Cue Biopharma at Cantor Conference: Strategic Focus on T-Cell Modulation

On Friday, 05 September 2025, Cue Biopharma (NASDAQ:CUE) participated in the Cantor Global Healthcare Conference 2025, presenting a strategic overview that highlighted both its innovative advancements and the challenges ahead. The company is steering its focus towards T-cell modulation, with promising developments in its pipeline. While financial stability through partnerships is anticipated, regulatory processes remain a critical hurdle.

Key Takeaways

• Cue Biopharma is advancing its T-cell engaging platform, with CUE-401 targeting autoimmune diseases and CUE-501 in partnership with Boehringer Ingelheim.
• The company ended the last quarter with $28 million in cash and expects strategic partnerships and milestone payments to bolster its financial standing.
• Regulatory interactions are crucial, with positive feedback from a pre-meeting with the FDA for CUE-401.
• CUE-101 has shown significant survival benefits in oncology trials, both as a monotherapy and in combination with Keytruda.
• The anticipated IND filing for CUE-401 is set for June 2026, with atopic dermatitis as the initial indication.

Financial Results

• Cash Position: Cue Biopharma concluded the last quarter with $28 million in cash.
• Annual Burn Rate: The company reports an annual burn rate of approximately $25 to $28 million.
• Funding Outlook: Anticipated strategic partnerships in oncology and milestone payments from the Boehringer Ingelheim collaboration are expected to provide additional capital.

Operational Updates

• CUE-401 Mechanism: The drug is designed to induce regulatory T cells (Tregs) from T effector cells, utilizing TGF-β binding signaling along with IL-2.
• Preclinical Success: In graft-versus-host models, CUE-401 showed significant survival benefits, with 50-60% of treated animals surviving at day 100 compared to 0% in the control group.
• Regulatory Progress: The company received positive feedback from a pre-meeting with the FDA, paving the way for an IND filing in June 2026.
• CUE-501 Partnership: This molecule, partnered with Boehringer Ingelheim, aims to enhance cell killing without adverse side effects, with two preclinical milestones expected in the next 12 to 18 months.

Oncology Program Updates

• CUE-101 Monotherapy: Demonstrated a median survival enhancement to almost 21 months in head and neck cancer.
• Combination with Keytruda: Increased overall response rate from 20% to 50% in frontline settings.
• Frontline Setting: Achieved a median survival of approximately 32 months, with 88% survival at the 12-month mark.

Future Outlook

Cue Biopharma is poised for growth with its innovative pipeline and strategic partnerships. The company is navigating regulatory pathways with optimism, aiming for significant advancements in autoimmune and oncology treatments.

For a more detailed account, please refer to the full transcript below.

Full transcript - Cantor Global Healthcare Conference 2025:

Prakhara Gurwal, Biotech Analyst, Cantor: All right. Hello, everyone. Welcome to day three of the Cantor Global Healthcare Conference. My name is Prakhara Gurwal. I’m a biotech analyst at Cantor. For the first session today, we are very excited to host the team of Cue Biopharma. Representing Cue, we have Dan Passeri, Chief Executive Officer. Dan, thank you for joining us today.

Dan Passeri, Chief Executive Officer, Cue Biopharma: Thank you for having us.

Prakhara Gurwal, Biotech Analyst, Cantor: Maybe for those who are not familiar with the company, if you can start with a brief overview?

Dan Passeri, Chief Executive Officer, Cue Biopharma: Sure. Cue Biopharma is based on a protein engineering platform that came out of the Albert Einstein School of Medicine. In essence, what it’s predicated upon is the ability to design molecules that interact with T cells, lymphocytes, I should say, with specificity. In other words, what we’re not doing is just making bispecifics that bind to various receptors on different target cells, but we’re designing molecules specifically engineered to provide conditional binding so that we’re fostering a mechanism of differentiation or activation. For instance, a CD8 T cell requires, it’s very well established, requires signal 1 and signal 2, forming an immune synapse. IL-2 is part of that cascade. We saw in the immuno-oncology sector in the past decade a lot of effort with IL-2. If you just provide IL-2 itself, you’ll foster proliferation but not activation and memory.

What we did is we designed a molecule that engaged the T cell receptors. That’s where the specificity comes from. That’s not just for targeting. That’s part of the signaling immune synapse. Along with that T cell receptor, we also have a modified IL-2. What we have is a signaling cascade. From those learnings, we moved into autoimmune. We have the 500 series. We partnered 501 with Boehringer Ingelheim. That’s for targeting specific cells by exploiting the intrinsic antiviral T cell repertoire we all harbor. I can explain that later. We have a 401 molecule, which is based on TGF-β biology, which is essential and basically tolerance, maintaining immune balance and tolerance. The protein engineering platform has been specifically developed to enable us to dial in specificity and to target particular pathways to modulate specific lymphocytes within the ecosystem of our immune system.

Prakhara Gurwal, Biotech Analyst, Cantor: Got it. Was this platform internally developed?

Dan Passeri, Chief Executive Officer, Cue Biopharma: It was initially developed at Albert Einstein, which was the framework of targeting T cell receptors through the HLA. From that sort of foundational observation, we have evolved the platform internally. The TGF-β component, that was completely in-house. The 500 series was completely in-house. They were derivatives from our observation from our oncology programs.

Prakhara Gurwal, Biotech Analyst, Cantor: OK, got it. Maybe we start touching on some of the bioprotein assets. You mentioned about CUE-401.

Dan Passeri, Chief Executive Officer, Cue Biopharma: Yeah.

Prakhara Gurwal, Biotech Analyst, Cantor: Just provide an overview of CUE-401 and the mechanism of action there.

Dan Passeri, Chief Executive Officer, Cue Biopharma: The specific mechanism of action that we engineered the protein to foster is observation. Everyone’s aware that T-regs are fundamentally important. Our immune system is an exquisitely regulated ecosystem of different cell types and lineages. There are T cells, B cells, and within T cells, you have different subsets. Regulatory T cells are essential for maintaining self-tolerance. That’s, in essence, how we go through life and not develop autoimmune disease. Obviously, there are circumstances where that balance and that regulation is not maintained. TGF-β is a critical, let’s say, master switch in maintaining that population of regulatory T cells. We have circulating through our bodies regulatory T cells that originated in our thymus. Those are called natural regulatory T cells. You also have a population that are in the periphery.

We believe it’s really essential to maintain the appropriate balance of regulatory T cells versus the disease-causing self-reacting effector T cell. TGF-β is essential to maintain that balance. CUE-401 was engineered to foster TGF-β binding signaling along with IL-2. The way we engineered it was we basically took our observations from our oncology program and dialed in conditional binding so that both TGF-β and IL-2 have been genetically engineered to basically dial down its affinity so that you need both of those molecules, the ligands, to bind to their receptors, kind of in avidity, where TGF-β will not dock and signal on its own. It needs IL-2 to also be there to have enough resonance time.

Prakhara Gurwal, Biotech Analyst, Cantor: OK. They both need to bind with a lower, I guess, you tone down the affinity to make sure that both have to bind to activate these targets. Is that a fair way to characterize it?

Dan Passeri, Chief Executive Officer, Cue Biopharma: Yeah, that’s right.

Prakhara Gurwal, Biotech Analyst, Cantor: I guess when you combine both targets, because TGF-β has historically had some safety issues, maybe just when you bind to its specific target, how do you get comfortable around the safety profile of combining both targets, which had safety issues?

Dan Passeri, Chief Executive Officer, Cue Biopharma: Yeah, really important question. We spent a significant amount of time on engineering this molecule to address that issue. We saw this in immuno-oncology. It was not effective when you inject a bolus of IL-2. You need to have some targeting element to it and context. What we did, as you pointed out, TGF-β is very challenging for a number of reasons. We believe we’re actually the first company to be able to agonize TGF-β with a good safety tolerability profile. We did that through several key modifications. In nature, TGF-β exists as a dimer. Two TGF-β molecules come together and form a dimer through disulfide bridges. One of the first things we did is we removed the disulfide bridges, so it exists as a drug as a monomer. It will form a dimer when it binds to the receptor.

We also affinity attenuated, so it is not attracted to its receptor with a strong force. On top of that, we put a mask. The mask on the molecule is part of its natural receptor, so that TGF-β moiety is more stably associated with its mask unless it’s able to dissociate because of stable association. That’s where the avidity or the two elements together come in. You have to have IL-2 concurrently binding with TGF-β. That will create enough stability where the two of them are bound. It’s sort of forming an avidity rather than affinity. Through that conditional binding, we’ve created a therapeutic window. Within a range, we’re seeing that you need those two elements, those two receptors to be bound, and that signaling will foster Treg formation, where you have self-antigens being presented.

The TCR is signaling, and then the TGF-β receptor with IL-2 will enable FOXP3 to be transcriptionally upregulated. IL-2 is essential there to demethylate to keep it stable.

Prakhara Gurwal, Biotech Analyst, Cantor: OK. Maybe, yeah, walk us through some of the impact on the T cells and the T-reg cells broadly.

Dan Passeri, Chief Executive Officer, Cue Biopharma: Sure.

Prakhara Gurwal, Biotech Analyst, Cantor: What’s the proliferation you have seen preclinically?

Dan Passeri, Chief Executive Officer, Cue Biopharma: You just asked about the proliferation, right?

Prakhara Gurwal, Biotech Analyst, Cantor: Yeah, of the T cells.

Dan Passeri, Chief Executive Officer, Cue Biopharma: Yeah. There’s been a lot of investment in the T-reg space. I want to emphasize the key competitive positioning of Cue Biopharma is we’re not just proliferating natural regulatory T cells (NT-regs). We’re also inducing new regulatory T cells (Tregs) from T effector cells that are receiving self-antigen. That’s a really important feature. That’s where the TGF-β pathway comes in. When you asked about the proliferation, we are seeing proliferation of NT-regs, but we have a very significant increase in the T-reg population overall. Probably the majority of them are coming from an induction or a transcriptional modification of T effectors converting into induced regulatory T cells (IT-regs). We’re seeing a very profound increase in the T-reg population. It’s not just stimulating NT-regs.

The difference of those two is when you increase the NT-reg population, what you’re likely to see with an IL-2 mutant fostering proliferation of NT-regs, you’re likely to see a quelching of inflammation in an autoimmune disease because you’re sequestering IL-2 on the receptor, the CD25 receptor that NT-regs have. The IT-regs are behaving differently. They’re specifically proliferating self-antigen TCR engagement. TGF-β and IL-2 will now convert those to IT-regs. We’re not just sequestering IL-2, but we have a T-reg population that should play a much greater role in the enabling of tolerance. That’s what we’re really fostering. We’re trying to quelch inflammation, but also reestablish immune balance and, in essence, implement or induce a process of immune tolerance, which gives you a longer control of the disease.

Prakhara Gurwal, Biotech Analyst, Cantor: Got it. What other preclinical data that you have generated to show activity of this molecule?

Dan Passeri, Chief Executive Officer, Cue Biopharma: Yeah, so preclinically, we obviously have a substantial amount of in vitro data showing the induction of T-regs, not just NT-reg proliferation, but induction of new T-regs from T effector cells. Where that translates into disease model activity, I want to emphasize the tolerance aspect. In a graft-versus-host model, where you’re, in essence, taking human lymphocytes and putting them into new mouse models, 100% of the vehicle-treated will of the mouse model for graft-versus-host will succumb to graft-versus-host and die within, let’s say, a 30-day period. We treated the animals transiently, not chronically. The reason is we’re trying to demonstrate not just quelching of the inflammatory cascade, but the induction of tolerance. The animals received three doses early on the study, day 0, I think 15 and 30. Those animals, 100% of them stayed alive for double the amount of time.

At day 100, remember, they didn’t receive any drug post day 30. At day 100, we still had about, I think, 60% or 50% of the animals still alive with the human lymphocytes in their bodies with T-regs. That’s evidence of tolerance. They didn’t receive any additional drug after day 30. The only thing keeping them healthy and balanced to their immune system was this population of T-regs that we developed. This is very distinctive data. You don’t see that with IL-2 mutants. With most of the biologics being developed for autoimmune disease, you need chronic exposure because it’s quelching inflammatory cascades. That’s the key differentiation of what we’re doing. We believe we’re reestablishing immune balance by not just fostering a diminishment of the inflammatory cascade, but an induction of the tolerance process through these new IT-regs that we’re inducing. We have that data in several disease models beyond graft-versus-host.

Prakhara Gurwal, Biotech Analyst, Cantor: OK. Got it. How do you envision the regulators viewing the T-reg induction mechanism versus the existing IL-2 therapies, which have been there for several decades?

Dan Passeri, Chief Executive Officer, Cue Biopharma: Yeah, we already had a pre-meeting with the FDA. That went very well. We’re on track for basically a conventional IND filing. We had very positive feedback. I think it’s really because of the wealth of data we have in disease models, but also to date, the tolerability data that we generated. This is non-GLP, but we had a dose escalation in three different species, presented that data to the FDA. We had very positive feedback.

Prakhara Gurwal, Biotech Analyst, Cantor: OK. What are the gating steps to the IND now?

Dan Passeri, Chief Executive Officer, Cue Biopharma: Yeah, we don’t see any hurdles that we have to overcome. We think this is going to be a conventional IND filing with CMC ongoing right now. We have GLP toxicology studies that we’re ramping up for. We should have that completed in the February time frame. It’s just conventional IND preparation, pre-IND studies that we’re doing.

Prakhara Gurwal, Biotech Analyst, Cantor: When do you plan to file an IND?

Dan Passeri, Chief Executive Officer, Cue Biopharma: We’re anticipating the IND filing to be in June of 2026 next year.

Prakhara Gurwal, Biotech Analyst, Cantor: OK. Got it. Maybe just talk about the development strategy here, the indications that you plan to go after.

Dan Passeri, Chief Executive Officer, Cue Biopharma: Sure. Important question because we feel the real value of this program is the broader application for multiple autoimmune diseases. Again, I want to emphasize it’s not just for ameliorating the flare-up of the autoimmune disease, but we think the key differentiating feature is the ability through this induction of T-regs from T effector of establishing immune balance and tolerance so that we believe this drug will not have to be dosed chronically. The objective is to have exposure to the molecule, having a prolonged PD effect where we’re generating these stable, durable T-reg populations that will then manage the disease, establishing tolerance and control.

What we want to do is use an indication such as atopic dermatitis as an exemplary model where we can very efficiently, in a timely manner, extract biomarker data that will demonstrate the molecule’s mechanism of action, that we’re modifying the ecosystem of the cell populations so that we’re changing the T effector population, increasing the T-reg population, and demonstrating the initiation of immune balance and tolerance in that setting, and then use that basically as an opportunity where we can take that data and apply it to multiple autoimmune diseases for phase two.

Prakhara Gurwal, Biotech Analyst, Cantor: Got it. You know within the atopic dermatitis space, I think some IL-2 mutant therapies had some data, like Nektar. Does it have implication for your approach?

Dan Passeri, Chief Executive Officer, Cue Biopharma: Yeah, so the IL-2 mutants basically are biasing CD25, which is on Tregs, CD4s. It’s also on T effectors. We think one of the things to watch there is that you’re likely to be proliferating not just the already existing Treg population, but also T effectors. We’re hoping that data continues to be positive because that will demonstrate the importance of NTregs. I want to reemphasize the differentiating feature of our approach. We’re not just proliferating that already existing Treg population, but inducing new Tregs from T effectors. That NTreg population, because of the CD25, is likely to, if you increase that population, you’re likely to be sequestering binding to IL-2. That will quelch inflammation. We’re hopeful that that sort of establishes a standard where you’re seeing NTregs quelch inflammation, which we believe will also demonstrate.

We’re confident that what our approach will also do is establish this population of ITregs to basically provide greater immune balance and tolerance longer term. We think that’s the key differentiating feature.

Prakhara Gurwal, Biotech Analyst, Cantor: Right. What could be the possible design of an atopic dermatitis trial?

Dan Passeri, Chief Executive Officer, Cue Biopharma: We’re obviously going to have to go in with healthies initially for dose escalation.

What we’re doing is designing the trial so that we have defined doses. We’re going to be treating patients. The objective is to be able to access patients and get pre and post samples, obviously blood samples. The objective would be to be able to get in a subset of patients pre and post-treatment skin biopsies. We can then look at the cellular makeup. We can look at various biomarkers. The objective is to use that data to not just establish the efficacy that we’re seeing, both near-term quelching of the inflammatory process, but long-term tolerance, but also get a wealth of data on biomarker analysis to demonstrate a changing in that sort of ecosystem of cells so that we’re fostering immune balance.

Prakhara Gurwal, Biotech Analyst, Cantor: OK. What’s the half-life for CUE-401? What’s the expected dosing frequency based on the half-life and in the context of some of the disease remission arguments that you have made around atopic dermatitis?

Dan Passeri, Chief Executive Officer, Cue Biopharma: Yeah, that’s a very important question because I want to emphasize this is not a classic biologic where you need a prolonged half-life for the drug to be circulating around. It’s not blocking a mechanism where you need that molecule to be around for a long time. What matters is its PD effect. You don’t want this molecule to be circulating around for two weeks, three weeks plus. Right now, we anticipate the T half to be something of the order of two days, three days. What matters is the PD effect. The molecule is inducing proliferation of Tregs and induction of induced Tregs. That population of cells represents the therapeutic. What we’re doing is fostering that population. What’s important is because we have both TGF-β and IL-2 concurrently, it’s a durable, stable induction of FOXP3. FOXP3 ends up demethylated because of IL-2, which stabilizes it.

That will enable that population to stay durable. In terms of the question about the T half, it really has to do with what is the dosing regimen. We don’t believe we’re going to have to have chronic dosing. We’re expecting to have transient dosing, let’s say several doses exposing the patient, and then possibly have to re-dose six months later. That’s something we’re going to work out in the phase 1B is define those parameters.

Prakhara Gurwal, Biotech Analyst, Cantor: Right. Maybe longer term, beyond atopic dermatitis, what other indications you could see applications for this drug?

Dan Passeri, Chief Executive Officer, Cue Biopharma: Yeah, we actually believe it has a potential application broadly to a series of autoimmune diseases, including ulcerative colitis, arthritis, rheumatoid arthritis. That’s one of the advantages of the mechanism. We don’t believe it’s just going to be derm or a TH17 or a TH23. This will have a broader application to a number of autoimmune diseases because of the mechanism of action of maintaining immune balance.

Prakhara Gurwal, Biotech Analyst, Cantor: Right. For CUE-401, I’m asking this question because for CUE-501, you partnered with Boehringer Ingelheim.

Dan Passeri, Chief Executive Officer, Cue Biopharma: Yeah.

Prakhara Gurwal, Biotech Analyst, Cantor: For CUE-401, do you expect to go alone or try to look for a partner early on?

Dan Passeri, Chief Executive Officer, Cue Biopharma: Thank you for asking that question. We have implemented a very deliberate business model where we partnered CUE-501, and I’ll touch upon that subsequently. We have a series of assets for oncology. We’ve allowed that data to mature, and it has strengthened. We intend to partner the oncology assets. CUE-501, we’ve partnered with Boehringer Ingelheim. We intend to hold on to CUE-401 ourselves to maintain control. That creates the greatest upside potential for our shareholders. The real objective is we believe over the next 18 to 24 months, we will have a body of data demonstrating that this represents a potential breakthrough disruptive innovation for autoimmune disease because of the ability to, what we believe will, reestablish immune balance and induce tolerance for patients, having broad applications. Our intention is not to partner that program until we create a data set that creates a premium for our shareholders.

Prakhara Gurwal, Biotech Analyst, Cantor: OK. That’s a good segue to CUE-501. Maybe just talk about CUE-501 and your partnership with Boehringer Ingelheim there.

Dan Passeri, Chief Executive Officer, Cue Biopharma: Yeah, we partnered with Boehringer Ingelheim very specifically. We’re very pleased to have them as a partner. They have a deep understanding of the biology. The reason they turned to us for that asset was the B cell targeting and depletion space was becoming very crowded with these bispecifics. As you know the history of that, you initially saw CAR T cell application depleting B cells. It showed some very impressive results. Following that were basically bispecifics, which would bind to CD19, which is a protein on the surface of B cells. On the other end of that molecule is CD3, which is a pan-activator of T cells. You ended up seeing a number of pharmaceutical companies basically deploying the exact same strategy with these bispecifics, CD19, CD20, BCMA, all markers on B cells with CD3. These are not trivial molecules. They’re pan-activators, and you have cytokine release.

You have to watch these patients carefully. What our approach is to basically use the intrinsic antiviral T cell repertoire we all harbor. All of us have been infected with the chickenpox virus, for instance. We don’t have shingles on an ongoing basis because our immune system keeps the virus at bay. CMV is another example. We harbor T cells that are circulating through our bodies that are in an activated state with memory, and if they see a cell with that protein, they’ll attack and kill it. We’re taking advantage of that. Boehringer Ingelheim saw our molecule as differentiated, where we are basically fostering cell killing without the deleterious side effects of pan-activation.

Prakhara Gurwal, Biotech Analyst, Cantor: Got it. As you compare with the T cell engagers, you mentioned the safety side, but anything else on the differentiating aspects, whether on the efficacy as well, ability to dose higher, anything that you can highlight?

Dan Passeri, Chief Executive Officer, Cue Biopharma: Yeah, what we’ve seen preclinically, and this is, I think, why Boehringer Ingelheim became so interested in the program, resulting in a partnership. We saw, in essence, equivalent killing in human blood, obviously ex vivo, where we are targeting B cells and, in essence, covering them with a molecule that presents a CMV epitope. The patients’ T cells that are anti-CMV see the B cells virally infected, attack, and kill. What we saw was equivalent killing to these bispecifics. The important feature is we didn’t see cytokine release. We believe we have a highly selective, specific means of targeting and eradicating the B cell population without the side effects you see with these bispecifics. It’s really the safety profile we believe is the key feature.

Prakhara Gurwal, Biotech Analyst, Cantor: OK. Which models did you test this in? What was the magnitude of B cell depletion that you saw compared to, let’s say, other T cell engagers?

Dan Passeri, Chief Executive Officer, Cue Biopharma: Yeah, I’m not at liberty to discuss the data that’s being generated under the Research Alliance right now. I can convey the data that we’ve generated and publicly released, and that’s been replicated, is taking human blood in vitro and exposing it to the molecule. The B cells become basically covered with this molecule. The antiviral T cells that are in the human blood will attack the B cells and destroy. In that setting, we saw equivalent killing with no cytokine release. We also have in vivo models where we’re seeing really effective killing.

Prakhara Gurwal, Biotech Analyst, Cantor: What would be the specific inflection points for this program in the next, let’s say, 12 to 18 months?

Dan Passeri, Chief Executive Officer, Cue Biopharma: I think you just asked what are the inflection points?

Prakhara Gurwal, Biotech Analyst, Cantor: Yeah.

Dan Passeri, Chief Executive Officer, Cue Biopharma: For sure. We received an initial payment of $12 million upfront. Boehringer Ingelheim, through a research collaboration with us, is supporting some of our scientists, providing funding on an annual basis, conducting preclinical studies to define the lead candidate to take to an IND. We have a series of milestones over the next, just as you stated, 12 to 18 months. We have two preclinical milestones that will provide us with a significant cash infusion. We haven’t disclosed what those milestones are, but that’s quite relevant for the company.

Prakhara Gurwal, Biotech Analyst, Cantor: OK. We didn’t touch upon this, but maybe if you can elaborate on what’s happening on the oncology side.

Dan Passeri, Chief Executive Officer, Cue Biopharma: Sure. We’ve treated, and this has to do also with the safety profile of CUE-401, because the IL-2 we’ve integrated into the CUE-401 molecule came from the oncology program. We have what’s called the 100 series. What we can do with that series is specifically target T cell receptor sequences that are relevant to cancer, proteins that are expressed on cancer. By targeting the T cell receptor, we’re concurrently delivering IL-2. What we believe we’re doing, we have a deep data set demonstrating PD effect, where we’re proliferating those specific T cells. We have shown with our lead program, CUE-101, monotherapy in second line and beyond, a really profound enhancement of survival. In essence, the molecule is enabling in vivo cell therapy. The tolerance profile, tolerability profile, is very attractive.

In the second line setting, monotherapy, just with our drug, these are refractory patients, head and neck cancer, HPV-driven head and neck cancer. Keytruda was approved as a standard of care by increasing survival from, I think, 6.5 months with chemoradiation to 8.4 months with Keytruda. In that setting, second line, these are refractory patients, we’ve pushed the survival, median survival, to almost 21 months, which is a profound advancement. Hazard ratio confidence is, I think, 0.23 in the head and neck trial. In the combination with Keytruda frontline, we increased the overall response rate from 20%, which is Keytruda monotherapy, to 50%. Importantly, we didn’t see a difference between high CPS score and low CPS score. That’s actually a differentiating feature. We believe it’s because, to remind everyone, Keytruda only has activity because the patient needs to have activated T cells trying to attack the tumor.

A low CPS score means those T cells aren’t there. We believe we’re activating T cells even when they’re not present. We’re stimulating and activating cancer-specific T cells. In the frontline setting, we have a median survival presently of approximately 32 months. Keytruda alone is 12 months. At the 12-month point, our survival is 88%. That data we’ve allowed to mature over the past 12 months. It’s continued to strengthen. We’re now in strategic partnering discussions on finding a partner who can take that portfolio and exploit it in a very meaningful way.

Prakhara Gurwal, Biotech Analyst, Cantor: Got it. One last question in the interest of time, current cash runway, and what does it cover?

Dan Passeri, Chief Executive Officer, Cue Biopharma: Sure. We ended last quarter with $28 million in cash. Our annual burn is right around $25 to $28 million. We’re anticipating an important strategic partnership in oncology that will give us an infusion of capital. We have these milestones from the Boehringer Ingelheim partnership that we’re also anticipating.

Prakhara Gurwal, Biotech Analyst, Cantor: OK. That’s all the time we have today. Thank you, Dan, for joining us.

Dan Passeri, Chief Executive Officer, Cue Biopharma: Thank you, Anish.

Prakhara Gurwal, Biotech Analyst, Cantor: Thank you to the audience for listening.

Dan Passeri, Chief Executive Officer, Cue Biopharma: Thank you. All right, we’ll get started. Good morning, everyone. Welcome to day three of our Cantor Global Healthcare Conference. My name is Olivia Brayer. I’m one of the Senior Biotech Analysts here at Cantor and have the pleasure of having the Cue Biopharma team here with us today. We have Dan Passeri, who’s CEO, and we have Simon Goodwin, who is Head of Corporate Finance and IR. Thank you guys for being here and for making the trip.

Silviu Itescu: Pleasure.

Dan Passeri, Chief Executive Officer, Cue Biopharma: You have a big launch going on. Maybe just, you know, tell us and characterize how that commercial launch has been going.

Silviu Itescu: Yeah, I’ll start. We’re doing a bit of a tandem show. Look, we’ve been providing the product for children with acute graft-versus-host disease, which is a devastating complication with a very high mortality, for a number of years under compassionate care. We got approval at the end of December last year. It took us about three months to put in place all of the logistics and the pieces required to launch the product. We launched it end of Q1. We’ve recently provided an update on our first quarter of real sales. Just to put it into context, when we started, we were concerned about a number of areas. Number one was, would payers support the pricing point and reimburse? Number two, would physicians get a little bit of sticker shock because they’ve been using this product for free for years and suddenly we’re providing it at a commercial price?

Three was, what kind of barriers would we encounter when we went through the various institutions and hospitals? What I can tell you is, to our pleasure, we were very pleasantly surprised, is that the insurers were fantastic. We’re covered by all of the major carriers, all of the commercial carriers. We’ve had zero pushback. We’ve got about 250 million lives covered. We’ve had no questions around discounts, no questions around step-throughs, etc. That was a pleasant surprise. We had federal Medicaid coverage in record time. Since July 1, we’ve had every state Medicaid is mandated to cover us. All of that, which we thought was going to be the most difficult part of this, turns out to be the easiest part. That was great. The initial physician view was, as I said, sticker shock, expensive.

Once they understood that we’ve got insurance coverage and that it doesn’t cost the hospital anything, actually, all of that is an easy barrier to overcome. In fact, the physicians are very much on board now. The third part of this turned out to be the most complex, which you wouldn’t be surprised, is the institutional bureaucracies. It is remarkable how much bureaucracy there is in the U.S. healthcare system. We’ve now got 32 hospitals fully onboarded out of the targeted 45, which are going to happen this quarter. What do we mean by onboarding? We have to go through the multiple committees, committees around high-priced medicines, committees around safety, committees around physician uses. I can’t tell you the bureaucracy, which takes weeks to get through in the first place. Really, who suffers through this bureaucracy? The patients do. The kids do.

Now that we’ve kind of gotten our way through all this, I would say that things are going pretty smoothly. What was complex on patient number one, by the time we get to second and third time in the same institution, is taking a fraction of the time that the first patient took to get treated. These are sort of the issues we had with the launch, which we’re very pleased are now kind of behind us. Hopefully, we’re going to see growth in quarters two and three.

Dan Passeri, Chief Executive Officer, Cue Biopharma: How many transplant centers? I know you mentioned, I think, 45 by the end of this quarter. How many are you hoping to eventually onboard? What are maybe some of the strategies that you can do or are actively doing to cut through some of that bureaucratic tape, so to speak?

Silviu Itescu: You know, the 45 that we’re targeting are the high-volume centers, right? There’s probably 80 to 100 sites across the U.S. that do transplants. Some of the smaller ones might do one a year, and the amount of effort to bring them all on board is different. The other strategy around why the first 45 are important is because they’re also the adult centers. At the same time as we’re in these hospitals with children, we’re able to work through the adult transplants. It’s going to become really important when we start the adult trial, which is happening in this quarter. We’re working with the NIH-funded Bone Marrow Transplant Clinical Trials Network. They work across 80 sites. Working in the 45 or so largest volume sites means that you can leverage all the work you’re doing with the adults.

In fact, I can tell you that already we’ve got many adult patients that are being referred to us, more than children, actually. We’re providing our therapy under compassionate care, free of charge, to adults because at the moment, the insurers are not covering it, as you would expect, until we get a clinical data set that supports label extension. We’re doing the right thing by the centers. We’re also doing the right thing by the same pediatric centers that have children sometimes who are not covered, and we’re providing it free of charge to those children too. This is about relationship building.

Dan Passeri, Chief Executive Officer, Cue Biopharma: Sure. We’ll come back to that adult trial design in a minute and some of the FDA feedback that you guys have received. Maybe just help contextualize the market opportunity here as you see it. Obviously, you’re in pediatrics now. I know you’ve talked about a number of pediatric transplants. As you think about the totality of the market, right, maybe the split between adults versus pediatrics, and then how you think about the overall market opportunity for Ryoncil?

Silviu Itescu: Maybe I’ll let Paul answer this question. Paul?

Paul Kampner: Yeah, sure. The way we think about it is just start from the top with the number of bone marrow transplants. There’s about 1,500 in pediatrics per year and about 8,500 in the adult market. We funnel down through the incidence of GVHD and then the effectiveness of steroids. Sort of 50% have a GVHD present, and then around 50% of those will be steroid refractory. For kids, in terms of patient numbers, adults or orphans, you know, 300 to 400 patients a year. It’s an acute disease for those that don’t know. It’s new patients every year, and you’re treating those. We have experience with our licensee partner in Japan, who launched a product five, six years ago, where they achieved about a 40% penetration in three years. From our perspective, we think it’s a reasonable data point, and it’s something that we’re targeting from that perspective.

For adults, that’s a three to four times larger market, which makes it about probably 1,000 patients a year potential.

Dan Passeri, Chief Executive Officer, Cue Biopharma: You know, doing the math, that comes out to what, about $1 billion peak sales kind of opportunity for the market?

Paul Kampner: Yeah, I think that’s a market in total, yeah. You take your, you know, what your assumptions are around a penetration from that perspective. Just some simple numbers, you know, we look at about $1.5 million a patient. You know, even in kids, you know, two patients a week, 100 patients, that’s $150 million. That’s kind of a 30% kids penetration. Those are sort of simple numbers to look at it.

Dan Passeri, Chief Executive Officer, Cue Biopharma: Paul, remind us, when does the actual revenue recognition occur with this product? Yeah, it’s obviously not a one-and-done annualized product, right? As you think about those tranches over the course of the year.

Paul Kampner: Yeah, it is related to the way the treatment rolls out to each patient. You know, it’s a product that has to remain on basically, you know, I think we’re nitrogen deep freeze. We’re shipping to patients every week. A patient is generally on a four-week course, two doses per week in the first instance. We’re shipping the duos that contain the frozen product every week. Revenue gets recognized as you’re selling infusion kits and not for, say, a whole course at a month.

Dan Passeri, Chief Executive Officer, Cue Biopharma: Yeah. I know you guys have gotten a number of questions over the last few months just around demand versus inventory dynamics. Maybe just speak to those. I mean, what is it? Is it really demand that is driving this launch? Has there been much inventory buildup in terms of revenue recognition?

Paul Kampner: Yeah, at the moment, we make our final drug product, which is in the vials in Singapore. We ship all those little vials to Sanquara, and that stays on our balance sheet. From there, it gets packed into the infusion kits. Those kits range from a one-vial kit to an eight-vial kit. There’s eight infusion kits in total. Then.

Silviu Itescu: Eight vials per kit, eight infusion kits, each one has a different amount of product.

Paul Kampner: Yes, a different infusion kit.

Silviu Itescu: Based on age and weight.

Paul Kampner: That’s all on our title, our inventory. As it’s required by patients, then it’s moved to Sanquara title, and then it’s shipped out from there. We promise to get product within 24 to 48 hours anywhere in the U.S. so that these patients can be treated almost on a just-in-time basis per week. Sanquara keeps, you know, sort of three or four kits, and those are replaced each time as it flows through. There’s not a large inventory stock. Most of it, because it’s at the same site, yeah, most of it sits on our side, and then it’s basically moved across to their title.

Dan Passeri, Chief Executive Officer, Cue Biopharma: As for the breakdown of margins for this franchise, maybe just can you run down the current sort of margin structure? As you think about the launch evolving and as you treat more patients and more centers, how could this gross to net and margin story ultimately play out?

Paul Kampner: Yeah, so the gross to net we reported last quarter is 14.6%. We don’t see that changing a lot. There’s no discounting of the product, so the gross to net adjustment is based purely on the proportion of patients that turn out to be Medicaid or have some sort of rebate required under that federal agreement. That’s a 17.1% rebate to those patients that goes back to CMS. Then it’s the distribution cost, so that’s 14.6%. We think that might move around depending on the patient mix, but it’s in the range. From a gross margin perspective, you’re looking at about a 90% gross margin. Because it’s an off-the-shelf product and not a patient-specific targeted product, it has normal sort of kind of drug margins, if you like. For this indication, I think that’s going to be pretty steady too. Gross margin is no huge economies of scale.

It’s an orphan product. As we move through to our next-generation products and we’re looking at larger volume and different manufacturing, so 3D bioreactors and things like that, you may see margin improve. At 90%, there’s not a lot of room to wiggle on that.

Dan Passeri, Chief Executive Officer, Cue Biopharma: Right, right. There is another player in this space, right? Jakafi is obviously approved, albeit in a smaller subgroup in terms of the age population versus what you guys are approved for. Maybe just speak to the dynamics there. Where are you seeing Ryoncil used versus Jakafi? Are there certain subgroups or subsets of age groups that you guys are seeing more use in? If it’s too early, do you expect to see more use in certain age categories?

Silviu Itescu: Jakafi was only approved in adults. In their study in adults, they had an inclusion criteria of 12 and up, but they actually had no patients under 18 in their study designs. Nonetheless, they’ve got a label for 12 and up. 75% of our children are under 12. 25% are between 12 and 18. I think that we’re going to share the 12 to 18 market with Jakafi. For the under 12s, Jakafi is not approved. Until recently, it was sometimes used by physicians, but it has a high rate of toxicity and it doesn’t work very well in the severe patients. I’ll come back to that in a minute. We don’t see that in time Jakafi is going to be used in children under 12. Not paid for, toxic, et cetera.

Dan Passeri, Chief Executive Officer, Cue Biopharma: I’m not to interrupt you, but just to chime in, is that because there will be payer restrictions specifically there now that you all are approved, or is it more because physician adoption will shift?

Silviu Itescu: I think both. I think both, for sure. It’s clear that the guidelines will be our cells should be the first line of therapy in children. Once you’ve got that, payers will restrict Jakafi. Physicians know that already. As long as there are no barriers to reimbursement of our product, physicians will always prefer our cells first. Where the growth that we see is in older than 12 and ultimately in adults, in patients with severe disease, right? Those with grade CD disease in particular. In that group, which is about 50% of the steroid-refractory GVHD population, in that group, in both the pivotal study called REACH-1 with Jakafi and its subsequent randomized controlled REACH-2 trial, in that group of patients, response to Jakafi was of the order of 40% to 50%, which is really bad, actually.

The 40% to 50% response is no better than half a dozen other drugs that are out there not approved for GVHD. That’s our market opportunity, both in 12 to 18-year-olds, as well as in the larger adult population. That’s what we’re targeting. We’re targeting 18-year-old and older with grade CD disease, where the mortality is of the order of 70%, 80%, where Jakafi gives you less than 50% response rates, even though it’s approved, where we think we can, we know actually that under compassionate care use in those who failed Jakafi, we improve survival rates from 25% to 70% plus. That’s the group that if you add our cells to, will give you a higher degree of synergy and much better outcomes. That’s exactly what we’re targeting in terms of label extension.

Dan Passeri, Chief Executive Officer, Cue Biopharma: You guys haven’t necessarily given guidance or even committed to giving guidance. When you think about the revenue trajectory over the next few quarters, what are you guys seeing real time so far? Just thoughts on, you know, the revenue ramp from here? Anything that you can?

Silviu Itescu: I’ll leave the revenue ramp to Paul, but I’ll tell you what we’re seeing in terms of the growth of patient demand. We’ve now got a second quarter under our belts, pretty much. Not completed yet, but end of September. July traditionally is a slower month for transplants, and that’s because of lots of issues. New physicians start, they do less transplants, et cetera. We saw a little bit of a seasonality. What we’re seeing now is a real ramp-up in demand in terms of number of referrals per week, in terms of repeat customers from the same hospitals that have had good experience. We’re seeing that ramp-up that I think is going to see an increase in revenues this quarter, next quarter, and so on. Paul, do you want to talk a little bit?

Paul Kampner: Yeah, no, I agree with that. I think it’s also linked to the pace that you get your hospitals onboarded and things like that. Obviously, you start with none at the start of the launch, and you build up from there. We’ve rapidly onboarded, and from what the feedback we’re getting is that it is a quick uptake in terms of getting hospitals signed up and ready to go. That directly links to the number of patients coming in as well. It’s been a real focus to get up to the 32 so far, and that’s not all of them. You do have a little bit of step-up as you go and as you onboard new centers and the like.

It is hard to pinpoint where your underlying rates of revenue ramp-up are, but you’re definitely getting benefit by the ongoing addition of new sites and things like that on top of repeat customers from already onboarded sites.

Dan Passeri, Chief Executive Officer, Cue Biopharma: It sounds like things are going well. Congratulations on the launch. Maybe I’ll just ask one last follow-up here, and then we can switch to the adult trial. You mentioned some seasonality in July. It sounds like maybe that is just a dynamic that we should expect, you know, maybe most years. I know it’s a little bit too early to put a finger on that. Are there other months that historically, or other times of year historically, that you’ve seen seasonality, whether it’s a tailwind or a headwind for transplants?

Silviu Itescu: I can tell you my experience at Columbia with the cardiac transplant group and renal transplants, always like this, because that’s when new residents and new fellows come in. They deliberately tend to push off the transplants if they can. It always depends on, but you don’t want people to be making mistakes. These are highly complex procedures. New residents and fellows coming in in July are, you know, not the people you want to be running some of these things. I think that’s, you know, we predicted that because it’s general medical principles. I think that’s what we’re seeing. Other than that, even the Christmas New Year period doesn’t really slow down. I don’t expect any other seasonality.

Dan Passeri, Chief Executive Officer, Cue Biopharma: OK, great. What can you tell us about your Type B meeting with the FDA this summer?

Silviu Itescu: Yeah, on the adult trial?

Dan Passeri, Chief Executive Officer, Cue Biopharma: On the adult trial, yeah.

Silviu Itescu: Yeah. They were actually very good. They guided us into where we are right now. We went there proposing a single-arm, third-line study in patients who’d failed Jakafi, exactly the data that we generate under compassionate care, where we wanted to rescue these patients with our therapy because of the high mortality. What the FDA really guided us towards is starting earlier in second line. They want us to show that when we add our cells to Jakafi, we get a superior outcome. They want that. Physicians want that. Actually, strategically, it makes even more sense for us to do that because the sooner we get our cells into use, the larger proportion of the target population we can address.

We’ve come out of that Type B meeting with alignment both with the FDA and with the NIH-funded Bone Marrow Transplant Clinical Trials Network, where we’re going to do a study in high-risk patients defined as this grade CD group where Jakafi gets you 40% to 50% responder rates. We’ll compare standard of care, where that’s the target that you get today, versus adding our cells on top of the standard of care. I would expect that we’re going to see something like, instead of a 50% responder rate, 80% responder rates. That’s based on our experience in third line, where the group that has failed and had zero response to Jakafi then gets a 67% to 73% responder rate with our cells. If you put it together at the same time, you should get about 80% response.

The advantage to us, assuming that those, and that’s likely to take about a 12-month enrollment period with a short primary endpoint of day 28 response as the endpoint. The strategic advantage to us is that we’re able to then capture the grade CD market from day one. We don’t have to wait for patients to not respond. We don’t have to risk that they die along the way or that they suddenly get some other unapproved therapy. I think that actually allows us to map out the revenue projections in a way that’s much more predictable.

Dan Passeri, Chief Executive Officer, Cue Biopharma: Have you disclosed yet how many patients will be enrolled in that study?

Silviu Itescu: We previously talked about a single-arm study of about 60 patients. I would expect that this would be two arms of about 60 patients. The standard of care will get their standard of care, which is Jakafi. The treated group, instead of staggered to get our cells later, are now getting them up front. Statistics say that with that same 60/60 kind of comparator, we’re statistically powered for success with those sort of numbers.

Dan Passeri, Chief Executive Officer, Cue Biopharma: OK. Essentially, you’re running a superiority study of the combo over Jakafi. Is there any mechanistic rationale for combining the two products? Can you guys hear me? Is there any mechanistic rationale for combining the two products, or is there any preclinical work that maybe you guys have done that would suggest seeing additive benefit on top of Jakafi?

Silviu Itescu: Yeah. There’s a lot of work. There’s clinical work too. Clinical pilot studies that suggest exactly what I’m just saying, that the two together give you 80% to 90% response rates. The pathways are highly synergistic. Jakafi turns off a particular pathway that activates inflammatory cytokines. When Jakafi works, you have complete turnoff of inflammation. It only works when at that dose, that pathway is turned off. That’s really in early-stage patients with mild disease, grade II disease, for example. In that scenario, there’s no residual inflammation that our cells can then act on. I wouldn’t expect that the two together have a lot of synergy in mild disease. In severe disease, grade CD, Jakafi barely works, which means the inflammatory pathways remain very active. We know that. We measure those. Those pathways are precisely what activate our cells and what are turned off by our cells.

There should be tremendous synergy together. It makes complete sense.

Dan Passeri, Chief Executive Officer, Cue Biopharma: Right. Given that you are planning on studying in more of a second-line setting in adults and third line, does that increase the market opportunity that you guys have previously talked about for Ryoncil? From a payer perspective, I imagine there will be some payer questions around a combination therapy with a high price point. Do you envision any pushback there?

Silviu Itescu: No, I don’t think any pushback. This strategy was designed by us specifically for adults who’d failed Jakafi and who have a likelihood of death being 75% at three months, right? If we can convert, you know, 25% survival to a 70% survival, which is what we do with children, then there’s a whole rationale for the same payment strategy for high-risk adults, which is these high-risk adults are about 50% of the adults with GVHD. Whether you treat with our cells after they’ve failed Jakafi or whether you treat them at the same time as they’re getting Jakafi should have no impact on pricing because the outcome with Jakafi is poor in this group. If you can convert a poor outcome to, you know, an outcome that’s based on response and ultimately long-term survival, then you can justify the same pricing.

Dan Passeri, Chief Executive Officer, Cue Biopharma: OK, understood. You do have some other programs going on. One of maybe the furthest along is Revascor. You are going after an accelerated approval. I know you’ve had some positive interactions with FDA. Can you maybe just kind of characterize your conviction, one, in this product, but two, in a potential accelerated approval pathway?

Silviu Itescu: Characterize what?

Dan Passeri, Chief Executive Officer, Cue Biopharma: Why do you all have conviction that you will potentially have an accelerated approval?

Silviu Itescu: First of all, it’s important to understand this is a second-generation product. It’s called rexlemestrocel. It’s a different product that uses monoclonal antibodies to isolate. It’s more concentrated. It’s more potent. It underpins potential approval for some other very large indications, cardiac being one, inflammatory back pain being a second. The underlying manufacturing and potency assays and CMC are all the same. The strategy here is to get an accelerated approval of the product in the first instance for end-stage heart disease. It’s really the product will be approved, and then the other indications become really label extension opportunities. The two big indications are ischemic heart failure with low ejection fraction. We’ve done one phase 3 program, and we would do a confirmatory study to show a reduction in two and three-point MACEs. We’ll talk about that in a minute.

The other program, of course, is the second study in back pain. Again, a first trial that demonstrated reduction in pain at 12 months with durability for three years, and the second trial that’s actively enrolling with the same endpoint. The clinical data sets should support broader label extensions. The CMC underpins both of them. The rationale for an accelerated approval is we’ve had very good interactions with the FDA in the past 12 months with recognition that the data from two large programs in heart failure support potentially approval in a very small sliver of patients with very end-stage disease who are being kept alive on an artificial heart. We want to take advantage of that because it then accelerates all of our programs. The team at the moment is working really hard on the documentation for a BLA.

There’s a huge amount of work going on in terms of putting together the clinical documents, putting together the CMC documents, the potency assays, et cetera. We know how much work there is because we did that with the Ryoncil product. That will take through to the end of this year with manufacturing that’s generating the commercial product in the manufacturing site that would then have to be inspected. All of that allows us to potentially file by the end of the year or sometime in Q1 with looking towards a six-month review process. The strategy is really it positions this product for a whole bunch of new indications that are real blockbuster opportunities.

Dan Passeri, Chief Executive Officer, Cue Biopharma: Maybe quickly remind us next steps. What do those look like specifically for the IBD and back pain programs or indications?

Silviu Itescu: IBD is a real opportunity. That leverages our Ryoncil franchise. Products are already approved on label for some indications. The GVHD market is effectively IBD. Children and adults with GVHD have inflammatory colitis, let’s say. We know how well we’re treating that. We’ve also got some pilot data in 12 patients with inflammatory colitis that was published about two years ago, where the cells were injected locally into the colon. That is a real growth opportunity in label extension for Ryoncil. The best-in-class drug in biologic refractory colitis gets you about a 20% remission rate. That’s the best in class today. 80% of people do not remit. That’s a huge market opportunity. We’re working with our key opinion leaders based on the data we’ve generated already, where we see a high rate of remission with local administration early at eight weeks.

We think that a trial of about 120 patients, randomized controlled trial, if we achieve a remission rate of that order, we can beat 20% easily in patients who otherwise have no options. That is a huge market potential for us. Paul, can you talk to the ulcerative colitis? What size of the market?

Paul Kampner: Yeah, I mean, it’s something like even on a new patient basis, I think there’s 40,000 to 50,000 new patients per year with a large prevalent population. It’s a wide range of what it is. It’s a circa 1 million to 3 million, depending on the data you read. That’s a combined UC and Crohn’s market. It’s a big market compared to what we’re talking about with the GVHD market and a big unmet need.

Dan Passeri, Chief Executive Officer, Cue Biopharma: OK, great. Unfortunately, we’re out of time. I could talk to you guys a lot longer about these programs. Silviu, Paul, thank you so much, and congratulations on all the progress.

Silviu Itescu: Thanks for having me.

Paul Kampner: Yeah, pleasure.

Steve Seedhouse, Biotech team, Cantor: I’m in my office to make sure you have a good time. Damn it, you’re going to have a good time. OK, please. Now, where’s your stuff?

Silviu Itescu: Good morning, everyone. Thanks so much for joining for our next session. I’m Steve Seedhouse with the Cantor Biotech team. It’s really a privilege to welcome our next participating company at the Cantor Global Healthcare Conference, Cue Biopharma. I’m joined on stage by CEO Dan Passeri, CFO Simon Goodwin. Thanks so much for being here. We’d love to kick it off, maybe just pass you the mic for some opening comments, current state of affairs at Cue, maybe recap some of the recent data and the ongoing phase three study. Then we’ll dig right into Q&A.

Ian Hirschfield, CEO, Viking: Sure, sure. Thanks. Thanks to Cantor for the opportunity to participate. Really appreciate it. Yeah, it’s been a busy year for Viking. Earlier this year, we announced the initiation of two phase 3 trials for the lead dual agonist, VK2735, for obesity. The VANQUISH 1 and VANQUISH 2 studies are up and running and rolling well. We’re happy with the progress there. Heavy lift for us since we’re a small organization. I’m glad we got everything off the ground on time. More recently, we announced some data from a phase 2 study of our oral formulation of the same compound, the Venture oral dosing study. We thought that was a very successful study, showed a beautiful dose response, very good efficacy at the top dose, good efficacy across the board. We think a really attractive tolerability profile as well.

Learned a lot from that study and look forward to receiving the full complement of data probably late this month or early next month and then moving forward with the next steps, which would be either a phase 2b or potentially a phase 3, probably in the first half of next year.

Silviu Itescu: Terrific. Can I just start? I mean, the stock reacted obviously the way it did negatively to the oral data. I was surprised by it. Maybe I shouldn’t have been because it’s just the expectations for obesity assets are so high these days. As you’ve been talking to investors, I mean, what’s your take on just how that landed with the market? What do you think people are either missing? Do you think it was appropriate?

Ian Hirschfield, CEO, Viking: Yeah, I think it seemed like there was a big focus on the right side of our tables, especially on the AE side.

Yeah, the high dose, yeah, which we will not be moving forward with. That seemed to take an outsized share of the attention. We saw a good dose response. Even the 15 mg, the lowest dose, showed a separation, a slow and steady separation throughout the 13 weeks. It’s doing something. Obviously, every dose did. The 120 mg showed the greatest separation with over 12% at 13 weeks. I think there was maybe too much attention put on the AE profile of the doses that are not relevant and not enough given to the kind of middle part of the table, which would be the more relevant doses for future development.

Silviu Itescu: Just reflecting back on that, the high doses, you just mentioned outright, those won’t be carried forward. How are you thinking about dosing going forward? What was the intent of putting in sort of 100, 120 milligram dose in the first place, just to establish that you’ve developed the formulation?

Ian Hirschfield, CEO, Viking: Yeah, just to see the range. You know, you don’t want to dose up and have people say, why did you go higher? Why did you go higher? We had gone to 100 in the four-week study. That seemed to be really well tolerated and showed a really encouraging trajectory through four weeks. We could have gone higher in that phase one. What we’ve done in a couple of earlier studies is just we understand what the profile looks like. Let’s push it a little bit to the extent reasonable. We can push it a little bit higher in the next study and see what it looks like, the full range of doses. That’s what we did. I think one consideration that maybe wasn’t discussed enough is that everybody here took four tablets, placebo, all the way through the 120 for a fully blinded study.

The tablet count and the tablet size probably played more of a role than we thought it would. That’s a focus for the future studies, to reduce the tablet count, reduce the tablet size. It didn’t matter so much in the four-week study because it was so short. Here, we did hear that from some participants that they don’t like taking four a day.

Silviu Itescu: Actually, it was interesting because I was going to ask you if each dose cohort had its own placebo match with maybe a different number of tablets. Everyone got four. The low-dose treated patients, did they get three placebo tablets and one drug test?

Ian Hirschfield, CEO, Viking: That’s right. Everybody, see, you don’t have to do that in the phase one because each cohort is sequential. In a parallel cohort, to be fully blinded, everybody’s got to take the same thing.

Silviu Itescu: OK, in the prior phase one, it was the case where there were two placebo patients, I guess, in each dose cohort.

Ian Hirschfield, CEO, Viking: Yeah, that’s right.

Silviu Itescu: It would have been.

Ian Hirschfield, CEO, Viking: Different structure, yeah.

Silviu Itescu: I guess the AEs were so low in that study that it’s hard to know if there was a sort of placebo effect correlation with the number of.

Ian Hirschfield, CEO, Viking: Yeah, the N is 2 there in the higher doses. We did see an increase in the GI AEs in the 100 mg versus, you know, the 60 and 80 in that phase 1. Really not problematic. When you look at the time course of the AEs, they’re really clustered clearly in that week 1, 1 and 2, and some in week 3. It wasn’t, I mean, they just go to zero or close to zero for the rest of the study.

Silviu Itescu: The weight loss data that was reported, I think it was up to 10%. Hopefully, this isn’t a typo in my notes. It says 10% to 9%. I think it was 10.9% placebo adjusted.

Ian Hirschfield, CEO, Viking: Placebo-adjusted, yeah.

Silviu Itescu: Yeah, OK.

Ian Hirschfield, CEO, Viking: Yeah, yeah.

Silviu Itescu: That was for all, the sort of footnote was that was for all randomized patients who received at least one dose and had a valid baseline and post-baseline weight assessment. Was that essentially all patients or because of the discontinuations?

Ian Hirschfield, CEO, Viking: Yeah, so the discontinuations then, if you had a baseline and post-baseline, you were included in the data set. If you dropped out midway, what was done with that person was they were modeled using what’s called the mixed model for repeated measures. That uses their cohort data to model how they would behave through the course of the study.

Silviu Itescu: OK, yeah, so it’s an imputation. OK. Do you know roughly how many patients fit in that category where they just didn’t, I guess all discontinuations?

Ian Hirschfield, CEO, Viking: When you look at the discontinuations, they would be the ones that.

Silviu Itescu: How many weren’t included altogether because they just didn’t have a post-baseline weight assessment?

Ian Hirschfield, CEO, Viking: Oh, very few.

Silviu Itescu: OK.

Ian Hirschfield, CEO, Viking: Two to five, maybe? I don’t know.

Silviu Itescu: OK. Just one other point of debate, I guess, post this is what’s the appropriate titration schema? You used the two-week titration here. It was a one-week titration in some cohorts, even in phase one, because that was a four-week study. What are you going to implement going forward?

Ian Hirschfield, CEO, Viking: Yeah, I think we used the two-week here, and we started at 30 here because we had such good tolerability in the phase one. We thought we could be aggressive. I think probably in the future, we would maybe start a little lower and just use a four-week block, you know, to start everybody at 10, for example. Just give them a 10 for four weeks, then go to 20 or the next increment for four weeks. I’m confident that would result in a pretty clean side effect profile.

Silviu Itescu: OK. What are the plans at this point to meet and speak with FDA? I think you invoked phase 3 plans here. Can we just talk about potential designs? I’m really interested in dose selection if you already have some definitive thoughts on that as well.

Ian Hirschfield, CEO, Viking: Yeah, not definitive yet. You know, that range from, call it, 20 to 80 might be of interest in a future study. Once we get the full data set, we’ll likely request an end-of-phase two meeting and then take the feedback there and go forward with whatever the feedback would allow us to do.

Silviu Itescu: OK, and that would mean if FDA is comfortable with you going right into phase 3 as they were with the subcutaneous formulation, that’s something you would do?

Ian Hirschfield, CEO, Viking: It depends on all the comments we got back. In a perfect world, like with the sub-Q, I’d say it’s a less than even odds that we could do that. We were able to with the sub-Q. If it feels like we’ve got a green light there, we would probably choose to go into phase 3, yeah.

Silviu Itescu: What would be the reasons why you couldn’t, though? I mean.

Ian Hirschfield, CEO, Viking: Yeah, you never know. I don’t know. I don’t know.

Silviu Itescu: Always managing expectations.

Ian Hirschfield, CEO, Viking: You never know what FDA will focus on when you submit a package to them. It’s hard to predict.

Silviu Itescu: As you think about the discontinuation rate in this study, it was another point of emphasis for a lot of investors. I guess for posterity, we could talk about why. I’m also interested in if this is a dynamic that’s concerning for all obesity studies going forward. As you think about phase 3, how do you control for preventing that in a much longer study?

Ian Hirschfield, CEO, Viking: Yeah, it’s a huge concern. You know, if someone is randomized to placebo and they’re not losing weight and they’re not feeling any of the hallmark side effects that they might expect from a GLP-1-based therapy, how do you keep them in? There’s no great answer for that. The most effective that we found in discussions with our CRO and our sites is to guarantee that the placebos can transition to active doses when they complete the study, but only when they complete the study. We give them coaching. We give them a lot of access to the investigators. That’s helpful for some people, knowing that they’re going to see a health care professional regularly. I’d say that ability to definitely receive drug in the extension period is the number one driver for keeping people in.

Silviu Itescu: That’s consistent. We hosted a panel, a KOL panel yesterday on obesity. It’s entirely consistent with what those experts said as well. They also emphasized just patient selection being so important. You want to figure out which patients are seemingly inclined to leave the study after two weeks if they don’t lose weight and screen them out. Is that doable? I mean, when you test it.

Ian Hirschfield, CEO, Viking: It’s probably easier said than done. We do want to make sure that someone doesn’t lose 10 pounds and then feel like they’re good and they want to get off the study. We do ask, if you lose weight in this range, is that enough or too much? How do you feel about that? Would you be satisfied there? Depending on some of those answers, you can help select people that would be more inclined to stay in.

Silviu Itescu: I guess those wouldn’t be like an inclusion or exclusion criteria.

Ian Hirschfield, CEO, Viking: No.

Silviu Itescu: How they respond to that. I guess you leave it up to the investigators, and you coach them on just sort of be judicious in general.

Ian Hirschfield, CEO, Viking: Yeah, you let them use some discretion, yeah. Because nobody wants to, I mean, the investigators, the company, it’s not really good for the subjects either just to come in for six months or whatever and then drop out. No one really gains anything from that.

Silviu Itescu: OK. The discontinuations, if not for AEs, what were the other reasons for some of the discontinuations?

Ian Hirschfield, CEO, Viking: Yeah, AEs were the number one reason. Nausea was the number one of the AEs. There were withdrawal of consents and loss to follow-ups. I guess those were the two other buckets, but they were smaller. Probably just based on the comments we heard, probably due to fatigue with the tablet size, fatigue with the weekly visits, tablet count. Those played more of a role than we would have expected.

Silviu Itescu: What tablet sizes do you have now and going forward? What’s that tablet count going to be in phase 3? Can it be modified at this point?

Ian Hirschfield, CEO, Viking: Yeah, we can modify it. That’s kind of a live exercise right now. We didn’t think that that would be a big deal, and it really isn’t. We took five tablets in the phase one and the 100-mg dose because they were 20s. The phase two used 30s, and they were a little larger. I think that combination of four over a longer period of time, you know, combined negatively in the longer study. You didn’t notice it in the shorter study because it was just such a rapid study.

Silviu Itescu: How big physically is the actual 30-mg tablet?

Ian Hirschfield, CEO, Viking: It doesn’t look that big. Smaller than a multivitamin, for sure. It’s not an abnormal size by any means.

Silviu Itescu: OK. Now that you’ve had time to reflect, I guess you’re waiting for the full data. As you think about the maintenance study that you’re also conducting, that’ll include both sub-Q and oral maintenance regimens. What are you thinking about in terms of things you want to test in the oral maintenance setting in that study at this point?

Ian Hirschfield, CEO, Viking: Yeah, we’ll look at two lower dose oral arms. Then we’ll look at a higher dose, those daily, and then a higher dose on a weekly basis. Higher dose, I think, is a little bit of a stretch. The weekly is a little bit of a stretch, but interesting to see if that works. Otherwise, you know, the two low doses will be really interesting to see. Everybody will titrate up to some high weekly dose and then transition either to a monthly dose, a range of monthly doses, or transition to an oral dose either on a daily or a weekly basis.

Silviu Itescu: I’m going to come back to the oral, but I want to make sure we cover the phase 3 subcutaneous study, obviously. Just indicators of demand, interest, enrollment, current state of affairs there. How’s everything going?

Ian Hirschfield, CEO, Viking: In the phase 3?

Silviu Itescu: In the phase 3.

Ian Hirschfield, CEO, Viking: Yeah, it’s going well. A huge amount of interest. We had an investigators meeting right around the time we announced the study, more well attended than we had planned for, really high level of enthusiasm. Even with the number of phase 3 trials and, you know, clinical research that’s occurring, really high level of engagement and interest across both sites and patients.

Silviu Itescu: You mentioned earlier, you’re a small lean company, right? You’re running these big 5,000 patient obesity studies. One of the questions we get is just, how can Viking manage the scale and scope of this? As you think about building out the organization to launch an obesity drug, I know you’ve talked about, you know, Viking is not going to be the company that executes a global launch into a multi-million patient obesity market. Just help frame Viking as a company. How is this going to evolve over the next couple of years as this phase 3 is executing? Do you need to do any hiring to support that study, whether it’s just monitoring or making sure data integrity is there? If you could just lay out.

Ian Hirschfield, CEO, Viking: Yeah, big focus. I mean, it’s a pain. I mean, everybody’s stretched pretty thin. We’ve nearly doubled, maybe we have doubled in size over the past year. We’re at 50, 51 right now, and still pretty lean for having two phase 3s ongoing. We will be growing substantially now over the next, call it, 18 to 24 months. How do you commercialize? We’ve got a pretty live, robust exercise ongoing now on the best strategy with a small company. How can you effectively compete? One thing that everybody’s kind of learning as the obesity space evolves, you probably don’t need 2,000 sales reps here. We’ve seen that from the compounders being so successful with no sales force whatsoever. You can probably get by with some blend of a smaller sales force and a substantial online presence with a kind of direct-to-patient portal.

I think you can really realize a meaningful share of the market for a company like us.

Silviu Itescu: That growth that you mentioned, the recent doubling in the last year and then the growth you expect, is that mostly like in clinical operations? Or where are you focused?

Ian Hirschfield, CEO, Viking: You know, it’s across the board. Yeah, we added a lot in operations. One place that I didn’t have a good appreciation for was in the quality. We’ve had a ton of quality engineer-type positions, quality control, and we’re continuing to hire there. An area that I just didn’t appreciate as much, and I really do now.

Silviu Itescu: For folks that are sort of following at arm’s length or newer to the story, I think as one of the leaders in this space or emerging players in this space, where do you think you have the sub-Q and the oral? You’re kind of tackling both. What’s your perspective on where the unmet needs are? Where do you think there’s opportunity in this market, high-level view of the obesity space?

Ian Hirschfield, CEO, Viking: I think the big market is the maintenance market. If we can get people to maintain their weight loss through continued use of the drugs, that’s when the long-term benefits really materialize. We’ve heard that from the payer discussions that we’ve had to date, you need to keep people on the therapy. That’s why we think for us, having a monthly formulation possible, having a low-dose oral possible, and having it be the same molecule is really a differentiator for us. It gives people, both the patient and the clinician, we think some level of comfort that transitioning to this different, either it’s a tablet or a less frequent injection, you’re probably not going to see some new side effect or see any difference in the way you feel or function.

Silviu Itescu: Just going back to what you mentioned about the compounding market, do you think there’s a role by the time VK2735 gets to market? I think we can all assume the phase 3 is going to work. People are going to lose weight here. I think we know enough about the mechanism and the molecule. Do you think a cash pay model is here to stay? Is that something that you’d be interested in thinking about?

Ian Hirschfield, CEO, Viking: Yeah, I think it is here to stay. I think there’s such high

Prakhara Gurwal, Biotech Analyst, Cantor: The level of interest in weight loss in general, I think it’s here to stay. What is the size? I don’t know. I think no one has a good concept of what the size of the market on any sliver is right now because everything is just expanding so rapidly. It’s a very large market, the cash market.

Dan Passeri, Chief Executive Officer, Cue Biopharma: The range you mentioned for the oral, 20 to 80 milligrams, I think some are skeptical that 80 milligrams is viable from a margin standpoint, but maybe just lay out where things are today, where you think they’re headed. At 80 milligrams, is that a situation where you’d look to down-titrate essentially to some lower maintenance dose?

Prakhara Gurwal, Biotech Analyst, Cantor: Yeah, that’s where you would see the best use of those higher doses. You maybe titrate up to some high dose, keep people there for a month, just like we did with this most recent study, and then bring them down to a maintenance dose. When we did that with the 90, we brought people up to 90 and held them there for four weeks. They lost about 8% in, like, seven weeks total. Yeah, six weeks total, they lost 8%. Then they came back down to 30 and lost another 1.2% or so. That tells you, you don’t need to sustain people at those really high dose levels. You can put them there for maybe just a little bit, bring them back down. I think for maintenance, we saw continued weight loss after that transition. For maintenance, you can probably go below 30 and have a really effective agent.

Dan Passeri, Chief Executive Officer, Cue Biopharma: In the maintenance study, do you have a sense of when you’ll be able to get data from that study? What would be the mode with which you’d bring that to our attention and present?

Prakhara Gurwal, Biotech Analyst, Cantor: Yeah, we’ll hope to start it late this quarter or maybe in October, but near term. It’s hard to predict the timing, but I’d say probably mid next year would be the rough estimate of when we would see something from that study.

Dan Passeri, Chief Executive Officer, Cue Biopharma: Okay. Lost in all this excitement about the oral recently is the fact that you’ve, you also are developing the amylin analogs and you’ve presented some preclinical data there. What’s the path forward for the amylin?

Prakhara Gurwal, Biotech Analyst, Cantor: Moving forward, we have a pre-IND meeting scheduled for the fourth quarter, and then, coming out of that, we’d file an IND and move forward. That looks like a really interesting compound and seems to be amenable to co-formulation with the VK2735 compound. If that works out, that would be a really nice agent.

Dan Passeri, Chief Executive Officer, Cue Biopharma: Have you tested that co-formulation in primates or in the DIO mice?

Prakhara Gurwal, Biotech Analyst, Cantor: We haven’t said a lot about that yet.

Dan Passeri, Chief Executive Officer, Cue Biopharma: Okay. Would that be conceptually how you think about developing that as, like, your own CAGRISEM?

Prakhara Gurwal, Biotech Analyst, Cantor: Yeah, I mean, historically that’s where we thought the biggest value was if you can add it on to a dual agonist, you know, when you add the amylin analog onto semaglutide, you see a really nice bump in efficacy. If you add it onto dual, you should see a similar bump in efficacy. We have seen that in some of the early primate work we’ve done. We often thought about that typically early on, we thought about it as a combo, but now you can think of amylin analog maybe as a good standalone for someone who’s maybe got a BMI of 32, 34, or doesn’t need the degree of weight loss that a GLP-1 based agent would provide, or maybe someone who can’t tolerate a GLP-1, an amylin analog would be a nice option for them. There are, we think, meaningful channels for an amylin analog monotherapy.

I guess our bias always originally was to have it in a combo.

Dan Passeri, Chief Executive Officer, Cue Biopharma: What is your perspective just on the strategic interest and, you know, those conversations happening in this space? How is it today versus a month ago versus six months ago?

Prakhara Gurwal, Biotech Analyst, Cantor: You know, it seems pretty constant. I would say today versus 12 months ago, there’s probably a higher degree of interest across the industry in participating in some way in obesity. There’s a high degree of indecision, I guess, in what’s the best way to approach. Do you use a brand new mechanism? Do you look at a proven mechanism, that’s sort of a second generation compound? Do you focus on, you know, muscle or, you know, these other sub-elements of the market? It’s hard to know where each individual company’s kind of focused, but definitely the interest has been a constant in the background.

Dan Passeri, Chief Executive Officer, Cue Biopharma: Okay. I’m assuming you saw this letter of intent in MASH, the LOI that the FDA has accepted. They’re now starting the process. I think the way that the Director of the Division put it is, it’s the long-awaited first step, or key step in a process towards maybe implementing some non-invasive tests as surrogate endpoints, pivotal surrogate endpoints for accelerated approval in MASH. I think the last time I talked to you a couple of months ago, I asked you, is there anything to do with 2809 in MASH? You said, you know, we would just not contemplate a MASH-based study unless non-invasive tests were available. My understanding is this may take years even for validation of that to play out. It’s uncertain if it would be accepted by the FDA ultimately. When you see that, what do you think?

Is that something that makes you kick the tires on thinking about a phase two combo with 2735, or how’d you read that?

Prakhara Gurwal, Biotech Analyst, Cantor: Yeah, I guess, you know, the letter of intent is generally accompanied by or followed quickly by a sort of a qualification plan. There wasn’t one submitted that we’re aware of. What is that qualification plan? What’s the agreement on it? Almost certainly, it would be a biopsy comparison study or something like that, which is not a fast study. You’re right. It’s a positive step in the direction of moving away from the biopsy, but I think everybody, including the FDA, has always wanted to move away from the biopsy, but there’s never been an accepted surrogate. You know, in 2020, I think there was a letter of intent accepted for a panel of blood markers for NASH. At that time, the FDA recommended for a qualification plan, a biopsy study to benchmark against the markers.

We know last year, about 10 months ago, we got a letter from the FDA that basically said there is no non-invasive test that’s an acceptable surrogate for a biopsy. Great, everybody’s aware that you got to replace a biopsy at some point, but I think the letter last week is a long way from saying biopsies are going away.

Dan Passeri, Chief Executive Officer, Cue Biopharma: Could you, in anticipation though, of maybe something happening years down the road, run a phase two study, no biopsy, not even a baseline, you just enroll MASLD patients, let’s say, a combination of the two agents, THR-beta and GLP-GIP, with FibroScan as the primary endpoint, anticipating that maybe something could culminate and at least to generate strategic value or whatever you could show that the combination of your two agents is.

Prakhara Gurwal, Biotech Analyst, Cantor: Yeah, the combination, I think, is really interesting, and it does show some benefit in animal studies. We could do that. I guess it’s the, does presumed NASH really encompass real NASH? What we found is when we were screening for the VOIAD study, everybody had presumed NASH and the screen failure rate was 90%. The presumed NASH bucket is a lot bigger than the real NASH bucket. I don’t know, you got to figure out how to filter them better, but that’s a good idea. It’s not something that’s going to be a near-term exercise for us.

Dan Passeri, Chief Executive Officer, Cue Biopharma: Very well.

Prakhara Gurwal, Biotech Analyst, Cantor: I will say there is an uptick in interest in that program externally. I think that’s a good sign for us.

Dan Passeri, Chief Executive Officer, Cue Biopharma: Okay, great. I appreciate the insights there. Nonetheless, notwithstanding that idea, obviously, exciting times ahead for the obesity programs, and we’re looking forward to following the progress as you advance the phase threes and as you update us on the plans for the oral. Thanks so much for joining us at the Cantor Global Healthcare Conference this year, and thanks to everyone in the room and on the webcast for listening.

Prakhara Gurwal, Biotech Analyst, Cantor: Thanks.

Dan Passeri, Chief Executive Officer, Cue Biopharma: Thank you.

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