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spk13: Greetings, and welcome to the CureVac fourth quarter and full year 2023 financial results and business update conference call. At this time, all participants are on a listen-only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. Please note this conference is being recorded. I will now turn the conference over to your host, Tara Fahey, where you may begin.
spk07: Thank you. Good morning, good afternoon, and welcome to our conference call. My name is Sarah Farkey, and I'm the Vice President of Corporate Communications and Investor Relations at CureVac. Please let me introduce today's speakers. On the call with me from CureVac are Alexander Sender, Chief Executive Officer of CureVac, Miriam Mandela, our Chief Development Officer, and Pierre Quimula, Chief Financial Officer of CureVac. Our Head of Intellectual Property, Marcus Dalton, will be present for the Q&A session. Please note that this call is being webcast live and will be archived on the events and presentation section under investor relations on our website. Before we begin, a few forward-looking statements. The discussions and responses to your questions on this call reflect management's view as of today, Wednesday, April 24th, 2024. We will be making statements and providing responses to your questions that state our intentions, beliefs, expectations, or predictions of the future. These constitute forward-looking statements for the purpose of the safe harbor provisions. These statements involve risks and uncertainties that could cause actual results to differ materially from those projected. CureVectors claims any intention or obligation to revise any forward-looking statements. For more information, please refer to our filings with the U.S. Securities and Exchange Commission. I will now turn the call over to Alexander.
spk04: Thank you, Sarah. Ladies and gentlemen, good morning, good afternoon to everyone on the webcast. After recently celebrating my first year as CEO of CureVac, I'm thrilled to be speaking to you today as a leader of a company that is dramatically transforming itself. As societies are moving beyond the COVID-19 pandemic, we are embracing a new normal where agility and innovation are more vital than ever. At CureVac, this means we are taking decisive steps in 2020 form to trim unnecessary residual pandemic infrastructure and have started redesign initiatives to increase efficiency, reduce operating costs, and extend our cash run way. These initiatives began in March this year with a voluntary lever program that aims to reduce 150 positions and is intended to align our workforce to our business scope and priorities. At the same time, based on the rapidly changing epidemiological environment following the end of the COVID-19 pandemic, together with our partner GSK, we have made the decision to wind down the pandemic preparedness agreement with the German government signed in April 2022. Based on our solid cash position of 402.5 million euros at the end of 2023, And despite a negative cash impact in 25 related to the wind down of the pandemic preparedness agreement, our efficiency initiatives are expected to result in a net extension of our cash runaway into the fourth quarter of 2025. While we continue to streamline the company and optimize costs, it is essential for us to preserve existing and create new value by maintaining a strong focus on advancing our research and development activities. Accordingly, we have made substantial progress in our clinical trials and are growing our pipeline of development programs in infectious disease and oncology. In infectious diseases, together with GSK, we have initiated a new Phase I-II study in avian flu, which is considered a potential future pandemic threat. It is the latest program progressing to clinical trials under a broad infectious disease collaboration with GSK. Our ongoing programs in seasonal flu and COVID-19 have provided promising phase two entering data confirming that our technology platform generates strong antibody titers at well-tolerated dose levels. In oncology, the dose escalation part A of our phase one study in patient with vasectomy has completed enrollment. Part A successfully progressed to a safety review confirming no dose-limiting toxicity and providing a recommended dose of 100 micrograms for the Part B of the study. This important growth driver, I'm particularly thrilled about our collaboration with Andy Anderson, one of the world's leading cancer centers with whom we are joining forces for the development of normal mRNA cancer vaccines. Further expanding such strategic collaborations will be a key focus for Taminda Ramanayake, a veteran in the biopharma industry who we are delighted to welcome as our new chief business officers as of June 1st this year. Also supporting our oncology strategy is the mRNA printer, CureVac's end-to-end solution for automated manufacturing of GMP-grade RNA vaccines and therapeutics. The printer achieved next important regulatory milestones by obtaining a framework license providing even greater freedom and flexibility to manufacture different mRNA cancer vaccine candidates. Taking a step back and looking at 2023 on slide five, I'm profoundly inspired by the progress that has been achieved by the entire CureVac team. Last year, we made critical advancements in our clinical trials, was notably the positive phase one data in COVID-19 and flu that allowed us to transition into the current phase two programs potentially differentiated vaccine candidates in collaboration with GSK. We started to phase one program in glioblastoma kicking off our strategy for the development of next generation cancer vaccines based on our proprietary second generation mRNA backbone. Our successful capital raise in February 2023 was a word of confidence of investors providing us with the resources to advance multiple programs and research activities. And last but not least, we strengthen our intellectual property position by adding new IP rights to ongoing patent litigation with Pfizer BioNTech, demonstrating that we continue to be at the forefront of mRNA innovation. Building on our achievements in 2023, we are poised to continue in 2024 with a clear focus to make CureVac fit for the future. To this end, we have put strategic emphasis on an organizational redesign which I will describe in more detail on the next slide. In our clinical trial programs, we continue to move forward with GSK, following the promising Phase II interim data in COVID and flu this year, as well as the newly started Phase I-II study in avian flu. In oncology, following the clearance of the Phase I, Part A, glioblastoma safety data, we anticipate advancing to the dose confirmation Part B mid-2024. We expect to report a first data readout in the second half of 2024, most likely at scientific conferences such as ESMO or CITI. Our efforts to build up our manufacturing facility, GMP4, are progressing, and we expect certification of the facility in the second half of 2024, contingent on regulatory approvals. With these catalysts driving our efforts, we are confident in our ability to make meaningful strides in maturing the company and advancing our clinical trial programs in 2024. In slide six, let me provide you with a more detailed overview of our corporate streamline and redesign initiatives in 2024. As already mentioned, the redesign aims to significantly increase efficiencies and performance while maintaining a strong focus on innovation and R&D activities. This encompasses a range of targeted actions to trim unneeded pandemic area infrastructure, reduce operating costs, and become a leaner, more agile, and focused organization. The cornerstones of our efforts include our strategic reorganization, streamlining reporting lines, and digitizing the company. The focus is on an improved interface between our discovery, research, and clinical development areas by bringing them together under the leadership of Miriam as Chief Scientific Officer. A unified leadership will allow for an optimal alignment on strategic goals, improved prioritization, resource allocation, and seamless transition from innovation from discovery to the clinic. Furthermore, we will double down on our company-wide digital and data strategy to enhance the use of data and AI throughout the company and enable accelerated business processes and pipeline innovation. The areas where we are trimming pandemic structures, as mentioned earlier, the targeted resizing via a voluntary leaver program to reduce 150 positions is ongoing. The reduction of workforce will be accompanied by an overall stronger financial discipline. This includes a much leaner budget in 24 compared to 23, which is driven by lower operating costs and lower expenses of raw materials as our commitments for first-generation COVID vaccines are mostly closed. Also, our capex spend will be significantly lower with the completion of our GMT-4 manufacturing plant. While these actions have already been initiated, we will continue to look for more opportunities to improve efficiencies throughout 2024. Pierre will go into more details in the financial update later in this call, and we will continue to inform you on the progress of these initiatives throughout the year. In parallel with our organizational redesign, we have made significant progress in achieving our goals through strategic collaboration, such as the co-development and licensing agreement we recently entered with one of the world's most renowned cancer institutions, the University of Texas MD Anderson Cancer Center. The collaboration focuses on the joint development of differentiated off-the-shelf mRNA-based cancer vaccines in selected hematological and solid tumor indications with higher mathematical needs. It combines CureVac's unique end-to-end mRNA capabilities for cancer antigen discovery, mRNA design, and manufacturing with Andy Anderson's world-class expertise in cancer antigen discovery and validation, translational drug development, and clinical research. This collaboration is more than just a synergy of skills. the shared commitment of CureVac as the pioneer of mRNA, and Andy Anderson as one of the most trusted leaders in cancer care to go further and faster in making a profound impact on the lives of cancer patients. Accordingly, both sites will contribute to the identification of novel cancer antigens based on whole genome sequencing, RNA sequencing, and cutting-edge bioinformatics. Preclinical validation of the highest quality cancer antigens is expected to be followed by Phase 1-2 studies with potential lead candidates conducted by MD Anderson. We are convinced that this collaboration will be instrumental in boosting our oncology strategy. It will be an engine for the development of new cancer vaccines, helping us to deliver novel treatment options faster and more efficiently. In this context, it's with great pleasure that I introduce Taminda Ramanayake as our new Chief of Business Officer. Taminda will join our management team on June 1st at this pivotal moment in our corporate revolution. Taminda joins from Affinity Therapeutics. He brings 15 plus years of international experience in business development and corporate strategy. He has a strong track record of successful clinical collaborations, M&A, licensing, and strategic financing across multiple therapeutic areas. He has previously had positions at Sanofi, Biomerion Pharmaceuticals, and Amgen. His wealth of knowledge is complemented by a strong foundation in science with focus on immunology and oncology. This broad expertise uniquely positions Taminda to build upon our current achievements and drive CureVac's corporate strategy forward. With this, let me hand over the call to Miriam for an update on our clinical development programs.
spk08: Thank you, Alex. Moving on to slide nine, I would like to take a moment to outline our most recent development pipeline, which forms the core of our business strategy. Based on the versatility of our unique mRNA platform, we address indications in the three therapeutic areas of prophylactic vaccines, oncology, and molecular therapy. In this updated layout, you can see that across these areas, we have focused our program resources and have discontinued legacy programs that no longer align with our development goals and expectations for adding value. In our most advanced area, prophylactic vaccines, the phase two COVID-19 and seasonal flu programs are ongoing, being developed jointly with GSK. Both phase two studies are fully enrolled. and recent interim analysis data confirmed that our platform elicits strong antibody titers at well-tolerated dose levels. The newly initiated combined phase 1, 2 study in avian flu is being conducted in the U.S. and assesses a modified monovalent vaccine candidate and coding an influenza A H5 antigen in younger and older adults against the placebo control. We continue to translate the progress in our prophylactic vaccines area into oncology. Our phase one study in patients with resected glioblastoma is currently preparing to start part B after having successfully completed the dose escalation part A as previously mentioned. In the third therapeutic area, molecular therapy, we are developing optimized mRNA therapeutics together with several collaboration partners which are intended to enable the expression of therapeutic proteins to treat diseases in different areas with unmet medical needs. We remain committed to broadening and diversifying our pipeline, being guided by our mission to advance innovation and health solutions for people and patients. And now on slide 10, which offers more detail on our development programs in COVID-19 and seasonal flu. The phase two part of the combined phase one study for flu assesses a potentially differentiated multivalent candidate encoding antigens matched to all four WHO-recommended flu strains. The candidate was selected from the phase one part of the study, which tested a comprehensive series of multivalent modified seasonal flu candidates with up to eight constructs per candidate. The phase two part of the study is fully enrolled with 480 younger adults aged 18 to 64 and 480 older adults aged 65 to 80. Both age groups were tested against age-matched licensed comparator vaccines. The vaccine candidate showed an acceptable safety and tolerability profile, with the majority of solicited adverse events reported as either mild or moderate. For influenza A strains, geometric mean titers generated by the vaccine candidate numerically exceeded the geometric mean titers of the licensed comparator vaccine consistently across all tested dose levels and age groups. For influenza B strains, geometric mean titers were generally lower than those elicited by the licensed comparator vaccine. Based on the challenges in addressing B strains across vaccine technologies, This is in line with our expectations and the results from early studies of other mRNA-based flu development programs. Together with GSK, we plan to assess targeted optimizations to further improve immune responses against these strains in an additional Phase II study. We are confident that planned optimizations will improve performance against these historically challenging influenza strains. In the Phase II COVID-19 study, we assessed different booster vaccinations of two vaccine candidates. CVO601, a modified monovalent construct encoding the Omicron BA45 variant, and CVO701, a modified bivalent construct encoding the Omicron BA45 variant, as well as the original SARS-CoV-2 strain. The study is fully enrolled with 427 participants aged 18 or older. According to the applicable standard of care at the time, the study employed a licensed B-valent mRNA comparator vaccine. Interim data was reported in early 2024 and confirmed a favorable tolerability profile combined with competitive immune responses at low doses. All tested dose levels were well below those used in any of the mRNA-based COVID-19 vaccines licensed in the US and EU. As can be seen in the left of the two graphs, both vaccine candidates showed a lower or similar proportion of participants reporting solicited adverse events compared to those who received the comparator vaccine. As illustrated in the right graph, CVO601, shown in orange, was tested at a medium dose level and elicited neutralizing antibody titers against the Omicron BA45 variant on day 29, which numerically exceeded the titers generated by the comparator vaccine by a factor of 1.4. For the low, medium, and high dose levels tested for B-valent CV0701, neutralizing antibody titers were 0.7, 1, and 1.3 times the titers of the comparator vaccine. The study is currently ongoing with an additional expansion cohort. Taken together, the promising interim data strongly underscore the strength of our proprietary technology platform. With this, let me shift our focus back to our oncology area. On slide 11, let me briefly remind you of the strategy for our oncology area, which we consider a cornerstone of our future growth. We have made significant strides in advancing our cancer vaccine programs based on our two-point strategy, which encompasses both off-the-shelf and personalized cancer vaccines. Our off-the-shelf programs target the discovery of shared antigens with high prevalence in specific cancer types and the potential to enable more scalable and rapid cancer care. In this part, we have achieved key milestones over the past several months. We are delivering on our glioblastoma study by targeting known glioblastoma antigens to validate our second-generation backbone in the oncology setting. At the same time, in collaboration with MyNeo Therapeutics, we have identified novel shared antigens based on MyNeo's advanced AI-powered technology platform, which showed strong immunogenicity in undisclosed preclinical studies. The combination of antigens evolving from the MyNeo collaboration with antigens discovered with our proprietary platform enabled selection of the next clinical candidate in oncology, We plan to advance this candidate to the clinic in 2025. Our collaboration with MD Anderson will also be an engine for the future development of new cancer vaccine candidates, further strengthening our off-the-shelf clinical development program. In parallel, we are also aiming to push the boundaries of personalized cancer vaccines tailored to the unique genetic makeup of a patient's tumor. We have evolved our antigen discovery platform acquired with framed cancer therapeutics and specifically directed the technology towards the identification of novel classes of personalized cancer antigens. Fast and flexible access to cancer candidates based on novel personalized antigens will be critically enabled by the RNA printer, which was just granted a framework license in the ongoing regulatory review. As we continue to navigate the challenges and opportunities of the oncology landscape, our achievements in both off-the-shelf and first-life cancer vaccines position us strongly for future growth and success in this important area. Turning our attention now to the clinical front in oncology on slide 12, let me give you a little bit more detail on our phase 1 study in patients with surgically resected MGMT unmethylated glioblastoma. On the slide, you can see the setup of the open-label phase 1 study with a multi-epitope cancer vaccine candidate, CBGBM. CBGBM features a single, unmodified mRNA encoding eight epitopes derived from tumor-associated antigens with demonstrated immunogenicity in glioblastoma. The exact nature of the epitopes is not disclosed. The dose escalation part A has successfully completed recruitment with 16 patients, across four dose levels between 12 and 100 micrograms. A review of the safety data for these dose levels by the Data Safety Monitoring Board, or DSMB, confirmed no dose-limiting toxicities. Accordingly, the DSMB gave a recommendation for a preferred dose of 100 micrograms for the subsequent Part B of the study. Part B, expected to start mid-2024, will enroll up to 20 patients. We are looking forward to sharing first immunogenicity data from the study in the second half of 2024 at the scientific conference. To finalize the encouraging news flow in the context of our oncology strategy, the RNA printer, our highly automated solution for GMP-grade manufacturing of cancer vaccines, has achieved the next important regulatory milestone. You might remember that we reported the first manufacturing license for the printer to support our oncology strategy in the third quarter of 2023. In an ongoing regulatory review, this license was expanded by a so-called framework license, which allows the flexible manufacturing of different mRNA constructs based on the established processes on the printer. In 2024, our goal is to further expand this approach to also include the formulation module of the printer to complete the end-to-end capabilities of the system. With this, let me hand back to Alexander.
spk04: Thank you, Miriam. Before we move on to the financial part of this call, on slide 14, I would like to briefly provide an update on our patent litigation against Pfizer-BioNTech in Germany and the U.S. Starting with the recent development in the U.S., shown on the left-hand side of the slide, Please recall that a total of 10 patents are currently at issue in this geography. In November 2023, our partner Acuitas Therapeutics moved to intervene, sever, or stay our US litigation against Pfizer-BioNTech. The motion is based on a co-ownership and co-inventorship claim related to one patent family covering four patents out of the 10 litigated in the US. These four patents cover the specific design of COVID-19 vaccine, using a lipid nanoparticle, which was used in Cominati, but first introduced to the clinic by CureVac in 2018. Recently, a magistrate judge granted intervention and recommendation to stay litigation of all 10 patents before the district court until the CureVac claim is resolved. So far, no decision has been made, and we are currently preparing objections to this recommendation and anticipate a decision within the next two months. Germany, shown on the right-hand side of the slide, on December 19, 2023, the German Federal Court Patent Court granted in the first instance the 2022 request by BioNTech to nullify the German part of our technology patent on GC enrichment. Given the broad scope of our robust patent portfolio, this initial decision does not the strength of our value of our intellectual property position, as this is only the first instance decision and proceedings are continuing in Germany with the remaining IP rights. We are currently waiting to receive the written judgment of the December decision, which will enable us to file an appeal before the German Federal Court of Justice that will firmly establish the merits of our case. Patent litigation is part of the business landscape, especially in industries driven by high-stakes innovations such as ours, and routinely take years to play out. However, delays and setbacks will not deter us from having our intellectual property rights acknowledged and fairly compensated. With this, I would like to conclude the business update and hand over to Pierre for a review of the financial data.
spk03: Thank you, Alexander. Good morning and good afternoon to everyone on the call. Before we go into financial statement details, I would like to provide a little more context on our updated runway guidance and the main factors that are impacting our 2024 and 2025 projections. Alexander already mentioned the joint CURVAC GSK decision to wind down the 2022 pandemic preparedness agreement with the German government. Based on the 2024 obligation from this agreement, we expect the wind down to have a positive cash impact supporting a 2024 runway. This relates to significant savings on raw materials stockpiling and reduction in running costs for a GP4 manufacturing facility. On the other hand, in 2025, we will no longer receive the standby fee that the German government would have paid for maintaining a warm manufacturing base, resulting in a decreased 2025 revenue. We will offset this overall negative cash impact with two things. First, we have closed all remaining raw material commitments related to our first-generation COVID-19 vaccine. And second, our organizational redesign, including voluntary lever program, will enable reduced operating costs, allowing additional investments into selected development programs. Another reduction in cash out in 2024 compared to 2023 will be driven by lower operating expenses in various SG&A functions. With our GMP4 facility expected to be certified in the second half of this year, subject, of course, to regulatory approval, the CAPEX requirements in 2024 will also be significantly reduced compared to 2023. Taken together, it allows us to extend our cash runway from mid-2025 into the fourth quarter of 2025. We will continue to look for more opportunities to increase efficiency in 2024, and we'll keep you updated. Looking at our cash position on slide 16, as already mentioned, we closed 2023 with €402.5 million. Cash used in operations was mainly allocated to R&D activities, expenditures for our GMP4 production facility, and purchases of R&D materials. I will underline in this presentation the significant one-off effects that took place in 2022 as a consequence of closing our first-generation vaccine efforts in COVID-19. First, let us look at revenues. Revenues increased by 10.9 million euros to 22.6 million euros for the fourth quarter and decreased by 13.6 million euros to 53.8 million euros for the 12 months of 2023 compared to the same period in 2022. The decrease year on year was primarily driven by lower revenues from our two GSK collaboration agreements. Revenues from both collaborations decreased year on year and amounted to a total of 47.1 million euros in 2023 compared to 62.3 million euros in 2022. The decrease was driven by the agreement of both companies to focus on the larger indications. Revenues for the fourth quarter was higher compared to the prior year period, as a significant portion of the milestone related to the initiation of phase two for the seasonal flu clinical trial was recognized. Operating loss was 88 million euros for the fourth quarter of 2023, presenting a 33.5 million euro decrease compared to the same quarter of 2022. For 12 months of 2023, operating loss increased by 24.7 billion euros to 274.2 million euros compared to the same period in 2022. The operating result was affected by several key drivers. First, cost of sales decreased year on year, mainly as the impact of our first generation COVID-19 vaccine subsided. This resulted in lower write-off of raw materials in 2023, as well as lower impact on cost-related termination of CMO activities. Second, R&D expenses increased with higher investment in later stage infectious diseases and oncology development programs, as well as strengthening the workforce. In 2022, R&D expenses were positively impacted by a 38.5 million euro related to the reversal of an outstanding CRO provision as well as by one-off net gain for change in contract termination provision resulting primarily in GSK taking over from the company committed capacity at the CMO. Third, until in 2022, other income was positively impacted by a 32.5 million one-off for reimbursement of prepayments and production activities set up at the CMO. Financial results increased by 8.7 million euros to a profit of 1.5 million euros in the fourth quarter of 2023. and increased by 13.9 million euros to a profit of 14.2 million euros for the 12 months of 2023 compared to the same periods in 2022. They were mainly driven by interest income on cash investments. Retax losses were 86.5 million euros for the fourth quarter and 260 million euros for the full year of 2023. For this overview, I would like to hand back the call to Alexander for the summary of today's key messages. Thank you, Pierre.
spk04: So building on our achievements in 2023, we have kicked off 2024 by delivering progress across several key areas and positioned ourselves for continued success throughout the year. For most, we have launched a comprehensive organizational redesign initiative that trims residual pandemic-era infrastructure, streamlines our organization, and applies increased financial discipline. We expect these measures to significantly improve our operational efficiency and agility and contribute to a stronger financial performance in 2024. This expectation is affected in the extension of our cash one way for mid 2025 into the fourth quarter of 2025. In the clinic, our infectious disease vaccine development pipeline continues to make significant progress, marked by most recently by a start of a new study in avian flu together with GSK. This is complemented by key data milestones in the phase two studies for COVID-19 and seasonal flu, confirming the competitiveness of our proprietary mRNA technology platform. In oncology, cornerstone of our strategy, the establishment of our cancer vaccine collaboration with Andy Anderson and the advancement of our phase one study in patient weekly of both reinforce our commitment to staying at the forefront of oncology innovation. The pandemic dramatically illustrated the utility of mRNA technology, and we believe that mRNA's most significant promise is still lays ahead of us, and CUREC is resolute in its mission to bring that tremendous potential to life. And with this, I would like to conclude our presentation and would now open the webcast to your questions.
spk13: Thank you. At this time, we will be conducting 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 key. One moment, please, as we poll for questions. And our first question comes from the line of Evan Wang with Guggenheim. Please proceed with your question.
spk00: Great. Thanks, guys. Thanks for taking the questions. I have two. One related to the infectious disease platform. Just wondering if you could provide any timelines with respect to some of the next steps that we'll see for, you know, COVID, seasonal flu, and a potential combo. I guess with the, you know, flu, one question I did have was, you know, should we be thinking about a trivalent going forward? Or try the, you know, with the WHO antigen. And then with GBM, glad to see the progress in selection of the go-forward dose. Anything you can share with respect to part A on immunogenicity? Was that evaluated? And how does the response there compare to some of the responses we've seen from some competitors recently?
spk12: Thanks. Okay. Thank you very much.
spk04: Maybe I can start and then, you know, I will let Miriam to comment as well. Maybe first on the IID platform, you know, as we mentioned, we just started a new trial, Phase 1-2 trial on avian flu, so that's an additional program as part of the GSK collaboration that is moving forward and I think might address an important future need. And then for COVID and flu, as we mentioned during the call, both Phase 2 studies are still ongoing. For flu, we are about to start the additional study to improve B strain response. And for COVID, the additional part of the phase two study to optimize for different presentations after, of the vaccines. And once we have all these data together from the relevant study, we will complete our discussions with the regulatory authorities for the setup of the pivotal phase three studies. And, you know, together with GSK, we are working on what is the most value driving strategy for both our collaborations. and that reflect the current needs for both indications. Your question to GBM and whether data is already available. Maybe I'll let Miriam comment on this.
spk08: Yeah, and maybe before that, Evan had another question on flu and whether we go with the trivalent vaccine. And yes, that's the WHO recommendation, and that would be the plan for phase three, that we would basically encode just for one B strain in the future. And we will always follow the WHO recommendation, but that's sort of the plan for phase three. And for GBM, you know, we are analyzing immunogenicity data, but haven't disclosed those. And as we said in the presentation, right, while we are analyzing and more data coming in, we plan to present those data at upcoming oncology conferences in the second half of 2024. So at the moment, our target is ESMO and potentially the CISI conference later this year in the U.S.
spk12: And thank you.
spk13: Our next question comes from the line of Roy Luchin with Citizens JMP. Please proceed with your question.
spk02: Hey, thanks for taking the question. I guess I'm not sure you can answer this one, but the seasonal flu phase three, do you think you might be in a position to start that trial as early as later this year or that most likely early next year? And then the frame, You probably can't say, or you would have said, was wondering when you might be in the clinic with the personalized approach and just what's gaining on that, getting that into the clinic at this point. Thanks.
spk04: Miriam, so question on timing of flu phase three and timing of personalized cancer vaccines to the clinic.
spk08: Yeah, so for flu phase three, right, we need to discuss with the health authorities. And our goal is, of course, to bring it to the clinic as soon as possible. But right now it's difficult and we are reluctant to commit to a basically start. So maybe, you know, once we have discussed with authorities and have a clear plan, we will for sure in alignment with GSK give an update on this one. For PCV, we're working on it and communicated that earlier. This is complex, and right now, we are planning to go into the clinic 2026 plus.
spk02: Okay, great. And then maybe, sorry, just one more on the, I think this is what you said, but the H5N1 program, that's another target selection by GSK, so it reduces their available targets by one.
spk12: Thanks. That's correct. So we can. Okay. Thank you. Thank you.
spk13: Our next question comes from the line of Manny Beruar with Linger Link Partners. Please proceed with your question.
spk11: Yes. Thank you for taking this call, this question. I wanted to pivot over to a financial one. I'm looking at the guidance slide here, slide 15. which would helpfully break down the bridge out to late 25. Can you give us a little bit of granularity on the assumptions around the voluntary leaver program that are baked into that and some of the economics of where we might see some of that severance expense versus some objects coming off as hedge accounts trimmed, just how that will flow through the financial statements and what your operational assumptions are for degree and tempo of uptake?
spk03: My name is Pierre speaking. Thanks for your question. I'm not sure I answered the last part, but we basically have on the slide, you know, I think the key elements or the key driving elements, right, that have an impact on the runway. We haven't disclosed, for instance, the PPA, the revenues. It's a consortium approach with GSK and the government, so it's difficult to comment on that. What you understand from my call is we have a an extension because we don't have to expense raw materials so far this year but we have less revenues from the ppa so it's a net you know small net negative over over the period right and this will be counterbalanced by of course you know uh a more focused spend i guess on on r d and you know state settings that we have you know on the infrastructure but also you know i would say on the gna going forward importantly As I tried to underline as well, we had a lot of swings related to the end of the COVID-19 first gen, right? And so these are, I mean, mostly behind us now, right? So I think this will help us. And we talked about GMP4 where you'll see in, you know, our documents, which we all uploaded tonight, we have kind of finished investing into the building and the machines, right? So this will not reproduce going forward. So, you know, this is the color I can provide. And all these pluses and minuses, you know, and specifically with the effort that we've done, you know, in terms of those lighter budgets, a leader budget, more efficient that, you know, Alexander was talking about, we were able to extend the runway despite having a bit of headwind, you know, over the two years in PTA.
spk11: Okay. And pivoting over in a quick follow-up to strategic and sort of clinical development question, when you think about the, used for your technology in oncology, whether one wants to call it a personalized cancer vaccine, neoantigen therapy, whatever various competitors are calling their products now. How do you think about indication collection and to what extent is that informed by positioning indications and data from your competitors, Moderna, Biontech, et cetera?
spk12: Thanks for the question.
spk08: Sorry, Alex. If you're okay. Yeah, I can take it. I think it's a great question. And yes, we're doing all of that, right? Especially for oncology, where you could go into 50 plus tumors. And if you subdivide them into molecular subtypes, it's even more. We did a strategic evaluation over the last quarter of last year, really looking at all of the different possibilities where to go and then applying different criteria with different weighting on how to rank those and then came up with basically a list of priorities, considering commercial opportunity, considering competitive landscape, available data, and then end. And that basically was an underlying basis or became the underlying basis for our oncology strategy. So we are going strategically into specific indications where we see the scientific need or the scientific rationale, the medical need, the commercial opportunity, maybe also an edge versus the competitors, and that sort of like is driving how we decide into which indications we're going. Does that address your question?
spk11: Yeah, broadly. I guess a more sort of narrow question would be where should we be looking for data sets from you guys, perhaps Melanova, perhaps elsewhere, that we could look at to provide a little bit of comparison on efficacy versus your competitors so that your stock can start getting some value for it. You can sort of evaluate your opportunity to differentiate.
spk08: Yeah, as I said, right, we haven't published clinical data, right? And if that's your question, so that's why right now those data are not available. from basically from our cancer vaccine in the clinic. Maybe I misunderstand your question, but.
spk11: Yeah, I'm thinking about what the timing, how we should think about the timing when we could see a data set that we could sort of, an indication where we can sort of compare it with an existing competitor.
spk08: That's a difficult to answer question because our current trial is ongoing in glioblastoma. And to my knowledge, there is no other mRNA vaccine ongoing in this space, right? So if you're specifically asking to compare our platform with other platforms. Our next phase one trial is in planning, right? So it will take some time until data will become available where you could probably compare across indications. But the one thing we all have to be cautious when we're comparing across trials, right? Because we're doing that ourselves as well. when we were looking at the other data. But we realized how difficult it is to compare data in one tumor indication based on different vaccine platforms, based on different assays, patient selection criteria, and so on. While we all want to have and do those comparisons, we also have to be cautious that cross-trial comparisons, cross-platform comparisons, will have their limitations. So while I understand the need, you would like to do that, there's also, I want to say, a limited value. So I think, you know, when we publish the GBM data, we have to take them as they are. Is this a validation of the platform? Will it show a great immunogenicity? And we can compare across other vaccine technologies. But, you know, those comparisons, again, have all their caveats and pitfalls.
spk04: Maybe just to add to that, I do believe here the Andy Anderson collaboration will be able to help us a lot. Because at the end, to have a differentiated product, it's all about having the right antigens, good backbone, good delivery, good translational capabilities. And I think this collaboration that we announced a few weeks back with Andy Anderson will really help us there and create an engine for us to produce hopefully differentiated products that make a difference for patients. So I think this is something that is going to increase our capabilities a lot. Now, it will still take some time, as Miriam alluded, until we see it at the clinic, but at least we have a great engine with this collaboration that should help us a lot to be faster and be more efficient as well and bring differentiated products to the market.
spk13: Thank you. Our next question comes from the line of Umer Rafat with Evercore ISI. Please proceed with your question.
spk10: Hi, guys. Thanks for taking my question. I have three here, if I may. First, I know you talked about your wind down of the pandemic agreement with the German government. How does that change your anticipated timelines to market with your COVID vaccine? I would have thought Germany would have allowed you a more rapid path to market. Secondly, for your largest and most advanced trial of everything you're running, which is the COVID vaccine, I noticed the slides keep mentioning 601 and 701 formulations, but not the 801, which is a monovalent strain that you do have also as part of this trial. Could you give us more color on the anticipated timeline to read off of that and the specific strain that the 801 covers? And then finally, on acute as related delay on your litigation, Wasn't Acuitas only hoping to be a co-owner on your formulation patents, meaning your CG and your polyA patents would have been unaffected anyways? And I'm just trying to think about why all those patents were also looped up as part of the broader state order. Thank you very much.
spk04: Thanks a lot, Umar. So three questions, one on the PTA and timelines, COVID vaccine strain, and then, Marcus, I will let you comment on Acuitas and the recent updates here. So Yuma on the PPA, PPA should not impact the timelines at all because following the pandemic emergency procedures that were replaced to accelerate some of the approvals, they are largely gone. So there's no impact at all related to PPA or discontinued PPA in terms of timelines in Germany. Miriam, do you want to comment on Yuma's questions on strains?
spk08: Yes, so 06-01 is a monovalent strain for the BA45 variant and the 07-01 is the b-valent and 08-01 was the wild-type SARS-CoV-1 strain. So that's why, you know, I'm not sure I answered your question, that's why basically there wouldn't be additional data coming. Maybe I misunderstood the question, but Our focus is definitely on the updated strain, and our focus is, again, continuing to develop a monovalent strain or a monovalent vaccine that is matching the most recent COVID or corona strain.
spk10: I guess maybe to clarify, shouldn't the 801 or the 901 have been the XBB1.5 instead of BA.4.5 at this point of development?
spk08: No, at the time when we started this phase one and phase two program, XBV1.5 was just basically on the rise. And yes, right, if we were to, when we are planning for the next clinical trial, whether it's the phase three or something different, Then we would, of course, encode for whatever is the next strain, now XBB15, but it could be, you know, until then, until we start the phase III, the strain could have changed. So we will always encode again in the next wave the most recent and updated strain that was recommended by the WHO or the VRBPAC. But again, at the time we designed this study, right, the current strains and circulating strains, was the BA.4.5 variant. Okay.
spk12: Okay, Marcus, do you want to comment on that on the Acutis?
spk01: Yeah, sure. So, your question was right that Acutis only asked for the severing of the four formulation patterns. The court didn't want to, so let me also be clear, there is no decision yet to sever or stay. There is a decision that acutus can intervene into the case, but the severer stays are recommendations by the magistrate judge that have to be endorsed by the trial judge. And that will take some time. We have grounds to object, which have to be in, and then there'll be a response from the other side. and so it isn't the trial is still ongoing and the um and the work for the trial is ongoing at the moment um so you're right um actually a tutor didn't ask for this nobody asked for the stay of the whole proceedings um a decision of the magistrate judge to recommend that to the trial judge um and as alexander said in his presentation we expect that to be resolved in the next two months or so. In the interim, all the work is carrying on.
spk12: Thank you very much.
spk13: Thank you. Our next question comes from the line of Ellie Merle with UBS. Please proceed with your question.
spk05: Hi, this is Sarah for Allie. Thanks so much for taking our questions. I have two. First on COVID flu, how are you and GSA thinking about prioritizing the combo vaccine versus individual vaccines? And then are you still planning to initiate clinical development in the second half? And how should we be thinking about sort of economics here? And then on your oncology program, for the data second half, what are you looking for? in particular to serve kind of as proof of concept for your platform in oncology.
spk04: Okay, so two questions. One on COVID and how we think about combo, I guess, and the second one in terms of on-call and what we are looking for in terms of the data. Maybe I can start with the first one, and then, Miriam, you can comment on the on-call one. Right. So, you know, we do not support it, even though the pandemic has ended, obviously, but it would like to most likely stay with us and will require seasonal booster vaccinations, especially for the patients at risk. And, you know, due to the continued need for these vaccines, we do believe that the COVID market is still expected to be a multi-billion dollar market. However, There's definitely added convenience and potential for better immunization, and it's clear for us, and I guess for GSK as well, that there is real value for the combination vaccine that will be attractive in population requiring both vaccines. And MNRA technology obviously is perfect to address opportunities to its potency and flexibility. And GSK has repeatedly made the comment that combo vaccine and flu, are a focus for them and with expectation of 3 billion plus peak sales, you know, for these vaccines. So, overall, we believe flu definitely still has a lot of potential, but the combination is definitely something that we're looking at very closely. And once we have the individual pieces from the two phase two data, I think we will be able to provide more guidance and detail with this moving forward. The second question in oncology, I guess, it was what kind of proof of concept data we would look for in GBM.
spk08: Yeah, thank you. And thanks, Sarah, for the question. So in the part A of the GBM trial, because it's a phase one dose escalation trial, primary endpoints, of course, are, first of all, to look at safety and tolerability. And then we do have secondary endpoints and exploratory endpoints regarding immunogenicity. And in that part A, We are looking at basically T-cell activation by ELISPOT, ex vivo as well as after in vitro stimulation. In the part B, we do a more expanded immunogenicity testing program where we, of course, continue to look at ELISPOT, but also do more quantitative T-cell measurements and more in-depth analysis of T-cell repertoire in those patients. And so that's what you can expect. And we have defined our internal sort of like hurdles we'd like to take, but I hope you can understand that at the moment. I don't feel comfortable to share those. But clearly, we want to be ambitious in what we would like to see to declare that the especially immunogenicity data from that trial confirm basically that the platform works in oncology. But we have defined it, if that's your question.
spk05: Okay, great. Thanks, guys.
spk13: Thank you. Our next question comes from the line of Chiara Montironi with Van Lanshaw Kempen. Please proceed with your question.
spk09: Hello. Thank you very much for taking my question. I'm Chiara Montironi on behalf of Suzanne Van Voorhouten. So I have to say my phone is connected, so I really hope I didn't miss what I'm about to ask. So I wanted to ask you if you could elaborate a bit more on the recently announced MD Anderson collaboration. So I was wondering, how do you go about choosing programs and indication? Are you going to use the same strategy that Miriam just discussed five minutes ago?
spk08: Yeah, so maybe I can take this one. Or Alex, did you want to start?
spk04: Go ahead, I can add.
spk08: Okay, super. So with MD Anderson, of course, we discussed the selection of indications and followed the same approach where MD Anderson had their priorities, we had our priorities, and then we thought of like, look, what is in the, where is it overlapping? And so we have agreed already on the indications that we will focus on our collaboration. And I don't recall what our second part of the question.
spk12: Oh, that was it.
spk08: Okay. Thank you.
spk12: Thank you.
spk13: Thank you. Our next question comes from Charlie Yang with Bank of America. Please proceed with your question.
spk14: Great. Thanks for taking the questions. I have a few, please. First one is, can you just talk about the regulatory pathway for glial blastoma trial? I guess, you know, my impression maybe perhaps was that, you know, this is going to be more of a proof of concept, but your focus will be on the other indications with the other kind of platforms. But, you know, if this is a pass for it, then what would that timeline kind of look like? And I guess my second question is just thinking about, you know, all the different kind of early stage programs that you have in the cancer vaccine and thinking the cash balance and the runway um how are you thinking about account prioritization you know you know among those programs as you know which one is kind of more important you know versus the others and why not just focus on one instead of kind of doing a few uh and lastly you know just you know with hiring of color new chief business officer uh what kind of kind of strategic deals that you're that the company is thinking of in coming, perhaps, months or quarters? And how should we think about, you know, from the therapeutic standpoint? Thank you.
spk12: Okay. Thank you, Charlie.
spk04: What was the regulatory part?
spk08: Yeah. Maybe I can take the first two, Alex, and then you can address the third one. So for GBM, as you rightly stated, right, for us, this is a proof of principle study. We already announced in earlier calls or disclosed in earlier calls that this is for us a trial where we are using basically our platform in oncology for the very first time. And our intention is to show it's safe and well tolerated and it's inducing an immune response against the encoded antigens. we didn't have and don't have plans to then to take this as a pox to proof of concept and then start a phase two or phase three program. If, and you never know, right? But if we would see, which is unexpected, you know, some strong, compelling efficacy signal, which would take time in the GBM trial, because we're here treating patients that have undergone surgery, so they don't have remaining tumors. And hence, assessing efficacy will always be based on an endpoint-driven parameter, such as disease-free survival or progression-free survival. But in case, with longer follow-up, we would see something compelling, then we will revisit that decision. Right now, we are not considering to take this all the way through clinical development and into phase three. But again, just want to use the GBM data as a proof of principle the platform works in oncology. Then regarding the prioritization of the different oncology programs and the sort of like cash runway we're having, it's of course something that will happen once we have the data. Right now, you know, we have the GBM program. We are preparing for another phase one program with a clinical candidate. And the collaboration with MD Anderson is just starting, right? And we need to see if we can find shared antigens that will enable us to nominate a candidate. And then again, based on what I described before, different parameters, we will see what we can take to the clinics and otherwise prioritize based on the scientific evidence and the signals we're seeing in terms of what we'll take it to the clinic.
spk04: Thank you, Miriam. And I think the last question was regarding with the incoming of the new CBO Taminda and strategic direction for business development or additional partnerships. I think there are a few focus areas for us, one being oncology. For sure, even though we have announced the collaboration with MD Anderson, this will not preclude us from additional partnerships for these assets if they make it through phase two. So oncology is definitely a big focus for us in looking for additional partnerships. We also still have opportunities on the infectious disease side for programs that are not partnered with GSK. And beyond this, in molecular therapies, we have a few programs ongoing that we haven't fully disclosed, but that could be interested for partnering in selective indications. So it's definitely something that we're looking at very broadly, and we are engaged. And with Amina coming on board, we can engage even further on this.
spk12: Thank you. Thank you.
spk13: Thank you. And we have reached the end of the question and answer session. I'll now turn the call back over to Sarah Fahy for closing remarks.
spk07: Thank you. With this, we would like to conclude this conference call. Thank you very much for your participation. Stay safe and please don't hesitate to contact us should you have any further questions. Thank you and goodbye.
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