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

Good day, and thank you for standing by. Welcome to the Connect Biopharma Conference Call to report topline data from the company's CBP-201 pivotal trial in China to treat severe to moderate atopic dermatitis in China conference call. [Operator Instructions] The slides for this presentation are available via the webcast, which has been posted on the Investors section of the Connect Biopharma webcast. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Ina McGuinness, Connect's Investor Relations. Please go ahead.

On today's call is Connect Co-Founder and CEO, Dr. Zheng Wei; Chief Medical Officer, Dr. Chin Lee; and Dr. Jonathan Silverberg, who is an Associate Professor of Dermatology at the George Washington University School of Medicine and Health Sciences in Washington, D.C. and is the Director of Clinical Research and Contact Dermatitis. Before we get started, let me remind you that during today's call, management will make various forward-looking statements. Investors are cautioned that these forward-looking statements are based on current expectations and are subject to risks and uncertainties that could cause actual results or outcomes to differ materially from those indicated by our forward-looking statements. Please read the safe harbor statement contained in the press release we issued earlier today as well as those contained in Connect Biopharma's registration statement and Form F-1 for a more complete discussion of these risks and uncertainties. Additionally, management's prepared remarks were recorded earlier to allow for the participation of Dr. Silverberg who is unable to join us on the live call. Now I'd like to turn the call over to Wei. Wei?

Thank you, Ina. And good morning, good afternoon and good evening to all of those participating on this call and webcast as we discuss the topline results from our pivotal trial of our lead candidate, CBP-201. This is a pivotal trial of CBP-201 in patients with moderate to severe atopic dermatitis in China, which I'm pleased to announce achieved all primary and secondary endpoints at a critical 16-week mark. As we have stated before, we anticipate engaging with the CDE in the next several months to determine the potential for a new drug application, which could be filed as early as 2024. Before I turn the call over to Chin, who will review the trial results in detail, I want to take a moment to thank the clinicians who have worked so hard to make this trial a success and the patients who have participated. In particular, I want to extend a special thank you to Professor Jianzhong Zhan, Director of Dermatology Department at Peking University People's Hospital, who is our principal investigator on the trial. Atopic dermatitis is a terrible disease that affects patients well beyond those symptoms that are [indiscernible]. We look forward to potentially bringing a new IL-4R alpha antibody treatment to the market to meet the continuing unmet needs. And with that, I turn the call over to Chin. Chin?

Thanks, Wei. It's my pleasure to review the topline results from Stage 1 of our CBP-201 pivotal trial in China. I'd like to start by highlighting some key takeaways from the study on Slide 3. First, as Wei indicated, our study successfully achieved all primary and secondary efficacy endpoints with highly statistically significant results at week 16. The trial showed low discontinuation rates and similar baseline characteristics between treatment groups, reflective of a well-conducted study. In addition, the safety results show CBP-201 was generally well tolerated with a safety profile consistent with targeting the IL-4 receptor alpha pathway. Most treatment-emergent adverse events were mild to moderate in severity and did not lead to discontinuation. The study design is shown on Slide 4 includes 52 weeks of treatment, and it's comprised of 2 stages: Stage 1 consists of a 16-week treatment period, whereas Stage 2 includes an additional 36-week treatment period. The entry criteria included adult patients ages from 18 to 75 years and individuals were required to have AD for at least 1 year or longer with moderate to severe disease based on an PP-NRS of 16 or greater, IGA of 3 or greater, BSA involvement of 10% or greater and PP-NRS, a pruritus measure, of 4 or greater. We enrolled 255 patients for the primary analysis population. Eligible patients were randomized 2:1 to receive subcutaneously administered CBP-201 or placebo. Patients assigned to CBP-201 received an initial 600-milligram loading dose followed by 300 milligrams every 2 weeks. The primary endpoint was a proportion of patients with IGA 0 or 1 and a 2 or more point decrease from baseline at week 16. There were multiple secondary endpoints, including EASI responses and PP-NRS, which represented key secondary endpoints. In Stage 2, responders defined as those achieving an EASI 50 or greater were rerandomized 1:1 to receive either CBP-201, 300 milligrams every 2 weeks or 300 milligrams every 4 weeks with the later allowing us to evaluate a more convenient dose regimen for longer-term use. Individuals not meeting our response criteria received CBP-201 300 milligrams every 2 weeks. For today's readout, our focus on the efficacy and safety results from our primary analysis population from the 16-week Stage 1 treatment period. Turning to Slide 5. Among the 255 patients randomized, a total of 170 were assigned to the CBP-201 treatment group and 85 to the placebo group. All patients received at least 1 or more dose of study drug and the discontinuation rate overall was low with only 4.7% discontinuing from the CBP-201 group, whereas 7.1% discontinued from the placebo group. The most common reason for discontinuation was from consenting withdrawn across both groups. In the CBP-201 group, 1 patient was discontinued due to poor compliance and another due to an adverse event of atopic dermatitis. Approximately 95% and 93% of patients in the CBP-201 and placebo groups, respectively, completed through week 16. The baseline profile of our study population, as seen on Slide 6 was indicative of the following: First, that the randomization was successful as the overall demographic and disease characteristics were comparable across treatment groups; second, the study population clearly reflected patients having active moderate to severe AD. On average, the study population included patients in their late 30s and early 40s, with slightly more than 1/3 of the population represented by females and the patients had a mean BMI of approximately 24. In terms of the disease characteristics, IGA; EASI score; body surface area percent involvement; PP-NRS, a measure of itch; and DLQI, a measure of quality of life were all reflective of a study population with active, moderate to severe atopic dermatitis. Let me now turn your attention to the efficacy results, starting on Slide 7. First, we achieved our primary endpoint, which is a regulatory endpoint of interest, reflecting the proportion of patients with an IGA of 0 or 1 and a 2-point or greater reduction at week 16. As seen on the left panel, 30.3% of patients in the CBP-201 group as represented by the green bar, achieved this IGA endpoint whereas only 7.5% improved on placebo, resulting in a 22.6% treatment difference between the 2 groups, which was highly significant. On the right panel, the treatment response over time clearly shows early improvement for CBP-201 with significant differences noted as early as week 4 with increasing clinical response observed over time for the CBP-201 group versus placebo. On Slide 8, the left panel showed the results for our key secondary endpoint for the proportion of patients achieving an EASI-75 at week 16. As seen in the green bar, 62.9% of patients treated with CBP-201 achieved an EASI-75 versus 23.4% of patients on placebo, resulting in a highly significant treatment difference of 39.5%. The right panel shows the proportion of patients achieving an EASI-75 response over time where we observed early and continued significant improvement across multiple time points favoring CBP-201 versus placebo through week 16. For additional EASI results seen on Slide 9, we observed early and continued significant improvement across multiple time points for percent change from baseline in EASI by study visit for CBP-201 versus placebo through week 16. The right panel displays the proportion of patients achieving EASI-50, EASI-75 and EASI-90 responses across the treatment groups. Notably, the placebo-adjusted treatment differences of 42%, 39.5% and 29.4% on EASI-50, 75 and 90, respectively, were all highly significant, favoring CBP-201. Slide 10 shows improvement in pruritus or itch for which we observed significant improvements favoring CBP-201 versus placebo based on improvements in PP-NRS of 3 or more as well as 4 or more point reductions at week 16 as seen on the left panel. Specifically, 46.7% of patients receiving CBP-201 experienced a 3 or more point reduction on PP-NRS versus 16.7% on placebo, resulting in a significant treatment difference of 30%. Likewise, we saw a significant treatment difference of 25.6% favoring CBP-201 for the proportion of patients with a 4 point or greater reduction on PP-NRS at week 16. The percent change from baseline in PP-NRS by study visit is seen on the right panel for which there was clear separation showing significantly greater improvements for patients receiving CBP-201 as early as week 1 and all subsequent time points as compared to those on placebo. By week 16, there was a 38.1% reduction in PP-NRS for CBP-201 versus 12.3% reduction for placebo. Turning to the safety results on Slide 11. The overall safety profile of CBP-201 indicated that it was well tolerated with no new safety signals. Specifically, the overall any treatment-emergent adverse event or TEAE rates were similar between treatment groups, with 73.5% and 72.9% and for the CBP-201 and placebo groups, respectively. Overall, there were fewer patients experiencing serious adverse events or severe adverse events in CBP-201 relative to the placebo group. There was a single patient with an adverse event leading to study drug discontinuation in the CBP-201 group that I mentioned earlier when reviewing the patient disposition, which was a patient with an event of atopic dermatitis, and there was 1 patient in each treatment group reporting Herpes virus infection. As for the adverse events of special interest, there were 8 to 11 patients in the CBP-201 group with conjunctivitis, keratitis and injection site reactions lasting longer than 24 hours, respectively, none of which were SAEs. Notably, all of these events of injection site reactions were mild in severity. A single event of anaphylaxis was considered not related to study drug and was a mild severity with the patient remaining in the study who continue to receive study drug over the 16-week treatment period. Otherwise, there were no other types of adverse events of special interest in the CBP-201 group. In the placebo group, there were 3 patients with adverse events of conjunctivitis and none with keratitis, injection site reactions lasting longer than 24 hours or anaphylaxis. Turning to Slide 12. Our large China-specific pivotal trial successfully achieved all primary and key secondary endpoints at week 16 in patients with active moderate to severe AD. Besides achieving the primary endpoint based on the IGA score, more than 8 out of 10 patients on CBP-201 achieved a 50% improvement in their EASI score and more than 6 out of 10 patients on CBP-201 achieved 75% improvement in their EASI score. The safety findings continue to support existing safety and tolerability profile for CBP-201, which remains consistent with targeting the IL-4 receptor alpha pathway with most treatment-emergent adverse events being predominantly mild to moderate in severity without leading to study drug discontinuation of CBP-201, which continues to be generally well tolerated. Looking ahead, Stage 2 maintenance period is ongoing and will potentially demonstrate sustained efficacy with continued dosing every 2 weeks as well as at a more convenient every 4-week dosing schedule. The results from the current trial support advancing the regulatory discussions with CDE for submitting an NDA in China. And now let me turn the call over to Jonathan Silverberg.

Hello. I'm Dr. Jonathan Silverberg. I'm a Professor of Dermatology at the George Washington University School of Medicine and Health Sciences in Washington, D.C. I just wanted to share some thoughts on atopic dermatitis burden and management and my thoughts on the data just presented. First, just thinking about atopic dermatitis overall, and in particular, moderate to severe disease. It is a difficult-to-treat disorder. I see these patients in my office every week suffering from moderate to severe disease who have severe itch, skin thickening, oozing, weeping and bleeding and myriad comorbidities, including cutaneous and extra cutaneous infections, atopic comorbidities, such as asthma and hay fever and mental health comorbidities, such as depression and anxiety. Patients very commonly experienced poor quality of sleep, psychosocial distress, and mental health disturbances because of their atopic dermatitis. And despite recent advances in the treatment of moderate to severe atopic dermatitis, there are still an enormous unmet need in the United States and around the world. Currently, we have good prescription topical medications and non-pharmacologic strategies to manage mild to moderate atopic dermatitis. For the moderate to severe population, biologics and systemic medications are often needed with biologics most commonly being utilized first line, followed by JAK inhibitors as second line due to potential safety concerns. Many people achieved a good response with these medications, but there's definitely a lot of room for improvement with respect to improved efficacy, safety and dosing. Now there is 1 approved biologic in the U.S. that targets the interleukin-4 receptor alpha subunit already. And CBP-201 is in -- is also an IL-4 receptor alpha inhibitor. So why is second drug in the same class? Well, as mentioned, existing treatments leave room for improvement for higher levels of clear skin, no itching, no depression, improved sleep, extending the dosing schedule so that patients only have to dose perhaps every 4 weeks after the initial treatment period instead of just consistently every 2 weeks, forever. And these all improve the patient's quality of life and minimize treatment burden. In addition, we have a lot of experience with cycling between different biologics within a class in other immune-mediated disorders such as psoriasis. We've seen patients do much better on 1 TNF alpha inhibitor than others, for example. I just want to also touch on the depression and quality of life again quickly. This is a real issue for patients and a big topic of my own research. Any medications we can add to our arm of [indiscernible] to help clear the skin of patients with atopic dermatitis is certainly welcomed by dermatologists and patients alike. That being said, I want to touch a bit on the data presented today and give my initial impressions. We are seeing clear evidence of clinical activity in the trial population of patients with moderate to severe atopic dermatitis. For example, the primary endpoint of achieving investigator global assessment of clear -- almost clear skin, and the key secondary endpoint of proportion of patients achieving an EASI-75, a 75% improvement in the Eczema area and severity index that are both highly significant in terms of their response rates, both clinically and sufficiently speaking. In particular, the kinetics for the proportion of patients achieving EASI 75 over the course of the trial demonstrated very impressive efficacy with no evidence of plateau at week 16. Said another way, the curve was still rising quite impressively even at week 16, suggesting the possibility of more efficacy beyond week 16. Additionally, with respect to all other endpoints, it was quite reassuring to see highly significant changes that all support the potential for CBP-201 to become an effective treatment for patients really across all endpoints with moderate to severe atopic dermatitis. And lastly, with regard to safety, the CBP-201 profile looks really clean, including even just conjunctivitis rates being quite low. There were certainly no new safety issues beyond what we've already seen with the class of medication and everything looks quite reassuring. So I look forward to having this drug as part of our treatment paradigm. Thank you very much for your attention.

[Operator Instructions] Our first question comes from Kelly Shi with Jefferies.

Congrats on the progress. My first question is can you actually help us to understand the patient baseline in terms of BSA and EASI score? And the second question is I noticed for EASI-50, the placebo response is particularly high. And can you help us to understand the rationale behind and what kind of adjustment do you do? And -- yes.

Kelly, thank you for the question. Good to hear from you again. So I think this is a question perhaps, Chin, would you like to address?

Thanks, Wei. So thanks for the question, Kelly. So in terms of the BSA and the other baseline characteristics, when we look at the population, I think it's pretty much in line with what we might expect in a patient population with moderate to severe AD. And this was the kind of patient population we we're very interested in enrolling for the study. So I think on that point, we successfully enrolled the population we were targeting. And again, I would think as you heard, from the presentation, this population represented patients with active, moderate to severe AD. And then in terms of the placebo response, I think when you look at the placebo rates for the different efficacy endpoint measures, I think what we're seeing is some variability that you might expect for any trial. When you look at any trial side by side, there's probably some variability and I think that's what we're seeing here. And we know that there may be potential geographic differences that could contribute to that. So I think, by and large, when I look at the responses from the placebo side, I don't think there's anything that really stands out to say this is an overt response of placebo effect.

Our next question comes from Louise Chen with Cantor.

This is Carvey on for Louise. A quick question from us. So atopic dermatitis getting to become a crowded development space. So based on the data presented today, what do you think are your top differentiated factors here?

Thank you. Probably I can take a stab at this first, and Chin can chime in as well. So this is -- obviously has been the reason why we are moving forward within -- with CBP-201. And the first of all, is the unmet need, as Dr. Silverberg just pointed out, the market is -- there is still unmet need out there for a molecule like IL-4R alpha inhibitor. That's number one. Number two, we want a molecule to be highly efficacious and to be able to maintain the high efficacy or prolonged treatment. And I think we believe that, that is where the advantage of a biologic treatment as it's going to be. So by looking at the profile that we have with this larger study is very clear that the molecule is very, very effective, right? So we're looking at over 80% patients achieving a response defined by EASI-50 and EASI-75 is over 60%. So we're talking about 8 out of 10, 6 out of 10 have very good response. We are looking also at long term is that if you look at the data today, it's very clear there is a good potential that prolonged treatment post 16 weeks will also give you increased efficacy even beyond 16 weeks. And the potential to maintain high level of response with excellent safety and being able to potentially also dose with a more convenient dosing of Q4W, which we have shown to be efficacious in our global Phase IIb study will provide a very, very competitive profile, and we think that profile like that will be successful in helping patients. Chin, do you want to add anything?

Yes, I think you hit on all the points that are clear differentiators for us in AD. I would say the one other point I would add is if you pan back away from AD and just the opportunity with this molecule and this mechanism, I think there are other diseases that we are currently evaluating, for example, asthma. So it allows us to potentially differentiate us from other classes that are in the AD space. And I think that's another point of differentiation for this class for us beyond AD.

Our next question comes from Thomas Smith with SVB Securities.

Congrats on the data. Just -- I was wondering if you could give us any more color on the nature of the regulatory conversations you need to have now with CDE to determine whether these data are going to be sufficient to move forward? And then is there any opportunity to leverage this data set to expedite the U.S. with a global regulatory filings?

Well, thank you, Tom. Let me answer the first question first and Chin can perhaps take the second one. Yes, so as we said previously, this data set and this analysis will be presented to the CDE and now that we have the topline data, we're in a position to submit a pre-BLA meeting requests to CDE and that is what we were guided to do. And so for the questions as far as whether or not this data set will be good enough for approval in terms of efficacy, that will have to wait until we have an opportunity to meet with CDE and we hope that we will be able to meet with them according to the official time line of 60 working days after submission for a meeting. And in terms of safety profile, I think we have communicated before is that the 52-week safety data set is going to be required. So we'll be happy to update once we have more information after we have our meeting with the CDE. Chin, would you like to address the potential use of this for the FDA submission?