Good afternoon. Welcome to the Selecta Biosciences phase II COMPARE Conference Call. At this time, all participants are in a listen-only mode. For opening remarks, I would like to introduce Brad Dahms, Chief Financial Officer of Selecta. Please go ahead, sir.
Thank you, and good afternoon. During this call, we will discuss top-line results from the phase II COMPARE study of SEL-212, a novel treatment for chronic refractory gout versus pegloticase. The press release reporting the results and the presentation that Carsten and Peter will walk through are available in the Investors and Media section of our website, www.selectabio.com. Joining me today are Carsten Brunn, our President and Chief Executive Officer, and Dr. Peter G. Traber, our Chief Medical Officer. During today's call, we will be making certain forward-looking statements, including, without limitation, statements about the potential safety, development, efficacy, and regulatory and clinical products of our product candidates, including SEL-212, future expectations, plans, partnerships, and prospects. These statements are subject to various risks, including those related to the COVID-19 outbreak that are described in our filings made with the Securities and Exchange Commission.
You're cautioned not to place undue reliance on these forward-looking statements, which speak only as of today, September 30th, 2020. Selecta disclaims any obligation to update such statements, even if management's views change. I would now like to turn the call over to Carsten Brunn, our President and CEO. Carsten.
Thank you, Brad. Good afternoon. I appreciate you joining us today, and I'm very pleased to be sharing the top-line results from the phase II COMPARE study. As Brad mentioned, SEL-212 is a novel treatment for chronic refractory gout, which contains a proprietary pegylated uricase enzyme, pegadricase, combined with a Selecta immune tolerance platform, ImmTOR. Before we review the results, I want to remind everyone of the unmet medical need in chronic refractory gout. Approximately 160,000 patients in the U.S. suffer from chronic refractory gout, a painful and debilitating condition in which patients are not able to get their SUA levels below 6 mg/ dL and therefore have several flares per year and can develop nodular masses of uric acid crystals known as tophi. Elevated SUA levels have been associated with diseases of the heart, vascular system, metabolism, kidney, and the joints.
There's only one approved product on the marketplace in the U.S., KRYSTEXXA or pegloticase, which is dosed every two weeks. There's a significant unmet medical need for more durable, once-monthly treatment for patients with this debilitating condition. The phase II COMPARE trial is a head-to-head study of a once-monthly dose of SEL-212, which is a combination of ImmTOR and pegadricase, compared to twice-monthly doses of pegloticase with a primary endpoint of the maintenance of serum uric acid or SUA levels of less than 6 mg/dL during months three and six combined. Pegloticase is the only approved product for chronic refractory gout and is approved only in the U.S. Key secondary endpoints include the same measurements of SUA at months three and six individually and over reduction in SUA levels. The trial enrolled a total of 170 patients.
In June of this year, we entered into a strategic licensing agreement with Sobi for SEL-212, so we will fund the phase III clinical program and will have commercial rights in all markets outside of China. Detailed in the press release on September 23rd, the phase III program, titled DISSOLVE, which will assess SEL-212 versus placebo, has randomized and dosed its first patient. We expect to report top-line data from the DISSOLVE program in the second half of 2022. We are thrilled to have Sobi as our partner and are excited to share the phase II COMPARE data with you today. First, we're very pleased that we were able to actually successfully complete the study during the COVID-19 pandemic. We modified the statistical analysis plan and submitted the change to the FDA prior to the database lock to account for an increase in protocol deviations.
Unfortunately, the SEL-212 arm was slightly more impacted by protocol deviations. While the COMPARE trial did not meet the primary endpoint of showing statistical superiority of SEL-212 to pegloticase during months three and six combined, we're extremely encouraged that the data consistently shows stronger performance of SEL-212 versus pegloticase across all endpoints and patient populations. SEL-212 showed a statistically significant higher response rate versus pegloticase during month three and a numerically higher response rate during month six and during months three and six combined. In the per-protocol analysis, the primary endpoint was missed by one patient. Additionally, SEL-212 showed statistically significant greater overall reduction in mean SUA levels versus the pegloticase.
Finally, in patients with tophi, SEL-212 showed a substantially higher overall response rate and a statistically significant overall reduction in mean SUA levels for SEL-212 versus pegloticase, which we believe is a very important finding to demonstrate the efficacy of SEL-212. In addition, the COMPARE data demonstrated that both SEL-212 and pegloticase were well-tolerated. Now, I'll turn it over to Peter to walk you through the data in more detail.
Thank you very much, Carsten. On slide three of the deck that was distributed, I will discuss the design of the phase II COMPARE trial. It was a phase II non-registration study that was conducted as a randomized, open-label trial in patients with chronic refractory gout with inadequate control of serum uric acid using conventional therapy. We, as a company, remained blinded to the primary endpoint of serum uric acid throughout the study. The U.S.-marketed intravenous uricase, pegloticase, was used at the recommended dose and interval of 8 mg every two weeks for six months, or a total of 12 doses. This was compared to our investigative agent, SEL-212, a combination of a proprietary uricase, pegadricase, and ImmTOR, our novel nanoparticle drug for inducing immune tolerance to sequentially administered antigenic compounds such as non-mammalian uricase enzymes. SEL-212 was administered intravenously once monthly for six months.
The primary efficacy assessment in the trial was the comparison of the percentage of patients on SEL-212 versus pegloticase who achieved and maintained reduction of serum uric acid less than 6 mg/dL for at least 80% of the time during three months and six months combined. The secondary endpoints included the same measurement in months three and six separately. Another important assessment of the relative potency and effectiveness of SEL-212 versus pegloticase is the absolute reduction of mean serum uric acid levels during the same treatment periods. In the following slides, I am pleased to report that all data are consistent with a stronger performance of SEL-212 versus pegloticase. As shown on slide four, 170 patients were randomized and dosed in the trial, with 83 patients assigned to SEL-212 and 87 patients assigned to pegloticase. This represents the intention-to-treat, or ITT, data set for analysis.
In addition, we will report analysis using the per-protocol data set, defined as patients who were administered any amount of study medication and having completed at least 65% of the study doses, unless they had early termination from the study after a study drug withdrawal due to meeting stopping rules or due to an adverse event, or early termination due to investigator discretion. Additionally, patients with major protocol deviations affecting the primary efficacy assessment were excluded from the per-protocol set. Moving on to slide five, clinical trials conducted during the COVID-19 pandemic must take into consideration potential impact on study conduct and analysis, as advised by the FDA in its June 2020 guidance. Only one patient in the trial, a pegloticase patient, had a confirmed case of COVID-19, and this led to discontinuation.
However, an increase in protocol deviations were noted due to disruptions in clinical operations and patients' personal life situations. The COMPARE trial statistical analysis plan was modified and submitted to the FDA prior to database lock in compliance with the FDA guidance. Modifications were focused on the potential impact of the COVID-19 pandemic on statistical analysis. We are pleased the COMPARE trial was completed during the COVID-19 pandemic. Trials conducted and completed during the pandemic may heighten the importance of the per-protocol data set more than usual in analysis of the data. We still have work to do on the impact of COVID-19 after we receive the full data set. On slide six, I will provide some background on patient baseline characteristics and demographics. Randomized patients were on average 52 years of age, over 95% male, 77% white, and with a body mass index in the obese range.
There was no difference between the ITT and the per-protocol groups. Importantly, approximately 41% of patients enrolled had clinically detectable tophi or urate crystal deposits at baseline. Slide seven shows the results on the primary endpoint measurement, or the percent of patients who achieved and maintained reduction of serum uric acid for at least 80% of the time on study drug. The results showed that SEL-212 demonstrated statistical superiority during month three and numerical superiority during month six and during months three and six combined. The month three and six combined period was designated as the primary endpoint in the protocol and SAP. For month three, the SEL-212 arm had 70% responders for both per-protocol and ITT populations, while the pegloticase arm had 54% and 52% responders per-protocol and ITT respectively. This difference was statistically significant in both protocol and ITT sets.
On a relative basis, SEL-212 showed a 30%-37% greater percentage of responders than pegloticase. Analysis of treatment period six alone and treatment period three and plus six both showed similar results, with numerically greater, but not statistically significant, difference in response rates. It should be noted that the per-protocol population in both month six and month three plus six nearly reached statistical significance with P values equal to 0.053 and 0.056, respectively. These data show clear superiority of SEL-212 therapy over pegloticase in the first three months of therapy. A reduction in patient numbers over the course of the study may be one of the reasons why statistical significance is lost in month six, despite maintaining numerical significance over pegloticase.
Moving to slide eight, evaluation of mean serum uric acid levels during month three and six combined demonstrates that SEL-212 induced a more robust reduction in serum uric acid than pegloticase. The baseline serum uric acids were numerically but not statistically higher in the SEL-212 group than pegloticase. Despite somewhat higher SUA levels at baseline, SEL-212 treatment resulted in a 48% and 40% greater reduction of serum uric acid than pegloticase in the per-protocol and ITT sets, respectively. These results were statistically significant with P values of 0.003. These data suggest that once-monthly dose of pegadricase, when administered with ImmTOR to induce immune tolerance, is a more potent uricase than pegloticase for lowering serum uric acid in chronic refractory gout patients.
Reducing serum uric acid to low levels in a sustained fashion is a critical goal of gout therapy, particularly tophaceous gout, where the lower the level of serum uric acid, the more efficient is the dissolution of the uric acid crystals in tophi. These impressive findings cause us to look at those patients with tophi. You would now move to slide nine. In the subset of patients with clinically evident tophi at baseline, which was 41% of the entire population, there was a 19 percentage point and 16 percentage point greater response rate for SEL-212 versus pegloticase during months three and six combined in PP and ITT sets, respectively. This represents a large relative treatment difference of 49% and 39% in per-protocol and ITT sets, respectively. Although low numbers likely restricted reaching statistical significance, the magnitude of the difference between therapies is greater than in the entire group of patients.
Comparison of response rates for SEL-212 shows similar results for the entire population and the tophi subset, with a response of 59% in the entire population and 58% in the tophi population, considering only the per-protocol set. In contrast, the response rates for pegloticase dropped from 46% in the entire population to 39% in the tophi population, again in the per-protocol set. On slide 10, we found a rather striking result when we looked at reduction of serum mean uric acid in patients with tophi at baseline. SEL-212 demonstrated a statistically superior 60% overall reduction in mean SUA levels, even greater than the robust reduction in uric acid seen in the entire patient population. For the SEL-212 group, a mean baseline serum uric acid of 9.48 mg/ dL would be reduced to 2.06 mg/ dL.
Whereas pegloticase would reduce the mean from a baseline of 8.58 to 3.94, nearly a 2 mg/dL difference between the two treatments. Because there is a significant inverse correlation between serum urate area under the curve and tophus resolution velocity, the greater potency of a single dose of SEL-212 per month versus two doses of pegloticase per month may be clinically relevant for treatment of tophaceous gout. On slide 11, top-line analysis of the safety database suggests that both therapies were generally well-tolerated, and there were no deaths during the study. There were no differences in serious Treatment Emergent Adverse Events, or TEAEs, treatment-related serious TEAEs, or infusion reactions between the two groups. A full analysis of safety signals, including gout flare incidents and severity, awaits evaluation of the full data set and will be reported along with full efficacy analysis at a future medical meeting.
On slide 12, just a reminder about the ongoing pivotal phase III program for SEL-212. The phase III DISSOLVE clinical program consists of two double-blind placebo-controlled trials of SEL-212, in which SEL-212 will be evaluated at two doses of ImmTOR, 0.1 mg/ kg and 0.15 mg/ kg, and one dose of pegadricase, 0.2 mg/ kg in both studies. Each trial will aim to enroll 105 patients, 35 at each dose level and 35 on placebo. In DISSOLVE I, safety and efficacy will be evaluated at six months and will have a six-month extension. DISSOLVE II will address safety and efficacy at only the six-month time point with no extension. The primary endpoint in both studies is serum uric acid control at six months. Secondary endpoints include tender and swollen joint counts, tophus burden, patient-reported outcomes of activity limitation and quality of life, and gout flare incidents.
The DISSOLVE program has dosed its first patient. Selecta and Sobi expect to report top-line data in the second half of 2022. I will now turn the call back to Carsten.
Thank you, Peter. To reiterate, we're very pleased that we were able to successfully complete the COMPARE trial during the COVID-19 pandemic. As outlined, we modified the statistical analysis plan and submitted the changes to the FDA prior to database lock to account for an increase in protocol deviations. As mentioned, the SEL-212 arm was slightly more impacted by protocol deviations. We'll further analyze this imbalance once the full data set is available. Overall, we're extremely encouraged that the data consistently shows stronger performance of SEL-212 versus pegloticase across all endpoints and patient populations. SEL-212 showed a statistically significant higher response rate versus pegloticase during month three and a numerically higher response rate during month six and during months three and six combined. In the per-protocol analysis, the primary endpoint was missed by one patient. Additionally, SEL-212 showed statistically significant greater overall reduction in mean SUA levels versus pegloticase.
Finally, in patients with tophi, SEL-212 showed a substantially higher overall response rate versus pegloticase and a statistically significant overall reduction in mean SUA levels for SEL-212, which we believe is a very important finding to actually demonstrate the efficacy of SEL-212. In addition, the COMPARE study demonstrated that both SEL-212 and pegloticase were well-tolerated. The clinical evidence on SEL-212 to date clearly demonstrates the promise of our ImmTOR platform to selectively mitigate unwanted immune responses and allow sustained therapeutic activity when combined with a highly immunogenic enzyme. We're confident that SEL-212 has the potential to improve the lives of patients with chronic refractory gout. We look forward to evaluating SEL-212 in partnership with Sobi in two double-blinded, placebo-controlled phase III trials and continuing to assess our ImmTOR platform to amplify the efficacy of biologic therapies, including redosing of life-saving gene therapies.
I also want to reiterate our gratitude to the many people who have been integral in moving SEL-212 forward to clinical development, including our patients and their families, our investigators who spearheaded the COMPARE trial, our participating trial sites, and our development partner, Sobi. Lastly, I'd like to thank the Selecta team who have worked tirelessly to bring SEL-212 to where it is today. We plan to share further updates about the broad potential of the ImmTOR platform throughout the year. On this remark, I'm closing the presentation and will open the call up for questions. Operator?
Thank you. 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're 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. Our first question will come from Eliana Merle with Cantor Fitzgerald. Please go ahead.
Hey, guys. Thanks for taking the question. Just on the protocol deviations, could you give us a little bit more color on, I guess maybe what the most common protocol deviations were by arm and I guess how these were treated statistically in the per-protocol analysis? Secondly, just in terms of the number of maybe missed visits or missed doses, is there any more color that you can give just in terms of the number of patients that did not miss any doses or did not miss any visits, and maybe what the data would've looked like for that group? I have a follow-up question. Thanks.
Yeah, thanks. That's a great question. I'll let Peter share some of the details in a second, but obviously it was a broad range of deviations. It was missed blood draws. It was delayed blood infusions. In some cases, there was a death in the family, actually, so patients didn't feel comfortable actually to come in to a site. I think what's important is if you look at the overall numbers, actually, Ellie, I mean, so we had a total of 83 patients for SEL-212 and a total of 87 in the ITT population. On the pegloticase arm, about 17 patients were lost in the per-protocol analysis, about 20%. For 212 was about 29%. There's an imbalance of seven patients that we're looking at. You can also see that, actually, that imbalance actually drives the efficacy outcome, right?
If you look at the overall number of patients lost until time point three, it's actually very consistent across all groups. If you look at our per-protocol, the loss between treatment period three and treatment period three and six, we lost about six patients or 14%, whereas we lost 24% in the per-protocol. That's largely driven through protocol deviations. As I said, we're going to look at this a little more closely. I think what is interesting is that there's an overall trend is actually very consistent. One of the findings that we were actually very positively surprised was quite significant, is the overall impact or efficacy of SEL-212 in patients with tophi. There, you actually don't see a large difference between the ITT and per-protocol population.
There we lost about 15% of patients between treatment period three and three plus six, very consistent. It's really in the ITT subgroup is kind of the outlier with an additional eight patients we've lost, which we're looking at into more details. With that, maybe, Peter, you can share a bit more details around the actual protocol deviations.
Yeah. Thanks, Carsten. That was a very good explanation, and I won't duplicate what you said. I'll just point out, Ellie, that all clinical trials have a large number of protocol deviations, and a smaller number of those are major protocol deviations. An even smaller portion of them are major protocol deviations that affect the efficacy signal. We are in the process of analyzing all of those. We did have a number of COVID-19 related protocol deviations as a small proportion of those deviations, and we're looking at those to see whether they disproportionately affected one arm versus the other. The way we define the protocol deviations, it was. I'll give you an example here in a moment. If it was a major protocol deviation that caused a change in the efficacy assessment, that led to removal from the per-protocol group.
For example, if somebody missed their day 21 uric acid blood draw by 10 days versus the operating window that we had of three days, that was a major protocol deviation and that would lead to a change in the efficacy endpoint because that's a critical measure on the SEL-212 arm. What we did not find was that they were all in one category or another, and we have not done the full analysis to try to understand how COVID might have impacted the rates, although we do see a general balance in COVID-related protocol deviations between SEL-212 and pegloticase. I don't know if that additional detail will help, but I'll turn it back to Carsten.
Thanks, Peter. Ellie, you had a follow-up question?
Yeah, that was helpful. I appreciate the color. Just on the safety, I'm curious, it seems like you saw a pretty balanced safety versus the KRYSTEXXA arm. Curious sort of what you think drove that and any points of differentiation that you did see emerge on the safety outside of course, the effect on tophi, although that's maybe perhaps more efficacy. Just how you think that the safety profile of SEL-212 would then compare to, say, KRYSTEXXA plus methotrexate from a safety perspective, and any key potential advantages or differences emerging from this data set.
Obviously, I don't want to speculate on a trial that is still ongoing with methotrexate. I think what we can look at, and obviously I'll hand it to Peter for some more color on the safety data. I think one good point to look at is actually discrepancies to the adverse events, and that number we do have. We lost a total of 10 patients to adverse events, and KRYSTEXXA lost about 13. It's obviously a very small numerical difference, but there is a small difference. Obviously, if you add another immune suppressant to a regimen, you obviously do have additional side effects. I don't want to belabor methotrexate. I think it's well known, some of the side effects, obviously has a black box warning around a number of end organ toxicities.
There's limitation around alcohol use, which, we believe obviously is quite important in this patient population. On methotrexate, you can't have more than three drinks. I think the other limitation that is really probably the most relevant actually, is that you have to exclude patients with chronic kidney disease, and that's a fairly large population in chronic refractory gout. In fact, in the KRYSTEXXA phase III study was 49% of all patients. We believe from an epi perspective, it's probably about 30% of patients that you have to exclude. As I said, we haven't seen any control data on the combination. We definitely believe that adding an additional immune suppressant will change the overall safety profile.
Thanks.
Ellie, related to specific adverse events and so forth, the full data set will have patient-level specificity around AEs. We're reporting here the serious TEAEs and treatment-related serious TEAEs that we didn't see any difference. The mild to moderate AEs and those of special interest to both drugs we'll be sorting out once we get the full data set and don't have much more to report on that at this point.
Thanks, Peter.
Thanks.
Our next question will come from John Newman with Canaccord. Please go ahead.
Hey, guys. Thanks for taking the question. First question I have is, just curious if you can give us any color on anything that you saw with regard to gout flares in terms of the difference between the SEL-212 arm and the KRYSTEXXA arm. The other question I had was just a follow-up. Can you give us a sense as to whether the difference between the SEL-212 arm and the KRYSTEXXA arm in terms of the primary endpoint, whether that difference widened as a higher percentage of patients in a group that you looked at completed most of the visits? I'm just curious if, as the number of completed visits goes up as a percentage, does the difference tend to also increase between the two arms? Thanks.
Great questions there, John, as always. Around the gout flares, that's part of the data set we'll get with the full data set, which we have not received yet. As Peter mentioned, we'll report on that once we have the data in hand. Around the difference on the primary endpoint, we, at this point, only have really top-line data, and we haven't really had a chance to dig too deep in terms of differentiation. I think one of the things, obviously, that is very profound is that there is statistical significance at month three. You still have a healthy numerical difference, actually, if you look at the per protocol, I mentioned during the presentation, there was actually one patient's difference. It's a P value of .056, or even tighter for the six-month endpoint is .053.
I think the other piece which I think is very important in terms of efficacy, actually, and I mentioned this briefly, and that's really, I think, a very relevant finding, is the patient with tophi showed really a profound difference. You're looking at, obviously the study wasn't powered for it, but showed a difference of 19 percentage points in the per protocol arm and 16 in the ITT arm, there's no real difference between the two. What's interesting as well is that we had about 41% of patients with tophi. If you look at the KRYSTEXXA phase III study, it was a higher number, actually 72, 73. Probably also, if you look at patients presenting and the most severe patients, actually, it's probably a higher number, right? We're probably a little bit on the lower end.
The learning here is really that we show consistent efficacy, in patients tophi and no tophi with SEL-212, whereas we see a lower response rate in patients on KRYSTEXXA with tophi. The other findings I think is interesting in terms of just differentiation on the endpoint, is the overall reduction in mean serum uric acid levels. If you stay with the patients with tophi, there's a pretty small number of patients, but we actually demonstrated statistical significance here. It's actually a quite profound 60% difference. Also for the primary endpoint for the ITT population, you're still looking at a reduction of 40% versus pegloticase with quite a significant P value of 0.003. I think there's a couple of nuggets that we still have to mine, John, but overall, we're quite impressed by the overall reduction and all the numerical trends we see.
Obviously we have to look at what happened kind of between treatment period three and the three plus six, where we lost an additional couple patients on protocol deviations.
Okay, great. Thank you very much.
Our next question will come from Raju Prasad with William Blair. Please go ahead.
Thanks for taking the questions. Carsten maybe, or Peter, can you just talk me through a little bit on your thoughts on why the change in responder rate declined so much from three months to six months in the SEL-212 arm versus the KRYSTEXXA arm? It's like 10%-11%, or I guess eight or 10% in the SEL-212 arm. Is there a mechanistic rationale for why that occurred? I'm going to follow up.
Yes. We obviously don't believe there is a mechanistic. I mentioned earlier, we see actually very consistent response. It's really in the ITT population where we lose an additional eight patients. Out of those eight, actually five are protocol deviations, and that we have to look at. We looked at some of those. Actually, some are just sheer bad luck. Three took a drug that was contraindicated during the course of therapy. Yeah, we definitely don't think there's anything mechanistic because the data actually is very consistent, and actually the dataset with the patients with tophi is kind of a good control where we see actually very consistent numbers, right. We see in the patients with tophi, obviously a smaller population, but about a 15% drop between treatment period three and three plus six.
We see a 14% drop with all patients, ITT, for all patients on the per protocol for 212, and it's a 24%. It's the additional eight patients really that drive it. We don't think this is anything mechanistical.
Okay. On the changes to the SAP that were submitted, can you just give me a little more color on what, was it just the per protocol analysis that was changed, or were there other changes that were made to the SAP?
Yeah. I'll let Peter give more detail. One of the key change definitely was the per protocol set. Inside, we give a bit more flexibility around dosing visits to allow obviously for people change schedules, and we had a couple of sites close down to COVID, so patients had to be redirected to other sites. Peter, maybe you can provide a bit more detail.
Yes. Sure. Thank you. Of course, in a clinical trial, there are many things that operationally need to be specified, in terms of measurements and so forth. Really the SAP was focused on allowing the per protocol set to absorb the potential for disruptions to operations from COVID-19. Of course, the intention to treat set is set. You can't do anything to change the intention to treat, but the per protocol is what we looked at. For instance, the per protocol set takes into account the period of time of treatment. How many treatments does one need to have to be considered part of the per protocol? Is it enough? All studies kind of look at that. A lot of studies have 80% versus less.
We decided that you had to have at least 65% of the treatment in order to be in per protocol. That was a change from before. The other areas were more related to measurement of things. You also define windows, like I mentioned earlier, windows around, say, day 21 blood draw or the day 28 blood draw. While we tried to make the windows a little bit larger in order to account for when sites might be closed due to COVID and so forth, or we needed to send home healthcare people to draw blood, et cetera, but not too large that they would affect the efficacy endpoint. Those were the kind of things that we defined and proposed to the FDA and we felt that everything was reasonable in what we had recommended. I don't know if that helps a little bit.
It does. Thank you.
Thank you.
Our next question will come from Chad Messer with Needham & Company. Please go ahead.
Great. Thanks. Good evening, and thanks for taking my question. Look, I think strongly trending data against your primary competition with half the doses and trending on efficacy, that is not a bad profile for SEL-212. I'm not concerned there at all. I don't think that's your most important long-term value creator. I think you'd agree with me. I'd like to drill into this similar safety profile as much as we can. I appreciate that the data set is still being analyzed. Maybe just to start, do you think the pegloticase arm on efficacy and tolerability performed in line with expectations?
Yeah. I would definitely say, look at what the job is of the uricase. The job is to reduce serum uric acid levels, right? There we have a profound impact, statistically significant, actually, across all the endpoints, right? We're reducing 40% versus pegloticase. Absolutely, yes. I think it does the job exceptionally well with giving it once a month only versus twice a month, right? I think that's a fundamental difference as well. I think what's important to consider as well, Chad, obviously, the pegloticase is given alone at the moment, whereas pegadricase is given with ImmTOR.
If you give the pegadricase alone, we've seen in our phase I study, I think it goes five or six patients with pegadricase alone, out of the six, only one patient actually made it to month one, whereas now you're able to redose six times and get a response rate between 50%-60%, depending which data set you're looking at, or even potentially higher for the patients with tophi. I think there's a profound. Number one, the pegadricase is a very effective enzyme, but it's also a highly immunogenic enzyme. I think ImmTOR does an outstanding job, actually, inducing tolerance. Actually, patients are able to tolerate, if you compare it versus pegadricase alone. Obviously, the price of the game here is to be differentiated. As you rightly said, we feel we actually have very strong data.
Of course, and you rightly said, there's a lot of value in the platform, and I think we definitely feel very strongly that we set a pretty high bar for ImmTOR with the pegloticase, and I'm extremely pleased, actually, with the data and the efficacy we see with the combination and the impact that ImmTOR has on that.
Yeah. I would just add that emphasis too, that I think it's a remarkable thing that ImmTOR did here, which is take a drug that you could get less than 20% people to respond to with only one month of therapy, and then turn it into one that you can give six months and have the kind of results that we have. I think it bodes very well for the platform of ImmTOR being able to induce immune tolerance, not just to pegloticase, but to other antigens that were in our pipeline.
Yeah. That's very helpful. Obviously, what I'm kind of focused on and concerned with as well. You had some interesting flare data in your earlier studies. Is that something you have now or anything you can comment on?
Yeah. You guys know the acid well, so John asked the same question. No, we don't have the gout flare data yet. That comes with a full data set, and we'll report on that, and obviously, we're also curious to see that data as well. We haven't received it. It wasn't part of the top-line readout.
All right. Okay. Great. Thanks. I appreciate the additional color and we'll be following this with interest.
Thank you, Chad.
Our next question will come from Derek Archila with Stifel. Please go ahead.
Hi, Bill on for Derek. Thanks for taking our question. We've talked a bit about your goals with differentiation. Can you talk a bit about how you're thinking about the phase III program now, you've got the additional dose in there and sort of what you would want to see and expect to see in that program to sort of confirm the differentiation that you've been talking about?
That's a great question. Obviously, as you've seen, we already started the phase III study. What's important is that the COMPARE trial, as Peter mentioned, is not a pivotal study, not a regulatory study. They're independent. We don't see any really major changes for the phase III protocol based on this data, to be honest. I think in terms of differentiation, obviously, it is a luxury to have direct head-to-head data already in a phase II. I think it's quite unusual. I think as Chad pointed out, there's very strong data here to mine and because ultimately, what you're trying to do in chronic refractory gout is to reduce serum uric acid levels, as fast and as low as possible. That's obviously the endpoint, below six, 80% of the time is a responder endpoint.
What is relevant clinically, and that's actually why our PI, Rob Keenan, is extremely excited, is the statistically significant reduction in overall SUA levels you see. I think that's really a key driver around differentiation. The other differentiation is obviously the convenience with a once monthly in a patient population that we know is not very compliant to begin with. We obviously think that's very important as well. Just as a reminder, the phase III is a placebo-controlled study, there's no active arm.
Right. That's great. Thank you.
Our next question will come from Ram Selvaraju with H.C. Wainwright. Please go ahead.
Thanks for taking my questions. Just a couple, if I may. Can you shed additional light on the specific nature of the protocol deviations seen so far, and what measures you might need to take in order to prevent these from being apparent in the DISSOLVE trials? Secondly, I wanted to know whether you can comment on, logistically speaking, whether the DISSOLVE studies are likely to proceed directly concurrent with one another, or if you expect them to be somewhat staggered in nature and therefore have differential in terms of the timing of the readout of the top-line results. Thank you.
Thanks, Ram. I'm not sure we can provide a lot more color on the protocol deviations, but maybe, Peter, you can summarize it one more time for Ram.
Yeah. Ram, those are very good questions. As you know, the moving parts in a clinical trial as complex as the one we just completed with COMPARE are great in terms of the operational issues. We learned a tremendous amount from the COMPARE trial that will be applicable to the operations of the phase III trial. It comes down to a whole variety of operational things in terms of ensuring that patients get the right tests at the right time and how they're screened and so forth. I would say that much of what we learned in the COMPARE trial will be implemented in the DISSOLVE trials, and it should make for a more effective operation because we know the things that cause deviations, and we can prevent them.
There are quite a list of those, but I think safe to say that there's a lot of learning. The second question you ask is that the DISSOLVE I and DISSOLVE II trials will be running concurrently. We will be enrolling the first patient in DISSOLVE II by the end of this year.
Thank you.
Thank you, Ram.
This concludes the question and answer portion of the call. I will now turn the call back over to Selecta CEO, Carsten Brunn, for any closing remarks. Carsten?
Yeah, thank you, operator, and thank you again for joining us, and this concludes today's call. Thank you very much.
Thank you again for joining us. This concludes today's call. Please have a great day.