Proteon Therapeutics, Inc. (PRTO)

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Proteon Therapeutics' (PRTO) Management Discuses Changes to the Ongoing Phase 3 PATENCY-2 Clinical Trial Conference (Transcript)

Changes to the Ongoing Phase 3 PATENCY-2 Clinical Trial Conference Call

March 16, 2017 8:00 AM ET

Executives

George Eldridge – Senior Vice President and Chief Financial Officer

Tim Noyes – President and Chief Executive Officer

Steven Burke – Senior Vice President and Chief Medical Officer

Analysts

Ally Bratzel – Raymond James

Stephen Willey – Stifel

Konstantinos Aprilakis – JMP Securities

Justin Collinshaw – Cowen and Company

Jason McCarthy – Maxim Group

Operator

Welcome to the Proteon Therapeutics Conference Calls to discuss our Clinical Trial update for PATENCY-2. [Operator Instructions] I'll now turn the call over to George Eldridge Proteon’s Chief Financial Officer.

George Eldridge

Good morning, and thank you for joining us to discuss the updates to PATENCY-2 our second Phase 3 clinical trial of investigation of vonapanitase. We issued a press release this morning announcing our financial results for 2016 and the focus of this call, the important changes to the ongoing PATENCY-2 trial.

This release and additional background can be found on our website proteontx.com. On today's call we'll be discussing the changes to PATENCY-2 with me today are Tim Noyes our President and CEO. And Dr. Steven Burke our Chief Medical Officer.

Before we begin, and I'd like to remind everybody that our remarks during this call may include forward-looking statements. These forward-looking statements, including statements regarding the number of patients to be enrolled in PATENCY-2, the timing of completing enrollment or releasing results from PATENCY-2, whether and when we may submit a biologic license application or BLA and other statements relating to the clinical and regulatory path forward are subject to risks and uncertainties.

Actual results may differ materially from our expectations. For a discussion of these risks and uncertainties please review the cautionary statements regarding forward-looking statements included in our earnings release and cautionary statements and risk factors included in our 2016 Form 10-K filed with SEC earlier today.

These are available also on our website. All forward-looking statements are made as of today’s date, except to the extent required by law. We do not undertake any obligation to update any forward-looking statement. We also caution you against relying on any forward-looking statements.

I’d now turn the call over to Tim.

Tim Noyes

Thanks George and thanks to everyone for participating in our call this morning. I'll just make a few comments regarding our clinical trial update and then open the call up to questions. So back in December, we announced top line data from Proteon’s first Phase 3 trial, which we call PATENCY-1.

And at that time we highlighted the fact that the trial did not meet the primary endpoint but that important pre-specified efficacy endpoints did show encouraging results. Specifically the pre-specified endpoints of secondary patency and fistula use for hemodialysis both demonstrated clinically meaningful improvements with p-values less than 0.05.

Now remember secondary patency is defined as the time from surgical creations of a fistula to abandonment of the fistula. We also highlighted the fact that vonapanitase appeared to be well tolerated and that adverse events were not different than placebo. So over the past few months Proteon studied the patents with data from PATENCY-1.

We then confirmed the original comments, we made in December and believe the trial was important from a drug development standpoint. And we actually believe the trial was a drug development success because it was well run in terms of important drug development metrics like adherence to protocol, performance of the placebo group compared to expectations and the consistency of the overall results.

It's important to note that vascular access failure is a recurring cause of misery for most patients on dialysis and a significant contributing factor to unacceptably high morbidity and mortality rates. Now despite this medical need, vascular access for hemodialysis is an area that's received very little attention in the Bio Pharma industry. And PATENCY-1 is one of the largest most rigorous trials of its kind in this space.

Proteon and really the entire vascular access community learned a great deal from PATENCY-1 and we feel now better positioned to complete development of our drug candidate that could be if successful in PATENCY-2 the most innovative treatment for vascular access in decades.

Since releasing the top line data in December and analyzing the data further, Proteon has engaged in a productive and highly collaborative conversation with the FDA. As you recall vonapanitase has fast track and orphan designations for hemodialysis vascular access.

Based on the review of our data and our discussions with the FDA we announced today changes to PATENCY-2, our ongoing Phase 3 trial and we outlined the regulatory path forward as agreed to with the agency.

Now I’ll take just a moment to emphasize two important areas of agreement with the FDA. First PATENCY-2 now has co-primary endpoints of secondary patency and fistula use for hemodialysis. As we previously announced in PATENCY-1 74% of vonapanitase patients retain secondary patency at the end of one-year versus just 61% of placebo patients, which corresponded to a 34% reduction in risk of secondary patency loss with a p-value of 0.048.

Additionally we announced that 64% of vonapanitase patients use their fistula for dialysis compared to only 44% of placebo patients with a p-value of 0.006. Second the FDA also agreed that if PATENCY-2 is successful in the co-primary endpoints meaning both p-values are less than or equal to 0.05 then data from PATENCY-2 would provide the basis for a BLA submission as a single pivotal study supported by PATENCY-1. And as a result, based on our discussions with the FDA, we believe that no additional trials would need to be conducted if PATENCY-2 is successful.

So given the potential for a BLA submission based on the results of PATENCY-2, we decided to increase the enrollment from 300 patients as originally planned to 500 patients. The expanded sample size provides greater than 90% power to detect the differences observed in PATENCY-1 trial, with a p-value less than or equal to 0.05 for each of the co-primary endpoints. Now based on the expanded sample size we expect to complete enrollment in PATENCY-2 in the fourth quarter of this year and to report top-line data in the fourth quarter of next year. That would add about six months to our original timeline. Also we're announcing for the first time that if PATENCY-2 is successful, we expect to submit a BLA 2019.

So in conclusion, we're clearly very excited to announce today the changes to our development plan. We believe the data from PATENCY-1 and our discussions with the FDA have created a clear path forward for vonapanitase. And if successful in PATENCY-2, we believe vonapanitase could change the standard of care for group of patients in desperate need of help.

So thank you again for taking the time to participate today on the call and with that I'll turn the call back over to the operator and open it up to Q&A.

Question-and-Answer Session

Operator

Thank you. [Operator Instructions] Our first question comes from the line of Chris Raymond of Raymond James. Your line is now open.

Ally Bratzel

Hi, good morning. Thanks for taking the question. This is Ally Bratzel on for Chris. So clearly it seems like discussions with FDA went well. Could you maybe clarify or describe what gave FDA the most comfort in acquiring just single pivotal trial for approval just sort of thinking about the Phase 2 in PATENCY-1 results? And could you maybe confirm that this would serve for full approval for vonapanitase?

Tim Noyes

Yes, hi Ally, this is Tim. Thanks for your question. I don't think there's anything specific to PATENCY-1 other than what the agency is always looking for is a substantial evidence of efficacy and safety. And so I think they clearly looked at the totality of the data in PATENCY-1 as we've described many times, looked at the important endpoints that we've been talking to them about really for many, many years, those being primary patency, secondary patency and use of the fistula for dialysis. And I think their view is clear in the agreement we've announced here today that with prospectively designing PATENCY-2 now as we have, they believe that one pivotal trial combined with the evidence in PATENCY-1 would provide that substantial evidence of efficacy required to meet their hurdle.

And I'm sorry the last part of your – the very end of your question, I didn't get that.

Ally Bratzel

Could you confirm that this would serve for full approval?

Tim Noyes

Yes correct this was – you mean as opposed to some type of – yes with the Phase 4 commitment or subpart H or something else, correct?

Ally Bratzel

Right, okay.

Tim Noyes

And there was no bells or whistles attached to that full approval.

Ally Bratzel

And then maybe if I could, I just got a second question. And could you just walk us through sort of how you're thinking about the value proposition for the two new endpoints? I know there's been a lot of focus on primary PATENCY for PATENCY-1 data. So maybe just from a clinical and pharmaco-economic perspective could you sort of put these new endpoints into context for us?

Tim Noyes

Sure, I mean, I think, it's a good question. And I think it's fair to say that those of you who have been talking to for awhile understand that we've always said and believed that the endpoints we’ve been studying really now for several years, those really focusing on primary patentcy, secondary patentcy and used for hemodialysis are really the most important endpoints to really everyone involved in caring for the patient, that being surgeons, nephrologists, payors, the FDA, patients themselves and we've been saying that all long.

We think the use of the fistula at the end of the day is linked very closely to abandonment our two endpoints now in PATENCY-2. And we think those are the most important endpoints really for all the audiences. So again secondary patency represents the final failure of fistula and its abandonment. And fistula used for dialysis represents whether or not the patient can dialyze with their fistula. So achieving a usable fistula and maintaining secondary patency enabled the patient to avoid use of a dialysis catheter, which as you all probably know is the worst form of access and clearly associated with increased risk of serious infection, hospitalization and death. So for patients to avoid the need for additional surgical procedures, as well is another benefit.

So I think each patient only has a limited number of access sites. So fistula abandonment increases the risk that the patient may exhaust access sites and be subject to permanent use of a dialysis catheter. And so we believe that although all of the endpoints we've been studying are important, really abandonment or secondary patency and use of the fistula are clinically the most important and are associated with very significant reductions in spending, as well.

Ally Bratzel

Thank you.

Operator

Thank you. Our next question comes from the line of Stephen Willey of Stifel. Your line is now open.

Stephen Willey

Good morning, thanks for taking the questions and congrats on the FDA guidance. So I guess just on the – on the use of dialysis now as a co-primary I guess what you’re referring to in terms of the PATENCY-1 data is the unassisted and assisted hemodialysis use. So just wondering why the assisted use here is going to be included as part of the co-primary, there wouldn’t just be unassisted use of the fistula for dialysis as a co?

Tim Noyes

Hey, Steve, it’s Tim. I think it’s a really good question. We have that debate as well. And I think both endpoints matter as you noticed in PATENCY-1, we had a very nice result and I will say directionally really not different, so if you look at the magnitude of benefit and use whether it's assisted or unassisted, you're seeing in PATENCY-1 a very nice effect with very nice p-values indicating a benefit of vonapanitase over placebo. I think at the end of the day, what we ended up deciding to do was make PATENCY-2 endpoints meaning any use or assisted use as you say, really the most common and easily understood definition possible.

We will track all these other data but at the end of the day, I think what we decided was that if you were a patient, what you care most about is whether or not you can use your fistula. You absolutely do care how many interventions you need along the way because as we've talked about now for a couple of years, interventions are really a poor outcome for patients. But that said, at the end of the day we thought it was the most easily understood endpoint and the most relevant to a patient, which is whether or not they're able to use their fistula because as we just pointed out it's so well documented that if you're not using your fistula and you're struggling to maintain it or you have to abandon it. The outcomes are truly devastating.

Stephen Willey

Okay. And then just with respect to primary unassisted PATENCY which was used as the primary obviously in the first study. That's a time-to-event endpoint and I guess I'm just kind of wondering why the FDA at this point is now I guess more on board with kind of utilization or functional endpoint as opposed to a time-to-event endpoint. And I guess was there anything specific within the PATENCY-1 data, I guess outside of what was either presented a top line to that for some reason makes time-to-event not really a relevant endpoint in this setting anymore?

Tim Noyes

So the short answer to your question is no. And again I highlight that we've been discussing these endpoints with the FDA for years of all three. We and the agency have liked primary PATENCY, secondary PATENCY and use for dialysis for years going all the way back to the design of the Phase 2 trial. And so we think they're all important, we think they're all relevant, we think they all matter to patients. So there's certainly nothing about time-to-event of primary PATENCY which is an appropriate way to review that endpoint versus the second two.

Our discussion with the FDA really centered around the very clear effect of drug in PATENCY-1 on secondary PATENCY and use for dialysis. Given that both those p-values were less than 0.05. And so I think from a statistical standpoint those were all pre-specified endpoints, I think we and the agency took comfort in those two endpoints given the very low p-values associated with them, p-values that are as we all know customarily looked at – to demonstrate adequate efficacy in a pivotal trial

So we'll continue to track primary PATENCY as an observational endpoint in PATENCY-2, we think it still matters to patients. But again given the very clear result in PATENCY-1 and what we've now called our co-primary endpoints, we thought it made the most sense to designate those as co-primaries. And therefore allow PATENCY-1 to be supportive of PATENCY-2.

Stephen Willey

All right. I appreciate the color and thanks for taking the questions.

Tim Noyes

Sure.

Operator

Thank you. Our next question comes from the line of Konstantinos Aprilakis of JMP Securities. Your line is now open.

Konstantinos Aprilakis

Good morning, guys. Thanks for taking the question and congrats on the positive FDA meeting. Perhaps as a question for George but given data readout in 4Q and cash of 3Q 2018, what steps if any, are you guys taking to ensure that you can fund the company for this readout. There's only so much you do in terms of sort of tightening the belt on costs especially considering you're expanding the PATENCY-2 trial, could you perhaps discuss what you are considering now, what you might consider in the future? Thanks.

Tim Noyes

George, go ahead.

George Eldridge

Yes. So good question, Konstantinos, you are actually right math comes out there were about one quarter short of having sufficient capital to fund operations to be able to see the data from PATENCY-2. We look at it is that we have about 18 months to solve that and you're right whether we're going to do that through belt tightening whether we're going to do that through additional fundraising or whether we're going to do it through some other means, we've got 18 months to get there. And I don't think we're going to comment on which one of those three or other options that come up we're going to solve that issue. But you're right that right now based upon the operating plan we have cash to get us into the third quarter and data is in the fourth quarter, obviously, if enrollment goes faster than that solves the problem as well. So anyway we will continue and people will hear more about this over the next 12 months to 18 months in terms of addressing that issue.

Konstantinos Aprilakis

Thanks for that. Congrats again guys.

Operator

Thank you. Our next question comes from line of Boris Peaker of Cowen and Company. Your line is now open.

Justin Collinshaw

Good morning. This is Justin on for Boris. Thanks for taking my questions. I was wondering if you could just tell us a little bit about the sites that you're currently using. Are you going to add new sites? What's the API familiarity with the procedure and technique? I know it's relatively simple it’s just really dropping the drug. And anything about the average number of patients enrolled as somebody sites, just trying to get an idea of the familiarity with the product. Thank you.

TimNoyes

Yes, thanks. I’ll ask Steve to comment on maybe average numbers, but first I’ll say that we’ve been using round numbers about 40 sites in PATENCY-2. Many of our productive sites from PATENCY-1 have rolled over into PATENCY-2 and so we feel that’s adequate in sites to continue enrollment, at this point enrollment is going very well. As you notice we announced where we are today in the press release. You may recall that that is right on target of where we said we would be in the first quarter based on the guidance we've been giving.

So enrollment is going very well. I can say and Steve could probably comment further that our investigators at the sites have responded very favorably, very enthusiastically to the data in PATENCY-1 that we announced. So the trial from that standpoint, it's really going very nicely. I think you had a question about average enrollment per site and I don't know – really said much about that, but Steve is there anything you want add to that?

Steven Burke

No. This is Steve Burke. I assume – mentioned most of the sites were also three 10 PATENCY-1 sites and then just continue to enroll. And we train all the surgeons, we do retraining. As you point out, it's very simple method of administration; you just trip the drug on to the outside of the fistula after it's been created. So we like the way enrollments going in. As Tim indicated, PI’s are all very excited and impressed by the results. And I think that they’re very clinically meaningful and that the endpoints are clinically meaningful. So we don't expect any significant changes from what's preceded. We enrolled over 300 of the 500 patients already. So it's just a steady hand on the material and complete the enrollment this year.

Justin Collinshaw

Okay. Thank you.

Operator

Thank you. Our next question comes from line of Jason McCarthy of Maxim Group. Your line is now open.

Jason McCarthy

Hi, guys. Congratulations on getting the protocol amended. I was just wondering if you can go back to PATENCY-1 on the secondary and we have a functional use endpoints, use of the fistula, and any powering assumptions. There was 90% power. I know you've increased the trial size in PATENCY-2. And I'm wondering if the delta that we saw in PATENCY-1 could be narrowed even further given the extra 200 patients. Thanks.

Tim Noyes

Yes. Jason, this is Tim. So, yes, I mean obviously PATENCY-1 as we said did have good powering for secondary PATENCY, but the trial was really designed based around primary PATENCY. So despite that we still had good powering, did reached statistical significant. You know in PATENCY-2 which we will see we have imagined both the actual benefit we saw in PATENCY-1. So we do believe as I said earlier that we now have the best indicator to us, the best evidence available to us of what we believe the true drug effect is.

So we think we're in a very good position to look at PATENCY-1, as I’ve described here today and understand what the true benefit on secondary PATENCY will be. So we have powered the study as we said, with increased enrollments, power secondary PATENCY based on the true benefit we saw in PATENCY-1, however we still have very good power to detect smaller differences than we actually saw in PATENCY-1. Does that answer your question?

Jason McCarthy

It does. Thank you, Tim.

Operator

Thank you. And I’m showing no further questions at this time. I’ll hand the call back over to Tim for any closing remarks.

Tim Noyes

Yes, thank you. Again, I just wanted to thank everyone for joining us on the call this morning. Clearly we are very excited about the outcome of the past couple of months and in the past we have going forward. So we look forward to keeping you updated on the progress and appreciate your continued interest. Thank you.

Operator

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

Source: http://seekingalpha.com/article/4055974-proteon-therapeutics-prto-management-discuses-changes-ongoing-phase-3-patencyminus-2-clinical?part=single