Yahoo Finance

Anish Suri

Thanks, Dan, and 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 the 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 patient safety.
Slide 6 provides an introduction to our immunoassay platform for resetting immune balance. We are selective modulation of disease-relevant immune cells, the core framework of an immunoassay that 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 PHLA.s in immunoscience.
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. Importantly, the immunotherapy 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, immune status can selectively engage and activate tumor-specific T cells while avoiding systemic immune activation. In contrast for autoimmune diseases, immuno stats can selectively down modulate autoreactive T cells while avoiding broad immunosuppression.
The next slide, Slide 7 highlights the pipeline of assets that we have developed for restoration of immune balance. In oncology, we have clinically validated the CUE-100 series that selectively deliver the potent cytokine IL-2, along with the TCR activating signal to preferentially activate tumor-specific T cells while sparing all other relevant T cells.
This selective stimulation allows for the generation of a therapeutic index for IL-2, which has eluded many others trying to develop IoT based cancer therapies in over 100 patients dosed. We have demonstrated a substantial increase in efficacy with favorable tolerability for a lead clinical candidate, Q. one oh one in recurrent metastatic head and neck cancer.
We have recently concluded a meeting with the FDA aligning on a registration path, which will be further elaborated upon momentarily, biomaterials with our next clinical candidate, Q. one or two that targets once Tumor one or WT1, we have 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.
Material will describe this efficacy data in detail along with the plans for our registrational path forward with you one-on-one on the autoimmune front, as shown here, we have developed novel and highly promising approaches for restoring immune balance.
Q4 oh one 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 T regs possess the ability to dampen and control autoreactive lymphocytes, which are responsible for inducing tissue damage in autoimmune disease.
Hence, in this regard, T-regs are the master regulators of maintaining immune homeostasis and help Q4 oh one is currently partnered with almost Ono Pharmaceuticals, and this collaboration is moving forward at a strong pace with much productivity. In addition to Q4 oh one, we've also developed a new 500 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. and T cell engagers or CAR CAR T cell therapies. 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?

Matteo Levisetti

Thanks, and good afternoon to everyone. Listening in on today's call. I'm 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 define the registration path forward, but also demonstrated the opportunity of the CUE-100 series as a potential breakthrough for improving patient outcomes across multiple cancers.
The clinical data from the ongoing Q1 oh one trial continues to demonstrate highly encouraging and robust metrics of clinical benefit for patients with newly diagnosed or recurrent metastatic HPV-positive head and neck cancer treated in combination with pembrolizumab in for heavily pretreated recurrent metastatic head and neck cancer patients treated with monotherapy.
We recently had an end of Phase one type B meeting with the FDA where we received guidance and aligned on a path forward to a registrational trial for 201. To that end, we plan to conduct a randomized Phase two study of Q1 oh one 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 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. We intend to pursue this registrational approach with two one to 1 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 Q1 oh one and Keytruda, the patient impact and durability would likely also further reduce the patient population available in the second line setting over time.
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 opportunity, as shown on slide 9, some data from the ongoing clinical trials with Q. one oh one as monotherapy and in combination with pembrolizumab have provided clinical proof of concept validation and derisking of our immunoassay platform.
The latest data generated to date in 2024 continues to bolster prior observations, further enhancing our confidence in Q. one oh one as a potential therapeutic to improve outcomes for patients battling HPV-positive head and neck cancer as previously and consistently stated.
We believe Q1 oh one'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 Q1 oh one monotherapy.
Notably, as previously presented, the median overall survival of patients treated in the second line and beyond. 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 nivolumab and pembrolizumab.
We believe this enhanced survival is due to the repeated stimulation and expansion of tumor-specific T cells given Q1 was 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 Q. one oh one in combination with pembrolizumab represents a greater than doubling of the overall response rate and progression-free survival compared to historical rates with pembrolizumab monotherapy.
Enrollment in the new adjuvant trial is progressing well and preliminary observations support expansion of E7 specific antitumor T cells and increases in NK cells within the tumor micro-environment. These findings are consistent with the pharmacodynamic changes observed in the peripheral blood of patients treated with Q1 oh 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.
And for MS, pembrolizumab is approved as the standard of care treatment of first-line patients with recurrent metastatic head and neck cancer that have tumors with CPS scores of greater than or equal to 1% CPS as a measure of PD-L1 expression based on response rate of 19% observed in the keynote 48 study following combination treatment with Q. one oh one, 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 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 patient. Importantly, 11 patients remain on treatment, including three with stable disease that exhibit reductions in their target lesions.
Notably for patients with low CPS scores, an overall response rate of 50%, 50% was observed with Q1 oh one and pembrolizumab, which represents a greater than tripling of the historical overall response rate of approximately 15% observed with pembrolizumab alone.
In totality, our data suggests that not only does Q. one oh one appear to demonstrably enhance the response rate of PD-1 inhibition, but 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 one to 19 represent approximately 50% of all patients that are CPS positive and eligible for treatment with checkpoint inhibitor in the front-line setting. 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 of note, the Kaplan-Meier estimate of the median progression-free survival for patients treated with Q1 oh one 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, the four migs per kg expansion dose in the ongoing Q1 oh one 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, 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 Q1 oh one. 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 cell-free HBV. Dna of this magnitude have also been observed in multiple patients with durable stable disease as defined by resist. The data from the Q. one oh one oh one 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 Q. one oh one plus pembrolizumab registrational trial, including guidance on the design of a small Phase two trial to confirm the Q. one oh one dose used for a subsequent registrational trial consistent with the Project Optimus directive.
An overview of the planned Phase two 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 Q. one and one doses in combination with pembrolizumab or pembrolizumab over overall response rate will be the primary endpoint with others, including PFS and OS as secondary endpoints.
The primary analysis of overall response is anticipated to occur approximately 24 months after the first patient is enrolled, as outlined on slide 14, the clinical benefit observed with 201 combination treatment in first-line patients with HPV-positive head and neck squamous cell carcinoma is compelling and compared to historical published data.
We believe this Phase two trial design and the resulting data will provide a clear estimation of treatment effect confirmation of the dose to be tested in Phase three and increase the overall probability of success for the registrational right, as demonstrated with the Q. one or two program, which I will now discuss we believe the data from Q1 one has provided a de-risking and mechanistic validation for additional biologics from the IL two based CUE-100 series.
As a reminder, shown on slide 16, Q1 oh two and two went to one shared 99% amino acid sequence identity. This enabled us to significantly decrease the development time and cost of Q1 oh two. As we were not required by the FDA to repeat IND-enabling toxicology studies for Q1 oh two.
And we were also able to initiate the Phase one dose escalation study at one milligram per kilogram dose at which we observed clear signs of biologic activity with Q1 at one, we have now completed the dose escalation portion of the Ib 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 note that these numbers are greater than a collective of 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 Q1 oh two therapy in the future. Emerging pharmacodynamic data from blood samples of patients treated with Q1 oh two is shown on slide 18.
As seen here on the left that and consistent with our preclinical datasets in our experience with Q1, one selective and robust expansion of WT1 specific T cells has been noted among the patients treated with Q1 of two with two representative examples shown here.
Expansion of these tumor-specific T cells is expected to enhance antitumor immunity with the potential to drive tumor reductions, as shown on the right, a patient with gastric cancer that progressed on three prior lines of therapy, including checkpoint inhibitor, has experienced a decrease in the sum of three target lesions of minus 34% 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 have now come off stream.
Also of note, a pancreatic cancer patient treated on this study has benefited through maintaining stable disease for greater than eight months, which is remarkable in the setting of this devastating the aggressive tumor types, 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, patient screening and enrollment rate continued to go exceedingly well, underscoring investigator enthusiasm in the need for effective therapies in WT1 expressing cancers 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 immunotherapies.
While many therapeutic modalities and combination approaches for immune modulation are being pursued, significant challenges exist with regards to sub optimal safety, tolerability and efficacy to enable broad patient reach.
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 stand-alone treatment options as well as combination approaches, for example, with checkpoint inhibitors.
As just conveyed the ability of Q1 oh one to selectively expand and activate targeted tumor-specific T cells complements the mechanism of checkpoint inhibition, thus expanding patient reach and enhancing therapeutic therapeutic benefits.
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 in enhancing the magnitude of that there. 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 Q1 oh two monotherapy antitumor activity across multiple indications where checkpoint inhibitors have been largely ineffective, and we look forward to presenting additional data on both programs at Asco in June.
And I will now turn the call over to Anish. Anish?

Anish Suri

Thanks, retail. Let me take a few minutes to update on the notable progress with our platform for autoimmune diseases, starting with Q4 oh one and regulatory T cells, as indicated on slide 20, 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 regs.
As mentioned previously, Q4 to one 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 T regs or ITRX.
In addition, Q4 oh one also strongly expands existing natural T-Rex. This program has been a very productive collaboration with Ono Pharmaceuticals, wherein Ono is supporting all of our ongoing preclinical work to identify and optimized clinical lead compound, which we are on track to accomplish in the second half of 2024.
The next slide, Slide 22 highlights the unique and differentiated mechanism of action of Q4 to one over the other CD25 biased IO to mid 10s for expansion of existing T-regs, as shown here, two four to 1 can expand pre-existing regulatory T cells and convert naïve CD4 positive T cells into new T-Rex, thereby enhancing the quantitative population and the qualitative features of T-regs to control the pathogenic cellular reactions in autoimmune patients.
Slide 23 provides examples of the potent activity of Q4 oh one in the conversion and generation of stable T-Rex cells. As shown in the left panel conversion and expansion of human CD4 T cells to T-regs only occurs when the IL-2 and TGF-beta signals are delivered via Q4 oh one.
Either signal alone does not result in direct conversion and Q4 to one represents the first singular biologic capable of delivering both signals simultaneously in the right panel is an in vivo study, demonstrating efficacy of Q4 four one in an animal model of autoimmune gastritis.
This is a model developed by Dr. Richard Apollo at St. Louis University, whether in a short treatment with Q4 oh one results and a long lasting protection from gastritis as shown by the histopathological analysis and disease scores. We believe this mechanism of action of Q. four one, including the demonstration of long-lasting efficacy after just a short duration of treatment will apply to many other autoimmune diseases.
Let's move on to Slide 24. That introduces a new series of imetelstat term, 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, recent datasets from small clinical studies have demonstrated remarkable efficacy in autoimmune patients treated with CAR T cells directed against CD19 to deplete B-cells. In many cases, long-term ongoing clinical remissions have been noted in patients with lupus myositis with no concurrent immunosuppressive regimens, which could be early signals of functional cures.
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, especially on the next slide, slide 26, the Q. 500 series builds upon the clinical derisking accomplished with the CUE-100 series.
That constant is the presence of a Biovail and peptide HLA molecule that selectively engages TCRs of selected T cells. In the case of the Q. 500 series. The peptide presented by the HLA is a well-characterized virus epitope recognized by virus specific memory T cells present in high frequencies in all of us.
Examples of such virus apoptosis, which include CMV, EBV CAR, Scooby-Doo, et cetera. In addition, the Q. 500 molecule also contains scFv is directed against B cell cell surface molecules such as CD. 19. This configuration allows for Q. 500 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 repertoire. 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 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 antiviral T cell repertoire and are present in large fraction of the population.
As shown here, B-cell killing is specific to the engagement of CMB's specific T cells in other words, IQ. 500 molecule harboring an HIV peptide does not mediate B-cell killing since this, since the HIV specific T cells are not present in circulation.
So the selective harnessing and redirection of the protective onto antiviral T cells to kill targets creates a very attractive opportunity for Q. 500 series stats. 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. Cue 500 series could also be effectively applied for the treatment of B-cell malignancies in the oncology therapeutic area.
Next slide, Slide 29 briefly summarizes the superior differentiation of the mechanism of action of Q. 500 over other competing modalities with B-cell depletion, including ADCC, CAR-T cellular therapy and Pan T-cell engagers.
We now recognize that ADCC mechanism has 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.
Furthermore, Fc receptor polymorphisms dictate high versus low ADCC factor genotypes. In the case of CAR T approaches, complex manufacturing and supply chains remain a challenge for broad access in addition, patient conditioning Magic regimens in patient administration and safety risks, including CRS and neurotoxicity, continue to pose challenges for CAR T therapies.
Pan T cell engagers that activate the T cells via anti-CD3 anti-CD20 at cross-linking are also not favorable for autoimmune applications. These modalities activate all T cells indiscriminately resulting in CRS and other toxicities. Hence, are suitable irons 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 that Q. 500 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 in both Q4 oh one and Q. 500 and their applications in autoimmune disorders. I'll turn the call to Kerri to review the financial details. Kerri?

Kerri-Ann Millar

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 Q4 line, 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 31st, 2023 and 2022, respectively. The decrease was primarily due to drug substance manufacturing projects for Q. one oh one and Q. one oh two that were completed in 2022.
General and administrative expenses were $4.6 million and $3.7 million for the three months ended December 31st, 2023 and 2020, respectively. The increase was primarily due to an increase in professional and consulting period fees during this time.
For the year ended December 31st, 2023 and 2022, the company reported collaboration revenue of approximately $5.5 million and $1.2 million, respectively, increases due to the revenue earned from our strategic collaboration agreement with Ono Pharmaceuticals.
Research and development expenses were $40.8 million and $38.6 million for the years ended December 31st, 2023 and 2022, respectively. The increase was due primarily to clinical development costs and research laboratory expenses, which were partially offset by decreases in employee costs and rent expense.
General and administrative expenses remained relatively flat at $16.7 million and $16.2 million for the year ended December 31st, 2023 and 2022, respectively. And as of December 31st, 2023, the company had approximately $48.5 million in cash and cash equivalents $34.4 million in working capital and $47.2 million common shares outstanding. We expect our current cash and cash equivalents to fund operations into the first quarter of 2025.
I'll now turn the call back over to Dan for closing remarks. Dan?

Daniel Passeri

Thanks, Kerri. As you 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 at Q2'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 Q. one oh one and Q1 oh two 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.
However, we 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.
And importantly, both Q. one oh one in Q1 oh two have demonstrated the potential to stimulate the patient's immune system to recognize the tumors growing in their bodies as far in marshaling in attack. Furthermore, the clinical observations to date support the putative mechanism of action for Q. one oh one and by implication Q. one oh 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 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.
As conveyed in slide number 31, we are well positioned for value inflection milestones over the coming year with, namely with Q. one oh one, 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've presented on in the 1a and 1b, which is our Q. one oh one plus checkpoint inhibitor versus the checkpoint inhibitor standard of care alone.
We expect interim analysis at 14 months and the overall response rate and median progression-free survival analysis between 22 and 24 months, both of which underscore breakthrough potential with Q1 oh one 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 immunoassay that platform our application in solid tumors per se by expanding patient reach and enhancing clinical benefits, enhancing clinical benefits of checkpoint inhibitors into a broad range of cancers.
Successful readout in the randomized Phase two would place cube in a position of leverage and strength as a partner of choice for checkpoint inhibitor franchises. Furthermore, Q1 oh two patient expansion positions combo 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 Q4 oh one for tiering induction currently partnered with Ono on with, of which we have retained an option for a 50% interest in the U.S. market with two near term milestones potentially being realized. In Q. five oh one for B-cell ablation with the potential to displace CAR T with a biologic for B-cell driven autoimmune diseases such as lupus.
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 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 checkpoint inhibitor sector and enhance market reach and have also demonstrated platform, modularity and scalability.
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 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 engaging and ongoing strategic discourse with multiple prospective strategic partners based on continued developments.
Through these ongoing discussions, we're highly confident will be successful, 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 our collaboration partners for their continued support guidance and trust and more.
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. And with that, I'd like to now turn the call back over to the operator to open up for questions. Operator?

Question and Answer Session

Operator

Thank you. Ladies and gentlemen, we will now conduct the question and answer session. (Operator Instructions)
Maury Raycroft, Jefferies.

Maury Raycroft

Congrats on the progress and thanks for taking my questions. I was going to ask about the randomized Phase two combo study. Can you talk about how many patients you anticipate you'll need in each arm? And if you're successful on that first interim on an overall response rate, would that allow you to advance into a registrational Phase three?

Daniel Passeri

Sure. Matteo, do you want to take that question and thanks, Mark.

Matteo Levisetti

Yes, yes, certainly. So the 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, will have a data safety monitoring board that will look at the results of that first interim and provide a recommendation to continue the trial of per protocol if everything looks good.
And it's really the final analysis at 24 months, 22 to 24 months and that that would serve as the substrate to proceed into a registrational trial, although a fair bit of a trial startup could be done once the interim analysis, the first one provides a positive record recommendation to move forward.

Maury Raycroft

Got it. That's helpful. And then, Dan, you talked about potential partnering. Can you clarify what stage you would look to potentially partner? Would it be as you're running the Phase two more before the Phase three? And then what could potential partnership look like from a development and economic standpoint?

Daniel Passeri

Sure. A very important question. And 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.
So pertaining to Q1 oh one Q. one oh two, I think the key there is on identifying an appropriate party with the sort of requisite insight on 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 on the economics 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, the sort of 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 really, 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, the structure of that partnership was very favorable. They've actually been an outstanding partner with an early asset that basically subsidizing the development we have.
It's 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 sort of optimal upside for our shareholders?
Well, 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 in a dynamic manner based on the various options we have in front of us.

Maury Raycroft

Got it. That's yes, that's helpful. And for the five oh one on program. Just wondering if you're talking more about where you're at with our preclinical development and 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 do you think about that?

Anish Suri

Yes, Maury, this is Anish. 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, we've tested this across a number of different memory T cell specificities of CMV being one, which is highly present in a majority of funds, but also star scores.
We do at this point in time, there's a very conserved capital from the spike protein that virtually all of us today in the world should have site-specific T-cells, whether it's by vaccination or natural infection. So that provides a great substrate to essentially use. There's nature's pandemic to redirect it to something good, which is destroying these pathogenic B cells and 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. 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 SCF. three of the B-cells to a cell surface tumor antigen.
I mean, think about PSMA, think about so to think about her to et cetera. 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 in 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 derisked very much by the 100 TVs as I that's why I sort of stress that the core component remains the same. It's a buy build and peptide HLA and obviously has no oil to. Instead of that, the model is an anchoring scFv. So again, there's a lot of good learnings from the 100 series, 1.11 or two, that sort of beneficially impact 500 series.

Maury Raycroft

Got it. That's really helpful. Thanks for taking my questions.

Anish Suri

Thank you.

Operator

Stephen Willey, Stifel.

Stephen Willey

Good afternoon. Thanks for taking the questions and apologize for the background noise. But Tom, maybe just a couple of more space. Few questions. Can you just maybe speak to the it's the second key one or one dose that you're contemplating, including into the randomized Phase two? And then can you also speak as to kind of what triggers the interim analysis is that just having? But given number of patients out beyond some specific duration of follow-up in the sense another question.

Matteo Levisetti

Okay. I can take that. Thank you very, very, very good questions. And so on the doses that we anticipate examining our certainly the four milligram per kilogram dose that we've really studied in 25 patients with no risk of objective response rate of close to 50%, and we haven't finalized the selection of the other dose.
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. And then in the dose escalation that two migs per kg with pembrolizumab. #
We also observed a very profound durable objective response. So so I think the answer there will be two doses certainly we believe at this point for mix per gig and then very likely to make per kick dose, we've seen really very strong activity as well.
With regards to the triggering of the first interim analysis, it really will be and determined when approximately 70% to 80% of patients have gotten through the cycle five scan.
Okay. So it's really I look at 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 five scan. And we'd anticipate that based on what we've observed to date in the one to one for one trial in the historical monotherapy rate that that would have progressed then to ultimately the final analysis and which again, that will be a complete analysis of the data set with all patients.
Now having follow-up to cycle five to get to your primary of overall response rate. That final analysis is very valuable because that your data then that can be brought forward to start your Phase three and the waste design then allows also for follow-up for the supplemental analysis for PFS and OS. But we don't have to wait for that to hold up the initiation of the Phase three trial.

Stephen Willey

Okay. I guess that's helpful. And can you maybe just talk a little bit about kind of the pushes and pulls that were under consideration as have you thought about carving out kind of an independent randomized Phase two versus trying to do something more Phase two, three, adaptive seamless and maybe in answering that you can speak to, I guess, to what extent if any, was this path forward kind of informed by some of these ongoing strategic discussions.

Matteo Levisetti

So very good question. And certainly an option to further develop. The combination is to go with, say, a Phase two, three sort of seamless design, the first component of that. And this has become, I think, quite common since a Project Optimus has sort of gone into effect as a directive or her mandate on is to have a lead in with the two doses to select your dose and then to go into the Phase three randomized portion.
So so I think there's multiple components to the considerations and the initiation of that Phase two three is a larger endeavor and investment, I think clearly, and the Phase two really offers the opportunity to generate data that confirms the dose to go into Phase three in there for this Phase three is simpler in design or there's no lead-in, which is actually takes quite a bit of time, at least a year to do and then also gives us the opportunity to have, if you will, a confirmatory analysis of that would increase one's confidence in being successful in ultimately the Phase three trial.

Stephen Willey

Okay. And then maybe just one quick follow-up, but I was just wondering if you had any thoughts around that pembro survival number that was recently presented from the LEAP 10 trial in GIST. I know we're still a couple of years away from a registrational study, but even in the context of the Phase two, how do you think that influences your expectation as to what that survival number might look like fix yet?

Matteo Levisetti

So I hate to say, well, it's a bit of a mystery to me I don't know that I've heard that I'm aware of a clear on the explanation. I'm also a surprise that the 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 than anticipated.
I think again, it then supports the value of doing a Phase two trial before engaging into a registrational Phase three with, you know, almost 5times to 10 times the investment to really just gain confidence that we're on track with regards to what we believe the combination treatment effect is to the current monotherapy effect. So so I think I hope that addresses the question I don't.
And again, when this was presented at the head neck conference in Arizona. There was quite a bit of a discussion with the head and neck experts, and no one really seems to have had an explanation. But but again, with regards to Linde vaccinated. But um, I think there is a cut ideas are conceptions that the sort of a broad array of kinase coverage may have some negative effects on the whole immunotherapy response to the checkpoint inhibitor. And that's conjecture on my part. But again, I hope that addresses your question.

Stephen Willey

It does. Thanks for taking the questions.

Operator

Reni Benjamin, JMP.

Reni Benjamin

Hey, good afternoon, guys. Thanks for taking the questions and congrats on the progress on this. And I think you mentioned that there was some data coming out of Asco for both one and one and one or two. Can you just give us a sense as to I mean, I think the one on one studies. It's largely just longer term follow-up, 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?

Matteo Levisetti

Yes, certainly. So I can share here that we're actually delighted to have been selected for an oral presentation on our Q. one oh one. Oh one dataset at ASCO in June, and it will be, as you alluded to a copper, very comprehensive analysis of all the data with longer follow-up with regards to the Q. one oh two, 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 zoom out to eight months.

Reni Benjamin

Terrific. And then as just going back to the strategic plan, sort of partnerships and things that you are evaluating as you as you think about, I guess still the way to move forward? And how are you thinking about potentially just wrapping up one one and one or two kind of in-house nice typo and presenting that as a as a potential an acquisition that provides a significant upfront.
It allows you to fund, let's say, the autoimmune programs, which investors are paying a lot more attention to. You're clearly seeing that in the cell therapy space as well. They seem to be very enamored by the autoimmune data. How do you take that kind of kind of decision making versus trying to find a strategic that can move with you both one, one and one or two while spending your own money and moving that forward?

Daniel Passeri

Yes, Brent, this is Dan probing question and a really important one, particularly, I think, in the of the headwinds in the current cap capital markets in oncology, I think it's clearly a prudent.
Our question was with I think strategic insight into the challenges in the oncology sector. So we are looking at so that dynamic, it hasn't evaded our thinking that and the timeframe and the capital requirement for increasing value for shareholders.
It would probably be more in favor of autoimmune 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 a registrational path. And the objective for us would be 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 capital requirements, which are pretty deep in oncology for a registration path. And that was, by the way, as part of the rationale that material articulated S's decision to do a randomized Phase two with a very defined discrete number of patients, we can add a substantial amount of confidence in value. A
nd I think that's also part of our analysis having to do with and some strategic alignment with parties. And the pharma companies are finding that structure to be very attractive where they the degree of confidence goes up dramatically if the randomized data repeats what we've seen in our Phase Ia and b, so it's a very important question, and it is part of our overall analysis and ultimately the calculus that determines what what path we choose.

Reni Benjamin

Got it. I guess one final question from me on the autoimmune side. On the one hand, I'm a little bit confused as to how on T cells that are targeting know, yes, targeting CMV, can I completely deplete kind of all the B-cells that are there. I can I can imagine some proportion, but all of it maybe Anish can help me understand this a little bit better. And when might we see some our preclinical data at any upcoming conferences this year?

Anish Suri

Yes, 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 depletion in circulation. So when the immunoassay that 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 effector mechanism.
One of the reasons we focus on the virus specific for this application, Graham is because of their ability to rapidly respond effector memory compartment and one that is not dependent much on co-stimulation. So you can actually rapidly we call these. They're present in high frequencies in a large majority of the population.
And importantly, they're not exhausted. We know that from a body of literature that and we've now had for decades in terms of the longer lasting memory repertoire so that those things together make for a really strong case for selective, harnessing of what major gave you as a major sort of 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 a 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 also cents CAR T data is with CD19 targeting, 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 that a large part of the organization is looking at this with a significant amount of intensity likely thinking 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 tried to find something that either in the second half of the year or early next year to be able to talk more about this.

Reni Benjamin

Thanks for taking the questions.

Kerri-Ann Millar

Hello? Buster?

Daniel Passeri

This is Dan. I think we have lost the operator.

Kerri-Ann Millar

I think we're having a technical difficulty.

Daniel Passeri

I know that probably with the operator.

Kerri-Ann Millar

So there's one more person waiting in the question queue that we're trying to get on.

Daniel Passeri

Okay. We seem to not be able to resolve the technical issue with the operator.
So this is, Dan. I'll with that, I think we will end the call. I want to thank everyone for listening in, and we look forward to providing everyone with substantive updates as they become available over the coming quarter. And as Mateo stated, we have presentations at Asco looking forward to presenting that data and autoimmune data at 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 Take care.