Q4 2023 Cue Biopharma Inc Earnings Call
Operator: Ladies and gentlemen, this is the operator. Today's conference is scheduled to begin momentarily. Until that time, your lines will remain on music hold.
Ladies and gentlemen, this is the operator todays conference is scheduled to begin momentarily until that time your lines will remain on music hold thank you for your patients.
Operator: Thank you for your patience. [inaudible] Greetings and welcome to the CUE Biopharma investor update. At this time, all participants are in listen-only mode.
[music].
Operator: A question and answer session will follow the presentation. If anyone should require immediate 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 Dan Passeri, Cue Biopharma's Chief Executive Officer. You may begin.
Daniel R. Passeri: All right, thank you, and good afternoon, everyone. As a reminder, this presentation and discussion are being recorded and will be available on our website for the next 30 days. Also, please be aware that the slides accompanying today's update may be advanced directly by those listening in on the call, and we'll notify you on what slide we're on throughout this presentation. Also, joining me on today's call is Dr. Anish Suri, our President and Chief Scientific Officer. Dr. Matteo Levisetti, our Chief Medical Officer, and Kerri-Ann Millar, our Chief Financial Officer. As shown on slide two, this presentation and overview may contain some forward-looking statements. And any forward-looking statement made during this call represents the company's views only as of today, April 8, 2024.
None: Greetings and welcome to the Q Biopharma Investor update call.
None: At this time, all participants are in listen only mode.
None: A question and answer session will follow the presentation.
None: If anyone should require immediate operator assistance during the conference. Please press star zero on your telephone keypad.
None: As a reminder, this conference is being recorded I would now like to turn the conference over to Jennifer sorry.
Jennifer: Cue Biopharma Chief Executive Officer.
Jennifer: You may begin now.
Alright, Thank you and good afternoon, everyone.
As a reminder, this presentation and discussion is being recorded and will be available on our website for the next 30 days.
Daniel R. Passeri: Okay, as shown on slide three, I'm gonna begin with a summary overview of the broad reach of our therapeutic platform and review our competitive positioning and key corporate objectives going forward. Anish will then provide an overarching summary of our platform approach in support of developments, reinforcing our positioning as a leading solution provider and the development of selective immunotherapeutic biologics to address pressing unmet medical needs. Matteo is then going to review and update our promising and evolving oncology clinical data sets, as well as provide a summary synopsis of our recent and productive type B meeting with the FDA, to align on registration paths forward for Q Anish will then return to provide an overview of highly promising data from our preclinical autoimmune programs with the potential to have a profound impact on the treatment of autoimmune disease. Cary will then join the call and provide a brief update on our financials, and I'll return for closing remarks prior to opening the call to questions.
Jennifer: Also please be aware that the slides accompanying today's update may be advanced directly by those listening in on the call and we will notify you on what slide we're on throughout this presentation.
Dr. <unk>: Joining me on today's call are Dr. <unk>, <unk>, our president and Chief Scientific Officer.
Matteo Levisetti: Dr. Matteo <unk>, our Chief Medical Officer, and Kerri Ann Miller, our Chief Financial Officer.
Matteo Levisetti: As shown on slide two of this presentation.
Matteo Levisetti: It may contain some forward looking statements any forward looking statements made during this call represents the company's views only as of today April <unk> 2024.
Matteo Levisetti: Okay as shown on slide three.
Im going to begin with a summary overview.
Matteo Levisetti: The broad reach of our therapeutic platform and review, our competitive positioning and key corporate objectives going forward.
Matteo Levisetti: <unk> will then provide an overarching summary of our platform approach and in support of developments reinforcing our positioning as a leading solution provider in the development of selective immuno therapeutic biologics to address pressing unmet medical needs in both oncology and autoimmune disease.
Daniel R. Passeri: Okay, so to summarize, the data generated to date from our ongoing clinical trials with Q101 and Q102, as well as our preclinical programs, continue to move us closer to achieving our core mission and vision of becoming a leading solution provider for realizing the tremendous therapeutic potential of selective modulation of the patient's immune system in the treatment of cancer and autoimmune disease. As shown here on slide number four, we aim to achieve this by engineering biologics that translate nature's cues, that is, signals from nature that are built into our biology, and to break through immunotherapy. We have continued to progress forward with positive and evident results in our ongoing clinical trials, demonstrating and further bolstering the therapeutic potential of our immunostat platform for treating cancer, to update the strengthening data from our ongoing clinical phase 1A and B trial, with Q101 for HPV-positive head and neck cancer, and Q102 for treating the numerous types of WT1, or Wilms Tumor 1, overexpressing cancers, strengthens our belief that we've developed a therapeutically effective and well-tolerated approach for the selective modulation of cancer-relevant T cells.
Matteo Levisetti: Matteo.
Matteo Levisetti: Review and update of our promising and evolving oncology clinical datasets as well as provide a summary synopsis of our recent and productive type B meeting with the FDA.
None: To align on registration paths forward for cue 101.
None: Our niche will then return to provide an overview of highly promising data from our preclinical autoimmune programs with a potential of having a profound impact on the treatment of autoimmune disease.
None: Gary will then join the call and provide a brief update on our financials and I'll return for closing remarks prior to opening the call to questions. Okay.
None: Okay, so to summarize that.
None: <unk> generated to date from our ongoing clinical trials with cue 101 in Q1 O two as well as our preclinical programs continue to move us closer to achieving our core mission and vision of becoming a leading solution provider for realizing the tremendous therapeutic potential of selective modulation.
None: Of the patient's immune system in the treatment of cancer and autoimmune disease.
Daniel R. Passeri: Importantly, we recently received guidance in alignment with the FDA through an end-of-phase-one type B meeting for the continued development of Q101 towards registrational trials, and Dale will provide further details on this prospect momentarily. We've also made significant progress with our preclinical autoimmune programs, principally Q401 in collaboration with our partner Ono Pharmaceutical, and the Q500 series, with both programs demonstrating clear evidence of the desired mechanistic effect of Anish is going to cover these in more detail momentarily.
None: As shown here on slide number four we aim to achieve this by engineering biologics that translate nature skus that as signals from nature, they're built into our biology and to breakthrough immunotherapies.
We have continued to progress forward with positive and evident results in our ongoing clinical trials, demonstrating and further bolstering the therapeutic potential of our immuno stat platform for treating cancer.
None: To date, the strengthening data from our ongoing clinical phase, one a and B trial.
None: With cue 101 for HPV positive head neck cancer.
Anish Suri: Through these ongoing developments, both in oncology as well as autoimmune disease, we're well positioned for strategic alignment with third parties for further increasing and enhancing our capacity to develop our highly promising and potentially transformative therapeutics. We've made significant progress towards our goal of consummating a transformational transaction that would enable greater capacity and enhance productivity. I'm going to come back at the end of this call and further elaborate on this topic in the closing remarks. I'll now turn the call over to Anish, who will describe our core competitive positioning and the strategic implications of our approach for treating both oncology as well as autoimmune disease. Thanks, Dan.
None: In Q1 O two for treating the numerous types of WT, one or wilms tumor one over expressing cancers strengthens our belief that we have developed a therapeutically effective and well tolerated approach for the selective modulation of cancer relevant T cells and.
None: Importantly.
None: We recently received guidance in alignment with the FDA through an end of phase one type B meeting for the continued development of cue 101 towards Registrational trial.
None: Matteo will provide further details on this.
None: Respect momentarily.
None: We've also made significant prospect with our preclinical autoimmune programs, principally Q4 hundred one in collaboration with our partner Ono pharmaceutical and the Q 500 series with.
Anish Suri: Good afternoon to all listening in on today's call. I'll provide a brief summary of our platform and the significant potential of our therapeutics for treating cancers and autoimmune diseases. As shown on slide 5, immune balance is a key central pillar of human health, and deviation from this state underscores diseases such as cancer and autoimmunity. Hence, an effective therapeutic strategy for resetting immune balance should focus on selective modulation of disease-relevant immune cells while avoiding broad perturbations of the immune system. Most importantly, this approach allows us to maximize efficacy while preserving patients' safety. Slide 6 provides an introduction to our Immunostat platform for resetting immune balance via selective modulation of disease-relevant immune systems. The core framework of an immunostab builds upon nature's selectivity for T cell engagement and activation; disease-specific T cells express singular T-cell receptors, or TCRs, that engage the stabilized peptide HLA molecules, or PHLAs, in an immunostimulator.
None: Both programs demonstrating clear evidence of the desired mechanistic effect of these novel approaches a niche is going away.
None: Cover these in more detail momentarily.
None: Through these ongoing developments both in oncology as well as autoimmune disease, we are well positioned for strategic alignment with third parties for further increasing and enhancing our capacity to develop our highly promising and potentially transformative therapeutics, we've made significant progress towards our goal of consummating a transformational.
None: Transaction.
None: That would enable greater capacity and enhanced productivity.
None: I am going to come back at the end of this call and further elaborate on this topic.
None: In the closing remarks.
Niche: I'll now turn the call over to our niche who will describe our core competitive positioning and the strategic implications of our approach for treating both oncology as well as autoimmune disease in each.
Thanks, Dan and good afternoon to all listening in on today's call.
Niche: Provide a brief summary of our platform and the significant potential of our therapeutics for treating cancers and autoimmune diseases.
Niche: Shown on slide five immune balance is a key central pillar of human health and deviation from the state underscores diseases, such as cancer and autoimmunity.
Niche: Hence an effective therapeutic strategy for resetting immune balance should focus on selective modulation of disease relevant immune cells, while avoiding broad motivations of the immune system.
Anish Suri: Only those engaged T-cells can then receive a disease-modifying secondary signal. This approach enables selective targeting and modification of disease-specific T-cells, while sparing broad effects on other T-cells that are not relevant to the disease of interest. Importantly, the Immunostat framework was engineered to be highly flexible and modular, enabling us to deploy the same or similar core functional elements for diverse therapeutic approaches. For example, in the case of oncology, immunostats can selectively engage and activate tumor-specific T cells while avoiding systemic immune activation.
Niche: Most importantly, this approach allows us to maximize efficacy while preserving patient safety.
Niche: <unk> six provides an introduction to our immuno stat platform for resetting the immune balance we are selective modulation of disease relevant to be himself. The core framework of an immuno stat builds upon natures selecting <unk> for T cell engagement and activation.
<unk> specific T cells express singular T cell receptors or TCR that engage the stabilized peptide HLA molecules or <unk> in the immuno stat.
Niche: Only those engage T cells can then receive a disease modifying secondary signal. This approach enables selective targeting and modification of disease specific T cells, while sparing broad effects on other T cells that are not relevant to the disease of interest.
Anish Suri: In contrast, for autoimmune diseases, immunostats can selectively down-modulate autoreactive T cells while avoiding broad immunosuppression. Slide seven highlights the pipeline of assets that we have developed for restoration of immune balance. In oncology, we have clinically validated the Q100 series that selectively delivers the potent cytokine IL-2 along with a TCR activating signal to preferentially activate tumor-specific T cells while sparing all other irrelevant T cells. This selective stimulation allows for the generation of a therapeutic index for IL-2, which has eluded many others trying to develop IL-2-based cancer therapies.
Niche: Importantly, the immuno stat framework was engineered to be highly flexible and modular enabling us to deploy the same or similar core functional elements for diverse therapeutic approaches for example in the case of oncology immuno stats can selectively engage and activate tumor specific T cells, while avoiding systemic immune activation.
Niche: In contrast for autoimmune diseases immuno stats can selectively down modulate autoreactive T cells, while avoiding broad immunosuppression.
The next slide slide seven highlights the pipeline of assets that we have developed for restoration of immune balance.
Niche: In oncology, we have clinically validated the cue 100 series that selectively de levers the potent cytokines IL two along with the TCR activating signal to preferentially activate tumor specific T cells, while sparing all other irrelevant T cells. This selective stimulation allows for the generation of a therapeutic index for <unk>.
Niche: IL, two which is alluded many others trying to develop IL two based cancer therapies and over 100 patients dosed, we have demonstrated a substantial increase in efficacy with favorable tolerability for a lead clinical candidate cue 101, and recurrent metastatic head and neck cancer. We have recently concluded a meeting with the ft.
Anish Suri: In over a hundred patients dosed, we have demonstrated a substantial increase in efficacy with favorable tolerability. For our lead clinical candidate, Q101, in recurrent metastatic head and neck cancer, we recently concluded a meeting with the FDA aligning on a registration path, which will be further elaborated upon momentarily by Matteo. With our next clinical candidate, Q102, that targets Wilms Tumor 1, or WT1, we have completed phase one monotherapy dose escalation in patients with gastric, ovarian, colorectal, and pancreatic cancers and have noted evidence of antitumor activity and disease control in multiple patients.
Niche: Aligning on a registration path, which will be further elaborated upon momentarily by retail.
Niche: With our next clinical candidate cue, one or two the targets wilms tumor one or WT. One we've completed the phase one monotherapy dose escalation in patients with gastric ovarian colorectal and pancreatic cancers and have noted evidence of anti tumor activity and disease control in multiple patients.
Anish Suri: Matteo will describe this efficacy data in detail, along with the plans for our registrational path forward with Q101. On the autoimmune front, as shown here, we have developed two novel and highly promising approaches for restoring immune balance. Q401 is a novel bispecific composed of an attenuated IL-2 and TGF-beta that together can stimulate the generation and expansion of regulatory T cells. Regulatory T cells, or Tregs, possess the ability to dampen and control autoreactive lymphocytes, which are responsible for inducing tissue damage in autoimmune diseases.
Niche: Material will describe this efficacy data in detail along with our plans for a registrational path forward with cue 101.
Niche: On the autoimmune front as shown here, we have developed two novel and highly promising approaches for restoring immune balance.
Niche: Q4 hundred one is a novel bi specific composed of an attenuated IL two and TGF beta that together can stimulate the generation in expansion of regulatory T cells.
The regulatory T cells or T. Rex possess the ability to dampen and control Autoreactive lymphocytes, which had responsible for reducing tissue damage and autoimmune disease. Hence in this regard T regs that the master regulators of maintaining immune homeostasis and help Q4 hundred one is currently partnered with almost Ono pharmaceuticals and this collaboration.
Matteo Levisetti: Hence, in this regard, Tregs are the master regulators of maintaining immune homeostasis in health. Q401 is currently partnered with Ono Pharmaceuticals, and this collaboration is moving forward at a strong pace with much productivity. In addition to Q401, we've also developed the Q500 series to enable T cell-mediated depletion of B cells. We believe this biologic holds the promise for achieving CAR T-like efficacy in autoimmune patients and is significantly differentiated from other competing approaches such as ADCC, pan T-cell engages, or CAR T-cell therapy. We will expand on both autoimmune programs in the later part of this presentation. With that background, I'll now turn the call over to Matteo to provide a detailed clinical update on the data and future plans. Matteo?
Niche: <unk> is moving forward at a strong base with much productivity.
Niche: In addition to Q4 hundred one we've also developed the Q 500 series to enable T cell mediated depletion of B cells.
Niche: We believe this biologic holds the promise for achieving car T like efficacy and autoimmune patients and a significantly differentiated from other competing approaches such as the ADC panties and engages or car T cell therapies.
Niche: He will expand on both autoimmune programs in the later part of this presentation with that background I'll now turn the call over to Matteo to provide a detailed clinical update on the data and future plans.
Matteo Levisetti: Thanks, Anish. Good afternoon to everyone listening in on today's call. I am particularly pleased to provide you with this summary update, as we have achieved important developmental milestones with the recent clinical data and believe we have not only defined the registration path forward, but also demonstrated the opportunity of the Q100 series as a potential breakthrough for improving patient outcomes across multiple cancers. The clinical data from the ongoing Q101 trial continues to demonstrate highly encouraging and robust results. Clinical Benefit for patients with newly diagnosed, recurrent metastatic HPV-positive head and neck cancer treated in combination with pembrolizumab and for heavily pretreated recurrent metastatic head and neck cancer patients treated with monotherapy
Matteo Levisetti: Thanks, and good afternoon to everyone listening in on today's call I am, particularly pleased to provide you with a summary update as we have achieved important developmental milestones with the recent clinical data and believe we have not only define the registration path forward, but also demonstrated the opportunity of the Q1.
Matteo Levisetti: <unk> hundred series as a potential breakthrough for improving patient outcomes across multiple cancers.
Matteo Levisetti: The clinical data from the ongoing cue 101 trial continues to demonstrate highly encouraging and robust metrics of clinical benefit for patients with newly diagnosed.
Matteo Levisetti: Required metastatic HPV positive head and neck cancer treated in combination with <unk> and for heavily pretreated recurrent metastatic head and neck cancer patients treated with monotherapy.
Matteo Levisetti: We recently had an end of phase one type B meeting with the FDA, where we received guidance and aligned on a path forward for Q101. To that end, we plan to conduct a randomized phase 2 study of Q101 in combination with pembrolizumab, compared with pembrolizumab alone, as first-line treatment of patients with recurrent metastatic HPV-positive head and neck cancer. This trial design and the resulting data will provide a clear assessment of treatment effect, along with confirmation of the optimal dose for the phase three registrational trial will increase overall confidence and probability of succeeding with the registrational trial. We believe this approach is the optimal means of generating the highest probability of success in the most cost-effective and direct manner.
Matteo Levisetti: We recently had an end of phase one type B meeting with the FDA, where we received guidance and aligned on our path forward to a registrational trial for cue 101.
Matteo Levisetti: To that end, we plan to conduct a randomized phase II study of cue 101 in combination with <unk> compared with <unk> alone as first line treatment of patients with recurrent metastatic HPV positive head and neck cancer.
Matteo Levisetti: This trial design and the resulting data will provide a clear assessment of treatment effect, along with confirmation of optimal dose for the phase III Registrational trial will increase overall confidence in probability of succeeding with the Registrational trial. We believe this approach is the optimal means of generating the highest probability of success in the <unk>.
Matteo Levisetti: Cost effective and direct manner.
Matteo Levisetti: We intend to pursue this registrational approach with 2101 in the first-line setting in combination with Keytruda. As this setting represents a significantly larger market, and we believe, due to the complementary mechanism of action between Q101 and Keytruda, patient impact and durability would likely also further reduce the patient population available in the second-line setting over time. It also represents a straight path forward to move upstream in the treatment paradigm, extending market reach potential into the adjuvant setting, which represents the largest market opportunity.
Matteo Levisetti: We intend to pursue this registrational approach with cue 101 in the first line setting in combination with Keytruda.
Matteo Levisetti: Is this setting represents a significantly larger market and we believe due to the complementary mechanism of action between Q1, and one and Keytruda the patient impact and durability would likely also further reduce the patient population available in the second line setting over time.
Matteo Levisetti: It also represents the straight path forward to move upstream in the treatment paradigm extending market reach potential into the adjuvant setting which represents the largest market opportunities.
Matteo Levisetti: As shown on slide 9, data from the ongoing clinical trials with Q101 as monotherapy and in combination with pembrolizumab have provided clinical proof of concept validation and de-risking of our immunostat platform. The latest data generated to date in 2024 continues to bolster prior observations, further enhancing our confidence in Q101 as a potential therapeutic to improve outcomes for patients battling HPV-positive head and neck. As previously and consistently stated, we believe Q101's unique mechanism of action, as evidenced by the data generated to date, enables effective and tolerated dosing and selective expansion of the targeted tumor-specific Notably, as previously presented, the median overall survival of patients treated in the second line and beyond at the 4 milligram per kilogram monotherapy expansion dose is currently greater than 20 months, which compares favorably to the historical median overall survival of approximately eight months observed in the second line trials of Nivolumab and Pembrolizumab.
Matteo Levisetti: As shown on slide nine data from the ongoing clinical trials with cue 101, as monotherapy and in combination with <unk> have provided clinical proof of concept validation and derisking of our immuno stat platform. The latest data generated to date in 2024 continues to bolster prior observations.
Matteo Levisetti: Further enhancing our confidence in Q1 on one as a potential therapeutic to improve outcomes for patients battling HPV positive head and neck cancer.
Matteo Levisetti: As previously and consistently stated we believe Q1's unique mechanism of action as evidenced by the data generated to date enables effective and tolerated dosing and selective expansion of the targeted tumor specific T cells. We continue to observe prolong survival in patients with advanced recurrent metastatic head and neck cancer treated with Q.
Matteo Levisetti: 101, monotherapy, notably as previously presented the median overall survival of patients treated in the second line and beyond.
Matteo Levisetti: At the four milligram per kilogram monotherapy expansion dose is currently greater than 20 months, which compares favorably to the historical median overall survival of approximately eight months observed in the second line trials of Nivola map and Pepper Lizardman.
Matteo Levisetti: We believe this enhanced survival is due to the repeated stimulation and expansion of tumor-specific T cells given Q101's mechanism of action, especially in the tumor microenvironment. As shown momentarily, the overall response rate in median progression-free survival observed in first-line patients treated with Q101 in combination with pembrolizumab represents a greater than doubling of the overall response rate in progression-free survival compared to historical rates with pembrolizumab monotherapy. Enrollment in the neoadjuvant trial is progressing well, and preliminary observations support the expansion of E7-specific anti-tumor T cells and increases in NK cells within the tumor microenvironment. These findings are consistent with the pharmacodynamic changes observed in the peripheral blood of patients treated with Q101, as previously reported. We believe these observations, in addition to the clinical efficacy observed in the recurrent metastatic setting, support a development strategy of moving further upstream into earlier lines of therapy, such as the adjuvant setting, where a larger number of patients may benefit. Pembrolizumab is approved as the standard of care treatment for first-line patients with recurrent metastatic head and neck cancer that have tumors with a CPS score of greater than or equal to 1%.
Matteo Levisetti: We believe this enhanced survival is due to the repeated stimulation and expansion of tumor specific T cells, given Q1 at one's mechanism of action, especially in the tumor microenvironment.
As shown momentarily. The overall response rate and median progression free survival observed in first line patients treated with cue 101 in combination with pampered lithium Matt represents a greater than doubling of the overall response rate and progression free survival compared to historical rates with <unk> monotherapy.
Matteo Levisetti: Enrolment in the new adjuvant trial is progressing well and preliminary observations support expansion of <unk> specific anti tumor T cells and increases in NK cells within the tumor microenvironment.
Matteo Levisetti: These findings are consistent with the Pharmacodynamic changes observed in the peripheral blood of patients treated with Q1 at one as previously reported we believe these observations in addition to the clinical efficacy observed in the recurrent metastatic setting support a development strategy of moving further upstream into earlier lines of therapy such as.
The adjuvant setting where a larger number of patients may benefit.
Matteo Levisetti: Pampered timber lithium app is approved as the standard of care treatment of first line patients with recurrent metastatic head and neck cancer that have tumors with cps score of greater than or equal to 1%.
Matteo Levisetti: DPS is a measure of PD-L1 expression based on a response rate of 19% observed in the Keynote 48 study. Following combination treatment with Q101, the overall response rate of 46%, as shown on slide 10, observed in patients with CPS greater than or equal to 1 treated to date represents a greater than doubling compared to the historical overall response rate of 19% observed with pembrolizumab monotherapy. As shown on the waterfall plot, we have observed significant tumor reductions across many patients, including confirmed partial responses in 10 patients and a confirmed response in one. Importantly, 11 patients remain on treatment, including 3 with stable disease that exhibit reductions in their target lead count.
Matteo Levisetti: TPS as a measure of PD lone expression based on a response rate of 19% observed in the 48 study.
Matteo Levisetti: Following combination treatment with cue 101, the overall response rate of 46% as shown on slide 10 observed in patients with Cps greater than or equal to one treated to date represents a greater than doubling compared to the historical overall response rate of 19% observed with <unk> monotherapy.
Matteo Levisetti: As shown on the waterfall plot, we have observed significant tumor reductions across many patients including.
Matteo Levisetti: Confirmed partial responses and 10 patients and a confirmed response in one patient.
Matteo Levisetti: Importantly, 11 patients remain on treatment, including three with stable disease that exhibit reductions in their target lesions, notably for patients with low CPA scores and overall response rate of 50%, 50% was observed with cue 101, <unk>, which represents a greater than tripling of the historical overall response.
Matteo Levisetti: Notably, for patients with low CPS scores, an overall response rate of 50% was observed with Q101 and pembrolizumab, which represents a greater than tripling of the historical overall response rate of approximately 15% observed with Pamela Jean-Mabel alone. In totality, our data suggests that not only does Q101 appear to demonstrably enhance the response rate of PD-1 inhibition, but it also does so by substantially enhancing responses in patients that are traditionally less likely to respond. This is particularly important since patients with low CPS scores, i.e. Values of 1 to 19, represent approximately 50% of all patients that are CPS positive and eligible for treatment with a checkpoint inhibitor in the frontline setting. The responses observed in these patients have been durable, an observation that is reflected in the improved progression-free survival, which is shown on the next slide, slide 11.
Matteo Levisetti: This rate of approximately 15% observed with <unk> alone.
In totality, our data suggests that not only does Q1 O. One appear to demonstrably enhance the response rate of PD, one inhibition, but also does so by substantially enhancing responses in patients that are traditionally less likely to respond to.
Matteo Levisetti: This is particularly important since patients with low CPA scores I E values of 1% to 19 represent approximately 50% of all patients that are cps positive and eligible for treatment with checkpoint inhibitor in the frontline setting.
Matteo Levisetti: The responses observed in these patients have been durable and observation that is reflected in the improved progression free survival, which is shown on the next slide slide 11.
Matteo Levisetti: Of note, the Kaplan-Meier estimate of the median progression-free survival for patients treated with Q101 in combination with pembrolizumab, as shown on the left, is currently 8.3 months, which compares very favorably to the historical median progression-free survival of 3.2 months observed with pembrolizumab monotherapy in the Keynote 48 trial, as shown on the right. Furthermore, 20 of the 25 patients treated to date with the 4 mg per kg expansion dose in the ongoing Q101 combination remain alive as of the last follow-up for each patient. This portends well for the median overall survival as it matures throughout the year.
Matteo Levisetti: Of note the Kaplan Meier estimate of the median progression free survival for patients treated with cue 101 in combination with <unk> as shown on the left is currently eight three months, which compares very favorably to the historical median progression free survival of $3 two months observed with <unk> lithium add manav.
Matteo Levisetti: Therapy in the keynote 48 trial.
Matteo Levisetti: On the right.
Matteo Levisetti: Furthermore, 20 of the 25 patients treated to date to four Meg per kg expansion dose in the ongoing cue 101 combination trial remain alive as of the last follow up for each patient. This portends well for the median overall survival as it matures throughout the year.
Matteo Levisetti: As shown in the panel on the left of slide 12, we have observed robust expansion of tumor-specific HPV E7-specific T cells in the peripheral blood of patients treated with Q101. Additionally, as shown in the graph on the right, we have observed an approximate 100% decrease in cell-free HPV DNA, which is an increasingly recognized biomarker of disease burden in all patients that have experienced objective responses tested to date, further supporting the magnitude of their responses. Reductions in cell-free HPV DNA of this magnitude have also been observed in multiple patients, leading to Durable Stable Disease as defined by Research. The data from the Q101-01 trial provided the substrate for a productive type B meeting with FDA, which occurred earlier this year. In the course of this meeting, we aligned with FDA on a path to support a future Q101 plus pambilizumab registrational trial, including guidance on the design of a small phase two trial to confirm the Q101 dose used for a subsequent registrational trial consistent with the Project Optimist Directive. An overview of the planned Phase 2 trial is displayed on slide 13. Treatment-naive first-line patients with recurrent metastatic HPV-positive head and neck cancer will be randomized to one of two Q101 doses in combination with pembrolizumab or placebo. Overall response rate will be the primary endpoint, with others, including PFS and OS, as secondary.
Matteo Levisetti: As shown in the panel on the left of Slide 12, we have observed robust expansion of tumor specific HBV <unk> specific T cells in the peripheral blood of patients treated with Q1 at one.
Matteo Levisetti: As shown on the graph on the right. We have observed an approximate 100% decrease in cell free HBV DNA, which is an increasingly recognized biomarker of disease burden and all patients that have experienced objective responses that were tested to date further supporting the magnitude of their responses reductions in <unk>.
Matteo Levisetti: Cell free HBV DNA of this magnitude has also been observed in multiple patients with durable stable disease as defined by resist.
Matteo Levisetti: The data from the cue 100, 101 trial provided the substrate for a productive type b meeting with FDA, which occurred earlier this year.
Matteo Levisetti: In the course of this meeting we aligned with FDA on a path to support our future cue 101, plus Pampa lithium add registrational trial, including guidance on the design of a small phase II trial to confirm the cue 101 dose used for a subsequent registrational trial consistent with the project Optimists dirt.
Matteo Levisetti: <unk>.
Matteo Levisetti: An overview of the planned phase II trial is displayed on slide 13.
Matteo Levisetti: Treatment naive first line patients with recurrent metastatic HPV positive head neck cancer will be randomized to one of <unk> Q1 O. One doses in combination with Pampa lithium at Pembina lithium that.
Matteo Levisetti: Overall response rate will be the primary endpoint with others, including PFS and OS as secondary endpoint.
Matteo Levisetti: The primary analysis of overall response is anticipated to occur approximately 24 months after the first patient is rolled, as outlined on slide 14, clinical benefit observed with 2-1-0-1 combination treatment in first-line patients that HPV-positive head and neck squamous cell carcinoma is compelling compared to historical published data. We believe this Phase 2 trial design and the resulting data will provide a clear estimation of the treatment effect, confirmation of the dose to be tested in Phase 3, and increase the overall probability of success for the registration. As demonstrated with the Q102 program, which I will now discuss, we believe the data from Q101 has provided de-risking and mechanistic validation for additional biologics from the IL-2-based Q100 series. As a reminder, shown on slide 16, Q102 and Q101 share 99% amino acid sequence identity.
Matteo Levisetti: Primary analysis of overall response is.
Matteo Levisetti: As anticipated to occur approximately 24 months after the first patient is enrolled.
Matteo Levisetti: As outlined on slide 14.
Matteo Levisetti: The clinical benefit observed with Q1, and one combination treatment in first line patients with HPV positive head and neck squamous cell carcinoma is compelling compared to historical published data.
Matteo Levisetti: We believe this phase II trial design, and the resulting data will provide a clear estimation of treatment effect confirmation of the dose to be tested in phase III and increase the overall probability of success for the Registrational trial.
Matteo Levisetti: Yes.
Matteo Levisetti: As demonstrated with the Q1 or two program, which I will now discuss we believe the data from Q1, and one has provided a derisking and mechanistic validation for additional biologics from the IL two based cue 100 series.
Matteo Levisetti: As a reminder, shown on slide 16, Q1 O. Two in Q1 shared 99% amino acid sequence identity. This enabled us to significantly decrease the development time and cost of Q1 or two as we were not required by the FDA to repeat IND, enabling toxicology studies for Q1 O two.
Matteo Levisetti: 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. We were also able to initiate the phase one dose escalation study at 1 milligram per kilogram, a dose at which we observed clear signs of biological activity with Q101. We have now completed the dose escalation portion of the one-to-two study without observing any dose-limiting toxicities and are currently enrolling patients in all four indications in the expansion phase of the trial, as shown on slide 17. Gastric, ovarian, pancreatic, and colon cancer represent areas of high unmet need.
Matteo Levisetti: And we were also able to initiate the phase one dose escalation study at one milligram per kilogram.
Matteo Levisetti: Dose at which we observed clear signs of biologic activity with cue 101, we.
Matteo Levisetti: We have now completed the dose escalation portion of the study without observing any dose limiting toxicities and are currently enrolling patients in all four indications in the expansion phase of the trial.
Matteo Levisetti: As showed on slide 17.
Matteo Levisetti: Strict ovarian pancreatic and colon cancer represent areas of high unmet need.
Matteo Levisetti: Note that these numbers are greater than 200,000 patients with recurrent metastatic disease in need of therapeutic options. In addition, an almost equal number of patients with other WT1-positive cancers are eligible to benefit from Q102 therapy in the future. Emerging pharmacodynamic data from blood samples of patients treated with Q102 is shown on slide 18. As seen here on the left, and consistent with our preclinical data sets and our experience with Q101, selective and robust expansion of WT1-specific T-cells has been noted among patients treated with Q102, with two representative examples shown here. Expansion of these tumor-specific T cells is expected to enhance anti-tumor immunity with the potential to drive tumor reduction, as shown on the right. A patient with gastric cancer that progressed on three prior lines of therapy, including a checkpoint inhibitor, experienced a decrease in the sum of three target lesions of minus 34 percent at week 36. Another example of reduction in tumor burden, this time in a patient with recurrent metastatic ovarian cancer, is shown on the right. Unfortunately, these two patients were found to have new lesions on subsequent scans, and Heather Alkama.
Note that these numbers are greater than a collective 200000 patients with recurrent metastatic disease in need of therapeutic options. In addition, an almost equal number of patients with other <unk> positive cancers are eligible to benefit from Q1 of two therapy in the future.
Matteo Levisetti: Emerging pharmacodynamic data from blood samples of patients treated with cue 102 as shown on slide 18 is.
Matteo Levisetti: As seen here on the left that and consistent with our preclinical datasets and our experience with cue 101 selective and robust expansion of WT. One specific T cells has been noted among the patients treated with Q1 of two with two representative examples shown here.
Matteo Levisetti: Expansion of these tumor specific T cells is expected to enhance anti tumor immunity with the potential to drive tumor reductions as shown on the right.
Matteo Levisetti: Ah patients with gastric cancer that progressed and three prior lines of therapy, including a checkpoint inhibitor has experienced a decrease in the sum of three target lesions of minus 34% at week 36.
Matteo Levisetti: Another example of reduction in tumor burden this time in a patient with recurrent metastatic ovarian cancer as shown on the right.
Matteo Levisetti: Unfortunately these two patients were found to have new lesions on subsequent scans.
Matteo Levisetti: And has now come off treatment.
Matteo Levisetti: Also of note, a pancreatic cancer patient treated on the study has benefited through maintaining stable disease for greater than eight months, which is remarkable in the setting of this devastatingly aggressive tumor. Given the encouraging signals of clinical activity, including multiple patients with stable disease observed across all four indicators, and the enthusiasm of the investigators, the protocol was amended to expand into all four indicators. The study is actively enrolling patients in all four of these indications. Patient screening and enrollment rates continue to go exceedingly well, underscoring investigator enthusiasm and the need for effective therapies in WT1 expressing cancer, as demonstrated on slide 19. It's important to note that while checkpoint inhibitors have had a major positive impact on changing the therapeutic options for patients, there remains a substantial need for improvement. There have been significant, persistent challenges in realizing the fullest potential of immunotherapy. While many therapeutic modalities and combination approaches for immune modulation are being pursued, significant challenges exist with regard to suboptimal safety, tolerability, and efficacy to enable broad patient.
Matteo Levisetti: Also of note our pancreatic cancer patients treated on the study has benefited through maintaining stable disease for greater than eight months, which is remarkable in the setting of this devastatingly aggressive tumor type.
Matteo Levisetti: Given the encouraging signals of clinical activity, including multiple patients with stable disease observed across all four indications and the enthusiasm of the investigators. The protocol was amended to expand into all four indications. The study is actively enrolling patients in all four of these indications.
Matteo Levisetti: Patient screening and enrollment rate continues to go exceedingly well underscoring investigator enthusiasm and the need for effective therapies and WT one expressing cancers.
Matteo Levisetti: As demonstrated on slide 19, it is important to note that while checkpoint inhibitors have had a major positive impact on changing the therapeutic options for patients there remains a substantial need for improvement they.
Matteo Levisetti: There have been significant persistent challenges in realizing the fullest potential of immunotherapies, while many therapeutic modalities and combination approaches for immune modulation or being pursued significant challenges exist with regards to sub optimal safety tolerability and efficacy to enable broad patient reach.
Matteo Levisetti: We believe solution providers to these challenges will emerge as best-in-class market leaders defining the paths forward for more effective therapies, both as stand-alone treatment options as well as combination approaches, for example, with checkpoint inhibitors, has just conveyed the ability of Q101 to selectively expand and activate targeted tumor-specific T cells complements the mechanism of checkpoint inhibition, thus expanding patient reach and enhancing therapeutic benefit, as demonstrated in this chart. We believe our platform has the potential to significantly expand patient reach by increasing the number of patients that benefit and enhancing the magnitude of that. In short, we believe our platform represents a major breakthrough towards realizing the full potential of immunotherapy. We are further encouraged by the early observations of Q102 monotherapy, anti-tumor activity across multiple indications where checkpoint inhibitors have been largely in effect. We look forward to presenting additional data on both programs at ASCO in June. I will now turn the call over to Anish. Thank you. Thanks, Matteo.
Matteo Levisetti: We believe solution providers to these challenge will emerge as best in class market leaders defining the path forward for more effective therapies, both as standalone treatment options as well as combination approaches for example, with checkpoint inhibitors.
Matteo Levisetti: As just conveyed the ability of cue 101 to selectively expand and activate targeted tumor specific T cells complements the mechanism of checkpoint inhibition, that's expanding patient reach and enhancing therapy therapeutic benefit as demonstrated in this chart. We believe our platform has the potential to significantly.
Matteo Levisetti: Expand patient reach by increasing the number of patients that benefit and enhancing the magnitude of that therapeutic benefits.
Matteo Levisetti: In short we believe our platform represents a major breakthrough towards realizing the full potential of immunotherapy.
Matteo Levisetti: We are further encouraged by the early observations of cue 102, monotherapy antitumor activity across multiple indications where checkpoint inhibitors.
It has been largely unaffected.
Matteo Levisetti: We look forward to presenting additional data on both programs at <unk> in June.
None: I will now turn the call over to <unk>.
None: <unk>.
None: Thanks, Matteo let me take a few minutes to update on the notable progress with a platform for autoimmune diseases.
Anish Suri: Let me take a few minutes to update on the notable progress with our platform for autoimmune diseases, starting with Q401 and regulatory T cells, as indicated on slide 20. Slide 21 describes the design and rationale for Q401 as an attractive approach to generate a new and differentiated class of regulatory T-cells, or T-RECs. As mentioned previously, Q401 is a bispecific molecule containing attenuated forms of IL-2 and TGF-beta, which are the two known signals that can convert peripheral T cells into regulatory T cells, also known as induced Tregs or ITCs. In addition, Q4O1 also strongly expands existing natural, This program has been a very productive collaboration with Ono Pharmaceuticals, wherein Ono is supporting all of our ongoing preclinical work to identify an optimized clinical lead compound, which we are on track to accomplish in the second half of 2024.
None: Starting with Q4 hundred one and regulatory T cells as indicated on slide 20.
None: Slide 21 describes the design and rationale for Q4 to one as an attractive approach to generate a new and differentiated class of regulatory T cells or T. Rex.
None: As mentioned previously Q4 to one is a bi specific molecule containing attenuated forms of IL, two and TGF beta which are the two known signals that can convert but referral.
None: T cells into regulatory T cells also known as induced T regs or IP rates. In addition, Q4 hundred one also strongly expands existing natural T. Rex. This program has been a very productive collaboration with Ono Pharmaceuticals, where and Ono is supporting all of our ongoing preclinical.
None: Work to identify and optimized clinical lead compound, which we are on track to accomplish in the second half of 2024.
Anish Suri: The next slide, slide 22, highlights the unique and differentiated mechanism of action of Q401 compared to other CD25 biased IL-2 mutines for expansion of existing Tregs. As shown here, Q401 can expand pre-existing regulatory T-cells and convert naive CD4 positive T-cells into new Tregs, thereby enhancing the quantitative population and the qualitative features of Tregs. Slide 23 provides examples of the potent activity of Q401 in the conversion and generation of stable Treg cells. However, as shown in the left panel, conversion and expansion of human CD4 T cells to Tregs only occur when Either signal alone does not result in Treg conversion, and Q401 represents the first singular biologic capable of delivering both signals simultaneously.
None: The next slide slide 22 highlights the unique and differentiated mechanism of action of Q4 to one over other CD 25 buyers to IL two mid teens for expansion of existing T. Regs as shown here Q4 hundred one can expand preexisting regulatory T cells and convert naive <unk> positive T cells into <unk>.
None: New T regs, thereby enhancing the quantitative population and the qualitative features of T regs to control the pathogenic cellular reactions in autoimmune patients.
None: Slide 23 provides examples of the potent activity of Q4 to one in the conversion and generation of stable <unk> and <unk>.
None: And on the left panel conversion and expansion of human CD four T cells to T. Regs only occurs when the IL two and TGF beta signals are delivered via Q4 hundred one either signal alone does not result in T. Reg conversion and Q4 to one represents the first singular biologic capable of delivering.
None: During both signals simultaneously.
Anish Suri: On the right panel is an in vivo study demonstrating efficacy of Q401 in an animal model of autoimmune gastritis. This is a model developed by Dr. Rich DiPaolo at St. Louis University, wherein a short treatment with Q401 results in long-lasting protection from gastritis, as shown by histopathological analysis and disease scores. We believe this mechanism of action of Q401, including the demonstration of long-lasting efficacy after just a short duration of treatment, will apply to many other autoimmune diseases. Now, let's move on to slide 24, which introduces a new series of imidastats termed the Q500 series that we have developed with the goal of achieving deep B-cell depletion via T-cell mediated approaches. As shown on the next slide, slide 25, recent data sets from small clinical studies have demonstrated remarkable efficacy in autoimmune patients treated with CAR T cells directed against TE19 to deplete B cells. In many cases, long-term ongoing clinical remissions have been noted in patients with lupus and myositis with no concurrent immunosuppressive regimens, which could be early signals of functional cure.
None: In the right panel is an in vivo study demonstrating efficacy of Q4 hundred one in an animal model of autoimmune gastritis. This is a model developed by Dr. Rich Depaolo at St. Louis University, where on a short treatment with Q4 hundred one results in a long lasting protection from gastritis as shown by the history about the logical analysis and disease.
None: We believe this mechanism of action of Q4 hundred one including the demonstration of long lasting efficacy. After just a short duration of treatment will apply to many other autoimmune diseases.
None: Let's move on to slide 24 that introduces a new series of immuno stats termed the Q 500 series that we have developed with the goal of achieving deep b cell depletion via T cell mediated approach as shown on the next slide Slide 25, our recent datasets from small clinical studies have demonstrated remarkable efficacy in <unk>.
None: Autoimmune patients treated with car T cells directed against 2019 to deplete b cells in many cases long term ongoing clinical remissions have been noted in patients with lupus in myositis with no concurrent immunosuppressive regimens, which could be early signals of functional cures.
None: This curative potential via immune reset is what propelled us to start working on the Q 500 series, which enables T cell mediated b cell, killing akin to what car Ts do except with an off the shelf biologic. This concept is best shown on the next slide slide 26, the Q 500.
Anish Suri: This curative potential via immune reset is what propelled us to start working on the Q500 series, which enables T-cell mediated B-cell killing, akin to what CAR T's do, except with an off-the-shelf biologic. This concept is best shown on the next slide, slide 26. The Q500 series builds upon the clinical de-risking accomplished with the Q100 series. The constant is the presence of a bivalent peptide HLA molecule that selectively engages TCRs of selected T cells. In the case of the Q500 series, the peptide presented by the HLA is a well-characterized virus epitope recognized by virus-specific memory T cells present at high frequencies in all of them; examples of such virus epitopes which include CMV, EVV, SARS-CoV-2, etc. In addition, the Q500 molecule also contains SCFEs directed against B-cell cell surface molecules, such as CD19.
None: Series builds upon the clinical Derisking accomplished with the cue 100 series. The constant is the presence of a bivalent peptide HLA molecules that selectively engages dcs of selected T cells.
None: In the case of the Q 500 series the peptide presented by the HLA is a well characterized with virus epitope recognized by virus specific memory T cells present in high frequencies and all of US examples of such virus epitopes, which include CMV EBV <unk> et cetera. In addition to <unk>.
None: 500 molecule also contains scf fees directed against B cell cell surface molecules such as CD 19. This configuration allows for Q 500 molecule to bind target b cells and make them appear as virally infected cells that can be recognized and destroyed by a protective Todd.
None: Memory T cell repertoire.
None: This novel mechanism of action is depicted in the left panel on the next slide Slide 27. This mechanism of natural target recognition via at Tcs is of similar sensitivity, if not higher compared to how a car T cell recognizes its target via the car domain on the right side of the slide.
Anish Suri: This configuration allows for Q500 molecules to bind target B-cells and make them appear as virally infected cells that can be recognized and destroyed by a protective antiviral memory T-cell replication. This novel mechanism of action is depicted in the left panel on the next slide, slide 27. This mechanism of natural target recognition via TCRs is of similar sensitivity, if not higher, compared to how a CAR T cell recognizes its target via the CAR domain. On the right side of the slide is an example of a Q500 molecule enabling cytomegalovirus-specific T cells, CMV T cells, to kill primary human B cells. It is well known that CMV-specific T cells are a significant composition of the protective antiviral T cell repertoire and are present in a large fraction of the population.
None: As an example of our Q 500 molecule, enabling cytomegalovirus specific T cells CMV T cells to kill primary human B cells. It is well known that CMV specific T cells are a significant composition of the protective anti viral T cell repertoire and are present in large fraction of the population as shown.
None: <unk> b cell, killing of specific to the engagement of CMV specific T cells in other words, Q 500 molecule inhibiting on HIV peptide does not mediate b cell, killing synthes since the HIV specific T cells are not present in circulation. So.
None: The selective harnessing and redirection of the protective antiviral T cells to kill targets creates a very attractive opportunity for Q 500 series immuno stats.
Anish Suri: As shown here, B cell killing is specific to the engagement of CMV-specific T cells. In other words, a Q500 molecule harboring an HIV peptide does not mediate B cell killing since HIV-specific T cells are not present in circulation. So the selective harnessing and redirection of the protective antiviral T-cells to kill targets creates a very attractive opportunity for Q500 series immunosuppressants. This is particularly exemplified in the next slide, slide 28, which highlights the market opportunity for a broad therapeutic pipeline with a single product. The therapeutic applications span from multiple autoimmune diseases where pathogenic B cells play a role to additional applications in transplantation and allergic inflammation.
None: Particularly exemplified in the next slide slide 28.
None: Which highlights the market opportunity for a broad therapeutic pipeline with a single product the therapeutic application spend from multiple autoimmune diseases, where pathogenic b cells play a role to additional applications in transplantation and allergic inflammation. The Q 500 series could also be effectively applied for the <unk>.
None: <unk> of B cell malignancies in the oncology therapeutic area.
None: Next slide Slide 29 briefly summarizes the superior differentiation of the mechanism of action of <unk> 500 over other competing modalities with b cell depletion, including ADC car T cellular therapy and patent diesel engages we now recognize that ADC mechanisms result, an incomplete depletion of b cells.
None: Primarily due to variable expression of the target antigen such as CD 19, low target expression allows for escape obese us from ADC, primarily mediated by NK cells. Furthermore, FC receptor polymorphism dictate high versus low ADC affected genotype in the case of car T approaches complex manufacturing.
Anish Suri: The Q500 series could also be effectively applied for the treatment of B-cell malignancies in the oncology therapeutic area. The next slide, slide 29, briefly summarizes the superior differentiation of the mechanism of action of Q500 over other competing modalities for B cell depletion, including ADCC, CAR-T, cellular therapy, and pan-T cell engagements. We now recognize that ADCC mechanisms result in incomplete depletion of B cells, primarily due to variable expression of the target antigen, such as CD19. Low target expression allows for escape of B cells from ADCC, primarily mediated by NK cells.
None: <unk> chains remain a challenge for broad access in addition, patient conditioning regimens inpatient administration and safety risks, including Crs and neurotoxicity continue to pose challenges for car T therapies and T cell engages that activate the T cells via anti CD, three or anti CD 28 cross linking our all.
None: So not favorable for autoimmune applications. These modalities activate all T cells indiscriminately, resulting in Crs and other toxicities, hence a suitable.
Anish Suri: Furthermore, FC receptor polymorphisms dictate the high versus low ADCC effect of genotypes. In the case of CAR-T approaches, complex manufacturing and supply chains remain a challenge for broad access. In addition, patient conditioning regimens, inpatient administration, and safety risks, including CRS and neurotoxicity, continue to pose challenges for CAR-T therapies. PAN T-cell engagers that activate T-cells via anti-CD3 or anti-CD28 cross-linking are also not favorable for autoimmune applications.
None: Hence our unsuitable for autoimmune patients. In addition, they posed a very real threat of further activating and propagating autoreactive T cells that may exacerbate the underlying autoimmune disease. In contrast to these modalities. The Q 500 series offers an elegant potential solution for selectively exploiting the long lasting.
None: Antiviral memory T cells to drive B cell depletion.
None: This off the shelf approach therefore offers the potential to achieve car T like efficacy, while avoiding the pitfalls associated with cell therapy modalities.
None: With that overview on both Q4 hundred one in Q 500 in their applications in autoimmune disorders, I'll turn the call to carry to review the financial details sorry, Anthony turning to slide 30, I would like to provide a brief update on our financial results for the three months and full year ended December 31 2023.
Anish Suri: These modalities activate all T cells indiscriminately, resulting in CRS and other toxins, hence are unsuitable for autoimmune patients. In addition, they pose the very real threat of further activating and propagating autoreactive T cells that may exacerbate the underlying autoimmune disease. In contrast to these modalities, the Q500 series offers an elegant potential solution for selectively exploiting the long-lasting antiviral memory T cells to drive B cell depletion. This off-the-shelf approach therefore offers the potential to achieve CAR T-like efficacy while avoiding the pitfalls associated with cell therapy modalities. With that overview of both Q401 and Q500 and their applications in autoimmune disorders, I'll turn the call over to Keri to review the financial details.
Carrie: The three months ended December 31, 2023, the company reported collaboration revenue of approximately $1 8 million as compared to 150000.
Gary in 2022.
Gary: Revenue in the fourth quarter was primarily due to work related to the collaboration and option agreement with Aerovironment fiscal Q4 alignments with executed in the first quarter of 2023.
Gary: Research and development expenses were $10 nine and $11 3 million for the three months ended December 31, 2023, and 2014, respectively.
Gary: This was primarily due to credit substance global fracturing project with cue 101 in Q1 or two that were completed in 2022.
Gary: General and administrative expenses were $4 6 million and $3 7 million for the three months ended December 31, 2023, and 2020, respectively. The increase was primarily due to an increase in professional and consulting period. During this time.
Keri: Thanks, Anish. Turning to slide 30, I'd like to provide a brief update on our financial results for the three months and full year ended December 31st, 2023. For the three months ended December 31st, 2023, the company reported collaboration revenue of approximately $1.8 million, as compared to $150,000 for the same period in 2022. Revenue in the fourth quarter was primarily due to work related to the collaboration and option agreement with Ono Pharmaceuticals for Q401, which was executed in the first quarter of 2023. Research and development expenses were $10.9 million and $11.3 million for the three months ended December 31, 2023 and 2022, respectively. The decrease was primarily due to drug substance manufacturing projects for Q101 and Q102 that were completed in 2022. General Administrative Expenses were $4.6 million and $3.7 million for the three months ended December 31, 2023, and 2022, respectively.
Gary: For the year ended December 31, 2023, and 2014 the company reported collaboration revenue.
Gary: <unk>.
Gary: Five.
Gary: Yes.
Gary: The increase is due to the revenue earned from our strategic collaboration agreement with <unk> Pharmaceuticals.
Gary: Research and development expenses were $40 8 million and $38 6 million for the year.
Gary: Is ended December 31, 2023, and 2019, respectively.
Gary: The increase was due primarily to clinical development costs and research and laboratory expenses, which were partially offset by decreases in employee costs and rent expense.
Gary: General and administrative expenses remained relatively flat at $16 7 million and $16 2 million for the year ended December 31, 2023, and totaled 22, respectively and as of December 31, 2023, The company had approximately $48 5 million in cash and cash equivalent of $34 $4 million.
Working capital and $47 2 million common shares outstanding.
Gary: We expect our current cash and cash equivalents to fund operations into the first quarter of 2025.
Gary: Now I'll turn the call back over to Dan for closing remarks.
Dan: Yes, Thanks Kerry.
Dan: As you've just heard our growing body of data in both clinical oncology.
Dan: And with preclinical autoimmune disease continues to support and reinforce our central premise and firm belief that.
Keri: The increase was primarily due to an increase in professional and consulting fees during the pandemic. For the years ended December 31st, 2023, and 2022, the company reported collaboration revenue of approximately 5.5 million and 1.2 million, respectively, an increase due to the revenue earned from our strategic collaboration agreement with O'Neill Pharmaceuticals. Research and development expenses were $40.8 million and $38.6 million for the years ended December 31, 2023, and 2022, respectively. The increase was due primarily to clinical development costs and research and laboratory expenses, which were partially offset by decreases in employee costs and rent. General and administrative expenses remained relatively flat at $16.7 million and $16.2 million for the years ended December 31, 2023 and 2022, respectively. And as of December 31, 2023, the company will have approximately $48.5 million in cash and cash equivalents, $34.4 million in working capital, and $47.2 million in common shares outstanding.
Dan: <unk> <unk> platform holds tremendous potential to transform immunotherapy for both cancer and autoimmune disease by selectively modulating the patient's immune system and a highly targeted and tolerated manner. We believe the data we've generated to date in oncology with cue 101, and Q1 O. Two have clearly demonstrated the selective.
Dan: <unk> targeted activation and expansion of cancer relevant CDA positive T cells, and a qualitatively distinctive manner.
Dan: Furthermore, these data demonstrate clear signs of durable anti tumor activity and mechanistic complementarity with checkpoint inhibitors.
Dan: Let me remind everyone listening in that the patients. We're treating are refractory that is resistant to prior therapy and metastatic that as their cancer has not only recurred, but is also spread to multiple locations. After primary treatment. As a result, these patients have a very poor overall prognosis and importantly.
Dan: Both cue 101 in Q1 or two have demonstrated the potential of stimulating the patient's immune system.
Dan: To recognize the tumors growing in their bodies as foreign marshaling an attack.
Dan: Furthermore, our clinical observations to date support the putative mechanism of action for cue 101, and by implication Q1 O two as well as the entire IL two based cue 100 series Mechanistically complementing immune checkpoint inhibitors, such as Keytruda, we see this compilation of data as a key strategic.
Dan: Advantage for expanding patient reach there and therapeutic benefit of checkpoint inhibitors positioning us well for strategic alignment with potential partners to enhance their competitive positioning.
Daniel R. Passeri: We expect our current cash and cash equivalents to fund operations into the first quarter of 2025. And I'll turn the call back over to Dan for closing remarks.
Dan: As conveyed in the slide number 31.
Dan: Well positioned for value inflection milestones over the coming year.
Dan: Namely with cue 101, moving into a randomized phase II study with the intention of providing confirmation of enhanced efficacy that we've seen in the.
Daniel R. Passeri: Yeah, thanks, Keri. As you have just heard, our growing body of data in both clinical oncology and with preclinical autoimmune disease continues to support and reinforce our central premise and firm belief that Cue's platform holds tremendous potential to transform immunotherapy for both cancer and autoimmune disease by selectively modulating the patient's immune system in a highly targeted and tolerated manner. We believe the data we've generated to date in oncology with Q101 and Q102 have clearly demonstrated the selective and targeted activation and expansion of cancer-relevant CD8 positive T cells in a qualitatively distinctive manner. Furthermore, these data demonstrate clear signs of durable anti-tumor activity and mechanistic complementarity with checkpoint inhibitors. I'll let you remind everyone listening in that the patients we're treating are refractory, that is, resistant to prior therapy, and metastatic, that is, their cancer has not only recurred, but has also spread to multiple locations after primary treatment. As a result, these patients have a very poor overall prognosis.
Dan: Prior studies that we've.
Dan: <unk> on in the <unk> and <unk>, which is our cue 101, plus checkpoint inhibitor versus the checkpoint inhibitor standard of care alone.
Dan: We expect interim analysis at 14 months and the overall.
Dan: Our response rate and median progression free survival analysis between 22% and 24 months, both of which underscore breakthrough potential with cue 101, plus checkpoint inhibitor to establish a new standard of care for these frontline refractory metastatic head and neck squamous cell carcinoma patients, but also has far reaching implications.
Dan: Occasions for our immuno stat platform.
Dan: Implication in solid tumors per se by expanding patient reach and enhancing clinical benefits enhancing clinical benefits of checkpoint inhibitors and to a broad range of cancers successful readout in the randomized phase II would place Q and a position of leveraging strength as a partner of choice for checkpoint inhibitor franchise.
Dan: Furthermore, Q.
Dan: Q1 O two patient expansion positions combo combinations with checkpoint inhibitors in large indications segments, where checkpoint inhibitors have historically failed to achieve approval.
Daniel R. Passeri: And importantly, both Q101 and Q102 have demonstrated the potential to stimulate the patient's immune system to recognize the tumors growing in their bodies as foreign, marshalling an attack. Furthermore, the clinical observations to date support the putative mechanism of action for Q101, and by implication, Q102, as well as the entire IL-2-based Q100 series, mechanistically complementing immune checkpoint inhibitors such as Keytruda. We see this compilation of data as a key strategic advantage for expanding patient reach and therapeutic benefit of checkpoint inhibitors, positioning us well for strategic alignment with potential partners to enhance their competitive position, as conveyed in slide number 31. We are well positioned for value inflection milestones over the coming year, namely with Q101 moving into a randomized phase two study with the intention of providing confirmation of enhanced efficacy that we've seen in the prior studies that we presented on in the 1A and 1B, which is our Q101 plus checkpoint inhibitor versus the checkpoint inhibitor standard of care alone.
Dan: We have also generated a body of data highly supportive of the mechanistic advantages disruptive potential of our autoimmune programs, namely Q4 hundred one for T. Reg induction currently partnered with Ono on width of which we have retained an option for a 50% interest in the U S market with two near term milestones potentially being <unk>.
Dan: <unk>.
And Q 501.
Dan: B cell ablation with the potential to displace car T with a biologic for B cell driven autoimmune diseases such as lupus.
Dan: As conveyed in the next slide number 32, we've positioned <unk> well for strategic and competitive positioning with the establishment of clinical proof of concept with our two lead oncology.
Dan: Programs, whereby our clinical data.
Dan: Generated to date.
Dan: Have the potential to shift the treatment paradigm and that we've demonstrated significant and meaningful increase in the overall response rate medium progression free survival and overall survival.
Dan: Resulting in the promise that we have the potential to revitalize checkpoint inhibitor sector and enhanced market reach and have also demonstrated platform modularity and scalability through this modularity and scalability, we have multiple applications of our novel platform.
Dan: Having the potential to address some of the largest pharmaceutical markets in the U S and global application for solid tumors and autoimmune disease indications through these ongoing developments, we have made significant progress over the past quarter with our corporate development and business development initiatives. We are presently engaged.
Daniel R. Passeri: We expect interim analysis at 14 months and the overall response rate and medium progression free survival analysis between 22 and 24 months, both of which underscore breakthrough potential with Q101 plus checkpoint inhibitor to establish a new standard of care for these frontline refractory metastatic head and neck squamous cell carcinoma patients, but also has far-reaching implications for our immunostat platform application, Successful readout in the randomized phase 2 would place CUBE in a position of leverage and strength as a partner of choice for checkpoint inhibitor franchises.
Dan: <unk>, an ongoing strategic discourse with multiple prospective strategic partners based.
Dan: Based on continued development through these ongoing discussions we're highly confident we'll be successful consummating, one or more of these transactions in a timely manner and enabling strategic alignment enhancing our capacity and enabling access to requisite capital towards the realization of our corporate mission.
Daniel R. Passeri: Furthermore, Q102 patient expansion positions combinations with checkpoint inhibitors in large indication segments where checkpoint inhibitors have historically failed to achieve approval. We have also generated a body of data highly supportive of the mechanistic advantages and disruptive potential of our autoimmune programs, namely Q401 for Treg induction currently partnered with Ono, of which we have retained an option for a 50% interest in the U.S. market, with two near-term milestones potentially being realized, and Q501 for B-cell ablation, which has the potential to displace CAR-T with a biologic for B As conveyed in the next slide, number 32, we've positioned Q-Well for strategic and competitive positioning with the establishment of clinical proof of concept with our two lead oncology programs, whereby our clinical data generated to date have the potential to shift the treatment paradigm and that we've demonstrated a significant and meaningful increase in the overall response rate, median progression-free survival, and overall survival, resulting in the promise that we have the potential to revitalize the Through this modularity and scalability, we have multiple applications of our novel platform, having the potential to address some of the largest pharmaceutical markets in the U.S. and global applications for solid tumors and autoimmune disease indications.
None: On that I'd like to or we would like to extend our sincere thanks and appreciation to our committed shareholders.
None: Passionate employees board of Directors Scientific Advisory Board clinical investigators and our collaboration partners for their continued support guidance and trust and most importantly, we extend our profound appreciation and respect to the patients and their families who have participated in our clinical trials, enabling us to gain insights into.
<unk> essential for continued progress in the fight against cancer and other debilitating diseases.
None: With that I'd like to now turn the call back over to the operator to open up for questions operator.
None: Thank you, ladies and gentlemen, we will now conduct the question and answer session.
None: If you have a question. Please press star one on your telephone keypad.
None: And if you wish to cancel your request please press star two.
None: Please ensure to lift the handset if youre using a speakerphone before pressing entities.
None: Our first question comes from.
None: Marvin you recall from Jefferies. Your line is now open.
Marvin: Hi, Congrats on the progress and thanks for taking my questions.
Marvin: I was going to ask about the randomized phase II combo study can you talk about how many patients you anticipate youll need in each arm and if you're successful on that first interim on.
Marvin: And overall response rate would that allow you to advance into a registrational phase III.
Marvin: Sure Matteo do you want to take that question and thanks Mark.
Matteo Levisetti: Yes, yes, certainly.
Matteo Levisetti: So the patient.
Sample size for the entire trial is planned to be less than 100 patients approximately 25%.
Daniel R. Passeri: Through these ongoing developments, we have made significant progress over the past quarter with our corporate development and business development initiatives. We are presently engaging in ongoing strategic dialogue with multiple prospective strategic partners. Based on continued development through these ongoing discussions, we're highly confident we'll be successful in consummating one or more of these transactions in a timely manner enabling strategic alignment, enhancing our capacity, and enabling access to requisite capital towards the realization of our corporate mission. On that, I'd like to, or we would like to extend our sincere thanks and appreciation to our committed shareholders, passionate employees, board of directors, scientific advisory board, clinical investigators And most importantly, we extend our profound appreciation and respect to the patients and their families who have participated in our clinical trials, enabling us to gain insights and knowledge essential for continued progress in the fight against cancer and other debilitating diseases. With that, I'd like to now turn the call back over to the operator to open up for questions. Operator?
Matteo Levisetti: Patients per arm.
Matteo Levisetti: And then regarding the first interim analysis.
Matteo Levisetti: Given that this is a randomized trial will have.
Matteo Levisetti: Data safety monitoring board that will.
Matteo Levisetti: Look at the results of that first interim and provide a recommendation to continue the trial per protocol.
Matteo Levisetti: Everything looks good and it's really the final analysis at 24 months, 22% to 24 months.
Matteo Levisetti: That would serve as the substrate to proceed into a registrational trial, although a fair bit of trial startup could be done.
Matteo Levisetti: Once the interim analysis the first one.
Matteo Levisetti: <unk> provides a positive record of recommendation to move forward.
None: Got it that's helpful.
None: Dan you talked about potential partnering can you clarify what stage.
Dan: You would look to potentially partner would it be as you're running the phase two.
Dan: Before the phase III.
And then what could potential partnership look like from a development and economic standpoint.
Dan: Sure a very important question.
None: And as you know, it's a dynamic question and if there is no.
None: One answer to that it's really looking at a number of factors that we will consider so we're presently in discussions, let's just say with multiple parties across the various asset classes. We have so pertaining to Q1 O. One Q1 O. Two I think the key there is.
Operator: Thank you, ladies and gentlemen. We will now conduct the question and answer session. If you have a question, please press star 1 on your telephone keypad. And if you wish to cancel your request, please press star 2. Please ensure that you lift the handset if you're using a speakerphone before pressing any key.
None: Identifying and appropriate party with the sort of requisite insight on the disease indication.
Operator: Your first question comes from... Marbury Raycroft, from Jeffries. Your line is now open. Hi, congrats on the progress and thanks for taking my question. I was going to ask about the randomized phase 2 combo study. Can you talk about how many patients you anticipate you'll need in each arm? And if you're successful in that first interim, on overall response rate, would that allow you to advance into registrational phase 2? Sure, Matteo, do you want to take that question? And thanks, Mark.
None: That can sort of enhance our own capacity.
None: And provide the requisite support we certainly don't want to be giving up.
None: On the economics.
None: Too much of the promise of those assets. So it's really going to be based on our continued involvement, particularly in the randomized phase two.
None: The type of support we would have in the economics downstream. So we're in discussions with various parties and we will be looking at different economic structures to make that decision and ultimately it's a board decision. So we will we've been in dialogue with the board on an ongoing basis and ultimately we will present various scenarios.
Matteo Levisetti: Yes, certainly. So the patient sample size for the entire trial is planned to be less than 100 patients, so approximately 25 patients per arm. And then regarding the first interim analysis, given that this is a randomized trial, we'll have a data safety monitoring board that will look at the results of that first interim and provide a recommendation to continue the trial per protocol if everything looks good. And it's really the final analysis at 24 months, 22 to 24 months, that would serve as the substrate to proceed to a registrational trial, although a fair bit of trial startup could be done once the That's helpful.
None: And make the decision accordingly, and regarding autoimmune same type of dynamic analysis I would just use <unk> as an example, the structure of that partnership was very favorable they've actually been an outstanding partner with an early asset. They are basically subsidizing the development we have a.
None: Very interactive partnership, but we've retained a 50% upside option.
Upon selection of the clinical candidate when we begin IND, enabling studies.
None: And that allows us to preserve sort of optimal upside for our shareholders as well.
None: Sort of risk capital, particularly in the early stages is being subsidized so I hope that answers your question, but we will be looking at it.
Daniel R. Passeri: And Dan, you talked about potential partnering. Can you clarify what stage you would look to potentially partner? Would it be as you're running Phase 2 or before Phase 3? And then what could potential partnership look like from a development standpoint? Sure.
None: In a dynamic manner based on the various options we have in front of us.
None: Got it.
None: Yes, that's helpful in for the 501.
Daniel R. Passeri: A very important question and, you know, Maureen, as you know, it's a dynamic question and that there's no one answer to that. It's really looking at a number of factors that we will consider. So we're presently in discussions, let's just say, with multiple parties across the various asset classes we have. As regards Q101 and Q102, I think the key there is identifying an appropriate party with the sort of requisite insight into the disease indication that can sort of enhance our own capacity and provide the requisite support. We certainly don't want to be giving up, you know, on the economics too much of the promise of those assets.
None: Program, just wondering if you talk more about where you're at with our preclinical development.
None: For that program, you talked a little bit about potentially partnering this one two would this be from the 500 series would it be one asset or would it be part of this 500 series platform. How would you think about that.
None: Yes.
Niche: This is a niche what we have so far is clear evidence that we've been able to make the scaffold and is biologically active as you can see.
Niche: We've tested this across a number of different memory T cell specificity, so <unk> being.
One which is highly present in a majority of us but also <unk> at this point in time, there is a very conserved epitope from the spike protein that virtually all of US today in the world should have <unk> specific T cells, whether it's by a vaccination or natural infection. So that provides a great substrate for SM.
Daniel R. Passeri: So it's really going to be based on our continued involvement, particularly in the randomized phase two, the type of support we would have in the economics downstream. So we're in discussions with various parties, and we'll be looking at different economic structures to make that decision, and ultimately, it's a board decision. So, you know, we've been in dialogue with the board on an ongoing basis, and ultimately, we will present various scenarios and make the decision accordingly. And regarding autoimmune, same type of sort of dynamic analysis. I would just use Ono as an example.
Actually use this nature spend to redirect it to something good which is destroying these pathogenic b cells.
Niche: Down the road, we started initially with CD 19, Laurie, but you can think about the concept actually extending beyond just be sales to other pathogenic cell types.
Niche: I also think and we think very strongly that this can also extend into very nicely into the oncology setting, particularly solid tumors, where you just swap out the CFO of the <unk> surface tumor antigen I mean think about BSO, maybe think about it.
Daniel R. Passeri: The structure of that partnership was very favorable. They've actually been an outstanding partner with an early asset. They're basically subsidizing the development.
Niche: To think about or two etcetera. So I think there is a vast potential for this.
Niche: As we started talking to the initial interest was actually.
Niche: An extraordinary amount of inbound interest from.
Niche: From companies and parties that have been interested in really getting car T lack efficacy and what was recently demonstrated in these small studies in autoimmunity.
Anish Suri: We have a very interactive partnership, but we've retained a 50% upside option upon selection of the clinical candidate when we begin IND-enabling studies. And that allows us to preserve some sort of optimal upside for our shareholders while the sort of risk capital, particularly in the early stages, is being subsidized. So I hope that answers your question, but we'll be looking at it, you know, in a dynamic manner based on the various options we have in front of us.
Niche: That is the starting position and we've made good progress.
Niche: The scaffold actually is.
Niche: <unk> very much by the 100 <unk>. So that's why I sort of stress that the core component remains the same it's a bivalent peptide HLA and obviously has no IL two instead of that the motors and anchoring Cfe. So again theres a lot of good learnings from the 100 series 101, one or two that sort of beneficially impact the firewall.
Niche: Third series.
None: Got it that's really helpful. Thanks for taking my questions.
Anish Suri: Yeah, that's helpful. And for the 501 program, just wondering if you could talk more about where you are with preclinical development for that program. And you talked a little bit about potentially partnering this one, too. Would this be from the 500 series, would it be one asset, or would it be part of this 500 series platform? How would you think about that? Yeah, Maurice, this is Anish.
None: Alright, thank you.
None: Your next question comes from Stephen Willey from Stifel. Your line is now open.
Stephen Douglas Willey: Yes. Good afternoon, thanks for taking the questions and I apologize for the background noise, but Tom.
Maybe just a couple more.
Stephen Douglas Willey: Two questions can you just maybe speak to the.
Stephen Douglas Willey: The second key 101 dose that you're contemplating.
Stephen Douglas Willey: Completing including into the randomized phase two.
Stephen Douglas Willey: And then can you also speak to kind of what triggers the interim analysis is that just happening.
Anish Suri: What we have so far is clear evidence that we've been able to make the scaffold and it's biologically active, as you can see. We've tested this across a number of different memory T-cell specificities, so CMV being one which is highly present in a majority of us, but also SARS-CoV-2. At this point in time, there's a very conserved epitope from the spike protein that virtually all of us today in the world should have SARS-specific T-cells, whether it's by vaccination or natural infection. So that provides a great substrate to essentially use this natural pandemic to redirect it to something good, which is destroying these pathogenic B-cells down the road. We started initially with CD19, Maury, but you can think about the concept actually extending beyond just B cells to other pathogenic cell types.
Stephen Douglas Willey: But give a number of patients out beyond some specific duration of follow up and then itself.
None: Other questions.
Okay.
None: No I can't.
None: Thank you very very good.
None: Questions and so.
None: The doses that we anticipate examining our certainly the four milligram per kilogram dose that we've.
None: Really studied.
None: In 25 patients with now objective response rate of close to 50%.
None: We haven't finalized the selection of the other dose.
None: However, we have quite a bit of experience with two milligrams per kilogram as monotherapy, where in that set of patients of nine patients, we actually see a very pronounced extended survival.
None: Then in the dose escalation that to mix per kg with pampered Lithia Matt.
None: We also observed a very.
None: Very profound durable objective response, so so I think the answer there will be two doses.
Anish Suri: I also think, and we think very strongly, that this can also extend very nicely into the oncology setting, particularly solid tumors, where you just swap out the SCFE of the B cells for a cell surface tumor antigen. I mean, think about PSMA, think about..., think about HER2, etc. So I think there's a vast potential for this. As we started talking, the initial interest has actually been an extraordinary amount of inbound interest from companies and parties that have been interested in really getting CAR T-like efficacy as what was recently demonstrated in these small studies in autoimmunity. So that is the starting position, and we've made good progress. The scaffold actually is de-risked very much by the 100 series, that's why I sort of stressed that. The core component remains the same; it's a bivalent peptide HLA, and obviously has no IL-2. Instead of that, the mod is an anchoring SCFV.
None: Certainly.
None: At this point for mix per gig and then very likely.
None: To make per kicked dose we've seen really very strong activity as.
None: As well we.
None: With regards to the triggering of the first interim analysis.
None: It really will be.
None: Determined.
When approximately 70% to 80% of patients.
None: <unk> gotten through.
None: The cycle five scan okay. So it's really a look to be sure that what we anticipate to observe or the the SMB would observe.
I can make.
None: That assessment once.
None: As I mentioned, 70% to 80% of patients have gotten to their cycle <unk> scan.
None: And we would anticipate that based on what we've observed to date.
None: 101, a one trial and the historical monotherapy rate that that would have progressed then two to ultimately the final analysis.
Anish Suri: So again, there's a lot of good learnings from the 100 series, 101, 102, that sort of beneficially impact the 500. Got it. That's really helpful. Thanks for taking my call. Thank you. Your next question comes from Stephen Wiley from Stifel. Your line is now open.
None: Which again that will be a complete analysis of the dataset.
None: With all patients now having.
None: Follow up through cycle five to get to your primary of overall response rate that final.
None: Our assessment is very valuable because that Youll data then that can be brought forward.
Matteo Levisetti: Yeah, good afternoon. Thanks for taking the questions and I apologize for the background noise. Maybe just a couple more phase two questions. Can you maybe speak to the second key one-on-one dose that you're contemplating including in the randomized phase two. And then can you also speak as to kind of what triggers the interim analysis? Is that just having?
None: To start your phase III and the way. It's designed then allows also for follow up with the supplemental analysis for PFS and OS.
None: But we don't have to wait for that to hold up the initiation of the phase III trial.
None: Okay.
None: Yes.
None: Okay.
None: Can you, maybe just talk a little bit about kind of the pushes and pulls that were under consideration as.
None: You thought about carving out kind of.
Matteo Levisetti: give a number of patients beyond some specific duration of follow-up, and then I just have another question. Certainly. Thank you. Very, very good questions.
None: Independent to randomize phase two versus trying to do something more phase two three adaptive seamless.
Matteo Levisetti: And so the doses that we anticipate examining are certainly the 4 milligrams per kilogram dose that we've really studied in 25 patients with an objective response rate of close to 50 percent. We haven't finalized the selection of the other dose. However, we have quite a bit of experience with 2 milligrams per kilogram as monotherapy, where in that set of patients, of 9 patients, we actually see a very pronounced, extended survival.
None: And maybe in answering that you can speak to.
None: I guess to what extent if any was this path forward kind of informed by some of these ongoing strategic discussions.
So very good question and certainly an option to further develop the combination is to go with a phase III three sort of seamless design.
None: The first component of that and this has become I think quite common sense.
Matteo Levisetti: And then in the dose escalation at 2 mg per kg with pembrolizumab, we also observed a very profound, durable objective response. So I think the answer there will be 2 doses. Certainly, we believe at this point, 4 mg per kg.
None: Our project Optimus has sort of gone into effect as a directive or her mandate.
None: Is too.
None: To have a lead in with two doses to select your dose and then to go into the phase III randomized portion. So so I think there's multiple components to considerations.
Matteo Levisetti: And then, very likely, a 2 mg per kg dose, where we've seen really very strong activity as well. With regard to the triggering of the first interim analysis, it will really be determined when approximately 70% to 80% of patients have gone through the cycle 5 scan. Okay, so it's really a look to be sure that what we anticipate to observe or the DSMB would observe can make that assessment once, as I mentioned, 70% to 80% of patients have gotten to their cycle 5 scan. And we'd anticipate that, based on what we've observed to date in the 101-01 trial and the historical monotherapy rate, that that would progress then to the final analysis, which, again, that will be a complete That final analysis is very valuable because that yields data then that can be brought forward to start your phase 3. And the way it's designed then allows for follow-up with the supplemental analysis for PFS and OS, but we don't have to wait for that to hold up the initiation of the phase 3 trial. Okay, I guess that's helpful.
None: The initiation of that phase III three is a larger endeavor and investment I think clearly.
And in the phase two really offers.
None: The opportunity to generate data that confirms the dose to go into phase III.
None: Therefore, the phase III is similar in design, where Theres no lead in which is actually it takes quite a bit of time at least a year to do.
None: And then also gives the opportunity to have if you will a confirmatory.
None: Now assess.
None: That would increase one's confidence in being successful and ultimately the phase III trial.
None: Yeah.
None: Okay.
None: And then maybe just one quick.
None: A follow up.
None: <unk> I was just wondering if you had any.
None: Thoughts.
None: Around the temporary survival number that.
None: It was recently presented from the beat.
Trial.
None: Just.
None: I know, we're still a couple of years away from a registrational study, but even in the context of <unk> two.
Matteo Levisetti: Can you maybe just talk a little bit about kind of the pushes and pulls that were under consideration as, you know, you thought about carving out kind of an independent randomized control versus trying to do something more phase 2, 3 adapted. And maybe in answering that, you can speak to, I guess, to what extent, if any, you know, this path forward was affected by some of these
None: How do you think that influences your expectation as to what that survival number might look like thanks.
None: Yes, so I think well, it's a bit of a mystery to me I don't know that ive heard or that I'm aware of are clear.
None: Explanation.
None: And also a surprise that the.
None: Objective response rate was 27% as opposed to the historical rate of 19%. So so that arm in the trial did appear to do better than anticipated.
Matteo Levisetti: So, a very good question, and certainly an option to further develop the combination is to go with a Phase II-III sort of seamless design. The first component of that, and this has become, I think, quite common since Project Optimist has sort of gone into effect as a directive or mandate, is to have a lead-in for two doses to select your dose and then go into the Phase III randomized portion. So I think, you know, there are multiple components to the considerations. The initiation of that Phase II-III is a larger endeavor and investment, I think, clearly. And the Phase II, you know, really offers the opportunity to generate data that confirms the dose to go into Phase III, and therefore, the Phase III is simpler in design where there's no lead-in, which actually takes quite a bit of time, at least a year to do, and then also gives the opportunity to have, if you will, a confirmatory analysis that would increase one's confidence in being successful in the ultimately the Phase III trial.
None: I think again it supports the value of doing a phase II trial.
None: <unk> engaging into.
None: A registrational phase three with <unk>.
None: Almost five to 10 times the investment.
None: Really just gained confidence that we're on track with regards to what we believe the combination treatment effect is to the.
None: Current monotherapy effect, so I think I hope that addresses the question I don't and again this was presented in.
None: At the head and neck conference in Arizona, There was quite a bit of a discussion with the head and neck experts and no one really seem to have had an explanation but.
None: Again with regards to Linzess of Nib.
None: I think there is.
None: Ideas are conceptions that debt.
None: The sort of broad array of kinase coverage.
Matteo Levisetti: Okay, and then maybe just one quick follow-up. Matteo, I was just wondering if you had any thoughts around the Pembroke survival number that has recently been presented. [inaudible] I know we're still a couple of years away from a registrational study, but even in the context, how do you think that is? What is that survival?
They have some negative effects on the whole immuno therapy response to checkpoint inhibitor, but.
None: That's conjecture on my part but.
None: Again, I hope that addresses your question.
None: It does thanks for taking the questions.
None: Your next question comes from Ren Benjamin from JMP. Your line is now open.
Matteo Levisetti: Yeah, so I think, well, it's a bit of a mystery to me. I don't know that I've heard or that I'm aware of a clear explanation. Also, it was a surprise that the objective response rate was 27% as opposed to the historical rate of 19%. So that arm in the trial did appear to do better than anticipated. I think, again, it then supports the value of doing a Phase II trial before engaging in a registrational Phase III with almost 5 to 10 times the investment to really just gain confidence that we're on track with regards to what we believe the combined treatment effect is to the current monotherapy effect. So I hope that addresses the question. And again, when this was presented at the Head and Neck Conference in Arizona, there was quite a bit of a discussion with the head and neck experts, and no one really seemed to have an explanation. But again, with regard to Linvatinib, I think there's a clear explanation, ideas, or conceptions that the sort of broad array of kinase coverage may have some negative effects on the whole immunotherapy response to the checkpoint inhibitor. That's conjecture on my part, but... Again, I hope that addresses your question. It does.
Hey, good afternoon, guys. Thanks for taking the questions and congrats on the progress.
Reni John Benjamin: I think you mentioned that there was some data coming out of Vasco for both one on one on one or two can you just give us a sense as to I mean.
101.
It's largely just longer term follow up.
Reni John Benjamin: Correct me, if I'm wrong, there and then for one or two about how many patients worth of data and what kind of follow up should we be expecting.
None: Yes, certainly so I can share here is that we're actually delighted to have been selected for an oral presentation on our cue 100 101 dataset at <unk> in June.
None: It will be as you alluded to.
Copper comprehensive analysis of all the data with longer follow up.
None: With regards to the cue 102, which was also selected for presentation as a poster.
None: At ESCO.
None: We anticipate now having.
None: Data on approximately 35 patients or more.
None: With some follow up as long as.
None: Ted.
None: Eight months.
None: Terrific.
None: And then.
None: Just going back to the strategic.
Matteo Levisetti: Your next question comes from Ren Benjamin from JMP. Your line is now open. Hey, good afternoon, guys. Thanks for taking the questions and congrats on the progress. Yeah, I think you mentioned that there was some data coming out of ASCO for both 101 and 102. Can you just give us a sense as to, I mean, I think the 101 studies are largely just longer-term follow-up. Correct me if I'm wrong there.
None: Sort of partnerships and things that you are evaluating.
None: As you think about.
None: Yes, the way to move forward.
None:
None: How are you thinking about.
None: Actually just.
None: Wrapping up 101 in and one or two kind of nice typo in and presenting that as.
None: The potential.
None: Acquisition that provides a significant upfront that allows you to fund, let's say the autoimmune.
None: Programs, which investors are paying a lot more attention to you are clearly seeing that in the cell therapy space as well they seem to be.
Matteo Levisetti: And then for 102 patients, about how many patients' worth of data do we have and what kind of follow-up should we be expecting? Yes, certainly. So I can share here that we're actually delighted to have been selected for an oral presentation on our Q101-01 data set at ASCO in June. It will be, as you alluded to, a comprehensive analysis of all the data with longer follow-up. With regard to the Q102, which was also selected for presentation as a poster at ASCO, we anticipate now having data on approximately 35 patients or more with some follow-up as long as, you know, out to 8 months. Terrific.
Very enamored by the autoimmune data.
None: How do you take that kind of.
None: Kind of decision, making versus trying to find a strategic that can we.
None: Move with you.
Both 101 in one or two while spending your own money.
Moving that forward.
None: Yes, Brent this is Dan probing question and a really important one, particularly I think in the <unk>.
None: Headwinds in the current capital markets and oncology.
Dan: I think it's clearly a prudent.
Dan: Question.
Dan: I think strategic insight into the challenges in the oncology sector. So we are looking at.
Daniel R. Passeri: And then, as you know, just going back to the strategic partnerships and things that you're evaluating. As you think about the way to move forward, you know, how are you thinking about... [inaudible] very enamored by the autoimmune data? How do you take that kind of decision-making versus trying to find a strategy that can move with you, both 101 and 102 while spending, you know, your own money and moving that forward. Yeah, Ben, this is Dan.
Of that dynamic.
Dan: It Hasnt evaded our thinking that.
Dan: The timeframe and the capital requirement for increasing value for shareholders.
Dan: Be more in favor of autoimmune and the current capital markets, but we have much deeper more mature data. So I think the key for oncology is to align with a company that has the capacity and competencies to get through a registrational path.
Daniel R. Passeri: A probing question and a really important one, particularly, I think, in light of the headwinds in the current capital markets for oncology. I think it's clearly a prudent investment with, I think, strategic insight into the challenges in the oncology sector. So we are looking at that dynamic. You know, it hasn't escaped our thinking that the time frame and the capital requirement for increasing value for shareholders would probably be more in favor of autoimmunes in the current capital markets, but we have much deeper, more mature data. So I think the key for oncology is to align with a company that has the capacity and competencies to get through the regulatory path, and the objective for us would be to be able to retain as much upside for our shareholders.
Dan: And the objective for us would be.
Dan: To be able to retain as much upside for our shareholders. So the calculus that we're ultimately going to decide upon is how we address caf.
Dan: Capital requirements, which are pretty deep.
Oncology for a registration path and that was by the way as part of the rationale that Matteo articulated as to the decision to do a randomized phase II.
Dan: With.
Dan: A very defined discrete number of patients we can add a substantial amount of confidence in value and I think that's also part of our analysis having to do with.
Dan: Strategic alignment with parties and the pharma companies are finding that structure to be very attractive.
Daniel R. Passeri: So the calculus that we're ultimately going to decide upon is how we address capital requirements, which are pretty deep in oncology for a registration path. And that was, by the way, part of the rationale that Matteo articulated as to the decision to do a randomized phase two, with a very defined, discrete number of patients, we can add a substantial amount of confidence and value, and I think that's also part of our analysis having to do with strategic alignment with parties. I think pharma companies are finding that structure to be very attractive, where the degree of confidence goes up dramatically if the randomized data repeats what we've seen in our phase 1a and b. So it's a very important question, and it is part of our overall analysis and, ultimately, the calculus that determines what path we choose.
Dan: Were they a degree of confidence goes up dramatically.
The randomized data repeats what we've seen in our phase <unk> and B.
So it's a very important question as part of our overall analysis and ultimately the calculus that determines what what path we choose.
None: Got it.
None: One final question for me on the autoimmune side.
None:
None: On the one hand them a little bit confused as to how.
None: T cells that are targeting.
Yeah I'm sorry.
None: CMV.
None: Ken.
None: Completely deplete kind of all the b cells over there I can I can imagine some proportion, but all of it maybe.
None: Our niche can help me understand this a little bit better and when might we see some.
None: Preclinical data at any upcoming conferences this year.
Niche: Yes, so the T cell mediated depletion is essentially pan B cell depletion is simply because of the CD 19 anchoring that delivery BSO.
Daniel R. Passeri: I got it. I guess one final question for me on the autoimmune side. On the one hand, I'm a little bit confused as to how T cells that are targeting, you know, that are targeting CMV can, you know, completely deplete all the B cells that are there. I can imagine, you know, some proportion, but all of it. Maybe, you know, Anish can help me understand this a little bit better. And when might we see some, you know, preclinical data at any upcoming... Yeah, Ren, so the T-cell mediated depletion is essentially pan B-cell depletion simply because of the CD19 anchoring that's on every B-cell out at least in circulation. So when the immunostat binds to the B cell displaying the CMV peptide HLA, for the CMV T cell, that's simply presenting it as a surrogate for a virally infected cell, and the cell goes into the effector mechanism.
Niche: At least in circulation.
Niche: So when the immuno stat binds to the B cell displaying the CMV peptide HLA for the CMV T cell that simply presenting it as a surrogate for a virally infected cell and the cell goes into the effective mechanism one of the reasons, we focus on the virus specific for this application Ren is because of the ability to rapidly.
Niche: <unk> respond the effector memory compartments and one that is not dependent much on co stimulation. So you can actually rapidly we call. These the president and high frequencies and a large majority of the population and importantly, they're not exhausted, we know that from a body of literature that we've now had for decades in terms.
The longer lasting.
Niche: Memory repertoire, so that.
Niche: Those things together make for a really strong case for selective Honda single, what major gave you is the nature of sort of long lasting killer population.
Anish Suri: One of the reasons we focus on the virus specific for this application, Ren, is because of the ability to rapidly respond to the effector memory compartment, and one that is not dependent much on co-stimulation. So you can actually rapidly recall these. They're present in high frequencies in a large majority of the population. And importantly, they're not exhausted.
Niche: You could make it specific to a discrete b cell subset, if one chooses to achieve selective b cell depletion that that would just mean that you would swap the marker from our CD 19 targeting to something else and so that optionality remains with us, but I think as a central early mechanistic proof of concept CD 19.
Niche: <unk> was attractive enough, particularly also since the car T data is with CD 19, targeting and that looks pretty robust cities with the early metrics. We've seen so we are in the midst of generating actually a body of data.
Anish Suri: We know that from a body of literature that we've now had for decades in terms of the longer-lasting memory repertoire. So those things together make for a really strong case for selective harnessing of what nature gave you as nature's long-lasting killer population. You could make it specific to a discrete B-cell subset if one chooses to and achieve selective B-cell depletion. And that would just mean that you would swap the marker from CD19 targeting to something else. And so that optionality remains with us. But I think as a central, early mechanistic proof of concept, CD19 was attractive enough, particularly since the CAR T data is with CD19 targeting.
Niche: Large part of the organization is looking at this.
Niche: With a significant amount of.
Niche: Intensity.
Niche: Likely thinking to aim for either an autoimmune meeting or some translational immunity meeting to be able to sort of bring out these concepts a bit more.
Niche: So hopefully maybe try to find something that either in the second half of the year or early next year to.
Niche: To be able to talk more about this.
Excellent thanks for taking the questions.
Niche: Yeah.
None: Oh, yes.
None: Oster.
None: Okay.
None: Lester.
None: Operator.
None: Yes.
None: Okay.
None: This is Dan I think we have lost the operator.
Anish Suri: And that looks pretty robust, at least with the early metrics we've seen. So we are in the midst of generating, actually, a body of data. There's a large part of the organization looking at this with a significant amount of..., intensity. Likely to aim for either an autoimmune meeting or some translational autoimmunity meeting to be able to sort of bring out these concepts a bit more. So hopefully, maybe try to find something either in the second half of the year or early next year to be able to talk more about that.
None: Okay, I think we're having a technical default.
None: Although the operator, so there's one more person waiting in the question queue that we'll try to get on.
None: Okay.
None: Okay, we seem to not be able to resolve the technical issue with the operator so.
None: Dan <unk> with that I think.
Anish Suri: Excellent. Thanks for taking the question. [inaudible] Lester. Operator. This is Dan.
Dan: We will end.
None: And the call I want to thank everyone for listening in and we look forward to providing everyone with <unk>.
Operator: I think we've lost the operator. I think we're having a technical difficulty with the operator, so there's one more person waiting in the question queue that we'll try to get on. Okay, we seem to not be able to resolve the technical issue with the operator. So, Dan, with that, I think... We will end the call.
None: Subsequent updates as they become available over the coming quarter and as Matteo stated we have two presentations at <unk> looking forward to presenting that data in.
Daniel R. Passeri: I want to thank everyone for listening in. We look forward to providing everyone with. Substantial updates as they become available over the coming quarter, and as Matteo stated, we have two presentations at ASCO. Looking forward to presenting that data and autoimmune data at the appropriate conferences coming up over the coming year. I want to thank everyone for your attention, and have a pleasant afternoon and evening. Thank you very much. Music Music Music Music Music Music Music Music Music Music Music
None: Autoimmune data at the appropriate conferences coming up over the coming year I want to thank everyone for your attention and have.
Have a pleasant.
None: Good afternoon and evening, Thank you very much take care.
None: Okay.
None: Okay.
[music].
None: Okay.
None: [music].