call. Representing Iveric Bio today, our Glen Spendorio, Chief Executive Officer, Dr. Pervine 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 Iverick by our future expectations regarding operational, financial, and research and development matters. These statements constitute forward-looking statements for the purposes of the State Harbor provision under the Private Security's litigation reform act of 1995. These statements cover many events and materials 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 November 4, 2022, for a detailed description of the risk factors of 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'd disclaim any obligation to do so except as required by law. I would now like to turn the call over to Glenn. Thanks, Kathy, and good morning, everybody. In 2022, we continue to deliver on our goal to deliver to provide potential treatments to patients suffering from retinal diseases with an avocent captive pegal for ACP.

achieving a statistically significant reduction in the rate of geographic atrophy progression at the 12 month pre-specified primary endpoint across two phase three clinical trials. We begin 2023 with the FDA's acceptance of the filing of our new drug application for ACP for the treatment of geographic atrophy or GA secondary to age-related macular degeneration. With the achievement of this important milestone we move closer to our goal of providing patients with a treatment for GA, a devastating disease at least irreversible blindness. Additionally our NDA has been granted priority review by the FDA and given a prescription drug user fee act or pedophidate of August 19, 2023. We were also informed that at the time of the FDA acceptance letter the FDA had not identified any potential reviews of due issues and the FDA was not currently planning to hold an advisory committee meeting for ACP. This morning we announced results of a post-toc analysis on the data from the ACP, gather one and gather two clinical trials, figling in up to 59% risk reduction in the rate of vision loss for the ACP 2 milligram groups compared to sham at 12 months of treatment.

For vegan, we'll discuss this new data in more details in a few moments. As we move closer to potential approval, our key focus in 2023 is to make ACP commercially available to physicians and their patients suffering with GA as quickly as possible. About a year ago, we started to build a world-class commercial team that includes sales leadership, reimbursement, marketing, and market access. Our commercial leadership team brings extensive experience in launching drugs for retinal diseases in large markets. We continue to accelerate our launch plans and expect to have a full US team, including a field-based sales team hired by early April of this year. Our commercial team, which is led by Chris Sims, expects to have a field force of approximately 50 to 70 sales representatives and an organization of about 120 in total.

We initiated an open label extension study for patients who have completed their month 24 visit in the Gather2 clinical trial.

with the aim of providing patients long-term access to ACP and collecting additional safety data. And we continue to invest in additional life cycle initiatives for ACP to expand the patient population and evaluate multiple sustained delivery technologies for ACP. On the financial front, in December of 2022, we raised approximately 324.3 million net proceeds in an underwritten public offering of our common stock.

Also, in 2022, we secured a term loan credit facility providing us with up to 250 million in non-deludive debt financing under which we have drawn down 100 million to date. These financing further strengthen our balance sheet and provide financial flexibility as we continue to build our U.S. launch readiness plan and prepare for the potential commercialization of ACG. Dave is going to provide some more details on our cash position in the moment. I also want to acknowledge Pervene's elections at the board of directors at the beginning of this year. Pervene has been instrumental in helping to shape the company's business strategy and in overseeing the development and regulatory strategy for ACP. Pervene is truly appreciative of work with you and I look forward to our continued work together. Before we turn the call over to Pervene, on behalf of Iveric Bio, we want to take a moment to congratulate a Pellis for the approval of Cipherary, which finally provides patients with the first treatment for GA. We also want to commend the FDA for their ongoing commitment to finding treatments for patient suffering from AMD. I want to thank all of you for your continued support of Iveric Bio. Now turn the call over to Pervene. Thank you, Glenn and good morning, everyone. I could not agree more with you, Glenn. I would be congratulated to our friends at a Pellis.

Our plans to drive ACP to a potential approval in GA has been clear and consistent throughout this journey. We believe our special protocol assessment for Gather 2, fast track and rolling review of our NDA, breakthrough therapy designation, and now priority review further strengthens our position as we get closer to a potential near-term launch of ACP for GA patients. We look forward to collaborating with the FDA throughout the remaining NDA review process. We are excited to announce a post-talk time-to-event analysis of the data from the Gather 1 and Gather 2 trials that signaled a reduction in the rate of vision loss for the ACP 2 milligram groups compared to sham after 12 months of treatment. In this analysis, we define vision loss as greater than or equal to 15-letter loss and best corrected visual acuity or BCVA from baseline measured at any two consecutive visits. These results were consistent in the Gather 1 and Gather 2 clinical trials when analyzed independently, which signaled a 44-percent reduction with a hazard ratio of 0.56 and a 59-percent reduction with a hazard ratio of 0.41 respectively in the rate of vision loss for the ACP 2 milligram groups compared to sham after 12 months of treatment. In the combined analysis that gather 1 and Gather 2 patients in the ACP 2 milligram groups experienced a 56-percent reduction with a hazard ratio of 0.41 respectively and hoped for finally a delivery of vision loss for the ACP 2 milligram groups compared to sham after 12 months of treatment. In the combined analysis of Gather 1 and Gather 2 patients in the ACP 2 milligram group experienced a 56-percent reduction with a hazard ratio of 0.44 in the rate of vision loss compared to sham after 12 months of treatment. This post-hawk analysis evaluates the potential vision loss signal through 12 months of treatment that is an exploratory analysis in nature. On average, it takes only 2.5 years for GPs.

We look forward to our PDUFA goal date of August 19, 2023. In the meantime, we will continue to work collaboratively with the FDA on review of our NDA. We believe we are well positioned to become a leader in the development and commercialization of safe and effective treatments for retinal diseases and to create long-term value for our shareholders. 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. Thank you, Praveen, and good morning, everyone. I'd like to highlight a few items from our press release of this morning and provide some guidance on our expected cash runway. For the quarter, our net loss totaled $59.1 million, or $0.47 per share, compared to a net loss of $33 million, or $0.29 per share, per Q421. For the full year, our net loss totaled $185.2 million, or $1.53 per share, compared to a net loss of $114.5 million, or $1.12 per share, for 2021.

This increased net loss was driven by increases in both R&D and GNA expenses. R&D expenses increased primarily due to the continued progress of the GATER2 trial, increased manufacturing activities for ACP, and increases in personnel costs associated with additional R&D staffing, including share-based compensation. GNA expenses increased primarily due to increases in commercial launch preparation expenses for ACP, and increases in personnel costs associated with additional staffing.

including share-based compensation. Turning to our cash balance expected cash run length. At December 31st, we had our approximately 646.8 million in cash, cash equivalents, and available for sale securities. With our successful equity financing and the flexibility provided by our term loan facility with Hercules Capital and Silicon Valley Bank, we believe we have the financial resources required to launch ACP for GA in the US if approved, and to meet our planned capital expenditures, debt service obligations, and operating expenses for at least the next 12 months. This estimate does not include any potential new borrowings under our term loan facility beyond the 25 million that we plan to borrow in 2023 based on the FDA's acceptance for filing of our NDA. Upon the FDA's approval of ACP, we may borrow an additional 75%

with Seifel, please go ahead. Hi everyone, thanks for taking my questions and congratulations on the progress. I'm getting to be really exciting and heated. So the vision loss benefit, I guess, is really interesting. I guess the way it's been phrased is that nobody really...

present yourself competitively to the market. And is there any more tangible functional measurement than that? Is this like the ultimate functional benefit that you can measure here? Annabelle, this is for Vene. Good morning and thank you for your question.

In regards to our labeling discussions, look, we are under review currently by the FDA and we obviously don't want to be talking about our discussions with the FDA. So I really have no comment on that whatsoever. The message that I think this post-talk analysis gives us, and again, I want to emphasize that this is a post-talk analysis of a pre-specified safety endpoint. And we should look upon this as exploratory data. However, having said that, we will also believe that it's quite impactful. The message here really is that vision matters and time matters. And let me take each one of them separately. The regulatory agencies has said that ultimately function will follow an admi. And we've looked at an end point that involves a slow analysis.

And I think what we've been able to show here with this post-doc analysis is that that loop may be closed. This is the first time that we've really demonstrated a vision, delta, vision benefit based on the anatomy. So, function did actually follow anatomy. In terms of time, time does matter. This is not like treating a wet AMD, for instance. In wet AMD, you can have fluid there. The fluid may be resolved with antivagia, vegef usage, and function may come back. Here, once the photoreceptor cells die, they don't come back. So, the time of onset really does matter. We were very pleased to see that the time of onset was early in this retrospective analysis. So, I think at the end of the day, this we consider supportive of our primary endpoint, which is the slope analysis. This is supportive data of the prime endpoint. And again, I think the message here is that vision matters. And yes, the time matters. And yes.

There will be data coming out that will be additive to this, and we will be talking about this in major meetings, and you will see other supportive data coming out as well. Thank you for a question. Great. And if I can ask one more question, you know, a lot of people are talking about target populations who's the low-hanging fruit, and I think you've even stated in the past bilateral patients whose lost vision in one eye and have risk of loss in another eye as well as possibly patients with gene-win-ion, wet AMD, and another because they're already in the practices. So I guess I'm curious about the latter target population. You had not.

study patients with what AMD and the other, I just want to make sure I understand it correctly. You had experience with what AMD and the other I think, you know, just to reduce the risk of conversion. So how do we square that with the target population that you might go after? Or maybe I just didn't understand it correctly. Maybe you can clarify. Thanks. Yeah, to be very clear, the reason that we excluded patients with a corollomy of ascalar membrane in the fellow I is really quite simple. It's because if we want to ensure that there is no crossover effect, these patients would effectively have it having to come in for up to two years every other week to be injected in one eye at a time. And we felt that that was an effective burden to be placed on these patients in clinical trials. And that's why those patients were excluded. That was the only reason no other.

In terms of the target patient population, I don't think the fellow I exclusion has any bearing on the target population whatsoever. I think what clinicians are looking for is an effective, efficacious and safe treatment. And I believe that as a clinician, I think all of my patients with geographic antithesis and also with severe intermediate-magnetic intergenerational patients that I would consider for treatment. So I think, again, what we provided here today, the postdoc analysis, is a basis for that conversation, which is that there is potential here. Again, this is an exploratory retrospective analysis, but there is potential here to prevent catastrophic vision loss. And I think that is quite impactful.

In terms of the target patient population, I don't think the fellow I exclusion has any bearing on the target population whatsoever. I think what clinicians are looking for is an effective, efficacious, and safe treatment. I believe that as a clinician, I think all of my patients with geographic antithesis, and also with severe intermediate macular degeneration are patients that I would consider for treatment. So I think, again, what we provided here today, the postdoc analysis, is a basis for that conversation, which is that there is potential here. Again, this is an exploratory retrospective analysis, but there is potential here to prevent catastrophic vision loss. And I think that is quite impactful. Okay. Great. Thank you so much.

The next question comes from Ken Ketchatory with DD Kallen. Please go ahead. Be team, congratulations on all the progress. I wonder if maybe you just step back and take a little bit of a crack at talking about the market itself, the size and maybe how we should be thinking about the evolution of it. And then, Praveen, you get to be, you're someone who's sat in front of real patients with this real issue. You can just talk about their motivation to treat. I know there's a lot of discussion about the frequency of treatment, but would really like to get your perspective on it. And then maybe within that, how the real world use on dosing may play out. And then just lastly, you keep on highlighting intermediate and it makes a lot of sense. You just talk about what the implications of that would be on utilization and how would it differentiate the label if you were able to get it. Thanks so much. Ken, thank you and good morning. Thank you for your questions. Let me first ask Chris Sims, who is their Chief Commercial Officer, to answer the first part of the question that you asked. And I'll handle the rest. Chris? Yeah, Praveen. Hi, Ken. Thanks for the question. I think the first part of your question is rolling it to market size. I think you'll...

share what we've shared previously. We believe it's a significant market. As we've said publicly, that measures that we've used about a million and a half and two million patients in the US alone that have some level or some stage of geographic atrophy. We also believe that number could be undiagnosed based on the sources of those data and the fact that some of that data is from a number of years back. And one of the things that we believe is important for this market is the education notably upstream where we believe a lot of these patients are not setting with retina practices today. We believe the majority are under the care of a upstream ophthalmologist or an optometrist. So therefore the need I think to educate and engage with that community is critical to help facilitate awareness and ultimately diagnosis and referral for treatment. So our modeling on the market has not changed. We still believe it's quite a significant market. However, the need for that education remains pretty high. I hope it helps. Thank you, Chris. The other questions I can't...

So the conversations with the patient and what this means to me as a clinician, this retrospective data, and as I mentioned Annabelle, this allows me a language that I can have with the patient, which is to say, when you have a loss of vision of 15 letters or more, that truly changes the patient's life. That is catastrophic. And to be able to decrease the risk of that is really quite meaningful. So that allows me an avenue to have a very direct and very transparent conversation with the patient. And the other question might be, well, what kind of patient? And I know there's been a lot of discussion regarding center involving or non-central involving patient. And I just want to clarify that as a clinician. Look, I believe all patients with geographic atrophy, center involving and non-central involving early and advanced. All of these patients, are eligible. A patient who has center involving geographic atrophy may not progress as quickly as a patient that doesn't have center involving geographic atrophy. However, a lot of these patients, when I was in practice, would come in. Their head may be a little bit tilted.

They would be looking from an island of paraffoval photo receptor cells that they've preserved, and that's what would allow them from tripping over furniture and burning their hands on stoves and etc. So this drug will be very valuable for those patients. I would argue that those patients would benefit directly from this drug. Now would I enroll a patient like that in a clinical trial? Probably less likely because it's less measurable. The delta would be, but that doesn't mean that the patient wouldn't have a great deal of benefit from this drug. So the bottom line to my answer is that yes, I think all patients, regardless of how big the geographic atrophy is and where it is, unless of course it's completely burnt out, would be eligible for safe and efficacious drug. In terms of dosing, look, you know that we will have every other month data in our second half of the day. And of the second half of the study, of course. And our first year, a card turn was on September 7th. So you can do the mathematics there. However, dosing is, in my opinion, is really not going, dosing frequency is not going to be determined by what's in the label. It's really going to be determined by what the patient can do. The conversation is going to go something like this. I'd say Mrs. Smith, we have a drug that will help you and reduce your chance of having catastrophic...

definition of 15 letters or greater and I guess why 15 and whether you looked at other thresholds as well. Thanks. LA Good Morning and thank you for a question. The 15 letter milestone or landmark is really traditionally accepted as one that is a devastating amount of vision loss or a significant amount of vision gain and that's the double.

analysis that we've done exhaustively that this trend is a real trend. Again, I want to emphasize that this is a pre-specified safety endpoint. It is a post-talk analysis, but yes, we've done numerous and exhaustive sensitivity analyses on this and are convinced that this trend is real and that it is impactful. Great, thanks. And maybe just in terms of those sensitivity analyses, is that data that we'll see at the presentation.

regarding this functional benefit or potential functional benefit, which will be presented in other major meetings as well. Thank you for your question. The next question comes from Mike Ults with Morgan Stanley . Please go ahead.

Good morning. Congratulations on all the progress as well. And thanks for taking the question. Maybe just a follow-up on the promising vision loss data you provided this morning. Just curious if you're considering maybe exploring that further and maybe a prospective lead. Thank you.

Design study. Mike, good morning, and again, thank you for your question. What we've shown today is a post-talk retrospective study, and we believe that this is very impactful, very important data that supports the primary endpoint. That's the reason we presented this. We also believe that it forms a basis for doing future studies that may well be perspective and randomized. Certainly, these are things that we can add on to with future studies. And in all future, all prospective randomized studies are really based on data that you get from encouraging.

designation and based on the primary endpoint which is that month 12.

and based on the primary endpoint, which is at month 12. Thank you. Thank you for your question.

The next question comes from Greg Harrison with Think of America. Please go ahead. Hey, good morning and thanks for taking the question. Are there any talks that you can share with us on the breadth of the appellate label and without going into your discussion? Maybe just if there's any implications that, you know, for your label as a result of what we've seen with them? Greg, good morning and thank you for your question again. It really would be inappropriate for any of us to comment.

be appropriate for us to comment on a competitor's label. Maybe I can pass it to Golan and see Golan have as a few words to say as well. Yeah, Greg. And thank you for the question. And I go back to what we just said in the script. I congratulate them. It's really exciting to see a company finally be able to have a drug that patients could use. I think that's just outstanding. As for Dean said, we wish them luck. You know, we will learn a lot from them.

and we just throw that patient and we throw the patients up a drug available to them and we throw it for a pellet. Okay, great. And then as you're in the review process here and preparing for US commercialization, where are you in the process of potentially finding our NXUS commercialization partner and what are you looking for on such a partner? Yeah, sure. Thanks. And thanks for the question, Greg. I think, you know, with today's data, we continue to build on the data set. And I think all of this is very important in defining a future partner. You know, as we said in the past, we do have a number of meetings in the first half of the year with European regulators, which will give us more guidance. Having data like we presented today, we believe may be helpful in those discussions. So that will continue to move forward. Our objective, as we have said in the past, is to focus on the US market and to find help overseas. Today's just another point of reference or data that will be helpful in that XUS discussion. So that will continue. And we'll keep you posted on our ongoing discussions with European regulators. Great. Thanks again for taking the question. The next question comes from Eddie Hickman with Guggenheim. Security. Please go ahead. Hi, good morning. It's on the progress. Just a few from me.

Throughout Gather 2, you were able to provide updates on the injection fidelity, which gave you confidence on meeting that primary endpoint. Are you able to give any color on how that's tracking so far in the second year? Eddie, good morning, and thanks for your question again. What I can tell you is that as of now we haven't guided the numbers yet, but I can tell you that we're very, very pleased with the way that that's tracking. We've got a fantastic clinical operations team and they're very, very hard at work to make sure that all these patients are retained and that the injection fidelity is as high as possible. So we haven't given guidance as to the numbers as yet, but I can tell you that we're doing very well and are very pleased with the ongoing process. Great. And then really interesting visual acuity data that you presented. I'm curious to that something you can share with the FDA as part of your back and forth that you get with your breakthrough designation without needing to file any additional amendments just to sort of show them the confidence that you're seeing on that functional endpoint throughout the early part of the review. Thanks.

Yeah, Eddie, as you know, we're under review at this time. We've said publicly that we're very pleased with our interactions with the FDA. We've found them as expected to be extraordinarily collaborative. And we feel that the questions that are going back and forth are exactly the right questions that we would like and that we are doing. We believe everything the way that the FDA would like us to. So we're very, very happy with the interactions. But other than that, we certainly don't want to be publicly commenting on any details regarding the discussions that we're having with the FDA. But thank you for your questions. The next question comes from Combys Yazdi with Jeffries.

Please go ahead. Morning, team. Can you provide us any more color on your interaction with the FDA on intermediate AMD? And then may have a few more thoughts after that. Come be good morning and thanks for the question. What we said publicly is that with the interactions that we've had, we will not be doing an intermediate AMD study. As we had, as we've announced, I think some time ago, we feel that we'll be able to target intermediate AMD without doing a specific study for intermediate AMD. Because this is considered a continuum of disease. We said that publicly and other than that, we have not guided us to any further details regarding our interactions with the FDA.

Excellent. Thank you, Ann. If ACP is approved in August , what would be the general time frame for receiving at permanent Jcode for ACP? Chris, maybe I can pass that question on to you. Yeah, thanks for being on and thanks. Thanks for the question. So, following our August Purdue Fed date, it's an important question, by the way. So, we plan to file at the first quarterly opportunity, which again, based on the August Purdue Fed date would be the second of October , would be the first opportunity to file for the permanent Jcode. And then following that time, we would expect to get the permanent and hope to get the permanent Jcode in the early second quarter of 24. And one final one, just to put a final point on every other month's dosing, if the data are positive from year two of gather two, would you presume every other month's dosing for ACP? Would this have become as an FND?

The answer to your question is, look, I'm not really sure what we will do with the 24-month data, whether it be on the label or not, that's yet to be determined. This concludes our question and answer session. I would like to turn the conference back over to Glen Doreo for any closing remarks. Donna, thank you, Andrew. And thanks everyone for listening this morning and we're very happy and pleased with our progress.

And we look forward to our continued work with the FDA and our NDA filing and hopefully a potential approval in late August of this year. We're also committed, as we talked about today, to building a world-class commercial team to be ready to engage physicians, healthcare providers, and patients if ACP is approved. And finally, we look forward to having our vision loss data presented at ARVO. So you can expect continued execution from us. We always enjoy speaking to all of you and have a great day. Bye-bye. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.