Connect Biopharma Holdings Limited (CNTB) Earnings Call Transcript

Hello. This is Craig Brelsford with RedChip Companies. Thank you for joining today's webinar with Connect Biopharma, which trades on the NASDAQ under the ticker symbol CNTB. With us today, we have Barry Quart, who is the CEO. We will begin with a brief presentation in a moment and then we will answer your questions. Users may submit a question at any time, click the Q&A button at the bottom of the Zoom window. Before we begin, please allow me to read the safe harbor statement. This call may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements pertaining to future financial and/or operating results along with other statements about the future expectations, beliefs, goals, plans or prospects expressed by management constitute forward-looking statements. Any statements that are not historical facts should also be considered forward-looking statements. Of course, forward-looking statements involve risks and uncertainties. I now turn this webinar over to Barry. Please go ahead.

Thank you, and thanks to everybody who's dialed in. Appreciate the opportunity to introduce to you the Connect 2.0 story that I'd like to think about it. When I arrived at Connect a little over a year ago, this was a Chinese-based biotech company focused on monoclonal antibody technology. They had a lead program, Rademikibart, which is a next-generation DUPIXENT going after the same target IL-4 receptor alpha. And the mandates that I received from the Board was to determine the best approach for further development of Rademikibart and make the company more U.S.-centric. On the latter, we've now moved the headquarters to San Diego. We've started to file 10-Ks and Qs. So you'll start to see the usual kind of communications to investors that you would expect from any other San Diego-based biotech. We've started to significantly reduce the footprint in China and then most recently, we converted from trading ADRs on the NASDAQ to ordinary shares. And that's basically the last box that we were looking to check in terms of the U.S.-centric focus of the organization. From the development perspective, after going through all of the data that's been generated on Rademikibart, it became very clear to me that the most appropriate approach was to move forward in terms of the respiratory targets of asthma and COPD and particularly looking at the opportunity to target acute treatment, patients having an active exacerbation Market research indicated that was a clear opportunity, no competition within the biologics. In fact, the other biologics, including DUPIXENT expressly say in their label not to be used to treat an acute exacerbation with a forecast of approximately $5 billion for both asthma and COPD, going after the target of both acute and chronic treatment. This seems like an ideal opportunity for the drug and I'll give you some of the data why the drug meets all the requirements. So perfectly for treatment of both acute and chronic. This just looks at some of the key studies that have been conducted with Rademikibart. As you can see the completed studies on the bottom. We've looked at both treatment of chronic asthma as well as atopic dermatitis. I should also add that we have licensed out the rights to Rademikibart for Greater China to a large pharmaceutical company in China, Simcere Pharmaceuticals. They paid us approximately $24 million in upfront and some regulatory milestones last year for the rights to further develop and commercialize Rademikibart in China. They -- in midyear filed NDA for atopic dermatitis. So we would be expecting hopefully approval for atopic dermatitis about midyear next year which would come with a significant additional milestones and tiered royalties going up to low double digits. They are also conducting a large chronic asthma study in China, and that should be completed, we hope sometime at the end of next year. We are focused on 2 acute studies, one in COPD, one in asthma, again, looking at patients having active exacerbations. Just a snapshot of what the market opportunities look like, asthma, COPD, large numbers of patients in the U.S. And probably our greatest importance are the 1 million emergency department visits for acute asthma exacerbations and about 1.3 million emergency department business for COPD. But I'd like to point out that, that's just actually the tip of the iceberg. This is a breakdown of where patients go for treatment of an acute exacerbation. Obviously, a large percentage of patients have medication at home, which takes care of those mild exacerbations, but when they are more significant patients go to the doctor's clinic. They go to urgent care, and then you have approximately 1 million asthma patients going to emergency department and then in the hundreds of thousands of patients being hospitalized. So you have a very large market opportunity for treatment of these patients, and they are being treated approximately the same way as they were 30 years ago. No real drug development progress has been made in terms of acute treatment. The same goes for Europe. Very similar numbers in terms of patients going to emergency rooms every year. Now just a little bit about Rademikibart itself, again, targeting IL-4 receptor alpha similarly to DUPIXENT. But it has very different binding. And just to highlight also the importance of these targets. IL-4 and IL-13, which are blocked by rademikibart. It's well established that IL-13 is directly involved in terms of contraction of smooth muscle in the airway. So that bronchoconstriction can be significantly enhanced because of IL-13. But another side effect of IL-13 is a shift in the efficacy curve of beta agonist. So one of the hallmarks of a patient having an acute exacerbation is they start getting tightness in their chest, difficulty breathing, that constriction of the airways. The patient then goes to use their rescue inhaler, albuterol, and it doesn't work and they use some more. It still doesn't work, and then they're on their way to the emergency room. The fact is that inhaler is not working as it normally would may have a lot to do with excess IL-13, which is why we believe that targeting IL-4 and IL-13 is really ideal in terms of treatment of an acute exacerbation in patients who have T2-mediated asthma. This just highlights very different binding between rademikibart and dupilumab and we think that has a lot to do with our enhanced efficacy and a very different safety profile as well, which I'll present shortly. So this is the design of the chronic asthma study that was completed a few years ago, pretty classic design, evaluated two different doses versus placebo. This is the primary endpoint to FEV1, the basically amount of air that you can expel out of your lungs in one second. And you can see that at the very first clinic visit, which was at 1 week, we saw a really remarkable improvement in FEV1, almost 250 mils across the study and it was approximately the full benefit that one sees from the low dose was already accrued at 1 week. So when I started going through the data, my question was, can we get any more granular than 1 week? And I found that patients had home spirometers that had not been fully evaluated. And looking at that data, I found that over 70% of the benefit at 1 week was already achieved the very next morning after a dose. So within hours of that dose, patients had very significant improvement in airway function. And that opened up the opportunity of considering the use of rademikibart for treatment of that acute episode. And then just very kind of top line comparison of our data versus other drugs that are used for asthma. You can see on the very far right, we're trying to compare as close as we can apples-to-apples in terms of cross-study comparisons. You can see the airway improvement with rademikibart from Phase II versus what was seen with dupilumab. And then with other mechanisms, clearly, the IL-4s improve airway function much better than the IL-5s with rademikibart improving it the most. But on the safety front, we see a very different profile, where on the left, you can see with dupilumab or DUPIXENT, you see an increase in eosinophils. Now this is in asthma patients from their Phase III program, and they saw this all the way through development for asthma that -- first of all, you're targeting patients that have high eosinophils to start with, that's the hallmark of identifying patients with T2-mediated asthma. So that's your target population. Patients get dupilumab and their eosinophils go up and they stay up for, in this case, it's 6 months, although they start trending down after about 12 weeks. Conversely, with rademikibart on the right, you see actually a continued decline in eosinophils over the course of the 24 weeks. So a very different profile and that relates also to the proportion of patients that get to excessive eosinophil levels. And that would be over 1,500 is where you would start to get concerned over 3,000, you would be quite concerned. And you can see with rademikibart, we actually reduce the portion of patients that go above 1,500 compared to placebo. While on the right, dupilumab substantially increases the numbers of patients going above 1,500. And the numbers of patients going above 3,000, where we had no such patients, looking at people starting above 500. So these are patients starting very high. You've increased their eosinophils and you have the opportunity to get to very excessive levels. And this is not just a laboratory abnormality. Here are serious adverse events reported to the FDA database for dupilumab, specifically for asthma patients. And these are all eosinophilic serious adverse events. So they are related to that excessive eosinophil level, which we do not have. Another comparison. Now looking at information that we collected in our atopic dermatitis study, 52-week study, demonstrating good tolerability and excellent efficacy with rademikibart. The other thing that we did was very similar to study done with dupilumab. After the 16-week induction period patients where they received the drug Q2 weeks. Patients were rerandomized to receive the drug either Q2 weeks or Q4 weeks. You can see that we maintained efficacy, whether it's the investigator global assessment or the EASI-75 score. We have maintained a very high rate of efficacy over the 52 weeks. And that was essentially the same. In fact, it maybe slightly better with the Q4 week dosing interval. We're with dupilumab when they did the same thing. They found that the Q4 week dosing interval was not nearly as effective as the Q2-week dosing interval which is why dupilumab is a Q2-week drug. And the other thing you can see across the drugs shown here. We had the highest rate of maintaining patients as responders for both of these very important endpoints. So we have very good continued activity in that atopic dermatitis study. So if we -- just to summarize the clinical experience with rademikibart, very fast onset of effect in the asthma study amongst the greatest increases in FEV1 across the biologics. We reduce eosinophils versus increasing them as seen with dupilumab. So we significantly reduce the risk of serious adverse events associated with increased eosinophils with the 600-milligram loading dose, which has been used and now well over 1,000 patients. We have excellent tolerability looking across both asthma and atopic dermatitis studies for chronic dosing, which is well tolerated. We will be looking at Q4 week dosing based on the good results in the AD program. We have met with the FDA in an end of Phase II meeting for both asthma and atopic dermatitis, and we're given a go-ahead to move into Phase III but we put those on pause for now, while we were focused on conducting the 2 studies in acute treatment. So here is the design of those 2 studies. One in asthma patients, one in COPD. These are 28-day end points, so very fast, relatively small numbers of patients for these kinds of trials because the expected failure rate in the control group is so high, it allows us to conduct relatively monetized trials. These studies are ongoing. We're continuing to set up new sites around the world with the target of having data in the first half of next year. And much of the design of these studies is based around recently published data from the ABRA study in the U.K. This was an investigator-initiated trial out of the U.K., where they looked at using benralizumab in the same way that we are trying to use rademikibart for treatment of an acute exacerbation. And here, you can see on the right in the time to treatment failure. So treatment failure is patient leaving the ER. And in this case, they followed the patients out for many more weeks. We're looking at just the 4-week time frame, and treatment failure would be patients who come back to the ER or go to another point of care because they are either continuing to get worse or having a new exacerbation. And the two important findings for us from this trial was that, number one, the failure rate in the control group receiving standard of care is about 45%. So very high rate of patients coming back to the ER which I'll point out in the 4-week period, we're looking at -- the hospital doesn't get paid again. And if the patient comes back, so they have a vested interest in keeping that patient home. And then also, as you can see, the separation with benralizumab didn't really start until about 3 weeks. So this is the kind of typical profile you would see with a biologic, taking days to weeks for it to work, where with rademikibart, we have data showing it starts to work in less than 24 hours. And we have put together all the data necessary to move this program forward in terms of acute treatment as well as hopefully going for chronic development. Once we've completed the 2 acute studies. Market research indicated that having this acute indication was a clear differentiator versus both dupilumab as well as all the other biologics, which, as I mentioned, explicitly say that they are not to be used for treatment of acute exacerbations. And this just highlights that market research data. You can see a very good preference share for using a drug acutely in naive patients with 40% to 45% on the top row. And then on the bottom, where a patient received the drug acutely 75% preference share for continuing that patient on rademikibart. So having this acute indication is a clear gateway to getting significant penetration in the chronic market, which is where the bulk of the revenue would come from. We have a manufacturing process that's already been transferred to a U.S. contract manufacturer. They've made multiple batches successfully. We have a new high-yield cell line, which will be transferred starting late this year into next year. The goal is to use that material ultimately in Phase III. So that would be the commercial material going forward, which gives us a lot of flexibility to charge a lower price in the hospital setting versus the outpatient setting by having 2 distinct presentations. And we've already talked about the Phase II data that we've generated as well as our current plans. We have long exclusivity running out to at least 2042. And then just highlighting some of the accomplishments so far this year. In addition to the 2 Phase II studies that I presented to you, we also have a small pharmacology study ongoing, looking at the potential for IV use of rademikibart, where the goal is now to reduce the time to onset of a benefit from hours down to hopefully minutes. The goal is to have data from that study in early next year. And then obviously, the -- we've already talked about the goal of completing the Phase II studies, having top line results first half of next year. And then last but not least, we have a very strong cash position with $72 million in the bank as of the end of second quarter. And even with paying for the currently ongoing studies, we have cash into '27. And this just shows the cash balance and utilization, as I said, approximately $72 million at the end of second quarter. And with that, that's the end of the official presentation. And I'm happy to take questions.

Thank you, Barry. Thank you very much. [Operator Instructions]. Barry, we have several questions already in the queue. Yes. Here we go with #1. What outcomes in the current Phase II trials would be considered very encouraging to the industry?

Well, so we've powered the studies for a 50% reduction in patients having what we call treatment failure. In other words, coming back to the ER or to another point of care. We think there is an opportunity to do even better than that, but that's how we've powered the trials. And I think that achieving that goal would be in and of itself a very dramatic improvement over what we currently see in terms of how patients are being treated. If you think about an asthma patient today going to the ER, spending 4, 6 hours, getting therapy there, walking out the door, going home. That almost half of those patients will either get worse or have another exacerbation in 4 weeks. We believe that there's a much better way in terms of how we're taking care of those patients.

Thanks, Barry. Can you provide any details on expected milestone payments in 2026?

Well, we haven't disclosed the full breakdown of milestones. What I can tell you is that there is approximately $110 million in milestones remaining in our agreement. And for '26, we are hopeful to see approval of rademikibart for atopic dermatitis that would bring with it a significant milestones. And then potentially the following year, if all goes well, a potential approval for asthma as well. And so between those 2 important milestones, it's quite possible we would be seeing approximately the same amount of milestone payments that we've received last year, but spread across those 2 years.

Barry, we are well aware that you addressed this issue a little while ago, but I think important points, can't hurt to repeat them. This person writes, considering the higher binding affinity of rademikibart with IL-4 and activity with IL-13, have you witnessed any safety issues or off-target concerns?

No. It's a great question. And obviously, all the safety data from our prior trials has been published, didn't go through it in the presentation, but the drug is very well tolerated. You do see typical kind of rates of injection site issues, almost always mild, very rarely, do patients discontinue due to adverse events with rademikibart. And in general, you see somewhat less conjunctivitis. But so far, the drug has really been very well tolerated.

And this person had a follow-up question to that, which is what might be the time line for maintenance indications? How much safety data might be necessary 1 year?

Yes. So another good question, and it does open up an opportunity for us that I did mention. And that is, as noted, our partners in China are just about now completing a 1-year atopic dermatitis study that the data from that, we anticipate to look stellar. And they're currently enrolling in a chronic asthma study, again, a 1-year study. Because both atopic dermatitis and asthma are treated similarly in China as they are in the United States, we believe there is a high likelihood that we can provide the FDA with the required justifications for acceptance of foreign data such that we can use the atopic dermatitis Phase III and the asthma chronic treatment Phase III as one of 2 Phase III trials. And so there's a significant opportunity to basically cut the cost of Phase III development in half for those indications, particularly asthma, where we're focused on, allowing us to ultimately just do one large Phase III trial. We would need to do 2 Phase III studies for the acute indication but that's obviously a much shorter time line versus a 52-week chronic asthma study. And so the expected time lines, which I think was the underlying question, is we hope to have the acute data around midyear and meet with the FDA, get plan agreed to in terms of Phase III for acute and also their willingness to accept the Phase III chronic study. So we could be initiating potentially Phase III studies for acute treatment by late next year. And -- but we would not move forward with Phase III chronic studies until we have a commercial partner or hopefully, ultimately, an acquirer.

Thanks, Barry. Are you exploring any nondilutive funding?