Great. Excellent. Thanks, Barry, for joining us. I'm Josh Cesaro. I'm a teammate of Corey Kasimov's Biotech Equity Research Team, and we're happy to have Barry here from Connect Biopharma. Barry, maybe we can start off with, if you could give us a little background, just for those maybe that are less familiar with the story, and just a quick elevator pitch on the company.
Absolutely. Appreciate the opportunity to be here. Thank you. Think of this as going to China to find an extremely interesting and novel antibody and then bringing it back here for further development. That's essentially the Connect story, although in this case, we're not going and acquiring a product from another company in China. It's our own. We're developing a next-generation IL-4 receptor alpha monoclonal antibody designed in our labs outside of Shanghai. It's been extensively evaluated in atopic dermatitis and asthma. As we look at the market opportunity, we found that it was the most differentiated in asthma and potentially COPD as well. It's differentiated from Dupixent in several different ways, but probably the most important and particularly important for our interest in treatment of acute exacerbations is the very rapid onset of effect.
When we think of biologics, we're usually thinking about days to weeks to see a beneficial effect. We see a beneficial effect in terms of airway function within hours of administering retimicavir by subcutaneous administration. We are using that very rapid onset and profound improvement in airway function that we observed in a phase two study. We are using that to potentially treat patients having an acute exacerbation. Patients going into the, there's a million-plus asthma patients a year, about 1.3 million COPD patients a year going to the millions more going to urgent care or doctor's clinics for acute exacerbations. This is an area that really has not been extensively studied with virtually no drug development in this setting. Patients are treated the same way as they were 30 years ago. They get steroids and very high-dose beta agonist to open up the airway.
Most of the patients with asthma are discharged home. What we found pretty shocking was that about 45% of those patients either come back to the or go to another point of care within four weeks of that discharge because we're really not treating the underlying cause of the exacerbation and, in fact, not really even treating that exacerbation very well.
Yeah. Okay. Maybe it'd be helpful if you could give us some background on retimicavir's previous asthma data, the phase 2b.
Yeah. So retimicavir, as I mentioned, has been evaluated in atopic dermatitis where it was demonstrated to be highly effective, dosed either q2 weeks or q4 weeks. In asthma, it has been evaluated in a large chronic asthma study. A 24-week trial showed excellent improvement in airway function, on average around 250 million-300 million improvement. When you look at patients with really clear T2-mediated asthma, we get up to over 400 million improvement in airway function, which is certainly amongst the largest seen with a biologic. That study has led us to the acute studies that we're currently doing. I should probably mention that we have licensed this drug to a large Chinese pharmaceutical company. They are developing it for both atopic dermatitis and asthma in China. They've already filed their NDA for atopic dermatitis. We're hopeful for an approval mid-next year.
They're well on their way in their phase three asthma study.
Got it. You also called it a next-generation IL-4 receptor alpha. What properties make it the next generation?
Yeah. This drug binds very differently to the target. We have a three-dimensional crystal structure showing a very different binding orientation. We hit very different epitopes. That, we believe, is the underlying rationale for some of the clinical differences that we see. As I mentioned, number one is we have demonstrated efficacy q4 weeks. That is something that we basically replicated a study that was done with Dupixent, and they showed a significant loss of benefit when they went from two weeks to four weeks. We have a longer duration of dosing. We have, in asthma patients, a different safety profile. Dupixent has demonstrated a pretty unusual and unique effect of increasing eosinophils. You are already treating patients with high eosinophils to begin with. When you increase the eosinophils, a high propensity of patients goes to excessive levels of eosinophils.
You see upwards of 40% of patients going above 1,500 and over 12% going above 3,000. This has led to hundreds of serious adverse events reported to the FDA FAERS database for excessive eosinophils and the sequelae associated with that. We see a decrease in eosinophils, so a very different profile in terms of the effect on eosinophils with retimicavir versus Dupixent.
Interesting. It is a validated pathway. The interesting approach, initially at least, is this acute focusing on acute care setting. Maybe walk us through what led to that decision to focus there.
The speed of onset of retimicavir is really the basis for moving forward in the acute setting. That is differentiated from Dupixent in terms of airway improvement. The only data that they've published is at two weeks. They've recently changed their commercial marketing information to indicate some patients have symptomatic benefit as early as three days. I think that we can take that as an indicator that they do not have data showing it works within less than 24 hours. That is clearly our most important differentiation versus Dupixent for this acute setting. We see this as a very unique opportunity because it is a complete wide open space with no competition. In fact, the approved drugs, Dupixent, Fasenra, others that are approved for chronic asthma and COPD, all explicitly say in their package insert to not be used for acute treatment.
If we achieve an acute indication, not only would we be the first and only biologic with that indication, the other drugs could not compete because they explicitly are labeled to not be used for acute treatment.
Got it. You mentioned in the beginning that there was like one million and 1.3 million patients. That's kind of like the ultimate size of this opportunity in the acute care setting.
That's really the tip of the iceberg because those are the ones going to the we know that for the million patient asthma patients going to the there's approximately 1.3 million going to urgent care and like 1.3 million going to their doctor's office for acute treatment. The total addressable number is something close to four million patients having acute episodes where they are out seeking medical care.
Does that account for the eosinophil count over 300?
The conventional wisdom in asthma is that about 60% of patients with asthma are T2-mediated. It would be the type of patient that would respond to an IL-4. There is data that patients with T2 underlying mediated asthma are more likely to have exacerbations. We think that in terms of patients coming into the it's probably 65%-70% of patients.
Got it. I've been trying to wrap my head around this. As far as the commercial opportunity, where do you see this drug being dispensed? Is it inside the ED? Is it like quick follow-up, leave it? As you're leaving the ED, you grab your shot and you go. How does that work?
Yeah. I think certainly initially, our target is for, and based on the clinical work that we're doing, is for acute treatment in the ED and urgent care patients going in with an acute exacerbation. That by itself is a several hundred million dollar opportunity based on market research. What the market research also indicated is that clinicians had a very strong opinion that if a patient received the drug acutely and did well, they would want to keep the patient on that same drug. We see that the acute treatment is really a gateway to significant chronic use. Ultimately, the goal would be to have both an acute indication as well as the standard chronic indication.
Have the drug used acutely, essentially getting to that patient first before they get on to any other biologic, and then transitioning that patient ultimately to chronic administration. That brings the commercial forecast into the multiple billions.
Got it. Got it. Okay. That's helpful. Maybe we could get a quick, like the latest on the CBP-201 stat trials and how they're going and maybe.
Yeah. We have two studies that have been initiated, one in acute asthma exacerbations, one in acute COPD exacerbations. Each study is 160 patients that we're targeting. These are global trials with around 50 sites, half of them in the U.S., half outside the U.S. We have more than half of the sites up and running, and we have several countries that are just coming online right now. We are targeting having data in the first half of next year, probably be towards the latter part of the first half. We are still very focused on delivering the data in the first half of next year. We have cash and runway into 2027. It is perfect timing to get what we think is going to be transformational data.
Maybe you can remind us of the trial design and the primary endpoint, which is interesting.
Yeah. The study is somewhat based on a recently published AbRA study, which gives us very contemporary information on what to expect in terms of the control group failure rate. We have a treatment failure endpoint. That means patient coming into the ED receives standard of care, then they are randomized to either retimicavir or placebo. They're followed for 28 days. In that 28-day period, we're anticipating about 45% of the control group to come back to the ED or to another point of care for further treatment. That acute treatment is not holding them for very long. They're either coming back because they're continuing to get worse, or they may get better for a week or two and then have a second exacerbation. The goal for that four weeks is to count time to treatment failure.
As I said, we're expecting the control arm to be somewhere around 45%, and we've powered for a 50% reduction in that rate. Both studies are essentially the same design. One is just asthma patients, one COPD.
I was listening to a previous transcript of yours earlier in the year, and you sounded very confident on the powering. How do you feel today?
Again, because we have very contemporary data from the AbRA study, and that was consistent with what we had found independently looking at both publications in terms of the return rate to and doing an investigation in a very large healthcare database in terms of claims. We had a fairly good target in terms of what we expect for the control arm, and then the AbRA study kind of just nailed it. Based on all of that data, we feel very confident that we will see something on the order of a 45% treatment failure rate in control. In the AbRA study, which they used Benralizumab as the biologic to see if it could benefit patients having acute exacerbation, Benra did not start working until three weeks and then resulted in about a 50% reduction in exacerbations at four weeks.
With a drug where we start working within hours, we would certainly anticipate seeing at least as good as what was seen with Benra. We anticipate actually much better.
Yeah. Do you see the COPD studies being riskier than the asthma study?
You know, the COPD study has certain attributes that are, I won't say riskier, but certainly very different in terms of those patients have a lot more underlying disease, more remodeling, the anticipated improvement in airway function generally with an IL-4, not as large as what you see in asthma patients. We've looked at our database with the prior chronic asthma study, and we did find asthma, I would just say COPD-like patients later onset and kind of their overall characteristics much more COPD-like. We saw very large improvement in airway function in those patients. We certainly, based on the mechanism, based on our own data, anticipate seeing a very good response in those patients. It brings a certain level of difference based on the underlying disease.
Has the interim passed yet for those studies?
Interim analysis has not been achieved yet.
Okay. Got it.
That's halfway through the enrollment.
Nice. Got it. Looking ahead, if both CBP-201 trials were to be successful in FORCE F26, what would be the next steps from that point?
Yeah. Once we have the data from the phase two studies, we previously had a discussion with FDA before we initiated trials. They're very interested in seeing the results of the studies and to work together to agree upon a phase three plan in terms of what the endpoint and size of the studies would be. It would be as soon as we have top-line results, setting up a type C meeting and maybe a B meeting in the phase two of a new indication and getting into as quickly as we can and getting agreement on a phase three pathway. We're hopeful phase three for the acute setting could start as early as late next year.
Would you be able to use the China trial for chronic? How would that work?
Excellent point. Because patients are treated in China under the GINA guidelines like they are here, we would anticipate that the phase three study that Simcere is conducting would qualify as a second phase three trial. For chronic, we would just need to do one additional trial. That is the same for atopic dermatitis as well. They are completing a large AD trial, and we think that would certainly be a very supportive second phase three trial in AD. We are not interested in AD. It is very crowded, and we think we have a much more interesting opportunity in respiratory. Certainly, ultimately, we anticipate that a much larger company will own the product for commercialization. If they want to bolt on an AD indication, it would be relatively inexpensive.
Yeah. Got it. Just last 20 seconds here, key value drivers for the next 12, 18 months, obviously the readout coming up.
Yeah. First quarter, we're anticipating data from an IV study that we're conducting where we hope to shorten the duration of time to onset from hours to hopefully minutes and some pharmacology data really nailing why we show significant differences in terms of safety profile and efficacy versus other drugs. Before the end of first half, the phase two data.
Perfect. Great. Thank you, Barry.
Thank you very much.