Study Update

Jun 15, 2018

Slides

Thank you for holding. Welcome to the Selecta Biosciences SEL-two twelve EULAR Phase 2 Data Conference Call. At this time, all participants are in listen only mode. This call is being webcast live on the Internet and Media section of Selecta's website at www dotselectabio.com, and it is being recorded. For opening remarks, I would now like to turn the call over to John Laymon, Selleck's Chief Financial Officer and Head of Corporate Strategy. Please go ahead. Thank you, Keith, and good morning, everyone. Earlier this morning, we issued a press release with expanded data from our ongoing Phase 2 trial for SEL-two twelve for the treatment of chronic severe gout. The release and the PowerPoint presentation being reviewed on this webcast can be accessed by visiting our website at www.selectabio.com. Today, you will hear introductory remarks from Werner Cottrells, our CEO and then Skip Sands, our CMO, will review the Phase 2 clinical data being presented today at the 2018 European League Against Rheumatism Annual European Congress or EULAR. Other members of the management will be joining for the Q and A portion of the call. Before we get started, please refer to Slide 2. We would like to advise that certain remarks that are made during the call about the company's future expectations, plans and prospects constitute forward looking statements for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward looking statements as a result of the various important factors, including those discussed in the Risk Factors section of Selecta's most recent report on Form 10 Q filed with the SEC, which can be accessed at selectabio.com. In addition, any forward looking statements represent the company's views only as of today, June 15, 2018, and should not be relied upon as representing the company's views as of any subsequent date. While Selecta may elect to update these forward looking statements at some point in the future, it specifically disclaims any obligation to do so even if management's views change. And now let me introduce Werner, who will kick off the discussion. Thank you, John, and good morning, everyone here from Euler in Amsterdam. We are really excited to be presenting this expanded 3 month Phase 2 data set today at Euler, which we believe may further strengthen SEL-two twelve's profile versus the current FDA approved uricase therapy, Krystexxa. Please turn to Slide 3. The expanded data presented at EULAR today are from the same patient cohorts that were presented at PANLAR in mid April, but include an additional 8 patients that reached week 12. These cohorts received 3 monthly doses of SEL-two twelve up to 0.15 milligrams per kilogram of SVP rapamycin in combination with 0.2 or 0.4 milligrams per kilogram of pexiticase and after 12 weeks received 2 monthly doses of pexiticase alone. We are now showing that approximately 81% of evaluable patients in cohorts 10 through 12 had serum uric acid control at week 12. In a separately conducted and designed study of the only FDA approved uricase therapy, the KRYSTEXXA triple study, 44% of patients had serum uric acid control at week 16 as reported last November at ACR. And there remains a low rate of gout flares in our Phase II trial. Only 27% of all patients treated with SEL-two twelve in the Phase II trial today experienced guard flares in the 1st month versus about 77% for KRYSTEXXA in their separately conducted Phase III trials. The strong clinical activity of SEL-two twelve after 3 monthly doses has provided the basis for us to initiate last February additional patient cohorts to receive 5 monthly doses of the SEL-two twelve combination product. The first patients in those cohorts are now receiving the 4th dose and are expected to receive their 5th dose of the combination product very soon. We plan to report data from those patients at a medical meeting in the Q3 of 2018. We believe that the comprehensive combination dose finding study in our Phase II trial will put us in a strong position to define the optimal dose regimen for our pivotal Phase III program that we expect to start later this year. And just as a reminder, SEL-two twelve is a combination of SVP rapamycin, our novel immune tolerance technology and pexiticase, our proprietary pegylated uricase and was designed to be the 1st non immunogenic version of uricase, which would allow for the effective and safe administration of multiple doses with concurrent mitigation of antidrug antibodies against the enzyme. The mechanism of action by which we believe our technology mitigates immunogenicity may also allow retreatment of patients at a future date if needed. The product profile continues to indicate that SEL-two twelve may provide better and more sustained serum uric acid control and fewer flares, which combined, which is less frequent dosing, that means monthly versus biweekly, and the potential option for retreatment in the future makes us believe this drug could change the gout treatment paradigm and the way rheumatologists treat their patients. With that, I will now turn the call over to Skip to review the new expanded data in some more detail. Skip? Thank you, Werner. Please turn to Slide 4. This slide provides an overview of the clinical development plan of SEL-two twelve for chronic severe gout. Today, I will provide an update on new data for the ongoing Phase II dose ranging trial that have the potential to position us well to execute on our planned Phase 3 program. Looking at Slide 5, as you can see in the top graph, 81% of the evaluable patients treated with 3 monthly doses of SEL-two twelve maintained serum uric acid levels of less than 6 milligrams per deciliter throughout the full 3 months. By comparison, in the bottom graph, only 1 of 6 patients treated with pegziducasalone or about 17% maintained serum uric acid control at week 4. We know from the analysis of the corresponding antidrug antibody data that the difference in this loss of control is well correlated with the level of those antidrug antibodies, which we believe are mitigated by the co administration of SVP rapamycin. The 3 following slides provide patient by patient data for the expanded cohorts reported today for serum uric acid levels in green and ADA levels in blue. As you can see from Slides 6, 7, and 8, the majority of patients have now reached the 12 week data point. Let's turn to Slide 7 as an example for some more detailed review of the available patient data. Let me clarify using this Slide 7, how the patient data are now presented as compared with our presentations of patient data in the past. On the top of the slide, we regrouped the evaluable patients. And on the bottom of the slide are the patients that we excluded from our current analysis. In the patient cohort shown on this Slide 7, 8 of the 10 evaluable patients maintained serum uric acid control throughout the 1st 3 months. 2 evaluable patients labeled with the letter A did not maintain serum uric acid control throughout the 1st 3 months. I would point out that the last patient with an A-twenty two upon audit was underdosed by the site. Thus, he has a protocol deviation, but we included him in the current analysis. The patients reported on the bottom of the slide were not a valuable because. One patient labeled with the letter E was stopped before the full dose was completed. One patient labeled with the letter F withdrew consent prior to receiving the first dose, and one patient labeled with the letter D was lost to follow-up after having received the first dose. Slides 68 provide individual patient data using the same format. The analysis of the data from the evaluable patients reported on Slides 6, 7, and 8 resulted in the 81% control at month 3, as I have mentioned before in this presentation. Slide 9 provides new gout flare data from these same cohorts to date, the same cohorts as reported on the slides 6, 7, and 8. You can see that the incidence of reported gout flares declined in subsequent months of treatment, with 33% of patients reporting a gout flare in month 1, 19% in month 2, and 8% in month 3. Slide 10 provides gout flare data for the entire patient population in our Phase 2 trial reported to date. As you can see, SEL-two twelve continues to show a low overall incidence of gout flares in the total trial patient population with 27% of patients reporting a gout flare in month 1, 19% in month 2, 6% in month 3, 14% in month 4 and 3% in month 5. These data remain very consistent with the GALFLA data we have reported previously for our Phase 2 trial and appear to be lower than the incidence of GALFLA's reported in clinical trials involving the current FDA approved uricase therapy. Turning to Slide 11. SEL-two twelve has been generally well tolerated at clinically active doses following repeated dosing, now representing more than 380 intravenous administrations in the trial. There have been 17 serious adverse events reported in our patient population, 9 of which were reported to be not related or unlikely to be related to study drug, 7 were infusion reactions that were previously reported in our June 2017 All SAEs were successfully treated without any further issues. All SAEs were successfully treated without any further issues. Before I turn the call back over to Werner, I would like to take a moment to thank the patients that participated in our clinical trials and extend our gratitude to the clinical trial site investigators and their staff. Werner? Thank you, Skip, for that update. So let's turn to Slide 12. At this stage of the development of SEL-two twelve, it is important to put our proposed target product profile in the context of available treatments for chronic severe gut. One product is FDA approved for his indication, Krystexxa, which utilizes a different uricase. From Skip's update on the clinical data, we believe the 3 month data presented today at Eular may provide a very promising product profile of SEL-two twelve that may meet many of the current unmet medical needs of chronic severe gout patients, including: 1st, the need for better and sustained serum uric acid control second, a lower rate of flares and third, convenient monthly dosing regimen. The data shown on Slide 12 are not from a head to head clinical trial, but with limitations on differing trial design and parameters in mind, provide a retrospective comparison based upon available published Krystexxa clinical data and our data presented on SEL-two twelve today at Euler. This retrospective comparison has provided guidance as we make plans for our Phase III program. Beyond 2 placebo controlled pivotal Phase III trials, we also are considering additional trials such as a head to head study versus Krystexxa and potentially a study to test the clinical activity of SEL-two twelve in patients who have failed KRYSTEXXA therapy. Turning to Slide 13. The continuing improved clinical activity of SEL-two twelve after the 3 monthly doses has provided the basis for us to initiate additional cohorts receiving 5 monthly doses of SEL-two twelve combination product. For instance, 0.15 milligrams per kilogram of SCP rapamycin and 0.2 milligram per kilogram of paxiticase. These data have the potential to show the extended benefit of SEL-two twelve over the entire treatment period. We are now dosing the 4th combination dose in this cohort, and we expect data for the 5 combination doses to be presented at a medical conference in the Q3 of 2018. We believe that the comprehensive combination dose finding study in our Phase 2 trial will put us in a strong position to define the design of our pivotal Phase III program, which we plan to start in 2018. Interviews with rheumatologists clearly identified the need for a non immunogenic uricase therapy that could lower serum uric acid in these chronic severe gout patients for a full 6 months treatment cycle versus the less than 3 months that a typical patient receives today with KRYSTEXXA. And because of the potential mitigation of immunogenicity, those patients may also be eligible for retreatment at a later time point if needed. So in conclusion, we are really eager to get the Phase III trial underway. With that, we will open up the call for questions. Keith? Yes. Thank you. We will now begin the question and answer And today's first question comes from Chad Messer with Needham and Company. Great. Thanks for taking my question and congrats on the continued positive data. Werner, in your opening remarks, you talked about the potential for retreatment with SEL-two twelve. Just wondering if that's something you would consider actually testing in a clinical trial? Thanks, Chad. Yes, absolutely sure. While it may not be part of the primary clinical endpoints in the pivotal trials that we would conduct against placebo, we certainly will consider that for the extension of those clinical trials. Okay. And then maybe just on safety, you had some incidents of infusion reaction. I was just wondering if you could give us some context on what infusion reactions are like with KRYSTEXXA, so we get that part of the profile, competitive profile as well? John, would you like to address that? Chad, yes. Good morning. So I think if you look at the pivotal trials from KRYSTEXXA, which obviously you take a look at on the label, about 5% of the patients that were treated had an infusion reaction. So when you think about it and doing a little bit of math in our heads, right, we've almost had 400 doses of our product. And if 5% of that, you would be looking at 20 cases of infusion reactions if we were consistent. I think what was reported here is at 8% were significantly less than that. All right, great. Thanks and congrats again. Thank you. And the next question comes from Difei Yang with Mizuho Securities. Hi, good morning. Thanks for taking my question. Just a couple. So, what's your expectation on safety profile when you expand from the 3 combo injection to potentially 6 monthly combo injection. Do you see significant changes on the safety side? Thanks, Difei. We expect no change of that safety profile and that is true for the more severe, but also for the overall safety profile. As you remember, we follow very carefully a number of parameters that could be rapamycin related. And so far, we only see like erratic transient changes that we believe is are not related to that. But Skip, anything to add on that? No. Hi, Difei. It's Skip. Remember, when we went from one treatment cycle to 3 treatment cycles, we didn't see any difference. And I don't expect us to see any difference going from 3 to 5 or 3 to 6. Okay. Thank you. So then the follow-up question is on the timeline. We're expecting to see this 5 combo dose data some time during Q3. So after that, what would happen? What do you have to do before starting officially starting the Phase 3? John, would you like to address that? Absolutely, Difei. So essentially, we have been prepping actively for the Phase 3 program behind the scenes. All the systems, we're getting the clinical sites up and running and we're ready. So I think post the data that will show Q3, we'll obviously have an end of Phase 2 meeting and our plans as we've guided to continue to be that we'll start that Phase 3 program this year in 20 18. Okay. So there will be a FDA meeting somewhere in between. Okay. Thank you very much. Thank you. And the next question comes from John Newman with Canaccord. Hey, guys. Good morning. Congrats on the data. My question is just, are you comfortable with the specific dose level that you'd be taking into Phase 3 in light of the data that we've seen here today? Yes. Good morning, John, or good afternoon for you. Good morning for you. It's afternoon in Amsterdam. Yes, I think the continuous, of course, looking at the Phase II data will guide us for the final decision. But we believe that we start to see a clear profile of what those doses would be. But again, a little more data to collect and then we can make that final decision. Okay, great. And then in the Phase 3 study, I know that you're still finalizing the protocol, but can you talk to us about the number of patient visits that the participants in the study will need to make versus the number of patient visits that they have been making in this study? Yes, sure. Skip, you want to quickly address that? Sure. Hi, John. The number will definitely be decreased probably close to half is what we expect. All right. As there are no more questions at the present time, I would like to return the call to management for any closing comments. Thanks, Keith, for your help. And thanks, everyone, for joining us this morning. We hope to see you at one of the upcoming investor meetings and the medical meetings in the future. Thank you so much and thank you for your attention. Thank you. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect your lines.