Conference Transcript - CNTB 2026-05-19

Brandon Folks, Analyst — HC Wainwright & Co.

good morning everyone my name is brandon folks i'm an equity research analyst here at hc wainwright next up we have a fireside chat with connect biopharma and joining joining me from connect is barry court to see you barry thanks very much my pleasure as always all right um so barry you know i'm just going to dive in because there's a lot to get through it's been a busy uh 2026 so far and a lot to come as well yep so maybe just you know i think one of the very consequential pieces of the data this year was the right of micbot mechanism of action data with it sort of published in january um can you just talk about what to make about mechanism of action what differentiates it and you know how do you think this drives for potential success in acute asthma at PD, but also potentially, you know, reducing ER admissions? Certainly. Yeah, thank you. Great

Barry Court, CEO

question. So, you know, one of the things that's been really exciting about the development of Rad and Micobard 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. So the same general category is 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. And so 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. and 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 but they don't all disappear within 24 hours but you do see a nice modest reduction which we think is beneficial in these t2 patients who have high eosinophils. And it certainly gives a clinician the opportunity to not be worried about using the drug in people who come in with high eosinophils. So right now, clinicians are highly unlikely to start to pick in a patient that has a thousand eosinophils. But they certainly shouldn't have that same concern about initiating radamicabart down the road once it's commercialized. So 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 effects. So in less than 24 hours, very significant improvement in airway function, FEV1, which at one week was improved 250 mil, which is a large change. Most of that was actually observed in Holmes barometry within less than 24 hours. And so we wanted to understand what's that mechanism, because 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. And what we found is, is that radamicavart has a very unique effect of producing, directly producing bronchodilation in lung slices, where we don't see that same effect with Dupixin. Now, we are going to look at other agents just to get a broader picture, but our initial work that was set up at a lab in the U.S. showed a very clear difference in the effects of radamicabart on basically resensitizing the airway to a beta agonist. So 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, and that shifts the dose response curve. Redimegabart shifts it back towards normal, where dupilumab has zero effect on that dose response curve. So a very clear difference in bronchodilation effect, and we think that has a great deal to do with this very rapid onset of airway improvement.

Brandon Folks, Analyst — HC Wainwright & Co.

fantastic and then you know you also released iv data earlier this year which looked to be very supportive of 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 um coming

Barry Court, CEO

out of that i wish i could say um yes but um that uh we put the data out it was still um the study was just still being cleaned up and we actually didn't have data from the very last patient had made it out to 43 days. And so that database is now being cleaned up and locked. So 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. But 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. And so 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 of the blood. And sure enough, we clearly did see that with, you know, fairly dramatic improvements

Brandon Folks, Analyst — HC Wainwright & Co.

in airway function, you know, within minutes to hours. Okay. And I do want to just delve a little bit deeper into that IV data. Sure. Right. And I think it's going to be no surprise, the question I'll ask next, but, you know, I want to 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 truly astounding right it was really good um but then the flip side is you know relative to asthma obviously um you know i think given how well performed in copd people would have expected sort of the asthma population to maybe perform a little bit better so can you just help us especially

Barry Court, CEO

that early onset yeah no look um 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 um and you know concomitant medications um these are obviously all different patients um and um you know we set the entry criteria for patients to have at least 200 eosinophil. So relatively low in the spectrum of T2 patients. We know that these drugs, certainly our drug works down to 150. And so we wanted to make sure we were above that. And so we used 200, but it turned out almost all the patients were between 200 and 250. And so we do need to take a look at the, you know, at the results and how it matches to their baseline characteristics. But what I can say is, is that, you know, if you take a step back, the, the asthma data is, you know, pretty much exactly as what we would have predicted to see right it took 18 hours to see it to 300 you know mil improvement with sub-q here we got it within four hours um so you know beautiful outcome sped up the onset copd that result is was outstanding uh no question and we will certainly delve into those patients and right to 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. So 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 and so had greater capacity for improvement.

Brandon Folks, Analyst — HC Wainwright & Co.

Great. And then, you know, sort of looking at the other side of those curves, right, the responses also seem to be pretty durable, right? So if I look at the day 29, how do you think about the validation? It's going to be sort of two parts in here, right? So how do you think about those curves when we look at, you know, sea breeze first and foremost, right? I think about hospital readmissions for those patients. And then secondly, what about the read throughs to potential once monthly chronic dosing as

Barry Court, CEO

Yeah, no, I think that's a really excellent point. So, you know, we, again, to look at the kind of full picture, we have data from atopic dermatitis where patients were treated with Q2 weeks and q4 weeks and the q4 week data are exactly the same works better the drug works extremely well q4 weeks in ad in the prior asthma study we do have kind of off-grid 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. So everything that we have up to this IV study would give us fairly high confidence that the drug should work for a month. Now, all those studies are with subcutaneous administration. that actually improves the duration because there is a basically six-day release period. So it's kind of giving it like a sustained release product where you have a T-Max at day six, and we clearly see month duration at least. In the IV study, I can tell you that the durability is very clear beyond a month. um and so given the fact that with iv there is no distribution delivery you know delay it's all you know all is administered within two minutes and then it starts to decay um but it's got a long long enough half-life where clearly a month looks like it should be extremely practical even for the iv presentation um and ultimately um you know it's important read through for Seabreeze, which is a 28-day endpoint, with sub-Q. So I think everything we have says no problem. We should not start to see people having a treatment failure day 27. And so that all holds together. But looking into the future, if we use IV for acute treatment, that patient's going to be covered for the next four weeks and 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

Brandon Folks, Analyst — HC Wainwright & Co.

have to wait all four weeks before moving to subcube i do want excuse me i want to come back to seabreeze but see because you touched on it i want to um ask that question right so look in a in a perfect world you get the iv approved for acute the sub-q for chronic how does a company manage that patient workflow and you've done a lot of good survey data that patients would like to keep the conditions would like conditions would like to keep the patients on the same therapy but 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 IV rytomecobot, and that the ER doc sort of gets that patient the chronic rytomecobot presentation?

Barry Court, CEO

Yeah, look, another excellent question. 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 is 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 um you know and obviously through commercialization um you know 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 um but 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 want to keep them on the same drug why would you want to switch was basically their response to us um and so 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

Brandon Folks, Analyst — HC Wainwright & Co.

somebody with much deeper pockets sure um now i do want to come back to sea breeze because that is you know i think arguably may is getting close to mid of middle of the year right and i think yeah we've got that readout coming from in 2026 but firstly maybe what have you learned or what do you read from ivy data through to the upcoming sea breeze um you know and then i guess yeah let's

Barry Court, CEO

just start there and then we can well i think that we already covered it really the only thing that we can take from the IV data. Well, there's a couple of 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 in the COPD patients, particularly where you saw hundreds of mill improvement in a matter of minutes, that's clearly not an anti-inflammatory effect. That's a direct bronchodilator effect. So the drug has that mechanism that's consistent with the preclinical data. All of that bodes well for a positive outcome. But 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 and 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, getting prednisone, prednisolone IV, in those patients, how much more can we improve? And so 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 uh and so if if the drugs that they're already getting are going to get them close then the magnitude of the effect may be

Brandon Folks, Analyst — HC Wainwright & Co.

smaller but still should be significant okay um and let's assume seabreeze reads out as expected what are the next development steps from connect with regard to the writer make about program as

Barry Court, CEO

Yeah, so, 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 agencies' agreement on the design of the Phase III program for acute indication. We've already had that meeting in the phase two meeting for chronic asthma. We know what they're looking for, agreement on the trial designs. The only factor there that we'll end up discussing with them is maybe getting a phase three chronic asthma study from China from our partners, Sincere, sometime early next year. And 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. But aside from that, we would meet with FDA, get agreement on the phase three endpoint for acute duration of the study, size that we need, a sample size we need 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, but we'll get that information from the

Brandon Folks, Analyst — HC Wainwright & Co.

agency as well. Fantastic. And maybe just coming back to CBREs, right, any sort of any endpoints you think are important in the greater landscape and the development decisions? Obviously, the primary endpoint is important, so the hospital readmissions are important but 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

Barry Court, CEO

of sort of the go-forward decisions well I think symptomatic improvement is going to be valuable I don't know that it's going to drive decisions go no go obviously you know we'd be very focused on FEV1 in the studies because that's an accepted regulatory endpoint. That's what was used for approval of Otavari and COPD patients. There's a long history of FDA looking at FEV1 as a critically important endpoint. So that's going to 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? So we certainly, you know, the data that's been published is 100 is enough, but we'll, you know, obviously make sure that we look very carefully at the symptomatic improvement. And then 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

Brandon Folks, Analyst — HC Wainwright & Co.

shorter duration along with they don't come back fantastic um we're almost out of time so i just want to pause and see if there's any questions in the room okay if not then um you know i just want to move you to mid mid to late april i think you know you announced the positive interim review from the Independent Data Monitoring Committee on Seabreeze. Beyond the sort of continuous planned recommendation, did the committee's review have any insight into sort of safety efficacy trends? Did you have any new insights? Well, so definitely no issues with safety.

Barry Court, CEO

They monitor safety actually much more frequently than this specific interim analysis, and they have no concerns about safety. um there was 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 check box do you need to increase the sample size could you decrease the sample size um and or you know recommend no change and so they did not recommend a change um which obviously was very positive because we didn't want to 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. But, you know, all good. And so, you know, from this point, it's just a question of completing the studies. Fantastic. Barry, we're all out of town, but I appreciate you joining me today. Well, thank you. It's always a pleasure. Great to see you.