UroGen Pharma Ltd.

Thank you for standing by, and welcome to the EuroGen Farmer Second Quarter 2020 Financial Results and Business Update Conference Call. At this time, all participants are in the listen-only mode. After the speaker presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star 0. I would now like to hand the conference over to your speaker today, to Peter Furenshue, CFO. Thank you. Please go ahead.

Thank you, operator. Good morning, everyone, and welcome to Urgent Pharma's second quarter 2020 financial results and business update conference call. Earlier this morning, we issued a press release providing an overview of our recent corporate highlights and financial results for the quarter ended June 30th, 2020. The press release can be accessed on the investors portion of our website at investors.urgen.com. Joining me on the call today are Liz Barrett, President and Chief Executive Officer, Dr. Mark Schoenberg, Chief Medical Officer, and Jeff Bova, Chief Commercial Officer. Please note that we are conducting our call today from different locations, so we appreciate your patience and understanding should we have any technical difficulties. In just a minute, I will turn things over to Liz, who will provide a summary of our recent corporate developments. Mark will then share a clinical development update And Jeff will discuss our commercial progress made since launching Gelmito in June. Following Jeff, I will provide an overview of our financial highlights for the second quarter before opening up the call for questions. As a reminder, during today's call, we will be making forward-looking statements. Various remarks that we make during this call about the company's future expectations and plans and prospects constitute forward-looking statements for the purpose of the safe harbor provision under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the risk factor section of the Urgent Pharma's quarterly report on Form 10-Q filed with the SEC this morning and other filings that URGEN PhRMA makes with the SEC from time to time, as well as any negative effects on URGEN's business, as well as any commercialization and product development plans caused by or associated with COVID-19 pandemic to the extent not disclosed previously. We encourage all investors to read the company's quarterly report on Form 10-Q and the company's other SEC filings. These documents are available under the SEC filing section of the investors page of URGEN's website at investors.URGEN.com. In addition, all information we provide on this conference call 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 undertake no obligation to update any forward-looking statements we may make on this call on account of new information, future events, or otherwise. I will now turn the call over to Liz.

Thank you, Peter. Good morning, everyone, and thank you for joining us today. I'm delighted to be speaking with you representing a company that has successfully transitioned from a clinical to commercial stage biopharmaceutical company. Since the June 1 launch of Gemido, for patients with low-grade upper tract ulithelial cancer or low-grade UTUC, we have been extremely pleased with the response from both physicians and patients. We are very pleased that as of June 30th, 20 doses have been administered to patients, and thanks to the preparedness of our team, we've been able to meet every request for product and support. Jeff will provide more details on the launch, but interest has been significant, and we continue to see increased demand despite the challenging environment. I would like to recognize and thank Jeff and the entire commercial team as they have proven their commitment to bringing this breakthrough therapy to patients. Further supporting our launch efforts have been the publication of results from the pivotal Phase III Olympus trial of Gemido in the Lancet Oncology and in a supplement to the April 2020 issue of the Journal of Urology. This data was also the focus of a virtual presentation at the 2020 American Neurological Association annual meeting in mid-May. Additionally, Dr. Kareem Chamey from UCLA highlighted the benefits of gel mito as a kidney-sparing option for low-grade UTUC and reviewed the clinical profile and safety data as part of a theater during the AUA live meeting at the end of June. The publication and presentation of Olympus data continue to underscore why Gemido is important to patients as the first and only approved non-surgical chemoablative treatment for those with this rare and difficult to treat disease. The Olympus study has now completed, and we submitted an updated label to the FDA, including the final safety and efficacy data. While there's no mandated timeline for review, We believe the FDA will approve an updated label in the second half of 2020. It's important to note that the final data is consistent with our previous results, so we don't anticipate significant changes to our label. In addition to the approval and launch of our first therapy, we continue to advance key initiatives designed to build a long-term growth company. This includes the presentation of updated data from the Phase II Optima trial, of UGN-102 at the AUA Annual Meeting in May. No drugs are currently approved by the FDA as first-line treatment for low-grade, intermediate-risk, non-muscle-invasive bladder cancer. This is a sizable opportunity with over 80,000 addressable patients in the U.S. alone, and we believe UGN-102 has the potential to be the first FDA-approved therapy in this setting. and an important non-surgical treatment alternative for this difficult-to-treat patient population. Mark will share our latest update to the data as of July, but we remain very encouraged by the positive complete response and 12-month durability data. This data, combined with the data from Olympus for low-grade UTUC, supports the potential of UGN-102 to have a profound impact on patients who deserve better options. We remain on track to share the final CR and durability data from the Optima II trial by year end, and we will initiate the pivotal Phase III clinical study. Mark will share the details of the trial design, including patient numbers and timing, which are in line with our previous discussions and expectations. Additionally, our UGN 302 program has generated a lot of excitement internally and externally. and it has the potential to transform how high-grade, non-muscle-invasive bladder cancer is treated. UGN302 is a combination of UGN201, our TLR7-8 agonist, and Xalafrilamab, the anti-CTLA-4 antibody we licensed from a genus. There remains a significant unmet need in these patients, despite recent approvals, as the data supporting these approvals reflects only incremental improvements and the continued need for treatment post-BCG. Lastly, we have a strong balance sheet and are pleased with our financial outperformance in Q2. Peter will discuss in more detail, but our cash position allows for our current operations well into 2022, and we have no need for additional capital at this time. We continue to search for new medicines and partnerships to ensure sustainable growth but early successes demonstrate the potential of our medicines and strengthen our belief that we can achieve peak revenue of more than $1 billion annually from our current portfolio. With that, I'll turn the call over to Mark to discuss our recent clinical update. Mark?

Thank you, Liz. We are very encouraged by the progress we've made and equally excited about what's to come. I can tell you firsthand that the excitement in the urologic community about our recent advances is palpable. As a practicing urologist, I'm particularly encouraged by the interest from my medical colleagues regarding the recent launch of gel mito and how they can incorporate this paradigm shift in therapy into their practices. We had two virtual presentations at the AUA annual meeting in May. The first featured data from the gel mito pivotal Olympus trial in patients with low-grade UTUC. The data in the presentation, also published in Lancet Oncology, demonstrated that 59% of low-grade UTC patients treated with gel mito achieved a complete response. Based on interim data, durability at 12 months was estimated to be 84% by Kaplan-Meier analysis, and median duration of response was not reached. Overall, the most frequently reported adverse events were ureteric stenosis, urinary tract infection, hematuria, flank pain, and nausea. We also shared interim data from the Phase 2b Optima 2 trial of UGN102 in patients with low-grade intermediate-risk non-muscle-invasive bladder cancer. These data were also published as a supplement to the April 2020 issue of the Journal of Urology. We are pleased to share updated results as of June 19, 2020, which are consistent with our previous reports, showing that 65% were 41 out of 63 patients treated with UGN102 achieved a complete response three months after the start of therapy. In this subset of patients, the interim Kaplan-Meier analysis shows a 72.4% estimated duration of response of 12 months. This analysis includes only patients who were present for evaluation at each time point. Follow-up of these patients will continue until all patients have reached the 12-month time point. The most common adverse events, greater than 10%, were reported as mild to moderate and include dysuria, hematuria, urinary frequency, fatigue, urgency, and urinary tract infection. These data continue to validate our hypothesis that increased dwell time significantly improves the effectiveness of intravesical therapy. Both UTUC and non-muscle invasive bladder cancer are treated by repetitive surgical intervention, which carries associated risks in an elderly population. Much like gel mito, UGN-102 may have the potential to fundamentally change the way low-grade, intermediate-risk, non-muscle-based bladder cancer is treated and help patients avoid recurrence of their cancer and repetitive surgeries, this time in a much larger patient population.

We have agreed to the design elements of our Phase III study with the FDA and are finalizing the protocol.

The study will be a randomized control trial in approximately 600 patients of UGN102 with or without TURBT versus TURBT alone in patients with low-grade non-muscle invasive bladder cancer at intermediate risk of recurrence. Patients will be randomized to either UGN102 plus or minus TURBT or TURBT alone. At the three-month time point, patients will be assessed for response. Patients who have demonstrated a complete response to either UGN-102 or TURBT will continue for long-term follow-up. Patients who demonstrate a recurrence in either arm will undergo a TURBT. Based on previous Phase II data generated in this population, we believe the majority of patients treated with UGN-102 will not require a TURBT at three months. The primary endpoint of this study is disease-free survival, and the study is designed to conclude superiority and or non-inferiority. We expect completion of the study within approximately three years with the potential to stop early at pre-specified interim analyses. We are excited by the robustness of the study design, which is important given the potential UGN-102 has to significantly disrupt the current treatment paradigm. We want to ensure patients have access as soon as possible, and the head-to-head comparison is expected to generate data demonstrating the value of treating patients with UGN-102 versus repetitive surgical intervention. Before I turn things over to Jeff, I want to provide a little more detail on UGN-302. A combination of UGN-201, which is our TLR7 agonist, as a monotherapy, and Xelafilumab, and anti-CTLA-4 antibody, which we are developing in high-grade non-muscle invasive bladder cancer. Patients with this disease are at higher risk for rapid progression, with an increased risk of developing a life-threatening illness. Since the disease primarily impacts people in their 60s and 70s, often with other comorbidities, non-surgical treatment options are of vital importance. The current standard of care for high-grade non-muscle invasive bladder cancer is transurethral resection of bladder tumor, or TRBT, in addition to BCG. Those who do not respond to BCG then receive alternative intravascular therapies, enroll in a clinical trial, or undergo radical cystectomy, which is a complex surgery involving bladder removal and urinary tract reconstruction using a segment of the intestinal tract. This operation is associated with all of the typical risks of a major surgery and specific risks such as dehydration, electrolyte abnormalities, urinary tract infection, bowel obstruction, and ureter blockage. A cystectomy is associated with high rates of complication, including gastrointestinal dysfunction, deep vein thrombosis, heart attacks, and death. The hypothesis that the preclinical team has been working on is that combinatorial immunotherapy is feasible and meaningful when applied locally which is a very novel idea. Delivering a combination intravesically may sidestep systemic side effects and adverse events associated with systemic immunotherapy. What we found is that a combination of UGM-201 with an anti-CPLA-4 antibody results in smaller tumors and better survival in mice and some changes in immunological markers such as decreased T regulatory cells and increased CD8 to Treg ratios in our murine model. We think these data support advancing this program into human trials, as this may represent a novel approach to managing high-grade disease that has otherwise failed therapy with contemporary standards of care. As Liz mentioned, this program has generated considerable interest based on its potential to dramatically change how we treat this disease. I'd like to now turn the call over to Jeff.

Thank you, Mark. I'm excited to speak with you today on the heels of our June 1st Jelmido launch, which was executed ahead of our timing and guidance to the street. As Liz shared, interest in Jelmido has been significant, and demand has continued to increase despite the challenging environment. Thanks to the efforts of our entire team, we booked almost $400,000 in net sales as of June 30th. We're definitely off to a solid start, and I remain optimistic that we can sustain our early momentum moving forward. While patient access is challenging in today's environment due to COVID-19, we are seeing patients able to be treated. Some of our field personnel have been limited in their live interactions with physicians, especially in areas of the country where infection rates are on the rise. But we have increased our investment in digital tools and are finding HCPs open to engaging with us virtually. Importantly, while some states are not allowing certain surgical procedures, including RNUs, gel mito can be instilled in a clinic. And when patients are treated in a hospital setting, it's an outpatient procedure, typically under local anesthesia. In fact, most installations to date have been under local anesthesia. Thanks to this flexibility, we haven't heard about procedures being canceled or delayed due to COVID-19. And we've been able to treat patients in states hit disproportionately hard by the virus, including California, and New Jersey, which is where our first patient was treated in June. While we are obviously early in our launch, we see many positive indicators. To date, we've activated roughly 100 sites, which means they've completed their internal processes and have or are ready to treat patients. This includes sites who participated in the Phase III Olympus trial. We have also had two accounts treat more than one patient. This is an important metric to show that the process we have put in place has been smooth and the account is identifying other patients who could benefit from the treatment with gel mito. To date, roughly 75% of treating physicians were not part of our Phase III trial. This isn't surprising, given UTUC is a disease predominantly diagnosed in the community, but it underscores the fact that we have been focused on the right targets and were able to generate broad awareness of gel mito amongst community urologists. It also validates our mixing strategy and the utility of the partnership we established with OptionCare. From a coding and reimbursement perspective, we have committed significant resources to working with our top LUGPA accounts and institutional accounts. As a result, multiple treatments have already been successfully reimbursed. Additionally, thanks to our market access team, we were able to complete both our C and J code applications. We are on track to receive our C code in September, which means it will go into effect in October, and our J code in January of next year. So, again, we are definitely off to a solid start and feel we are well-positioned to build on the momentum we've generated since our June 1st launch. Before I turn things over to Peter, I want to recognize and applaud the efforts of healthcare providers and staff who have worked collaboratively with us to bring Jelmido to patients. It's certainly been a challenging couple of months, but our team has overcome every obstacle and remain committed to do so whatever is necessary to address the unmet need in the urologic community with this novel and effective kidney sparing treatment option. The work we are doing now will not only help us to achieve our short-term goals, but will build a foundation for future success with UGN 102 and the other opportunities in our pipeline. And with that, I'd like to turn the call over to Peter, who will discuss financials.

Thank you, Jeff. And good morning, everyone, on today's call. Virgin recorded net product sales of gel mito for the second quarter of 2020 of approximately 371.5 thousand, reflecting sales only during the month of June 2020. Associated cost of revenues were approximately 48.2 thousand including certain one-time initial costs. In periods prior to receiving FDA approval for gel mito, the company recognized inventory and related costs associated with the manufacturing of gel mito as research and development expenses. We expect this to continue to impact our cost of revenues through the fourth quarter of 2021, as we produced gel mito at costs reflecting the full cost of manufacturing and as we deplete these inventories that we had expensed prior to receiving FDA approval. For the second quarter ended June 30th, 2020, we recorded a net loss of $31.3 million or $1.44 per share. This compares to a net loss of approximately $22.5 million, $1.08 per share for the same period in 2019. The net loss for the second quarter ended June 30th, 2020 includes $7.1 million in non-cash share based compensation expense as compared to $7.2 million for the same period in 2019. For the six months ended June 30th, 2020, we recorded a net loss of 69.1 million or $3.22 per share. This compares to a net loss of approximately 43.9 million or $2.19 per share for the same period in 2019. The net loss for the six months ended June 30th, 2020, includes $14.7 million in non-cash share-based compensation expense as compared to $14.7 million for the same period in 2019. Research and development expenses for the second quarter ended June 30, 2020, were $8.1 million as compared to $10 million for the same period in 2019. Research and development expenses also include $1.6 million of non-cash share-based compensation expense for the second quarter ended June 30, 2020, as compared to $2 million for the same period in 2019. The decrease in research and development expenses from 2019 to 2020 was mainly attributable to the completion of the Phase III clinical trials and regulatory activity for UJN 101. a decreased activity related to UGN 102 Phase II clinical trials, partially offset by an increase of headcount and related costs in anticipation of UGN 102 Phase III clinical trials. Research and development expenses for the six months ended June 30, 2020 were $24.7 million as compared to $19.7 million for the same period in 2019. Research and development expenses also include $3.5 million of non-cashier-based compensation expense for the six months ended June 30, 2020, as compared to $4.3 million for the same period in 2019. In addition to the above, the increase in research and development expenses for the six months ended June 30 from 2019 to 2020 was manually attributable to a one-time payment of $6.6 million to unwind the company's obligation to the Israeli Innovation Authority during the first quarter of 2020. Selling and marketing expenses for the second quarter ended June 30, 2020 were $12.8 million as compared to $3.2 million for the same period in 2019. Selling and marketing expenses include $1.2 million of non-cash share-based compensation expense for the second quarter ended June 30, 2020, as compared to $0.5 million for the same period in 2019. The increase in selling and marketing expenses resulted from the increased costs and activities related to the launch of Jelmito, including headcount and related costs associated with our sales force. Selling and marketing expenses for the six months ended June 30, 2020 were $23.4 million compared to $5.8 million for the same period in 2019. Selling and marketing expenses include $2.3 million of non-cash share-based compensation expense for the six months ended June 30, 2020 as compared to $0.9 million for the same period in 2019. The increase in selling and marketing expenses resulted from increased costs and activities related to the launch of Jelmito, including headcount and related costs associated with our sales force. General administrative expenses for the second quarter ended June 30, 2020, were $11.3 million as compared to $10.6 million for the same period in 2019. General administrative expenses include $4.3 million of non-cash share-based compensation expense for the second quarter ended June 30, 2020, as compared to $4.7 million for the same period in 2019. The increase in general administrative expenses from 2019 to 2020 resulted primarily from an increase in costs as part of the build-out of our company with commercialization of our first products, and consulting and other outside fees. General administrative expenses for the six months ended June 30, 2020 were $22.6 million as compared to $20.7 million for the same period in 2019. General administrative expenses include $8.9 million of non-cash share-based compensation expense for the six months ended June 30, 2020, as compared to $9.4 million for the same period in 2019. The increase in general administrative expenses from 2019 to 2020 resulted primarily from an increase in costs as part of the build-out of the company for the commercialization of our first product and consulting and other outside fees. We closed the second quarter of 2020 with $151.6 million in cash, cash equivalents, and marketable securities. This excludes restricted cash. Our current balance sheet supports the company well into 2022 as we ramp the commercialization of Jelmido and start to see offsetting operating margin and cash inflows from commercial sales. This will allow us to vigorously advance the clinical development of UGM-102, as well as other clinical programs already in the pipeline. With that, operator, I would like to turn the call over for questions.

Thank you, sir. As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, please press the pound key. Please stand by while we compile the Q&A roster. I share our first question. It comes from the line of Ram Selvaraju from HC Wainwright. Please go ahead.

Hi, this is Blair on for Ram. A couple questions from me. First, can you talk a little bit more about how COVID-19 has affected the launch of Jelmido, and what kind of strategies are you employing to mitigate this impact? Do you anticipate any more normalized commercial environment to materialize later on, and how has your virtual platform been functioning thus far, and what has attendance been like?

Hi, Blair. It's Liz. Thanks for joining. I would just make a couple comments. I'm going to turn it over to Jeff so I can give you more specifics around it. I think as Jeff mentioned earlier, we have not seen an issue in patients actually get scheduled with them coming in to have their medicine. And Jeff also mentioned that in some states, you know, they're not really allowing face-to-face interactions with the representative, and so that's why a lot of what we're doing is a virtual, but I do want to comment that we also have, as we've talked about before, nurse educators and medical science liaisons, and they are able to go in and educate doctors and answer any questions that they have. My personal opinion, and we have no data that sort of shows this, but if you look and read overall, you are seeing sort of a, I would say, a reduced patient engagement with physicians overall, not just for us but for everyone. I will tell you that despite any of that, we are well ahead of where we expect it to be right now. So we don't really see it impacting us specifically right now. I think the impact of COVID will be yet to be determined. And what I mean by that is it depends on what happens over the next few months. because like I said, you can read everywhere that they'll show that cancer diagnosis and treatment is down over 40%. But to Jeff's point, we haven't seen that specifically, but we are seeing some of the limited engagement because of that. So I think, and Jeff can talk to you more about the strategies to impact, I think we're just going to have, it's a fluid situation. But despite all of that, I think it's really important for you to know that the number of patients we have in the pipeline is and the number of patients that we've treated so far is well above where we're expected to be right now. So I think it's still something we need to be very cognizant of, and I'll turn it over to Jeff to talk more about our strategy. So, Jeff?

Sure. Thanks, Liz. So what we've done is we've increased our resources and investment in our digital platform as well as a non-personal promotion. So I think everyone got to see the virtual AUA that was successfully rolled out continues to get what we can measure click-throughs, how long folks stay on the site, continues to be well above industry average. And as Liz said, I mean, it is a fluid situation. Actually, a lot of hospitals can't perform an RNU. It's an overnight surgery. I talked to a couple physicians where that's a surgery that they cannot perform right now. And so gel mito becomes another option because, as we've said, it can be given in an outpatient setting under a local. But those are some of the, you know, certainly the increase just to keep the awareness high in, you know, major periodicals that urologists read. We're increasing our investment there. And really anything that's The things that we're working through are typically the internal processes of our customers, whether that's an informal formulary review, whether that's just making sure we sit down and meet with billing and coding. We haven't had delays due to COVID-19.

Okay, great. And could you talk a little bit about the impact of the inclusion of the NCCN clinical practice guidelines for Gemida?

Sure. First of all, it's a record inclusion. I think NCCN also recognizes the unmet need in this area, and so they included it quickly in their guidelines. We'll work with NCCN to communicate that. That will be a piece we can promote, that the inclusion of the guidelines Any sort of inclusion like this is certainly something that will help the brand, that will help the promotional team go out with. And so it's been a positive, and even more so that it came, you know, very soon after launch.

I think the other only comment about the NCCN guidelines is, you know, a lot of payers follow NCCN guidelines. And so that also helps us when we think about any reimbursement as we go forward. So thanks, Blair.

Okay, great. And then if I could just squeeze in one more real quick. Do you anticipate any impediments to enrollment with 102, the pivotal study, due to COVID-19?

We actually do not at this point, and mainly because we have increased our number of sites. outside of the U.S. and in some of the Eastern European markets where we don't see, where they're not seeing the COVID or the delays because of that. So we expect it may have some delay in the U.S., but we've already planned for that and don't expect it to impact our enrollment at all.

Okay, great. Thank you.

Thank you. Our next question comes from Derek Archila from Stiefel. Please go ahead.

Hey, thanks, guys. This is Ben for Derek. Thanks for taking my call. Just wondering if you guys could comment on the number of patients who are actually using the drug right now, and then how many docs are actually doing it, too, and then does this vary by, I guess, vary by parts of the country? And that's it for us. Thanks.

Yeah, it's Liz. The number we had talked about, the 20 doses, I will share with you that that was eight patients in June. Going forward, we're not going to every month or every quarter give all of the patient numbers as we start to get into our revenue generation. But I think it's important for you to know that. And the reason I share that is because it shows that we've gotten both new patients as well as repeat patients. So, you know, as you know, as we go into the months and weeks, these patients are getting six weekly doses, so it's important that they continue to get all six doses. So we do have patients in that June timeframe that got one. We've got patients that, you know, got multiple doses. I'll let Jeff talk about the physicians that are engaged. But just please, and like I said, we can't share numbers after Q2, but I'll just remark that we're continuing to see progress and happy with our progress, you know, as we go into Q3. So, Jeff, do you just want to comment about physicians, you know, without giving, you know, too much specific information that's in this early stage?

Yeah, no, we've had a growing number of interest in physicians, both immediately and academic setting. And to your question around do we have sort of pockets, we don't. I'm not seeing that. I can say we've had patients in California. Our first patient was in New Jersey. We just recently had a patient in Long Island, which, as you know, is a hard-hit area. We also had patients in Missouri. And so we're not seeing sort of a geographical impact with regards to patient access. So hopefully that helps.

Yep. Okay. Thanks, guys.

Thank you. Our next question comes from the line of Boris Peeker from Cowan. Please go ahead.

Good morning. For Joe Mehta, I'm just curious, do you anticipate a stronger uptake in the academic or community settings? And if you could also expand on what are some of the economic implications for using the drug in both of these settings?

Yeah, Jeff, why don't you answer that?

Sure. So we believe that most of this, and it's proven to be true in the patients that we've got today, most of the diagnosis occurs in the community. We think that that will be probably 75% of patients. Having said that, some of the patients that we've received went to our Phase III physicians. They were part of Olympus. So those are, as you know, big referral centers. They'll continue to be that. So they'll be very important for gel mito as well. But as we stated, the majority of patients are diagnosed in the community, and depending on where the urologist does his or her surgery, that'll be dependent on where they go to actually administer the question. And with regards to From a financial standpoint, this is a buy-and-bill drug, so Part B as in boy. And so physicians now are lining up their claim submission. They will fill out the appropriate forms to be reimbursed at buy-and-bill. Reimbursement will be consistent until we get an established ASP. And depending on the MAC carrier, There are 9 to 10 MACs that cover Medicare throughout the nation. They'll reimburse either a 95% of AWP or WAC plus model until we establish an ASP, which we expect the ASP to be in January. But, yeah, they certainly understand Buy and Build from drugs like Provenge and Zofigo, so this is nothing new to them, which we're fortunate that we don't have to kind of face that hurdle. They're very familiar with the Viandell landscape.

Gotcha. And my last question, what's the status of the European update? What should we be hearing from there?

Yeah, we just recently engaged a small firm there that had two principals that actually were part of the EMA, and we're working through that, as we've said before. So we expect to have a plan In the next couple of months, as we've stated before, the issue isn't so much getting an approval. It's really getting reimbursement. So we've got to work through countries like Germany and France, and we've got upcoming meetings around what would it actually take to get good reimbursement there because they use a comparator model. That's a challenging situation for 101. With the head-to-head in 102, we won't have that issue anymore. but we do want to make sure that we have it available. We also have engaged in Japan on the regulatory authorities, and so we're working through those, and I think we'll see something in the next three to four months. We'll have a more clear plan on do we need to do another study or what exactly we would need to commercialize in those geographies.

Great. Thank you very much for taking my questions.

Thank you. Thanks, Derek. Thank you. Our next question comes from the line of Leland Gershel from Oppenheimer. Please go ahead.

Hey, good morning. Thanks for taking my questions. First, a question on commercial, I guess for Jeff, but also maybe for Mark as well. You know, we've had some recent publications in the urological literature that reviewed the data from past studies in different areas. tumors with regard to, you know, how long patients can go without treatment and what the outcomes would be, you know, as we're in the COVID-19 environment, as urologists sort of triage, you know, those patients who are more important to see first versus later in terms of intervention. I want to ask about, you know, with low-grade UTUC, to what extent do you think that urologists will defer therapy, even though you haven't seen evidence perhaps of that, to prioritize treatment of patients who have more aggressive or later stage disease. At the same time, with hospitals not, perhaps some hospitals not doing RNUs, urologists may have more office time to do those types of in-office procedures for earlier stage cancers. So how should we think about kind of those two push-pull factors as we get through the pandemic? Then I've got a couple of R&D questions. Thanks.

Yeah, so Jeff, why don't you start first and then Mark can give his perspective from a physician standpoint and then answer your R&D questions.

So, Jeff. Sure. So, what we've heard is just like everyone is trying to find solutions to the COVID-19, our physicians are doing that as well. And so, you know, I'll give you an example where a patient didn't want to go to the hospital and serve a physician. actually sought out some surgery centers to where the patient would feel more comfortable because, as this physician said to me, and I'll let Mark allude to how long patients would wait, but the patients reminded perhaps every day that their cancer is back. There can be a significant amount of blood in the urine, and so their anxiety levels, as you can imagine, go up. as the time before any sort of treatment occurs. So we're finding physicians are working with their patients. They're working to make their patients feel comfortable in areas where either hospital access is not there right now, they're prioritizing other patients, or just a patient, as I alluded to, the patient in this case isn't comfortable going to a hospital. Mark, you want to comment?

Yeah, Leland, it's a great question. I think, as you might well anticipate, everyone is struggling. We're all struggling with huge backlogs of patients who were delayed because of the limitations on the availability of elective surgery time for patients just like this. So we're doing all the things that Jeff just described. But I do think actually the circumstances provide an opportunity for physicians to think creatively about how to treat patients with low-grade disease. So in a very paradoxical way, COVID has provided an interesting opportunity for physicians to really think through alternative therapies for patients with low-grade disease, and obviously gel mito is such an alternative. So in a paradoxical way, it may actually push physicians and patients to consider this therapy more readily than they might otherwise have.

All right. Thank you. And then on the R&D side, one question on gel mito. I believe you had a study, either it was Olympus or maybe a separate study where you were looking at gel mito in the maintenance setting for a longer-term use and or patients coming back on gel mito after initial use, if they have recurrence, want to ask about where the status of those data are. And also, with regard to the upcoming bladder trial, Mark, you mentioned a couple of interim opportunities, maybe to earlier kind of moving, you know, advancement into a file and want to ask if you could give any more color around what the bars would be for those interims. Thanks.

Sure, thanks. So with respect to maintenance, I think the Lancet article actually gives a very good description of what we do and don't know about maintenance. And what we do know is that most patients in the trial received a dose at least of maintenance therapy, but the application of maintenance across the trial was so individualized as to make it very difficult for us to draw any conclusions about the value of maintenance in this context. So that's really the use of maintenance is really left to physician discretion in the context of the use of gel mito in the treatment of upper tract low-grade disease. With respect to re-treatment, we are contemplating a re-treatment program because obviously that would be very valuable to patients who had a good response and then relapsed. So we would want to study the utility of re-treatment and plan to do that. We had a retreatment trial open, but unfortunately, we didn't have any patients to treat. So we're going to reinitiate that program as we continue to follow patients in the gel mito group, because we can continue to follow those patients for up to three years for additional information. And then finally, with respect to the bladder program and the bladder phase three, we haven't really disclosed what the bars would be for earlier closure or reevaluation of the data, but it's obviously part of the design. And as we initiate the trial and start to accumulate information, if there are exciting updates, I'm sure we'll be sharing them with you, but we haven't specifically talked about that yet.

Great. Thanks so much for giving the questions.

Thank you. Our next question comes from Paul Choi from Goldman Sachs. Please go ahead.

Hi. Thank you, and good morning, everyone, and congrats on all the progress. Two pipeline questions for me, if I could. First, on 102 and the plan phase three that's going to start later this year, can you maybe just clarify for us just in terms of potential patient stratification, how, if any, you're going to include with regard to risk factors and or prior turbid experience or only naive patients. And then I had a follow-up question with that.

Mark, you want to go ahead and answer that?

Yeah, sure. Paul, thank you. So, great question. This is in our Phase II study. As you know, the study included both patients with new disease, patients who had not previously been treated, as well as patients who had recurred. And, in fact, we know that the majority of patients in the Phase II trial were patients with a prior history of which is very characteristic, as I'm sure you know, of the group we are focusing on, which is the intermediate risk low-grade population. And just to remind everyone, intermediate risk is disease that is low-grade for the most part, and in our study will be low-grade. multifocal larger tumors, and very importantly, a history of prior treatment for relapsing disease. So we will be focusing on exactly the same population that we looked at in the Phase II trial and would expect that there might well be a greater number of patients with recurrent disease because that is the nature of the population. There will likely also be patients with de novo disease as well.

Okay, thanks for that clarification, Mark. And then my second pipeline question is on 302, and specifically with regard to sort of next steps and potential data updates, either for 201 or for the Xelaforiflumab CTLA-4, either when you might potentially provide either monotherapy or combination updates. Thank you very much.

Paul, thanks. So we are working in earnest internally. As we have announced previously, our plan is to initiate a human trial as part of this composite program this year. And that is still our intention, but we haven't disclosed any additional details about that. And some of this is, as I think you can well imagine, a series of the complex interactions of the planning of the clinical trial with various preclinical activities as well, including certain aspects of formulation. But our plan is to go ahead with clinical experiments toward the end of this year, and we'll certainly update you as we have more specifics to share.

Thank you very much.

Thank you. Our last question comes from the line of Matt Kaplan from Leidenberg Allman. Please go ahead.

Hey, guys. Good morning. Thanks for taking the question. Just wanted to follow up a little bit more on the 102 Phase III clinical trial design and timeline. Mark, maybe perhaps you can give us some additional detail in terms of what what you expect the primary endpoint to be and the potential timeline for the completion of that study.

Yeah, I think – hi, Matt. Thanks for joining. Mark gave most of the data during his comment section, but it's around 600 patients, and we expect enrollment to be completed within a year, as I mentioned during an earlier Q&A. a large portion of the patients will be outside of the U.S. to ensure that our enrollment is not slowed down at all by the pandemic. And we're very confident in what we've been doing, the work that the development team has been doing under MARC and specifically around, you know, getting some accelerated CROs in place. And, you know, so we are well underway to start that study. And so we feel really good about it. And as what mentioned, we have a couple of pre-specified interim analysis to ensure that at points – look, it's an event-driven trial, so we can't tell you exactly what the timing will be, but our very conservative projections say that it would be complete within three years. And that's assumed it goes all the way through It had both non-inferiority and superiority. And so that's sort of the data and the kind of guidelines that we'll be following. Again, it's an event-driven study. There will be a data monitoring committee, you know, who will be taking a look at the data, you know, because it's blinded to us. And so I think that sort of gives you all of the information we have at this point. I'm not sure, Mark, if I missed anything or something you want to add.

No, Liz, thanks. Matt, I think that's what we can share right now.

Well, I'm sorry. You asked about the endpoint. Yeah, I'm sorry, Mark. He asked about the endpoint. Let's talk about that endpoint.

Yeah, so obviously in this game with this disease, the issue is managing recurrence. So, you know, in a typical setting, we'd be talking about recurrence-free survival for this population. So I hope that helps with that particular question.

Thanks, Liz. Thanks, Mark. And congrats on the progress.

Thank you.

Thank you. This concludes our Q&A session. At this time, I'd like to turn the call over to Liz Barrett for closing comments. Please go ahead.

Great. Thank you. Thank you, Operator. We've made significant progress in 2020. We look forward to continuing the momentum. It has been, as I've mentioned a couple of times on the call, better than we expected, even including in the pandemic. You know, we've hit the ground running from a commercial standpoint. We've hit every milestone with a positive outcome. You heard Peter talk about our financial and financial situation. You know, the team has really shown creativity and resilience in launching our first product as we navigate through COVID-19. And I'm really confident in our ability to continue to advance the mission of to pioneer new treatments to improve patient care, especially cancers and neurologic diseases. Our overall fundamentals and long-term prospects remain strong. Our team continues to work around the clock to make sure that we provide gel mito to patients who have been waiting for better options. And as we make progress with our commercial launch, we advance our pipeline of innovative medicines, You know, we look forward to providing you with further updates. So we really appreciate your time and interest in our company and for your continued support. So, operator, you may disconnect at this time. Thank you.

Thank you. Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect. Good day.