Cue Biopharma (CUE) trial results, September 21, 2026 transcript

Good morning, and thank you for joining us today. Before we begin our formal comments, let me remind you that during today's webcast, we will be making forward-looking statements that represent the company's intentions, expectations, or beliefs concerning future events. These statements represent our views as of the state, are subject to risks and uncertainties, and should not be relied upon as representing our views or of any subsequent date in the future. As a reminder, this call is being recorded, and a replay will be made available on the Investor section of Cue Biopharma's website following the conclusion of the event. With me on the call today are Dr. Shaoli Lin, our President and Chief Executive Officer, and Dr. Dominic Borey, our Chief Medical Officer and Head of R&D.

Dr. Lin will open the call and then hand off to Dr. Borey to walk through the study data. Dr. Lin will then close our prepared remarks and we will take questions.

With that, I will now turn the call over to Shaoli.

Thank you, Agnes, and good morning, everyone. Thank you for joining us. Today, we are reporting results from the Phase II study of Q221 in the Chronic Spontaneous Urticaria, or CSU. We're pleased to share that the study results were positive and that we will be reviewing together those top-line clinical results with you today. The key takeaway is that Q221 met its primary and key secondary endpoints in a manner that reinforces our enthusiasm for the precision-engineered, unique dual mechanism of action of Q221 and its potential to offer clinically meaningful and differentiated benefit in IgE-mediated disease.

Slide three summarizes the salient findings from the study. The study demonstrated robust, durable, and dose-responsive clinical effects. The primary endpoint of complete resolution of hives, or HSS7 equals zero, at week 12 was met, with the treatment effect further increasing past the final dose at week 16 to its peak at week 22. The key secondary endpoint of complete response, or UAS7 equals zero, was statistically significant in the high-dose group further supporting the clinically meaningful impact of Q221. These results were achieved in a context of a favorable safety and tolerability profile.

Of note, for the Q221 high-dose group, both the complete resolution of hives and the overall complete response persisted for 12 weeks or a full quarter and on the order of five half-lives after the last dose. This was not seen for the lower doses or for omelizumab, despite a comparable dose level, highlighting a fundamental clinical difference consistent with the biological design differences between the two drugs, and supporting the concept that Q221 has the potential to be a disease-modifying therapy. This marked difference observed off-drug at week 28 relative to omelizumab provides our first clinical evidence supportive of the Q221-engineered dual mechanism of action that includes not only blocking of the IgE-mediated allergic cascade, like omelizumab, but also supports the clinical potential of down-regulation of new IgE production unique to the design of Q221.

Additional PK and IgE data are of interest, and while not available today, we'll be the subject of further modeling analyses and future presentations at upcoming medical meetings. Based on this demonstrated potential for differentiated clinical efficacy in CSU and the potential to develop a new tool to target disease modification and the concept of functional cure for IgE-mediated diseases, We are more than excited to now plan both a Phase II BIII next study in CSU, as well as a Phase II study for food allergy.

I will now hand the call over to Dominique Bori, our Chief Medical Officer and Head of Research Development. Dominique?

Thank you, Charlie. So let me take a couple of minutes to quickly walk the audience through the science behind Q221. First, reminding ourselves that IgE drives allergic disease by engaging two receptors, the high affinity receptor shown here on the left, through which IgE and the allergen will trigger degranulation and allergic symptoms. And the low affinity receptor, also known as CD23, shown on the right, which is expressed on the surface of B cells and has an important role too, as when bound by IgE, it triggers a natural negative feedback loop that results in reduced IgE synthesis. On slide five, Q221 was designed to block IgE binding to the high affinity receptor, and in doing so, provides potent IgE neutralization or IgE blocking.

Q221 high binding affinity for IgE, shown here on the left, supports a greater potency at preventing IgE-mediated cell degranulation over omelizumab, As shown on the graph on the right. On slide 6, on the flip side, Q221 was also designed to preserve IgE binding to CD23. And this was achieved through selecting binding sites on IgE that are distant from the IgE region that engages CD23, Whereas the binding site on IgE for omalizumab and its analog, RPK904, is the same as shown on the right and overlaps with the C23 binding site and therefore does not allow the drug IgE complexes to bind C23. On slide seven, as the result of the difference in engineering, increasing concentrations of IgE in complex with Q221 can bind to the CD23 receptor, as shown by the orange curve on the right, whereas no binding at all was measured with IgE in complex with omelizumab, as shown by the gray triangles.

On slide eight, the biologic pro-impact of preserved binding to CD23 was demonstrated both at the mRNA and at the protein level, where addition of Q221 resulted in a significant reduction in IgE synthesis shown by the orange bar that was not observed for omelizumab in gray bars, indicating that omalizumab in complex with IgE cannot block new IgE production. On slide nine, it was therefore very exciting to test the clinical impact of these fundamental biological differences in the context of a phase two randomized, double-blind, and placebo-controlled study. A nomadizimab arm was included for comparative efficacy and safety, but no formal statistical testing was planned. The study enrolled participants with moderate to severe chronic spontaneous urticaria, or CSU, inadequately controlled with H1 antihistamines, and patients were randomized to either one of Q221 dose groups at one, two, or four milligrams per kilogram administered subcutaneously or to a malizumab at the registered dose or to placebo.

All patients received subcutaneous injections every four weeks, and the primary endpoint was assessed at week 12 and measured the rate of complete resolution of HIVE, or HSS7 score This endpoint leverages an objective assessment of the number of hives, which is carried out by the physician, and achievement requires all clear skin or no hives. The final dose in the study was administered on week 16 for all groups, and after which patients were monitored off-drug for 20 weeks through week 36. Slide 10 shows the subjects' dispositions for the trial. Two subjects were randomized, but not dosed, one in the four milligrams per kilogram group, and one in the omalizumab group. The dropout rates are in range with expectations for a clinical trial of that duration, further considering the five-month observation period of drugs.

This study was analyzed using a modified intent to treat approach. The two subjects were not those, were not part of that analysis, but all other subjects were included in the modified intent to treat analysis. On slide 11 the baseline characteristics were overall well across groups Disease duration range approximately for four to six years across groups And mean baseline urticaria activity score seven or UAS seven were in the 28 point range indicative of severe disease activity On slide 12, getting to the results, we are excited to report that the study primary endpoint was met. Complete resolution of highs, HSS 7 equals 0 at week 12, was significantly higher than placebo for all dose groups in a dose-responsive manner with a high p-value of less than 0.005 for the high dose group.

On slide 13, the key secondary endpoint of complete response, or UAS 7 equals zero, was also met. And the difference versus placebo was statistically significant for the high-dose group. On slide 14, another way to visualize the depth of response is to measure the change from baseline in UAS 7 score at week 12, which was found to be profound and statistically significant across all those groups. On slide 15, this slide captures the depth of response at week 12 by presenting the percent reduction from baseline in UAS 7 across various mechanisms. Although we note that cross-trial comparisons are for illustrative purposes only and should not be interpreted as direct comparison of efficacy, across various modalities, Q221 seems to come closest to providing full control of disease activity.

On slide 16, if you allow me to shift gears now, I want to focus on additional exciting findings arising after the Week 12 primary endpoints. On the middle graph, across all Q221 dose groups, complete resolution of highs continued to increase beyond week 12 and picked at week 22, which is six weeks after the last injection, in a dose-responsive manner.

More than two-thirds of subjects in the high-dose group responded and achieved complete resolution of highs. Now, if we look at the WIG28 results, this is a time point when patients have been off drugs for 12 weeks. This corresponds to approximately five half-lives after a last dose for both Q221 and omelizumab, given expected half-lives of two to three weeks for these IgG monoclonal antibodies. Let's also note that the formeg per cake dose is, for a 70-kilo patient, the molar equivalent of a 300-milligram zolayer dose.

At that week 28 time point, where 60% of Q221 patients are still experiencing complete resolution of hives, only 24% of patients in the omelizumab group are. And this stark contrast cannot be explained only by pharmacokinetics, as residual circulating drug concentrations are likely extremely low to nil for both groups. Rather, we think that this indicates a fundamental difference in biology and provides clinical data indicating that for the Q221 dose group, there is something different happening, which is more than just hygiene neutralization. Note that a post hoc Fisher's exact test was run and found that the difference between Q221 and omalizumab was statistically significant. On slide 17, to provide further perspective, we are providing here this line graph showing the rate over time of HSS7 for the 4 meg per kg Q221 dose group, shown in orange, versus omelizumab and placebo.

After the initial injections, there is a rapid clinical impact, and we can then clearly see the curve diverging after the last injection, reaching the maximal difference of week 28, as we previously discussed. This graph clearly shows the sustained high rate of complete high revolutions throughout the 12 weeks that follow the last Injection of Q221. After week 28, both curves are converging again, trending towards the placebo response in the absence of further administration of drug beyond the week 16 dose. On slide 18, similar to the recent scene for HSS 7 of 0, a similar pattern of efficacy was seen with the complete response rate, or UAS7 equals zero, which was also sustained for over 12 weeks of drug for the high-dose group.

Again, with the same pattern of marked clinical impact of aromanezumab, and supportive of a fundamental difference in biology that is consistent with a differentiated mechanism of action. On slide 19, building on the prior slides, we can start contrasting the features of IgE-targeted therapies. What we think stands out from the week 12 data is that IgE neutralizer like omalizumab or RPT904, which share the same binding epitopes and therefore the same biology of IgE neutralization, They appear to perform closer to Q221 low doses rather than Q221 high dose. Later time point data has not been made publicly available for RAPT, but again, we are extremely pleased with the different efficacy profiles seen with Q221 over homelizibab at week 28 off drug as it supports, you know, fundamental biological differences which may be directly deriving from Q221 engineering.

On slide 20, from a safety standpoint, Q221 was well tolerated. There was no treatment-related serious adverse event, or SAE, and no adverse events of anaphylaxis. Treatment-related adverse events of special interest was limited to one case of grade 2 injection site reaction. There were two instances of treatment-related adverse events leading to study discontinuation, Namely, one case of worsening urticaria and one incident of insomnia. As expected, there were no deaths in the study. On slide 21, to help place these safety findings in context, and because safety considerations will be part of the benefit-risk analysis when comparing across different mechanism of action, this slide provides a summary of anticipated side effect profiles for different mechanisms Investigated currently in CSU.

We believe that Q221 dual MOA should not introduce specific mechanism-related safety that will be different from sole IgE neutralizer, even in the presence of possibly more potent IgE control, and this will be contrasting with the recognized mechanism-related safety findings of other MOAs. We do recognize that broad interest for the field of allergy And IgE-mediated disease results in additional MOAs currently tested at earlier stages of clinical development. We believe that although still emerging, Q221's potential is already more developed, and we look forward to further characterizing Q221 safety and efficacy profile for IgE-mediated disease. On slide 22, altogether we are extremely excited to have clinical results in hand that indicate the potential to reach a functional cure for IgE-mediated disease.

This did not happen by chance, but may result from the fact that from the very beginning, Q221 was engineered to be different from olizumab, and to not only block the high affinity receptor, but do so while preserving the binding to CD23. The preserved capacity of Q221 IgE complexes to bind CD23 results in reduced IgE synthesis at the mRNA and protein level, something that was not seen with homalizumab.

And here, we now have clinical data strongly supportive of fundamental biological differences between Q221 and homalizumab. We are eager to characterize the PKPD relationship, and we'll be presenting these additional results at an upcoming scientific conference. On slide 23, I won't read this final slide, but it may be helpful to keep it staying up during the Q&A session. And thank you for your attention, and now I will hand it And back to Charlie.

Thank you, Dominique. And thanks to those who have dialed in to be with us today. As you can see, we are very pleased with the potential that Q221 has now demonstrated clinically, and which is consistent with its novel precision-engineered dual mechanism of action. Based on these exciting positive results, we are working towards the initiation of a Phase 2b3 study in CSU, in addition to our planned Phase 2 study in food allergies. I would like to thank the Genesis Life Sciences team for designing and executing a robust phase two trial I would also like to extend our gratitude to all the patients investigators and study staff who participated in this trial and supported the advancement of Q221 for allergic disease It has been a privilege to be at Cue over the past five months and witness all the hard work and progress across our portfolio.

And I want to thank the entire Cue team for their commitment to our mission to identify and advance transformative therapies designed to enable functional cures across immunologic diseases. We could not do what we love to do without the support of our board, investors, and the patients we strive to serve.

With that, I'll open the call for Q&A.

Yeah. Hey, good morning, Maury, and thanks so much for joining us, and thanks for the question. So, yeah, I think we wanted to indicate with the 2B part of the Phase 2B3 that, you know, we're interested in, you know, understanding a little bit more about the PK-IgE and response. And so we're likely, we feel like we have a fantastic dose at this point with monthly dosing that's differentiated. So we'll likely utilize that as an anchor, but nothing's definitive yet. And then we're going to also explore, given the biology that we're seeing, you know, how best to optimize dosing for each indication. And so for CSU, or actually for any indication, for instance, we think that we have something where we can think about fixed dosing.

We think based on the profile that we're seeing, there's a potential to think about things like an induction and a maintenance regimen where we're fundamentally modifying some disease biology in the background. We think about this bathtub analogy and, you know, sort of not just emptying the bathtub from blocking or neutralizing IgE, but also turning off the spigot relative to the formation of new IgE. And so one can imagine if you can continue to turn that off better and better over time, that you might reach a point where the interval of dosing now, instead of induction to achieve that time point, becomes a lower dose and less frequent in terms of a maintenance. So all of these things I think we're going to explore, interrogate the data carefully, and determine what the best, you know, sort of approach is to continuing to collect information about this new tool that we have to help patients with IgE-mediated disease.

And so that's how we're thinking about it for CSU. From a timing perspective, you know, obviously we think we have something important for patients, and we'll move as quickly as we can relative to that. I'd say for food allergy, something completely different. So we think of food allergy as a life-threatening disease. And in the context of thinking about that in that way, you know, we think that this new tool gives us, as Dominique was saying, the potential to approach this from a functional cure perspective, meaning that, you know, we don't want just two-thirds of patients having protection against three peanuts some of the time. And we want to get as close as possible to 100% of people having 100% protection all the time, as close to that as one can imagine getting.

And so we'll approach this sort of new tool, new mechanism, new potential to modify disease in a way that will aggressively pursue that ideal. And we don't think about this from a convenience perspective. You know, I care less in that instance if it's achievable, whether this is dosed every six months, three months, or even weekly, but really about whether or not I can create an entirely different paradigm for, you know, ourselves and our kids and our families who have this life-threatening condition. So I hope that helps, and thank you for your question.

Yeah, the patterns that we've seen across the endpoints have been very similar, which has been, you know, comforting to us from a robustness of the signal that we're seeing. So, you know, and we chose the change from baseline percent to compare with others because, you know, there are some studies that have placebo and some don't and some have active preparators and others don't. And this was the best way to have an internal sort of, you know, given arm to itself comparison within the context of its own study.

Thank you so much, Maury.

Yeah, Mayan, thank you for that. You know, so I think maybe the best place to see that is in the line graph or in the bar chart before that. And I know we're not, you know, sort of synchronized in terms of projecting, so I'll have to ask you, the audience, to go to those slides yourselves. But the bottom line is all of these representations are actually for complete resolution of. So resolution of hives is what we've shown the line graph for.

And so there's no, you know, sort of deepening of response beyond the zero, right? And so the percentage just tells you the percentage of individuals that achieve that complete resolution of, in this case, hives. So we are definitely getting that. And if you look at the, you know, what we think is particularly amazing about the line graph is what I'm looking at currently is you start to see the separation by week eight.

You see the space between the gray line and the orange line, which is Olaire versus the four milligram group. And that area under the curve is really quite striking. If you follow the gray line, which is omelizumab from the last dose, which is week 16, sort of, and follow your eye down to the week 30 time point and extend that line, you can really see how that continues to degrade towards the placebo line. There was maybe one subject that sort of even off drug at that period of time spontaneously improved, which happens in this disease state and certainly happens with small numbers. But you can see how that's degrading towards placebo, which you expect five months off of drug.

What was surprising was the durability of the four milligram group off of drug. Again, as Dominique pointed out, you know, sort of same milligram dose level, therefore same molarity because they're both monoclonal antibodies, same sort of number of half-lives off of drugs, which is like four to five, so the drug itself should really be gone. And yet the effect is still there. And so it tells us that there's something fundamentally different in terms of the biological effect that's happening in those outer weeks between ovulizumab and 221. And for us, given that 221 was engineered specifically with a second mechanism, our assumption at this point is that that's that second mechanism in terms of synthesis of new IgE that's kicking in.

And one can imagine then, for instance, that over time, if you are in fact, you know, effective against, again, turning that spigot off and decreasing free IgE over time, that that may actually cross zero at some juncture and modify the way that you approach the dosing of the disease itself as well. So you can think about mechanistically things like total IgE and receptor engagement on the effector cells or the high affinity receptor, really downregulating those receptors and making those effector cells more quiescent over time. And then you can think about also turning off the synthesis of new IgE and reaching some sort of steady state that fundamentally is disease modifying for these patients. And so that what we going to explore you know at a bare minimum purely clinically all of the scientific hypothesizing aside the bottom line is that we have a remarkable clinical difference here that we think is meaningful for patients and pointing to the fact that this molecule is providing a new tool by which we can approach you know getting more for each of these patient types Thank you.

Yes, thank you for that, Inc. I mean, I think we're very excited to be able to provide specific IgE, PK, you know, PK response data and modeling associated with that and how we're thinking about that relative to each of these disease states, as we said, at a future scientific meeting. And that's not us being coy, to be clear. We have the clinical data at this juncture. We definitely wanted to, you know, make good with our promise to provide data by the end of the third quarter, which is what we are delighted to be able to do at this time. And those data otherwise are just not available at this juncture. But, you know, the way I think about this, and, you know, obviously, it would be a tremendous grand slam to have both of those pieces together today and tell you the other piece of the story.

But the way I think about this, certainly as a clinician and a drug developer, is if I had the bioassay data today, I would be asking myself, yes, but is it clinically relevant? What does it really mean clinically? And that's really ultimately the takeaway. And I think that we're incredibly fortunate to have very clear clinical data, despite the relatively small numbers. I mean, it's a phase two trial. It's not tiny, but it's also not massive. And to get the kind of clarity across endpoints, the kind of statistical significance that we're seeing with these numbers, we're very pleased by, we think it's very clean and very consistent. And it's telling us that there's something different. And we can argue about what that thing might be, but we think the most likely, you know, Occam's razor and all, we think it's most likely the thing that it was engineered to do.

And so, you know, more to come there.

Yeah, and I apologize, Inc. I didn't quite hear the first part of your question, but I'll go ahead and address the second part, which is from a safety perspective, we feel very, very good about the profile. You saw the table with all the zeros all over it. There hasn't been anything. And that subject in the phase one, I think it stated clearly in the supplemental as well, was not deemed to be related to study drug, if I recall correctly.

Sorry, the first part was about ADA or any immunogenicity comments? Yeah, I mean, like PK, like IgE, ADAs are also things that are, these are things that require assays to be run. And, you know, with typical studies, and this is not specific for this particular study, you know, we'll batch them at the end so that they're all run at the same time, which eliminates some variability associated with them and some noise. And so they typically come after the clinical data. And that's what you're seeing here.

Yeah, no, great question. And maybe I'll take the second question first, which is, are we planning to design a head-to-head trial, I think is what you're asking us. And I think that's to be determined. Well, you know, I think we had shared previously that we, based on the phase one data, and what we were seeing relative to, you know, a single IV dose really having a very prolonged effect on suppressing IgE below limit of quantification, that, you know, we were especially interested in this molecule and its potential in food allergy, because it's such a strictly IgE-mediated disease. So it seemed like the perfect place for something like this. We now feel, you know, sort of doubly excited about food allergy as a result of that.

We'd also always stated that, you know, CSU is a more complex disease, has lots of potential mechanistic aspects that are involved in the disease state. And so how much more we would get with better IGE coverage was an unknown, and we would commit to CSU if it had the potential to be differentiated. I think that what we're seeing with these data, we feel, again, very clean, very consistent. Those responses, statistically significant, and the line graph really kind of says it all in terms of the difference between those curves, you know, not just at one point, But across the experience of what these patients are achieving, and then a durability 12 weeks thereafter. So with these data, we're committed to the Phase 2B3 for CSU.

Some of the things, as I sort of shared with Maury earlier as well, is in terms of exactly what those dose levels will be, and whether it will run an active comparator in a head-to-head fashion, I think, is TBD as well.

Yeah, maybe to the first part of your question about the differences or potential differences between the 2 meg per keg and the 4 meg per keg dose. So you're correct that there is a slight difference at week 22, but that may not be where it's the most relevant to look at it. I think we can agree, for example, when we look at site 16, that these two dose levels seem to behave somehow similarly at week 12, but maybe with some slight separation at week 22. What we think is really relevant is to look at week 28, you know, after those, and that's where maybe we start unmasking this second mechanism by the fact that we are at the four-meg per cake dose, you know, really seem to have done something in excess of the two-meg per cake.

And maybe to add on to that, you know, just to reiterate that that isn't an exposure issue, because, again, these are antibodies that are, you know, have a regular monoclonal antibody half-life of two to three weeks, and so we're four to five half-lives out at week 28. We don't expect a lot of drug around, so it's less about an exposure issue in our minds and more likely a biological threshold of effect. And, you know, we obviously are biased, given, again, the design of the molecule, to have one explanation for all of this, which is, you know, we know we were designed to turn off, to have the potential to continue to utilize the natural mechanism to dampen new IgE synthesis.

We think as the total IgE complexes are formed, as they stabilize as a total IgE complex, we have the benefit not only of, you know, sopping up the IgE, preventing it from binding to the high affinity receptor, but also utilizing that complex to, you know, be a high IgE state, if you will, and dampen new IgE production. And it's not, you know, sort of unreasonable to think that that has a threshold associated with it. So, very excited for CSU patients, we think for food allergy patients, and then, frankly, the CSU study being a complex disease and having this kind of effect gives us enthusiasm for other disease states like atopic dermatitis, allergic asthma, et cetera.

So, you know, sort of more to come as we continue to explore the biology and think about our study designs moving forward.