Development.
Great. Love to. Thank you very much, Emily. Great to be here. I'm Barry Quart, the new CEO of Connect. Joined the company in June of last year, along with David Sakaris as President. The board of directors made a decision to change the direction of Connect, bring in individuals with much greater experience in drug development and working with the investment community. We have spent the last several months really trying to not only redo the management structure of the company, but really change the complete focus as well. Our primary asset is rademikibart, the next-generation IL-4 antibody, so a second-generation Dupixent, essentially, that has demonstrated superior improvement in FEV1 compared to any biologic that we've seen published, with really dramatic improvements in airway function.
What's particularly exciting to us is that this improvement was observed within 24 hours of the first dose, which is important because in the U.S., we have greater than a million patients a year with asthma going to the emergency room with an acute exacerbation, and over 1.3 million COPD patients experiencing acute exacerbations that end up at the emergency room. No biologic has been approved or systematically studied for the treatment of acute exacerbations. In fact, all of the biologics that are approved for asthma or COPD explicitly say in their label to not be used for treating acute symptoms or acute exacerbations. This is a complete white space, which we feel we have the ideal product for this opportunity, something that works extremely fast, extremely well in terms of improvement of the airway.
We are endeavoring to initiate phase 2 trials to demonstrate the benefit of rademikibart in this setting, where there's an opportunity for over $5 billion in forecast for a product like ours with an acute and chronic indication. We have significant cash resources that allow us to fund the phase 2 studies and have a runway into 2027. That's a very quick overview of kind of where we are in our new direction, and love to chat with you further.
Correct. You mentioned rademikibart is almost like a next-generation Dupixent. How does it differ from Dupixent in structure, and how do you think that might lead to the better efficacy that you're seeing in asthma?
Sure. It was designed to have tighter binding. It has 33% more hydrogen bonds to the binding site. It also binds differently than rademikibart. We recently had a poster showing the structure of the antibodies and their binding to the ligand. We know that there are clear differences in structurally how these products bind, and that certainly relates to differences that we see clinically. One of the interesting differences is in the safety profile as well, where Dupixent has this unusual effect of increasing eosinophils and, in fact, producing really a hyper eosinophilia in some patients, resulting in significant adverse events. We do not see any of that. In fact, we lower eosinophils on average. The structural differences clearly relate to differences in the clinic.
Great. How did your data that you had in your phase 2 asthma study kind of inform you on this new strategy to focus just on acute exacerbations from asthma and COPD?
Yeah. One of the things that the company did, which helped us move this program forward, was collect data. The official first data point for FEV1 was collected at one week, and that's much sooner than in other prior asthma trials, where particularly for biologics, which take a while to work, usually the first data points are either two weeks or even four weeks. We had a one-week data point showing highly statistically significant improvement in FEV1, as noted on this slide, where we saw over 300 mL improvement in people with real eosinophilic-driven asthma. The company also provided home spirometers for patients, which allowed us to dig a little deeper. We found that over 70% of the benefit seen at one week was obtained the next morning after that very first dose.
Really, almost immediate benefit was being seen in terms of airway function with the product.
Great. Maybe for those who are a little less familiar with the space, what exactly is an acute exacerbation, and how similar are asthma and COPD exacerbations, and why do you feel like rademikibart could potentially treat both types?
Sure. When we think about asthma and particularly asthma patients being treated with biologic, these are patients that are receiving the usual background standard of care, a bronchodilator. They may be receiving an inhaled steroid and on a day-to-day basis are being maintained. A couple of times, once, twice a year, possibly more, they have an acute exacerbation. This is where they have difficulty breathing. Their breathing is not improved with their usual doses of bronchodilator. They get to the point where the breathing difficulty is so significant, they have to go to the emergency room for more extreme care.
The usual treatment at the emergency room is pretty much the same thing they would have received 30 years ago, which is a steroid and a very high dose of bronchodilator, 20 puffs of beta agonist in order to overcome the beta agonist resistance that's occurring as to why their usual one or two puffs didn't work at home. The situation is relatively similar for COPD, although these patients may have more underlying infections or other stimulants that's producing this exacerbation. The reason that we have high confidence in terms of the opportunity to treat both asthma as well as COPD comes from our global asthma study, which demonstrates very substantial improvement in airway function, reductions, and exacerbations. We were also able to pull out of the population patients that are kind of COPD-like.
These are older patients that their airway function kind of mimics a typical COPD patient. We see very substantial improvement in airway function in those patients. We know mechanistically that Dupixent has demonstrated that this mechanism does work in chronic COPD. We certainly have all the background information to give us a high level of confidence to at least evaluate the drug in COPD patients.
Okay. Great. You mentioned that you're initiating a phase 2 study in this setting. Can you walk us through the intended study design a bit more in detail and also what steps are remaining till you can initiate the trial?
Sure. This is going to be definitely a different kind of program than people are used to in terms of asthma or COPD studies. In fact, all of the studies that have been done with biologics exclude the period of time that we're going to be looking at. To get into a typical COPD study, a patient cannot have had an exacerbation in the last four to six weeks. We're actually taking patients who are actively having an exacerbation. They are showing up with difficulty breathing, or they're contacting their pulmonologist saying that they are having an exacerbation. They would come in for treatment. They're going to get randomized to either active rademikibart or placebo in a blinded fashion. We're going to be following them with a primary endpoint of four weeks. Why four weeks?
Number one is we know during that four-week period, they have a very high likelihood of having another exacerbation. It's a very vulnerable period where upwards of 50% of these patients will have another exacerbation. Why is that important? From a health economic point of view, the hospital does not get paid again if the patient comes back in that four-week period. Their single bundled payment is designed to cover that patient for four weeks. It is a very important period both for the patient and for the payer where they have an incentive to not want that patient to return. We believe we have a very substantial opportunity to reduce these recurrences during that four-week period.
More importantly, with the very fast onset and very substantial improvement in airway function, we hope to have that same benefit in people having an exacerbation where the whole goal is to improve airway function.
Given that up to 50% of patients return have another exacerbation, what would you consider to be a significant decline in that rate of secondary exacerbations?
Yeah. So we've powered the study for a 50% reduction during that period, which we feel would be more than sufficient to demonstrate the value of the product. We feel that there's an opportunity to show an even greater benefit. There was a recently published investigator-initiated trial where they used benralizumab for the same target of reducing these secondary exacerbations in people having an acute exacerbation in both asthma and COPD patients and showed about a 50% reduction in that four weeks. What was interesting is not surprising for a product with a long half-life, it took about three weeks for it to start to work, where we know from our data that we see very, very rapid onset of effects. We think we're being conservative by looking for a 50% reduction.
We hope that we'll see something even more substantial than that, but we're certainly very confident we'll see at least a 50% reduction.
Okay. Why do you think other IL-4, IL-13 receptor antibodies haven't looked into this indication like Dupixent, for example?
Sure. Look, I think that number one, there's a certain interest in focusing on chronic use. That's certainly where the money is because patients are receiving these products month in and month out versus a single dose in the hospital. Obviously, if you're going to target being the first IL-4 to market, you're going to want to go after the biggest market. Makes perfect sense. Now that they're well established and their period of exclusivity is coming to an end in 2031, 2032, they're not about to go back and start to look at new indications for Dupixent. We don't anticipate them taking our lead and trying to go back and expand their label. We also don't know how fast the time of onset is of Dupixent. There's never been any published data looking at less than two weeks.
We do not know if it would even start to work as quickly. For other products, and I think importantly, most, if not all, the products kind of coming behind us, the mantra now is looking at longer and longer half-lives. Let's get something that is every three months or every six months. We know from basic pharmacokinetics that the longer the half-life, the longer it takes to see an onset of effect. It takes four to six half-lives to get to steady state. The likelihood is that the newer products are definitely not going to start working within 24 hours. I do not think that we are likely to see competition from behind. The products in front of us really were focused on the golden goose, which was chronic dosing.
What we found was that to break into this market now is obviously second in next generation IL-4. We need an important advantage, and that advantage is working acutely. What we found in market research was that clinicians really resonated with using a biologic in the acute setting and felt that they would, in most cases, keep the patient on. If they did well acutely, they'd keep the patient on chronically. It is our opportunity to really kind of get those patients on the drug before they ever have a chance to see another product.
Okay. That's really interesting. In terms of pricing, given potentially some of these patients would only get one dose of the treatment, how do you think about potential pricing and market opportunity?
Yeah. Number one, in terms of pricing, what's really important is to have a low cost of goods. We have a very high-yield process to manufacture the product, and that's going to help us with profitability across a spectrum of prices. The other thing is that we have a lot of experience in the management team and working in the hospital market. We understand how that operates. Our plan is to have a separate presentation for the hospital at a lower price point that the hospital is going to find tolerable and beneficial to them. It's important to make sure there's an economic driver as long as in addition to a patient healthcare driver.
We would have a different price point for the hospital and then really match kind of in terms of the outpatient dosing, probably match the Dupixent price or something in that general neighborhood. The economics in the chronic marketplace would be excellent. The economics in the acute market are good, but really we kind of look at it as the driver to build the chronic market by getting those patients first.
Okay. We have a question from online coming in. If you could elaborate a bit more on the unmet needs, so maybe what percentage of patients aren't being helped by current standard of care?
Yeah. As I said, I think that in terms of acute treatment of asthma and COPD, standard of care is the same as it has been for 20-30 years. They come in, they get a steroid, they get bronchodilators, they get sent home. I think everybody felt like, "Okay, that's fine." As we now look more carefully at what happens to these patients, we see that far too many of them end up with another exacerbation, end up coming back. Over 20% come back, 10% get hospitalized after that first exacerbation during that four-week period with another exacerbation. I think that the reality is that there is a clear unmet need in terms of preventing these secondary exacerbations in these patients during this very vulnerable period.
Okay. Makes sense. Maybe with our last few minutes, if you can just discuss the status of your partnership with Simcere in China in terms of the atopic dermatitis and asthma programs there.
Yeah, absolutely. They are well on their way in terms of completing a phase 3 trial in China with atopic dermatitis. It's fully enrolled, and they're continuing to prosecute that study. When they have the data from that study, they would plan on filing the BLA in China for AD. They are enrolling an asthma study as we speak, a phase 3 asthma study. They are very dedicated to moving this program along. They see a very significant market opportunity for an improved IL-4 in China. They've been really excellent partners. When we published our financials in June of last year, we had received over $24 million in payments from Simcere. We'll be putting out our first 10-K next week.
This is also kind of the change in focus of the company to be more US-centric and put out normal filings with 10-K and 10-Qs in the future. You'll see that they have continued to pay us milestones, and we anticipate significant milestones over the next few years.
Great. Maybe to kind of end the conversation, if you could just sum up some of the upcoming catalysts and milestones you're expecting in the remainder of this year and into next year.
Yeah. Very shortly, we should be putting out information on a recent meeting with the FDA on our phase two studies. We anticipate starting these phase two studies, starting to enroll patients in the Q2, and really within the next few months. The great thing about these studies looking at acute exacerbation is that, as I said, it's a one-month endpoint, and we anticipate the ability to have data in the first half of next year. Much faster than the usual COPD or asthma study and much less expensive, which allows us to finance these studies ourselves with the cash we have on hand and continue to have a runway into 2027. It's the update on the FDA meeting, initiation of the trials, and within a year, having data.
Awesome. Great. Thank you very much, Barry, and thanks to everyone who tuned in. We'll conclude the fireside here.
Thank you very much. Take care.