Good morning, and welcome to the Connect Biopharma conference call. All participants are now in a listen-only mode. There will be a question-and-answer session at the end of this presentation. If you would like to ask a question, you may press star one to join the question queue. Please be advised this call is being recorded at the company's request, and a replay will be available on the company's website. Attending today's call are Dr. Zheng Wei, Co-founder and CEO; Steven Chan, CFO; Dr. Raul Collazo, VP of Medical Affairs; and Dr. Jonathan Silverberg, Associate Professor of Dermatology at The George Washington University School of Medicine and Health Sciences. I would now like to turn the call over to Steven Chan, CFO of Connect Biopharma. Please go ahead.
Thank you, operator, and thank you all for participating in today's conference call. Before we start, I would like to point out that there is a slide deck that accompanies today's presentation. It can be viewed using the webcast link provided on the investors page of the Connect Biopharma website. Also posted on this webpage is the press release issued earlier today, announcing top-line data from stage 2 of Connect's China pivotal trial of rademikibart in atopic dermatitis, or AD, as it will be referred to during today's presentation. In addition, I would also like to call your attention to the second press release we issued today regarding our partnership with Simcere Pharmaceutical for the commercialization of rademikibart in Greater China.
Before moving on to the presentation, I'll first note that during the course of this conference call, company management may make forward-looking statements within the meaning of the U.S. Federal Securities law regarding future events or performance of the company. Actual events or results could differ materially. We refer you to the documents the company files from time to time with the SEC, specifically the company's most recently filed Form 20-F on April 11, 2023. The company's filings contain and identify important factors that could cause actual results to differ materially from those contained in any forward-looking statements. Please note that the forward-looking statements made during this call are as of today's date, and we undertake no obligation to update them to reflect subsequent events or circumstances, except to the extent required by law. With that, I'll pass the call on to Dr. Zheng Wei, our Co-founder and CEO.
Thank you, Steve. Let me start right away with a key takeaway from today's presentation on the top-line results from our stage 2 of our China pivotal trial in AD, which evaluated rademikibart safety and efficacy over 52 weeks. I am very pleased to announce that rademikibart, our anti-IL-4Rα antibody, demonstrated strong efficacy with every four weeks, or Q4W dosing, which appears to outperform the current available biologics on the market that are dosed every two weeks, or Q2W. As a reminder, we have shown that we have met all our primary and secondary endpoints in stage 1 of this trial. Our week 16 efficacy has been impressive and was similar, if not better, than the approved biologics for AD. Today, we will review the top-line data on maintenance of clinical response and continued improvement beyond week 16, starting with maintenance of clinical response.
In stage 2, 87% of patients maintained their clear or almost clear skin, and over 90% of patients maintained their EASI- 75, itch scores, and quality of life through week 52 with Q4W rademikibart treatment, meaning that rademikibart had sustained efficacy in both physician and patient-reported outcomes. When we evaluated continued improvement beyond the one achieved at week 16 with rademikibart, we saw up to 30% more patients achieving clear or almost clear skin and up to 16% more patients achieving EASI 75 by week 52. Rademikibart continued to be well-tolerated, which was consistent with the results we have seen in stage 1, with no new safety signals observed. Together, the results suggest that rademikibart can offer a highly efficacious treatment with more convenient dosing. With that, I would like to hand over the call to Raul to take you through the data in detail. Raul?
Thanks, Wei. It's my pleasure to review the top-line results from stage 2, the maintenance period of our rademikibart pivotal trial in China. On slide four, as a reminder of the China pivotal trial design, the left side of this slide outlines stage 1, or the induction portion of the study. These 16-week data were released at the end of last year and presented as an oral presentation at the 2023 American Academy of Dermatology meeting, showing that all primary and key secondary endpoints were met with very high significance. At that time, we presented data on our primary analysis patient population of 255 patients.
In order to increase the number of patients exposed to 52 weeks of treatment, the completed study enrolled an additional 75 patients for a total of 330 patients r andomized 2 to 1, in which 219 received subcutaneously administered rademikibart, and 111 received placebo. On slide five, we can see the comparisons of these two patient populations. There were no differences in week 16 efficacy between the primary analysis population of 255 on the left, which was disclosed earlier, and the expanded 330 patients analysis on the right that is being presented today. The remaining slides will focus on the 330- patient expanded analysis.
Going back to the China pivotal trial design, after 16 weeks, responders were defined as those as achieving an EASI- 50 or greater score, and they were re-randomized 1:1 on the right side of the figure to receive 300 mg every two weeks or 300 mg every four weeks, with the latter allowing us to evaluate a more convenient dosing regimen for longer term use. These groups were evenly distributed, with 113 receiving two-week dosing and 112 receiving four-week dosing. Additionally, 86 non-responders were placed into an open label arm to receive rademikibart every two weeks during the maintenance stage. Here we see the patient disposition of the stage 2 maintenance period. There were 311 patients who entered the maintenance period.
On the left side, we see that 225 week 16 EASI- 50 responders were evenly re-randomized, with 111 receiving Q2W dosing. These are represented by the two green boxes, and 112 in the blue boxes, receiving Q4W dosing. Of the 225 responders, 182 were active drug responders and 43 were from the placebo group. On the right side, all 86 non-responders from the induction stage received Q2W dosing for the maintenance period. Overall, there were very few discontinuations, and over 90% of participants completed all 52 weeks of dosing. The demographics of the maintenance population are similar to the induction phase of the study and in line with expected baseline values, which were well-balanced across the arms of the trial.
Importantly, just over 50% of patients were considered as having severe atopic dermatitis and had an IGA score of 4, with a mean initial baseline EASI score of approximately 21, indicating that the study population reflected patients having active, moderate to severe atopic dermatitis at initial baseline. Now, let's get to the exciting part of the presentation. First, we will look at the investigator-rated outcomes of IGA 0/1, meaning patients that achieved clear or almost clear skin and EASI- 75. On the left panel, we're looking only at patients who achieved an IGA of 0/1 at week 16. Of these patients, an impressive 87.2% were able to maintain their clear or almost clear skin with dosing of rademikibart once monthly or every four weeks over the 52-week period. Additionally, 76% of patients maintained an IGA 0/1 response with the Q2W dosing.
On the right panel, we're looking at patients who achieved at least an EASI 75 response at week 16. Of those patients, again, impressively, over 90% of patients in both the four-week and two-week dosing regimens were able to maintain their 75% skin clearance rating with dosing of rademikibart in 52 weeks. Now, let's move to patient-reported outcomes of PP-NRS, measuring pruritus or itch, and the DLQI, examining patients' quality of life. Similar to the investigator ratings, patient-reported outcomes were also highly maintained over 52 weeks of rademikibart treatment. On the left panel, of the patients who achieved a clinically meaningful, greater than or equal to 4-point reduction in PPNRS, over 95% were able to maintain that level with Q4W dosing and 82% with Q2W dosing at the end of the study.
With respect to the quality of life, a greater than or equal to 5-point reduction on the DLQI is considered clinically important, and over 90% were able to maintain this level at the end of the 52-week study. Together, these data are very exciting, and they show that rademikibart treatment of every four weeks makes a clinically meaningful difference in both objective and subjective measures. Now, let's turn our attention to the evaluation of continued improvement. As we previously shared, the induction data did not plateau at week 16 for either IGA 0/1 or EASI- 75, which can be seen in the green panel of both graphs. This indicates that greater efficacy could be achieved with longer dosing.
When we continue rademikibart treatment beyond week 16, we see that continued treatment leads to greater efficacy and places more patients into deep remission, where their responses can be sustained with rademikibart maintenance. First, let's focus on IGA 0/1 on the left. Following the induction period, we re-randomized the 182 EASI- 50 responders to continue Q2W dosing or switch to Q4W dosing. In the blue panel, you can see that at the end of the study, approximately 60% of patients were able to achieve an IGA 0/1 for clear or almost clear skin... compared to the re-randomized baseline to each group, this represents an additional 20%-30% of patients placed into deep remission who would subsequently be maintained with long-term rademikibart treatment at either two- or four-week dosings.
Similar responses are seen on the right side with EASI- 75 data, with an impressive 85% of patients achieving EASI- 75 by week 52, with both Q2W dosing and importantly, Q4W dosing regimens. As seen on the previous slide, rademikibart may be able to maintain this response or better in over 90% of these patients. What about patients who do not respond to rademikibart treatment after 16 weeks? We wanted to examine if these 26 patients would continue to have improved clinical response with continued Q2W dosing. On the left side of the slide, we see that indeed, these patients' EASI scores continued to improve another 45% over what was observed at week 16, ending in an overall improvement in EASI score of 72% from the initial baseline levels.
On the right side, continued rademikibart treatment led to clinical response in all categories, with over 50% of patients reaching 75% skin clearance by week 52 and 36% reaching an impressive 90% skin clearance. While we need to be cautious when comparing across trials, this slide compares published long-term maintenance data with the current CN02 pivotal trial. In order to make the comparisons as similar as possible, the very conservative non-responder imputation, or NRI data, was used for each of the programs on this slide. These data indicate that rademikibart dosed every four weeks may be more efficacious at maintaining IGA 0/1 and EASI 75 responses than other approved and investigational biologics dosed every week or every two weeks.
Turning our attention to safety data, when looking at the safety across both the induction and maintenance phases of the study, rademikibart continued to be well-tolerated, with no apparent new safety signals with long-term treatment out to 52 weeks. The rates of adverse events were similar across groups. There were no serious adverse events reported to be related to the study drug, and discontinuation rates were low throughout the study period. The rate of conjunctivitis-related adverse events continues to be low. Overall, the AE profile appears consistent with the induction phase, previous rademikibart trials, and the IL-4/13 class of medications as a whole. With that, I'll hand the call back to Wei for closing remarks.
Thank you, Raul. To conclude today's presentation, rademikibart demonstrated its best-in-class potential with high sustained efficacy with every four weeks dosing that appear better than other biologics for treatment of AD. In addition to its impressive week 16 efficacy results, rademikibart with both Q2W and Q4W dosing regimens continue to show further improvements in clinical response, giving more patients the opportunity to benefit from rademikibart maintenance with a convenient monthly dosing schedule. In terms of safety, rademikibart continues to be well-tolerated with long-term treatment. As for next steps, this has been a very exciting day for us. As in addition to the very compelling data we presented for rademikibart, we announced a strategic partnership with one of China's top pharmaceutical companies.
We have granted Simcere exclusive right to develop and commercialize rademikibart in Greater China, and we are very excited to start our collaboration in preparation for NDA submission to China CDE by end of Q1 2024. Simcere is an ideal partner to help us bring rademikibart as a new, highly efficacious treatment with convenient dosing to patients with atopic dermatitis in Greater China. These data will now be utilized in our ongoing discussions with other potential partners in regards to the development of rademikibart in the rest of the world. I would also like to remind you that we have another data readout coming, and that we are on track to announce the top-line results from our global phase IIb study in asthma in this quarter. Before we open it to question and answer, I would like to ask Dr. Silverberg to provide some observations on the data reported today.
Thank you, Wei. It's really a pleasure to be able to comment. You know, I'm actually quite excited about the data. I think that the, y ou know, this provides us with a new context, a new insight into where the differentiation potential is and where the value is for this asset. You know, we know that there's a growing toolbox and a number of other options that are approved. And as we've always known about the very clean safety profile that was established. The 16-week data looked great, but I think we were left with, up until these data, sort of a sense of, well, where's that differentiation?
I think that for me, the money slide is when you look at that, the comparison of the NRI results between the trials. You know, of course, it's always a challenge making a cross trial comparison, but those differences are not subtle. These are the best numbers we've seen for any maintenance data. Even looking across the landscape, when you look at, like, you know, those 40 and 40 lives, all these different classes that are trying to find their niche in long-term data. What we're seeing here is, with this asset, we're getting there, and we're actually establishing what the—I think what could be clearly stated at best in class. And I think that is a really quite fascinating data.
I also find the gain of efficacy with the Q4 week dosing to be fascinating because, you know, we've seen, other drugs show a gain in efficacy with continued highest dosing. But to even see that at that half dose, we're getting that gain in efficacy, suggests that there might even be an opportunity here for out of the gate, you know, more spread out dosing. And that's something that I think, you know, needs to be explored in future partnerships. But, I think this is, something that we have not seen previously, with other drugs within this class. So from my perspective, I'm really seeing that differentiation potential now.
Well, thank you, Dr. Silverberg. We can now open to a question and answer. Operator?
Thank you. At this time, we'll be conducting a question- and- answer session. If you'd like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you'd like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Our first question comes from the line of Thomas Smith with Leerink Partners. Please proceed with your question.
Hi, this is [Nat Sharon on for Tom Smith. So the first question is, could you provide more color on the Simcere transaction? Was the process competitive, and what drove your decision to partner with Simcere?
Thank you, Thomas. Steve, would you like to take a stab at this?
Yeah, sure. Thanks, Wei, and thanks for the question there. Yeah, it was a competitive process. It's been something that we've been working on, and honestly, this is the outcome that we wanted. Simcere Pharmaceutical is a company with a great reputation, extensive track record, capabilities in clinical development and operations, manufacturing, and including sales and marketing, right? We've been looking for a partner that can help us take over commercialization, and combined with the good data that we're seeing today, including the long-term efficacy that we've seen with this data, we feel like we're really well set up from a competitive perspective going forward. So, feeling really good about the potential of this Simcere partnership, especially from a commercialization perspective.
How confident are you on getting, like, Q4W approved in China, and what's the commercial outlook there?
Yeah, so I can take a stab on this. You know, the data is really so strong that it certainly make it a lot easier to apply for the Q4W NDA. Obviously, you know, how to, you know, to design the label and to discuss with CDE in terms of the label is going to be in a collaboration between us and Simcere. And I think that, you know, the bottom line is that the data here is really strong to support both dosing regimens. And again, I have to mention that, you know, in China so far, there is no other studies, including dupi, that have a Q4W dose in any of the sections of the trial, either in stage 1 or stage 2.
So, this is going to be a point where Simcere, and we together can really point to the differentiations and provide that kind of benefit to patients. I think one thing to remember is in China, it's still quite, still quite common for patients to come to the, dermatologist office to get their next injections. And it's a very common practice, even though the injection in, at home is available, for example, for biologics. And so with the Q4 dose, it's going to make the life a lot easier for patients who need to, receive, regular dosing.
All right, last one from us. How's today's result, like, impact the global AD study planning or partnership? Do you think the asthma result remain an important key factor for the partnership?
So first of all, obviously, the AD data is so strong here that for the China partnership, that's going to have a very strong kind of strategic collaboration going on and and put us in a strong position to commercialize that molecule in China. For global partnership, obviously we are looking at all indications, right? So, AD is in discussions, and we certainly, based on this very strong data, a point of differentiation from what's available and what's in investigations in the clinic, we believe that this data will support our ongoing AD discussion first. The asthma data obviously will come in and help as we expand the indications of rademikibart. And, you know, just as we would expect, this molecule eventually will be used for multiple type two diseases.
So I think that the asthma data is going to be very important. We'll be, you know, we'll use that data again to support our global discussions on BT. Steve, do you want to chime in?
No, I think that's, that's correct, Wei. I think we see this data set as strong. We see its differentiation, and it's data that we've been looking for. Should really bolster our partnership discussions going forward.
That's good. Thank you, and congrats on the data.
Thank you.
Thank you. Ladies and gentlemen, that concludes our question and answer session. I'll turn the floor back to Dr. Wei for any final comments.
Well, thank you all for attending today's call. As I mentioned earlier, we will be reporting our top-line data on a global phase II asthma trial in the coming weeks. We look forward to providing this and other updates in the near future. Thank you, and have a great day.
Thank you. This concludes today's conference call. You may disconnect your lines at this time. Thank you for your participation.