Cue Biopharma, Inc.

Greetings, and welcome to the QBioPharma fourth quarter and full year 2022 earnings call. At this time, all participants are in a listen-only mode. A question and answer session will follow the formal presentation. If anyone were to require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. I would now like to turn the conference over to your host, Mr. Dan Passeri, Chief Executive Officer. Please go ahead.

Yeah, thank you, and good afternoon, everyone. As a reminder, this conference will be recorded and available on our website for the next 30 days. Also, as a reminder, those listening in, just be aware of the webcast. You need to advance the slides as you are listening, and we'll notify you which slide we're on at a given time. Joining me on today's call is Dr. Matteo Levesetti, our Chief Medical Officer, Dr. Ken Pienta, now in the role as Clinical Advisory Cue, Dr. Anish Suri, our President and Chief Scientific Officer, and Kerry Millar, our Chief Financial Officer. Also joining us briefly on today's call is Dr. Sarah Pei, Surgical Oncologist and Director of Translational Head and Neck Cancer Research at the Mass General Hospital. She's an investigator on our ongoing trial with Q101. We'll provide a brief perspective of clinical observations to date. In addition to Dr. Pienta, Dr. Pei has also recently become a clinical advisor to QBioPharma, helping to define our clinical strategies going forward. As shown here on slide two, this presentation and overview may contain some forward-looking statements, and any forward-looking statements made during this call represents the company's views as of today, March 21st, 2023. On the next slide, please, you'll see our agenda. for today's call. I just want to please note that on this slide, under the financial results, that's meant to read fourth quarter 2022, not third quarter. Apologies for that. We just noticed that before the call. Okay, I'll begin by providing an overview and status update of our current corporate positioning, and we'll describe our competitive advantage, which we believe places us in a differentiated strategic position of strength and opportunity despite the present challenges of the capital markets. We're also well positioned with capital into the second half of 24, and importantly, our platform has generated numerous programs at various stages of development, representing multiple partnering opportunities. As a reminder, we recently entered into a strategic partnership with Ono Pharmaceuticals for the development of Q401, which is our buy-specific regulatory T cell inducer and activator for potentially addressing a broad spectrum of autoimmune diseases. Importantly, this transaction was structured to provide us with requisite capital through program funding, thereby subsidizing the ongoing research and development costs with Q retaining a 50% co-development option for the U.S. market. So this was obviously a very balanced transaction for the company. Q101's clinical data continues to support the clinical validation and the corresponding reduction of risk for the entire IL-2-based Q100 series and importantly appears to provide us with defined options for potential registration paths. Both Q101 and Q102 currently in clinical development address significant unmet medical need across multiple cancer indications. Based on the clinical data generated to date, we believe we're now well positioned with our oncology portfolio to seek partnerships and transactions similarly structured to the ONO partnership to ensure we retain involvement and upside, optimal upside potential while addressing capital access for building out our promising pipeline of potentially breakthrough therapeutics. As seen in the next slide, that's slide number four, we believe our corporate positioning and competitive advantage are firmly established on solid foundational data. And Q101, as an exemplary of the Q100 series, represents a potential therapeutic breakthrough. To date, Q101 has demonstrated, as you'll see on this slide, monotherapy activity in late stage cancer patients. What's important here is this is single agent activity in patients that basically are refractory to various chemotherapies, but also checkpoint inhibitors. To date, we're observing significant increase, that is at least a doubling of the overall response rate in combination with checkpoint inhibition compared with historic monotherapy with checkpoint inhibitors. Favorable tolerability, we've dosed greater than 70 patients to date with no evidence of vascular leak syndrome or cytokine release syndrome. Antibody-based design gives us favorable cost of goods for manufacturability, and actually the drug to date has demonstrated astonishingly stable characteristics where stability has gone out to greater than 36 months. Significant regulatory advantages, we have fast track designation and both mono as well as combination. And importantly the FDA authorized Q102 IND based on the safety data from Q101, basically viewing Q101 as an analog with no requirement for IND-enabling toxicology and approval to start the trial at a higher dose, saving significant time and cost. Matteo will elaborate upon these observations momentarily. We view the cumulative data as supportive of our central premise, namely that the Immunistat platform, and more specifically the IL-2-based Q100 series, represents a therapeutic breakthrough by harnessing nature's specificity. That's through targeting the T cell receptor, or TCR, enabling the targeted delivery of cytokines, such as IL-2, to disease-relevant T cells. We believe this approach enables the achievement of a therapeutic index for IL-2 and other cytokines by avoiding the deleterious side effects of non-selective indiscriminate activity, often seen with other modalities. As a reminder, our platform modularity allows us also to deploy other modulatory co-stimulators beyond IL-2 based on the same principle. I'm now going to turn the call over to Matteo, and then he'll be followed by Ken and Sarah to generally describe the emerging clinical observations from our ongoing Q101 and Q102 trials. Anish will then provide a brief summary for our autoimmune programs, emphasizing the recent developments, including the Q401 partnership with ONO. Mateo?

Thanks, Dan. The clinical data from the ongoing Q10101 trial continues to demonstrate robust metrics of clinical benefit for heavily pretreated recurrent metastatic HPV-positive head and neck squamous cell carcinoma patients treated with monotherapy and for newly diagnosed patients with recurrent metastatic HPV-positive head and neck cancer treated in combination with pembrolizumab. As shown on slide five, data from the ongoing clinical trials with Q101 as monotherapy and in combination with pembrolizumab have provided clinical proof of concept and de-risking of our Immunostat platform. The latest data generated to date in 2023 continues to support prior observations and further enhances our confidence in Q101 as a potential therapeutic for patients battling HPV-positive head and neck squamous cell carcinoma. As previously and consistently stated, we believe Q101's mechanism of action, as evidenced by the ongoing data generated to date, provides effective and tolerated dose levels, enabling selective expansion of targeted tumor-specific T cells directly in the patient's body. Recurrent metastatic HPV-positive head and neck cancer is a tough and curable disease. The data we have observed throughout the monotherapy trial bolsters our position and enhances our confidence that Q101 is in fact stimulating the targeted cancer-specific T cells within a subset of these patients, resulting in demonstrable anti-tumor effect. Furthermore, and importantly, we continue to observe an evolving pattern of enhanced survival in the monotherapy trial. We believe this enhanced survival is due to the persistent expansion of tumor-specific T cells given Q101's mechanism of action. As shown on slide six, Q101 demonstrates well-behaved pharmacokinetics with low interpatient variability at the recommended phase two dose of four milligrams per kilogram. The exposure pattern is consistent throughout multiple cycles of treatment without any attenuation of PK parameters, supporting the premise that there is no evidence of clinically relevant immunogenicity. Regarding its pharmacodynamic, or PD, profile, Q101 treatment also results in a consistently observed sustained increase in natural killer cells, or NK cells, a positive attribute associated with an antitumor response, as NK cells are known to assist in tumor killing. Importantly, we observed only a modest and transient increase in regulatory T cells. Regarding the intended PD effect, i.e., activation of targeted tumor-specific T cells, we have observed, as shown in the middle panel, robust expansion of tumor-specific E7-reactive T cells in the peripheral blood of patients as early as one week after administration of Q101. Paired and post-treatment biopsies demonstrate an increase in tumor-infiltrating T cells and associated tumor necrosis. In addition to the favorable PK and PD just described in patients with advanced HPV positive head and neck cancer are experiencing intriguing patterns of clinical benefit. Three examples are shown on slide seven. Patient A experienced a durable partial response with an approximate 60% reduction in tumor burden evident at six weeks after two cycles of Q101. This response lasted close to one year. This patient demonstrated a significant reduction in HPV cell-free DNA that coincided with the initiation of the partial response, and the HPV cell-free DNA was undetectable for most of the time on treatment. Patient B, who remains on treatment at the present time for approximately one and a half years, has had stable disease with tumor burden reduction of approximately 20% observed at week 48, and maintained to the present time at greater than 75 weeks. Notably, this patient has also had complete disappearance of HPV cell-free DNA in the blood since week six. The undetectable HPV cell-free DNA, which is an increasingly recognized biomarker of disease activity, is suggestive of a pathologic complete response, i.e. a potential cure in this patient. who we expect may have surgical resection of the lesion for histopathological analysis. Patient C has experienced tumor reduction after a prolonged period on drug where no resist-based subjective response was initially observed by imaging. In this patient treated with Q101 at 2 milligrams per kilogram, we can see that the first several months appear to demonstrate gradual tumor growth even beyond the 20% threshold used by resist criteria. However, Based upon the overall clinical status, the patient continued treatment. After approximately six months, the tumor began to shrink, and the patient remained on therapy for greater than 18 months after starting treatment with Q101. This observation, consistent with observations made by others, demonstrates that kinetics of T-cell antitumor activity may manifest over a long period of time. The next slide, slide eight, conveys our ongoing survival swimmer plot for the 20 patients dosed the recommended phase two dose of four milligrams per kilogram. The swimmer plot for the 20 patients dosed at the RP2D of four mgs per kg demonstrates a trend of increased survival of approximately 12 months median overall survival compared to the historic reported survival of approximately eight months observed in patients treated in the second line in the Keynote 40 trial of pembrolizumab. As any experienced oncologist understands, the survival with third-line treatment is expected to be less as the disease has further developed and become more unstable. Our evolving data continues to support the premise that treatment with Q101 stimulates the patient's immune system and results in what appears to be a meaningful increase in survival for patients with advanced recurrent metastatic HPV-positive head and neck cancer. This monotherapy data has encouraged our principal investigators and offers a potential path forward to a registrational trial. As showed on slide 9, Q101 and checkpoint inhibition have complementary mechanisms of action, and preclinical studies have demonstrated enhanced response and survival when both are given in combination. In this aggressive HPV-positive murine tumor model, shown in the right panel, the survival curves demonstrated survival of 90% for mice treated with combination of Q101 and anti-PD1, compared to 0% and 20% end-of-study survival for anti-PD1 and Q101 monotherapy, respectively. The demonstration of monotherapy activity in patients bolsters our belief that we should observe complementary mechanistic effects in combination with pembrolizumab. As a reminder, the data from patients treated in the Q101 monotherapy trial clearly supports that Q101 increases the number of tumor-specific T cells in the patient's body. In the combination study with pembrolizumab, it appears that these activated T cells have greater capacity to kill cancer cells when coupled with inhibition of the PD-1 pathway, a major mechanism used by cancer cells to prevent immune-mediated killing. As reported at CITC in November of last year, and as shown on the waterfall plot on slide 10, four of the first 10 available patients treated at the recommended phase two combination dose of Q101 at 4 milligrams per kilogram plus pembrolizumab have experienced partial responses, i.e., at least two consecutive scans demonstrating a cumulative reduction of tumor burden of minus 30 percent or greater. Notably, three of the four partial responses have been observed in tumors with low PD-L1 expression as evidenced by CPS scores of 20 or less. As has been indicated by other studies, tumors that had CPS scores greater than 20 have been more responsive to PD-1 blockade and exhibit higher objective response rates compared to tumors with CPS scores less than 20. The overall response rate of greater than 40% observed with Q101 in combination with pembrolizumab to date compares favorably to the historical objective response rate of 19% observed with pembrolizumab monotherapy in the Keynote 48 study. The follow-up data on these first 10 patients, as well as new emerging data on additional patients treated with combination therapy continues to strengthen, and we look forward to providing an update on the cumulative data at an upcoming oncology meeting. Key observations in patients treated with Q101 monotherapy in the third line and beyond include, as detailed on slide 11, demonstration of single-agent antitumor efficacy evidenced by resist-based partial response in durable, stable disease in third-line and beyond recurrent metastatic head and neck cancer patients, and immediate overall survival benefit emerging from survival follow-up in the RP2D cohort. As previously announced, the robust data on Q101's activity in monotherapy and in combination with pembrolizumab enabled the granting of fast-track designation for the treatment of patients in both the first and third line setting. The cumulative data from these ongoing trials with Q101 have provided us with clear evidence of targeted expansion of HBV-E7-specific T cells with antitumor activity as a single agent and as a complementary mechanism with checkpoint inhibition what we believe will broaden patient reach and enhance efficacy of checkpoint blockade therapy as such as such we believe q101 as our first biologic therapeutic from our q100 series represents a potential therapeutic breakthrough for patients and we look forward to providing you with updated additional data at an upcoming oncology conference furthermore We believe the data from Q101 has provided a de-risking and mechanistic validation for additional biologics from the Q100 series, beginning with Q102, as shown on slide 12. Regarding our progress update pertaining to Q102, which targets Wilms Tumor 1 positive tumors in a trial that is enrolling patients with advanced colorectal, gastric, pancreatic, and ovarian cancers, We anticipate completing the dose escalation portion of the trial by mid-year. The treatment has been well tolerated with no DLTs observed to date. We plan to present preliminary data from the dose escalation portion of this trial at an upcoming oncology conference. As a reminder, Q102 and Q101 share 99% amino acid sequence identity. This enabled us to significantly decrease the development time and cost of Q102 as we were not required by the FDA to repeat IND-enabling toxicology studies for Q102. And we were also able to initiate the phase one dose escalation study at one milligram per kilogram, a dose at which we observed clear signs of biologic activity with Q101. As slide 13 shows, we are conducting the Q102 dose escalation study in colon, gastric, pancreatic, and ovarian cancers. This design offers us the ability to perform monotherapy expansion studies in any or all of the indications being evaluated in the dose escalation phase of the trial. This trial is actively accruing and will be open at 15 sites throughout the United States. We plan to present additional data at an upcoming oncology conference and look forward to presenting the corresponding data. I will now turn the call over to Ken. Ken?

Thanks, Matteo. You know, the evolving and maturing data from these programs is so extremely gratifying for me to see. Early on as an advisor to Q, I recognized the potential promise of the platform for engineering biologics that could target cancer-specific T cells and could potentially deliver clinically meaningful levels of IL-2 to patients without the well-known toxicities associated with IL-2 that we all are aware of, such as vascular leak syndrome and cytokine release syndrome observed with aldisleukin. I subsequently took on the role of acting CMO to establish the initial clinical trials that would assess the behavior and therapeutic activity, and I am so proud to have shepherded 101 and 102 to those initial clinical trials. and very pleased to have handed the CMO role over to you, Matteo, as you've taken on the role to bring these maturing and promising programs forward. Now, once again, in the role of clinical advisor to the company, I look forward to continuing to help develop the Q101, 102, and future assets for the benefits of patients. At this time, I'd like to take this opportunity to introduce Sarah Pei, MD, PhD, who has served as our lead investigator for the Q101 program and has now joined me as a clinical advisor to the company. Dr. Pei is one of the world's foremost experts, not only in HPV-driven head and neck cancer, but all head and neck cancer, and has deep expertise as a surgeon, scientist, taking care of patients with this disease, as well as running a lab studying this disease, as well as the development of clinical trials for testing agents in the treatment of cancer. Sarah, welcome.

Thank you, Ken. Well, it's exciting for me personally to have helped design the original Q101 studies and to take part as an investigator on the trials. It is important to emphasize that recurrent and or metastatic HPV associated head and neck cancer patients need new and promising therapies that have anti-tumor activity while also maintaining a good quality of life without the debilitating side effects of cancer treatment. What we have consistently observed with Q101 is activity as a monotherapy and furthermore, what appears to be synergistic activity in combination with Keytruda, even in those patients with a low PD-L1 biomarker score, and these patients are often the most difficult to treat with immunotherapy. Therefore, Q101 is certainly hitting the mark by addressing this unmet clinical need. Importantly, we have observed that Q101 is well tolerated at clinically active doses, without many of the side effects associated with IL-2 when given systemically. This attribute of Q101 is key since it creates a therapeutic index for IL-2, which historically has been a significant challenge and has limited the assessment of the full potential of this important cytokine for effective cancer immunotherapy. To have some cancer patients on an immunotherapy agent for over a year with readily manageable side effects underscores the potential importance of Q101 or immunostats. This observation is highly relevant in the setting of an increasingly aging cancer patient population in which the median age is now 66. I'm really looking forward to seeing the continued results of the trials. I will now hand the call back to Ken.

Thanks, Sarah. And again, I want to thank you for your thoughtful offer to be available for, you know, a brief comment today and giving us your thoughts. We really appreciate your participation and benefit from your advice and guidance throughout this process. And, you know, we continue to want to do that as we march forward to help these patients afflicted with this alpha disease. We'll talk again soon. I'll now turn the call over to Anish, who will discuss some recent developments in the autoimmune applications of the Q platform, along with the collaboration with Ono Pharmaceuticals for the development of Q401. Anish?

Thanks, Ken, and welcome to all joining this call. Let me begin by providing a perspective on the significant opportunities for resetting immune balance or functional tolerance within the broad spectrum of autoimmune diseases with our platform assets. As shown here in slide 14, we have developed an overarching strategy for addressing autoimmune and inflammatory disorders by focusing on three key approaches. The first approach is the selective induction and expansion of regulatory T cells, which are the natural guardians for controlling pathogenic inflammatory immune responses. To that end, we have developed a unique bispecific biologic composed of an IL-2 variant and a variant of TGF-beta termed Q401. that has the potential to convert pathogenic T cells into regulatory T cells, as well as expand the naturally occurring regulatory T cells. We recently announced our collaboration with Ono Pharmaceuticals that supports the development of Q401 through defined milestones. The second approach is a selective dampening and control of autoreactive T cells via our Immunostat platform. This approach applies to those diseases with strong HLA association and known dominant driver autoantigens. We have previously shared the proof of concept data for this approach in type 1 diabetes via selective inhibition of insulin reactive T cells. And the third approach is the generation of bispecific molecules that incorporate the non-classical HLA-G molecule, which has been implicated in activation of tolerogenic dendritic cells, expansion of regulatory T cells, and suppression of autoreactive T cells. Incidentally, HLA-G is also recognized as an important checkpoint for cancer immunotherapy, wherein tumors upregulate HLA-G to escape immune detection. For the remainder of this section, I will focus and highlight the significant differentiation and competitive position of Q401 in the induction of regulatory T cells, representing a significant potential value driver. As shown in the next slide, Q401 is a highly differentiated approach from all other IL-2 mutines being pursued for expansion of regulatory T-cells. Q401 builds upon a wealth of knowledge gained within the immunology community over the past two decades, describing the fact that IL-2 and TGF-beta signals can convert peripheral CD4-positive T-cells into regulatory T-cells, also known as induced T-REX or IT-REX. Hence, in contrast to all other IL-2 mutine approaches that simply focus on the pre-existing small fraction of natural T-REX or N-T-REX, Q401 generates new populations of induced Tregs and can also expand the preexisting natural Tregs. Importantly, and as we have demonstrated, Q401 can convert pathogenic autoreactive T cells into regulatory T cells, hence providing a very attractive opportunity to reset immune tolerance. This significant differentiation is highlighted in the table shown at the bottom of the slide comparing Q401 to other CD25-biased IL-2 mutine approaches. An example of Q401 activity is shown on the next slide, slide 16. In this in vitro assay, CD4-positive T cells from patients suffering from inflammatory bowel disease or rheumatoid arthritis were treated with Q401 and then followed for the induction of FOXP3 as shown on the y-axis of the graph. FOXP3 is the master transcription factor expressed by regulatory T cells and is obligatory for the lineage differentiation of T cells into regulatory T cells. As noted here, treatment with Q401 resulted in significant induction and expansion of regulatory T cells. The base level of natural Tregs is around 2 to 5% of the CD4-positive T cells. Upon treatment with Q401, up to 50% or greater of the CD4-positive T cells differentiated into the Treg phenotype. We have extensively characterized the Tregs induced and expanded by Q401. The phenotype and genotype of these T cells is stable and robust. and they demonstrate functional suppression in cell-based assays. In a collaboration with Dr. Richard DiPaolo's laboratory at the St. Louis University, we've also demonstrated in vivo conversion of T-Rex and the functionality in murine models of autoimmunity. An example is shown on the next slide, slide 17. In this model of T-cell mediated autoimmune gastritis, mice were treated with only two doses of Q401 at day one and day 14, and the disease assessments were performed post 60 days. As shown here, the histological analysis of the stomach tissues showed extensive pathology and destruction in the mice treated with PBS, which is the control middle panel. In contrast, the mice treated with Q401 demonstrated protection from autoimmune destruction, and their stomach tissue histology looked more similar to the healthy control mice. The graph on the right measures various metrics to generate a composite castritis score. In this blinded assessment of histology sections, the Q401 treated mice exhibited significant reduction in the gastritis scores compared to the PBS treated disease mice. The next slide highlights the vast therapeutic opportunities with Q401. These indications span from the well-known autoimmune diseases such as lupus, IBD, rheumatoid arthritis, type 1 diabetes, et cetera, to opportunities in neuroinflammatory disorders such as multiple sclerosis, ALS, Alzheimer's, to pulmonary and metabolic diseases and solid organ transplantation and GVHD. We are most excited about developing Q401 to address many of the indications noted here. The recently announced partnership with Ono Pharmaceuticals provides us with resource support as well as a series of defined milestone payments to support the further development of Q401 towards IMD filing and clinical development. we have retained an option for 50% interest in the U.S. market, providing significant commercial potential to Q if the drug is successfully developed and approved. With that, I'll now turn the call over to Kerry to give us a brief financial update.

Thanks, Anish. Turning now to slide 19, I'd like to provide a brief update on our financial results for the year into December 31, 2022. The company reported collaboration revenue of approximately $0.15 million and $8.3 million for the three months ended December 31, 2022, and 2021, respectively. The decrease was primarily due to the completion of the research phase of the LGC collaboration in the first quarter of 2022. Research and development expenses were $11.3 million and $11.5 million for the three months ended December 31, 2022, and 2021, respectively. The decrease was due to the completion of enrollment in the Phase I monotherapy clinical trial of Q101 in recurrent or metastatic head and neck squamous cell case genoma in the beginning of 2022. General and administrative expenses were $3.7 million and $4.7 million for the three months ended December 31, 2022 and 2021, respectively. The decrease was primarily due to lower stock-based compensation expense recorded during the first quarter of 2022 as compared to the same period in 2021. The company reported collaboration revenue of approximately $1.2 million and $14.9 million for the years ended December 31, 2022 and 2021 respectively. The decrease is primarily due to the completion of the research phase of the LGC collaboration in the first quarter of 2022. Research and development expenses for the year were $38.6 million and $41.3 million. for December 31, 2022, and 2021, respectively. And the decrease was due to a decrease in costs related to clinical trial activity for the Q101 monotherapy and combination clinical trials, and lower manufacturing costs related to the Q101 and Q1022 clinical material. General and administrative expenses were $16.2 million and $17.3 million for the years ended December 31, 2022, and 2021, respectively. The decrease in general and administrative expenses is due primarily to lower professional and consulting fees, stock-based compensation, and rent in 2022. As of December 31, 2022, the company had approximately $76.3 million in cash, cash equivalents, and marketable securities, as compared to $64.4 million as of December 31, 2021. Our current cash, cash equivalents, and marketable securities will fund operations into the second half of 2024. I'll now turn the call back over to Dan, who is closing the rocks. Dan?

Thanks, Carrie. You can go to the next slide. In summary, we believe we're well-positioned to achieve our stated objectives. With Q101 exemplary of the IL-2-based Q100 series demonstrating clear evidence of single-agent clinical activity and what appears to be at least a doubling of overall response in combination with Keytruda and frontline patients, We believe we're beginning to observe what may prove to be a therapeutic breakthrough. Importantly, Q101 has demonstrated clinical activity in combination with Keytruda in patients having a low CPS score, that is, in patients whose tumors appear to be immunologically inactive or less active, where a checkpoint inhibitor is thought to be less likely to provide benefit. We believe our drug is mechanistically complementing checkpoint inhibition by activating and expanding targeted cancer-specific T cells in a well-tolerated manner, thereby broadening the patient reach and enhancing therapeutic outcome. We're focused on the following core initiatives and milestones intended to further strengthen our competitive positioning. The emerging survival data in the Q101 monotherapy expansion cohort in the third line, refractory metastatic HPV-positive head and neck cancer patients, is approaching a median overall survival of 12 months and beyond, which represents a substantial benefit when compared to the historical median overall survival of eight months observed in second line with checkpoint inhibitors. The strength of this data provides us with the opportunity of conducting a potential registrational trial in patients that have progressed on prior chemotherapy and checkpoint inhibitor therapy. Q101 plus pembrolizumab or Keytruda combination in the expansion cohort is expected to complete enrollment of the full 20 patients mid-year with a potential registrational trial being defined by the end of the year. As reported, we continue to be highly encouraged by the data presented at CITSE on the first 10 patients enrolled. To date, follow-up analysis of these initial 10 patients as well as additional patients dosed and evaluated to date continue to hold or enhance what appears to be a doubling of the ORR compared to the checkpoint inhibition alone based on historical data as reported. Our observations from the ongoing clinical trials appears to support the premise that Q101 and by implication the entire Q100 series mechanistically complements checkpoint inhibition. And as such, we believe our platform and growing pipeline expands patient reach and therapeutic benefit of checkpoints. Turning to Q102, the monotherapy dose escalation trial is going quite well. Q102 targets Wilms Tumor 1, just to remind you that WT1 expressing cancers represents a very broad opportunity. We believe that evidence of clinical activity would be a significant catalyst for further validation and value enhancement of our platform, and we expect data from the dose escalation trial to report in the second half of the year. with significant potential market opportunities, as I stated, in WT1-positive cancer indications. With that, we look forward to providing you with ongoing updates in the coming months, and we'd like to thank those listening in very much for your attention and interest in QBioPharma, and I'd like to turn the call back to the operator for questions. Operator?

Thank you. Ladies and gentlemen, if you would like to ask a question, please press star 1 on your telephone keypad, and a confirmation tone will indicate your line is in the question queue. You may press star 2 if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment, please, while we pull for questions. Our first question comes from the line of Ted Tentoff with Piper Sandler. Please proceed.

Great. Thank you very much. And I'm looking like it's picking up to be a really exciting year for you guys. I want to get a sense for what else we should be expecting from 101 in terms of data. And, you know, what else do you guys expect to learn in terms of helping define or design, sorry, the registrational trial? Thank you.

Sure. So thanks, Ted. Good to hear from you. I'll take that generically and then I'll turn that over to Matteo and Ken. So, you know, right now we're still in the dose at the patient expansion phase of the combination. We are going to be filling that out, let's say, by mid-year. And, you know, as we've stated, that data continues to be followed and looks promising. We're clearly looking at overall response rate, and we're very encouraged by what we're seeing. We're also looking at biomarker metrics such as the cell-free circulating HPV DNA as a proxy of response. Anisha's group evaluates the PKPD of these patients, so we're following those metrics accordingly. And obviously, progression-free survival is being monitored. as well as overall survival. All of these metrics are currently looking very supportive and promising. So that's, you know, what we intend to be gathering and reporting, you know, say second half of the year, and all of that will go into the corresponding registration strategy. Regarding strategy going forward, you know, we have potential registration path for the monotherapy principally based on median overall survival, but a lot of supporting metrics going into that. And we have registration trial potential with the combination. What we're doing is just looking, we feel fortunate that we have options there. Just based on the current capital markets and limited resources, we need to be very prudent on what we prioritize and focus upon. We're going to have discussion with the FDA and obviously you know, discussions with potential partners to determining which approach we're going to take, the actual design of the trial we're working out in discussion with our participating investigators, et cetera. I'm going to stop there, turn it over to Matteo and Ken if you want to add something in further more detail.

Thanks, Dan. No, I think you've covered it quite well. I would just reemphasize that it's really the strength of the data as it's evolving and maturing that really provides options from a regulatory registrational point of view for development both, you know, as a monotherapy in latter lines, in really late-line patients, so patients that have progressed on prior chemo and checkpoint inhibitor. That's really an area that represents an unmet need where there's really no standard of care. And so one could really, I think, envision considering a a very, you know, efficient randomized trial, you know, looking at the monotherapy versus an investigator's choice of regimens. With regards to the combination, you'd ask about the data sets, you know, really by the end of the year, we should have rather matured data on the response rates for the 20 patients to be enrolled in Part D. And really the efficacy that we're observing to date, you know, if that's maintained and strengthened, positions that to enable a trial really that could have a proximal endpoint of PFS or objective response rate in the context of a confirmatorily enrolled patient trial that could potentially support an earlier approval. So just a couple additional thoughts. It's really the strength of the data in both lines. as it evolves, I think, that gives us many options to consider.

Excellent. That was very helpful. I'm looking forward to the next update.

Okay. Thanks, Ted.

Our next question comes from the line of Wren Benjamin with JMP Securities. Please proceed.

Hey, good afternoon, guys. Thanks for taking the questions, and congratulations on the progress. I guess I'd like to just kind of start off, you know, you mentioned patient A, patient B, patient C. I'd love to just kind of get your thoughts maybe from, you know, Ken or Sarah since she's on as to, you know, one, reasons for potential relapse. You know, is there any work or anything that you might be able to gather from patients interacting with the patient or any of the biomarker studies that might give you some clues as to that. And then the other kind of related to it, more on the combo side, is you have these objective responses like the PRs, but have you observed, I think you did in the monotherapy portion of the study, a deepening of response where STs are becoming PRs and you know, what is driving those kinds of responses. And then I have a follow-up.

So this is Ken. Sarah had to drop off a few minutes ago to go to see a patient. But basically, you know, patients fail primary therapy because tumor cells are left behind Currently, an activated immune system is not in place to wipe out any remaining microscopic nests of cells that we just don't see. With radiation or surgery, we just have left a cell behind and our own immune systems don't clean them up. We're very interested, for example, in the neoadjuvant study we have going on to see if we can activate T cells by using Q101 to try and get those last cells cleaned up. And that's what we're seeing over and over again in all of cancer, including head and neck cancer, that it's these unseeable few cancer cells that are left behind that we have to figure out how to get cleaned up by activating the immune system. So I'll stop there and see if that answered your question or if you need further, you know, need more.

Yep. So you mentioned the neoadjuvant study, and, you know, as I was kind of quickly typing out the milestones for this year, I might have missed, you know, when we might see something – regarding the neoadjuvant study. Can you just give us an update as to how that's progressing and when we might see some initial results from that study?

I'll give that one to Matteo.

Yeah, the neoadjuvant trial is going well. The first cohort of patients in Schema 1 have been fully enrolled. And the preliminary data looks, you know, very, very intriguing, whereby we've seen evidence of expansion of V7-reactive T cells and increases in NK cells. So the study now is currently recruiting and enrolling Schedule B, which is the two doses prior to surgery or definitive treatment. And we anticipate completing enrollment of that cohort by the end of the year. Got it.

Okay, thank you. And then just, you know, as we think about the registrational, you know, potential registrational studies, I guess, Dan, you know, if we take out the potential for a partner, let's just say that, you know, that's a discussion that winds up taking too long. Can you just maybe take us through the steps? um that would you know i guess help you decide like which trial to go ahead and start like you know i would think that the relapse refractory monotherapy is the way to go but i don't know what are the other factors that you might be you know thinking about as you decide to commit to one or the other yeah and so it's a really important question ren and it's one that you know we obviously are looking at you know very seriously and and dynamically um

and the various factors we have to consider. So, for instance, you just mentioned monotherapy may be the more attractive one since it is monotherapy, direct path forward. Its primary readout is basically median overall survival. You have to follow patients. Also bear in mind it's a smaller market. And so part of countering that is in the front line, which is further upstream, broader market of patients, we're seeing these very promising results. So by essence of the promise of those results, we would be potentially shrinking that downstream market even further. And what we'd be measuring there is your primary would be overall response rate, clearly we'd be following median overall survival, but it's a broader market. And we're also looking at moving even more upstream there with the neoadjuvant adjuvant setting, for instance. So these are the various factors we have to consider, and it also has to do with the capital access that we have, whether this is through a partnership. If we're doing it ourselves, we have to think about the size of the study and the duration of that study. So all of those variables are being considered. I think the important take-home for us right now at this point in time is we have the prospect of more than one potential registration path to choose from.

Thanks very much for taking the questions. Okay. Thank you, Ryan.

Our next question comes from the line of Mark Breidenbach with Oppenheimer. Please proceed.

Hey, good afternoon. Thanks for taking our questions. Just some timing questions for me to make sure I heard you guys correctly. We should be expecting the next data both from the Q101 combination study in the second half of this year, as well as the initial data from Q102. So, first of all, is that correct? And second, what should we expect in the Q102 data? Is this just going to be safety and PK? data initially, or should we kind of expect a more complete analysis of the dose escalation cohorts from that trial? And I have a follow-up. Sure.

All right. Thanks, Mark. Appreciate it. So the first question, just to clarify, when we said the second half of the year, that's the sort of completed analysis or the analysis of the completed 20-patient expansion. The next update we'll be providing is at an upcoming oncology conference, so that could be mid-year. We're not going to wait until the second half of the year to release an update. So what we're referring to the second half is that's all 20 patients completed, surveyed, et cetera, a more deeper analysis. So I hope that's helpful. We're looking at an update probably mid-year at a cancer conference. And then regarding the metrics on 102, I think the way you couched the question, that's actually the answer, is we'll be doing the dose escalation, completing that by mid-year, and we'll be providing the corresponding metrics that we're measuring along the way, which in fact has to do with PKPD, a possibility, obviously, of some clinical activity as well. And that's going to be mid-year, second half of year. Okay.

Okay.

Okay. I don't know if you want to add anything to that. If not, that's fine.

Nope, that's fine. Nothing to add.

Okay. That's super helpful. Thanks for that clarification. And I'm just, you know, maybe one for Anish on Q401. I'm just wondering if you have any plans to present head-to-head preclinical comparisons versus some of the other IL-2 mutines that are out there. Is that something that's on the agenda for 2023?

Yeah, Mark, we've actually, in previous meetings, and there's an upcoming TREG meeting in May where we're talking, but in a meeting in Paris last year, we presented on this where we compared this to CD25-bias IL-2 mutine where we showed clear induction by Q401 where the IL-2 mutine, as expected, did not convert. And that's not surprising. It is the anticipated immunological outcome. We're continuing to build on that data in in vivo models as well, and we'll be discussing that in the future. But so far, the biology strongly supports the induction and generation of new populations of Tregs that 401 can do, but obviously a CD25-biased IL-mutine cannot.

Okay, thanks for taking the question. Thanks, Mark.

Thank you. Ladies and gentlemen, as a reminder, if you would like to ask a question, please press star 1 on your telephone keypad. And our next question comes from the line of Stephen Willey with Stiefel. Please proceed.

Yeah, good afternoon. Thanks for taking the questions, and congrats on the progress. Hey, Dan. Thank you. So on Q102, I know that you were talking about monotherapy dose escalation, initiating dose expansion monotherapy. But are there plans to initiate dose escalation with Q102 in combination with a checkpoint inhibitor? And I guess, is that something that you would expect to start in parallel with monotherapy dose escalation?

Very good question. And the answer is yes. I mean, obviously, it's very similar to 101. We expect the same general pattern. We are, just to remind everyone, our first trial is with pembrolizumab. but we expect that our drugs and platform will work with any checkpoint. So we're looking at various options and alternatives presently, but that is our intent to also survey in combination. It's first to show, you know, the monotherapy tolerability profile, which we expect to, in essence, mirror what we've seen with 101, but obviously having that data will be important. And then, as you have stated, that's the natural next step.

Okay. And would you be pre-specifying tumors to be WT1 positive with the combination as well? And then I guess does the monotherapy dose expansion then maybe inform select tumor types for expansion with combo?

So the answer is yes to both of those questions. Yeah, we will be stratifying patients based on WT1 expression. And then also in terms of the type of cancers, And the 101, I'm sorry, the 102 monotherapy will certainly guide our thinking of tumors that are more responsive. So that's absolutely spot on, both questions.

Okay. And I guess there appears to be a bit more discussion just around the pursuit of partnering opportunities. And I guess just philosophically curious if you think that the more Proximal opportunities for you are also autoimmune focus, maybe with the Q300 series, or do you think that there's an opportunity here with either the two Q100 programs we know about, maybe some more that we don't know about that could be kind of put out to bid?

Yeah. So, Steve, it's a really important question, complicated question, because there are a lot of, you know, different perspectives on that and variables we have to consider. I think what we're trying to emphasize is this partnership we just announced with Ono, it's not a sort of classic license, you know, for some money. We're actively involved. They're a collaborator. They're supporting the preclinical development work. We have an option to co-develop. They pay milestones along the way. Those milestone payments go a long way to subsidizing our portion if we decide to co-develop. And that allows us to basically retain a significant upside. And what we're trying to basically state here is we have no intention of partnering assets where we're doing preclinical work and then licensing the upside so that we're just monetizing assets. We want to be involved, but the key is to have leverage through the power of the data that we're generating. And we think with the 101 and hopefully 102 following behind data sets that we're developing. This basically validates the whole 100 series. And what we'd like to do is be in a position of leverage in terms of structuring partnerships that allow us to subsidize some of the costs, i.e., capitalization risk, but retain significant upside. We also would benefit from, you know, the depth of clinical development capabilities from various partners in the checkpoint space. We're not adverse to partnering 101 and 102, but we're certainly not going to hand over the upside of the asset to somebody and just do preclinical work. So we intend to be involved so we have retained interest and involvement and commercialization rights, hopefully, in co-development. But also what you stated, the 300 series is also a natural point for partnering as well. We have a very attractive data set there.

All right, that's very helpful. Thanks for taking the questions. Yeah, thank you.

Thank you. If there are no further questions at this time, I'd like to turn the call back to Dan Passeri for closing remarks.

Yeah, thank you. Again, just want to thank everyone for your time and attention during these trying times in the market and really appreciate your time. And we look forward to providing you with ongoing updates, particularly mid-year. All right, thank you very much. Bye-bye.

This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation and have a great day.