Thank you for holding. Welcome to the Selecta Biosciences SEL-212 ACR phase II 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. If you require operator assistance, please press star then zero. For opening remarks, I would like to turn the call over to John Leaman, Selecta's Chief Financial Officer and Head of Corporate Strategy. Please go ahead.
Thank you, Andrew. Good morning, everyone. Earlier this morning, we issued a press release with the new interim data on five monthly combination doses of SEL-212 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-212 program from Werner Cautreels, our CEO, and then Skip Sands, our CMO, will review in more detail the new data being presented today at the 2018 American College of Rheumatology, ACR, or Association of Rheumatology Professionals, ARHP, annual meeting in Chicago. Other members of management will join us for the Q&A portion of this call. Before we get started, please refer to slide two.
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. Any forward-looking statements represent the company's views only as of today, October 23rd, 2018, and should not be relied upon as representing the company's views as of any subsequent data. 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.
Now let me introduce Werner, who will kick off the discussion.
Thanks much, John. 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-212, 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, all of that with convenient monthly dosing. Please turn to slide three for a high-level summary of the new interim data being presented today. These interim data consist of new cohorts of patients that received five monthly combination doses of 0.1 or 0.15 milligram per kilogram of SVP-rapamycin in combination with 0.2 milligram per kilogram of pegadricase. I just want to stop here and just note that pegadricase was formerly called pegsiticase.
Pegadricase is simply the new U.S. 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-212 combination cohorts. Pre-clinical 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 SEL-212. Of course, we focus also on the sustained serum uric acid control into months four and five in these most recent cohorts of patients treated with the five 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 five-month treatment period. During that period, also, we have not observed any emerging safety signals in months four or five. In the new cohorts, receiving five monthly doses of SEL-212, we currently project that 66% of evaluable patients could maintain serum uric acid level control below six milligrams per deciliter throughout five months of therapy, which correlates with the mitigation of anti-drug antibodies against the enzyme. Very important to note is that all 16 patients controlled at months three and completed months four and five maintained serum uric acid control during those months four and five of treatment.
It is on this basis that we are projecting results for the patients for which data are still pending. We have assumed that these patients will likewise maintain serum uric acid control during months four and five as the completed patients have. The sustained maintenance of serum uric acid levels near 0 milligrams per deciliter has appeared to lead to 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 uric 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-212 over the entire five-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 also allowed us to propose the dose regimens to the FDA that we plan to evaluate in our phase II 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 four. This slide provides an overview of the clinical development plan for SEL-212. Altogether, more than 200 patients have been dosed with SEL-212, about 50 patients in the phase I-B trial, and about 150 patients in the phase II trial. We believe that this is the most comprehensive phase I/II program conducted with a 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 III program, as you see here on this slide. Looking at slide five, as you can see in the graph, we are projecting that 66% of the evaluable patients treated with five monthly combination doses of SEL-212 could maintain serum uric acid levels of less than six milligrams per deciliter throughout the full five months.
These projections are based on the fact that while the full five months data are pending for five patients, all of these patients have shown serum uric acid control at three months, and current data from the phase II trial suggest that 100% patients controlled at month three maintain serum uric acid control in months four and five when treated with SEL-212. Slides six, seven, and eight 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 four maintain control over the entire treatment period with monthly doses of SEL-212. Turning to slide nine. We presented today DECT imaging data for a subset of phase II 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 nine, and you will notice the substantial reduction of tissue urate volume observed in the majority of these patients. Slide 10 illustrates the potency of SEL-212 in eliminating 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 urate burden over the entire five-month period. Turning to slide 11, you can see the incidence of reported gout flares in the recent five 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 one, 34% in month two, 9% in month three, 6% in month four, and again, 6% in month five. 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 II trial. Approximately 29% of the patient population treated with SEL-212 experienced gout flares during the first month after treatment, with continued reduction of gout flare rates out to month five. Overall, 96% of all gout flares observed in our phase II 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 in the dosed for five 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 flares. Monosodium urate crystals are known to cause inflammation by activating the inflammasome pathway, resulting in IL-1β production. The data shown today at ACR indicate that SVP-rapamycin, but not rapamycin Inhibited IL-1β 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. Werner?
Thank you so much, Skip. Now turning to slide 15 for a quick summary and next steps. As you heard this morning, we believe the clinical activity of SEL-212 observed in our phase II study to date, after five monthly doses, shows the potential benefit of SEL-212 over the entire five-month treatment period. Importantly, we have not observed any new emerging safety signals during this five-month treatment period. Based on clinical data collected to date, we continue to believe that SEL-212 may provide sustained serum uric acid control with low flare rates. Combined with a proposed monthly dosing schedule, we believe that SEL-212 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 III program later this year with proposed dose regimens based on our phase II data. We also plan to conduct a head-to-head trial against the current FDA-approved uricase therapies while accelerating our plans for commercialization for SEL-212. With that, we will open the call for questions. Operator Andrew?
We will now begin the question and answer session. To ask a question, you may press star then one on your touch tone phone. If you are using a speakerphone, please pick up your handset before pressing the keys. If at any time your question has been addressed and you would like to withdraw your question, please press star then two. At this time, we will pause momentarily to assemble our roster. The first question comes from Derek Archila of Stifel. Please go ahead.
Hi, good morning, guys, and congrats on the data. Just a couple questions from me. I guess, first off, 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 deviation? Any color around those patients. Can you just remind us of the stopping rules in the study? That'd be great. Thanks.
Thank you, Derek. This is Werner. Indeed, we do have a number of patients that decided to withdraw consent during the trial. I think 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. 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. 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. We have looked at that very carefully at day 21.
When we see at day 21 that there is a loss of activity that is normally linked to the formation of ADAs, we have been very careful in monitoring that. We will learn from this phase II study about it and then implement whatever we believe is the best paradigm to go forward into the phase III 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 on 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 potentially evaluating in the phase III? I guess what other kind of topics, I guess, is on your wish list when you think about engaging with the FDA on the phase III design? Thank you.
Thanks, Carter. Maybe I'll take a shot at it and maybe, Skip, you can step in. The proposed doses that we take to FDA is 0.1 plus of SVP-rapamycin plus 0.2 of pegloticase and also 0.15 plus 0.2 of pegloticase. Cohort 15, FDA is very keen of having lowest effective dose, that was a way to maybe address that. From both the safety and the efficacy, we have seen that is not required. In terms of the other points, I think it should be very straightforward with FDA, because the primary endpoint for the clinical trials is well-defined. We don't really see any very specific other items that needs to be addressed. Skip, 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 III to occur on time.
Yeah.
I think we're in good shape.
Yeah. I think Skip mentioned this program is pretty comprehensive, as we have more than 50 patients in our phase I and II. We have now 150 patients in the phase II program in this clinical trial, of which about 40 or so are in the five monthly doses, where patients still are seen every week, where they have blood draws. We are very careful in looking at that we haven't seen, as Skip 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, thanks for taking my question. Just a couple. Would you comment with a little bit more color on the drug-related serious adverse events? Secondarily, not all the patients have been completed the month five measurements. From timing perspective, do you plan to wait until these data mature before meeting with the FDA, or do you plan to meet with the FDA even ahead of getting all of the data?
Hi, Difei. Yeah. Let me take your second one, and then I'll turn it over to Skip, maybe on your first, which is on the SAEs. 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 SAEs that are related or potentially related, Skip, you want to address that?
The SAEs that are considered to be potentially related are all timing associated with infusion reactions as early on in the trial. As we move forward, as we have adjusted timing associated with the dosing, we have not seen any treatment emergent adverse events that created SAEs or discontinuations. 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 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 also just wanted to confirm how your success rate might change if you were to evaluate based on the way that Krystexxa ran their phase III, which, if I remember correctly, really didn't have any stopping rules. Just kind of curious about that. 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. In this phase II trial, it was really important for us to define what was the dose regimen of this combination. We had to be thoughtful and careful going forward. Indeed, over time, we have, in that trial, applied that stopping rule as you mentioned. That is confirmed. 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. 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. Congratulations on the data. You decided to look at two doses of SVP-rapamycin in the phase III study. I wonder, have you seen any material difference between the two doses in terms of either efficacy or safety?
Thank you. This is Werner. Remember, these are still relatively small numbers. The fact that we may take two doses forward is the following. As you look at the data, if a patient is controlled at week 4, there is an extremely high likelihood that that patient remains controlled for the whole 5 months. It is really important that 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 it, the discussion with FDA will be whether we take both or whether we just take one forward.
I see, okay. This is actually related to my next question. Looks like most of the loss of control occurred in the first month. Based on baseline patient demographics, are you able to tell what kind of patient are more likely to lose control in the first 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 is also 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 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, I think about the head-to-head study versus Krystexxa that you talked about. I assume the dosing is still to be determined based on your discussion with the FDA?
That is correct, that dose will be the dose that we will take into the pivotal phase III program.
Okay, great. Thank you.
Again, if you have a question, please press star then one. This concludes our question and answer session. I would like to turn the conference back over to Werner Cautreels, President and CEO, for any closing remarks.
Thank you so much, Andrew. Thanks everyone for joining us this morning and spending some time with us. We look forward to seeing you around and talking more. With that, I would like to close and thanking you again so much.
The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.