Sesen Bio, Inc.
Q4 2018 Earnings Call Transcript

Published: 4 Mar 2019

[Operator:]

Good day, ladies and gentlemen and welcome to the Sesen Bio's 2019 Business Update Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session and instructions will be given at that time. [Operator Instructions] And as a reminder today's call is being recorded. I would now like to turn the conference over to Erin Clark, Director of Strategic Planning & Investor Relations. Please go ahead.

[Erin Clark:]

Thank you and good morning everyone. Earlier this morning, we issued a press release outlining our fourth quarter and full year 2018 financial results. The press release and the slides to which we will refer are available in the Investors section of the Company's website at sesenbil.com. On the call with me today are Dr. Thomas Cannell, President and CEO, Dr. Dennis Kim, Chief Medical Officer, Richard Fitzgerald, Chief Financial Officer, and Dr. Chad Myskiw, Head of Global CMC Project Management. Today's discussion will include forward-looking statements related to the Company’s current plans and expectations which are subject to risks and uncertainties. Actual results may differ materially due to various factors including those described in Sesen Bio’s most recent Annual Report Form 10-K and other SEC filings. These statements represents Sesen Bio’s views as of this call and should not be relied upon as of any future date. Sesen Bio undertakes no obligation to publicly update these forward-looking statements. With that, I’ll turn the call over to Tom.

[Thomas Cannell:]

Thanks, Erin and thanks everyone for joining us. A lot has happened since our last call in January 3rd, where we announced positive preliminary data from our Phase III trial Vicinium called the VISTA trial. Today I am excited to share a number of updates on our progress toward bringing Vicinium to patients with non-muscle invasive bladder cancer. If you turn to Slide 3, our agenda slide, there are really five key parts to the Sesen Bio story that I wanted to provide an update on today. First, bladder cancer is an area of significant unmet need and we are seeing strong support for new treatments from regulators, payers, patients and physicians. Second, our Phase II and Phase III clinical trials are highly aligned with FDA guidance. We are confident in the probability of regulatory approval and we look forward to upcoming discussions with the FDA. Third, we believe Vicinium has a unique dual mechanism of action, which made physician it as a preferred choice for combination therapy with checkpoint inhibitors. Fourth, we see the potential for action and advocacy from physicians, patients and their caregivers and payers in support of Vicinium and we believe the commercial opportunity is significant. And finally, unlike many biologics, and especially Antibody Drug Conjugates or ADCs, Vicinium is a fusion protein with a straightforward and elegant microbial expression system that has the potential to reduce cost of goods and create a simple and reliable manufacturing supply chain. If you turn to Slide 4, we always start with the patient journey for bladder cancer which is a long arduous and humbling experience. We believe that bladder cancer is different from most other diseases in this regard. In fact, patient surveys have shown that the experience of those with bladder cancer is one of the poorest when compared to other cancers and we heard from physicians that quality of life is the most important factor in treating these patients. Nothing is more damaging to the patient’s quality of life than full bladder removal known as radical cystectomy. Turning to slide 5, the huge unmet need in bladder cancer is really a function of two things. First, the tremendously high disease burden bladder cancer is the most expensive cancer to treat in the United States with the significant impact from both radical cystectomy and disease progression. And second, the treatment choices are very limited. BCG is first-line and we know BCG therapy most eventually fail from those patients. Radical cystectomy is second-line with a significant impact on mortality, morbidity and quality of life. And because of this, stakeholders are extremely supportive of any new therapy that could be used in lieu of radical cystectomy. Slide 6 helps to describe carcinoma in situ, which is the most difficult type of non-muscle invasive bladder cancer to treat. Carcinoma in situ is a field change disease which may involve microscopic changes with the entire bladder urothelium. This form of bladder cancer is always considered high-grade and higher risk. If left untreated carcinoma in situ will persist, and over 50% of patients will progress to muscle-invasive tumors. There are few cancers that are sometimes expressive to field change such as lung cancer and colorectal cancer and these field change cancers are extremely difficult to treat. To provide some clinical context for the results we will show in a few minutes, patients in the VISTA trial failed on two courses of BCG, which is the gold standard for treatment of high risk non-muscle invasive bladder cancer. Each patient needed to be confirmed cancer-free throughout a rigorous, local and independent central review of all urine cytology and biopsy samples and a complete response met that the bladder is completely clean at each time point. Now let’s turn to the discussion of our confidence in the probability of regulatory approvals for Vicinium. Please turn to Slide 8 and just a reminder that Vicinium is a small single-protein strand comprised of an antibody fragment tethered to a cytotoxic payload. Vicinium selectively targets cancer cells while generally avoiding healthy cells, which we believe ties to its favorable safety profile. Vicinium inhibits protein synthesis and is able to kill both rapidly proliferating and slow-growing cells, which ties to its strong and durable anti-tumor activity. Please turn to Slide 9, which in my mind is one of the most important slides. We have been highly collaborative with the FDA and we have designed our Phase II and Phase III clinical trials based on the FDA’s input every step of the way. We now feel we are aligned with all key elements of the 2018 guidance and this alignment, along with the clinical trial results observed to eight to-date give us confidence in the probability of regulatory approval. In a recent teleconference with the FDA, they requested that we come in for a pre-BLA Meeting in mid-2019. We will be scheduling that meeting and look forward to future discussions with the agency. The graph on Slide 10 captures all the primary and secondary endpoints of our Phase III VISTA trial. As a reminder, our VISTA trial studied a 133 patients across three cohorts divided by histology and time to recurrence after BCG. We have previously reported on the complete response rate which is one of the primary endpoints. Today, I’ll provide an update on three other efficacy endpoints, duration of response, time to disease recurrence including recurrence-free rate, and time to cystectomy. What you will see is robust and durable efficacy data for Vicinium across a spectrum of endpoints. Equally important is our strong safety and tolerability profile. We feel we have a favorable profile relative to BCG, Valstar and checkpoint inhibitors. The fact that Vicinium targets cancer cells while generally avoiding healthy cells is important as is our Intravesical administration, consistent with that to BCG which is a preference of the FDA. What I want to emphasize in this slide is that FDA guidance says that the approval of a marketing application is based on a favorable risk benefit assessment and that ratio for Vicinium is really the basis of our confidence in our approvability. Please turn to Slide 11 for a quick review of the complete response data from our Phase II and Phase III clinical trials for Vicinium. Two things are very meaningful. First, the significant and reproducible complete response rate between Phase II and III giving us two important trials for BLA submission. Second, we believe that the lower bound of the 95% confidence interval rules out a clinically unimportant complete response rate per FDA guidance, which is illustrated by the confidence band shown on the graph. Slide 12 shows all carcinoma in situ patients who had a complete response at three months in our VISTA trial, as you can see, based on a Kaplan-Meier estimate for patients that achieved a complete response at three months, 49% had a complete response duration of nine months or longer. That means if you are a responder at three months, you have roughly a 50% chance of maintaining a complete response through your first year of therapy. We will have more information when we present the updated 12-month dataset mid-2019, but we are certainly pleased with the durable anti-tumor activity that was reflected in these preliminary data. Slide 13 shows data for cohort 3 from our VISTA trial which is high-risk, non-muscle invasive bladder cancer patients who have progressed to Ta or T1. These patients have no visible evidence of disease at days thereof the trial and therefore rates of disease recurrence and time to disease recurrence are appropriate endpoints to evaluate response. As you will note on the Slide, the FDA guidance recommends including these patients in the overall benefit risk analysis, however these patients should not be included in the primary endpoint. An important reminder is that these are high-risk patients for whom radical cystectomy is the next step if they have disease recurrence. You can see on this slide that at six months, 56% of patients remain disease free and at 12-months, 36% of patients remain disease-free. We believe this further supports Vicinium’s demonstration of clinically meaningful anti-tumor activity in a high-risk patient population. On Slide 14, is the time disease recurrence for all papillary patients. As you can see, median time to disease recurrence, based on the Kaplan-Meier estimate is 270 days. Again, we believe this demonstrates Vicinium’s significant and durable efficacy and we will have an update on this endpoint as well in mid-2019. On Slide 15, we see time to cystectomy data across all patients. As shown on the slide, the FDA provides guidance that says one, the goal of therapy in patients with BCG unresponsive non-muscle invasive bladder cancer is to avoid cystectomy. And two, that there are variations in patients and healthcare provider preferences that can confound the interpretation of this endpoint. Nonetheless, the FDA notes that a delay in radical cystectomy is a direct patient benefit and they recommends just collect these data and submit as supportive evidence of effectiveness. Because the number of cystectomies observed to-date is so low, a median time to cystectomy cannot be calculated. Therefore, the median was estimated using an intensive, nonparametric approach commonly used in clinical trials to generate estimates and confidence intervals for data sets that are incomplete by sampling existing data with replacements. Based on this method, we estimate that the median number of cystectomy-free days for all patients in the VISTA trial is 519 days or approximately 18 months, based on current trends of preliminary data. Despite this significant delay in cystectomy, it is important to note that no patient develop metastatic bladder cancer while on therapy and either or Phase II or Phase III clinical trials through the cut-off dates. We will continue to provide updates on this important endpoint as we felt these data are very meaningful importance to payers, physicians and patients. On Slide 16, we see the consistent safety and tolerability demonstrated by our Phase II and Phase III clinical trials. Again, this appears to be the benefit of an intravesical product that selectively targets cancer cells while leaving those healthy tissues alone. We have had some investigators say that Vicinium is so well tolerated that their patients sometimes ask whether they are even on treatment and it seems to be the view of key opinion leaders and high-prescribing urologists that the safety profile for Vicinium is favorable relative to BCG, Valstar and checkpoint inhibitors. Turning to Slide 18, we first showed this slide on January 3rd call, so I will go through it on a – at a high level, but it is important part of our story and we are happy to discuss it in more detail during Q&A. Vicinium has a very unique, dual mechanism of action, which leads us a scientific hypothesis that Vicinium could have an additive or even synergistic effect, when given in combination with checkpoint inhibitors. Slide 19 shows preclinical and clinical data that we have presented before that support our scientific hypothesis by demonstrating the ability of Vicinium to activate the patient’s immune system. And Slide 20 shows that we are testing this hypothesis with the National Cancer Institute to assess the combination of Vicinium and Durvalumab, which is an anti-PD-L1 checkpoint inhibitor. In the future, we think it could be significant to be positioned as the preferred choice for combination therapy with checkpoint inhibitors and that combination could be a valuable alternative for patients who do not achieve the complete response on either BCG or Vicinium. I’d like to shift to a discussion of the exciting commercial opportunity we have for Vicinium. As you will see on the next few slides, we have begun preliminary market research among patients, physicians and payers. This work sets the foundation for our overall go-to-market strategy, but of course, any significant commercial investment will be stage-gated until after BLA submission. So please turn to Slide 22. We have recently conducted 11 in-depth interviews with high-prescribing urologists and key opinion leaders to get their view on our most recent clinical data. These interviews went one to three hours and we were very pleased with the results. In general, after viewing all of our data, prescribing urologists stated they would prescribe Vicinium to approximately 60% of their BCG unresponsive, high-risk non-muscle invasive bladder cancer patients, while key opinion leaders stated, they would recommend Vicinium to approximately 70% of their colleagues. From talking to these physicians, we know that their average patients is in their mid-to late 70s, and have endured a grueling journey since diagnosis. Because of this, it is clear that at the forefront of their treatment decision-making is the significant unmet need and patient quality of life. All prescribing physicians in our research rated our dual mechanism of action ten out of ten for relevance and importance, which is remarkable and the duration of response and time to cystectomy data resonated with them due to the potential for significant impact on the lives of their patients. This efficacy data was further enhanced by the general safety and tolerability of Vicinium, which they believe was favorable to currently available treatments such as Valstar and checkpoint inhibitors. Overall, we feel these are very promising results and look forward to collecting and sharing additional data. Slide 23 responds to a lot of requests we have been getting on the overall market opportunity and potential price benchmarks for bladder cancer. I am not going to go through in detail today, as I think it’s self-explanatory and well referenced. But I’d be glad to address any questions in Q&A. We have a good understanding of the addressable market and price benchmarks that exists in the U.S., and we are moving forward at this time with quantitative research and demand-based forecasts. We are also doing market research outside the U.S. and we have been talking to potential partners from outside the U.S. While the U.S. accounts for about 20% of the total global market opportunity, Europe, Latin America, the Middle East and Asia-Pacific, also represents sizable market opportunities. Because of this, we believe that OUS sales could outpace U.S. sales of Vicinium in the future. We know that OUS partnering process can take a minimum of six to 12 months. So, as we get closer to BLA submission in the U.S., I’ll be sharing more with you on the OUS opportunity as well. Turning to Slide 24, just a reminder that BCG has indicated first-line use and we are pursuing second-line use in lieu of radical cystectomy. In understanding the patient journey, we know the change is hard for physicians and patients. In the future, when the patients switch from BCG to Vicinium, they will still drive to the same treatment center, talk to the same urologists and nurses, utilize the same type of urinary catheter into our infusion and undergo the same lab test including cytology and cystoscopy. However, if the patient is prescribed to systemic intravenous therapy, they would have to go to a new treatment center or a hospital, talk to a new medical oncologist and new nurses and then go to a new intravenous infusion center for their therapy. Therefore, we believe that continuity of care between BCG and Vicinium is a huge advantage and will lead to much more rapid adoption and uptake of Vicinium at launch. Slide 25, to me is a very compelling slide. We are gaining a clear understanding of what will drive action and advocacy from our three customer segments. We believe that this is a unique situation where we could have a virtuous cycle driving demand and while the drivers of behavior are very different for each segment, we see the opportunity for a very favorable response from all three customer groups. We think doctors will be highly motivated from our clinical trial data and if approved will recommend Vicinium to their patients. We think patients, their caregivers and their families will be motivated by the opportunity to avoid or delay radical cystectomy and disease progression and be very likely to ask their doctor for Vicinium. Finally, we believe that payers who are currently spending over $4 billion a year for bladder cancer will be delighted by the introduction of therapies that could actually reduce overall healthcare cost. We have started talking to commercial payers, as well as Medicare and we know that they are interested in value-based contracts that appropriately share risk based on value. We believe that there is a potential for significant reimbursement and advocacy by payers for the appropriate use of Vicinium. As I said, we believe this could be a unique market dynamic where all of the key customer segments are advocates and motivated to take action. And given the smooth transition that will be possible from first-line BCG to second-line Vicinium, we think there is an opportunity for strong and sustained growth after gaining regulatory approval. I am very pleased with the progress made in our commercial planning today and believe it begins to outline the significant commercial opportunity. As we get closer to launch, I’ll be sharing more details on this important area. On Slide 27, you can see an illustration of our supply chain. In the interest of time, I will walk through this quickly, but we have a lot more information on this topic and we are happy to discuss it further in Q&A. On the top of this slide is an illustrative example of our single-step supply chain. We believe this simple inelegant process is much different than ADCs and most biologics and enables us to optimize reliability and efficiency. Finally, turning to Slide 28, we filed our 10-K on Friday, March 1st and we finished 2018 with roughly $50 million in cash and cash equivalents. As we noted on our last call, we have a financial runway that runs into 2020 and we have multiple options available to ensure that we have the capital required to advance this important work as we manage the evolution from a late-stage development company to a commercial one. So please turn to Slide 29, as a reminder of the five key parts of our story right now. We are very excited about the opportunities we have ahead of us to fulfill our mission to save and improve the lives of patients, while providing value for shareholders. Let me conclude today by congratulating the entire Sesen Bio team who have worked incredibly hard to advance Vicinium to this stage of development. We have tremendous confidence in Vicinium and our company. Finally, I would like to thank our patients and their families for their courage, and for the honor of being part of their important journey. With that, we will open the line to take your questions. Operator?

[Operator:]

[Operator Instructions] And our first question comes from John Newman of Canaccord. Your line is now open.

[John Newman:]

Hey, good morning and thanks for taking my question. Congrats on the good progress that the maturing data. Tom, I just wondered if you could talk to us, just for a few seconds about what types of things do you think you would like to discuss with the agency when you meet with them for the pre-BLA meeting? Thanks.

[Thomas Cannell:]

Yes, thanks, John and good morning. So, as I mentioned, we had a recent teleconference with the FDA and they requested that we go through the formal process of requesting a pre-BLA meeting in mid-2019 that’s of course a Type-B meeting. So, we will be submitting that formal meeting request and then, roughly 30 days later, supporting briefing book that goes with it. As we talked about before, there is really two outstanding areas that we want to discuss with them and we have specific questions on that. First of all, is of course the 12-month data set from the VISTA trial. We want to make sure that that is the entirety of what they need along with our Phase I and Phase II data as well as preclinical data for BLA submission. So, we are really looking forward to that conversation. And then, of course, John, the other part of it that we talked about is preparing for module 3 for the CMC module. As you know, and as we announced last October, we are working with Fuji in terms of we have a tech transfer going on and Fuji will provide commercial supply for us as we prepare for launch. As we just noted in the press release this morning, we are doing this full GMP run, full-scale GMP run in the second quarter and then the question for the agency that will come up as well is, how we achieved comparability between the supply we use that came out of our Winnipeg site for Phase II and Phase III and the supply produced by Fuji. So the question is, one of an analytical comparability protocol that can be used to ensure that if the same high-quality product. So, I think those are the two outstanding issues that we want to talk to the agency as we move down the path toward BLA submission. Does that make sense, John?

[John Newman:]

Yes, it does. Thank you.

[Thomas Cannell:]

Thank you.

[Operator:]

Thank you. And our next question comes from Yale Jen of Laidlaw & Company. Your line is now open.

[Yale Jen:]

Thanks for taking the question and congrats on the progress. My question is that, this morning you have additional data besides response rate. So, those seems to be very promising. Would you might give us a recap or maybe an assessment that this is in totality so far in this combination in terms of data. What you think the risk benefit profile of the drug? And is there any insufficiency you think you might have or you feel that’s very good about it? Thanks.

[Thomas Cannell:]

Yes. Thanks, Yale. I’d be glad to do that. So, as you know, and as you saw in Slide 10, it’s really important to understand the whole scope of the primary and secondary endpoints for the VISTA trial. So there are seven efficacy endpoints. On January 3rd, I presented the complete response data. We feel very good about that, because we think it excludes the clinically unimportant CRR which is consistent with the guidance of the FDA. Today, I took you through the duration of response, time to disease recurrence and time to cystectomy endpoints. And I think what you are seeing in all of those is not only strong efficacy, but a durable anti-tumor effect. And then, what will be part of the package by the time we get to the pre-BLA meeting will be the data we have on it, event-free survival, progression-free survival and overall survival. And so far, as I mentioned, we feel very good about the efficacy and the durability of Vicinium in those endpoints. But, probably even more important is the safety and tolerability. So, again, we have a very unique mechanism of action. We are the only agent we are aware of an Phase II or Phase III clinical trials that selectively attacks the bladder cancer cells and leaves the healthy tissue alone. We think that confers a significant safety advantage. We also are administered Intravesically which is the strong preference of the FDA and we feel now like we have a data set that shows that we have a significant safety and tolerability advantage relative to BCG, relative to Valstar and relative to checkpoint inhibitors. And as you know from reading the guidance from us here from the FDA, they say very clearly that the approval of a marketing application is based on a favorable risk benefit assessment. So, it’s so important to realize that while there is seven efficacy endpoints, as important is the safety and tolerability data and we feel that it’s the benefit risk assessment that gives us the confidence that we have in approvability for Vicinium. Does that make sense, Yale?

[Yale Jen:]

Sure, absolutely. And maybe just follow-on a little bit on the endpoint you have not discussed which is the survival base would it be event-free or progression-free. Do you think by mid-year, you will get the meaning of that? Or you simply might just get a certain – let’s say 12 months or whatever month of percentage of survival – progression-free survival? What do you think the majority of that the data might be at the time you report the 12 months data?

[Thomas Cannell:]

Yes. It’s a really good question. I think it could very well be the case as what we described with the cystectomy data that the events are so low that we are not able to achieve a median and therefore we’ll use projection methodologies and working with the FDA to project what we think time to cystectomy event-free survival, progression-free survival and overall survival are. And we are working closely with the FDA on how to do those analyses, but it’s very possible with all of those that will need additional methodologies because with the low event rates.

[Yale Jen:]

Okay, great. And thanks and again, congrats on the progress so far.

[Thomas Cannell:]

Great. Thank you, Yale.

[Operator:]

Thank you. And our next question comes from Swayampakula Ramakanth of H.C. Wainwright. Your line is now open.

[Swayampakula Ramakanth:]

Thank you. Good morning, Tom. Couple of quick questions. So, by the cut-off date that you presented today, the data that you presented today, what was the follow-up time that you have seen in these patient score? And how much of a complete follow-up would you have by the time you come up with the next update?

[Thomas Cannell:]

Yes, thanks, thanks, RK. So, of course, the cut-off for this was December 3rd and it’s the same cut-off date as the data we presented in January. We follow in terms of patient, we follow the FDA guidance. So it’s quarterly for the first two years for a patient, then it’s every six months for the next two years and it’s annually after that. And again, we’ve said that we will present the data mid-2019, so I think you can expect the next cut-off to be kind of in the March, April timeframe I would guess. And so, you will see an extra three to four months of data at that time, that’s just a general estimate of what we can expect. RK, does that make sense?

[Swayampakula Ramakanth:]

Yes, yes. And then, in terms of FDA, how much of this data could – did they see in that conference call that you had or it was just an administrative call?

[Thomas Cannell:]

Yes, and I won’t go into the specifics of the detail of it. But as you can imagine at this stage of the process, we are approaching a pre-BLA meeting. We are sharing everything with the agency preparing all of the data for the agency. So, it’s really, at this point a very in-depth conversation. I don’t want to go into the specific details of the call, other than future calls where it’s minute and we will build our share of that. But, at this point, there is a – it’s a very in-depth discussion going on with the agency.

[Swayampakula Ramakanth:]

Okay. And the last question I have is, I am just trying to understand the profile of the patients that you had in the current VISTA trial versus the Phase II studies that you have just put that earlier and also against the Valstar patients and the patients in the Valstar study, just so that we get a good sense of the risk benefit profile that you believe very strongly that Vicinium has against any other competition at this point?

[Thomas Cannell:]

Yes. So, thank you. That’s a very good question. So, again, I’ll just reference you to the back-up. So you have at the patient demographics on back-up slides 31, in case you want to reference it. But as we gather more information, we are able to kind of have a more complete comparison to Valstar. So, again, as you know, Valstar is a cytotoxic agent, it penetrates healthy and cancerous cells. Valstar has very high rates of bladder pain and bladder spasm greater than 30% whereas as with Vicinium it’s those – for those categories it’s less than 5% and when we talk to key opinion leaders and high-prescribing urologists they tell us that they see significant toxicity and side-effects with Valstar and again, some of those same investigators are saying, when the patients are on Vicinium. They are not even sure if they are on the therapy or not if so well tolerated. If you go back and review the original FDA application, again, this was back in 1998, what 20 years before the FDA put out its official guidance. But if you go back and look the FDA only validated seven of the 90 complete responses in the original submission, so. And that was at six months. So even though eventually, Valstar filed with 18% complete response rate at six months, the agency still what saying, gotcha, it looks like 7.7% for us and I think, if Valstar were held to today’s standards, they have a much lower six months complete response. Just a reminder that even they are 18%, it’s significantly lower than our 27% complete response at six months. Valstar only had 70% of patients that had two full courses of BCG. So much more prognostic, heterogeneity than our VISTA trial, where all patients had to go through two full courses of treatment, a minimum of seven doses of BCG, so, Valstar was treating an easier to treat. I’ll also point out that, during the trial, Valstar had more depths for metastatic bladder cancer and that’s reported in their original submission to the FDA. As I mentioned, at this point, there have been no cases of metastatic bladder cancer out of our Phase II or Phase III clinical trials for Vicinium. So, those are the – those I think, RK, are the significant differences. I mean, don’t get me wrong, there have only in the history, since the FDA was formed in the early 1900s there was only been three products that were approved for non-muscle invasive bladder cancer. An old product in the 50s, BCG in the 80s, and Valstar in the 90s. So, Valstar plays an important role for patients. We just think that there is significant differences in terms of efficacy and especially in terms of safety for Vicinium versus Valstar, which again gives us great confidence in terms of our overall approvability. Does that make sense, RK?

[Swayampakula Ramakanth:]

This is very, very helpful. Thank you very much. Thanks for all that color and good luck and talk to you soon.

[Thomas Cannell:]

Great. Thanks, RK.

[Operator:]

Thank you. [Operator Instructions] And our next question comes from Chris Howerton of Jefferies. Your line is now open.

[Chris Howerton:]

Great. Thank you. Well, thanks for the updates and lots of good progress. And I think most of the questions have been answered at this point. The only question that I had was, Tom, you mentioned a little bit about some of the commercial work you’ve been doing in Europe. And just maybe you could remind us on the regulatory status ex-U.S.? And maybe a little more color around what potential partnering might be for regional deals outside the U.S.?

[Thomas Cannell:]

Yes, great. Thanks, Chris and good morning. So, we have had some initial discussions with regulators in Europe. But I have nothing really to report. And I think as I’ve mentioned previously, we envision our commercial model outside the U.S. where we rely on partners. We picture that those partners become the marketing authorization holder and they manage everything from regulatory to safety. It’s been my experience that if you use strong local companies, they have much stronger relationships with the regulatory authorities and that can really expedite the submission process and approval as well as other issues such as pricing. What we envision is probably anywhere between six and ten regional partnerships. So, I mentioned, you might have a partner for Latin America, a partner for Europe, a partner for the Middle East, maybe North Africa, Asia, maybe Japan, that going to be such a big market, maybe Japan is alone, but maybe Asia-Pacific and other region. And we picture that ultimately we will have partnerships with six or ten partners that cover 60 to 80 countries outside the U.S. As we’ve said, we look at 50-50 value share partnerships and then, the value is transferred with upfront payments, with milestones and then some type of royalty payments. So that’s kind of the construct. We’ve had a lot of very promising discussions. But as I mentioned, and having been through this a few times before, it’s a process - that’s partnership process and I would expect it to take six to 12 months before we’d actually be signing deals. So, I wouldn’t expect anything imminently. But I think around the time of BLA submission, really that process will accelerate, we will be able to finalize some of those partnership agreements and then, we will be able to provide much more transparency publicly. Does that make sense, Chris?

[Chris Howerton:]

Yes, yes, definitely. And I know that you are saying that you just had some preliminary discussions with other regulators. But at this point, should we be expecting additional clinical work in other regions? Or do we believe that the VISTA trial will be sufficient for approval in other regions as well?

[Thomas Cannell:]

Oh, it’s a really good question. I think it will be a mix. I think in certain countries – well, almost certainly there will be some sort of additional study in patients from that geography that’s required. And then, I think there will be many markets where the FDA and/or the European approval suffices. So, I would expect a mix of those that’s certainly been my experience in the past and we’ll provide more color on that going forward.

[Chris Howerton:]

Okay, all right. Great. Well, thanks for taking the questions and congrats again.

[Thomas Cannell:]

Great. Thanks, Chris.

[Operator:]

Thank you. That concludes our question and answer session for today. I would like to turn the conference back over to Tom Cannell for closing remarks.

[Thomas Cannell:]

Great. Well, thank you everyone for calling in today and thanks so much for all the great questions. I mean, ours is a pretty straightforward story. At this point, we think it’s an execution story. We know bladder cancer is an area of huge unmet need and we want to work with stakeholders to help bring new treatments to the market. We are confident in the probability of regulatory approval and we’ll work closely with the agency on the path forward. We think our dual mechanism of action gives us the unique advantage and we could have an additive or even synergistic effect with checkpoint inhibitors. We will continue to explore that area. As I presented, there is strong – a strong commercial opportunity in the U.S. and OUS and we have a lot of work in finalizing our go to market strategies and our commercial plans. And then, we will continue to move forward with our manufacturing and supply chain plans. We think we have a very reliable, elegant and efficient supply chain approach that gives us the unique advantage. So, I really appreciate you all calling in and hope you all have a great day. Thank you.

[Operator:]

Ladies and gentlemen, thank you for participating in today’s conference. This does conclude the program and you may all disconnect. Everyone, have a great day.