Welcome to Gritstone bio Q2 2022 Conference Call. Please note this event is being recorded. It is now my pleasure to introduce George MacDougall, Director of Investor Relations and Corporate Communications at Gritstone bio. Please go ahead, sir. Thank you, operator, and thank you, everyone, for joining us for Gritstone's conference call to discuss our financial results, clinical, and business updates for Q2 of 2022. 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. Joining us for the Q&A portion will be Karin Jooss, our Head of R&D. Today, after the market closed, we issued a press release providing our Q2 2022 financial results, clinical, and business updates. The press release is available on our website. I'd like to remind you that today's call is being webcast live via a link on Gritstone's investor relations website, where a replay will also be available after its completion. 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 based on current expectations. These forward-looking statements are subject to a number of significant risks and uncertainties, and our actual results may differ materially from those described. We encourage you to review the risk factors in our most recent Form 10-Q, filed with the U.S. Securities and Exchange Commission and available on our website. 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. With that, let me turn the call over to Andrew. Andrew. Thank you, George, and good afternoon, everybody. Thanks for joining us for our Q2 2022 Conference Call, which is Gritstone's first earnings call. We decided to hold a call this quarter because we believe it's helpful to speak to our updates in a little more detail than can be provided in today's press release, and also to provide you an opportunity to ask and for us to answer questions. We hope you'll find it useful, and we intend to hold calls for future earnings on an as-needed basis. This is an exciting time for Gritstone. Significant momentum is building for our clinical stage oncology programs. Granite is now in two randomized trials in earlier stage colorectal cancer, and Slate is progressing nicely in phase II for the treatment of advanced solid tumors. For our infectious disease programs, we are making great strides in realizing the incredible potential of our T-cell enhanced self-amplifying mRNA vaccines for viral diseases. Financially, we have sufficient runway to see all of our 2022/2023 clinical catalysts through, and Celia will walk through all of the details on our financials towards the end of this call. First and foremost, I'm excited for the data that we expect to deliver in the coming months, which we believe will further validate our platforms and overall approach in both infectious disease and cancer. Between now and year-end, we expect several data sets from CORAL, a second-generation T-cell enhanced COVID-19 vaccine program using our self-amplifying mRNA or samRNA technology platform. We are all well aware of the need for a vaccine that generates broad and durable responses to both the current and future variants of SARS-CoV-2, and we saw much discussion of these goals at last week's White House summit. Neutralizing antibodies elicited by first generation vaccines to SARS-CoV-2 variants appear to have quite short half-lives, and measurement of antibody duration has assumed greater importance. We at Gritstone are leaders in the samRNA field, having been the first to study this novel vector class in clinical trials, and the likely extended duration of antigen expression associated with samRNA may positively impact antibody duration. We're optimistic that our samRNA vaccine approach to SARS-CoV-2 and other pathogens could provide significant, meaningful clinical differentiation. Now in January of this year, we shared data from the first cohort of our phase I CORAL-BOOST study, showing that our samRNA vaccine candidate was effective at generating strong immune responses when used as a boost following two doses of Vaxzevria or the AstraZeneca vaccine. Specifically, our vaccine candidate demonstrated peak neutralizing antibody titers comparable to the best-in-class mRNA vaccine, Moderna Spikevax. We observed induction of de novo T-cell responses to conserved regions of non-spike genes included in the vaccine construct. This was when our samRNA vaccine candidate was administered at just 10 micrograms, one-tenth of the dose of the Moderna vaccine. What I'm excited to share with you today is that follow-up data from the first two cohorts of subjects boosted with just a single dose of either 10 or 30 micrograms of the samRNA vaccine candidate demonstrated that the robust neutralizing antibody response seen in January persisted without decay for at least six months. You can see a slide on these data in our corporate presentation available on the investor relations section of our website. Now, this is a small subset of seven subjects, but nonetheless an early and highly encouraging signal that samRNA can generate more durable immune response than first generation products. It is a small number of subjects since to study the long-term response to single boost vaccination, we had to exclude those many subjects that chose to receive more than one boost over the six-month period. The breadth of the neutralizing antibody response elicited by our samRNA boost is also encouraging. While neutralization of wild type spike is the highest, as expected, of course, since that is the variant delivered within the vaccine, the drop-off of neutralizing potency against key variants such as Omicron is only around 10-fold versus the 40-fold typically seen with first generation products. The reactogenicity of the vaccine candidate is as expected for potent vaccines and remains consistent with data we presented in January of this year. The degree of reactogenicity of the 30 microgram dose level is slightly greater than that for 10 micrograms, although tolerable, and we have selected 10 micrograms as our go-forward dose. It is important to recognize that self-amplifying mRNA is fundamentally different from the first generation mRNA vaccines. The continued rounds of RNA replication deliver different immune response kinetics, and long-term antigen persistence may be driving the potentially superior and more durable immune response that we're observing in these early data. We will be presenting additional results from further cohorts from the CORAL-BOOST study at IDWeek 2022 in October, and we plan to share preliminary data from CORAL-CEPI as well. We've dosed over 100 subjects in the CORAL-CEPI study in South Africa, and these are all vaccine-naive subjects, so those data are very important to the characterization of this compelling platform. The recent publication of our non-human primate challenge study data in Nature Communications provides nice third-party recognition for this program. Let's turn to cancer. In September of this year, we'll share data from Slate, our off-the-shelf neoantigen vaccine program, in a mini oral presentation during the European Society for Medical Oncology or ESMO annual meeting. Recall that results from version one of Slate were encouraging. You can review these in our previous press releases. That early immunogenicity data from this phase II trial with the second generation product candidate focused exclusively on KRAS and termed Slate KRAS, were presented at AACR in April, suggesting that Slate KRAS was driving stronger CD8+ T cell responses to mutant KRAS than the first version or version one. In our mini oral presentation at ESMO, we intend to share initial clinical efficacy and safety data from the ongoing phase II single arm study of Slate KRAS in patients with advanced non-small cell lung cancer and colorectal cancer. SLATE-KRAS is an exciting immunotherapy candidate, in part because it includes not only the famous KRAS G12C mutation, but several other KRAS mutations, all in a single immunotherapy product candidate, which gives it the potential to address a substantial patient population across multiple tumor types. Observing molecular and clinical responses in end-stage patients would catalyze a strong desire to launch clinical trials in earlier disease settings where immunotherapy has more time to drive an immune response and consequently impact disease. Of note, the initial results we plan to share at ESMO could provide proof of concept beyond just targeting KRAS. There are many other neoantigen targets that are shared between cancer patients that could be the basis for novel product candidates. In other words, where mutant KRAS leads, others may follow. Granite is our individualized neoantigen vaccine program for solid tumors, and it is rapidly advancing in the clinic. This year we've taken the program into a randomized, potentially registrational phase II/III trial in newly diagnosed metastatic colorectal cancer or CRC patients. The phase II/III is underway, and we're looking forward to sharing initial phase II data in the second half of next year. We also have a randomized controlled phase II trial that is open for enrollment for patients with high-risk stage 2/3 colon cancer who are circulating tumor DNA positive or ctDNA positive after their definitive surgery. This, of course, is a population at very high risk of recurrence. The follow-up data phase I/II study in Granite has demonstrated a correlation between molecular response as measured by a reduction in ctDNA and extended overall survival. These are very encouraging data. The use of ctDNA as a short-term efficacy biomarker for novel immunotherapies is becoming more widely accepted for two good reasons. Firstly, traditional radiology is failing as a reliable tool for assessment of immunotherapy benefit. Secondly, ctDNA response appears to be performing as a reliable surrogate for overall survival in multiple settings. The FDA has taken notice and issued draft guidance a few months ago regarding the potential role of ctDNA in drug development in early stage solid cancers. Two weeks ago, the Friends of Cancer Research held a public meeting, including high-level members of the FDA, on potential roles for ctDNA analysis in drug development in more advanced disease, highly pertinent to our Granite program. Turning back to our data with ctDNA, the median overall survival of CRC patients who demonstrated molecular response within phase I/II study has not been reached, and as last reported in May, is 18 months and growing. This compares to 7.8 months median overall survival in patients who did not have molecular response, which is in line with the six to seven months median overall survival typically seen with multiple therapies in the third-line colorectal cancer setting. Additionally, some of our patients had protein biomarkers such as CEA and CA 19-9, which tracked with their disease burden, and changes in these biomarkers were highly correlated with what was observed in ctDNA. This consistency within the small data set provides encouraging validation for our Granite program, and importantly, no new safety concerns have arisen. The patients enrolled phase I/II trial had been treated with two prior therapies and have a low probability of survival beyond a year. What we're observing, even in these very advanced CRC patients, is that Granite has the potential to profoundly change the disease kinetics in approximately half of patients. As we move into an earlier disease context with healthier patients, better immune systems, and more time for immune responses to mount and take effect, it is likely that the frequency and magnitude of Granite benefit will increase. This is a truly exciting prospect for a large population of patients for whom immunotherapy has not yet delivered any benefit. Beyond Granite, Coral, and Slate, we continue to apply our broad set of capabilities in oncology and infectious diseases through some promising preclinical work and strategic partnerships. Our partnership with Gilead for development of a therapeutic vaccine for HIV remains in place and active. The IND for this program was cleared in Q4 of 2021. You may recall that Gilead has an option to advance beyond the phase I study in this program, which would trigger a $40 million milestone payment to Gritstone. Ongoing preclinical projects include a pan-coronavirus program, where we're deploying our samRNA platform to deliver multiple spike elements plus broadly conserved T-cell epitopes from family members beyond just SARS-CoV-2 to drive potentially broad clinical coronavirus immunity. We also have a program aiming to develop an optimal immunogen in the context of human papillomavirus, which is being funded by the Gates Foundation. We continue looking at other infectious disease pathogens for future therapeutic and prophylactic programs. The suite of capabilities we've developed in infectious diseases, from T-cell antigen identification within viral genomes to the clinical application of a potential best-in-class form of mRNA vaccine vector to robust assessments of T-cell responses in clinical trials, are all highly desirable. Our partnerships with Gilead, NIAID, the Bill & Melinda Gates Foundation, and CEPI underscore this, and these capabilities are likely to be of interest to other potential partners. Regarding our financial status and the status of capital markets, I'm confident in how we as a company are navigating these turbulent times. We are being prudent, prioritizing programs, and implementing continuous capital conservation measures. We're also being proactive. The credit facility that Celia and team have established provides us an option to tap non-diluted funds should we choose. Gritstone has been through cycles of capital markets before, and I'm confident in our ability to navigate this one. As I stated, this is an exciting time for Gritstone. We have a very attractive clinical stage and partnerable platform, a potentially best-in-class self-amplifying mRNA vaccine that has broad potential applicability, and multiple potential value creation milestones in the near future. I'll now turn the call over to Celia, who will discuss our financial results for Q2. Celia? Thank you, Andrew. Good afternoon, everyone. Gritstone ended Q2 with $159.2 million in cash equivalents, marketable securities, and restricted cash. As Andrew already mentioned, we have taken several measures to fortify our cash position and extend our runway in recent months. These include, but are not limited to, discontinuation of the CORAL immunocompromised study, since passive immunization has now addressed this need for now. We've only been hiring into critical new positions and backfills, and we're reducing our general and administrative costs where possible. Additionally, we established a credit facility with Hercules Capital and Silicon Valley Bank for up to $80 million subsequent to the quarter's end, and we withdrew $20 million of the $30 million that's available at closing. Our capital conservation measures alone extend our runway by a quarter into Q4 of 2023. The credit facility provides us further flexibility. With respect to the details of the credit facility, an additional $10 million is available at our request through March 15th, 2023, and the remaining $50 million remains available in tranches upon our achievement of certain milestones through June 15th, 2024. We are under no obligation to draw funds in the future, and there are no warrants associated with this transaction. Turning to our Q2 2022 operating results, we reported research and development expenses of $27.3 million for the quarter that ended June 30, 2022, compared with $22.1 million for the same period last year. The increase in R&D costs was mainly related to the launch of our new Granite studies, phase II/III in first-line colorectal cancer, and a phase II in adjuvant therapy for colon cancer, along with our CORAL programs, both the CORAL-BOOST and CORAL-CEPI studies that were initiated at the end of 2021 and the beginning of 2022. We also reported that general and administrative expenses were $7.8 million during Q2 of 2022, compared with $5.9 million for the same period last year. The net loss was $29.5 million for Q2 of 2022, compared with $25.1 million for the same period last year. Finally, as of June 30, 2022, Gritstone had approximately 73,006,089 shares of common stock outstanding and pre-funded warrants outstanding to purchase 13,573,704 shares of common stock at a nominal exercise price of $0.01 per share as of June 30, 2022. I'll now turn the call back over to Andrew for some closing remarks. Andrew? Thank you, Celia. As we look ahead to the remainder of this year, I can speak on behalf of the entire Gritstone team to say that we're more excited than ever about the potential of our innovative cancer and infectious disease platforms, and very much looking forward to the critical data outputs that will be flowing over the next few months and throughout 2023. At this time, I'd like to thank you all for joining us today, and I'll turn the call over to the operator for questions. Operator? Thank you. Ladies and gentlemen, if you would like to ask a question, please signal by pressing star one on your touch-tone phone. If you're using a speaker phone, please make sure your mute function is turned off to allow your signal to reach our equipment. Again, press star one to ask a question. We pause just for a moment to assemble the queue. We take our first question from Mark Breidenbach with Cowen. Your line is open. Please go ahead. Hey, thanks for taking the questions and congrats on the data. For Andrew and I guess Karin, just given the data you showed today and kind of the potential durability benefits that you're seeing on titers, I guess, can you confirm that, you know, these patients aren't seeing any kind of evidence that they've been infected or, you know, or what gives you confidence that they're not getting exposed to Omicron, since I believe the data you're comparing to the samples were actually taken when maybe Omicron and particularly BA.4/5 was not circulating. Yep. Thanks for the question, Mark. Karin, our head of R&D is joining us for Q&A, so I'll ask Karin to answer that question. Karin? Yeah. Thank you very much. Of course, this was obviously our focus to make sure that post the self-amplifying RNA vaccination, the individuals did not get infected with Omicron, and so we looked for nucleocapsid serology. We had actually two individuals who did get infected, so the nucleocapsid serology increased significantly. They are not part of our data set. We removed them, and so the subjects that we are showing in our data graphs, they have not been infected. Very good question. Thank you. All right. That's very helpful. Thanks. Then a similar idea, just, you know, when we look towards the CORAL-CEPI data in the vaccine-naive patients later, you know, how should we interpret that data and kind of what's a good response there, given again, that these patients, you know, have, while they may not have received vaccine in South Africa, they likely have had at least one, if not multiple COVID exposures, you know, before? Yeah. Excellent question. Basically, again, at baseline, we of course get a pre-vaccination baseline sample. We look for spike serology, we look for nucleocapsid serology. We know that anyone infected previously with COVID is positive, and therefore, even in the naive cohort, we will see who has had previous exposure to COVID. Obviously very important for us to assess, and we will have the data to really understand who is naive and who had previous exposure. Yeah. Great. Thank you, Karin. Just for clarity, Mark, the we actually treat two cohorts in South Africa at each dose level, and the subjects are divided into quote, "convalescent and naive." As Karin stated, they're allocated to each of those cohorts based upon their baseline anti-nuclear protein serology. We separate them out consciously mindful of exactly what you just said. Those who are N antibody positive at baseline receive a single dose of vaccine, the quote, "convalescent group," whereas those who are N antibody negative, the quote, "naive group," are given two doses of the vaccine. Okay. It's very helpful. Maybe just following up on all those, you know, what the next steps might be, and kind of what appetite you see out there among maybe non-commercial entities to help fund your novel vaccines rather than just continuing to iterate on the approved vaccines? Yeah. I think the recognition that the first generation products, while clearly extremely effective at limiting the impact of the pandemic, do have some constraints and limitations. Clearly variant proofing is one limitation, and compounding that is lack of antibody persistence. If you receive, you know, spike vaccine that is Wuhan spike, let's say, or the so-called ancestral variant, then you'll mount a good antibody response with a first generation product. The potency against some of the variants is significantly lower, as we know. With Omicron, for example, it's often about 40-fold lower potency. That's problem number one, is that the variant is not anticipated very effectively. Number two is that over time, those titers then decay and fairly quickly fall below the protective threshold. You have this double whammy effect that the variant proofing is limited and the decay is relatively swift. With antibodies, obviously, what we may be seeing with our samRNA product is that the decay concern is mitigated. Therefore, if I'm able to generate good titers of neutralizing antibody at baseline, obviously that potentially will help sustain clinical protection against the variants that are covered by those antibodies. Of course, we have the T cell side of the house, which is separate. I think the more we demonstrate differentiation, the more interested people will be in this program. I think there's a convergence now of growing interest amongst third parties in the notion of superior vaccines that address the emerging limitations of the first generation products and our ability to demonstrate meaningful differentiation along those key axes. Obviously, it's the combination of those two elements that potentially will drive us towards a pivotal trial. We're obviously not quite there yet, but that's potentially where we are heading. Okay. Thank you. Thanks, Mark. Thank you. We take our next question from Kaveri Pohlman with BTIG. Your line is open. Hi. Thanks for taking the questions. It's Tom on with Kaveri. I had a few questions about the remarkable SAM effect. How much do you understand it? Is the RNA still around? Are you adding T-cell epitopes, or is it just samRNA when you get it right, you get inherently more T-cell response? I guess the bigger question is, are you generating IP around this approach? On the second question, yes. We're obviously pioneers in the self-amplifying mRNA field. We were the first to put this construct into humans, and of course, that helps from an intellectual property perspective. Also recognize that as ever with complex biologics, manufacturing is really important, and we are manufacturing our own products. It's not just patents, but also know-how and trade secrets that can provide real benefit. So that's the answer to the second part of your question. In regard to the fascinating first part of your question, I'll pitch that one over to Karin. Yeah. Thank you very much. What do we know about self-amplifying RNA? We did perform a biodistribution study. Our colleagues from mRNA, they have published data suggesting a half-life of around 20-24 hours. When we did a biodistribution study, we see self-amplifying RNA in the muscle cells for a couple weeks. The duration of antigen presented to the immune system is significantly longer. At the same time, the replication, during the replication phase of self-amplifying RNAs, intermediate forms of RNA are being generated, which we know triggers innate immune responses, which we believe is also helping to mature the dendritic cells leading to potent T cell activation. I think it's a combination of the durability of antigen expression as well as presenting the antigen to the T cell and the dendritic cell actually in a dangerous milieu leading to these T cell activation and also durability of the immune response. Yeah. Okay. Thank you. If I can ask a quick question on the first-line CRC trial. You're probably very interested in ctDNA responses, but from a regulatory point of view, is this really a pure OS trial? Is there anything you would see before OS that would matter? Yeah, it's a good question, Tom. The primary endpoint for the phase II is ctDNA response. Now, obviously, that is not currently recognized as a registrational endpoint, although there is a lot of activity in the space. As we've discussed previously, I think there are two reasons for that. Number one, radiology and standard RECIST assessment has clear limitations with immunotherapy. I think it both misses some benefit and also misclassifies people as progression when it is not true progression. It is a so-called pseudoprogression. This may be more of an issue in something like colorectal cancer, where the lesions are pretty cold at baseline. If we're successful with our product, we generate T cells that recognize tumor neoantigens. Those T cells infiltrate tumors, and we've demonstrated this, and then they proliferate. That's the intention. At some level, you actually want to see "expansion" of a lesion as a marker that your T cells are doing what they're intended to do. Now, of course, they should then start killing tumor cells. This is the challenge. We don't know the relative balance of how many bad guys are there, i.e. tumor cells that are being killed and how many good guys, T cells proliferating, because it's the sum of those two populations that is measured by radiology, which is a very crude tool that simply can't tell them apart. This is the challenge with RECIST. You know, we're seeing lots of examples now where RECIST is leading us a little bit in the lurch by misclassifying patients and even just missing benefit. Immunocore being probably the best-known example. ctDNA is, of course, potentially a better biomarker, and there's more and more data accumulating to suggest that that may be true with novel immunotherapies. Again, I'm not referring here to chemotherapy or targeted therapy. There we understand the value of RECIST. Novel immunotherapy is a different beast for which RECIST radiology was not devised. ctDNA looks very interesting, and the regulators are paying attention. Now, there is of course, an endpoint between ctDNA and overall survival, which is progression-free survival. The concern about using standard PFS per regular RECIST is that you will misclassify patients, and that lesions will expand because of T-cell proliferation, that will be classified as progressive disease per RECIST, even though actually the patient is doing very well. That is clearly a real concern with what we're doing. You've seen from some of our images in the phase one study that we've presented, that we observe expansion of lesions followed by contraction, cavitation, and shrinkage. We've clearly observed pseudoprogression radiologically with this therapy. We're nervous about PFS with RECIST. Now, there is iRECIST, which is developed specifically for immunotherapy, that allows you to have one scan that shows pseudoprogression. Again, it wasn't developed for our immunotherapy, it was developed for checkpoints. Checkpoints generally work in patients who already have T-cells in their tumor that recognize neoantigens. What we're doing is clearly proximal to that, and therefore, maybe iRECIST is not yet calibrated for our purposes and for our therapy. We're exploring that in the phase II study that we're currently running, so we will generate data to answer all these questions. The fallback is overall survival, as you say. You know, unfortunately, in metastatic colorectal cancer, overall survival is not a terribly remote endpoint. You know, median survival's in the two years or so range. This is an endpoint that can be used and of course, there's no crossover with the trial that we're running, given the nature of the product. I think the answer to your question is, as you think about registration, OS is the conservative fallback. iPFS, I think is a possibility if our phase II data suggests that it does capture and deal with pseudoprogression appropriately. Upside would be that ctDNA advances to a point where it is widely recognized, potentially as an endpoint for accelerated approval on the basis that it is, to quote the legislation, "reasonably likely to predict clinical benefit," in this case, reasonably likely to predict overall survival benefit. So that's kind of the way we think about endpoints in that context. Great. Thank you for the thoughtful answer. Yep. Thanks, Tom. Thank you. The next question is from Sean Lee of H.C. Wainwright & Co. Your line is open. Good afternoon, guys, and thanks for taking my questions. My first one is on SLATE and the upcoming presentation at ESMO. Could you provide us with a bit more color on the number of patients and what kind of results can we expect? Like, what the type of results in terms of endpoints and biomarkers? Yeah. This is a phase II study. The N is relatively modest. We'll be showing it with both the second generation so-called SLATE KRAS product. We'll also remind you of the first generation SLATE version one data as well. We'll be putting those together. You know, it's a regular phase II study, and it has a standard efficacy endpoint of response. That obviously can be measured using radiology, recognizing the limitations that I've just articulated. Also, of course, we're measuring ctDNA. We'll be showing data primarily on lung cancer and colorectal cancer subjects. As you would imagine, all of the lung cancer subjects have previously been treated with immune checkpoint blockade. We're in the post-ICB environment for these data. Colorectal, obviously, we're typically treating after FOLFOX or FOLFIRI. Typically in the second or third line setting, depending upon what the patient receives as frontline chemo. You'll get a pretty complete dataset as well as, of course, always safety. That's what you should be looking out for. Great. Thanks for that. My second question is a bit of a high-level one regarding the CORAL program. A lot of discussion right now on the regulatory side, they seem to be favoring an annual vaccine taken in the fall, similar to the flu one. How do you envision CORAL fitting into this paradigm? Or do you think that, because the longer-lasting CORAL durability, we could be able to exceed this paradigm? Yeah. I think it's an unsatisfying paradigm. No one, I think, would regard the current model for influenza vaccination as a glorious success. You know, we have to try and predict which serotypes will be prevalent in the upcoming flu season, and our predictions are far from perfect, meaning that we often actually immunize with variants that end up not being particularly important in that future flu season. It requires annual boosts. I mean, neither of those is particularly attractive. I think we would all prefer to have less frequent vaccinations that have greater, broader protective utility. The T-cell component is obviously central to this question. There are lots of indirect data sets suggesting that T-cell immunity to influenza does provide broad protection against severe disease, but it hasn't been tested prospectively in a phase III trial with a vaccine that elicits strong T-cell responses to conserved epitopes and measures them. Obviously, if we are to be successful in developing these broadly protective vaccines, whether it's for coronavirus or for influenza, come to that matter, you need to start running phase III trials where you measure not just antibody, but also T-cell response. That's a key topic obviously for us that we're quite focused on. In terms of the antibody side, there are some variants which appear to provide broader protection than others. There's a reasonable amount of data in the literature now suggesting that with beta spike, the so-called B.1.351 variant, the antibodies that you generate to beta spike provide broader cross-reactivity, cross-protection than, for example, antibodies elicited by an Omicron variant spike. Omicron appears to generate pretty narrow immunity, whereas beta is potentially broader acting. Now, we only have two years of experience with SARS-CoV-2 to know whether we're gonna see continued significant changes in the forms of spike that we're dealing with. It's a little early to answer the question on the antibody side. I think the notion of having broadly neutralizing antibodies is not completely impossible. You combine that with T-cell immunity. I think there is a hope for vaccines that do not require predictions and annual boosts, and then we'll get free of this rather clunky paradigm that we're currently living with. I think we should and potentially can do better than the annual boost with a prediction as to what matters in the coming season. I see. That was very helpful. Are there further questions I have? Thanks, Sean. Thank you. The next question is from Corinne Jenkins of Goldman Sachs. Your line is open. Hi. Good afternoon, everyone. I'm curious, since the last CORAL update you provided in the winter, have you gotten any specific regulatory guidance or an update on the regulatory path ahead for CORAL? And if so, could you just share any details there? No, we're not yet at liberty to share any regulatory conversations that we've had, Corinne. Obviously, what we'll put into public domain in October, as we said, is a much more complete data set at multiple dose levels with some RNA in both as both a boost and also in vaccine-naive subjects. We'll be looking at antibody immunity, T-cell immunity, and reactogenicity/safety as well, of course. This is the foundation upon which we'll build, but we're not yet at liberty to discuss what a pivotal trial might look like. Okay. Would you plan to go to regulators with that data in hand then sometime after you present it this fall? Yeah. Obviously, we're not doing this for academic purposes alone. I think there is unmet need for a potentially second generation SARS-CoV-2 vaccine along the lines that we've discussed. Clearly, that's of interest to us. It's a phase three trial, an expensive trial. Exactly how expensive obviously does depend on the size and the design. Funding for that trial and having a partner together with the regulatory dialogue are intermixed. That is our goal, yes. Okay. Thank you. Yeah. As we think about the upcoming SLATE update in a couple of weeks, are patients in this study screened for HLA subtype, and what are the potential implications for efficacy of HLA subtype? Yeah. They are screened for HLA subtype. This is fundamentally different from, for example, sotorasib. I think it's sotorasib. I'll go with that. Obviously, sotorasib and adagrasib, the Mirati product, are small molecule drugs that covalently bind to the G12C mutant form of KRAS by forming a covalent bond with a cysteine residue. This is sort of fairly well understood, you know, medicinal chemistry. Therefore, those products work for, in principle, any G12C mutant irrespective of HLA background because they're just binding to the protein inside the cell. SLATE is different. SLATE tries to generate an immune response to the fragment of mutant KRAS that is processed and presented on the cell surface. We're obviously trying to drive T-cells that recognize that fragment. It's fundamentally different and does require an understanding of HLA restriction. Now, the bad news is you then have to screen for HLA, which means this is not something you will simply give to everybody who has KRAS mutant disease. The good news is that we actually do have identified HLA alleles that present KRAS G12C, G12V, G12D, and actually Q61H. This one product can treat multiple mutant forms of KRAS. The population actually is quite substantial. We estimate that somewhere between 10%-15% of patients with colorectal cancer and non-small cell lung cancer adenocarcinoma will be candidates for this form of immunotherapy against KRAS mutations. Pancreatic cancer is a harder nut to crack, and we've not done a lot of work there recognizing its challenges. Actually, pretty much everybody with pancreatic cancer has a KRAS mutation, so that is quite a large population once we've optimized the product and potentially prepared to move into pancreatic. Obviously, the data you'll be seeing at ESMO will be focused, as I said, on non-small cell and colorectal cancer. Okay, great. Thanks. Yep. Thank you. Thanks, Corinne. Thank you. We take our next question from Umer Raffat with Evercore. Your line is open. Hi, guys. Thanks for taking my question. I'm quite surprised and pleasantly surprised to look at the data. My question is, have you attempted to characterize the structure of these antibodies? I'm trying to understand if there's like an Fc tail that helps it go on for this long. And also, have you characterized the subset of the antibodies elicited by Moderna and Pfizer, which do go out for six months? And if there's any commonalities in what the structure of the antibodies, I'm very curious about that. Secondly, I think everybody attempted to make comparisons of the NAb titer post-boost, the data you put out in January. Yours was like eight-10 times increase. Some of the mRNA datasets were perhaps higher. To what extent was that re-exposure boost differences driven simply by B cell memory response to taking the same thing for a third time versus taking a slightly different thing on during the third shot? Then finally, if this regimen were to be truly competitive, I gotta believe you need a BA.5 specific, and it could perhaps be an annual shot. I'm curious, as you think about progression forward, are you taking a wild type vaccine forward, or do you think you actually do need a BA.4, BA.5, which is kind of the feedback FDA seems to be sharing with the vaccine manufacturers right now. Thank you very much. Thanks, Umer. Great to have you join us. Karin, I'll ask you to answer questions one and two, but I'll take on question three, first of all. In terms of BA.4, BA.5, as I said, I think the immunity you generate with Omicron and its siblings such as BA.4, BA.5, appears to be quite narrow. I think that's why there's a little bit of anxiety that with a fall campaign, we're boosting backwards as it were. You know, we're boosting the variant that was around before with low expectations, perhaps, that it's gonna be really helpful against whatever comes next. 'Cause of course, we don't know what's gonna come next. If we assume that it will be in some ways immunologically distant from BA.4, BA.5, the worry has to be that the immunity we're all gonna get generated with another booster is not gonna be that helpful. For that reason, of course, one can think about blended products, which indeed is what the first generation folks are doing. If you think about blending, as I said, Beta looks pretty interesting as a partner for the blend because of the apparent breadth of immunity that it generates. Of course, it also wasn't a variant that was particularly common globally, and so there may be some relative global naïveté towards the Beta variant. It was common in South Africa and a few other territories, but not global. I think there's some flexibility to think about what to put into the product going forward. I agree with you. It's not gonna be ancestral spike for sure. I think a blended approach is entirely credible, and you might pick something like Beta for the reasons I've articulated. Okay, let's turn back to your questions one and two, which are both good questions. Karin, over to you. Yeah. Currently for our vaccine, we are currently looking at the nature of the B cell response. We are not comparing it to Moderna and BioNTech. We don't have the serum samples there, but we are analyzing our samples accordingly. We still believe what I said earlier, that the durability of the antigen exposure, the immune system exposure to the antigen drives these durable B cell responses, and we are analyzing the nature thereof as we speak. Thank you, guys. Thank you. Did I cut your question any, anymore? Yeah. Oh, no, I was just gonna say congrats, Celia. Thank you, Umer. Thanks, Umer. Indeed, congrats to Celia, who's heading off to get married tomorrow. Have more cookies for her afterwards. Yeah. Right, right on. Okay. Thank you. This concludes question and answer session. I would like to turn the conference back to you, Andrew Allen, for any closing remarks. Well, thank you very much, everybody. Thanks for joining us today. I hope you found this call interesting and informative. As you've heard, we are very excited about the progress that we've been making. We're a company that builds step by step. We're trying to innovate here, both in terms of the design of our vaccines and the immunogen within them, and we're using a novel technology. We're building this fortress brick by brick, and we bring to you today, I think another step forward in this progress. We look forward to updating you further as our programs continue to advance, and in particular with some data at ESMO and then at IDWeek in October. Lots to look forward to in the next couple of months. With that, we'll close the call. Thank you. The conference is now concluded. Thank you for attending to this call. You may now disconnect.