ISEE (2020 - Q2)

Good day and welcome to the IVERIC bio Second 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 is 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, operations and financial position and on the practices of retinal provision and the conduct of clinical trials; our expectations to use GATHER1, our previously announced clinical trials of Zimura for the treatment of geographic atrophy as a Phase 3 clinical trial; our development and regulatory strategy for Zimura, and our other product candidates, including our expectations for a second Phase 3 clinical trial GATHER2 evaluating Zimura for the treatment of geographic atrophy; and our expectations Zimura Phase 2b treating trial evaluating Zimura for the treatment of autosomal recessive Stargardt Disease, our hypothesis regarding complement and the Htra1 inhibition and the mechanism of action for the treatment of geographic atrophy 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 activity and regulatory information; the potential utility and development potential of our product candidates; the size of the potential market for indications our product candidates are intended to treat; and the potential of our business development strategy. These statements constitute forward-looking statements for the purpose 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 statement, including risks relating to the future progression of the COVID-19 pandemic and its impact on our research and development programs, operations and financial position; initiation and the progress of research and development programs and clinical trials; availability of data from these programs; reliance on contact development and manufacturing organizations, 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 8-K filed on June 17, 2020, for a detailed description of the risk factors affecting our business. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our view 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, except as required by law. I would now turn the call over to Glenn.

Thanks Kathy. And good morning everyone we appreciate and thank you for joining our call this morning. First, I hope you and your families are safe and healthy as we continue to navigate through these very challenging times. Here at IVERIC we are very pleased with the level of execution we have achieved during the second quarter. We are thrilled to have reached another major milestone with Zimura. In June we announced positive 18 months results from GATHER1. Our first Phase 3 clinical trials for Zimura a novel complement C5 inhibitor for the treatment of geographic atrophy or GA, secondary to age-related macular degeneration or AMD. The GATHER acronym for Zimura Phase 3 clinical trials represents GA’s therapy. The 18-month results from GATHER1 indicated continuous Zimura treatment benefits with a favorable safety profile in patients, the GA secondary to AMD. We think this is an impressive achievement since we believe GATHER1 is currently the only Phase 3 clinical trial showing suppression of GA growth with continuous treatment for 18 months. Shortly following the positive results from GATHER1, we initiated patient enrollment in GATHER2 to our second Phase 3 clinical trial for Zimura for the treatment of GA, secondary to AMD. Our main priority is to aggressively drive patient recruitment and retention in the GATHER2 clinical trial. The primary endpoint is achieved at month 12 we intend to file for approval of Zimura, with the US Food and Drug Administration and the European Medicines Agency. Initiation of patient enrollment GATHER2 brings us another step closer to potentially delivering clinical meaningful therapy safely to patients which currently in treatment. We continue to work closely with the FDA and we are pleased to receive FDA Fast Track designation for Zimura for the treatment of GA secondary to AMD. In addition to the complement systems potential role in GA and Stargardt's disease, we believe, based on scientific data, that Zimura may have a potentially impactful role in treating intermediate AMD as well as what AMD. We believe there was strong scientific rationale to support the development of Zimura in multiple form of AMD early and advanced, dry in vet. We believe Htra1 or high temperature requirement A serine peptidase protein 1 could be another important target in the treatment of AMD. We call this program IC-500 Htra1 is a small molecule inhibitor that is promising compound in our pipeline. Htra1 upregulation has been implicated as a strong risk factor in the development of dry AMD. We are particularly encouraged by IC-500’s ability to engage to target both extra interest so certainly in early preclinical work. Based on current timelines, we are planning to submit an IND to the US FDA IC-500 and GA secondary to AMD in 2021. Bringing Zimura education is our top priority. We continue to focus on our gene therapy program in orphan inherited retinal diseases. Kourous will review the details of our gene therapy pipeline in a few moments. Following the positive GATHER1 18-month data, we strengthened our balance sheet with an underwritten public offering and concurrent private placement with [indiscernible] capital, and [indiscernible] bio capital raising approximately $160 million in gross proceeds. Dave will cover our cash flow runway later in this call. We believe this fundraising enables us to further execute on our strategy to develop and deliver retinal treatments through Zimura our gene therapy programs, and IC-500 with potential to create long-term shareholder value. At the beginning of the second quarter we welcome Dr. Pravin Dugel who many of you know to I verify [ph]. Pravin is a globally recognized retinal specialist who has an extensive network and long-standing relationships with the bio and pharma founding industry. As our Executive Vice President and Chief Strategy and Business Officer, Pravin's experience and network would be instrumental in helping us build alliances with potential future collaborators, investors and other stakeholders. Pravin is helping to lead the company’s strategy as we advance our portfolio of therapeutics and gene therapy R&D programs targeting multiple retinal diseases. In July, we had the privilege of announcing the addition of Dr. Mark Blumenkranz, to our Board of Directors. Mark is a biotech industry leader and internationally known vitro retinal specialists with a notable expertise in pharmaceuticals to age related macular degeneration, and ocular gene therapy. Mark has co-founded multiple biotech and medical technology companies. His experience and expertise in leading and building biotech companies further strengthens our Board. I'd now like to turn the call over the Pravin.

Good morning, everyone. I hope you're all well. Thank you, Glenn for the kind introduction. This is an exciting time at the company. And it is my great pleasure to work closely with Glenn, David, Kourous and all my new colleagues. We're very excited by these 18-month GATHER1 results. This is a significant milestone for Zimura and potentially a significant advancement for patients with GA secondary to AMD. We believe the 18-month data that we reported this past June further validates our 12 months results regarding Zimura’s continuous positive treatment effects with a favorable safety profile in GA secondary to AMD and highlights the potential role of compliments C5 inhibition in this disease. In the GATHER1 clinical trials in Zimura net, it is pre-specified primary efficacy endpoints at 12 months and reached statistical significance in the international multicenter, randomized double-masked sham-controlled Phase 3 clinical trial in GA, secondary to AMD. The reduction in the mean rate of GA growth over 12 months was 27.38% with the P value of 0.0072 for the Zimura 2 milligram group as compared to the corresponding sham-controlled dose, and 27.81% with a P value of 0.0051 with Zimura 4 milligram group as compared to the corresponding sham-controlled dose. These data for both dose groups were statistically significant. These positive 12 months of data are further supported by the 18-month results, which we reported in June. Over 18 months, the reduction in the mean rate of GA growth was 28.11% for the Zimura 2 milligram group as compared to its corresponding sham group, and 29.97% for the Zimura 4 milligram group as compared to its corresponding sham-controlled group. The primary efficacy endpoint, which pre-specified a 12 months using all of the power to detect a statistically significant difference. Therefore, the P values at the 12 months statistical analyses are descriptive in nature. The descriptive P value for the treatment effects at month 12 were a P value of 0.0014 for the Zimura 2 milligram group, and a P value of 0.0021 for the Zimura 4 milligram group. We believe having 18 months positive data with continuous treatment is a key differentiating factor for us, when compared to other product candidates being developed for GA. Another key differentiating factor for this trial is that the treatment effect was observed in the very first measurement at six months with an increasing absolute difference between the treated group and the sham at each subsequent measurement time point. In other words, if these results are replicated in GATHER2 trial, we believe a doctor would be able to tell his or her patients that this drug has shown an effect as early as six months and then may have an increasing effect with every subsequent injection thereafter. We do not believe this impactful efficacy profile has been observed in any other GA clinical trial to date. Zimura’s favorable safety profile, another potential differentiating factor was maintained throughout the 18-month trial with no investigator reported Zimura related adverse events, no cases of [indiscernible] and no Zimura related information. The reported incidents of CMB [ph] in the untreated fellow eye was the 11 patients 3.8%, and in the study eye was 3 patients, 2.7% in the sham-controlled group; two patients, 7.7% in the Zimura 1 milligram group; eight patients, 11.9% in the Zimura 2 milligram group; and 13 patients, 15.7% in the Zimura 4 milligram group. Note, we believe these rates of CMB were lower than what has been published for Q3 in addition, despite the fact that there were more Zimura injections administered over a longer period of time in a patient population with faster progressing disease. This is particular case, when you look at the ratios of the incidents in the treated arms versus sham. The most frequent, we reported ocular adverse event in GATHER1, and we related to the injection procedure and not the drug. These GATHER1 reports are from the pre COVID era. Making the trial, what we believe is the only pure pre COVID positive Phase 3 clinical trial in GA. We believe there is a new environment for clinical trial execution and that the robust data from GATHER1 may have helped drive recruitment and retention of patients in GATHER2 and any future trials we may conduct for Zimura. In the challenging COVID-19 pandemic era, we believe that investigators will be more enthusiastic and comfortable recruiting and retaining patients in a clinical trial with a drug that already has high quality, positive Phase 3 data. We recognize the challenges that retinal physicians face with their practices and conducting clinical trials in the COVID era. And we're working closely to support collaborative physicians. Kourous will discuss how we plan to leverage the quality of the GATHER1 results to maximize patient recruitment and retention for GATHER2 Phase 3 clinical trial. Turning to our business development. We plan to continue our aggressive but selective efforts as we continue to explore our options for future development and potential commercialization of Zimura, including potential outright use and collaboration opportunities. 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. Presented at the Association for Research and Vision and Ophthalmology, ARVO annual meeting [indiscernible]. [Indiscernible] senior scientist and Director of the Molecular Ophthalmology Laboratories at the Retina Foundation of the Southwest and also presented at the American Society of Retinal Specialists ASRS annual meeting run two weeks ago, by Dr. Baruch Kuppermann, Chairman of the Department of Ophthalmology at the University of California, Irvine. In the coming months, we are planning for our data to be presented by key opinion leaders at the major retina meeting in the U.S. and around the world. The positive GATHER1 clinical trial data has ignited a significant enthusiasm in our investigators to participate and enroll patients in the GATHER2 clinical trial. Further, we believe that the early onset and continuous treatment effect demonstrating the GATHER1 clinical trial will be a key motivator for retention and the GATHER2 trial. Our experienced clinical trial team has worked tirelessly in the past few months to support the smooth and expeditious initiation of the GATHER2 clinical trial. Some of these efforts include posting multiple virtual websites with investigators and study coordinators in the US and around the world. We plan communications with the clinical trials coordinators to assess and support their preparedness for COVID-19 and minimizing any potential disruption. Making arrangements for patients to remotely perform certain time related tasks to minimize the time spent by the patient at the clinical trial site, and to reduce your exposure risk and ensure a safe environment for our patients. We thank all our principal investigators and the staff for their enthusiasm and support for the GATHER2 clinical trial. Now, I would like to provide some details regarding the design of the GATHER2 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 edge related macular degeneration. We are planning to enroll approximately 400 patients in this clinical trial. Patients will be 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. The pre-specified primary efficacy endpoints with the new rate of change in geographic atrophy growth over 12 months, measured by fundus autofluorescence at three time points: baseline, month 6 and month 12 very similar to the GATHER1 clinical trial. If the primary efficacy endpoint is met at month 12, we are planning to file for marketing approval of Zimura for the treatment of geographic atrophy secondary to age related macular degeneration with the FDA and EMA. Among 12, we plan to re-randomize patients in 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 of our patients. Turning now to Stargardt’s disease. We currently have an ongoing Phase 2b screening clinical trial assessing the safety and efficacy of Zimura in patients with autism or recessive Stargardt’s disease. Initially, we enrolled 95 patients in this trial. We have reopened enrollment in this trial to add approximately 25 patients with the goal of enrollment a total of 120 patients as was initially intended in the protocol for this trial. We remain [indiscernible] for this trial and plan to perform data analysis when all the patients have reached the 1.18 time points. Regarding our gene therapy programs, we continue with our IND enabling activities and natural history studies for IC-100, our product candidate for adoption mediated autosomal dominant retinitis pigmentosa and are planning to initiate a Phase 1/2 clinical trial for the first half of 2021. We also continue with the IND enabling activity and natural history studies for IC-200, our product candidate for BEST1 related retinal diseases, and are planning to initiate the Phase 1/2 clinical trial next year in 2021. Our minigene programs continue to move forward. We're currently optimizing the minigene construct for our miniCEP290 program and plan to select the construct later this year. Thank you for your time and please stay safe. I will now turn the call over to Dave. Dave?

Thank you, Kourous, and good morning, everyone. I'd like to highlight a few items from 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 $18.6 million or $0.32 per share, compared to a net loss of $14.4 million or $0.35 per share for Q2 2019. This increase in net loss is driven primarily by an increase in R&D expenses, offset by a favorable settlement of a state income tax audit. As you can see, our net loss totaled $33.7 million or $0.61 per share compared to a net loss of $26.9 million or $0.65 per share for the same period in 2019. Again due to an increase in R&D expenses offset by a favorable settlement of state tax audit. Turning to our expected year-end cash balance and cash runway. We reached approximately a $150 million in our June 2020 public offering and concurrent private placement. We now expect our year-end cast balance to range between $215 million and $220 million. We estimate that our cash will be sufficient to fund our capital expenditures and operating expenses as currently planned through at least in 2024, excluding any potential approval or sales milestones payable to the Archemix Corporation or any potential commercialization expenses for Zimura. These estimates are based on our current business plan which includes the continuation of our clinical development programs for Zimura, the progression of IC-100 and 200 gene therapy programs used in clinic and the advancement of our IC-500 development program. Our estimated [indiscernible] approximately 300 [ph] patients for the GATHER2 trial. In fact, if circumstances change, we adjust our guidance accordingly. Of course these estimates do not reflect any additional expenditures resulting from the potential in-licensing or acquisitions of additional product candidates or technologies or any associate development that the company may pursue. I’ll now turn the call back over to Glenn. Thank you for your time.

Well thanks, Dave. And appreciate that. So just to recap, the second quarter despite these very challenging times was a good quarter for IVERIC bio. There’s a number of key takeaways. We completed our 18 months results for GATHER1 and as you see, we discussed today, will continue to reflect in good safety profile. Second, we raised a $160 million in gross proceeds, further strengthening our balance sheet and heading to our cash runway. And third, although, it was a difficult decision back in March, when we decided to pause the GATHER2 trial, we have now begun the trial and are recruiting patients. So, good quarter for us. So, I’d like to thank all of you for listening today to our call, and for your continued support. And now I’ll turn the call over to the operator, so that we can open up the line for any questions.

Thank you. [Operator Instructions] We will now take our first question from Stacy Ku of Cowen. Please go ahead.

Good morning, thank you for taking my questions and congratulations on the progress. So first question, given the time spent for sites revise the experience of the recent trial initiation. How should we be thinking about the pace of enrollment? Would you be willing to give us some guidance on timing? And my second question is upon something that was previously mentioned during the prepared remarks. So curious if you could elaborate what you were thinking in terms of potential exUS partnerships and would you update conversations? Thanks.

Yeah, thank you Stacey. It is Glenn and thanks for the questions. First on the timing for GATHER2. Well I mentioned a couple of things. It is early days. It is also very competitive environment. I think you’ve seen our execution in the past. We’re dealing with unique situation here with COVID. And I think as we’ve updated you through the second quarter, we’ve kept a very active and continuous dialog with the investigators. So at the current time, we’re not going to provide any guidance as to when we finish the trial. But we will continue to move at a pace that’s as quick as we can. The key to that success will be the number of sites acquired new sites, and obviously the patient enrollment. So I am going to not provide you detailed guidance at this point. I believe, in fact that we got a pretty experience to doing this. As for the second question as it relates to collaborations. I think Dave in his prepared statements did talk about that, again priority number of the days we’ve put in retention of patients in GATHER2. But we are going to continue to secure our options for potential commercialization of Zimura including potential outline. As you know we do not have operations of disease, even with the successful capital is a small company to partnership, but at the right time will be an important part of our efforts to commercialize Zimura. Thanks for the questions Stacy.

And we will now take our next question from David Nierengarten of Wedbush. Please go ahead. Please go ahead, David. You may be on mute.

I'm sorry, I was on mute. Apologies. A couple of questions from me. First off the --

David it is Glenn. I'm not sure we can hear you. We did hear you on your introduction. Can you repeat the questions?

It appears Dave has actually just disconnected. As there are no further questions, I'd like to hand the call back to you.

Operator, thank you for your help this morning. And thank you everybody for listening and look forward to speaking to you during the third quarter. Thanks. Bye, bye.

Thank you. That now concludes the call. Thank you all for your participation. You may now disconnect.