Alright, good morning everyone. My name is Brandon Foulks, and I am one of the biopharma analysts here at HC Wainwright. Next up, we have a fireside chat with Connect Biopharma, and with me from Connect Biopharma is CEO Barry Quart. Barry, pleasure to have you. Maybe if you can just start and give us a very high-level overview of Connect and what the good things you're doing over there.
Yeah, I'd love to. Thank you very much for the opportunity to be here today. For those not familiar with Connect, Connect was previously a China-based biotech focused on monoclonal antibody discovery and development. I've been with the company for just a little over a year, and the mandate that I received when I joined was to make the company more U.S.-centric and to find the best approach for development of our lead program, which is a monoclonal antibody called rademikibart. It's a second-generation Dupixent, so IL-4 receptor alpha targeted monoclonal. Since I've been with the company, we've completely redone the management team with people with a long history of drug development and working in public company operations. We've refocused our energies in terms of development of rademikibart.
We've moved the headquarters to San Diego, started filing Ks and Qs, so the goal is to look like any other San Diego-based biotech from the point of view of the investor community.
Great, and congrats on all that progress. I'm going to just dive right in. You know, can you just walk us through the clinical rationale for focusing rademikibart on acute exacerbations, rather than pursuing sort of the traditional chronic-only strategy we've seen?
Yeah, absolutely. As I went through the phase 2 data with rademikibart in chronic asthma, which is the typical type of approach towards development of a biologic in the asthma space, I realized that it had a very unique differentiation compared to other biologics, which was a very rapid onset of effect. That opened up the opportunity for looking at the drug in the setting of acute exacerbations. It's just important to appreciate that you have millions of patients a year having acute exacerbations, with approximately a million of them going to emergency departments, many more going to urgent care to their doctor's offices, and they're still receiving treatment today the same as they would have 20 years ago. They get a steroid, and they get a high-dose bronchodilator.
There's unquestionably an unmet need for better treatment for these patients, particularly in that half of them will come back to the or seek medical care elsewhere within four weeks of their first visit because they either get worse or they have a second episode. We can definitely improve these patients' both quality of life and benefit the hospital by preventing these patients from coming back.
Great, and based on the phase 2 data, we saw a pretty strong FEV1 benefit within 24 hours. That's extremely promising. Can you talk about what that does in a competitive landscape? How does Dupixent look and maybe other biologics within those first 24 hours?
Yeah, certainly. The primary endpoint in the phase 2 study was FEV1, a typical endpoint looking at lung function, how much air can be expelled out of the lungs in one second. Normally with biologics, people come back to the clinic at two weeks or even four weeks for their first FEV1. We started looking in the clinic at one week, where you see very dramatic improvement in FEV1 of about 250 mL, and this is maintained or even improved over the course of 24 weeks. We also had home spirometers, and that allowed us to take a look at what was happening to that patient in a much more granular sense than that first week visit at the clinic.
We found that over 70% of this benefit was achieved within 24 hours, basically the next morning, so pre-bronchodilator FEV1 was already almost completely improved at that point, and it certainly was by the next day. What we were seeing was improvement in FEV1 within hours of receiving the drug, and no one had ever reported that kind of speed in terms of onset of effect. In fact, we have some data showing that, in terms of improvement of patients, benzimab, which is a drug that's popular in the asthma space, took about three weeks for it to start showing a benefit. Being able to show a benefit within hours definitely opens the door for improvement of patient care, people having an exacerbation.
The other thing that's important to note is that all of the other biologics currently approved for asthma or COPD explicitly say in their label, do not use to treat an acute exacerbation. Obtaining an indication for that would be a completely unique opportunity for us to really own that market, where nobody else could potentially promote against us until someone else was able to generate the data to obtain an indication.
Do you think there's structural binding profile differences between rademikibart and these other products? If so, even if they went after that clinical data, do you think there's challenges to try to generate data, sufficient data to compete in the acute space? What do you see, or do you just see white space ahead of you given some structural differences?
Right. Certainly, we hit a very different pattern of epitopes versus Dupixent, even though we both are targeting the IL-4 receptor alpha, and so we bind very differently. Because of that and other differences, we really are differentiated in that, as I said, speed of onset. We have a differentiated safety profile. I wish I could say that that was designed in, but we just happen to be lucky in terms of, because of the structural differences, we do not see the hyper-eosinophilia that is seen with Dupixent. With Dupixent, patients frequently get very high eosinophils. Many of them end up with serious adverse events because of that. We do not see that at all. In fact, we decrease eosinophils. We have data showing we can be used q4 weeks.
Our goal is to differentiate ourselves in every way possible, and we think that we have covered most of the key important differences in terms of efficacy, safety, duration of dosing, and there is more to come.
Great. I'm just going to jump ahead before we dive into the clinical trials you have ongoing now, all the way to commercialization, right? You've got potentially this acute opportunity ahead of you. Many patients may present with acute exacerbations first and then go into chronic medication. Can you just talk about the potential commercial opportunity here, right? Whether it's with you or your partner, if a patient's presenting and getting rademikibart for acute exacerbations, what's the chance or the potential that that patient may just stay on rademikibart in a chronic setting if they're getting sort of good results there? I know we don't talk about chronic too much and the tremendous differentiations in this acute, but what about, I don't want to call it a Trojan horse, but using that acute that maybe we're underestimating the potential chronic use here?
Yeah, no, that's a great question. We are currently developing the product in terms of the conducted two phase 2 studies looking at the acute opportunity. Our long-term strategy and the greatest commercial opportunity is matching this acute indication with a chronic indication. We did market research and we initially thought, let's just develop this acutely. It's fast. It's a 28-day endpoint versus a year asthma trial, chronic asthma study. Much cheaper, with the opportunity of getting a phase 3 program underway and completed in a much shorter period of time. We did market research and what we found was really quite exciting in that clinicians, number one, were very interested in using a new tool to treat patients, 40-45% preference share for using the drug acutely.
What was really exciting was that, overwhelmingly, they said if the patient did well acutely, of course, we'd want to keep them on the same drug. You're exactly right. The acute indication for us is the gateway to breaking into a somewhat crowded chronic market. Now COPD, not nearly as crowded, but definitely asthma, where the opportunity for significant commercial upside is much greater as you're dosing patients every month, month in and month out. This acute indication really is the gateway into significant chronic use.
Great. Just a follow-up there, any safety signals that you've seen in the data generated to date that we should be cognizant of when we think about that gateway potentially into a chronic use?
Yeah, so far the drug has been very well tolerated. Realistically, the only difference that we've seen between placebo and active patients has been the usual but infrequent injection site reactions that are typical with any kind of injected product. We don't see the increase in eosinophils, as I mentioned, that you see with Dupixent in asthma and COPD patients specifically. We don't really see any other differences to the control arm. I'll point out that the drug now has been in over a thousand patients. It's completing phase 3 in atopic dermatitis. In China, we have licensed the drug to a large Chinese pharmaceutical company. They've filed an NDA for atopic dermatitis. They're well on their way to completing a phase 3 in asthma, in chronic asthma, and so large patient numbers already treated. We're pretty sure that we're not going to find any surprises going forward.
Fantastic. Maybe just, you know, segueing into the studies you have going on right now, can you just update us on the enrollment progress for the CBRE-STAT studies, and if you're still on track for the data readout?
Yeah, so our plan is to have top-line results in the first half of next year. The site startup is moving ahead as with any trial. That's the first step towards enrollment. The other thing that's somewhat unique about these studies is that we're looking for people having an acute event, where they would normally show up in the emergency room or in urgent care. Sitting around waiting for those patients to come can be time-consuming, and we want to make sure we meet our target in terms of top-line result. We have a second track that patients can get enrolled. They can certainly be enrolled if they come to one of our sites for urgent care, but they can also be pre-enrolled by the usual pulmonology research sites.
The clinicians are going through their patient records, finding people who have had recent exacerbations, putting them at risk for another one in the next six months, and we pre-enroll those patients so they're already signed informed consent. We have a really excellent baseline in terms of data collection, and they get a card that says, when you start having an exacerbation, call this number and come to this clinic or site, and they're already pre-enrolled. Very smooth process. All of that is now up and running. We're opening up sites in Europe as well. That's ongoing and in Latin America, so we have the benefit of two seasons in a year.
Great. Can you just talk about the regulatory interactions you had in terms of the trial design, how this trial perhaps supports regulatory alignment on an acute label? That's something a little different than what we've seen. Can you just talk about what shaped this trial design and then how do we look going forward?
Yeah, so this is, you know, our approach here is to collect as much data as possible in terms of both the acute benefits. What's happening to the patient right after they get the medication, monitoring FEV1 frequently, looking at symptomatology in these patients. Now, the primary endpoint is what we call treatment failure. That's if a patient comes back and goes to another location for medical care within four weeks. As I've said, we anticipate seeing top-line results because it's only a four-week primary endpoint. We know from a recently published trial, very similar design out of the UK, that we expect to see about 45% treatment failure. These are patients leaving with normal standard of care, prednisone, a bronchodilator. 45% of those are expected to come back to that or another location for additional medical care because they're either getting worse or they have a second episode.
All of that is part of the data that we'll bring to the FDA when we talk about what the phase 3 program is going to look like. It's going to look similar, but it'll have a lot more attention on that first couple of days.
Yeah, I think embedded in that primary endpoint is some health economic data, right? If sort of not returning to treatment in 28 days, can you just talk about how you think about the health economic prospect here versus, and you sort of touched on this a little bit, taking this into a phase 3 development strategy, a development pathway, and what we should think about a phase 3 looking?
We think phase 3 will be for the acute setting, not very different than the studies that we're currently doing. It should be a fast endpoint, relatively small studies, because we're looking at a situation with a very high rate of failure. These studies should be small, relative to the usual chronic phase 3. The approach would be move forward with the acute indication, partner the product, hopefully, and, as I said, we partner in China, but we still own rights everywhere else in the world, find the right commercial partner to assist in paying for phase 3, and move forward once we have this data, both acute and chronic indications. Obviously, the acute would come first, start, launch the product initially in the acute setting, and then, as quickly as possible, bring up the chronic indication.
Great. I just want to sort of change gears here in the interest of time, but I do want to touch on your capital and your cash runway, right? It's always a question. Can you just remind us sort of what that cash runway includes in terms of these various studies and the indications that you would pursue within the cash runway?
Yeah, definitely. We had $72 million at the end of the second quarter. That cash, plus the expected milestones coming from our partnership in China, gets us cash into 2027. As I said, data first half of 2026, and we're certainly very comfortable in terms of our cash runway right now. We're very focused on getting these studies done as quickly as we can.
Great. Thanks very much, Barry. We're all out of time, so I'm going to just wrap it up there, but I appreciate you being with us today.
Thank you very much. Appreciate the opportunity.