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Edited Transcript of SESN earnings conference call or presentation 4-Mar-19 1:00pm GMT

Q4 2018 Sesen Bio Inc Earnings Call

Cambridge Mar 10, 2019 (Thomson StreetEvents) -- Edited Transcript of Sesen Bio Inc earnings conference call or presentation Monday, March 4, 2019 at 1:00:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Erin Clark

Sesen Bio, Inc. - Executive Director, Strategic Planning & IR

* Thomas R. Cannell

Sesen Bio, Inc. - President, CEO & Director

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Conference Call Participants

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* Christopher Lawrence Howerton

Jefferies LLC, Research Division - Equity Analyst

* I-Eh Jen

Laidlaw & Company (UK) Ltd., Research Division - MD of Healthcare Research & Senior Biotechnology Analyst

* John Lawrence Newman

Canaccord Genuity Limited, Research Division - Principal & Senior Healthcare Analyst

* Swayampakula Ramakanth

H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst

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Presentation

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Operator [1]

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Good day, ladies and gentlemen, and welcome to the Sesen Bio 2019 Business Update Call. (Operator Instructions) And as a reminder, today's conference call is being recorded.

I'd now like to turn the conference over to Erin Clark, Director of Strategic Planning and Investor Relations. Please go ahead.

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Erin Clark, Sesen Bio, Inc. - Executive Director, Strategic Planning & IR [2]

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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 sesenbio.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 represent 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.

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Thomas R. Cannell, Sesen Bio, Inc. - President, CEO & Director [3]

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Thanks, Erin, and thanks, everyone, for joining us. A lot has happened since our last call on January 3, where we announced positive preliminary data from our Phase III trial of 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 5 key parts to the Sesen Bio's story that I want 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 may position 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 hear 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 2 things: First, the tremendously high-disease burden. Bladder cancer is the most expensive cancer to treat in the United States with a 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 will eventually fail for most 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 of the entire bladder urothelium. This form of bladder cancer is always considered high grade and high risk. If left untreated, carcinoma in situ will persist, and over 50% of patients will progress to muscle invasive tumors. There are a few cancers that are sometimes expressed as 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 2 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 method the bladder is completely clean at each time point.

Now let's turn to discussion of our confidence in the probability of regulatory approval 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 antitumor 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 today -- 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 133 patients across 3 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 3 other efficacy endpoints; duration of response, time to disease recurrence, including recurrence-free rate; and time to cystectomy. What you'll see is robust and durable efficacy data for Vicinium across the 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 of BCG, which is a preference of the FDA.

What I want to emphasize on 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 rates between Phase II and III, giving us 2 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 bands shown on the graph.

Slide 12 shows all carcinoma in situ patients, who had a complete response at 3 months in our VISTA Trial. As you can see, based on the Kaplan–Meier estimate for patients that achieved a complete response at 3 months, 49% had a complete response duration of 9 months or longer. That means, if you are a responder at 3 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're certainly pleased with the durable antitumor 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 day 0 of the trial and, therefore, rates of disease recurrence and time to disease recurrence are appropriate endpoints to evaluate response. As you'll 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 6 months, 56% of patients remained disease-free, and at 12 months 36% of patients remained disease-free. We believe this further supports Vicinium's demonstration of clinically meaningful antitumor activity in a high-risk patient population.

On Slide 14 is the time to 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'll 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 patient and health care 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 recommend sponsors collect these data and submit as support of 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 interval for datasets that are incomplete by sampling existing data with replacement.

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 the significant delay in cystectomy, it is important to note that no patient developed metastatic bladder cancer while on therapy in either our Phase II or Phase III clinical trials through the cutoff date.

We will continue to provide updates on this important endpoint as we feel these data are very meaningful and important 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 most healthy tissue 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 or Vicinium is favorable relative to BCG, VALSTAR and checkpoint inhibitors.

Turning to Slide 18, we first showed this slide on January 3 call, so I will go through it on a -- at a high level, but it is an important part of our story, and we're happy to discuss it in more detail during Q&A.

Vicinium has a very unique dual mechanism of action, which leads us to 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 discussion of the exciting commercial opportunity we have for Vicinium. As you'll 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 1 to 3 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 patient 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 10 out of 10 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'm not going to go through it 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 exist in the U.S., and we're moving forward at this time with quantitative research and demand-based forecasts.

We are also doing market research outside the U.S., and we had 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 represent 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 6 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 is indicated for first-line use, and we are pursuing second-line use in lieu of radical cystectomy. In understanding the patient journey, we know that change is hard for physicians and patients. In the future, when the patient has switched from BCG to Vicinium, they will still drive to the same treatment center, talk to the same urologist and nurses, utilize the same type of urinary catheter into our infusion and undergo the same lab tests, including cytology and cystoscopy.

However, if the patient is prescribed a systemic intravenous therapy, they would have to go to a new treatment center or 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 a much more rapid adoption and uptake of Vicinium at launch.

Slide 25 to me is a very compelling slide. We're gaining a clear understanding of what will drive action and advocacy from our 3 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 3 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 health care costs. We have started talking to commercial payers as well as Medicare, and we know that they're 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's an opportunity for a strong and sustained growth after gaining regulatory approval. I'm very pleased with the progress made in our commercial planning to date 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're happy to discuss it further in Q&A.

On the top half of the slide is an illustrative example of our single step supply chain. We believe this simple and elegant 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 1, 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 5 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'll open the line to take your questions. Operator?

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Questions and Answers

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Operator [1]

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(Operator Instructions) And our first question comes from John Newman of Canaccord.

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John Lawrence Newman, Canaccord Genuity Limited, Research Division - Principal & Senior Healthcare Analyst [2]

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Congrats on good progress with the maturing data. Tom, I just wondered if you could talk to us just for a few seconds about what types of things you think you'd like to discuss with the agency when you meet with them for the pre-BLA meeting?

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Thomas R. Cannell, Sesen Bio, Inc. - President, CEO & Director [3]

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Yes, thanks, John. 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'll be submitting that formal meeting request, and then roughly 30 days later some supporting briefing book that goes with it. As we've talked about before, there's really 2 outstanding areas that we want to discuss with them and we have specific questions on. First of all, is, of course, the 12-month dataset 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're really looking forward to that conversation. And then, of course, John, the other part of it that we've 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 the full GMP runs, full-scale GMP runs in the second quarter. And then the question for the agency that will come up as well is, how we achieve 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 it's the same high-quality product. So I think those are the 2 outstanding issues that we want to talk to the agency as we move down the path toward BLA submission. Does that make sense, John?

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John Lawrence Newman, Canaccord Genuity Limited, Research Division - Principal & Senior Healthcare Analyst [4]

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Yes, it does.

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Operator [5]

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And our next question comes from Yale Jen of Laidlaw & Company.

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I-Eh Jen, Laidlaw & Company (UK) Ltd., Research Division - MD of Healthcare Research & Senior Biotechnology Analyst [6]

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And congrats on the progress. My question is that this morning, you have additional data besides the response rate, so those seem to be very promising. Would you mind giving us a recap and/or maybe assessment that this is -- in totality so far in this combination in terms of data, what's 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?

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Thomas R. Cannell, Sesen Bio, Inc. - President, CEO & Director [7]

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Yes. Thanks, Yale. I'd be glad to do that. So as you know and as you saw on Slide 10, it's really to understand -- important to understand the whole scope of the primary and secondary endpoints for the VISTA Trial. So there are 7 efficacy endpoints. On January 3, 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're seeing in all of those is not only strong efficacy, but a durable antitumor 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 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're the only agent we're aware of in 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 intravesicaly, which is the strong preference of the FDA. And we feel now like we have a dataset 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 last year 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 are 7 efficacy endpoints as important as a 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. Let me -- does that make sense, Yale?

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I-Eh Jen, Laidlaw & Company (UK) Ltd., Research Division - MD of Healthcare Research & Senior Biotechnology Analyst [8]

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Sure. Absolutely. And maybe just follow-up a little bit on the endpoint you have not discussed, which is survival base, whether that will be event-free or progression free. Do you think by midyear, you will get the mean of that? Or you simply might just get certain, say 12 months or whatever months of a percentage of survival -- progression-free survival? What do you think the mature data might be the time you report a 12-month data?

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Thomas R. Cannell, Sesen Bio, Inc. - President, CEO & Director [9]

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

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Operator [10]

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And our next question comes from Swayampakula Ramakanth of H.C. Wainwright.

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Swayampakula Ramakanth, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [11]

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Tom, a couple of quick questions. So by the cutoff date that you presented today, the data that you presented today, what was the follow-up time that you have seen these patients for? And how much of a complete follow-up would you have by the time you come up with the next update?

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Thomas R. Cannell, Sesen Bio, Inc. - President, CEO & Director [12]

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Yes, thanks, thanks, RK. So, of course, the cutoff for this was December 3, and it's the same cutoff date as the data we presented in January. We follow -- in terms of patient follow-up, we follow the FDA guidance. So it's quarterly for the first 2 years for a patient, then it's every 6 months for the next 2 years and then it's annually after that. And again, we've said that we'll present the data mid-2019. So I think, you can expect the next cutoff to be kind of in the March-April timeframe, I would guess. And so you'll see an extra 3 to 4 months of data at that time. That's just a general estimate of what you can expect. RK, does that make sense?

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Swayampakula Ramakanth, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [13]

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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?

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Thomas R. Cannell, Sesen Bio, Inc. - President, CEO & Director [14]

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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're 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 mandated and we'll be able to share that. But at this point, there's -- it's a very in-depth discussion going on with the agency.

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Swayampakula Ramakanth, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [15]

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Okay. And then -- 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 study that you had quoted earlier and also against the VALSTAR patients, 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?

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Thomas R. Cannell, Sesen Bio, Inc. - President, CEO & Director [16]

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Yes. So thank you, that's a very good question. So again, I'll just reference you to the backup, so you have the patient demographics on backup Slide 31, in case you want to reference it. But as we gather more information, we're 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 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're not even sure if they're on the therapy or not, it's so well tolerated. If you go back and review the original FDA application, again, this was back in 1998, you know what 20 years before the FDA put out its official guidance. But if you go back and look, the FDA only validated 7 of the 90 complete responses in the original submission. So -- and that was at 6 months. So even though eventually, VALSTAR filed with 18% complete response rate at 6 months, the agency still was saying, "gosh, it looks like 7.7% for us." And I think if VALSTAR were held to today's standards, they'd have a much lower 6-month complete response. Just a reminder that even their 18% is significantly lower than our 27% complete response at 6 months. VALSTAR only had 70% of patients that had 2 full courses of BCG, so much more prognostic heterogeneity than our VISTA Trial where all patients had to go through 2 full courses of treatment a minimum of 7 doses of BCG. So VALSTAR was treating an easier-to-treat. I'll also point out that during the trial, VALSTAR had 4 deaths from metastatic bladder cancer, and that's reported in the 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. You know, I mean, don't get me wrong, there have -- only in the history since the FDA was formed in the early 1900s, there's only been 3 products ever 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's 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?

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Swayampakula Ramakanth, H.C. Wainwright & Co, LLC, Research Division - MD of Equity Research & Senior Healthcare Analyst [17]

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This is very, very helpful.

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Operator [18]

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(Operator Instructions) And our next question comes from Chris Howerton of Jefferies.

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Christopher Lawrence Howerton, Jefferies LLC, Research Division - Equity Analyst [19]

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Well, thanks for the update and lots of good progress. 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. 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.?

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Thomas R. Cannell, Sesen Bio, Inc. - President, CEO & Director [20]

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Yes. Great, thanks, Chris. So we have had some initial discussions with regulators in Europe, but I have nothing really to report. And I think, as I have mentioned previously, we envision a 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 6 and 10 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 because Japan, that's going to be such a big market, maybe Japan's alone, but maybe Asia Pacific another region. And we picture that ultimately we'll have partnerships with 6 or 10 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 payment. 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, it's a partnership process, and I would expect it to take 6 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, that -- really that process will accelerate, we'll really be able to finalize some of those partnership agreements and then we'll build -- provide much more transparently -- much more transparency publicly. Does that make sense, Chris?

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Christopher Lawrence Howerton, Jefferies LLC, Research Division - Equity Analyst [21]

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Yes, yes, definitely. And I know that you were saying that you've 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?

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Thomas R. Cannell, Sesen Bio, Inc. - President, CEO & Director [22]

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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. We'll provide more color on that going forward.

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Operator [23]

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Thank you. And that concludes our question-and-answer session for today. I'd like to turn the conference back over to Tom Cannell for closing remarks.

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Thomas R. Cannell, Sesen Bio, Inc. - President, CEO & Director [24]

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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're 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 a unique advantage, and we could have an additive or even synergistic effect with checkpoint inhibitors. We'll continue to explore that area. As I presented, there's 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'll 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 a unique advantage. So I really appreciate you all calling in, and hope you all have a great day. Thank you.

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Operator [25]

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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.