This conference call transcript was computer generated and almost certianly contains errors. This transcript is provided for information purposes only.EarningsCall, LLC makes no representation about the accuracy of the aforementioned transcript, and you are cautioned not to place undue reliance on the information provided by the transcript.
spk07: Good morning, ladies and gentlemen, and welcome to Vero Incorporated's investor conference call. All participants will be in a listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After this morning's discussion, there will be an opportunity to ask questions. Please note that this event is being recorded. I would now like to turn the conference over to Mr. Sam Fish, Barrow Incorporated's Executive Director, Investor Relations and Corporate Communications. Please go ahead.
spk03: Good morning. The statements made on this conference call may be forward-looking statements. Forward-looking statements may include, but are not necessarily limited to, statements of the company's plans, objectives, expectations, or intentions regarding its business, operations, finances, and development and product portfolio. Such forward-looking statements are subject to known and unknown risks and uncertainties, and our actual results may differ significantly from those projected, suggested, or included in any forward-looking statements. Risks that may cause actual results or development to differ materially are contained in our 10-Q and our 10-K SEC filings, as well as in our press releases from time to time. I would now like to turn the conference call over to Dr. Mitchell Steiner, Vero, Inc.' 's Chairman, CEO, and President.
spk04: Good morning. With me on this morning's call are Dr. Gary Barnett, the Chief Scientific Officer, Michelle Greco, the CFO and CAO, Michael Purvis, EVP, General Counsel in Corporate Strategy, and Sam Fish, Executive Director of Investor Relations and Corporate Communications. Thank you for joining our call. Vera is a biopharmaceutical company focused on developing novel medicines for COVID-19 and other viral and ARDS-related diseases and for the management of breast and prostate cancers. The company has a commercial sexual health division called UREV, which includes two FDA-approved products and Tadfi, a new treatment for benign prostatic hyperplasia, and the FC2 female condom, internal condom, for the dual protection against unplanned pregnancy and the transmission of sexually transmitted infections. The revenue from the sexual health division is being used to largely fund the clinical development of our late-stage drug candidate assets, which aim to address multibillion-dollar premium market opportunities. This morning, we will provide an update on the COVID-19 Subicibulin clinical program and franchise, the clinical development of our oncology drug pipeline, and the commercialization of our products. We will also provide financial highlights for our second quarter fiscal year 2022. While there have been recent emergency use authorizations for antiviral drugs, molnupiravir from Merck and Paxilovir from Pfizer, for the treatment of unhospitalized patients with COVID-19, with less than five days of symptoms, who are at relatively lower risk of dying. Sibizabulin, in contrast, is being developed for hospitalized moderate to severe COVID-19 patients who are at high risk of acute respiratory distress syndrome and death, patients for whom there is currently no clearly effective treatment, and the population which molnupiravir, the antiviral agent for Merck, did not demonstrate efficacy. Subisibulin disrupts intracellular transport of coronaviruses along the microtubules. This is a highly conserved biologic process that's required by all variants of COVID-19, including Omicron, to cause infection. We conducted a Phase III COVID-19 clinical trial, which was a double-blind, multicenter, multinational, randomized 2-to-1 placebo-controlled study evaluating daily oral 9-milligram dose of subisibulin for up to 21 days versus placebo, in approximately 210 hospitalized moderate to severe COVID-19 patients who had high risk for ARDS and death. Both the placebo and subisobulin treated groups were allowed to receive standard of care, which could include dexamethasone, remdesivir, anti-IL-6 receptor antibodies, and JAK inhibitors. Moderate to severe COVID-19 symptoms in this study means patients that were hospitalized and required supplemental oxygen, forced oxygen, or mechanical ventilation. Furthermore, one of the inclusion criteria is that patients must have a peripheral capillary oxygen saturation of less than or equal to 94% on room air. This is a very sick patient population and high risk for ARDS and death. The prespecified primary efficacy endpoint is the proportion of patients who die on study up to day 60, not up to day 29 like other studies reported in literature. Our day 60 endpoint allowed us to capture a more accurate number of deaths caused by COVID-19 infection. Secondary endpoints included the proportion of patients without respiratory failure, days in the ICU, WHO ordinal scale for clinical improvement change from baseline, days of mechanical ventilation, days in the hospital, and viral load. The study was conducted in the United States, Brazil, Argentina, Mexico, Colombia, and Bulgaria, and COVID-19 infections in the study included the Delta and Omicron variants. In January of 2022, the FDA granted fast-track designation to the Phase III COVID-19 registration program. Fast-track designation aims to expedite the development and review of new drugs that are intended to treat serious or life-threatening conditions and demonstrate the potential to fill unmet medical needs. Filling an unmet medical need is defined as providing a therapy with nonexistence of providing a therapy which may be potentially better than an available therapy. Thus, having fast track is a distinction that underscores the urgent need for new, novel, and effective therapies to be used alongside with vaccines to combat this COVID-19 pandemic. On April 8, 2022, the Independent Data Monitoring Committee conducted a planned interim analysis in the first 150 subjects randomized in the Phase III COVID-19 study After reviewing the unblinded data, the Independent Data Safety Monitoring Committee unanimously recommended that the Phase III study be halted early due to overwhelming efficacy. They also remarked that no safety concerns were identified. The pre-specified primary endpoint was death at or before Day 60. Subisibulin treatment resulted in a clinically and statistically meaningful 55.2% relative reduction in death P-value equals 0.0043 in the intent-to-treat population. Placebo group, N equals 52, had a 45% mortality rate compared to the 20% mortality rate in the subisobulin-treated group, N equals 98. At day 29, the death rate in the placebo group in our study was 35%, which is the same death rate as reported in the Lancet publication in May 2020 to 2021 for the placebo group of a similar hospitalized patient group consisting of 2,094 patients for the tocilizumab recovery study. Furthermore, one could expect the death rate in the placebo group at day 60 to be higher than day 29 death rate. The placebo group at day 60 death rate of 45% in our study underscores how sick these patients really were. Patients in the Phase III COVID-19 study were allowed to receive standard of care, which was balanced between the subisobulin and placebo groups, with approximately 80% receiving dexamethasone and about 30% receiving remdesivir. Thus, high death rates in the placebo group demonstrate the inadequacy of the current standard of care. We plan to publish the secondary efficacy endpoints in a peer-reviewed medical journal as soon as practical. Subvisivulin treatment was well tolerated in this patient population with no clinically relevant safety observations in the subvisivulin treated group compared to placebo. We had a pre-emergency use authorization meeting with FDA on May 10th to discuss the next steps, including the submission of an emergency use authorization application. The outcome of this meeting is as follows. FDA agreed. that no additional efficacy studies are required to support an EUA or a full NDA. FDA agreed that no additional safety data are required to support an EUA and collection of safety data under the EUA will satisfy the safety requirement for a full NDA. Therefore, FDA agreed that the request for EUA is supported by efficacy and safety data from our positive phase three COVID-19 study and hospitalized moderate to severe COVID-19 patients who are at high risk for ARDS, and no additional clinical studies are required to support an NDA submission. We plan to submit the EUA application in this quarter. Furthermore, we have scaled up manufacturing processes to produce commercial drug supply to address the anticipated drug needs following a potential FDA authorization in the U.S. and a potential subsequent authorization in other countries and territories. We're also making progress building out our own U.S. commercial infectious disease franchise. We are actively seeking an advanced purchase agreement with the U.S. government. In fact, we're meeting with government officials. Usually, an advanced purchase agreement is awarded after emergency use authorization is received. We're also moving forward to submit regulatory applications to the MHRA in Britain and to the COVID-19 European Medicines Agency Pandemic Task Force for the European Union as well as other countries. We're in discussions with numerous potential distribution partners. COVID-19 global cases, hospitalizations, and deaths are on the rise again. We have reached a sad milestone. Over 1 million Americans have died from COVID-19. We must reduce the risk of death from COVID-19. New variants of COVID-19 are brewing. COVID-19 surges will happen. Vaccines are not enough. And some of the antibody drugs are not effective against Omicron variant BA1 or BA2. And as I already pointed out, antivirals, Paxilovir, and Monopiravir target the pre-hospital general population who've experienced less than five days of symptoms, a narrow window of opportunity. It's clear that an effective and safe oral therapeutic that prevents deaths in hospitalized patients with moderate to severe COVID-19 infection who are at high risk for ARDS and death is desperately needed. We strongly believe that sabizabulin, with its dual antiviral and anti-inflammatory properties, can be that greatly needed oral therapy for the hospitalized moderate to severe COVID-19 patients as a new standard of care. We will continue to update you on the regulatory progress towards EUA in the U.S. and other countries, manufacturing, additional clinical data release and publications, BARDA and other government agency discussions, U.S. and global distribution plans, and partnership discussions. Furthermore, Given these exceptional clinical efficacy and safety results, we plan to initiate new clinical studies against other viruses that cause ARDS, including influenza A virus, which causes up to 52,000 deaths and 710,000 hospitalizations each year, and respiratory syncytial virus, also known as RSV, which causes 14,000 deaths and 177,000 hospitalizations each year in the United States. These new clinical studies will allow us to expand sabizabulin to other large, serious infectious disease indications. I will briefly discuss the progress of our oncology drug portfolio focused on breast and prostate cancers. For patients with greater than or equal to 40% AR expression, we are actively enrolling a global phase three R-test registration clinical study in approximately 210 patients to evaluate Inovasar monotherapy for the third-line treatment of AR-positive, ER-positive, HER2-negative metastatic breast cancer. In January of 2022, FDA granted fast-track designation to our Phase III R-test registration program. We're also moving in Novosong therapy earlier in the treatment sequence into the second-line treatment setting for AR-positive, ER-positive, HER2-negative metastatic breast cancer. We are actively enrolling in the Phase III multicenter open-label randomized one-to-one active control registration program enable a two-clinical study to evaluate the efficacy and safety of anobisarm and abemiciclib combination therapy versus an alternative estrogen-blocking agent in subjects with AR-positive, ER-positive, HER2-negative metastatic breast cancer who have failed first-line therapy with palpociclib, a CDK4-6 inhibitor, plus an estrogen-blocking agent who have greater than or equal to 40% AR expression in their breast cancer tissue. We plan to enroll approximately 186 subjects in this Phase III clinical study. We recently announced that we've entered into a clinical trial collaboration and supply agreement with Lilly for the Enabler 2 clinical, Enabler 2 Phase 3 clinical study. And under the terms of the non-exclusive clinical trial collaboration and supply agreement, Vera is responsible for conducting the clinical trial, while Lilly will supply a bemacite cyclib for the study. Vera maintains full exclusive global rights to Inova's arm. We've also made great progress in our prostate cancer programs. Our first indication is evaluating subisobulin for the third-line treatment of metastatic castration-resistant prostate cancer in the VERACITY Phase III study. We will be presenting final clinical data from the positive Phase Ib2 study of subisobulin in 80 men with metastatic castration-resistant prostate cancer who have progressed on at least one novel antireceptive-targeted agent at the ASCO conference being held in June of 2022 in Chicago, Illinois. We are actively enrolling in open-label, randomized 2-to-1 multicenter Phase III veracity clinical study evaluating subisobulin 32 milligrams versus an alternative antireceptor-targeted agent for the treatment of chemotherapy-naive men with metastatic castrate-resistant prostate cancer who have had tumor progression after previously receiving at least one antireceptor-targeted agent. The primary endpoint is radiographic progression-free survival. Enrollment for the Phase III veracity clinical study is on track, and we expect to enroll approximately 245 patients from 45 clinical centers in the U.S. Our second clinical study in prostate cancer is evaluating Vero100, a GnRH antagonist three-month depo formulation, in a Phase II dose-vinding clinical study for the treatment of hormone-sensitive advanced prostate cancer. We're conducting the Phase 2 dose-finding clinical study of VIR-100, androgen deprivation therapy in 45 men with hormone-sensitive advanced prostate cancer. Although this study is ongoing, the preliminary clinical data are promising. The Phase 3 registration clinical study design has already been agreed upon with FDA. It will be a single-arm study, which will involve approximately 100 men. Maintenance of castrate blood concentrations of testosterone is the primary endpoint. And after the Phase 2 dose-finding study is completed, we will initiate the Phase 3 clinical study. The Bureau has a commercial sexual health division called UREV, which includes two FDA-approved products, the FC2 for the dual protection against unplanned pregnancy and transmission of sexual transmitted infections, and the recently FDA-approved Intafi, which is Tadalafil finasteride capsule, and new treatment for benign prostatic hyperplasia. We have built the infrastructure to allow for broad market access to FC2 across the U.S. As a result, FC2 is now available through multiple sales channels. In particular, we have partnered with fast-growing, highly reputable telemedicine platform companies to bring our FC2 product to patients in a cost-effective, highly convenient manner. A strategy to continue to drive robust FC2 sales is not only to seek additional telemedicine and internet pharmacy service partners, but also to create our own direct-to-patient telemedicine and internet pharmacy services platform. This telemedicine platform is now up and running and is expected to be a new source of revenue. We've also developed Entadfi, a new treatment for BPH. The most common side effects of currently prescribed BPH medicines are sexual adverse events, including impotence. Entadfi has been shown to be more effective for the treatment of BPH than Finasteride alone, without causing impotence. Intafi was approved by FDA in December of 2021. The plan is to officially launch Intafi next quarter. We are waiting for the FDA to sign off on the manufacturing release criteria for the Intafi commercial product. Intafi is expected to be marketed and distributed by a third-party direct-to-patient telemedicine and internet pharmacy services platform partnership. We have also partnered with GoodRx. a U.S.-based digital resource for healthcare, to reach their almost 20 million monthly visitors, which include both consumers and healthcare providers, to build awareness about INTASFI. There are over 45 million prescriptions filled annually for drugs to treat BPH. We plan to augment our marketing and sales efforts by seeking additional partners in the U.S. and ex-U.S. I will now turn to call over to Michelle Greco, CFO, CAO, to discuss the financial highlights. Michelle?
spk08: Thank you, Dr. Steiner. As Dr. Steiner indicated, we're having a great year. Let's start our highlights with the second quarter results for the three months ended March 31st, 2022. Overall, net revenues were $13 million compared to $13.3 million in the prior year second quarter. The company reported quarterly sales for its U.S. prescription business of $11.6 million, an increase of 12% from $10.3 million in the prior year second quarter. Overall gross profit was $11.2 million or 86% of net revenues compared to $10.9 million or 82% of net revenues in the prior year quarter. This was our highest gross margin for any quarter. The increase in gross profit and gross margin is driven primarily by increased sales in our USFC2 prescription business. We saw a decrease in sales in the global public sector during the quarter due primarily to 2.8 million units sold to Brazil in the prior year period for tenders, which have ended and therefore did not repeat in the current year. Operating expenses for the quarter increased to $22.9 million compared to the prior year quarter of $12.4 million. The increase of $10.5 million is primarily due to research and development costs, which increased $7.9 million to $15.5 million compared to $7.6 million in the prior year quarter. The increase in research and development costs is due to the increased number of clinical trials. This quarter, we had four Phase III clinical trials and two Phase II clinical trials ongoing, while in the prior period, we had two Phase II clinical trials ongoing. The operating loss for the quarter was $11.8 million compared to $1.5 million in the prior year quarter. Non-operating expenses were $2.4 million compared to $1.4 million in the prior year second quarter and primarily consisted of interest expense and the change in the fair value of the derivative liabilities related to the synthetic royalty financing. For the quarter, we recorded a tax benefit of $27,000 compared to a tax expense of $22,000 in the prior year second quarter. The bottom line results for the second quarter of fiscal 2022 was a net loss of $14.2 million or 18 cents per diluted common share compared to a net loss of $2.8 million or 4 cents per diluted common share in the prior year second quarter. Now turning to highlights for the results for the six months ended March 31st, 2022. For the first six months of fiscal 2022, total net revenues were $27.2 million, compared to $28 million in the prior year period. Net revenue from the U.S. prescription business was up 19% to $23.2 million from $19.4 million in the prior year period. Overall, gross profit was $23 million, or 85% of net revenues. compared to $21.7 million or 78% of net revenues in the prior year period. The increase in profit and gross margin is due primarily to the increase in the U.S. prescription business. We saw a decrease in sales in the global public sector during the first half of the year due primarily to 6.9 million units sold to Brazil and 1.8 million more units sold to South Africa in the prior year period for tenders which have ended and therefore did not repeat in the current year. Operating expenses increased by $17.3 million to $39.7 million compared to the prior year period of $22.4 million. The increase is primarily driven by research and development costs, which increased by $12.3 million to $25.6 million from $13.3 million in the prior year period. The increase in research and development costs is due to the increased number of clinical trials, which I previously discussed. Operating loss for the period was $16.7 million compared to an operating income of $17.7 million in the prior year period. The change of $34.4 million is primarily due to the gain on sale of pre-boost of $18.4 million in the prior year period and the increase in research and development costs during the current year period. Non-operating expenses were $3.7 million compared to $3.2 million in the prior year period. and primarily consisted of interest expense and the change in the fair value of the derivative liabilities related to the synthetic royalty financing. For the six-month period, we recorded a tax expense of $87,000 compared to $100,000 in the prior year period. The company has net operating loss carry-forwards for U.S. federal tax purposes of $38.6 million, with $29.5 million expiring in years through 2040, and $9.1 million, which can be carried forward indefinitely. And our UK subsidiary has net operating loss carry forwards of $63.5 million, which did not expire. The bottom line result for the first six months of fiscal 2022 was a net loss of $20.6 million, or 26 cents, per diluted common share, compared to net income in the prior period, which included the gain on sale of pre-boost of $14.4 million. or 18 cents per diluted common share. Turning to our balance sheet, as of March 31, 2022, our cash balance was $112 million, and our accounts receivable were $8.1 million, and our note receivable related to the sale of pre-boost was $2.5 million. Our net working capital was $119.3 million on March 31, 2022, compared to $136 million at September 30, 2021. During the six months ended March 31st, 2022, we used cash of $12.6 million for operating activities, compared with 1.9 million used for operating activities in the prior period. The expected future revenues from Subisabulin for COVID-19, the continued revenue from sales in the USFC2 prescription business and the global public sector business, coupled with the expected future revenue from the launch of Entadfe, and add it to our strong balance sheet should continue to be the source of funds we use to invest in our promising pharmaceutical clinical development programs as we continue to transform our company into a premium biopharmaceutical company focused on developing novel medicines for COVID-19 and other viral and ARDS-related diseases and for the management of breast and prostate cancers. Now I'd like to turn the call back to Dr. Steiner.
spk04: Thank you, Michelle. In summary, we continue to advance our deep late clinical stage breast cancer and prostate cancer programs with three actively enrolling phase three clinical studies, and we will continue to grow revenue from our base sexual health business and have authorized the future revenues from Subisibulin for hospitalized COVID-19 patients at risk for ARDS. Being opportunistic and successful in developing Subisibulin COVID-19 has led to the most eventful and transformative quarter in Viru's history. We are preparing for the global commercial launch of Subisabulin 9mg for the treatment of hospitalized, moderate to severe COVID-19 patients who are at high risk for ARDS. We have created an infectious disease franchise for this purpose. This is anticipated to be a worldwide, multi-billion dollar opportunity. This will be a real chance for significant near-term revenue for Viru. I would like to directly respond to several criticisms that have been made about the Phase 3 COVID-19 clinical trial. Concern number one, the mortality rate is too high in the placebo group. Not true. The placebo death rates in our Phase 3 study are consistent with what has been reported in the literature for similar patients at day 29. As mentioned previously, at day 29, the death rate in the placebo group in our study was 35%. which is the same death rate as reported in the Lancet publication for May 2021 for the placebo group of similar hospitalized patients consisting of 2,094 patients for the Tocilizumab recovery study. Furthermore, one would expect the death rate in the placebo group at day 60 of our trial to be higher than the day 29 death rate. Concern number two, death rates were higher in the ex-U.S. clinical sites than for the U.S. clinical sites. Not true. The death rates in the placebo group were higher in the U.S. clinical sites compared to clinical sites outside the U.S. Furthermore, the reduction in the risk of death between the U.S. and ex-U.S. clinical sites by subizobulin was the same in the U.S. compared to ex-U.S. This will be clear when our data are published in a peer-reviewed medical journal. Concern number three. Our phased clinical trial held no standard of care requirements. Not true. Standard of care was allowed for both the placebo and treatment groups. Standard of care was well balanced between the treatment and placebo groups. Approximately 80% received dexamethasone. About 30% received remdesivir. Other agents, including anti-IL-6 antibodies and JAK inhibitors, were also allowed. Subisibulin demonstrated clear benefits. over standard of care. Concern number four, there is a high risk that the FDA will not accept an EUA application because our phase three study was too small. Not true. As we have previously reported, we've had a pre-EUA meeting with FDA on May 10th, 2022. FDA agreed that no additional efficacy studies are required to support an EUA or an NDA. FDA agreed that no additional safety data required to support an EUA and a collection of safety data under the EUA will satisfy the safety requirement for an NDA. Therefore, FDA agreed that the request for EUA is supported by efficacy and safety data from our positive phase 3 COVID-19 study in hospitalized moderate to severe COVID-19 patients with high risk for ARDS and no additional clinical trials are required to support an NDA submission. Short sellers might like to lob unfounded criticisms, but our audience is the FDA, who helped develop the study design and who have now told us that the data are sufficient to proceed. As patients are waiting, we will work diligently to prepare and to submit the EUA application now that we receive the green light and encouragement to do so from FDA. With that, I'll now open the call to questions.
spk07: Ladies and gentlemen, at this time, we will begin the question and answer session. To ask a question, you may press star, then 1 on your telephone keypad. If you are using a speakerphone, we ask that you please pick up your handset before pressing the keys to ensure the best sound quality. To withdraw your question, please press star, then 2. please limit yourself to one question and one follow-up. If you have further questions, you may re-enter the question queue. Once again, that is star then one to rejoin the question queue. We will pause momentarily to assemble our roster. The first question today comes from Brandon Foulkes with Cantor Fitzgerald. Please go ahead.
spk00: Thanks for taking my questions and congratulations on all the progress. Maybe just sort of to focus on the same thing for me. So, Mitch, you sound very confident on the manufacturing side. Can you just give us some additional detail in terms of how you thought about the addressable market? I guess, what capacity do you need to satisfy the FDA on this EUA? And then secondly, along those lines, with your partner, are you putting any capital at risk for reservation of capacity or anything like that ahead of the EUA? Thank you.
spk04: Good. Thank you. So the first question is basically about manufacturing. So I'm going to answer it two ways. One, I'm going to answer what we think the patient numbers are going to be if this was a pandemic, more like an endemic. This doesn't include the surge. It doesn't include stockpiling. It doesn't include any of that. So just this way you have a rule of thumb, a benchmark. So in the United States right now, When we did the analysis, we said the hospitalization rate is about 1,955 new admissions a day. That number, by the way, has gone up to 2,597 as I looked at it this morning. But we're going to stick with the lower number, 1,955. And the number of patients that are hospitalized that would fit supplemental oxygen, forced oxygen or ventilation, it's about 52% of hospitalizations. And so that means for that week, if you look at it per week, it's about 7,116 patients a week. And so for the month, you're looking at close to 28,464 patients, okay? That's before this new surge that's becoming. So if you think, if you say the rule of thumb is we've got to, in the U.S., we've got to hit about 30,000 patients, that will give you a feel for how well we've been able to accelerate our manufacturing. So I'm going to ask Dr. Gary Barnett to give you some insight in how robust our manufacturing is and how it will be ready. And there's no capital at risk. There's no capital at risk. Go ahead.
spk02: Yeah, so we've been planning for this EUA. And right now, in the month of July – we would have approximately 50,000 patients worth of drug. This is assuming a patient gets about 12 doses, which is approximately the average number of doses that each patient in the treated group got in our phase three study. In August, we would have sufficient drug, an additional 100,000 patients, and then from September moving forward, up to approximately 250,000 patients' worth of drug every 30 days. We believe that this will satisfy and cover the addressable market in the United States as well as the rest of the world.
spk04: And also will help towards stockpiling so people can be prepared for the surge. If there's a surge, as you saw with the surge we just had, right now the problem, of course, that we have is that people are taking home testing. And so we don't really understand where the hospitalizations may peak. And we'll just have to watch that. But at this point now, assuming that the authorization, if authorized, will happen in sort of mid-summer, then we'll be ready.
spk05: Great, thanks very much, and all the best with the submission. Thank you.
spk07: The next question comes from Chris Howerton with Jeffrey. Please go ahead.
spk06: Excellent. Thank you so much for taking the questions, and I will also offer my congratulations.
spk05: Thank you.
spk06: For, yeah, so for, I guess, Mitch, with respect to the Subisabulin program in COVID-19, I wanted to follow up on the manufacturing question just to kind of understand if there was any inspections that might be required and I think at least it's a little vague to me in terms of the process of CMC evaluation for an EUA so I guess if you could just help us understand what procedural steps from your understanding might be happening on the CMC side for the review that would be really helpful yep we'll do that so Gary yeah you know the FDA
spk02: has to have regulatory rigor in any kind of authorization or approval. However, with what we believe to be the accelerated process of the EUA, we believe that the inspection piece will be minimal, of course. The sites that we're using have a long record with FDA inspections and a history of quality at their sites. We do believe that as we move forward to the NDA, the FDA will probably do a pre-approval inspection of our facilities. But right now, I suspect that they will rely on the long history that they have with these facilities to support the application.
spk04: You know, one of the interesting things I was able to take away from the meeting from the FDA is how they view this process as sort of a, you know, ultimately getting to a full NDA is sort of a rolling process. So rolling process means if you submit an NDA under normal circumstances, you have to have everything done, buttoned up, in it goes, and the full application comes in and 75 days later they review everything and they tell you we can review it and you move forward. With the fast track designation and with the potential for the EUA, it's more along the lines of let's get this thing reviewed as quickly as we can. Let's get this to patients as quickly as we can. During the review process and during the movement towards a full NDA, you can keep sending new information, additional information, additional information. So it's really a rolling kind of situation. So inspections and other things, all that have to be done can be done in real time as opposed to you have to get everything together and throw it in and then you hold your breath. So we're going to have, you know, this is going to be a very active process where, you know, success one will be the EUA authorization and ultimately success two will be a full NDA and then, you know, and then it's done and then you're ready to go. Excellent.
spk06: Well, that's really helpful. Thank you. And then, if I may, as a follow-up, what do you think, how should we be considering pricing for subisobulin in the context of COVID-19 and perhaps broader ARDS?
spk04: Yeah, it's a great question. So, first of all, I will tell you that the numbers we've used, and you'll see on our website, is purely assumptions right now. We're doing the formal work to get our arms around what should be the appropriate price. I will tell you something very interesting for ARDS in general. There is no drug on the market that has the reduction in death that this drug demonstrated in our Phase III study. And ARDS is what's killing these patients. And so for the first time, as interesting as it sounds and people are not recognizing, this antiviral, anti-inflammatory effect is leading to an unprecedented reduction in deaths in the ICU in critical care for patients with ARTS. End of story. And if you go back and look, they have supportive care, just like we do for COVID-19, for other virally-intuced ARTS. And you have, other than that, they've got some antivirals, and we already know antivirals are weak. In fact, molnupiravir, which is an antiviral that's being used in a pre-hospitalized setting, they had an IDMC meeting, an independent data monitoring committee meeting, and the conclusion in that committee was to stop the study because there's no efficacy. So the thing about ARDS is the virus triggers this cytokine storm that creates this allergic response. The lungs start to fill with fluid to a point that they become fibrotic, and they're filled with fluid, and the oxygenation goes down, and the patient dies. and usually that will happen after you have the viral part. So at some point, the viral load is, you know, it doesn't matter. You've already triggered the immune response, and the immune response is what's leading to the demise of the patient, almost like a bee sting causing an anaphylactic reaction. You pull the stinger out, or you give the patient epinephrine, which is not an antiviral, and it saves the patient's life. And so from that standpoint, ARDS is wide open, and we want to go after it. With that said, for COVID, what we're doing now is we've commissioned a group to do a formal pricing analysis. We're also going to be looking at how it impacts other things in society. So, for example, remember, death is the last step. I mean, the whole reason we're afraid of COVID is not because you get sniffles. We're afraid of COVID because you're going to die, and you're afraid of dying. Not that you're going to die, but you're afraid of dying. And vaccines helped, but herd immunity didn't work. And vaccinating 80% of the patients, still the patients can get COVID, they can get symptoms of COVID, they can die with COVID, they can pass COVID. It helps. Vaccines are important. Don't take it wrong. But it didn't solve the problem. Antivirals are coming in in a pre-hospitalized setting, and hopefully somebody gets a sniffle for three or four days. You get them in that window, and it's an effective drug. But That's a tight window to get into the doctor, get the prescription, get the prescription filled, and start the medicine. So right now, the last stop, the last opportunity to rescue a patient is in the hospital. So when the patient comes in hospitalized on oxygen, and you'll see when the publication comes out, the peer review publication comes out, I will tell you that there's going to be no surprises on the secondary endpoints. Secondary endpoints all go the way you expect. If you reduce deaths, you're going to reduce ICU. You're going to reduce mechanical ventilation. You're going to reduce days in the hospital. I mean, it's intuitive and it's proven. And so what I'm trying to tell you is that all of those metrics can be used to understand the impact of the hospital system in terms of what a drug like this can do. And so all of those factors will be built in to coming up with a price. I didn't give you the answer, which is what is the price, but as you can see, we've got to understand the balance between saving major resources for the system, because if you think about it, the biggest expenditure for a patient sick with COVID is the hospital. That's the biggest. That's the most intense resources, people, Time, money, I mean, materials, I mean, that's where it's happening. And so what we're saying is we want to come up with a fair price, and the system will benefit, but we need to understand what that is.
spk05: Okay. All right. Well, thanks for those thoughts, Mitch. I really appreciate it. Thank you. Thank you.
spk07: The next question comes from Leland Gershaw with Oppenheimer. Please go ahead.
spk09: Hi, good morning. Thanks for taking my questions. Mitch, I want to ask, as you prepare for the EUA request submission and the manuscript that will detail the fuller data from the phase three, are there any pieces of data that you are still awaiting to collect from the site or to compile, perhaps viral load data on the patients? And I also want to ask if you see what the possibility you may see of having the manuscript published. prior to what may be the EUA granting by the FDA, which presumably could be sometime in the next few months or the summer. Thank you.
spk04: Yeah. So to answer your question, the first question is basically, you know, what's outstanding? And as I mentioned to you that we're going to have a few, we just got the data. And, you know, three weeks ago or something like that. And so there are going to be a few, when I say outstanding, it's going to be things like PK and and other things that, you know, sparse sampling, PK, and that kind of stuff. What we understand from the submission for the EUA is all that, as I mentioned in my earlier comment, that's real time. You're allowed to continue to submit information as you get it. So the EUA, you pull what you have, you submit it, and then you continue as the data comes from the CRO, and you continue to supplement that information while they're doing their review. So that's a really critical point. So that's why we have an aggressive timeline to submit the request for EUA as being in this quarter because we've got what we need. We're going to put it together. We're going to submit it. So from that standpoint, it won't hold us up. As it relates to the question about the manuscript, the manuscript's written. It's done. And so I think that's record time as well And so it's in the process of being reviewed. And our job is to sit and wait for the peer review process. And that's a little harder to tell. But my guess is it will be an online publication initially, so it gets out as quickly as possible. And the idea would be, hopefully, that it's coordinated in such a way that the manuscript and the EUA authorization happen around the same time so that you guys can see the information. But that's, you know, we're on track for that. Great.
spk09: And just to follow up, you know, as you see an eventual NVA possibility for sibizabulin and COVID-19, I wanted to ask, you know, given the performance of the drug in the phase 3 population, perhaps there could be similar benefits to non-COVID patients with ARDS Wondering if this has encouraged you to look into any further clinical development in non-COVID-19 or other types of conditions. Thanks.
spk04: As I mentioned in my prepared remarks, absolutely. I mean, when I went back and reviewed the literature, I was shocked to see that ARDS remains an incredibly important critical care problem and that to viral-induce ARDS is incredibly common. Influenza A and RSV are the two big ones that come to mind. Influenza A, which we all can relate to, we've accepted to the endemic, which is roughly 52,000 deaths and about several hundred thousand hospitalizations a year, and you have to get a new shot, a new booster shot, a new flu shot every year. So if that's the model that COVID ends up hitting... And from an endemic standpoint, that's a huge market for an endemic disease. And by the way, influenza A virus follows the same life cycle, if you will, as COVID-19, meaning that it goes through, binds to the outside of the cell, it uses microtubules to go into the cell, uses microtubules to take the new viruses and get it out of the cell. And then, of course, the cytokine storm is what it triggers to cause ARDS. Very similar pathogenesis and pathophysiology as COVID-19. And so, yes, we've already started writing the protocols for the clinical development. So that would be the first one we roll out because it's such an obvious one. And we have something that's different than what's out there. So, again, you can imagine a situation where we allow standard of care, supportive care, versus abysmobulin plus supportive care. And that would really greatly expand our patient population. And then second, RSV is the other area. When I gave the numbers in the presentation, it was for RSV not in children. It was RSV in the greater than 65-year-olds. But we have to think about children as well as a potential population. And in fact, we've been asked to supply a protocol to move this into children by FDA. And so we're going to be clearly responsible and diligent in doing that. But ARDS is an interesting group to go into. Also, because of the anti-inflammatory activities, we're getting interest in going after the more aggressive inflammatory diseases with something with this kind of anti-inflammatory slash side effect profile could be useful. So stay tuned. I think there's a lot of room for subisobulin being an oral agent with this kind of side effect profile to play a role in virally induced ARDS and potentially some of the inflammatory diseases. Great. Thank you.
spk05: Thank you. Thank you.
spk07: The next question comes from Yi Chen with H.D. Wainwright. Please go ahead.
spk10: Thank you for taking my questions. My first question is, once you obtain the EUA for sub-disability in the U.S., how easy would it be to obtain similar authorizations in other countries and territories? Great question.
spk04: So if you look at Pfizer, and again, I'm just getting this from the news, so I don't know any secrets, but they have something like 60 EUAs that have been granted. And so usually what happens is that the two big regulatory agencies that the world looks to to do the work in lieu of what they would do in their own regulatory agencies is U.S. and the E.U., specifically the EMA. So if we get U.S. approval, then about 80% of countries will follow that lead and also very quickly expedite approval in their country. And if you get the EU, roughly 80% of the countries will do the same, but they may not be the same 80%. And so the goal would be, and our strategy is U.S., And now we're starting in EU and the MHRA because of Brexit, because Britain's a big market. We've already started that process. We're working in Brazil and the neighboring countries that follow the treaty, South America. And we're looking into South Africa now because that's the most hard-hit country and also the country that has the most resources to direct this kind of therapy to their folks. And then furthermore, and again, each of those have regulatory, but again, U.S. regulatory will go a long way. So we think that if we can get U.S. regulatory, we believe that once we have U.S. regulatory and we're starting the process to get the other countries at least the information into their system, that we should see a series of EUAs after we get the formal EUA authorization from U.S.
spk10: Thank you. And my follow-up question is, recent news reports show that patients who received Pfizer's new COVID drug, Paxlovid, in the outpatient setting, they have symptoms rebound after the treatment, potentially showing that Paxlovid is not such an effective drug. So with that, do you have any plans to use Paxlovid use your drug to capture the patients in the outpatient setting?
spk04: Yeah, the answer is yes. We believe subizobulin could have activity in the pre-hospital setting, so the general population. The reason we went into the hospitalized setting is the FDA told us to. So the FDA said that your clinical benefit-risk ratio would be best in patients that are dying in the ICU and dying in the hospitals If you can show something there, then that would be great. And, of course, a lot of drugs try to do that. A lot of drugs have failed. Or they showed something less than a 5% mortality benefit. And this is the first one that shows a 25% absolute reduction and a 55.2% relative reduction in deaths. But because the mechanism is antiviral, anti-inflammatory, we do believe that we can go earlier. And it's something to think about in the future. But you raise a good point. And that is, we're still trying to understand, it's called the rebound phenomenon. So it kind of makes sense if you're giving somebody an antiviral and you stop the antiviral, you're not curing that patient. And if you stop the antiviral, then the cells that have the virus in them will start growing again. And so rebound may happen. And we're seeing that. And so there is going to be room even in the pre-hospital general population to augment, you know, the vaccines. And now with the BA4 and BA5 variant coming out of South Africa, again, we always hear this. They always try to scare you to think it's going to circumvent the vaccine. And it may. This one looks like it may. But, you know, but still, the vaccine isn't the final answer because people can still pass it. People can still get it. And so it's not uncommon to get COVID-19 and hopefully be less severe, the immunocompromised, and for patients with, you know, severe major comorbidities, it's still becoming a big problem. So, yeah, so we could potentially go earlier.
spk05: Got it. Thank you. Thank you.
spk07: Again, if you would like to ask a question, please press star and 1. To withdraw your question, please press star then two. The next question comes from Kumar Raja with Brookline Capital Markets. Please go ahead.
spk01: Thanks for taking my questions and also congratulations. So it looks like you need to follow the patients for safety once you have the EUA approved. What are your expectations in terms of, like, you know, how many patients or how long they have to be followed for the safety data with regard to the potential NDA filing?
spk04: So I'm going to ask Dr. Gary Barnett, our Chief Scientific Officer, and handles regulatory to answer that question. So this way you'll see with the process under the EUA.
spk02: Yeah, so under the EUAs, you are obligated to collect what they call spontaneous reports reporting of adverse events, and we believe that that is exactly, we'll just follow the normal EUA process. We do that for NDA-approved drugs as well, and with what's called a MedWatch form, and it's very formal, and they submit these things to the FDA, and they submit these adverse events and serious adverse events to the sponsor. Spontaneous reporting in a fully NDA-approved product is I mean, a lot of times the physicians don't comply with that requirement. But under an EUA, they follow it pretty well. And then we will, of course, encourage our investigators or PIs to follow these things. And so that's what we're planning. We're planning on collecting the standard EUA safety requirements, which is spontaneous reporting of serious adverse events during the EUA process.
spk04: And let me just also remind you that we're very, you know, this program isn't just about the COVID-19 program. We do have a history with civizibulin in our oncology program. So in prostate cancer, between, you know, between the 80 patients in the phase 1B2 and then in the phase 3, you know, I think we were able to count something like 250 patients that have been exposed to nine milligrams or higher. And in some cases, particularly in the cancer products, they're getting 32 milligrams a day for three years. So, you know, this drug is well tolerated. And so do you add that plus the data from the phase two and phase three COVID-19, and we have 199 patients in the phase three total data set that we have safety data on. And then now you add in after the EUA, during the EUA period, you'll add in all the spontaneous reporting that will take place. You know, all of that's sufficient. And as I said in my comments, we were told that no additional safety clinical trials will be required.
spk01: Okay, that's great. And in terms of the negotiations regarding stockpiling, how is that going to work as the EUA kind of moves through the channels?
spk04: Well, the good news is we have been incredibly active with government. We started, as you can remember from our comments from the phase two, we have started discussions with BARDA. We have made some good friends with BARDA. So we talk to BARDA on a regular basis. As you know, they have a tech watch group. How many people are involved with TechWatch? It's like how many agencies?
spk02: Oh, it's 15, 20 agencies.
spk04: Yeah, 15 to 20 agencies that are part of the TechWatch. We've presented the information. And then furthermore, our company has hired several lobby groups to also help us navigate through government. And so what we're hearing loud and clear is, is don't look at what's happening in Congress with the $10 billion or the $33 billion that will be earmarked next year. I mean, if you can see, the reason the Republicans are mad at the Democrats is because the states have tons of money that's just sitting on that was allocated for COVID, and they want them to spend some of their money. And then there are other budgets that they're allowed to go 5% of the budget and move it to something that wasn't originally earmarked. So what we're hearing is a drug like this, which is a therapeutic that reduces deaths in the last opportunity you have to grab a patient. I mean, and again, let me dream for a moment. If we reached a million deaths this year, I mean, a million deaths this year from the two and a half years of the pandemic, it's a terrible milestone. But if our drug was available at the beginning of the pandemic, that means 550,000 people could be home right now. I mean, that's like half the population of San Francisco or Seattle. So the discussions we're hearing is, guys, get your EUA. Once the EUA is authorized, then it will trigger a series of events that will give government cover to move politically towards the money.
spk05: Okay, great. Thanks so much.
spk07: Ladies and gentlemen, this concludes our question and answer session. I would like to turn the conference back over to Dr. Mitchell Steiner for any closing remarks.
spk04: Thank you. Thank you, operator. I appreciate you all joining us on today's call. I look forward to updating you all on the progress on our next investor's call. We're very, very excited about our progress with COVID-19, and we look forward to continuing to update you specifically on Sibizabulin. Thank you.
spk07: The digital replay of this conference call will be available beginning approximately noon Eastern time today, May 12th, by dialing 1-877-344-7529 in the U.S. and 1-412-317-7000. You will be prompted to enter the replay access code, which will be 821-5063. Please record your name and company when joining. The conference has now concluded. Thank you for attending today's discussion.
Disclaimer