Study Result

Oct 23, 2018

Slides

Thank you for holding. Welcome to the Selecta Biosciences SEL-two twelve ACR Phase 2 Data Conference Call. At this time, all participants are in a listen only mode. This call is being webcast live on the Investors and Media section of Selecta's website at www.selectabio.com, and it is being recorded. For opening remarks, I would like to turn the call over to John Laymon, Selecta's Chief Financial Officer and Head of Corporate Strategy. Please go ahead. Thank you, Andrew, and good morning, everyone. Earlier this morning, we issued a press release with the new interim data on 5 monthly combination doses of SEL-two twelve from our Phase II trial for the treatment of chronic severe gout. This release and the PowerPoint presentation being reviewed on the webcast can be accessed by visiting our website, www.selectabio.com. Today, you will hear remarks on the SEL-two twelve from Werner Cottrells, our CEO and then Skip Sands, our CMO, where we view in more detail the new data being presented today at the 2018 American College of Rheumatology, ACR, or Association For Rheumatology of Health Professionals, ARHP, Annual Meeting in Chicago. Other members of management will join us for the Q and A portion of this call. Before we get started, please refer to Slide 2. We'd 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 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, October 23, 2018, and should not be relied upon as representing the company's views as of any subsequent data. While Celecta 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. Now let me introduce Werner, who will kick off the discussion. Thanks much, John, and good morning, everyone, from ACR in Chicago. We are very happy with the new interim data being presented this week at ACR. Four posters were presented yesterday and today, highlighting key results from our clinical development programs for SEL-two twelve, namely that sustained control of serum uric acid, low rate of gout flares and rapid elimination of tissue urate burden have been observed in the Phase II trial to date and all of that with convenient monthly dosing. Please turn to Slide 3 for a high level summary of the new interim data being presented today. These interim data consist of new cohorts of patients that received 5 monthly combination doses of 0.1 or 0.15 milligram per kilogram of SVP rathomycin in combination with 0.2 milligram per kilogram of picadric I just want to stop here and just note that picadricase was formerly called pexiticase. PKADRI case is simply the new United States adopted name or USAN. I mention this here so that there is no confusion about this name change. We observed a low rate of flares in the Phase II trial in all SEL-two twelve combination cohorts. Preclinical data presented also today at ACR suggest that SVP rapamycin may have a beneficial anti inflammatory effect, which we believe may provide a potential underlying mechanism of action of the observed low flare rate. We presented also DECT imaging data in a subset of patients from the Phase II trial, from which we observed rapid and substantial reduction of tissue urate burden during treatment with SGL-two twelve. But of course, we focus also on the sustained serum uric acid control into months 45 in these most recent cohorts of patients treated with the 5 once monthly combination treatments. Based on the data collected to date, we project that approximately 66% of patients could have sustained serum uric acid control over the entire 5 month treatment period. During that period also, we have not observed any emerging safety signals in months 4 or 5. In the new cohorts receiving 5 monthly doses of SEL-two twelve, we currently project that 66% of evaluable patients could maintain serum uric acid level control below 6 milligrams per deciliter throughout 5 months of therapy, which correlates with the mitigation of antidrug antibodies against the enzyme. Very important to note is that all 16 patients controlled at months 3 and completed months 45 maintained serum uric acid control during those months 45 of treatment. It is on this basis that we are projecting results for the patients for which data are still pending. And we had assumed that these patients will likewise maintain serum uric acid control during months 45 as the completed patients have. The sustained maintenance of serum uric acid levels near 0 milligrams per deciliter has appeared to lead to a a substantial reduction in uric acid deposits as measured by DECT imaging. The DECT scans were performed as an exploratory measure to evaluate reduction of tissue urine burden in a subset of patients in this Phase II trial. Altogether, we believe the data presented at ACR this week provide additional evidence of the clinical potential of SEL-two twelve over the entire 5 month treatment period. We also believe that once monthly dosing could provide an important benefit for patients and importantly for their compliance with the treatment. The interim data from the Phase II trial allowed us to propose the dose regimens to the FDA that we plan to evaluate in our Phase III program and in the head to head study that we plan against the current FDA approved uricase therapy. With that, I will now turn the call over to Skip, our CMO, to review the data in some more detail. Skip? Thank you, Werner. Please turn to slide 4. This slide provides an overview of the clinical development plan for SEL-two twelve. Altogether, more than 200 patients have been dosed with SEL-two twelve, about 50 patients in the Phase 1b trial and about 150 patients in the Phase 2 trial. We believe that this is the most comprehensive Phase III program conducted with the uricase enzyme product. Today, I will review the new interim data from the combination dose finding study, which we believe has positioned us well to execute on our planned Phase 3 program as you see here on this slide. Looking at Slide 5, as you can see in the graph, we are projecting that 66 percent of the evaluable patients treated with 5 monthly combination doses of SEL-two twelve could maintain serum uric acid levels of less than 6 milligrams per deciliter throughout the full 5 months. These projections are based on the fact that while the full 5 months data are pending for 5 patients, all of these patients have shown serum uric acid control at 3 months and current data from the Phase 2 trial suggest that 100 percent patients controlled at month 3 maintained serum uric acid control in months 45 when treated with SEL-two twelve. Slides 6, 7 and 8 provide patient by patient data for the new cohorts reported today for serum uric acid levels in green and ADA levels in blue. These data show that the majority of patients that achieved control of serum uric acid levels after the first treatment at week 4 maintained control over the entire treatment period with monthly doses of SEL-two twelve. Turning to Slide 9. We presented today DECT imaging data for a subset of Phase 2 patients. These DECT scans were performed as an exploratory measure to evaluate reduction of tissue urate burden. Data from 19 patients are shown on Slide 9 and you will notice the substantial reduction of tissue urate volume observed in tissue urate from one of these patients. DECT imaging provides quantitative evidence that the patients who sustained maintenance of serum uric acid at very low levels showed a decrease in urate deposits in joints and tissue. The interim data show that the progressive reduction in tissue urea burden over the entire 5 month period. Turning to Slide 11, you can see the incidence of reported gout flares in the recent 5 combination cohorts. Flare rates have declined over the months after initiation of treatment with 35% of the patients in these new cohorts reporting a gout flare in month 1, 34% in month 2, 9% in month 3, 6% in month 4 and again 6% in month 5. These data are consistent with the total cohort FLARE data on the next slide. Here on Slide 12, you can see the continued reduction in FLARE frequency observed for all 152 patients in our Phase 2 trial. Approximately 29% of the patient population treated with SEL-two twelve experienced gout flares during the 1st month after treatment with continued reduction of gout flare rates out to month 5. Overall, 96% of all gout flares observed in our Phase 2 trial have been mild or moderate in severity. None of the gout flares were reported as SAEs nor resulted in study discontinuations. Slide 13 provides a safety summary for the patients dosed for 5 months. As we have mentioned earlier today, there have been no new emerging safety signals observed during the extended treatment periods. On Slide 14, we summarize the findings of the preclinical data also presented today at ACR regarding the potential impact of SVP rapamycin on the inflammasome pathway and which we believe may be related to reductions in in flares. Monosodium urate crystals are known to cause inflammation by activating the inflammasome pathway resulting in IL-one beta production. The data shown today at ACR indicate that SVP rapamycin but not rapamycin inhibited IL-one beta production induced by monosodium urate crystals in a mouse model. Before I turn the call back over to Werner for closing remarks, 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 staffs. Thank you. Juana? Thank you so much, Kipp. Now turning to Slide 15 for a quick summary and next steps. As you heard this morning, we believe the clinical activity of SEL-two twelve observed in our Phase II study to date after 5 monthly doses shows the potential benefit of SEL-two twelve over the entire 5 month treatment period. And importantly, we have not observed any new emerging safety signals during this 5 month treatment period. Based on clinical data collected to date, we continue to believe that SEL-two twelve may provide sustained serum uric acid control with low flare rates. Combined with the proposed monthly dosing schedule, we believe that SEL-two twelve is a product candidate that if approved could change the treatment paradigm for patients with chronic severe gout who are in real need of additional treatment options. We look forward to initiating our Phase 3 program later this year with proposed dose regimens based on our Phase 2 data. We also plan to conduct in parallel a head to head trial against the current FDA approved uricase therapies whilst accelerating our plans for commercialization for SEL-two twelve. With that, we will open the call for questions. So, operator, Andrew? We will now begin the question and answer session. The first question comes from Derek Archila of Stifel. Please go ahead. Hi, good morning guys and congrats on the data. So just a couple of questions for me. I guess first off, can you give any color on the patients that were well controlled in the study that end up stopping because of it looks like withdrawal of consent or protocol deviations. So any color around those patients? And then also, can you just remind us of the stopping rules in the study? That would be great. Thanks. Thank you, Derek. This is Werner. So indeed, we do have a number of patients that decided to withdraw consent during the trial. I think this was while it is very convenient monthly dosing, these patients still had to come in weekly for their blood draws and the like, Something that will be simpler in the Phase III trial, but we do have a number of patients that have been withdrawn for that. In terms of the protocol deviations, those were patients that had missed a dose or had an incomplete dose. And so those are a number of options or opportunities that we have seen for that trial that we can improve. In terms of the stopping rules, obviously, not all patients can be protected against the formation of ADAs. Unfortunately, that's the way the immune system is built. So we have looked at that very carefully at day 20 one. And when we see at day 21 that there is a loss of activity that is normally linked to the formation of ABAs. We have been very careful in monitoring that. We will learn from this Phase 2 study about it and then implement whatever we believe is the best paradigm to go forward into the Phase 3 program. Great. Thank you. The next question comes from Carter Gould of UBS. Please go ahead. Great. Hey, guys. Thanks for taking the question. I just wanted to dig in a little bit more on sort of the focal points and your forthcoming conversations with FDA. I guess there's a decision to be made on kind of the dose you're going to take forward. I also recognize, I guess, in Cohort 15, you did sort of the step down dosing. Is that something you're looking at, essentially evaluating the Phase 3? And then I guess, what other kind of topics or I guess is on your wish list when you think about engaging with the FDA on the Phase III designs? Thanks, Carter. Maybe I'll take a shot at this and maybe, Skip, you can step in. So the proposed doses that we take to FDA is 0.1 plus of SVP rapamycin plus 0.2 of picadricase and also 0.15 plus 0.2 of picadricase. Cohort 15, FDA is very keen of having lowest effective dose. So that was a way to maybe address that. But from both the safety and the efficacy, we have seen that, that is not required. In terms of the other points, I think it should be very straightforward with FDA because the endpoint for the primary endpoint for the clinical trials is well defined. So we don't really see any very specific order items that needs to be addressed. Skip, do you want to add anything to that? I believe that we have prepared a package which the FDA should find very acceptable and we have prepared our operational move for Phase 3 to occur on time. Yes, I think we're in good shape. Yes. And so I think Skip mentioned this. This program is pretty comprehensive As we have more than 50 patients in our Phase 1 and 2, we have now 150 patients in the Phase II program in this clinical trial, of which about 40 or so in the 5 dose in the 5 monthly doses where patients still are seen every week where they have blood draws. And we are very careful in looking at that. And we haven't seen, as Cliff had mentioned, any new emerging events. Great. Thank you. The next question comes from Difei Yang of Mizuho Securities. Please go ahead. Hi, good morning and thanks for taking my question. Just a couple. Would you comment with a little bit more color on the drug related serious adverse events? And then secondarily, it sounded like not all the patients have been completed the month 5 measurements. So from timing perspective, do you plan to wait until these data mature mature before meeting with the FDA or do you plan to meet with the FDA even ahead of getting all of the data? Hi, Difi. Yes. So let me take your second one, and then I'll turn it over to Skip maybe on your first, which is on the SCA. No, we are not waiting. We have a scheduled meeting with FDA. We'll take that forward so we don't have to wait. We have everything in hand to have that meeting. On your first question in terms of the SEAs that are related or potentially related, Skip, you want to address that? So the SAEs that are considered to be potentially related are all timing associated with infusion reactions as early on in the trial. So as we move adjusted timing associated with the dosing, we have not seen any treatment emerge in adverse events that created SAEs or discontinuations. So it's all related to the initial dosing events and we have adjusted accordingly. Okay, great. Thanks. The next question comes from John Newman of Canaccord. Please go ahead. Hey, good morning guys. Congrats on some really nice data. I think it shows a sustained response for the product. Just had a couple of questions on the stopping criteria. If I remember correctly, you stopped dosing patients if they had an SUA of greater than one at day 21 of any given study month. I just wanted to confirm that. And I also just wanted to confirm how that how your success rate might change if you were to evaluate based on the way that KRYSTEXXA ran their Phase 3, which if I remember correctly, really didn't have any stopping rules. So, I'm just kind of curious about that. And then wondering how you will approach whether you will or will not have stopping rules in your upcoming studies? Thanks. Okay. Thanks, John. This is Werner. Yes, so in this Phase II trial, it was really important for us to define what was the dose regimen of this combination. And so we had to be thoughtful and careful going forward. And indeed, over time, we have in that trial applied that stopping rule, as you mentioned. So that is confirmed. Now going forward, we are looking at all the data to see if that is still the appropriate way going forward. And that will then also be discussed in our Phase III protocol with FDA. Going forward in Phase III, I believe we have had learnings from this Phase II in terms of how to manage patients. And in that Phase III trial, I believe that the investigators are going to be very experienced with these patients and being able to actually deal with that also in the clinical setting. Great. Thank you. The next question comes from Yun Zhong of Janney. Please go ahead. Hi. Thank you for taking the question and congratulations on the data. So you decided to look at 2 doses of SPP replatformizatin in the Phase 3 study. And I wonder, have you seen any material difference between the two doses in terms of either efficacy or safety? Thank you. This is Warner. If you look at all the data, but remember, these are still relatively small numbers. The fact that we may take 2 doses forward is the following. As you look at the data, you have if a patient is controlled at week 4, there is an extremely high likelihood that that patient remains controlled for the whole 5 months. So it is really important that, that first after that first administration, patients are controlled and stay into the trial. We know from our Phase I data that indeed with some higher doses of SVP rapamycin that you may indeed have some more patients that stay controlled after week 4. That is one of the ideas behind this. And then the discussion with FDA will be whether we take both or whether we just take one forward. I see. Okay. Yes, this is actually related to my next question. So looks like most of the loss of the control occurred in the 1st month. And based on baseline patient demographics, are you able to tell what kind of patients are more likely to lose control in the 1st month? That's a real good question. I wish we would. Unfortunately, I think as in the case of the other way around in vaccinations, it's very difficult to predict what patients will be protected or not. In this case, we believe we have to deal with a similar situation. The best we will do is make sure that that first 4 weeks where we pay a lot of attention to the patient and to their doctor. In the case of Phase III, there will be a very much closer relationship, we believe, between the doctor and the patient, And we should be able to optimize that further. Okay. Last question. And I think about the head to head study versus CRISPR that you talked about, I assume the dosing is still to be determined based on your discussion with the FDA? That is correct. And that dose will be the dose that we will take into the pivotal Phase 2 program. Okay, great. Thank you. This concludes our question and answer session. I would like to turn the conference back over to Werner Cottrells, President and CEO, for any closing remarks. Thank you so much, Andrew. And thanks, everyone, for joining us this morning and spending some time with us. We look forward to seeing you around and talking more. And with that, I would like to close in thanking you again so much. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.