Q1 2024 Gritstone bio Inc Earnings Call

LaTanya: Greetings. My name is LaTanya, and welcome to Gritstone Bio's first quarter 2024 conference call. Please note this event is being recorded. At this time, I'd like to introduce George MacDougall, Head of Investor Relations and Corporate Communications at Gritstone. Please go ahead, sir.

Greetings My name is Latanya and welcome to the grid Stone Bio's first quarter 'twenty 'twenty four conference call. Please note. This event is being recorded at this time I'd like to introduce George Macdougall head of Investor Relations and corporate communications at quit stone. Please go ahead Sir.

George MacDougall: Thank you, LaTanya, and thank you, everyone, for joining Gritstone's conference call to discuss our financial results, clinical, and business updates for the first quarter of 2024. With me on the call today from Gritstone are Andrew Allen, Co-Founder, President, and CEO; Celia Economides, Executive Vice President and Chief Financial Officer; and joining us for the Q&A portion will be Karen Youse, Executive Vice President and Head of R&D.

George MacDougall: Thank you Latanya and thank you everyone for joining grid Stones conference call to discuss our financial results clinical and business updates for the first quarter of 2024.

George MacDougall: With me on the call today are from grid stone or Andrew Allen <unk> co founder President and CEO, Julia economies Executive Vice President and Chief Financial Officer, and joining us for the Q&A portion will be carrying use executive Vice president and head of R&D.

George MacDougall: Today, after the market closed, we issued a press release providing corporate updates and financial results for the first quarter of 2024. The press release is available on our website. I'd like to remind you again that today's call is being webcast live and via a link on Gritstone's Investor Relations website, where a replay will also be available after it's completed. After our prepared remarks, we will open up the call for Q&A. During the course of this call, we will make forward-looking statements that are based on current expectations.

George MacDougall: After the market closed we issued a press release, providing corporate update and financial results for the first quarter 'twenty 'twenty four.

George MacDougall: The press release is available on our website I'd like to remind you again that today's call is being webcast live and via a link on grid Jones Investor Relations Web site, where a replay will also be available after its completion.

George MacDougall: After our prepared remarks, we will open up the call for Q&A during.

George MacDougall: These forward-looking statements are subject to a number of significant risks and uncertainties, and actual results may differ materially from those that are described. We encourage you to review the risk factors in our most recent Form 10-Q, which is filed with the U.S. Securities and Exchange Commission and is also available on our website. All statements in this call are made as of today based on information currently available to us, except as required by law. We disclaim any obligation to update such statements, even if our views change.

George MacDougall: During the course of this call we will make forward looking statements that are based on current expectations. These forward looking statements are subject to a number of significant risks and uncertainties and actual results may differ materially from those that are described.

George MacDougall: We encourage you to review the risk factors in our most recent Form 10-Q.

George MacDougall: With the U S Securities and Exchange Commission and is also available on our website.

George MacDougall: All statements on this call are made as of today based on information currently available to us except as required by law, we disclaim any obligation to update such statements. Even if our views change Bridgestone host. These calls on an AD hoc basis, and we hope you'll find today's call. He useful with that let me turn it over to Andrew Andrew.

George MacDougall: Gritstone hosts these calls on an ad hoc basis, and we hope you'll find today's call useful. With that, let me turn it over to Andrew.

Andrew R. Allen: Thank you, George, and good afternoon, everybody, and thank you for joining our first quarter of 2024 conference call. This is a very exciting time for Gritstone, and I'll begin today's call with a review of our most recent data from our personalized cancer vaccine program, Granite, as well as provide other clinical and corporate updates. Ben Seeley will present the financials, and I'll come back to share closing remarks. Okay, let's get

Andrew: Thank you George and good afternoon, everybody and thank you for joining our first quarter of 'twenty 'twenty Four conference call. This is very exciting time, so bernstein.

Andrew R. Allen: I'll begin today's call with a review of our most recent data from our personalized cancer vaccine program granite as well as provide other clinical and corporate updates.

Speaker Change: Then <unk> will present, the financials and I'll come back to share closing remarks, okay lets get guy.

Andrew R. Allen: So we recently shared preliminary data from our randomized Phase II study of granite in frontline metastatic microsatellite-stable colorectal cancer patients. These early data are highly encouraging, and they suggest that our personalized neoantigen vaccine is inducing therapeutically beneficial immune responses in the 67 patients included in our preliminary data. Let's review what we showed.

Andrew R. Allen: So we recently shared preliminary data from our randomized phase two study of granite in frontline metastatic microsatellite stable colorectal cancer patients.

Andrew R. Allen: These early data highly encouraging and they suggested all personalized neo antigen vaccine inducing therapeutically beneficial immune responses in the 67 patients included in our preliminary data set.

Andrew R. Allen: Let's review what we showed.

Andrew R. Allen: Firstly, the patients we're treating in this study are typical colorectal cancer patients. Approximately 75% of them have liver metastases, and approximately half of them have KRAS mutations. In terms of efficacy, we observed a trend towards progression-free survival, or PFS, benefit with a hazard ratio in the overall population of 0.82. The median progression-free survival, or PFS, duration in this indication is approximately 11 months. The last patient randomized in this study entered in August 2023.

Andrew R. Allen: Firstly the patients we're treating in this study all typical colorectal cancer patients.

Andrew R. Allen: Proximately, 75% of them have liver metastases and approximately half of them have K Ras mutations.

Andrew R. Allen: In terms of efficacy, we observed a trend towards progression free survival or PFS benefit.

Andrew R. Allen: The hazard ratio in the overall population of zero point H two.

Andrew R. Allen: Median progression free survival or PFS in this indication is approximately 11 months.

Andrew R. Allen: The last patient randomized in this study entered in August 2023 and these data were cuts in early March 'twenty 'twenty for me.

Andrew R. Allen: And these data were cut in early March 2024, meaning that the last patient was on study for only approximately eight months, obviously short of the median BFS of 11 months. That renders these data rather immature, but even though these data are preliminary, with over 60% censoring, meaning that over 60% of patients have not yet achieved an event of progression or death, this is a promising signal. As you may know, a hazard ratio of less than one implies a treatment benefit, and the lower the hazard ratio, the stronger the treatment effect, i.e., the greater the benefit.

Andrew R. Allen: That last patient was on study for only approximately eight months, obviously shorted the median PFS of 11 months.

Andrew R. Allen: That rent disease states, it rather immature, but even though these dates are all preliminary with over 60% censoring.

Andrew R. Allen: Meaning that over 60% of patients had not yet achieved in the event of progression or death. This is a promising signal.

Andrew R. Allen: As you May know hazard ratios less than one implies a treatment benefit the lower the hazard ratio of <unk>.

Andrew R. Allen: But the treatment effect I E. The greater the benefit.

Andrew R. Allen: Now, to get a better understanding of what outcomes we may see as the overall data set matures. We identified at baseline, prior to therapy, a subset of patients that would be likely to progress faster than the overall population. Nearly all of these patients, and we refer to them as high-risk, had liver metastasis. As expected, the PFS data in this group were more mature, with 44% sensor.

Andrew R. Allen: Now to get a better understanding of what outcomes, we may see as the overall data set matures.

Andrew R. Allen: We identified at baseline prior to therapy, a subset of patients that would be likely to progress faster than the overall population.

Andrew R. Allen: Nearly all of these patients and we refer to them as high risk had liver metastases.

Andrew R. Allen: As expected the PFS stage, when this group with more mature with 44% censoring and.

Andrew R. Allen: And the apparent PFS benefit associated with granite therapy was much stronger in this high-risk population than in the overall population. We reported a hazard ratio of 0.52, which is striking and equates to a 48% relative risk reduction of progression or death with granite versus control. The early data in these high-risk patients, who give us information fast, give us a potential window into the future. As our data mature, meaning more patients experience disease progression, we expect the clinical benefits of granite versus standard of care to become more pronounced. We're excited to share the mature PFS data on all patients in the third quarter of 2024, and then we plan to discuss the final phase 3 endpoints with the FDA.

Andrew R. Allen: The apparent PFS benefit associated with Atlanta therapy was much stronger in this high risk population than in the overall population.

Andrew R. Allen: We reported a hazard ratio of 0.5 to what.

Andrew R. Allen: It is striking and equates to a 48% relative risk reduction of progression or death with granite versus control.

Andrew R. Allen: The early data in these high risk patients, who give us information foster.

Andrew R. Allen: As a potential window into the future and this is all data mature, meaning more patients experienced disease progression, we expect the clinical benefits of granite versus standard of care to become more pronounced.

Andrew R. Allen: We're excited to share the mature PFS data on all patients in the third quarter of 2024, and then we plan to discuss the final phase three endpoints with the FDA.

Andrew R. Allen: The encouraging PFS data at this early time point are important because PFS has historically been a proxy for overall survival in this disease and has therefore been used by regulatory authorities as the basis for approval of novel therapies. Previously, we've been cautious about PFS as an efficacy endpoint, given the potential for pseudoprogression with immunotherapy. Pseudoprogression is a phenomenon where lesions actually grow at the beginning of treatment prior to shrinking, which can lead to the attendant risk of patients being incorrectly labeled as having progressive disease.

Andrew R. Allen: The encouraging PFS stage. This early time points are important.

Andrew R. Allen: CFS has historically been a proxy for overall survival in this disease and has therefore been used by regulatory authorities as the basis for approval of novel therapies.

Andrew R. Allen: Previously we've been cautious about PFS as an efficacy endpoint.

Andrew R. Allen: Given the potential for pseudo progression with immunotherapy.

Andrew R. Allen: The progression is a phenomenon where lesions actually grow at the beginning of treatment prior to shrinking which can lead to the attendant risk of patients being incorrectly labeled as having progressive disease.

Andrew R. Allen: To date, we have seen no evidence of pseudoprogression in our Phase 2 study, which supports the use of PFS as a Phase 3 efficacy endpoint, perhaps as the basis for approval. And this topic will be discussed with FDA at our end-of-Phase 2 meeting. It's also worth noting that we've seen apparent extension of PFS with granite before.

Andrew R. Allen: To date, we have seen no evidence of pseudo progression in all phase two study, which supports the use of PFS as a phase III efficacy endpoint, perhaps as the basis for approval in this topic will be discussed with FDA at all end of phase II meeting.

Andrew R. Allen: It's also worth noting we've seen our parents extension of PFS with granite before we.

Andrew R. Allen: We observed PFS and OS extension in third-line colorectal cancer patients treated in our Phase I-II study of granite, where in the 50% or so of patients with biochemical and molecular responses to granite, meaning reductions in tumor markers, we saw extended PFS and OS compared with the non-responding patients. The interim data from this phase 1-2 were published in Nature Medicine in 2022. And recall that we also saw similar signals of apparently extended OS, again linked to biochemical and molecular responses, in a Phase I-II study of Slate, our off-the-shelf cancer vaccine that uses the same platform technologies as Granit, but this was in patients with advanced non-small cell and microsatellite-stable colorectal cancer.

Andrew R. Allen: We observed PFS and OS extension in third line colorectal cancer patients treated in our phase one two study of granite.

Andrew R. Allen: We're in the 50% or so of patients with biochemical molecular responses to granite, meaning reductions in tumor markers, we saw extended PFS and OS compared with a non responding patients.

Andrew R. Allen: Interim data from this phase one two what published in nature Medicine in 2022.

Andrew R. Allen: And recall that we also saw similar signals of a power of the extended O S again linked to biochemical and molecular responses in a phase one two study of slate are off the shelf cancer vaccine that uses the same platform technologies as granite, but this was in patients with advanced non small cell and microsatellite stable colorectal cancer.

Andrew R. Allen: The fact that we are seeing these concordant signals across different studies, different settings, and different disease types gives us further confidence that granite could be driving meaningful clinical benefits. Now, to limit the potential impact of pseudoprogression, we set PFS as the first secondary efficacy endpoint for our Phase II trial. And the primary endpoint was set as molecular response, a specific method of measuring change in circulating tumor DNA, which I'll abbreviate to ctDNA. And this was based on what we'd seen in Phase I-II. And, of course, there were no controls on that.

Andrew R. Allen: The fact that we are seeing these concordant signals across different studies different settings and different disease types gives us further confidence the granite could be driving meaningful clinical benefit.

Andrew R. Allen: Now to limit the potential impacts of pseudo progression, we set PFS as the first secondary efficacy endpoint for all phase II trial, and the primary end point with such as molecular response, a specific method of measuring change in circulating tumor DNA, which I'll abbreviate C. T. DNA and this was based on what we'd seen in phase one two.

Andrew R. Allen: And of course, they were no controls in that study.

Andrew R. Allen: So therefore, we had to make an assumption about how chemotherapy would affect ctDNA going into this study. What we observed is that chemo actually has an unexpectedly prolonged effect, rendering a single time point definition of ctDNA response, which is what we used, unreflective of clinical benefits. Now, importantly, when we look at ctDNA trends across the entire study period, we see broad evidence that granite patients are indeed experiencing greater reductions in ctDNA versus those in the control group. This finding is consistent with the PFS signal.

Andrew R. Allen: So therefore, we have to make an assumption about how chemotherapy would affect C. T DNA going into this study.

Andrew R. Allen: What we observed is that chemo actually has an unexpectedly prolonged effect rendering a single time point definition of C. T. DNA response, which is what we used unreflective of clinical benefit.

Andrew R. Allen: Now importantly, when we look at C. T DNA trends across the entire study period, we see broad evidence the granite patients are indeed experiencing greater reductions in C. T DNA versus those in the control group. This finding is consistent with the PFS signal.

Andrew R. Allen: So the data emerging from the randomized Phase 2 of our GRANiT trial build upon what we observed in the Phase 1-2 trial and suggest that granite neoangina-directed immunotherapy could deliver a strong PFS result in metastatic colorectal cancer patients in a few months' time. And again, we expect those mature data in the third quarter of this year. But why would positive data be significant for patients? Because colorectal cancer is now the leading and second leading cause of U.S. cancer deaths in males and females under 50, respectively, in addition to being the second leading cause of cancer mortality worldwide.

Andrew R. Allen: So the data emerging from the randomized phase II of our granite trial build upon what we observed in the phase one two trial.

Andrew R. Allen: And suggests the granite and you mentioned directed immunotherapy could deliver a strong PFS result in metastatic colorectal cancer patients in a few months' time.

Andrew R. Allen: Again, we expect those mature data in the third quarter of this year.

Andrew R. Allen: But why would positive data would be significant for patients because colorectal cancer is now the leading and second leading cause of U S cancer deaths in males and females under 50, respectively. In addition to being the second leading cause of cancer mortality worldwide.

Andrew R. Allen: Microsatellite-stable tumors comprise about 95 percent of all metastatic colorectal cancer diagnoses, and treatment options are few, with no approved immunotherapies for this highly resistant cold tumor. The positive randomized trial result would therefore offer desperately needed hope for one of the largest and most underserved solid tumor communities worldwide. Why would positive granite data be significant for the field?

Andrew R. Allen: Microsatellite stable tumors comprised about 95% of all metastatic colorectal cancer diagnoses and treatment options are few with no approved therapies for this highly resistant cold tumor.

Andrew R. Allen: A positive randomized trial result would therefore off a desperately needed hope for one of the largest and most underserved solid tumor communities worldwide.

Andrew R. Allen: Why would posted granite to be significant to the field.

Andrew R. Allen: because immunotherapies are generally believed to be ineffective in so-called cold tumors such as microsatellite-stable colorectal cancer, and since checkpoint inhibitor therapy alone has not delivered benefit in this setting. To date, to our knowledge, all of our neoantigen-directed personalized cancer vaccine competitors have studied cold metastatic tumors and have reported little to no signals of efficacy with their platforms, hence their current focus on adjuvant indications and or hot tumors. Success for Granite in a cold metastatic tumor could open the door to effective immunotherapy to the majority of solid tumor patients, both in metastatic and adjuvant settings. Potentially, a dramatic expansion of the overall opportunity. And finally, why would positive mature PFS data be meaningful for Gritstone?

Andrew R. Allen: Because immunotherapies generally believed to be ineffective in so called cold tumors, such as microsatellite stable colorectal cancer.

Andrew R. Allen: And since checkpoint inhibitor therapy alone is not delivered benefits in this setting.

Andrew R. Allen: To date to our knowledge all of all new engine directed personalized cancer vaccine competitors have studied cold metastatic tumors and have reported little to no signal of efficacy with their platforms handset current focus on adjuvant indications.

Andrew R. Allen: Or hot tumors.

Andrew R. Allen: Success for granted and a cold metastatic tumor could open the door for effective immunotherapy to the majority of solid tumor patients both in metastatic and adjuvant settings.

Andrew R. Allen: The dramatic expansion of the overall opportunity.

Andrew R. Allen: And finally, why would positive mature PFS stay to be meaningful for <unk> because of course, it suggests potential for a big opportunity immediately ahead of us in metastatic colorectal cancer.

Andrew R. Allen: Because, of course, it suggests that there is a big opportunity immediately ahead of us in metastatic colorectal cancer and that our objective of unlocking the broad set of immunologically cold tumors may be within reach. Having PFS as a reliable early measure of the effectiveness of our therapy gives us a potentially faster regulatory path in colorectal cancer and any other indications we pursue. Expanding the scope of immunotherapy to a wide spectrum of cancer patients is the holy grail of immuno-oncology for good reason. It's challenging, and it hasn't been done before despite decades of effort.

Andrew R. Allen: And that our objective of unlocking the broad set of immunologically cold tumors may be within reach.

Andrew R. Allen: Having PFS is it reliable early measure the effectiveness of our therapy gives us a potentially faster regulatory path and colorectal cancer and other indications we pursue.

Andrew R. Allen: Expanding the scope of immunotherapy to a wide spectrum of cancer patients is the Holy Grail of immuno oncology for good reason.

Andrew R. Allen: It's challenging and it has not been done before despite decades. So that's it.

Andrew R. Allen: Now, along with Granite, we continue advancing our other promising programs and platform technologies, and we're attracting great recognition and... A recent Slate publication, In Nature Medicine, highlights the promise of our off-the-shelf platform for solid tumors, which we believe is ready for plug-and-play applications across a spectrum of solid tumors. This promise is underscored by the ongoing collaboration with Dr. Steven Rosenberg of the National Cancer Institute to evaluate a mutant KRAS-directed vaccine candidate in combination with an autologous mutant KRAS-directed TCRT cell therapy.

Andrew R. Allen: Now along with granite, we continue advancing our other promising programs and platform technologies, and we're attracting great recognition and support the recent slate publication in nature medicine highlights the promise of our off the shelf platform for solid tumors, which we believe is ready for plug and play applications across the spectrum of solid tumors. This problem.

Andrew R. Allen: This is underscored by the ongoing collaboration with Dr. Steven Rosenberg at the National Cancer Institute to evaluate our mutant K Ras directed vaccine candidate in combination with an autologous mutant K K raws directed T C. L T cell therapy.

Andrew R. Allen: The recent presentation of the latest improvements to EDGE, our state-of-the-art prediction platform that leverages artificial intelligence to identify the neo-ancient targets we encode in granite, further underscores our leadership position in the field of neoantibiotic cancer vaccines. EDGE now predicts HLA Class 1 presentation of epitopes with greater than 80% positive predictive value, performance well beyond that of public models, and it offers what we believe to be a leading technology within the field.

Andrew R. Allen: The recent presentation of the latest improvements to edge, our state of the art prediction platform.

Andrew R. Allen: Leverages artificial intelligence to identify the new engine targets, we encoding granite.

Andrew R. Allen: Further underscores our leadership position in the field that new engine direct to cancer vaccines.

Andrew R. Allen: H now predicts HLA class, one presentation of epitopes with greater than 80% positive predictive value performance well beyond that as public models and it also has what we believe to be a leading technology within the field.

Andrew R. Allen: EDGE also now includes a comprehensive, state-of-the-art model for predicting peptide presentation by HLA class 2 in the context of active vaccination, which could serve to further strengthen T cell responses to our novel vaccine. We were among the first players to leverage AI technology in this fashion and will continue to invest in Edge to further what we believe to be a key potential strategic advantage.

Andrew R. Allen: And you're also now includes a comprehensive state of the art model for predicting peptide presentation by HLA class II in the context of active vaccination, which could serve to further strengthen T cell responses to our novel vaccines.

Andrew R. Allen: We were among the first place to leverage AI technology in this fashion and we will continue to invest in edge to further what we believe to be a key potential strategic advantage.

Andrew R. Allen: Beyond oncology, we continue pushing forward in infectious disease, largely leveraging external dollars. Our recent presentation at the Escomit Conference reinforced previous Phase 1 findings and highlighted the durability and potential broad utility of our self-amplifying mRNA vaccine against COVID-19. The efforts and dialogue with BARDA regarding running a Phase 2b head-to-head study in COVID-19 continue, and we remain very excited about this important 10,000-subject study. Along with Bada and others engaged in prophylaxis efforts, we've garnered support from other leading players, including Gilead Sciences, for a therapeutic vaccine for HIV.

Andrew R. Allen: Beyond oncology, we continue pushing forward in infectious disease, largely leveraging external dollars.

Andrew R. Allen: A recent presentation at the estimate conference reinforce previous phase, one findings and highlighted the durability and potential broad utility of our self amplifying mrna vaccine against COVID-19.

Andrew R. Allen: The efforts in dialogue with BARDA regarding running a phase to be head to head studying COVID-19 continue and we remain very excited about this important 10000 subject study.

Andrew R. Allen: Along with BARDA and others engaged in prophylaxis efforts, we've gone with support from other leading players, including Gilead Sciences fourth therapeutic vaccines for HIV.

Andrew R. Allen: And we remain excited about the broad potential applicability of our capabilities and self-amplifying mRNA platform in infectious disease. As our data mature across our portfolio, we continue to execute on our mission of delivering the most potent and durable vaccines. Now, I'll turn over to Celia to speak about our financial position.

Andrew R. Allen: And we remain excited about the broad potential applicability of our capabilities and self amplifying mrna platform and infectious disease.

Celia: As our data mature across our portfolio, we continue to execute on our mission of delivering the most potent and durable vaccines and now I'll turn it over to see here to speak to our financial position.

Celia Economides: Thank you, Andrew. Good afternoon, everyone.

Celia: Thank you Andrew good afternoon, everyone.

Celia Economides: We ended the quarter with cash, cash equivalents, marketable securities, and restricted cash of $52.8 million. As you are aware, in April of 2024, we completed an underwritten public offering resulting in gross proceeds to Gritstone of $32.5 million, bringing our pro forma cash, cash equivalents, marketable securities, and restricted cash to approximately $85.3 million. In February, we made the difficult decision to reduce our workforce by approximately 40%.

Celia Economides: We ended the quarter with cash cash equivalents marketable securities and restricted cash of $52 8 million.

Celia Economides: As you are aware in April of 'twenty 'twenty, four we completed an underwritten public offering resulting in gross proceeds to great stone of $32 5 million, bringing our pro forma cash cash equivalents marketable securities and restricted cash to approximately $85 3 million.

Celia Economides: In February we made the difficult decision to reduce our workforce by approximately 40%.

Celia Economides: Combined, these actions have reduced our estimated quarterly cash burn rate and extended our runway into the fourth quarter of 2024. As you know, our priority is driving the grant program forward, and our OPEX reflects this. On the infectious disease side, to date, we have primarily funded our programs with non-dilutive outside capital. Several of our longstanding infectious disease collaborations continue and could potentially serve to bring additional capital to the company. As we think about the next steps for our IG business, we are exploring strategic funding approaches to support our growing infectious disease programs and business. In addition to our current collaborations, new partnerships in both oncology and infectious disease could serve as additional sources of capital.

Celia Economides: Bind these actions have reduced our estimated quarterly cash burn rate and extended our runway into the fourth quarter of 2024.

Celia Economides: As you know our priority is driving the branded program forward and our Opex reflects that.

Celia Economides: Infectious disease side to date, we have primarily funded our programs with <unk> to have outside capital.

Celia Economides: Several of our longstanding infectious disease collaborations continue and could potentially serve to bring additional capital to the company.

Celia Economides: As we think about the next steps for <unk> for <unk> business.

Celia Economides: We are exploring strategic funding approach is to support our growing infectious disease programs and business. In addition to our current collaboration new partnerships in the oncology and infectious disease could serve as additional sources of capital.

Celia Economides: Turning now to our Q1 2024 operating results, we reported a net loss of $40.4 million compared with $34 million for the same period last year. The increase in our net loss is primarily attributable to a decrease in collaboration revenue of $0.7 million, an increase in research and development expenses of $2.5 million, and an increase in our G&A expenses of $1.8 million. The establishment of collaborations and partnerships is a core part of our business strategy as we continue to leverage our unique platforms and capabilities.

Celia Economides: Turning now to our Q1 'twenty 'twenty four operating result.

Celia Economides: We reported a net loss of $40 4 million compared with 34 million for the same period last year. The increase in our net loss is primarily attributable to the decrease in collaboration revenue of <unk> 7 million, an increase in research and development expenses of $2 5 million and an increase in our G&A expenses of $1 8 million.

Celia Economides: The establishment of collaborations and partnerships as a core part of our business strategy as we continue to leverage our unique platform and capabilities.

Celia Economides: Our collaboration, license, and grant revenue for the first quarter ending March 31, 2024 totaled $1.7 million. This is compared to $2.4 million for the same period in 2023. Our research and development expenses were $33 million for the three months ended March 31, 2024, compared with $30.5 million for the same period in 2023. The increase in R&D costs was primarily due to a one-time severance and impairment charge and increases in facility-related costs, which were partially offset by decreases in lab supplies, personnel-related costs, and outside services.

Celia Economides: Our collaboration license and grant revenue for the first quarter ending March 31, 2024 totaled $1 7 million. This is compared to $2 4 million for the same period in 2023.

Celia Economides: Our research and development expenses were 33 million for the three months ended March 31, 2024, compared with $30 5 million for the same period in 2023 the.

Celia Economides: The increase in R&D costs was primarily due to a one time severance and impairment charge and increases in facility related costs, which were partially offset by decreases in lab supplies and personnel related costs.

Celia Economides: Or is that.

Celia Economides: G&A expenses for the period will be $8.5 million. Up from $6.7 million for the same period last year, the increase in G&A expenses for the period ending March 31st was primarily attributable to personnel-related expenses, facilities-related costs, outside services, and a one-time severance charge. As of March 31st, 2024, Gritstone had approximately 97.6 million shares of common stock outstanding, pre-funded warrants outstanding to purchase approximately 7.2 million shares of common stock at a nominal exercise price of $0.01 per share, and approximately 13.3 million shares of common stock at a nominal exercise price of $0.01 per share.

Celia Economides: G&A expenses for the period was $8 5 million.

Celia Economides: Up from $6 seven up $6 7 million for the same period last year the increase in G&A expenses for the period ending March 31st It was primarily attributable to personnel related expenses facilities related costs outside services and a one time severance charge.

Celia Economides: As of March 31, 2020 for quite some had approximately 97 6 million shares of common stock outstanding pre funded warrants outstanding to purchase approximately seven 2 million shares of common stock at a nominal exercise price of one cent per share.

Celia Economides: And approximately $13 three shares million shares of common stock at a nominal exercise price of one 100th of a fad per share.

Celia Economides: In summary, we are confident in our ability to execute on our strategic objectives and toward our growth inflection point. I'll now turn the call back over to Andrew for some closing remarks. Thanks, Celia. We started Gritstone to expand the emerging benefits of immunotherapy to all patients with solid tumors, and we're unwavering in our focus on that critical goal and very pleased with the progress we've made supporting the potential for new antigen-based cancer vaccines.

Celia Economides: In summary, we are confident in our ability to execute on our strategic objectives and toward our growth inflection point I'll now turn the call back over to Andrew for some closing remarks.

Andrew: Thanks Julia.

Andrew R. Allen: We started Gritstone to expand the emerging benefits of immunotherapy to all patients with solid tumors, and we're unwavering in our focus on that critical goal and very pleased with the progress we've made supporting the potential for neoantigen-based cancer vaccines. You're back live. Okay, thank you.

Celia Economides: We started grid stone to expand the emerging benefits of immunotherapy to all patients with solid tumors.

Andrew R. Allen: Unwavering and I'll focus on that critical goals I'm very pleased with the progress we've made supporting the potential for new engine based cancer vaccines.

Andrew R. Allen: Yeah.

Andrew R. Allen: Yeah.

Andrew R. Allen: Yeah.

Andrew R. Allen: Yeah.

Andrew: You're back live.

Andrew: Okay. Thank you thank.

Andrew: Thank you Celia.

Andrew R. Allen: Thank you, Celia. We started Gritstone to expand the emerging benefits of immunotherapy to all patients with solid tumors. We are unwavering in our focus on that critical goal.

Andrew R. Allen: We started grid stone to expand the emerging benefits of immunotherapy to all patients with solid tumors. We are unwavering in our focus on that critical go very pleased with the progress we've made supporting the potential for new engine based cancer vaccines.

Andrew R. Allen: I'm very pleased with the progress we've made, supporting the potential for neoantigen-based cancer vaccines. Importantly, we're getting ever closer to randomized phase 2 data that we believe will demonstrate much-needed benefit in a key population of newly diagnosed metastatic, microsatellite-stable colorectal cancer patients. This large group of patients is in desperate need of a therapeutic advance since median overall survival from the time of diagnosis has remained stuck at just around two years. We anticipate sharing mature PFS data as well as additional ctDNA data in the third quarter of this year.

Andrew R. Allen: Importantly, we're getting ever closer to randomized phase two data that we believe will demonstrate much needed benefit and a key population of newly diagnosed metastatic microsatellite stable colorectal cancer patients.

Andrew R. Allen: This large group of patients who are in desperate need of a therapeutic advance since median overall survival from the time of diagnosis has remained stuck could just around two years.

Andrew R. Allen: We anticipate sharing mature PFS data as well as additional C. T DNA data in the third quarter of this year.

Andrew R. Allen: The preliminary PFS data we shared recently, accompanied by the supportive ctDNA over time analyses demonstrating early trends in favor of granogymnotherapy, are all very encouraging. And to remind you, these data are following on from and consistent with highly supportive Phase I-II data from a single-arm trial in patients with very advanced metastatic disease. We're on the cusp of definitive data from this novel platform in a large patient population that has traditionally been considered unresponsive to immunotherapy.

Andrew R. Allen: Preliminary PFS data, we shared recently accompanied by the supportive C. T DNA overtime analyses demonstrating early trends in favor of granting the therapy are all very encouraging.

Andrew R. Allen: And to remind you. These data are following on from and consistent with highly supportive phase one two data from a single arm trial in patients with very advanced metastatic disease.

Andrew R. Allen: We're on the cusp of determinative data from this novel platform in a large patient population that has traditionally been considered unresponsive to immunotherapy. This.

Andrew R. Allen: This is a truly exciting prospect for Gritstone, for the field, and, most importantly, for patients and their families. I'd like to thank you all for joining us today, and I'll turn the call over to the operators for questions.

Andrew R. Allen: This is a truly exciting prospect for grit stone for the field and most importantly for patients and their families.

Operator: Thank you. We will now conduct a question and answer session. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star 2 if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Once again, that's Star 1 at this time. One moment while we poll for our first question. Our first question comes from Marc Frahm with TD Cowan. Please proceed.

Speaker Change: I'd like to thank you all for joining us today, and I'll turn the call over to the operator for questions.

Marc Alan Frahm: Thank you we will now conduct a question and answer session. If you would like to ask a question. Please press star one on your telephone keypad.

Marc Alan Frahm: A confirmation tone will indicate your line is in the question queue you.

Marc Alan Frahm: You May press Star two if you would like to remove your question from the queue for participants using speaker equipment. It may be necessary to pick up your handset before pressing to sarkies. Once again Thats star one at this time, one moment, while we poll for first question.

Operator: Our first question comes from Marc Frahm with TD Cowen. Please proceed.

Marc Alan Frahm: Thanks for taking my questions. Andrew, can you speak to how event rates in the CRC trial have evolved since the February update? Given where they are now, how much uncertainty there still is, or isn't, that the mature PFS data will really be available in Q3?

Marc Alan Frahm: Hi, Thanks for taking my questions.

Marc Alan Frahm: Maybe Andrew can you speak to kind of how the event rates and the CRC trial has kind of evolved since the February update and you know given where they are now just kind of how much uncertainty there still is or isn't.

Marc Alan Frahm: The mature PFS data will really be available in Q3.

Andrew R. Allen: Yeah, it's a little early to give definitive answers because we don't obviously do exhaustive data cuts regularly that sites find tiresome. But we have no reason to doubt the maturity of the data at this time point because a lot of phase 3 trials have been run in this very same population with highly consistent data. So the control arm, I strongly expect, will behave as many other control arms have before with that median PFS of around 11 months.

Andrew: Yeah, it's a little early to give a definitive answer because we then obviously do exhaustive data cuts regularly that sites find that tiresome.

Andrew R. Allen: But we have no reason to doubt.

Andrew R. Allen: Doubt the maturity for data at this time point, because a lot of phase III trials have been run in this very same population with highly consistent data so the control arm.

Andrew R. Allen: Strongly expect will behave as many other control arms have before with that medium PFS of around 11 months.

Andrew R. Allen: As you know from the baseline disease and demographic data that we shared recently, this population of patients is very typical, with 75% having liver metastases. So there's no reason to believe that this is a particularly good or bad population of patients. There is, of course, some degree of informative censoring in the way we collect data, meaning that you get data on the patients who progress the fastest. And that is probably working against the granite arm because most people believe, with good reason, that vaccine immunotherapy is going to be more effective in people with lower volumes, less extensive disease.

Andrew R. Allen: You're aware from the baseline disease and demographic data that we shared recently this population of patients is very typical.

Andrew R. Allen: With 75%, having liver metastases. So theres no reason to believe that this is a particularly good or bad population of patients.

Andrew R. Allen: There is of course, some degree of informative censoring and the way we collect data, meaning that you get data on the patients who progressed the fastest and that is probably working against the granite home because most people believe with good reason that vaccine immunotherapy is going to be more effective in people with lower volume.

Andrew R. Allen: Les <unk>.

Andrew R. Allen: Extensive disease those patients will progress on average a bit more slowly.

Andrew R. Allen: Those patients will progress on average a bit more slowly. And of course, that means we have less data in that population, but we have more data in the high-risk group that progresses faster, and we showed you those data, and obviously that gave us further reason to be optimistic about mature data in Q3.

Andrew R. Allen: And of course that means we have less data in that population, but we have more data in the high risk group the progress Foster and we showed you those data and obviously that that gave us. So the reason to be optimistic for mature data in Q3.

Andrew R. Allen: Okay, that's helpful. And then maybe on the BARDA front, can you just remind us, you know, how that money has actually been allocated? And, you know, does it, is it required to be spent on COVID? Or is there some risk here, maybe with the avian flu? Yeah, an epidemic going on, at least for now, on the veterinary side, that some of it may get moved over to the flu and, you know, related to that, any work you guys are doing on the avian flu side?

Speaker Change: Okay. That's helpful. And then maybe on the BARDA front can you just remind us.

Andrew R. Allen: How that money has actually been allocated and.

Andrew R. Allen: Does it.

Andrew R. Allen: These are required to be spent on COVID-19 or is there some riskier than maybe what the avian flu.

Andrew R. Allen: Yeah epidemic going on at least for now on the veterinary side that some of it may get moved over to flu.

Andrew R. Allen: Related to that any work you guys are doing on the avian flu side.

Andrew R. Allen: Yeah, so the specific contracts that we were awarded back in the fall of 2023 were part of Project Next Gen, which was focused on the next generation COVID vaccine. As you may recall, there were several periods for that contract, and we were in the base period of that contract, which expired at the end of March, and we are now in a no-cost extension period of that contract while we work out the GMP raw materials for launching the Phase 2B study, so those particular dollars in that particular contract were specific to COVID. Now, you may or may not recall that. BARDA has actually shifted those funds into a different funding vehicle called RRPV. So we have applied for that vehicle as well and are now

Andrew R. Allen: Yeah. So the specific contracts that we were awarded back in the fall of 2023 was part of project next Gen, which was focused on next generation Covid vaccines.

Andrew R. Allen: As you May recall, there were several periods for that contract and we were in the base period in which that time expired at the end of March and we are now in a no cost extension period of that contract, while we work out.

Andrew R. Allen: The G M P raw materials for launching the phase <unk> study. So those particular dollar in that particular contract was a specific to COVID-19 how are you.

Andrew R. Allen: You may or may not recall that.

Andrew R. Allen: BARDA has actually shifted those funds into a different funding vehicle called R. R. P. V. So we have applied to that vehicle as well and are now waiting to hear back.

Andrew R. Allen: And then we've got your question on flu, Marc. The same principles apply to flu as apply to SARS-CoV-2, which is obviously the concern is always that there is ongoing mutation within those surface proteins, particularly the hemagglutinin and the neuraminidase, that can lead to immune evasion. And that means, of course, you're often reacting to what is in the environment around you.

Andrew R. Allen: And then your regard to your question on flu remarks.

Andrew R. Allen: The same principles apply to flu as applied to Sars Covid, two which is obviously the concern is always that there is ongoing mutation within those surface proteins, particularly the hemagglutinin and the neuraminidase that can lead to immune evasion.

Andrew R. Allen: And that means of course, you're from reacting to what is in the environment around you.

Andrew R. Allen: The same principles that we deployed against SARS-CoV-2 are relevant here, i.e., that you want durable antibodies, and ideally, you want T-cell immunity against conserved regions of the virus, because even if surface proteins are mutating, many of the other non-structural proteins are not mutating because they're highly constrained, i.e. Their function is so critical to the virus that they can't change. That's the basic science that underpins our so-called chimeric SARS-CoV-2 vaccine, where we include both the surface protein, in the case of SARS-CoV-2, of course, that spike, and we include regions of other non-structural proteins that have conserved epitopes, particularly for CD8 T cells. You can apply that same logic to the flu, and we are doing preclinical work on the flu, as you would imagine.

Andrew R. Allen: The same principles that we deployed against Sars Cov, two irrelevant here I E that you want durable antibodies and ideally one T cell immunity against conserved regions of the virus because even if surface proteins are mutating many of the other non structural proteins on not mutating, because theyre highly constrained.

Andrew R. Allen: E. Their function is so critical to the virus that they can't change.

Andrew R. Allen: That's the.

Andrew R. Allen: Spacex signs that underpins all circled chimeric Sars cov, two vaccine, where we include both the surface protein and Acacia sauce kv to cross that Spike and we include regions of other non structural proteins that have conserved epitopes, particularly for CDA T cells.

Andrew R. Allen: Can apply that same logic to flu and we are doing preclinical work in influenza as you would imagine.

Speaker Change: Okay. Thank you.

Andrew R. Allen: Yep.

Operator: The next question comes from John Miller with Evercore. Please proceed. Oh, hi.

Andrew R. Allen: The next question comes from Jon Miller with Evercore. Please proceed.

Chen Xiang: Hi, this is Chen Xiang from Drone. Thanks for taking our question. I guess the first one is, for the readout in the second half of the year, what is your bar for success? Do you need to see PFS benefits from patients with low cdDNA at baseline to feel confident moving forward?

Operator: Oh, Hi, this is Jane Hsiao, often Joel Thanks for taking my question I guess the first one is for the readout in the second half of the year, but what is your bar for success do you need to see.

Chen Xiang: This benefit from patients with low <unk> DNA at baseline to feel confident moving forward.

Andrew R. Allen: Yeah, the median PFS is 11 months, I think. Obviously, we're looking for a meaningful improvement on that, which means a hazard ratio probably better than 0.75, and certainly, the data we've generated so far suggests we're on track to exceed that bar. Your question about low ctDNA... There are two populations that really do have low ctDNA that we study. There's the group that begins the study with low ctDNA, and that group generally would be called the lower risk group because we know, and we've shown, indeed, a few weeks ago that if you have low ctDNA at baseline, the rate of progression is lower than if you have high ctDNA. So that population is a lower-risk population, although they are all expected to progress. So it's not that they have some kind of benign disease.

Chen Xiang: Yeah.

Chen Xiang: The median PFS is 11 months.

Andrew R. Allen: I think <unk>.

Andrew R. Allen: We were looking for.

Andrew R. Allen: A meaningful improvement on that which means the hazard ratio.

Andrew R. Allen: The better than 0.75.

Andrew R. Allen: Certainly the data we've generated so far suggests we're on track to exceed that ball.

Andrew R. Allen: Your question about low C T G&A.

Andrew R. Allen: There are two populations really that have low CTG in a that we study. This is the group that begins this study with low C. G DNA and that group generally would be called the lower risk groups, because we know and we've shown indeed, a few weeks ago that if you're at low Cte DNA at baseline.

Andrew R. Allen: Rates of progression is lower than if you have high C. T. G. N. A so that population is a lower risk population. Although they all are expected to progress. So it's not that they have some kind of benign disease. They will progress and sadly that disease will kill nearly all of these patients in relatively short order, but they do progressive it's <unk>.

Andrew R. Allen: They will progress, and sadly, that disease will kill nearly all of these patients in relatively short order. But they do progress a bit slower, and perhaps vaccine-based immunotherapy will be more effective in that population. There is generally a link between ctDNA level and disease burden, so it is reasonable to assert that the low ctDNA population has a lower disease burden, which is therefore perhaps more amenable to vaccine-based immunotherapy. This is obviously the idea behind the focus on adjuvant indications that Moderna and BioNTech are pursuing. So it is an important population.

Andrew R. Allen: Lower than perhaps vaccine based immunotherapy will be more effective in that population. There is generally a link between C. T DNA level and disease burden. So it is reasonable to assert that the low C. T. DNA pulp shipped population have lower disease burden, which is therefore, perhaps more amenable to vaccine based immunotherapies.

Andrew R. Allen: This is obviously the idea behind the focus on adjuvant indications that medallion biotech are pursuing.

Andrew R. Allen: So it is an important population then there's a second group of low CTG in a which is the patients who complete their induction chemotherapy and then I'll rendered C. T DNA negative by that induction chemo that is good for those patients you, obviously means they've done well on chemo sadly most of them will recur. However.

Andrew R. Allen: Then there's a second group of low-CTDNA, which are patients who complete their induction chemotherapy and then are rendered ctDNA negative by that induction chemo. Now, that's good for those patients. It obviously means they've done well on chemo. Unfortunately, most of them will recur, however, and that's an analysis that you may recall we presented a few weeks ago. And what we were able to show is that although the numbers obviously are quite small, there is a difference between the two arms whereby patients receiving vaccines stay negative for longer than patients in the control arm.

Andrew R. Allen: And that's an analysis that you may recall, we presented a few weeks ago and what we were able to show is that although the numbers. Obviously are quite small there is a difference in the two arms whereby patients receiving vaccine stay negative for longer than the patients in the control arm and there is more.

Andrew R. Allen: And there is more radiologic progressive disease in the control group than in the vaccine-treated group. So those data are certainly encouraging, and obviously we'll be following up in that population as well. So two different ways to answer your question, but both of them are important, and both of them, in principle, could do even better on vaccine than the high-risk group where we currently have the most mature PFS data.

Andrew R. Allen: Radiological progressive disease in the control group than in the vaccine treated group. So those states were certainly encouraging and obviously, we'll be following up in that population as well. So two different ways to answer your question, but both of them are important and both of them in principle.

Andrew R. Allen: Could do even better on vaccine then the high risk group, where we currently have the most mature PFS data.

Andrew R. Allen: Thanks so much. I just want to follow up on the ctDNA. I guess why did ctDNA continue to decrease in the chemo arm after induction therapy? And do you have any thoughts on what sort of ctDNA endpoint might be more predictive for survival?

Speaker Change: Thanks, So much just want to follow up on the C. D DNA I guess.

Speaker Change: Why do you see the dealer continued to.

Speaker Change: The decrease in the chemo arm after induction therapy and do you have any thoughts Paul.

Andrew R. Allen: Sort of CBD on the endpoint might be more predictive for survival.

Andrew R. Allen: So, we don't know; we did not anticipate that, obviously, we wouldn't have set the endpoint the way we did. So, clearly, we had a failure of the endpoint in the study, and that's an important distinction that I think has been lost by a lot of people. You can have an endpoint fail or a product fail or both.

Andrew R. Allen: So.

Speaker Change: We don't know no one we did not anticipate that obviously, we wouldn't have set the end point the way. We did so clearly we had a failure of the endpoint in the study and that's an important distinction that I think has been lost on a lot of people.

Andrew R. Allen: You can have an endpoint fail or products fail all boats in this case the endpoint sales because we saw C. T DNA dropping in the control group just for the first three to four weeks after the completion of induction chemo and so that's presumably telling us that there was some delayed or persistent.

Andrew R. Allen: In this case, the endpoint failed because we saw ctDNA dropping in the control group just for the first three to four weeks after the completion of induction chemo. And so, that's presumably telling us that there is some delayed or persistent effect of induction chemotherapy. We had no data to guide us before we designed the study, so this is a new observation, and obviously it's one that tripped us up.

Andrew R. Allen: The effect of the induction chemotherapy.

Andrew R. Allen: We did have we had no data to guide us before we designed the studies. So this is a new observation that obviously is one that trips us up but at some level not that important because obviously what matters a is the PFS.

Andrew R. Allen: But at some level, not that important, because obviously, what matters, A, is that PFS is delivering clear signals here and is a more relevant regulatory endpoint, as we discussed in this call. And secondly, the long-term ctDNA analysis is highly consistent with the PFS signal. In other words, patients on vaccine do better, ctDNA is controlled for longer, and that certainly is what you would expect from an active therapy in this disease

Andrew R. Allen: Is delivering clear signals here and is a more relevant regulatory endpoint as we discussed in this call and secondly, the long term C. T. DNA analysis is highly consistent with the PFS signal in other words patients on vaccine do better Cte dnas controls for longer.

Andrew R. Allen: That certainly is what you would expect from an active therapy in this disease setting now moving forward in this disease, we will not be worried about C. T. DNA, because we know you know potentially entry phase III and we will be using traditional endpoints.

Andrew R. Allen: Now, moving forward, in this disease, we will not be worried about ctDNA because we're now, you know, potentially entering Phase 3, and we'll be using traditional endpoints, you know, PFS or OS, and obviously that's something we'll be discussing with the agency at the end of the Phase 2 meeting. And as you know, PFS has been used for approval in this first-line disease setting. So that's what we'll be doing in metastatic colorectal cancer. However, obviously, if all goes well, we'll be developing the program in other settings.

Andrew R. Allen: PFS or OS and obviously, that's something we'll be discussing with the agency at the end of Phase two meeting and as you know PFS has been used for approval in this first line disease settings.

Andrew R. Allen: So.

Andrew R. Allen: That's what we'll be doing in metastatic colorectal cancer. However, we obviously if all goes well we'll be developing the program in other settings, and particularly in earlier stage trials, especially single arm C. G. DNA outcomes are potentially very important as an early efficacy metric before.

Andrew R. Allen: And particularly in earlier stage trials, especially if they are single-arm, ctDNA outcomes are potentially very important as an early efficacy metric before you get to big randomized studies. And therefore, it is important that we understand how to interrogate ctDNA in a way that renders it a useful surrogate for clinical endpoints such as PFS and OS. Today, I can't give you the answer because we don't have the mature PFS and OS data. But, of course, the data we're generating will be an invaluable resource to enable us to figure out a way to use ctDNA that adeptly captures long-term clinical benefit and can then be deployed in single-arm smaller trials in other indications.

Andrew R. Allen: You get to Big randomized studies and therefore, it is important that we understand how to interrogate Cte DNA in a way that renders it a useful surrogate for clinical endpoints, such as PFS and OS today I can't give you the answer because we don't have the mature PFS and OS data, but of course the day to regenerate.

Andrew R. Allen: She will be an invaluable resource to enable us to figure out a way to use C. T. DNA that adeptly captures long term clinical benefit and can then be deployed in single arm smaller trials in other indications.

Speaker Change: Alright, thank you so much.

Speaker Change: Thank you.

Operator: The next question comes from Mayank Mamtani with B. Reilly Securities. Please proceed.

Andrew R. Allen: The next question comes from me at my Tommy with B Riley Securities. Please proceed.

Madison: Hey, guys. Madison here, all for Mayank. Thanks for taking our question. So, wondering what you guys anticipate the touch points will be with the FDA whenever you meet to discuss it, phase three? Also curious how those patients could look relative to what we've seen in granite, if the 75% liver matte, 50% KRAS, if that's just kind of representative of the population. And then, lastly, the fact we didn't see any pseudo-progression. Do you expect that would hold in a Phase III trial, or is that something that you'll attempt to address in the design in the event there is pseudo-progression? Appreciate it, guys. Yeah, thanks, Madison. Good questions.

Mayank Mamtani: Hey, guys Madison here on for Mike Thanks for taking our question.

Madison: So wondering what do you guys anticipate the touch points will be with the F. D. A.

Madison: Whenever you meet to discuss it.

Madison: Phase three.

Madison: And.

Madison: Also curious how those patients could look relative to.

Madison: What we've seen in granite to up to 75% liver met 50% K Ras if that's just kind of representative.

Madison: The population.

Speaker Change: And then lastly.

Madison: The fact, we didn't see any pseudo progression do you expect that would hold in a phase III or is that something that your attempt to address and the design in the event. There is pseudo progression I appreciate it guys. Thanks.

Andrew R. Allen: Yeah, thanks, Madison. That's a good question. So, in a slightly different order than you asked the question. By design, this was a very straightforward front-line study across the United States in a variety of centers with very straightforward inclusion and exclusion criteria, very standard. And that's good, of course, because it means there's not much opportunity for patient selection. You're just taking the patients that come through the door. And there aren't that many trials in front-line colorectal cancer, so most people who were clinical trial eligible and at a site where our trial was operating would have been offered our study, which is why it enrolled very swiftly, particularly in the first half of 2023. So there's unmet need there. The trial is very straightforward and recruits patients without any special selection. We don't anticipate changing that for Phase III. Why would you?

Speaker Change: Thanks Madison Good question Sir.

Andrew R. Allen: In a slightly different order in which you asked the questions.

Andrew R. Allen: By design this was a very straightforward frontline study.

Andrew R. Allen: Across the United States and a variety of centers.

Andrew R. Allen: With very straightforward inclusion and exclusion criteria very standard.

Andrew R. Allen: And that's good of course, because it means there's not much opportunity for patient selection, who is taking the patients that come through the door.

Andrew R. Allen: And there aren't that many trials in frontline colorectal cancer. So most people who are clinical trial are eligible.

Andrew R. Allen: And at a site, where our trial was operating would've been offered all study, which is why it enrolls very swiftly, particularly in the first half of 2020 right. So there's unmet need that the trial is very straightforward and recruit patients without any special selection, we don't anticipate changing that phase III why would you want to representative.

Andrew R. Allen: You want a representative population. So that's good news, and obviously, we would anticipate that the degree of liver metastases and KRS mutations will be constant in Phase 3 because, of course, your dream is to run a Phase 3 that is basically unchanged from your Phase 2. That reduces the chance that something new, you've made some new assumption, or something else is happening that's altering the outcome. You want that so-called sleep-easy Phase 3.

Andrew R. Allen: Population.

Andrew R. Allen: So that's good news and obviously, we would anticipate that the degree of liver metastases and carries mutations will be constant in the phase III because of course. Your your dream is to run a phase III that is basically unchanged from your phase II that reduces the chance that something you you've made some new assumption or something else.

Andrew R. Allen: This is happening this altering the outcome you want that so called sleep easy phase III.

Andrew R. Allen: So, our incentive is to change as little as possible. And obviously, we'll go to the FDA, and the traditional forum is an end-of-Phase 2 meeting, which we'd anticipate towards the end of this year, taking with them the data from this study, which, of course, we'll have in hand in Q3. And then we'll be discussing, among other things, the primary efficacy endpoint of the Phase 3 trial, and that is likely to be a choice between PFS and OS.

Andrew R. Allen: So our incentive is to change as little as possible and obviously, we will go to the FDA and the traditional forum is an end of phase two meeting, which we would anticipate.

Andrew R. Allen: Towards the end of this year.

Andrew R. Allen: Taking to them the data from this study which of course will have in hand.

Andrew R. Allen: In Q3.

Andrew R. Allen: And then we will be discussing among other things.

Andrew R. Allen: The phase III primary efficacy endpoint.

Andrew R. Allen: And that is likely to be a choice between PFS and OS. We also of course need to align with the F. T E on manufacturing because you know these are complex products.

Andrew R. Allen: We also, of course, need to align with the FDA on manufacturing because, you know, these are complex products. And we've obviously been in lockstep with the FDA from the very get-go. In fact, we first spoke to the FDA about manufacturing before we were in the clinic, when we were literally designing the layout of our biomanufacturing facility. So, we held a Type C meeting back then, just to solicit FDA input, to make sure that we were on the right track in terms of the way we make these products.

Andrew R. Allen: We've obviously been in lockstep with the F D. A from the from the very get going fact, we first spoke to the FDA about manufacturing before we were in the clinic. When we were literally designing the layout of our bio manufacturing facility. So we held a type C. Meeting back then just to solicit fda's input to make sure that we were on the right.

Andrew R. Allen: Track in terms of the way we make these products. There is obviously a step up in regulatory quality as you move to a phase III and commercial and we need to make sure that we're aligned with the agency. That's also part of the end of Phase two meeting alongside the clinical endpoint discussions.

Andrew R. Allen: There's obviously a step-up in regulatory quality as you move to Phase 3 and commercial, and we need to make sure that we're aligned with the agency. That's also part of the end-of-Phase 2 meeting, alongside the clinical endpoint discussion.

Andrew R. Allen: Got it. Thank you.

Speaker Change: Got it thank you.

Operator: The next question comes from Kaveri Pullman with BTIG. Please proceed.

Andrew R. Allen: The next question comes from Caveri Polman with B T. I G. Please proceed.

Christian: Hi, this is Christian. I'm on for Kaveri today.

Operator: Hi, This is Christian on for <unk> today.

Christian: My first question is.

Andrew R. Allen: My first question is... I would like an update on the CORO program. I saw that you guys presented positive data recently in the Coral Study on South African Patients, and there was positive data for the three vaccine candidates, so is there any development there? Are you guys planning to move forward with any of the candidates? Which candidate are you guys planning to move forward with?

Christian: I would like to an update on the Coral program I saw that you guys presented positive data recently on.

Andrew R. Allen: Coral study on the South African patients.

Andrew R. Allen: And.

Andrew R. Allen: There was positive data and the three vaccine candidates. So is there any development there or are you guys planning to which candidate are you guys planning to move forward.

Andrew R. Allen: The.

Andrew R. Allen: Obviously, if successful with our BARDA study, we'll be moving forward another candidate because, of course, we're expecting there to be an update of the strain that is required for the fall season of 2024. As you're aware, WHO and the EU have issued guidance to use the JN1 variant. But if you remember, obviously, last year it was the XBB1.5 variant.

Andrew R. Allen: Obviously, if it's successful with our BARDA study, we will be moving forward.

Andrew R. Allen: Another candidate because of course, we're expecting that to be an update of the strain that is required for.

Andrew R. Allen: So the full season of 2024.

Andrew R. Allen: As Youre aware W. H O and the EU has issued guidance to use the J and one variant.

Andrew R. Allen: If you remember last year. It was the ex PD 1.5 variant. So there will be a strain change we've not disclosed the exact nature of the T cell component that will include in the vaccine, but that will be included that as part of our <unk>.

Andrew R. Allen: So there will be a strain change. We've not disclosed the exact nature of the T cell component that we'll include in the vaccine, but that will be included. That's part of our chimeric vaccine design intended to induce protective antibodies as well as those protective T cell responses against conserved antigens. So that's the expectation going forward, and that's the primary focus of the program right now.

Andrew R. Allen: Mirick vaccine design intended to induce protective antibodies as well as those protective T cell responses against conserved antigens.

Andrew R. Allen: So that's the expectation going forward and that's the primary focus of the whole program right now.

Andrew R. Allen: Okay, thank you. And regarding the BARDA study, I just noticed in the press release that it says the company will be initiating that as soon as they can. Should we still expect that in fall 2024, or is that being re-evaluated?

Speaker Change: Okay. Thank you and regarding the BARDA study I just noticed in the press release.

Speaker Change: As the company you can.

Speaker Change: We'll be initiating that as soon as they can or should we still expect that in fall of 2024 or is that being reevaluated.

Andrew R. Allen: Yeah, it depends a little on our ability to meet the FDA's criteria around GMP raw materials. So obviously, that's a little contingent on further interactions with the agency, which is why we are cautious about specific guidance at this point.

Andrew R. Allen: Yes, it depends a little on our ability to meet the fda's criteria around GMP raw materials. So that obviously, that's a little contingent on further interactions with the agency, which is why we are cautious about specific guidance at this point.

Speaker Change: Okay. Thank you so much.

Speaker Change: Thank you.

Andrew R. Allen: Okay, thank you so much. Thank you. The next question comes from Catherine Novek with Jones Trading. Please proceed. Oh, hi, guys. Good afternoon. Thanks for taking

Operator: The next question comes from Catherine Novak with Jones Trading. Please proceed.

Andrew R. Allen: The next question comes from Catherine Novack with Jones trading. Please proceed.

Operator: Yes.

Catherine Clare Novack: Oh, Hi, guys. Good afternoon, Thanks for taking my question.

Catherine Clare Novack: Just a couple I guess.

Catherine Clare Novack: I wanted to ask about the prevalence of high risk disease versus low risk and you know do you consider that the predictive enrichment factor or you know mainly stop benefit due to the fact that patients had more mature PFS curves.

Catherine Novak: Yeah, thanks, Catherine. So the way we did this analysis was to look at the baseline circulating tumor DNA in every subject where we had that information, and then we took the control group, and we split it right down the middle. And we just bifurcated that population.

Catherine Clare Novack: Yeah. Thanks Catherine.

Catherine Clare Novack: So the way we did this analysis was to look at the <unk>.

Catherine Novak: We calculated the baseline circulating tumor DNA on every subject, where we had that information.

Catherine Clare Novack: And then we took the control group and we split it right down the middle.

Catherine Novak: And we just bifurcated that population.

Andrew R. Allen: We then applied that same cutoff to the vaccine arm, the test arm, and it actually was slightly lower than the median for the vaccine arm. So the vaccine patients actually had slightly higher baseline ctDNA than the control arm, which obviously works against the vaccine arm, all things being equal, which is good from a conservative data analysis point of view. So that's how we set it.

Catherine Novak: We then applied that same cutoff to the vaccine on the test arm.

Andrew R. Allen: And it actually.

Andrew R. Allen: It was slightly lower than the median for the vaccine arm. So the vaccine patients actually had slightly higher baseline C. T DNA.

Andrew R. Allen: And then the control arm, which obviously works against the vaccine arm all things being equal which is good from a conservative data analysis point of view. So that's how we set it. So it was a 50 50 in the control arm.

Andrew R. Allen: So it was a 50-50 in the control arm, slightly more in the vaccine arm. The reason we did that was simply to try and generate a more mature data set because, of course, everybody is asking the question, ourselves included, what will these data look like when we have the mature data? And so what we were trying to do was find a very fair way of identifying a population of patients. And baseline ctDNA is remarkably efficient at selecting for the patients who have faster events, and that's clear from the Kaplan-Meier curves that we showed. So that's why we did it.

Andrew R. Allen: Slightly more in the vaccine.

Andrew R. Allen:

Andrew R. Allen: The the reason we did that was simply to try and generate a more mature data set because of course, everybody is asking the question ourselves included.

Andrew R. Allen: Will these data look like when we have the mature data.

Andrew R. Allen: And so what we were trying to do is find a very fair way of identifying a population of patients.

Andrew R. Allen: Have events foster and baseline Cte DNA is remarkably efficient at selecting for patients who have foster events and thats clear from the capital Mark hubs that we showed.

Andrew R. Allen: So that's why we did it and.

Andrew R. Allen: You could reasonably argue that the high-risk population is the population that's going to do the worst on vaccines because, as I mentioned in my response to another question, there is a general belief, based now on data, that lower-volume disease does better on immunotherapy and perhaps particularly on vaccine immunotherapy. The lowest-volume disease is in the adjuvant setting, and that's where, of course, we've seen particular success with Moderna, who obviously did not see a signal in advanced metastatic disease but have seen a signal in high-risk adjuvant melanoma.

Andrew R. Allen: You could argue reasonably that the high risk population is the population that is.

Andrew R. Allen: Getting to do the worst on vaccine because as I mentioned in my response to another question. There was a general belief based on our data, but lower volume disease does better on immunotherapy, and perhaps particularly on vaccine immunotherapy the lowest volume diseases in the adjuvant setting and that's where of course, we've seen particular success by Madonna.

Andrew R. Allen: Who obviously it did not see signal in advanced metastatic disease, but have seen signal in high risk adjuvant melanoma. So within a metastatic colorectal population. There are obviously some patients with very extensive disease in some patients with.

Andrew R. Allen: So within a metastatic colorectal population, there are obviously some patients with very extensive disease and some patients with very mild or minor disease, but they all have metastasized colorectal cancer. CTDNA splits them up, and it gives you more data faster in that high-risk group with more extensive disease. So the fact we saw such a strong signal there is reassuring that as the data mature, we will then see a signal at least as strong in the low-risk group, maybe stronger.

Andrew R. Allen: Very miles of main the disease, but they will have metastatic colorectal cancer <unk>.

Andrew R. Allen: CTG in a split them.

Andrew R. Allen: And it gives you more day to foster in that high risk group with more extensive disease. So the fact, we saw such a strong signal there is reassuring.

Andrew R. Allen: Data mature we will then see a signal at least as strong in the low risk group may be stronger.

Andrew R. Allen: And therefore, our intention is not to think about this high-risk stratification once we're past Q3. And at that point, we anticipate we'll be including everybody and treating everybody and, hopefully, seeking a label for everybody because, in principle, if the product works for everybody, which is what we anticipate, then, of course, you don't want to be selecting out against particular patients.

Andrew R. Allen: And therefore, our intention is not to think about this high risk stratification. Once we're past Q3 and at that point, we anticipate we'll be including everybody in treating everybody and hopefully seeking a label and everybody because in principle. If the product works in every body, which is what we anticipate then of course, you don't want to be selecting.

Andrew R. Allen: Out against particular patients.

Speaker Change: Got it. Thank you that's very helpful.

Andrew R. Allen: Yeah.

Operator: The next question comes from Roy Buckman with Citizens JMP. Please proceed.

Andrew R. Allen: Yeah.

Andrew R. Allen: The next question comes from Gary Bachman with citizens JMP. Please proceed.

Roy Buckman: Hey, thanks for taking the questions. I think you just answered my granite question, which is stratifying by ctDNA, so it sounds like you're not going to do that. Going forward into Phase 3.

Roy Buckman: Hey, Thanks for taking the questions I think you've just answered my.

Roy Buckman: Question, which is stratify.

Roy Buckman: By Cte DNA, so it sounds like youre not going to do that.

Roy Buckman: Going forward into the phase III.

Andrew R. Allen: Well, let's be clear, Roy. We haven't got the data yet in the low-risk group. So everything we're saying today is speculation. What we have got is data on the high-risk group, which looks very good. Now we wait for data in the low-risk group. So I want to be super clear about this. It's not that we have no signal in the low-risk group; we have no data in the low-risk group because very few of them, as of early March, had achieved a progression or death event.

Roy Buckman: Well, let's be clear right, we haven't got the data yet in the low risk group. So everything we're saying today is speculation what we have got as data in the high risk groups looks very good.

Andrew R. Allen: Now, we wait for data and the low risk group, so I want to be Super clear about this is not that we have no signal in the low risk group, we have no data in the low risk group because very few of them as of early March had achieved a progression or death event. So it's not evidence of absence of effect its absence of any evidence about.

Andrew R. Allen: So it's not evidence of an absence of effect. It's absence of any evidence about anything. And therefore, you just wait. But what you would expect, based on the literature and what we've seen from others, is that the effect of the vaccine in that low-risk group will be at least as good as in the high-risk group, perhaps better. And if that's indeed what we see, then there would be no reason to worry about patient selection going forward.

Andrew R. Allen: Anything and therefore, you just wait but what you would expect based on the literature and what we've seen from others is that the effects of the vaccine in that low risk group will be at least as good as in the high risk group, perhaps better and if that's indeed, what we see then there would be no reason to worry about patient selection going forward.

Andrew R. Allen: Okay, got it. Okay, thank you. I guess I'll see you on Coral.

Speaker Change: Okay got it okay. Thank you.

Andrew R. Allen: A few on coral.

Andrew R. Allen: So this is RRPV, the holding vehicle or whatever it is, and you're waiting to hear back from them. Yes, any sense of when you might hear back on that? And is that a new set of people that are going to decide whether they like, you know, this program or that program or technology versus the first decision on the grant?

Speaker Change: So this is our our PV.

Andrew R. Allen: Holding vehicle or whatever it is and you're waiting to hear back much if any Samsung when you might hear back on that and is that it is that a new set of people that are going to decide whether they like this program or that program or technology.

Andrew R. Allen: Versus the first decision on the grant.

Andrew R. Allen: It is a different entity, but obviously, there is relatedness. But the exact nature of those relationships is not very apparent to outsiders like us. So, related but distinct.

Andrew R. Allen: It is a different entity, but obviously there is related nurse, but the.

Andrew R. Allen: The exact.

Andrew R. Allen: The nature of those relationships is not very apparent to outside is like us.

Andrew R. Allen: So related but distinct.

Andrew R. Allen: It is a consortium that's under, it's a consortium that's under BARDA's direction.

Andrew R. Allen: Okay.

Andrew R. Allen: It is a consortium that's under its a consortium that under our BARDA as direction.

Andrew R. Allen: And do you have any timelines of when they're going to get back to you?

Andrew R. Allen: Do you have any timelines of when we're going to get back to you.

Andrew R. Allen: We have not provided any guidance on that.

Speaker Change: We have not provided any guidance on that.

Andrew R. Allen: Okay.

Andrew R. Allen: Okay, and then you mentioned potentially partnering to fund the ID program, so that potentially includes COVID-19. All right, yes.

Andrew R. Allen: And then you mentioned potentially partnering to fund the IV programs will that also potentially include COVID-19.

Andrew R. Allen: Yes, potentially.

Andrew R. Allen: Yes potentially.

Speaker Change: Okay. Thank you.

Speaker Change: Thanks, Ron.

Operator: The next question comes from Author A with HC Wainwright. Please proceed.

Andrew R. Allen: The next question comes from Arthur He with H C. Wainwright. Please proceed.

Ashram: Hey, good afternoon, Andrew and team. This is Ashram on behalf of Sean. I just had a quick one regarding the granite. Just curious, when you see the ctDNA reduction post the chemo, did you see any correlation between the reduction and the baseline character of the tumor? I'm just curious, is there any way to get you guys to minimize this noisy background if you're going to use ctDNA further as a biomarker for the evaluation in the future?

Author A: Hey, good afternoon, Andrew and team.

Speaker Change: Oh for sure.

Ashram: Yes.

Ashram: I just had a quick one regarding the grant.

Ashram: Just curious where you see the.

Ashram: CDMA reduction opposed to the chemo.

Ashram: Did you see is there any correlation right for the reduction with the baseline character of the tumor.

Ashram: I was just curious is there any any way you guys could minimize these.

Ashram: Nor has the background footwear you if you could go into use the C. D. C. D C T DNA through further as a biomarker for evaluation in the future.

Andrew R. Allen: We haven't performed those analyses yet. Obviously, it's a phenomenon that relates to the tumor response to chemotherapy, specifically to Folfox or Folfoxiri plus bevacizumab, and that regimen is only used in colorectal cancer. Derivatives of it, I guess, could be used in pancreatic cancer, but they wouldn't have great utility outside of this colorectal cancer setting. And so determining who does well on chemotherapy is obviously not particularly critical to our development program going forward.

Speaker Change: We haven't performed those analyses yet.

Andrew R. Allen: Obviously, it's a phenomenon that relates to the tumor response to chemotherapy, specifically to full Fox or full Fox series, plus Bevacizumab and that regimen is only used in colorectal cancer.

Andrew R. Allen: Derivatives of it I guess used in pancreatic cancer, but it wouldn't have great utility outside of this colorectal cancer setting.

Andrew R. Allen: And so determining who does well on chemotherapy is obviously not particularly critical to our development program going forward.

Andrew R. Allen: All right, thanks. And my second question for the further readout in the third quarter. Besides the PFS, mature PFS, and more CT DNA data, what other data could we expect that could give us more information regarding the pivotal study?

Speaker Change: Alright, Thanks, and my second question for the so the.

Speaker Change: The updated arena further readout in the third quarter.

Speaker Change: Besides the PFS mature PFS and.

Speaker Change: More city DNA data.

Speaker Change: What other data could we expect.

Speaker Change: And give us more.

Speaker Change: Information regarding the pivotal study design.

Andrew R. Allen: Yeah, so the overall survival data will still be very immature at that point. The median overall survival is around two years in this disease. So again, following the same logic, if PFS is basically around one year or just shy, you need to give it another year to get to very mature OS data. Now, we are doing some additional analyses. Karen, our head of R&D, is on the phone here. So, Karen, perhaps you want to give a little flavor as to what additional correlates we might have for the Q3 update.

Speaker Change: Yeah. So the overall survival data will still be very immature that point median survival overall survival is around two years in this disease.

Karen: So again following the same logic, if PFS is basically around one year, just shy you need to give us another year to get to a very mature OS data.

Andrew R. Allen: Now we are doing some additional analyses caring our head of R&D is on the on the phone here. So Karen perhaps you want to give a little flavor as to what additional.

Karen: Carlos we might have.

Karen: The Q3 update.

Karen Youse: Yeah, we are looking at a subset of the patient population. We perform TCR-Seq. We perform ELISBOT analysis.

Karen: Yeah, we are looking in a subset of the patient population the pro forma petr's seek.

Karen Youse: So, we do look at translational data, which we actually have published significant data on in our Nature Medicine paper. So, we do some of that work, but we don't anticipate the data to look any different from our goal for nanoscript. But TCR-Seq and ELISBOT, you can anticipate that. We can also potentially, if we have enough cells, perform ICS looking for polyfunctionality or even killing. So, we have a great toolbox, and depending on the number of cells we have from these blood trials, we were in a subset of these patients looking for T-cell responses, TCR-Seq, as well as T-cell functionality.

Unknown Executive: And it's but analysis.

Karen Youse: So we do look at translational data, which we actually have published significant data on in our nature Medicine paper. So we do some of that work.

Karen Youse: But we don't anticipate the data to look any different.

Karen Youse: I'll go for a minute script, but Keith Jerry Fujian elite spot you can anticipate that we are also potentially if we have enough cells coupon.

Karen Youse: ICF looking for poly functionality or even killing.

Karen Youse: We have a great toolbox and depending on the number itself we have a problem.

Karen Youse: Deep <unk> in a subset of these patients looking for.

Karen Youse: T cell response teeth here at <unk>.

Karen Youse: As far as functionality of the teach outs.

Karen Youse: Great. Thanks for the addition of color. Thanks for taking my question. Thank you. The next question comes from Corinne Johnson with Goldman Sachs. Please proceed. Hi, this is Omari on behalf of Corinne.

Speaker Change: Great. Thanks for the additional color. Thanks for taking my question.

Operator: The next question comes from Corinne Johnson with Goldman Sachs. Please proceed. Hi, this is Omari Owen on behalf of Corinne. I have a couple questions.

Omari: Thank you.

Omari: The next question comes from Corinne Johnson with Goldman Sachs. Please proceed.

Omari Owen: Hi, This is Mario on for Karen So a couple of questions. What gives you confidence that the PFS will strengthen the osprey data matures.

Omari Owen: On the hazard ratio, if the piecewise Cox ph model a pre specified analysis.

Omari Owen: So, the confidence comes from two primary sources, directly and one indirect source. First of all, we saw the same phenomenon of PFS and OS extension in the Phase 1-2 study in third-line colorectal cancer patients.

Omari Owen: So the confidence comes from two primary sources directly in one indirect source first of all we saw the same phenomenon of PFS nurse extension in the phase one two study in third line colorectal cancer patients not a randomized study, but those who had reductions in there.

Andrew R. Allen: Not a randomized study, but those who had reductions in their bone biomarkers, including ctDNA, had this apparently extended PFS and OS. So we're repeating that observation in this study, which gives you a way of peering into the future. And it's obviously not a perfect analysis. No one can foretell the future. If they could, it would be easy.

Andrew R. Allen: Biomarkers, including <unk> had this apparently extended PFS and OS. So we're repeating that observation in this study.

Andrew R. Allen: Secondly, the high risk analysis.

Andrew R. Allen: It gives you a way of peering into the future and it's obviously not a perfect analysis no one can foretell the future if they could we'd obviously you it would be easy.

Andrew R. Allen: But it's a reasonable way of asking the question, if I expect the low-risk group to behave similarly to the high-risk group, then what will I see in the future? And obviously, the high-risk analysis is quite mature and looks very encouraging. So that's the second direct bit of evidence to encourage optimism for the Q3 mature data. The indirect support comes from the notion that the data we're waiting for is in the low-risk patients, and data from other players, most notably Moderna, suggests that those low-volume disease patients are the ones that do best on vaccine-based immunotherapy.

Andrew R. Allen: But it's a reasonable way of asking the question if I expect the low risk group to behave similar to the high risk groups than what would I see in the future and obviously the high risk analysis is quite mature and looks very encouraging. So that's a second direct bid of evidence to encourage your optimism for the Q3 mature data the.

Andrew R. Allen: The indirect support comes from the notion that they too are waiting for are in the low risk patients and data from other players most notably Madonna suggests that those low volume disease patients are the ones with two best on vaccine based Immunotherapies. Therefore, if you believe that that applies to this study we should see signals at least.

Andrew R. Allen: Therefore, if you believe that that applies to this study, we should see signals at least as strong, if not stronger, in the lower-risk population as the data set rounds out and matures. Your second question was about the GPW statistical test, and I couldn't quite catch it. It was the question, "Are we using that in the summer?" Thank you. Yes.

Andrew R. Allen: As strong if not stronger in the low risk population as the dataset rounds out to matures.

Andrew R. Allen: Your second question was about the G. P. W Statistical tests and I couldn't quite catch it was the question are we using that in the summer.

Andrew R. Allen: In Q3.

Andrew R. Allen: Piecewise Cox ph motto with a pre specified analysis for this study.

Andrew R. Allen: Yeah, so we've actually been in a lengthy dialogue with FDA around the way to statistically analyze the study because it is clear that patients are randomized at the beginning of their induction chemotherapy, and for the first, on average, five months, treatments are identical across the two arms of the study, and then the treatments diverge. And, therefore, the Kaplan-Meier plots of progression-free survival will not meet the proportional hazards assumption, and that is a requirement if you're going to use the standard log-rank test.

Speaker Change: Yes, yes, so we.

Andrew R. Allen: We've actually been in a lengthy dialogue with FDA around the way to statistically analyzed study because it is clear that patients are randomized at the beginning of their induction chemotherapy.

Andrew R. Allen: So the first on average five months the treatment saw identical across the two arms of the study and then the treatments diverge.

Andrew R. Allen: Therefore, the Kaplan Meier plots of progression free survival will not meet the proportional hazards assumption.

Andrew R. Allen: And that is a requirement if you're going to use the standard low grant test. So we knew the way. The study was designed low grant was not the appropriate statistical tests in the appropriate way to analyze these curves.

Andrew R. Allen: So we knew that the way the study was designed, the log-rank was not the appropriate statistical test and the appropriate way to analyze these curves. In fact, what you wanted to do was a time-weighted system. So we entered this discussion with the agency, and we settled with them on GPW, the Global Generalized Piecewise Analysis, and we've done a very simple model for this study. Any progression event prior to six months is given a weighting of zero, and any progression event after six months is given a weighting of one. That's the way we've analyzed these data, and that was pre-specified, yes.

Andrew R. Allen: In fact, what you wanted to do was a time wasted system.

Andrew R. Allen: So we entered this discussion with the agency and we settled with them on GP W. The global German sorry, generalized piecewise analysis, and we've done a very simple model for this study any progression event. Prior to six months is given a weighting of zero and any progression then after six months given the weighting of one that's the way we've analyze these data.

Andrew R. Allen: And that was pre specified yes.

Andrew R. Allen: Yes.

Speaker Change: Thank you.

Operator: Thank you. At this time, there are no further questions in queue. I'd like to turn the call back to Andrew Allen for closing comments.

Andrew R. Allen: Thank you at this time there are no further questions in queue I'd like to turn the call back to Andrew Allen for closing comments.

Andrew R. Allen: Thank you very much. That represents the end of our call, so we have nothing further to add. I'd just like to thank you for your time and attention. Obviously, we're very excited to see these data in Q3, and we hope to be able to really move the ball forward for these patients who've been waiting a long time for some reasons for optimism. And with that, thank you very much. Thank you. This does conclude today's program.

Andrew R. Allen: Thank you very much that represents the end of all of our coal. So we have nothing further to add just like to thank you for your time and attention. Obviously, we're very excited to see these data in Q3, and we hope to be able to really move the ball forward for these patients who've been waiting a long time for some reasons for optimism in with that.

Andrew R. Allen: You very much.

Operator: Thank you. This does conclude today's teleconference. You may disconnect your lines at this time. Thank you for your participation and have a great day.

Speaker Change: Thank you. This does concludes today's teleconference. You may disconnect. Your lines at this time. Thank you for your participation in Africa, Great day.

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