Thanks, and good morning, everyone. Welcome back to another session here on the first day of our 34th Annual Oppenheimer Life Sciences Conference. We're delighted to have with us as our next presenting company Cue Biopharma. Cue is a company that we cover in our universe, with an Outperform rating, and we're excited about the company's approach to tumor biology T-cell biology using its novel platform for the treatment of cancer could be quite broad in scope. With the company, we have the CEO, Dan Passeri, and we may have a few minutes at the end for questions, so please submit those through the Q&A function on Zoom. And with that, I'll hand it over to Dan.
Okay, thank you very much. Good morning, everyone. First, I want to thank Oppenheimer for giving us the opportunity to present. And as a reminder, we are a NASDAQ-listed company with the symbol CUE. This presentation may contain some forward-looking statements. Okay, to start off with, our vision is, in essence, translating nature's cues into breakthrough immunotherapies. And when we describe nature's cues, we're describing the interactions. Basically, that the body uses to control and direct T-cells. Nature has already perfected protein engineering. And the design of these regulatory signals basically gives us an excellent starting point to emulate, from a protein engineering blueprint perspective. By deciphering these cues, our signals, we've basically created a highly T-cell engager platform for T-cell therapy by taking advantage of nature's built-in selectivity and specificity.
These T-cell engagers will only modulate the targeted and specific disease-relevant T-cells while sparing the patient from the significant adverse events associated with broad immune modulation. Turning to the next slide. The key message here is that immune balance in our immune system is essential for maintaining human health. As we all know, cancer and autoimmune disease are two major causes of human suffering and mortality, with very high numbers of patients suffering from debilitating and pressing unmet medical need. Susceptibility to cancer is likely due to inadequate immune activity against aberrant cancer cells, and inversely, too much immune activity against self-tissue induces autoimmunity. The key point there is the immune system is key to maintaining control in both of those disease settings. Through Cue Biopharma's approach of emulating nature's cues, we've T-cell engager therapeutics.
To selectively modulate disease-relevant T-cells, effectively preventing indiscriminate widespread T-cell activation or inactivation of vast non-targeted T-cell populations contained within the patient's body, thereby sparing the patient from the deleterious side effects of broad carpet bombing of the immune system or widespread immunosuppression. In essence, we believe we've achieved the desired effect of T-cell modulation without compromising patient safety. Importantly, immunotherapy promises to dramatically change and advance the practice of medicine in treating cancer and autoimmune disease, and we believe we've developed a breakthrough approach to help that, that promise become a reality. The next slide. Recognizing that T-cells as the heavy artillery of the human immune system. They're regulated with a highly selective command and control instruction process via the antigen-presenting cell T-cell interaction. We have endeavored to emulate this command and control system through the Immuno-STAT platform.
Based upon this interaction, in essence, specificity is achieved through the T-cell, T-cell receptor binding to a targeted epitope from an antigen from a cancer antigen, antigen in the case of cancer, along with a co-stimulatory signal such as IL-2. The 2 cues are signals when engaged concurrently, as in the case with our Immuno-STATs, are able to dial in or dial out. For instance, if we had a PD-L1 signal rather than IL-2, selective T-cell activity with disease antigens for both cancer and autoimmune disease. That is, we can either activate or suppress. I'm gonna first focus on oncology applications where we're dialing inactivity. Then I'll switch to autoimmunity. First, let's go to oncology. Okay, next slide. This is the CUE-100 series which is an oncology focus based upon IL-2 being the co-stimulatory moiety.
It's our belief that we have not only established foundational support to have T-cell engager, solving the major challenge of how to therapeutically deploy IL-2 in a tolerable manner, but also have a best-in-class approach. It's important to recognize that our clinical data supports the premise that we've generated a therapeutic index for IL-2. That is, we've shown a range of doses demonstrating clinical activity with a favorable safety profile. We've demonstrated clinical validation and proof of concept in over 100 patients treated as monotherapy and in combination with checkpoint inhibitor. We have a favorable tolerability profile, no capillary leak syndrome observed, no clinically significant cytokine release syndrome, and this is based on a once-every-three-week dosing schedule. And we've actually treated patients up to 24 months, so I'll go to that in a moment.
We have strong metrics of manufacturability. The drug basically has antibody-based modular design expression, CMC, and cost of goods, highly stable. We've had stability greater than 36 months. And the platform's flexibility provides us with significant regulatory advantages, which I will touch upon momentarily. So from next slide, from the structural design of this IL-2 based 100 series, the molecule enables modularity of the various components. Key features the ability to readily swap out the targeting epitope, as represented by the colored circles you see here in the molecule. And thereby enabling the ability to readily generate a spectrum of therapeutic molecules targeting a broad range of cancers. Our 1st two drugs exemplify the platform's modular nature. And the resulting efficiencies. For example, due to the analog nature.
Of the molecular scaffold, we were able to utilize the data obtained in the clinical trial for 101 as a surrogate for the IND filing of 102, where the FDA basically accepted the safety and tolerability profile of the 101 clinical data. Basically as a model for 102, resulting in our ability to proceed into the clinic with no preclinical tox studies for 102 and our ability to start at a starting dose of 1 mcg per kg, which is biologically active. In essence, this saved us up to a year of time and cost. Okay, on the next slide here, on slide nine, beginning with our 1st drug candidate in clinical development, which is 101. It's representative and exemplary of our approach to selective activation of cancer-specific T-cells. I'll provide an overview of our development strategy in HPV positive head and neck cancer.
And then touch upon sort of broad reaching implications for moving forward. Further upstream into the adjuvant setting, representing the broadest patient population, which is prior to the onset of refractory metastatic disease. We first went into the second line setting, which includes third line, fourth line, beyond. Patients, where their cancers become hot even more unstable. Life expectancy typically continues to diminish with each next line of therapy. We've recently had an end of phase I meeting with the FDA. On the second line to review the data and discuss potential paths forward. We had a very productive meeting with the FDA, where we arrived at alignment in the next steps for a possible registration path for CUE-101 monotherapy, as well as combination. So the data generated in the second line has not only provided a registration path forward.
In this advanced setting, but has also allowed us to demonstrate clear evidence of single agent activity, underscoring and supporting the mechanistic alignment and benefits of combining this drug, as well as other drugs in the platform with checkpoint blockades. Where checkpoint inhibitors in the front line setting, where we have standard of care, thereby providing a much broader patient population. We also believe that recent scientific published data has implicated IL-2 in the generation of T-cells with superior effector phenotypes, including stemness-like properties, that is, like memory. These attributes could further enhance the biologic clinical properties of the 100 series, thereby allowing us to move into the adjuvant setting, representing kind of the optimal patient population from a perspective of patient reach. Alright, next slide. Okay, so I'm gonna review the data on the single agent monotherapy.
This is our most recent survival data in the monotherapy trial. We're extremely pleased to see such significant benefit in survival, which is the gold standard metric for cancer therapy. The survival curve shown on the left demonstrates a median overall survival of almost 21 months in 20 patients treated at the recommended phase II dose of 4 mg/kg. As shown on the right, the observed median overall survival of almost 21 months in patients treated in the second line setting is beyond is highly notable when compared to the historic median overall survival of approximately eight months observed in patients treated in the second line from a CheckMate 141 and KEYNOTE trial reported with nivo and pembro, respectively. We believe a significant enhancement of survival is reflective of selective modulation of cancer-specific T-cells by 101.
Which is evidenced in the next slide. So, as shown here in the panel on the left, we observed robust expansion of tumor-specific HPV E7 specific T-cells in the peripheral blood of patients treated with 101. And in the right, you can see pre- and post-treatment paired patient biopsies. Where we show clear signs of tumor-infiltrating T-cells. And as clearly demonstrated here in this biopsy staining, treatment with 101 resulted in a significant increase in the activated Granzyme B-positive cytolytic killer T-cells infiltrating the tumor. And that's indicated by the yellow and orange staining in the section on the right. Okay, the next slide. We have a waterfall in our combination with Keytruda. We report the updated data from our front-line combination. And in this front-line population, Keytruda as a monotherapy standard of care for patients with.
Tumors that are overexpressing or expressing PD-L1 has a historic overall response rate of 19% in this patient population. Where here we've observed, and this is in our updated data, of 25 patients, we've observed an overall response rate of 46%. As shown on the waterfall plot on the right, we've observed significant durable tumor reductions across many patients, including confirmed partial responses in 10 patients and a confirmed complete response. Importantly, 11 patients remain on treatment, including three with durable stable disease demonstrating reductions in target lesions. To note if these patients continue demonstrating further tumor reductions in subsequent scans, we may have an overall response rate approximating 50%. Notably for patients with CPS scores that are low, that is between one and 19, we have an overall response rate of 50%.
In the combo study, which represents a greater than tripling of the historic response in these patients, which is about 15% with Pembro alone. Okay, so I'm now gonna turn to the progression-free survival that we've seen. And, as a reminder, the median progression-free survival denotes the timeframe in which patients remain on drug until observation of tumor growth beyond 20%. Of note, the median progression-free survival from this study is still maturing and is currently at 8.3 months, which compares quite favorably to the historic median progression-free survival of 3.2 months observed with Pembro monotherapy in the KEYNOTE-048 trial. This is likely due to the complementary nature of the mechanism of action, where we're enhancing the patient's endogenous anti-tumor T-cell population, which is required for a checkpoint to have a therapeutic effect. The next slide. This is a comparative study.
This is showing the response rates of checkpoints in a number of cancers where they've been approved. Those are the yellow circles and where they haven't been approved to date, which is in the red circles. And this is actually showing the ability of 101 to selectively activate and amplify targeted tumor and tumor-specific T-cells in the patient's body, complementing the mechanism of checkpoint where we've enhanced the overall response from 19% to 46% in head and neck cancer. 101 also has potential application in HPV driven cervical cancer, anal cancer and penile cancer as well. It's important to note that, well, checkpoint inhibitors certainly have had a highly positive impact on changing therapeutic options for patients, particularly pertaining to quality of life on therapy. That is a better tolerability profile than classic cytotoxics. There still remains a pressing and substantial need for improving patient outcomes.
In that line, we're, we're now expanding our efforts into those cancers on the right that have historically not been responsive to checkpoint inhibitors. Despite widespread efforts, and this is shown on the right where you have the bracket for 102. We're presently surveying those cancers, which I'll now get into. The 102 data and update. Okay, next, slide. As a reminder, 102 has a 99% sequence similarity to 101. This similarity allowed us to gain alignment with the FDA to utilize the 101 safety data. To gain acceptance for moving forward with our IND. Again, just to remind you, without any additional IND enabling talks. We got to start the trial at 1 mg per kg. Next slide. This slide exemplifies a significant unmet need in vast numbers of patients across WT1 positive cancers and shown on the left of the four indications currently being prioritized.
And pursued in our ongoing 102 trial. Note that these numbers represent a collective population of greater than 200,000 patients with refractory and metastatic disease and significant need of therapeutic alternatives. Okay, shown on this next slide, this is emerging PD data from the blood samples of patients treated with CUE-101 in our ongoing phase I trial, and as you can see here. And consistent with our preclinical data sets, we see selective and very robust expansion of WT1-specific T-cells being amplified here, pretreated on the left and then post-treated. Expansion of these tumor-specific T-cells is expected to enhance anti-tumor immunity with the potential to drive tumor reductions. And that we can see here on slide 19, where these reductions in the tumor burden have been observed in patients treated in dose escalation portion of the study.
On the left is a patient with gastric cancer that progressed on three prior lines of therapy, including a checkpoint inhibitor. They have experienced a decrease in the sum of three target lesions of -34 at week 36 and continues on treatment. I just want to caution everyone, this is not an unconfirmed PR because the patient concurrently also had a new lesion, I believe, in her lymph node. But because of the patient's health condition improving, the physician is keeping them on drug. So we'll give you updates as that emerges. Another example is observed at 2 mcg per kg in dose escalation, and that's in an ovarian cancer patient on the right. In addition, we've also observed disease control in some patients with pancreatic cancer, including a pancreatic cancer with durable stable disease that remains on treatment for greater than 6 months.
Given this encouraging sign of clinical activity across all four indications, investigators have expressed enthusiasm about the prospects of expanding patient enrollment in all four tumor types. Okay, so on slide 20, the key take home messages here. We've demonstrated clear signs of clinical efficacy through selective targeting of IL-2 to tumor-specific T-cells, achieving significantly greater efficacy without compromising patient safety. This is a very important accomplishment. We've defined a registration path, clear alignment on next steps, for our FDA interaction. Platform has been de-risked, in essence, with the data we've generated from 101, 102, which lends itself to the 100 series. And through this platform modularity, we basically have significant market expansion opportunities and cost efficiencies. All of this bodes well for strategic positioning and partnering opportunities across multiple assets. I'm now gonna provide you an overview of our autoimmune platform on slide 22.
Changing gears, we move on and discuss applications for autoimmune and inflammatory diseases. This is particularly important and timely since the current approaches mostly encompassed in this set of indications basically deploy broad immune suppression, resulting in limited efficacy and durability and safety considerations. And it's really not amenable to early disease interception and immune reset, which we believe our key competitive advantage. We believe the Immuno-STAT platform offers very attractive opportunities for resetting immune balance which has potential for enhanced efficacy and potentially curative outcomes. So I'm now gonna move to our first program, which is CUE-301. This is where the antigens are the epitopes for the autoimmune disease. That is the self antigens are well known and characterized. In this case, it's type 1 diabetes. What this is in essence an Immuno-STAT just like the 100 series, except it's a class 2 Immuno-STAT.
We have, rather than IL-2, we have an off switch PD-L1. What you see on the right is, in essence, the control is the circle with that line going across straight across, there's no change. Here what you're seeing is interferon gamma expressing T-cells with the CUE-301 series with no off switch. And it's actually having an effect that dampening the autoreactive T-cells, and then with the off switch, we see a profound shift in terms of dose escalation. This has potential application in a number of autoreactive diseases, where the antigens are well known, such as type 1 diabetes, celiac, rheumatoid arthritis, MS, etc. So now switching to a very important program. This is designed for selective Treg induction and expansion for the CUE-401 mechanism of action can be broadly developed for many autoimmune diseases. This has very significant potential.
Treating autoimmune disease where the antigens are not well known or characterized. In essence, we've deployed our protein engineering expertise for selective induction and expansion of regulatory T-cells known as T regs. 401 is key to two key signals, IL-2 and TGF-beta for the induction of these T regs. To note that the IL-2 variant is the same as the one used in the 100 series. This program is currently partnered with Ono Pharmaceutical. It's actually been an extremely productive partnership. They're funding our ongoing research activities, and importantly, we've retained a 50% co-development and co-commercialization in the U.S. In essence, this next slide just shows schematically IL-2 muteins used with CD25, biased IL-2 muteins. Can stimulate existing natural T regs. The issue here is it's often not enough. It gives you a minor increase in that T-cell population.
The advantage of 401 is IL-2 and TGF-beta concurrently. It can not only expand naturally occurring Tregs, but induce new Tregs with a much broader proliferation and suppression of autoreactive T-cells. That's evidenced in this next slide where we're harnessing multiple signals to induce these Tregs. You can see on the control, IL-2 alone, TGF-beta alone, and 401, a massive increase in Tregs. So here we're looking at a disease model of autoimmune gastritis. You can see on the left healthy control, the gastric tissue columnar cells grossly inflamed in the control group with a high gastritis score, as you can see in the plot on the right. After two doses of our drug, long-term protection from gastritis and tissue destruction. So it looks very attractive.
So this is a very important program, and we look forward to giving you updates as they become available. So in closing, we are very well positioned for near-term value inflection. We have multiple milestones in the year ahead. We've met with the FDA. We have a registration defined for monotherapy. Also giving us insight on the registration paths available. For the combination with Pembro and expansion into the adjuvant setting, which I described. 102 monotherapy, the data looks just as we had expected. Very encouraging early data. We look forward to providing updates there. 401, mid-year update, second half, co-development option decision. And importantly, we have basically the platform very well primed for multiple opportunities for strategic partnering. So in closing, the company is extremely well positioned with clinical proof of concept data with our two lead programs, basically de-risking the platform. We have data sets generated.
That have the potential to basically shift the treatment paradigm in oncology. We've clearly demonstrated a profound enhancement of overall survival as a monotherapy. It's clear signs of anti-tumor activity, and then in the combination, as we expected, the complementary mechanism of action with checkpoints positions us extremely well for multiple partnering opportunities. We're in deep discussions with parties right now, and the key is we're trying to assess what is the best strategic alignment for us to optimize shareholder value on a going forward basis. I want to thank everyone for listening, and we look forward to providing you with further updates in the future.
Great, thanks very much, Dan. That was terrific. I think we have time maybe for just one question here. Which is, so you got clarity from the FDA on the monotherapy in terms of the combo. It sounds like we might get that later this year, just wondering how that may impact your thought process with respect to partnering the lead program, you know, 101 and whether that may facilitate, you know, such a deal.
S ure, it's actually a really important question, and that's exactly how we look at it. The guidance we've received from the FDA is how it's very encouraging. It was a very supportive discussion. We have a defined path now from monotherapy. And I would say that insight gives us a defined path on the combination as well. The implications of that from a partnering standpoint is it's basically de-risk the program. We have had those interactions with the FDA, this clear guidance, and as I stated, the really attractive feature of our approach.
It's that we've demonstrated single agent activity in the second line and beyond setting. We moved upstream into the combination where it's a broader patient population. The results we're seeing are very significant. And this has the prospect of moving even further up now into the adjuvant setting, which is the, you know, the broadest patient reach one can achieve. So all of this bodes very well for the ongoing discussions we have with pharma, and I think it creates our strategic flexibility for us. So I think that's correct. It gives us good leverage and gives us sort of a better negotiation standing point from a perspective of de-risking the asset with clarity of paths, and I would the path, or I would say paths, plural forward for registration, and this bodes well for the whole platform. It's not just 101.
Great, we look forward to that additional clarity and also I think to further data updates as we get through the year. So thanks. Thanks again, Dan, and thanks everybody for joining the session.
Great, thank you very much, and thank you everyone for listening in. Take care.