Thank you for holding. Welcome to the Selecta Biosciences SEL-212 EULAR phase II 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.selectabio.com, and it is being recorded. For opening remarks, I would now like to turn the call over to John Lehmann, Selecta'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 II trial for SEL-212 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 Cautreels, our CEO, and Earl Sands, our CMO, will review the phase II 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&A portion of the 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 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 15th, 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.
Now let me introduce Werner, who will kick off the discussion.
Thank you, John, good morning, everyone, here from EULAR in Amsterdam. We are really excited to be presenting this expanded three-month phase II data set today at EULAR, which we believe may further strengthen SEL-212'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. That include an additional eight patients that reached week 12. These cohorts received three monthly doses of SEL-212, up to 0.15 milligrams per kilogram of SVP-rapamycin in combination with 0.2 or 0.4 milligrams per kilogram of pegloticase, and after 12 weeks, received two monthly doses of pegloticase 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 pivotal study, 44% of patients had serum uric acid control at week 16, as reported last November at ACR. There remains a low rate of gout flares in our phase II trial. Only 27% of all patients treated with SEL-212 in the phase II trial today experienced gout flares in the first month, versus about 77% for KRYSTEXXA in their separately conducted phase III trials. The strong clinical activity of SEL-212 after three monthly doses has provided the basis for us to initiate last February, additional patient cohorts to receive five monthly doses of the SEL-212 combination product. The first patients in those cohorts are now receiving the fourth dose and are expected to receive their fifth dose of the combination product very soon.
We plan to report data from those patients at a medical meeting in the third quarter 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. Just as a reminder, SEL-212 is a combination of SVP-rapamycin, our novel immune tolerance technology, and pegloticase, our proprietary pegylated uricase, and was designed to be the first non-immunogenic version of uricase, which would allow for the effective and safe administration of multiple doses with concurrent mitigation of anti-drug antibodies against the enzyme. The mechanism of action by which we believe our technology mitigates immunogenicity may also allow re-treatment of patients at a future date if needed.
The product profile continues to indicate that SEL-212 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 re-treatment 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 four. This slide provides an overview of the clinical development plan of SEL-212 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 III program. Looking at Slide five, as you can see in the top graph, 81% of the evaluable patients treated with three monthly doses of SEL-212 maintained serum uric acid levels of less than six milligrams per deciliter throughout the full three months. By comparison, in the bottom graph, only one of six patients treated with pegloticase alone, or about 17%, maintained serum uric acid control at week four. We know from the analysis of the corresponding anti-drug antibody data that the difference in this loss of control is well correlated with the level of those anti-drug antibodies, which we believe are mitigated by the co-administration of SVP-rapamycin.
The three 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 six, seven, and eight, the majority of patients have now reached the 12-week data point. Let's turn to Slide seven as an example for some more detailed review of the available patient data. Let me clarify using this Slide seven, 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've 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 seven, eight of the 10 evaluable patients maintained serum uric acid control throughout the first three months.
Two evaluable patients, labeled with the letter A, did not maintain serum uric acid control throughout the first three months. I would point out that the last patient with an A, 0022, upon audit, was underdosed by the site, thus he is a protocol deviation, but we included him in the current analysis. The patients reported on the bottom of the slide were not evaluable 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. One patient, labeled with the letter D, was lost to follow-up after having received the first dose. Slides six and eight provide individual patient data using the same format.
The analysis of the data from the evaluable patients reported on slides six, seven, and eight resulted in the 81% control at month three, as I have mentioned before in this presentation. Slide nine provides new gout flare data from these same cohorts to date, the same cohorts as reported on the slides six, seven, and eight. 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 one, 19% in month two, and 8% in month three. Slide 10 provides gout flare data for the entire patient population in our phase II trial reported to date.
As you can see, SEL-212 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 one, 19% in month two, 6% in month three, 14% in month four, and 3% in month five. These data remain very consistent with the gout flare data we have reported previously for our phase II trial and appear to be lower than the incidence of gout flares reported in clinical trials involving the current FDA-approved uricase therapy. Turning to slide 11. SEL-212 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, nine of which were reported to be not related or unlikely to be related to study drug.
Seven were infusion reactions that were previously reported in our June 2017 data readout, and one infusion reaction in the most recent cohorts. No infusion reactions have been reported after the second treatment cycle. 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. Let's turn to slide 12. At this stage of the development of SEL-212, it is important to put our proposed target product profile in the context of available treatments for chronic severe gout. One product is FDA-approved for this indication, KRYSTEXXA, which utilizes a different uricase. From Skip's update on the clinical data, we believe the three-month data presented today at EULAR may provide a very promising product profile of SEL-212 that may meet many of the current unmet medical needs of chronic severe gout patients, including, first, 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-212 today at EULAR. This retrospective comparison has provided guidance as we make plans for our phase III program. Beyond two 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-212 in patients who have failed KRYSTEXXA therapy. Turning to slide 13. The continuing improved clinical activity of SEL-212 after the three monthly doses has provided the basis for us to initiate additional cohorts receiving five monthly doses of SEL-212 combination product. For instance, 0.15 milligrams per kilogram of SVP-rapamycin and 0.2 milligrams per kilogram of pegloticase.
These data have the potential to show the extended benefit of SEL-212 over the entire treatment period. We are now dosing the fourth combination dose in this cohort, and we expect data for the five combination doses to be presented at a medical conference in the third quarter 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 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 six months treatment cycle versus the less than three months that a typical patient receives today with KRYSTEXXA.
Because of the potential mitigation of immunogenicity, those patients may also be eligible for retreatment at a later time point if needed. 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 session. To ask a question, you will press star then one on your touchtone phone. If you are using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star then two. At this time, we will pause momentarily to assemble the roster. Today's first question comes from Chad Messer with Needham & Company.
Great. Thanks for taking my question, congrats on the continued positive data. Werner, in your opening remarks, you talked about the potential for retreatment with SEL-212. 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 trial that we would conduct against placebo, we certainly will consider that for the extension of those clinical trials.
Okay. 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 competitive profile as well.
John, would you like to address that?
Chad. Good morning. I think if you look at the pivotal trials from KRYSTEXXA, which obviously you can take a look at on the label, about 5% of the patients that were treated had an infusion reaction. 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. At 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 eight, we're significantly less than that.
All right. Great. Thanks and congrats again.
Thank you. The next question comes from Difei Yang with Mizuho Securities.
Hi. Good morning. Thanks for taking my question, just a couple. What's your expectation on safety profile when you expand from the three-combo injection to potentially six-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 erratic, transient changes that we believe are not related to that. Skip, anything to add on that?
No. Hi, Difei. It's Skip. Remember, when we went from one treatment cycle to three treatment cycles, we didn't see any difference, and I don't expect us to see any difference from going from three to five or three to six.
Okay. Thank you. The follow-up question is on the timeline. We're expecting to see this five-combo dose data sometime during Q3. After that, what would happen? What do you have to do before officially starting the phase III?
John, would you like to address that?
Absolutely. Difei, good morning. Essentially, we have been prepping actively for the phase III program behind the scenes. All the systems, we're getting the clinical sites up and running, and we're ready. I think post the data that we'll show Q3, we'll obviously have an end of phase II meeting, and our plans, as we've guided to, continue to be that we'll start that phase III program this year in 2018.
There will be a FDA meeting somewhere in between. Okay, thank you very much.
Thank you. 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 III in light of the data that we've seen here today?
Yeah. Good morning, John, or good afternoon for you. A good morning for you. It's afternoon in Amsterdam. Yeah, I think the continuous, of course, looking at the phase II data will guide us for the final decision. We believe that we start to see a clear profile of what those doses would be. Again, a little more data to collect, and then we can make that final decision.
Okay, great. Then in the phase III study, I know that you're still finalizing the protocol, can you talk to us about the number of patient visits that the participants in this study will need to make, versus the number of patient visits that they have been making in this study?
Yeah, sure. Skip, do you want to quickly address that?
Sure. Hi, John. The number will definitely be decreased, probably close to half is what we expect.
Okay, great. Thank you.
Thank you. Once again, please press star then one if you would like to ask a question. 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 is now concluded. Thank you for attending today's presentation. You may now disconnect your lines.