Connect Biopharma Holdings Limited (CNTB) Earnings Call Transcript & Summary

Good morning, and welcome to the Connect Biopharma Conference Call. [Operator Instructions] 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; Raúl 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 call -- 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 web page 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 the key takeaways from today's presentation. On the top line result from our Stage 2 of our China pivotal trial in AD, which evaluated rademikibart's safety and efficacy over 52 weeks, I am very pleased to announce that rademikibart, our anti-IL4R alpha antibody, demonstrated strong efficacy with every 4 weeks of Q4W dosing which appears to outperform the current available biologics on the market that are dosed every 2 weeks, or Q2W. As a reminder, we have shown that we have met all our primary and secondary end points 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 continues 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 4, as a reminder of the China pivotal trial design, the left side of the 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 Association 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, randomized 2:1, in which 219 received subcutaneously administered rademikibart and 111 received placebo. On Slide 5, we can see the comparisons of these 2 patient populations. There were no differences in week 16 efficacy between the primary analysis population of 265 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 achieving an EASI-50 or greater score, and they were re-randomized 1:1 on the right side of the figure to receive 300 milligrams every 2 weeks or 300 milligrams every 4 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 2-week dosing and 112 receiving 4-week dosing. Additionally, 86 nonresponders were placed into an open-label arm to receive rademikibart every 2 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 Q2-week dosing. These are represented by the 2 green boxes, and 112 in the blue boxes receiving Q4-week dosing. Of the 225 responders, 182 were active drug responders and 43 were from the placebo group. On the right side, all 86 nonresponders from the induction stage received Q2-week dosing for the maintenance period. Overall, there were very few discontinuations, and 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 29, 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 4 weeks over the 52-week period. Additionally, 76% of patients maintained an IGA 0/1 response with the Q2-week 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 4-week and 2-week dosing regimens were able to maintain their 75% skin clearance rating with dosing of rademikibart over 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 PP-NRS, over 95% were able to maintain that level with Q4-week dosing and 82% with Q2-week dosing at the end of the study. With respect to the quality of life, 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. The other data are very exciting, and they show that rademikibart treatment of every 4 weeks makes 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 Q2-week dosing or switch to Q4-week dosing. In the blue panel, you can see that at the end of the study, approximately 50% of patients were able to achieve an IGA of 0/1, or clear or almost clear skin, compared to the re-randomized baseline for each group, which represents an additional 20% to 30% of patients placed into deep remission who would subsequently be maintained with long-term rademikibart treatment at either 2- or 4-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 Q2-week dosing and, importantly, Q4-week 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 Q2-week dosing. On the left side of the slide, we see that indeed these patients' EASI scores continue 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 CN002 pivotal trial. In order to make the comparisons as similar as possible, a very conservative nonresponder imputation, or NRI, data was used for each of the programs on this slide. These data indicate that rademikibart dosed every 4 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 2 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 after 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 AD 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 4-week dosing that appears better than other biologics for treatment of AD. In addition to the impressive week-16 efficacy results, rademikibart with both Q2W and Q4W dosing regimens continued to show further improvement 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 rights 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. I'm actually quite excited about the data. I think that the -- this provides us with a new context, a new insight into where the differentiation potential is and where the value is for this asset. We know that there's a growing toolbox and a number of other options that are approved. And as we -- we've always known about the very clean safety profile that was established, the 16-week data look great. But I think we were left with, up until these data, sort of a sense of, well, where is that differentiation? And I think that for me, the money slide is when you look at that -- the comparison of the NRI results between the trials. And of course, there'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 the OX40 and 40 ligand, all these different classes that are trying to find their niche in long-term data, what we're seeing here is, with this asset, that we're getting there, and we're actually establishing what -- I think what could be clearly stated as best in class. And I think that is really quite fascinating data. I also find the gain of efficacy with the Q4-week dosing to be fascinating, because 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, more spread out dosing. And that's something I think 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 the question and answer. Operator?

[Operator Instructions] Our first question comes from the line of Thomas Smith with Leerink Partners.

This is [indiscernible] 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?