ISEE (2020 - Q3)

Good day and welcome to the IVERIC bio Third Quarter 2020 Results Conference Call. Today's conference is being recorded. At this time, I would like to turn the conference over to Kathy Galante. Please go ahead. Kathy Ga

Good morning and welcome to IVERIC bio's conference call. Representing IVERIC bio today are Mr. Glenn Sblendorio, Chief Executive Officer and President; Dr. David Guyer, Executive Chairman; Mr. Dave Carroll, Chief Financial Officer; Dr. Pravin Dugel, Chief Strategy and Business Officer; Dr. Kourous Rezaei, Chief Medical Officer; Dr. Abraham Scaria, Chief Scientific Officer; and Mr. Keith Westby, Chief Operating Officer. I would like to remind you that today we will be making statements relating to IVERIC bio's future expectations regarding operational, financial, and research and development matters including statements regarding the impact of the COVID-19 pandemic on our research and development programs and the conduct of clinical trials; our expectations to use GATHER1, our previously announced clinical trial of Zimura for the treatment of geographic atrophy as a Phase 3 clinical trial; our expectations for and the progress of GATHER2 our second Phase 3 clinical trial evaluating Zimura for the treatment of geographic atrophy; our development and regulatory strategy for Zimura and our other product candidates including our expectations to additional indications for which we may pursue the development of Zimura; our hypothesis regarding complement and the HtrA1 inhibition as a mechanism of action for the treatment of AMD and potentially other retinal diseases; our projected use of cash and cash balances; the timing progress and results of clinical trials and other research and development activities and regulatory submissions; the potential utility and development potential of our product candidates; the size of the potential market to indications our product candidates are intended to treat; and the potential for our business development strategy. 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 in any forward-looking statements including risks related to the future progression of the COVID-19 pandemic and its impact on our research and development program operations and financial position; initiation and the progress of research and development programs and clinical trials; availability of data from these programs; reliance on contract development and manufacturing organization, university collaborators, and other third parties; establishment of manufacturing capabilities; expectations for regulatory matters; need for additional financing and negotiation and consummation of business development transactions and other risks. I refer you to our SEC filings and in particular to the risk factors included in our quarterly report on Form 10-Q filed on August 6th, 2020 for a detailed description of the risk factors affecting our business. In addition any forward-looking statements represents 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 required by law. I would now like to turn the call over to Glenn.

Well, thanks Kathy and good morning everybody and thank you for joining our call this morning. We're excited with the level of execution we have achieved with our therapeutics and our gene therapy programs. We're thrilled to have reached several milestones with Zimura in the past year. First, we reported positive 12-month and 18-month results from our GATHER1 Phase 3 clinical trial of Zimura for the treatment of geographic atrophy, secondary to age-related macular degeneration. We think this is an impressive achievement since we believe GATHER1 is currently the only completed Phase 3 clinical trial showing suppression of GA lesion growth with continuous treatment effect over 18 months. Second, the GATHER1 data was published in a highly respected journal, Ophthalmology, which is the journal of the American Academy of Ophthalmology. And we initiated patient enrollment in GATHER2, our second Phase 3 clinical trial for the treatment of GA secondary to AMD. If the primary endpoint is achieved at month 12, we intend to file for marketing approval of Zimura with the U.S. Food and Drug Administration and the European Medicines Agency. The initiation of patient enrollment in GATHER2 brings us another step closer to potentially delivering a clinically meaningful therapy safely to patients with GA. We also continue to move our other programs forward. We have advanced our two lead gene therapy product candidates, IC-100, which is intended to treat rhodopsin-mediated ADRP and IC-200, which is intended to treat BEST1-related retinal diseases. We expect both product candidates to be on track to enter into clinical trials next year. We have also identified a lead compound for IC-100, our HtrA1 inhibitor program. In June 2020, we strengthened our balance sheet with an underwritten public offering and a concurrent private placement with Vivo Capital and Samsara BioCapital, raising approximately $160 million in gross proceeds. These successful capital raises in addition to our previous follow-on offering in December 2019 that resulted in net proceeds to the company of approximately 42.6 million enable us to further execute on our strategy to develop and deliver retinal treatments through our Zimura, gene therapy and HtrA1 programs, with the potential to create long-term shareholder value. We've also assembled a team of an experienced -- we have also experienced a team of seasoned Board of Directors and leadership, whom we believe could have a major impact on the future treatment of retinal diseases. Over the past several months, we continue to strengthen our team by welcoming three well-known respected veterans in the retinal community to our team. First, Dr. Mark Blumenkranz, who joined our Board of Directors in July. Mark is a biotech industry leader and internationally known vitreoretinal specialist with notable expertise in pharmaceuticals for AMD and ocular gene therapy. Mark has also cofounded multiple biotech and medical technology companies. Dr. Pravin Dugel joined us in April as Chief Strategy and Business Officer and has been a tremendous addition to the team. Pravin is a retinal expert, recognized globally in both the medical community and the biotech pharma ophthalmic industry. And most recently, Dhaval Desai, formerly medical unit head at Novartis EyeCare, joined IVERIC bio as Chief of Staff. Dhaval is well known throughout the retinal community. Our main priority is to aggressively drive patient recruitment and retention in the GATHER2 clinical trial. Meanwhile, we continue to monitor the COVID-19 pandemic closely and engage with our clinical trial sites to support the health and safety of our clinical trial patients. While we're bringing Zimura to patients is our top priority, we continue to focus on potential opportunities, to expand and advance our footprint in AMD, which Pravin will address in a moment. After that, Kourous will review our GATHER1 and GATHER2 clinical trials in our gene therapy pipeline in orphan inherited retinal diseases. Thank you, and I'd like to now turn the call over to Pravin.

Thank you, Glenn. Good morning everyone. I hope that you are all well. As Glenn mentioned, we have accomplished quite a lot over the past year. We're extremely enthusiastic about our mission to bring transformative treatments to patients, with many retinal diseases for which no treatments currently exist. AMD is the most common cause of vision loss in developed countries, especially in people older than 50 years of age. As the worldwide population continues to live longer, we expect the prevalence of AMD is only going to increase with a reported projection of $170 million in 2020 and $288 million in 2040 worldwide. Dry AMD is reported to account for 85% to 90% of all AMD cases. Wet AMD, which accounts for approximately 10% to 15% of all AMD cases, has various anti-VEGF treatment options available to patients. There are no -- there are currently no FDA or EMA-approved treatments for GA, which is the advanced or end stage of AMD. Based on a comprehensive epidemiology study published in 2004 in archives of Ophthalmology, we estimate that they're made -- there are currently 1.5 million people in the United States alone with GA. As the size of our ageing population continues to increase, we believe based on an annual U.S. population growth of approximately 3.25%, this number may grow to approximately 1.8 million by 2030. Our goal at IVERIC bio is to expand our footprint in all of macular degeneration; dry and wet. We intend to do this by evaluating potential clinical trials for Zimura in additional indications and by advancing the development of IC-500, our HtrA1 inhibitor. We believe there's solid scientific evidence to study Zimura in both wet neo-vascular AND, as well as earlier stages of dry AMD. We have already completed 2 exploratory studies of Zimura administered in combination with LUCENTIS in patients with wet AMD. We believe the results are encouraging and consistent in both studies. In the Zimura 2-milligram plus LUCENTIS groups in both studies, 60% of patients gained three lines or more vision as measured by ETDRS letters. We also believe the association between complement activation and earlier stages of dry AMD is well established. Therefore the available science supports the investigation of Zimura in both wet AMD and earlier stages of dry AMD. Our strategy is focused on developing not just one, but multiple complementary assets to establish an AMD franchise. Our excitement for our Zimura Phase III GATHER program carries over to another -- one of our top priorities our HtrA1 program known as IC-500. HtrA1 is a trimeric serine protease that is widely expressed in the retina and the target has a compelling genetic association with AMD. We believe that IC-500 has the potential to be best-in-class HtrA inhibitor due to its binding characteristics and size. We continue to advance the development of IC-500 and plan to submit an IND to the FDA for IC-500 and GA secondary to AMD in the second half of 2021. Taken together, we think Zimura and IC-500 will complement each other very well. We believe at a treatment targeting downstream in the complement cascade such as Zimura should be agnostic to genetic subtypes of AMD. And the inclusion criteria we used in GATHER1 and are using in GATHER2 are not limited by genetic subtype. On the other hand, IC-500 may have a more specific application to the proportion of patients with AMD with over-expression of HtrA1 identified by genetic subtypes who are believed to be at higher risk for the continued development and progression of AMD. We intend to execute a development strategy that will involve both Zimura and IC-500 in a complementary fashion to impact multiple forms and stages of AMD. Turning to business development. We plan to continue our aggressive, but selective efforts as we continue to explore our options to the future development and potential commercialization of Zimura including potential out-license and collaboration opportunities. We expect to make great strides throughout the rest of 2020 and into 2021, as we continue to move our pipeline of therapeutics and gene therapy product candidates forward. We look forward to keeping you updated on our progress in the months to come. Thank you for your time. I will now turn the call over to Kourous.

Thank you, Pravin, and good morning, everyone. We are excited to have the robust Zimura GATHER1 results recently published in the journal Ophthalmology, one of the leading ophthalmology journals in the journal of the American Academy of Ophthalmology. The article entitled, C5 Inhibitor Avacincaptad Pegol for Geographic Atrophy Due to Age-Related Macular Degeneration: A Randomized Pivotal Phase 2/3 Trial, is publicly available online at www.aaojournal.org. We're excited to announce that the previously reported positive Data 1 data will be presented at the American Academy of Ophthalmology Annual Meeting Retina Subspecialty Day on November 13 by Dr. Donald J. D'Amico, Professor and Chairman of Ophthalmology at Weill Cornell Medical College and Ophthalmologist-in-Chief at the New York Presbyterian Hospital. Additionally, the GATHER1 data were recently presented at medical conferences around the world, including at the Virtual Annual Meeting of EURETINA by Dr. Frank Holz, Professor and Chair of the Department of Ophthalmology, University of Bonn; Retina Society by Dr. Carl Regillo, Chief of Retina Service at Wills Eye Hospital; the prestigious meeting of the Club Jules Gonin by Dr. Glenn Jaffe, Robert Machemer, Professor of Ophthalmology and a member of the Vitreoretinal Faculty at Duke University Eye Hospital; and the American Society of Retina Specialists by Dr. Baruch Kuppermann, Chairman of the Department of Ophthalmology at UC Irvine. As previously reported in the GATHER1, clinical trial Zimura met its pre-specified primary efficacy endpoint at 12 months with statistical significance in this international multicenter, randomized, double-masked, sham-controlled Phase 3 clinical trial for GA secondary to AMD. The reduction in the mean rate of GA growth over 12 months was 27.38% with a p-value of 0.0072 for the Zimura 2-milligram group as compared to the corresponding sham-controlled group and 27.81% with a p-value of 0.0051 for the Zimura 4-milligram group as compared to the corresponding sham-controlled group. The data for both groups were statistically significant. These positive 12-month data are further supported by the 18-month results, which we reported in June. Zimura's favorable safety profile was maintained throughout the 18-month trial. As Glenn mentioned earlier, on June 30, we announced that the first patient have been dosed in our GATHER2 clinical trial. GATHER2 is an international randomized, double-masked, sham-controlled, multicenter Phase 3 clinical trial, evaluating the safety and efficacy of Zimura 2-milligram in patients with geographic atrophy secondary to AMD. In total, we are planning to enroll approximately 400 patients in this clinical trial. Patients are randomized 1:1 into two cohorts: the first cohort receiving monthly administration of Zimura 2-milligram for 12 months, and the second cohort receiving monthly administrations of sham. It trained to be pre-specified primary efficacy endpoint is the main rate of change in GA growth over 12 months, measured by fundus autofluorescence at three time points: baseline, month six and month 12 similar to the GATHER1 clinical trial. The primary efficacy endpoint is met at month 12. We plan to file for marketing approval of Zimura for the treatment of GA, secondary to AMD with the FDA and EMA. At month 12, we plan to re-randomize patients and the Zimura 2-milligram arm to receive either monthly or every other month administrations of Zimura 2-milligram. The final safety evaluation will be performed at month 24 for our patients. We believe many principal investigators are enthusiastic about enrolling patients with GATHER2 clinical trial, leveraging the quality of the GATHER1 results to maximize patient recruitment and retention for GATHER2 trial. Further, we believe that the early onset and continuous treatment effect demonstrated in GATHER1 trial will be a key motivator for retention in the GATHER2 trial. We thank all our principal investigators and their staff for their enthusiasm and support for the GATHER2 clinical trial. As Pravin mentioned, we are excited about our IC-500 program. Genetic association studies, in-vitro studies and histologic studies of eye with MD have indicated the potential role of HtrA1 in AMD. I see 500's potential to block both intracellular and extracellular Htra1 activity may provide additional advantages as a potential treatment option for GA and potentially other stages of AMD. Our preclinical IND-enabling activities for IC-500 are currently ongoing. Having both Zimura and IC-500 in our pipeline for the treatment of GA secondary to AMD positions IVERIC bio potentially provide treatment for patients with various parts on stages of age-related macular degeneration the leading cause of vision loss in elderly. Regarding our gene therapy programs, we continue with our IND-enabling activities for IC-100 and are planning to file an IND with the FDA in early 2021 and initiate a Phase 1/2 clinical trial in the first half of 2021. We also continue with IND-enabling activities and natural history studies for IC-200 and are planning to file an IND with the FDA in the middle of 2021 and initiate a Phase ½ clinical trial in the second half of 2021. Our minigene programs continue to move forward. We are optimizing the minigene constructs for our miniCEP290 program and plan to select the lead construct in the fourth quarter of 2020 or early 2021. I would like to thank you for your time and we'll now turn the call over to Dave. Dave?

Thank you, Kourous, and good morning, everyone. I'd like to highlight a few items from our press release of this morning and also update our year-end cash guidance and our expected cash runway. For the quarter our net loss totaled $25.5 million or $0.27 per share, compared to a net loss of $14.4 million or $0.35 per share for Q3 2019. This increase in net loss was driven primarily by an increase in R&D expenses associated with our Zimura clinical programs, our pre-clinical gene therapy programs and the progression of our IC-500 program. During the quarter, we continued to start up in recruitment activities for GATHER2 and also recognized a $6 million milestone payable to Archemix. Year-to-date our net loss totaled $59.1 million or $0.87 per share, compared to a net loss of $41.4 million or $1 per share for the same period in 2019, again primarily due to an increase in R&D expenses. Turning to our expected year-end cash balance and cash runway, we now expect our year-end cash balance to range between $210 million and $215 million. We estimate that our cash will be sufficient to fund our capital expenditures and operating expenses as currently planned through at least mid-2024. Excluding any potential approval or sales milestones payable to Archemix or any commercialization expenses for Zimura. These estimates are based on our current business plan, which includes a continuation of our ongoing clinical development programs for Zimura, the progression of our gene therapy programs into the clinic, any advancement of our IC-500 development program. Our estimates assume that we will enroll approximately 400 patients in GATHER2. These estimates do not reflect any additional expenditures related to potentially studying Zimura in other indications or resulting from a potential in-licensing or acquisition of additional product candidates or technologies or any other associated development that the company may pursue. I'll now turn the call back over to Glenn. Thank you for your time.

Well, thanks David and thank you everyone for the time this morning and for your continued support. I'd now like to turn the call over to the operator so that we can open up the line for questions. Operator?

Thank you. [Operator Instructions] We can now take our first question from Tiago Fauth from Credit Suisse. Please go ahead.

Hey, thanks so much for taking the question, and congrats on the progress. I just have a couple. My first one is related to any regulatory interactions that you might have. Should we expect any updates from formal regulatory interactions before the GATHER2 12-month results by any chance? And another question unrelated to that but for IC-100 with an IND kind of coming fairly shortly, I'm wondering if you could just perhaps talk about what could be the expected data flow or any early insights on the trial design for that program? And how can we kind of follow the progression there? Thank you.

Well thank you Tiago for the question. And as to the regulatory interaction, I think we have put in our disclosures that we've had a number of informal conversations with the regulators that we are comfortable that there is a path forward with GATHER2. As to whether or not there'll be other interactions more to come on that, but right now we're comfortable with the progress on our clinical program for Zimura. On IC-500, I'll ask both Kourous and maybe Pravin to talk a little bit about that program. As you heard from the script, we're very excited about that early days and looking forward to a possible IND next year. Kourous?

I think Tiago if I heard you correctly the question was regarding IC-100. Is that correct?

Yes, that's correct.

Yes. So regarding the IC-100, it is for the rhodopsin-mediated autosomal-dominant retinitis pigmentosa, which is an orphan indication. The design is potentially going to be very similar to other gene therapy trials for orphan indications where you look at the dose escalation at different dose levels. And obviously, it's an orphan indication, so it's going to be a smaller size clinical trial. And then when we look at to see both a slowdown of progression or potential improvement.

Okay. Thank you very much.

Next question comes from Stacy Ku from Cowen and Company. Please go.

Good morning. Thanks for taking my question. I've just two. So a point of clarification. Can you remind us of your European approval strategy or discuss your conversations with the EMA? Should we be expecting relatively close timing in terms of potential approval for Zimura in both the U.S. and ex U.S.? And then a question on enrollment. Given the initiation of enrollment in late June, we see on clinical trials an update showing a primary position date of June 2022. So wondering, if we can interpret this as the base case enrollment to be complete in roughly one year. And do you guys have any plans to disclose completion of enrollment? Thank you.

Well thanks, Stacy. First on the EU, I think as we have said in the past, our footprint is largely U.S.-based although we are doing sites in Europe for GATHER2, we've also done this for GATHER1. So at the appropriate time, we will potentially look for someone to help us with that European regulatory strategy. I think we're checking all the boxes in our trials to be prepared for that. As for the timing, I think that's something that we'll talk about as we get a little bit closer to the end. Our primary focus has been to talk about GATHER2 in our U.S. strategy here. But as I did mention in our call, the strategy is twofold not only to seek approval here but to seek approval in Europe as well. As for the enrollment timing, I'm going to ask Pravin to address that question for you.

Thank you for your question, Stacy. Our enrollment is going very well. We're on target. We've prepared ourselves meticulously for the potential of any kind of COVID-19 resurgence during the wintertime. And we put together a plan to maximize patient safety while maintaining the momentum of our re-treatment and retention. To give you an example a few of these of the procedures that we're putting in place. We're providing private transportation for our patients. We're providing these e-kits as well as minimizing the amount of time these patients spend, during the study with us. We've been in very close communication with our investigators, and our network, and study coordinators. And have direct feedback on the COVID situation at each of these sites. We also have an increasing number of participating sites and countries, to mitigate the impact for any kind of local resurgence And we're certainly very much on, the lookout constantly for any kind of change in the COVID situation. And for this time I want to take the opportunity to thank the investigators, and their staff working for very closely with us. I also want to let you know of course that we have an extremely experienced clinical staff, that's led by Keith Westby Evelyn Harrison, as low as our CMO, Kourous Rezaei. So we're very confident, that we're taking a strategic path given the COVID situation. It is as efficient as possible for both, recruitment as well as retention.

And if I could ask a follow-up on, that if you have plans to disclose completion of enrollment?

Stacy, not at this point, I know in clintrials.gov there's always a date there. But I think as we progress we'll consider updating on, the actual progress. But as of this current time, we're not giving a specific timeline for completion. I think what is important is the, discussion in this call, the discussion on the questions that recruitment and retention remains the highest priority of a company. And I think as Pravin just said, we have a very experienced team working on this to do this as quickly and efficiently as possible. So as time goes on, we'll continue to update, but no specific timing to disclose at this point.

All right. Thank you so much. And good luck for the progress.

Thank you. Thank you, Stacy.

There are no further questions at this time. I would now like to turn the call back to the host, for any additional or closing remarks.

Operator, thank you. And thank you for hosting today. And as I always say, I appreciate everybody listening in to our call. We're focused on execution and bringing these programs, forward for patients. Thank you. And I appreciate everybody listening today. Bye-bye.

Thank you. That concludes today's conference. Thank you for your participation. Ladies and gentlemen, you may now disconnect.