Good morning, everyone. My name is Brandon Folkes. I'm an equity research analyst here at H.C. Wainwright. Next up, we have a fireside chat with Connect Biopharma. Joining me from Connect is Barry Quart, CEO. Barry, thanks very much for joining me.
My pleasure, as always.
All right. Barry Quart, you know, I'm just gonna dive in because there's a lot to get through. It's been a busy 2026 so far, and there's a lot to come as well.
Yep.
Maybe just, you know, I think one of the very consequential pieces of data this year was the rademikibart mechanism of action data that sort of published in January. Can you just talk about rademikibart's mechanism of action, what differentiates it, and, you know, how do you think this drives for potential success in acute asthma and COPD, but also potentially, you know, reducing ER admissions?
Certainly, yeah. Thank you. Great question. You know, one of the things that's been really exciting about the development of rademikibart is we have the opportunity of looking at the clinical profile and then using that to ask questions about the biology, where normally you're trying to learn everything about the biology before you get into the clinic. We've seen such a unique clinical profile with the product versus what's anticipated for the mechanism, which is it's an IL-4 receptor alpha monoclonal antibody. The same general category as DUPIXENT, but has very different profile. For example, it lowers eosinophils, while DUPIXENT in asthma patients is well described to increase eosinophils, with that not being just a laboratory abnormality. There are hundreds and hundreds of serious adverse events reported to FDA from that increase in asthma patients.
We delved into what could be the underlying reason for that difference, and we believe that it all stems from a very different binding profile hitting a different epitope. With that, we're seeing much greater internalization of the drug receptor complex, and that ultimately results in a faster turnover of eosinophils, hence the decrease in eosinophils. It's not the kind of decrease that you see with an IL-5. They don't all disappear within 24 hours. You do see a nice modest reduction, which we think is beneficial in these T-2 patients who have high eosinophils. It certainly gives a clinician the opportunity to not be worried about using the drug in people who come in with high eosinophils. Right now, clinicians are highly unlikely to start DUPIXENT in a patient that has a 1,000 eosinophils.
But they certainly shouldn't have that same concern about initiating rademikibart down the road once it's commercialized. That was one important area trying to understand this very clear difference in the clinic. The other area that we focused on is from the previous chronic asthma study. We saw very rapid onset of effect. In less than 24 hours, very significant improvement in airway function, FEV1, which at 1 week was improved 250 mil, which is a large change. Most of that was actually observed in home spirometry within less than 24 hours. We wanted to understand what's that mechanism, 'cause that's an unusual effect from a biologic that theoretically is reducing inflammation. You don't normally expect to see that with simply changing inflammation.
What we found is that rademikibart has a very unique effect of directly producing bronchodilation in lung slices, where we don't see that same effect with DUPIXENT. We are gonna look at other agents just to get a broader picture. Our initial, you know, work that was set up at a lab in the U.S. showed a very clear difference in the effects of rademikibart on basically resensitizing the airway to a beta-agonist. One thing that's very well known is that IL-13 and IL-4 shift the dose response curve for beta-agonists, making them less effective, which kind of fits with the clinical presentation where you have a patient that goes and uses their rescue inhaler when they start to feel an exacerbation, and it doesn't work.
We now have a pretty clear understanding it's not working because they have probably excessive IL-13. That shifts the dose response curve. Rademikibart shifts it back towards normal, where dupilumab has zero effect on that dose response curve. A very clear difference in bronchodilation effect, and we think that's, you know, has a great deal to do with this very rapid onset of airway improvement.
Fantastic. You know, you also released IV data earlier this year, which, you know, looked to be very supportive of the mechanism of action and a lot of those things that you talk about. You know, as you had time to go through that IV data, have you learned anything new, anything additional, coming out of that?
I wish I could say yes, but that we put the data out. The study was just still being cleaned up, and We actually didn't have data from the very last patient hadn't made it out to 43 days. That database is now being cleaned up and locked. We have not had the opportunity yet to really delve into it and understand, you know, which patients did extremely well. Some patients had, you know, no benefit, which is exactly what we see with the sub-Q. You know, just to highlight the genesis of the IV experiment was that the onset of effect with the subcutaneous administration mirrored the time it takes for the drug to get out of the subcutaneous space.
If there was a direct relationship between drug in the blood and airway improvement, we should be able to see that with an IV dose where you're getting drug directly into the blood. Sure enough, we clearly did see that with, you know, fairly dramatic improvements in airway function, you know, within minutes to hours.
Okay. I do want to just delve a little bit deeper into that IV data.
Sure.
Right? I think it's gonna be no surprise the question I'll ask next. you know, I wanna just how do you view that early asthma data versus COPD, especially on the FEV1, right? That asthma response in the first 90 minutes you talked about sort of individual patients, right? Compared to the COPD where, you know, the COPD response was, you know, truly astounding, right? It was really good. The flip side is it, you know, relative to asthma obviously, you know, I think given how well it performed in COPD, people would've expected sort of the asthma population to maybe perform a little bit better. Can you just help us, especially that early onset?
Yeah, no, look, you know, certainly a question that we will spend a lot more time on once we have unblinded the data and can really drill into baseline characteristics, and you know, concomitant medications. These are obviously all different patients. And, you know, we set the entry criteria for patients to have at least 200 eosinophils. Relatively low in the spectrum of Type 2 patients. We know that these drugs, certainly our drug works down to 150. We wanted to make sure we were above that. We used 200, but it turned out almost all the patients were between 200 and 250.
We do need to take a look at the, you know, at the results and how it matches to their baseline characteristics. What I can say is that, you know, if you take a step back, the asthma data is, you know, pretty much exactly is what we would have predicted to see, right? It took 18 hours to see a 200, 300, you know, ml improvement with sub-Q. Here we got it within four hours. You know, beautiful outcome, sped up the onset. COPD, that result was outstanding. No question, we will certainly delve into those patients and try to understand, you know, where we might be able to hopefully select that kind of patient out for the future, and make sure we concentrate them in the study.
It may also be that those patients just had greater capacity for improvement. One of the things we'll look at which hasn't been done is, you know, the percent predicted FEV1 in these patients, how much we improved it, and the people coming in with COPD, I'm fairly confident probably came in at a lower level. Had greater capacity for improvement.
Great. you know, sort of looking at the other side of those curves, right? The responses of course seem to be pretty durable, right?
Correct.
If I look out at day 29, how do you think about the validation? It's gonna be sort of two parts in here, right? How do you think about those curves when we look at, you know, SEABREEZE first and foremost, right? I think about hospital readmissions for those patients. Secondly, what about the read-throughs to potential once-monthly chronic dosing as well?
I think that's a really excellent point. You know, again, to look at the kind of full picture, we have data from atopic dermatitis where patients were treated with Q 2 weeks and Q four weeks, and the Q four-week data are exactly the same. The drug works extremely well Q four weeks in AD. In the prior asthma study, we do have kind of off-grade data which shows that the drug clearly works for longer than four weeks. Beyond four weeks, we started to see patients start to have exacerbations, but very clean in that first four to six weeks after dosing. Everything that we have up to this IV study would give us fairly high confidence that the drug should work for a month. All those studies are with subcutaneous administration.
That actually improves the duration because there's a basically six-day release period. It's kind of giving it like a sustained release product where you have a Tmax at day six. We clearly see months duration at least. In the IV study, I can tell you that the durability is very clear beyond a month. Given the fact that with IV there is no distribution delivery delay, it's all, you know, all is administered within two minutes, and then it starts to decay. It's got a long enough half-life where clearly a month looks like it should be extremely practical, even for the IV presentation. Ultimately, you know, it's important read through for SEABREEZE, which is a 28-day endpoint with sub-Q. I think everything we have says no problem.
We should not start to see people having, you know, a treatment failure at day 27. That all holds together. Looking into the future, if we use IV for acute treatment, you know, that patient's gonna be covered for the next four weeks. The goal would be obviously to convert them to chronic administration, hopefully two weeks, three weeks down the road, and not, you know, not necessarily have to wait all four weeks before moving to sub-Q.
I do want excuse me. I wanna come back to SEABREEZE, but see, because you've touched on it, I wanna ask that question, right? Look, in a perfect world, you get the IV approved for acute, the sub-Q for chronic. How does a company manage that patient workflow? You've done a lot of good survey data.
The clinicians.
The clinicians would like to keep the patients on the same therapy. Given the differential in terms of setting where those two patients may present, how do you ensure continuity of care that you go into the ER, you get an IV rademikibart, and that the ER doc sort of, you know, gets that patient the chronic, rademikibart presentation?
Clearly this is a situation where you need an organization that's commercializing the drug, that has both hospital sales force as well as outpatient, that focuses on pulmonology, allergists and pulmonologists. The patient's going to leave with discharge documents, which is going to show the fact that they received that biologic. Hopefully you can get that patient to go see their allergist or their pulmonologist after discharge. Obviously through commercialization, make sure that there's that pull-through. It's not something that's going to be automatic. I think that we are all aware of that difference in prescriber.
I think that the feedback we got was that, "Hey, if I saw a patient who did well and received the drug acutely, I would definitely wanna keep them on the same drug. Why would you wanna switch?" Was basically their response to us. I think that the opportunity is clearly there for that pull-through, but it will take, you know, a certain amount of commercial horsepower, which is why ultimately we think that the drug should be commercialized by somebody with much deeper pockets.
Sure. Now I do wanna come back to SEABREEZE because that is, you know, I think arguably May is getting close to middle of the year, right?
Yes.
I think, you know, we've got that readout coming mid-2026. Firstly, maybe what have you learned or what do you read from the IV data through to the upcoming SEABREEZE? You know, then I guess, let's just start there.
Well, I think that we already covered it.
Yeah.
Really, the only thing that we can take from the IV data. Well, there's two things. Number one is clearly the drug works for a month, even when it's administered IV, which has got the shortest durability. The other thing that certainly the IV study does is it reconfirms this unique mechanism of almost direct bronchodilation, you know, in the COPD patients, particularly where you saw hundreds of mL improvement in a matter of minutes. That's clearly not an anti-inflammatory effect. That's a direct bronchodilator effect. The drug has that mechanism that's consistent with the preclinical data. All of that bodes well for a positive outcome. Beyond that, you know, we have to appreciate that the patients in SEABREEZE are very different than every other patient we've treated, right?
We've treated mostly stable patients with asthma or COPD in the IV study. They responded extremely well, large improvements in FEV1, because they had the capacity to continue to improve. What we don't know about patients who are getting massive doses of bronchodilator, are getting prednisone, prednisolone IV, in those patients, how much more can we improve? I won't be surprised if we don't see the same magnitude of improvement. Obviously, we expect to see improvement, but it may be of lower magnitude, just because they don't have the capacity. You can't go up, you know, beyond 100% predicted FEV1. If the drugs that they're already getting are gonna get them close, then the magnitude of the effect may be smaller.
Fantastic
Still should be significant.
Okay. Let's assume SEABREEZE reads out as expected. What are the next development steps from Connect with regard to the rademikibart program as a whole?
You know, once we have the SEABREEZE data, we would immediately put together a background document for an FDA meeting, try to get a meeting as quickly as we can, because we need agency's agreement on the design of the phase III program for acute indication. We've already had that meeting in the phase II meeting for chronic asthma. We know what they're looking for, we've agreement on the trial designs. The only factor there that we'll end up discussing with them is the beginning of phase III chronic asthma study from China, from our partner, Simcere, sometime early next year. Assuming that looks as good as we expect, we'd certainly like to get the FDA to accept that as one of two chronic studies.
Aside from that, we would, you know, meet with FDA, get agreement on the phase III endpoint for acute, duration of study, you know, size that we need, a sample size we need, you know, to meet their safety concerns if there are any. So far, the drug's been remarkably well-tolerated. We have over 1,500 patients that have completed clinical trials with no issues, so I don't think we have to do a big study. And we'll get that information from the agency as well.
Fantastic. Maybe just coming back to SEABREEZE, right? Any sort of, any endpoints you think are important in the greater landscape and the development decisions? Obviously, the primary endpoint's important, the hospital readmissions are important. Do you think there's any, you know, maybe it's secondary or exploratory endpoints in that study that are inherently extremely important in terms of sort of the go forward decisions?
Well, I think symptomatic improvement's gonna be valuable. I don't know that it's gonna drive decisions go, no-go. Obviously, you know, we'd be very focused on FEV1 in the studies because that's a accepted regulatory endpoint. That's what was used for approval of OHTUVAYRE in COPD patients. There's a long history of FDA looking at FEV1 as a critically important endpoint. That's gonna be a significant focus for us. Symptomatic improvement along with that because people always ask, "Well, you increased FEV1 by 150 mil. Is that enough?" We certainly, you know, the data that's been published is 100 is enough. We'll, you know, obviously make sure that we look very carefully at the symptomatic improvement.
The stuff that you already mentioned, you know, for patients that go from the ER to a hospital bed, how long do they stay? Right. The hope is, number one is they, you know, it's a shorter duration along with they don't come back.
Fantastic. We're almost out of time, I just wanna pause and see if there's any questions in the room. Okay. If not, you know, I just wanna move to mid to late April, I think, you know, you announced the positive interim review from the independent data monitoring committee on SEABREEZE. You know, beyond the sort of continuous plan recommendation, did the committee's review have any insight into sort of safety efficacy trends? Did you know, any new insights that you mentioned?
Definitely no issues with safety. They monitor safety actually much more frequently than this specific interim analysis. They had no concerns about safety. You know, this is a situation where there's really no dialogue between the company and the DMC after they get the unblinded data. They have a checkbox. Do you need to increase the sample size? Could you decrease the sample size? Or, you know, recommend no change. They did not recommend a change, which obviously was very positive because we didn't wanna have to increase the sample size. Would have been great if they said, you know, you can decrease it by 20 or 30 patients. We'd be pretty close to done. You know, all good.
You know, from this point, it's just a question of completing the studies.
Fantastic. Barry, we are out of time, I appreciate you joining me today.
Well, thank you.
Thank you.
It was a pleasure. Great to see you.