We did not recall. It was not a drug recall. We asked them to ship that drug back. In addition to that, we received drug from the third-party logistics company who handles package labeling, shipping of the product. We also went back to our CDMO and pulled samples from those lots, as well as other lots that were on study and being held from the CDMO from drug substance drug product. Had those all blinded and shipped to an independent third-party lab who ran a comprehensive blinded analysis and found that there was no difference in any of the product from any of the other lots, including that lot, and that there were no issues with the drug in that lot. There was no degranulation of that or a degradation of briquilimab in the drug that was used in the sites. It had not separated from solution, etc.
It led us to the conclusion that there's no problem with the drug substance drug product that was used. In addition to that, when we looked at the clinical data from these patients, they had PK. They had serum concentrations of briquilimab that were similar to the PK concentrations we've seen with these doses in the past. In addition to that, when we looked at their tryptase, we saw tryptase responses that were similar to what we've seen with active drugs. It led us to the conclusion that briquilimab was on board on these patients. It was hitting mast cells, and it was depleting mast cells by looking at the PK or the tryptase data. It brought us to the conclusion that, yes, this is not related to the drug product drug substance.
Got it. What can you explain? Because if I remember correctly, two out of the 10 patients responded, which is a stark contrast from everything else we've seen, where it's usually kind of seven out of 10, six out of 10, seven out of 10 are responders, right?
Right.
What's the latest thinking?
Yes. So you're correct. Two of the patients that were treated in the study had complete responses. 10 of the patients had essentially no response, which was completely anomalous for what we've seen with a 240 dose, where we've seen essentially 100% complete response at the 240 dose. These results were completely anomalous. When we saw these results, we took a couple of actions. One was to redose these patients because we do know that some patients—and we've seen this with Celldex's data as well—that some patients are "late responders." Let's give them more of a chance to respond and see what happens. More than likely, what's happened here is probably multifactorial, but it's probably all related to patient selection. We did have one site that enrolled five of these patients. That in and of itself is really anomalous.
We're looking into that site, both study conduct as well as patient selection. If we look at the remaining five patients across five sites, that's not that anomalous. When we speak with KOLs and we look at our data and we look at Celldex's data, the KOLs will tell you that likely one in four, one in five patients that are currently being treated for CSU don't, in fact, have mast cell-mediated disease. As one KOL told me, he said, "We've been looking for a diagnostic for CSU for decades, and maybe we've found one in briquilimab because if you don't respond, you probably don't have mast cell disease." When we conclude the investigation coming up here in the fourth quarter, as part of that investigation, we will have the redosing data on all of these patients.
All 10 of those patients will have at least three doses. We will be able to look to see if there are any late responders, if they continue to be non-responders. I think, importantly, out of that data set, what we will get that is really important for us—and we can talk more about this when we talk about the phase II—but we are going to get safety data on repeat dosing of 240. That is a really important piece of information. We know that 240 is very active and leads to most patients having a complete response that looks durable for eight weeks. What we have not had is what is the safety, though, if you repeat dose. While these patients may not continue to show or may continue to show no efficacy, the safety data will be very real because we know that they are receiving active drug.
I think to your question about what do we do moving forward to ensure this doesn't happen, some of those we've already put into place. Another course of action we took upon seeing these results is we've enrolled more patients. We've enrolled, and our target is 10-12 new patients across these two cohorts. We prioritize dosing in the cohort so-called nine, which is 240 followed by 180, because that's a really important question we want to answer. You get significant efficacy with 240. Can we maintain that by stepping down to 180 and potentially avoid some of those kit-related adverse events? We took that course of action. In addition to that, we have been much more scrutinizing the inclusion-exclusion criteria. As an example, we're looking to ensure that patients have a documented diagnosis of CSU from a CSU expert physician.
As an example, we had one patient that was referred in for the new patients in cohort nine. This patient came via a referral but did not come with any medical history. We could not verify how long they've had their CSU, how the diagnosis was made. Unfortunately, we declined that patient. We're being much more rigorous in our inclusion-exclusion criteria.
Okay. Got it. As you kind of—and we're also going to get—maybe we'll stay on what to expect by the end of the year. It's also going to be the asthma data. We're expecting the asthma data, whatever you have on the asthma data. Give us a sense because that study for now has been sort of terminated. You're still very interested in asthma in general for future studies, assuming everything gets resumed. What can we expect from that asthma study?
Sure. As you state, that study has been halted and terminated. Unfortunately, we likely made a hasty decision to halt that study. The reason we did that was because when we saw the anomalous results in the Beacon study, we realized that the patients in the asthma study were treated with that same lot of drug. Until we were able to clear that issue up around that lot of drug, we were not clear about what to do with that study. In hindsight, it is unfortunate that we closed the study early because we are keenly interested in those data. Having said that, yes, before the end of the year, we will have data on 12-15 patients from the asthma study.
Okay. How long were they treated for? Did they get sort of, I imagine, just one dose, maybe two doses?
They received a single dose at 180. This is an asthma challenge study in mild asthmatics. They receive an asthma challenge, measure their FEV1, and then they receive a single dose of briquilimab. They come back at six weeks and receive another asthma challenge, measure their tryptase, and take their sputum and measure their FEV1 again, look at LAR, EAR, and LAR on the study. That is the primary endpoint. We revisit that again at 12 weeks. It is a single dose at 180.
Okay. It was a single—yeah. It's two challenges with a single dose.
That's correct.
With baseline and then a six-week challenge.
That's correct. Six weeks is what we're really looking at here. We built in the 12-week. That's part of the normal protocol. Knowing what we know about the biology of the disease and about the half-life of briquilimab, and when we look at briquilimab in other settings like CSU and we look at the tryptase, the 180 dose is probably a six to eight-week dose. Looking at that six-week EAR and LAR will be really important.
Okay. Got it. And so you're looking at the early asthmatic response and the late asthmatic response, right?
That's correct.
Can you give us a little bit more info what that means?
We'll be looking for the effect of this allergen challenge on both the early response and the late asthmatic response. Part of that late is in the recruitment phase in asthma. We'll be looking at FEV1 in both of those.
Got it.
This is a true proof of concept study. It's well understood that mast cells are the conductor in the orchestra in the release phase. They get the party started. They release histamine, prostaglandin, a whole array of things that they release to create the asthmatic response. The question is, if we reduce or eliminate mast cells, can you reduce or eliminate that response of that release phase? I think the interesting thing here will be mast cells are also known to be involved in the recruitment phase. What isn't understood, because no one's ever depleted mast cells before, is if you deplete mast cells, is there another immune cell that is also involved or that will step up in the mast cells' absence or recruitment or not? Those findings could be really interesting as well.
We're as much interested in the biology here as we are in signals around FEV1.
I mean, when the study was sort of terminated early, I mean, this is a study that you have a baseline and you have a six-week challenge, right?
Correct.
You do a baseline without drug on board, right?
Correct.
You do a challenge. And then do you do, when you do an early asthmatic, you do, usually you challenge with the allergen, right? And you give a shot at baseline, right? Or in this case, you don't.
That's correct. We did.
You do. Exactly.
Yes.
They come back six weeks later, and again, you do a challenge at that point.
No shot.
No shot. And then they come back four-10 hours later to look at the late response.
That's absolutely correct, Your Honor.
Okay. Got it. Okay. What about just remind us on Sindhu where you are and what the next steps might even be there?
Sure. We presented data on the final findings at EAACI this summer on the 180 milligram dose level. We saw really nice responses, great complete responses at the 180 milligram. That was a single dose. All of those patients, whether they were at the 40, the 120, or the 180, then had the eligibility to roll over into the OLE study, which is 180 milligrams q8 week. We will have the findings from that study at 180 milligrams q8 week. We'll have at least 12 weeks' worth of data on about 15 patients. We'll have that data available with the other data set available early in Q1 of next year. I am keenly interested to see if we're able to maintain that significant response that we saw with the single dose of 180 or maybe even better that response. Those data will be available in early Q1.
These were using different manufacturing lots. That study.
That's correct.
Right? That study continued. Yeah.
That's absolutely correct. Yes.
Got it. All right. So I mean, it sounds like we're going to get an update. It sounds like from everything you're doing, and I don't want to preempt the update, but is that you're thinking this was a patient selection. This wasn't a drug substance drug product, which I know in some ways it's not maybe it would have been easier in a nice package with a bow tie if it's a drug substance and drug product, but that opens a whole bunch of other concerns. It is good that it's not. It sounds like from what I'm reading between the lines, is that next year you'll go back into a phase II-B in CSU.
That's correct. Our plans are to initiate our phase II-B mid-2026. That's absolutely correct. We believe that based on all the data we've generated to date as well as the data that are coming in early Q1, which include these new, so we'll have all the redosing data on cohorts eight and nine, the new patients we've enrolled. In addition to that, we'll have the OLE study from Beacon, which as a reminder is 180 q8 week. In July, we showed the data from the first 11 patients in that study. At 12 weeks, we already saw a 73% complete response rate with the 180 q8 week. We are very encouraged by that data.
By the time we have the early Q1 data, the end of that OLE study will be approaching 40, so 40, so a sizable cohort of data at the 180 q8 week level. Based on all of that data, we'll be able to select what we know are two efficacious doses to take into our phase 2B.
Okay. And that 40 is the Sindhu, including the OLE?
That's CSU.
That's CSU.
CSU will have approximately 40, somewhere between 35 and 40, depends on when we cut the data. Sindhu will add another 15-ish patients. Then we'll have the new patients also that we enrolled in cohorts eight and nine. We'll have the 10 patients redosed as well as longer follow-up on all of those patients. There will be a large amount of data that will be coming in early Q1.
Okay. Right. Just to make sure, the redosing, right, that was the 10 patients in cohort, exactly eight and nine. The new patients enrolled, that's into the CSU study.
That's correct. That's in Beacon.
Yeah. Yeah.
Specifically, we prioritized enrolling cohort nine. We did not go in numerical order because what we really wanted to see, again, we have a lot of data now generated to know what the efficacy looks like with 240. We will have a lot of safety data, what repeat doses of 240 look like. What we really want to be able to answer is what the efficacy and safety look like if we load with 240, but then back off to a maintenance dose of 180.
Yeah. Got it. The upwards of 35-40, these are going to be the new patients potentially from cohort nine?
Those are from the OLE study in Beacon. Those are all at 180 q8 week. Right. The new patients in cohort nine are probably somewhere in the 8-ish patient range.
Okay. Got it. Okay. So 10 from cohort eight and nine redosed. Cohort nine, about eight patients new. Beacon OLE, that's going to be upwards of 35-40?
Correct.
Those 35-40, that's early next year?
Yes.
The Sindhu, 15 patients ongoing, is also early next year?
That's correct.
Got it. So really, the cohort eight and nine, the redosing, that's also early next year?
We will have the redosing data on those patients available for the conclusion for the investigation. Then we'll have longer-term follow-up on the safety of those patients in early Q1 along with everything else. We'll tie a nice bow around the investigation and then have a very large quantum of data in early Q1.
Yeah. And then the new cohort nine, those eight patients, can you get those by year-end, or is that early next year?
That's early next year.
That's early next year. Yeah. Okay. All right. Terrific, Ron. Thanks so much. Good to see you. We appreciate it. We'll be in touch.
Thank you, Yaron . Always appreciate the opportunity. Great to see you.
You too. Thanks.