CureVac N.V. Price & Performance (CVAC)

My name is Sarah Faki 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 Zehner, Chief Executive Officer of CureVac Miriam Mendele, our Chief Scientific Officer and our Chief Financial Officer, Axel Marcomas. Please note that this call is being webcast live and will be archived on the Events and Presentations section on the Investor Relations on our website. Before we begin, a few forward looking statements. The discussion and responses to your questions on this call reflect management's view as of [indiscernible] Thursday, 04/10/2025. 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. CureVac disclaims 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. Thank you, Sarah. Ladies and gentlemen, good morning, good afternoon to everybody on the web webcast.

The fourth quarter of twenty twenty four completed a transformational year for CureVac, which was marked by significant strategic shifts and positive financial milestones positioning the company for future growth in oncology and infectious diseases. In July 2024, we took decisive action streamline and right size the company, laying a solid foundation for future success in 2025 and beyond. We have now refocused the company on what we do best, technology innovation and R and D, and have made substantial progress in expanding and advancing our pipeline of early proprietary clinical development programs. These programs have the potential to address critical unmet medical needs and capitalize on compelling market opportunities. In oncology, we continue to make progress with our lead program in patients with resected glioblastoma. The phase one study successfully completed enrollment of Part B. The speed of the enrollment underscored the urgent need for new treatment options, this aggressive form of brain cancer, and we are encouraged the rapid progress we are making. Our off the shelf precision immunotherapy program in patients with squamous non small cell lung cancer achieved a significant regulatory amount milestone, with the IND clearance from the US Food and Drug Administration to proceed with phase one.

We anticipate treating the first patient in the second half twenty twenty five. Transitioning to infectious diseases are new licensing agreement with GSK prophylactic vaccines continues to progress. In November, GSK initiated a combined phase one onetwo study for seasonal influenza COVID combination vaccine based on our proprietary second generation mRNA backbone, which triggered a €10,000,000 milestone. The milestone payment was invoiced in the fourth quarter of twenty twenty four received in the first quarter of twenty twenty five. Additionally, in its full year and fourth quarter earnings report, GSK confirmed its clinical program for standalone seasonal influenza is being prepared for phase three. Transition to phase three would trigger another significant milestone payment by further validating our technology. On the IP front, as you may have seen recently, the European Patent Office or EPO upheld the validity of our split folate tail six sixty eight patent in amended form. This outcome is particularly important as it validates our pioneering role in developing foundational mRNA vaccine technology. And finally, thanks to this steady progress across our portfolio at successful execution of our restructuring plan, we closed 2024 with a strong cash position of €482,000,000 reaffirming our expected financial runway into 2028.

On slide five, I would like to highlight the key accomplishments in 2024 which has set CureVac on a trajectory for increased performance and innovation. Our previously mentioned licensing agreement with GSK signed in July 2024 and valued to €1,450,000,000 plus royalties marked a pivotal moment for This agreement provides us with significant capital and leverages GSK's expertise in infectious diseases for successful development and commercialization. Importantly, then embarked on a strategic corporate restructuring to streamline the company including a headcount reduction of approximately 30%, which was completed in 2024. The restructuring has positioned us to achieve higher efficiency and agility in executing our pipeline priorities, allowing us to focus on developing potentially transformational mRNA therapeutics in oncology and infectious diseases. Our oncology pipeline of phase one glioblastoma study demonstrated promising dose escalation data last year confirming acceptable tolerability and antigen specific T cell responses in the majority of valuable patients. We also added a new program for squamous non small cell lung cancer to our pipeline, featuring a multiepitope immunotherapy with novel antigens derived from our collaboration with MyNeo. In prophylactic vaccines, we initiated a program against uropathogenic E. Coli bacteria, or UPAC, urinary tract infections. Is one of the most common bacterial infections with high unmet medical need supported by promising preclinical data.

In the GSK license programs in infectious diseases, positive phase two headline data for season in implants that was reported in September 2024. Confirming strong antibody titers against both influenza A strains and the notoriously challenging influenza B strains. And as I mentioned, starting the phase three trial would trigger another significant milestone payment from GSK. On the management side, welcome two new members to our leadership team, Tominda Rabanayake as Chief Business Officer and Axel Malcomas, as Chief Financial Officer. Both are seasoned industry experts, and bring significant expertise and experience to CureVac. Building on our momentum in oncology, infectious diseases, and senior leadership, we further anticipate key catalysts in twenty two thousand one hundred five, that will further expand our pipeline and reinforce our R and D priorities. Beginning with oncology, we expect to share data from the fully recruited phase one Part B glioblastoma study in the second half of twenty twenty five. And pending results we will take a decision to advance to Phase two, which is expected in the second half of twenty twenty five. Following the IND clearance in The US, the first patient in a program for squamous non small cell lung cancer is scheduled to be treated in the second half of this year.

The clinical development of our new prophylactic vaccine program for UPEG is underway, and we expect to file an an IND submission in the second half of this year for a Phase I study to commence in the first half of twenty twenty six. Also in the infectious disease area, we expect GSK to advance programs with current candidates based on licensed CureVac technology. And lastly, in 2025, we will continue to defend our broad innovative IP portfolio and and this further key decisions throughout the year in Europe and The US. Together, these upcoming milestones position CureVac for another year of great momentum, and with a sharpened focus and innovative pipeline, we've probably remained a leader of innovation within the RNA ecosystem. In March 2025, the decision of the European Patent Office, or EPO, to uphold the validity of our split poly tail six six eight patent in amended form represents an important step in our ongoing litigation with Pfizer BioNTech. This decision supports our pioneering role at significant contributions to mRNA vaccine technology, particularly in the space of COVID 19 Vaccines. You Should Recall That In Europe, each IP right is handled as a separate case, for which validity, infringement, and potential damages will be decided separately.

Damages will be assessed only when validity and infringement both have been established. On slide six, you can see a schematic of this bifurcated process. On the left side, infringement proceedings are displayed. For an IP dispute, infringement is decided by the regional court to [indiscernible] well as potential damages related to all six IP rights at issue. On the right side, validity proceedings are displayed, validity for IP rights is served by different authorities, depending on the nature of the IP rights. Validity of the split poly ATL patterns is heard by the EPO. Following the EPO's positive decision on our first split polyA six sixty eight pap last month, adhering to rule on infringement is scheduled for 07/01/2025. And should validity of the second split for the ATL patent also be confirmed by the EPO in a hearing which is scheduled for May 13 to fifteen twenty twenty five would also be included in the joint infringement hearing. So we remain confident of our position in the upcoming infringement case, and believe that the validated patent is infringed in its amended form. As the earliest pioneer in mRNA technology, we are determined to have our contributions recognized and compensated.

And with this, let me now hand over to Miriam for a review of our pipeline development activities.

Thank you, Alexander.

Moving on to Slide seven, I would like to provide an overview of our development pipeline, which prioritizes high value programs where our mRNA technology can make a substantial difference in addressing diseases with significant unmet medical need.

As Alexander already mentioned, our oncology pipeline is led by our Phase I glioblastoma study with CV GBM, an off the shelf precision immunotherapy encoding eight secondtors from four known tumor associated antigens demonstrated relevance in this indication. The promising initial data we presented from the completed dose escalation part a of the study at a scientific conference in September and November demonstrated successful induction of cancer antigen specific T cell responses in seventy seven percent of thirteen evaluable patients.

Eighty four percent of these immune responses that generated in Novo meaning T cell responses are successfully infused in patients with no preexisting T cell activity against encoded antigens prior to treatment with cVGVM. At the recommended one hundred microgram dose for the expansion part of the study, majority of responses were sustainable over a ninety nine day monitoring period. The treatment was generally well tolerated with no dose limiting toxicities reported. The dose expansion part b of the study is ongoing and has already completed enrollment of 20 additional patients who are treated at the selected dose of one hundred micrograms. First data from this part are anticipated to be available in the second half of this year. Our new off the shelf multi episode precision immunotherapy candidate for patients with squamous non small cell lung cancer encodes established antigens as well as novel antigens derived our collaboration with MyNeo Therapeutics. I will provide more detail on the study later in this presentation. Infectious diseases please recall that we are directing our proprietary research and development efforts towards new non respiratory indications. As mentioned, our programs targeting respiratory indications are fully licensed to GS In our proprietary non respiratory infectious disease portfolio, our program for a prophylactic vaccine against uropathogenic E. Coli by to prevent urinary tract infections is well on track.

The clinical candidate targets CIMH, a highly conserved protein, which facilitates adhesion of the bacteria to bladder tissue and biofilm formation, thus enabling invasion of the cells in the urinary tract.

The candidate mRNA design applies a unique technology resulting in an in vivo self assembly of a protein nano part with clustering of sigma h antigen on its surface. Which has shown superior immunogenicity in preclinical studies.

In the respiratory infectious disease area, licensed to GSK, programs for seasonal influenza, avian influenza, COVID nineteen are currently in phase two development. The newly initiated combined phase onetwo study for seasonal influenza COVID-nineteen combination vaccine is in Phase I development. All current candidates of the GSK trials are based CureVac's proprietary second generation mRNA backbone. We believe that there's great potential of our growing pipeline and look forward to reporting on its further development in the future. On slide eight, dive deeper into our oncology strategy.

Over the last decade, there has been significant progress in treating solid tumors with immunotherapies either alone or in combination with chemotherapy. Okay. However, achieving significantly better patient outcomes remains elusive due to genetic differences in tumors, ability to develop resistance, the complexity of the tumor microenvironment, and the weakening of the patient's immune system over the course of various therapies. In this complex landscape, we see tremendous opportunity for our mRNA therapeutics to revolutionize ize immunotherapy for large patient populations with more precision. We are confident that our mRNA therapeutics could be a game changer based on two factors. First, our unique mRNA technology, which uses our second generation mRNA backbone. This backbone is optimized for strong and broad immune responses, and most importantly, targets also cellular immune responses has been clinically validated in Phase I and II studies in both infectious diseases and oncology.

Second, our proprietary and highly differentiated whole genome based antigen discovery platform. This platform provides access to new classes of tumor antigens enhancing the precision and effectiveness of our therapies. In our upcoming clinical development, we plan to combine our precision immunotherapies with checkpoint inhibitors. Checkpoint inhibitors release the brakes on the immune system. Thereby boosting the ability of our mRNA therapeutics to trigger power and precisely targeted immune responses. Timing is critical in this approach. Intervening earlier when patients' immune systems are healthier tumor burden is lower, and resistance to therapy is less established, offers the best chance for improved and durable outcomes. Accordingly, we aim to apply mRNA therapeutics at early stages of cancer in the adjuvant or perioperative setting. We believe by intervening early, have the potential to increase the chances of improved outcomes of patients whose tumors are surgically resected when their immune system is still strong and tumors are easier to control. Let me show you on the next two slides how we intend to make a difference with our precision immunotherapy approach. Specifically, how we expect to deliver strong and precise immune responses in combination with a checkpoint inhibitor in our new program for squamous non small cell lung cancer.

Worldwide, there are more than two million patients diagnosed every year with lung cancer. In The United States only, there are approximately two hundred and twenty five thousand new cases of lung cancer each year, eighty seven percent of which are non small cell lung cancer or NSCLC according to the American Cancer Society. Squamous non small cell lung cancer represents approximately twenty percent to thirty percent of all NSCLC cases, making it one of the most prevalent cancers worldwide.

It's considered a more aggressive form of non small cell lung cancer, with five year survival rates of patients with advanced disease just around twenty percent. And even if diagnosed in earlier stages, and if treated with perioperative immunotherapy, about thirty percent to forty percent of patients relapse within two years. Squamous non small cell lung cancer thereby poses significant challenges in disease control and treatment, contributing to the high unmet medical need in this indication. Importantly, squamous non small cell lung cancer has shown a particularly high prevalence of shared tumor antigens among patients, providing a unique opportunity for developing targeted precision immunotherapies. We aim to leverage this opportunity with an mRNA precision immunotherapy to improve outcomes for a larger patient population. Our selected investigational physician immunotherapy candidate is built on our advanced second generation mRNA backbone. It features two different mRNA constructs, encoding eight tumor associated antigens with high prevalence across squamous non small cell lung cancer patients. Four of these antigens are known with established relevance in solid tumors, providing a strong foundation for efficacy. The remaining four antigens were discovered within our collaboration with MyNeo Therapeutics and are uniquely derived from MyNeo Therapeutics cutting edge AI powered technology platform.

All four of these novel antigens were discovered outside the exome, and have not been previously tested in cancer immunotherapy trials. Our patient population coverage calculation for our candidate predicts that approximately ninety five percent of patients will express and present epitopes from at least one of the encoded antigens. Approximately fifty percent of patients are predicted to express and present epitopes from at least four of the encoded antigens. For our phase one study, this high patient coverage means that we can proceed without the need for specific patient selection beyond this squamous non small cell lung cancer diagnosis.

The general setup of the phase one dose finding open label study is illustrated on slide 10.

In this study, we will assess the safety and tolerability of our candidate as first line maintenance treatment in combination with a checkpoint inhibitor pembrolizumab in patients with advanced squamous non small cell lung cancer. In the dose escalation part a, our candidate will be tested in doses ranging from one hundred to four hundred micrograms in combination with pembrolizumab maintenance therapy for up to twelve months or until disease progression or undue toxicity occur. In Part A, expect to include patients with metastatic stage four squamous non small cell lung cancer, who have received at least three cycles of febrolizumab either as monotherapy or in combination with chemotherapy.

Following Part a, an opt dose expansion, part b will be conducted. The primary endpoints of the phase one study include the incidence of dose emitting toxicities, and treatment related and treatment emergent adverse events, and secondary endpoints include overall response rate, progression free survival, duration of response, and disease control rate. A positive outcome from this study would enable us to evaluate this combination in earlier stages of the disease, with our goal to apply MR mRNA precision immunotherapy at early stages of cancer. Moving on to diseases on slide 11, let me provide you with a brief overview of the details of the respiratory disease program, was fully licensed to GSK under our new licensing agreement from July. The most advanced program for seasonal influenza read out positive Phase two headline data last year. As Alexander already mentioned, GSK confirmed earlier this year that the program is in preparation for a phase three study, which will be associated with a significant mice payment for CureVac. The program for a pre pandemic vaccine against avian influenza is currently in phase two of the combined phase onetwo study initiated in April. As previously mentioned, a new program for seasonal influenza COVID nineteen combination vaccine entered phase one in November.

And lastly, phase two of the standard alone stand alone COVID nineteen vaccine program was completed. Please note that disclosure of study timelines and availability of clinical data is at the discretion of GSK.

By having licensed these programs to GSK, leverage their expertise in vaccine development and commercialization to bring innovative vaccines based on our mRNA technology to market. The new licensing agreement strongly validates the potential of our proprietary mRNA platform while the financial and strategic benefits from the agreement support our continuous innovation and development efforts. To further enhance mRNA effectiveness in oncology and infectious diseases, we are advancing our proprietary mRNA delivery technologies with improved proprietary lipid nanoparticles, or in short, LNPs. As highlighted on Slide 12, specific requirements apply to develop efficacious precision immunotherapies in oncology and prophylactic vaccines in infectious diseases.

LNPs are critical in meeting these specific requirements, underscoring the potential for LNP systems that are tailored to the respective therapeutic area. Prophylactic vaccines for infectious diseases treat healthy individuals. Necessitating activation of the immune system with minimal reactogenicity and side effects. In contrast, cancer immunotherapies treat seriously ill patients requiring robust activation of cellular signaling pathways to induce strong systemic immune responses. And allow greater tolerance for reactogenicity. Prophileptic vaccines often target inductor of high antibody titers, and T cell responses only where relevant. For cancer immunotherapies, activation of tumor killing T cells is critical, even if this is associated with increased reactogenicity. Additionally, prophylactic vaccines need to be stable for longer periods at refrigerator or room temperature given their seasonal use. For precision cancer immunotherapy applications, maximized efficacy is key. With stability being a secondary goal.

In previously reported, a proprietary LNP system for infectious diseases featuring a pack free lipid composition that demonstrated strong humerus and cellular immune responses in preclinical models, and highly localized biodistribution in the immune compartment. Showing no or very low expression in distant organs such as the liver, spleen, and lung, avoiding potential side effects while maximizing immunogenicity. Focusing on the additional need for stability in prophylactic vaccines we have now advanced our infectious disease LNP system to achieve promising thermal stability as well. On Slide 13, you can see data from our ongoing stability study with the BFO infectious disease LNP system over a period of twelve months.

MRNA encoding a rabies antigen was formulated within the new LNP system and stored either as a freeze dried powder at room temperature of 25 degrees Celsius equivalent to 77 degrees Fahrenheit or under refrigeration at two to eight degrees Celsius which equates to 36 to 46 degrees Fahrenheit. The formulated mRNA was also stored as a frozen liquid at minus 80 degrees Celsius or minus one twelve degrees Fahrenheit as a control.

The data on the left show that with the new LNP system, mRNA integrity remains stable. With the mRNA being intact and securely formulated for at least twelve months under all three storage conditions. As shown in the middle, LNP size also remained stable over time and under different storage conditions. In vivo experiments in mice, confirmed that throughout the test period, the vaccines stored under the different conditions maintained their ability to induce strong neutralizing antibodies. These findings provide a competitive advantage in addressable patients.

As our vaccines can be utilized globally without the need for complex cold chain storage requirements. On Slide 14, let me now summarize our upcoming pipeline catalysts provides a strong development path through the end of twenty twenty six. On the oncology front, starting with our most advanced Phase I off the shelf program in glioblastoma, as already mentioned, Part B of the study is fully enrolled and first data is expected in the second half of twenty twenty five.

This data will provide the basis for potential potentially continuing to a Phase II study, which could start in the second half of twenty twenty Following FDA clearance of the IND submission, the Phase one study of our off the shelf program in squamous non small cell lung cancer is expected to start dosing patients in the second half of twenty twenty five. With our antigen discovery work continuing, we intend to disclose additional off the shelf programs and select new clinical candidates in different indications in 2026. Lastly, the first clinical phase one study with a personalized cancer vaccine candidate is a expected to start in the second half of twenty twenty six. Infectious diseases for our proprietary UPAT program we expect to file an IND application in the second half of twenty twenty five. And to start Phase I clinical development in the first half of twenty twenty six. Additional discovery work in other non diseases is ongoing, and we anticipate expanding our pipeline in this area with additional programs in 2025 from from which clinical candidates could be selected in the second half of twenty twenty six. For the respiratory programs licensed in GSK, as stated in GSK's fourth quarter and full year earnings report in February, the seasonal influenza program is in preparation to progress to Phase III.

Taken as a whole, this slide illustrates that we have before us a strong path of pipeline catalysts in both oncology and infectious diseases. With a substantial set of anticipated upcoming milestones, we are in a strong position to make lasting impact on the future of mRNA medicines. I would now like to conclude the portfolio update and hand over to Axel for a review of the financial data.

Thank you, Miriam. Looking at the significant progress we have made in streamlining our operations and focusing on strategic priorities on slide 15. I would like to provide context to key financial metrics in 2024 demonstrating our financial health and enabling us to reinvest in key areas of growth innovation.

Today, we report a strong cash position of €401,700,000 at the end of twenty twenty four, and reaffirm our expected cash runway into 2028. Our results are driven by the new licensing agreement with GSK which positively impacted our cash position as well as revenues. The €400,000,000 upfront from the agreement was received as a nonrefundable payment for granting licenses to GSK and the exclusive right to use CureVac intellectual property relating to applicable vaccine programs with no further R and D work obligation on our side. As such, it was fully recognized as revenue and 2024. Given that under the terms of the new license licensing agreement, obligations from prior collaborations relating to R and D services had expired remaining contract liabilities amounting to AT €400,000 were also recognized as revenue in 2024. Additionally, in 2024, a development milestone of €10,000,000 was reached under the new license agreement for the initiation of a Phase I for the combo vaccine, which was also fully recognized as revenue. Setting the course for increased future financial stability our strategic redesign is key to enhancing our operational efficiency to further reduce costs. The 30% workforce reduction was completed by end of twenty twenty four, with incurred costs 17% below the allocated budget.

From 2025 onwards, we anticipate a substantial decrease in operating expenses by over 30% including a notable €25,000,000 reduction in personnel costs. Our licensing agreement with GSK and renewed focus on innovation and r and r and d activities have also eliminated the need for commercial buildup, and large scale manufacturing activities. Streamlining of our in house manufacturing capacities provide a new manufacturing footprint, better suited to our needs. Was accompanied by an impairment of our large scale production facility. Lastly, we have successfully terminated all remaining raw material commitments and closed all contract manufacturing organization, or CMO, related arbitrations for our first generation COVID-nineteen vaccine. Ensuring no further related payments for CVN COV going forward. Taken together, in 2024 extraordinary payments related to CVN Cove, our strategic redesign, and ongoing patent litigation amount to a total of €137,000,000 Moving on to our condensed financial statement on slide 16. You can see that our cash position of €481,700,000.0 increased from €42,500,000.0 at the end of twenty twenty three based on the €400,000,000 upfront payment from GSK in August 2024. The increase is partially offset by our ongoing R and D activities as well as a total of €137,000,000 one off [indiscernible] related to our first generation COVID-nineteen vaccine, as already discussed.

Revenues decreased by €8,100,000 to €14,500,000 for the fourth quarter and strongly increased by €481,400,000 to €535,200,000 for the twelve months of 2024, compared to the same periods in 2023. As the year on year increase was primarily driven by the new licensing agreement with GSK, such increase must be considered to be a positive onetime event. Operating loss was €43,800,000 for the fourth quarter of twenty twenty four compared to an operating loss of €88,000,000 for the same quarter of twenty twenty three. For the full year 2024, operating profit was €177,700,000 compared to an operating loss of €274,200,000 for same period in 2023. The operating result was affected by several key drivers. First, cost of sales decreased year on year mainly due to the change in strategy associated with the new license agreement with GSK resulting in adapted R and D activities. The costs of CureVac's manufacturing organization are no longer supporting revenue generating activities, and are thus no longer classified as cost of sales. Additionally, higher material costs appeared in the prior year, which were driven by write offs, of raw materials originally purchased for the stockpiling of the terminated pandemic preparedness agreement. Second, R and D expenses increased due to the strategic change mentioned, classifying CureVac's manufacturing organization R and D rather than in cost of sales, with higher investments in oncology development programs, as well as increased expenses related to the litigation to enforce intellectual property rights and higher personnel expenses related to the redesign of the organization.

Third, general and administrative expenses expenses decreased compared to the prior period, mainly driven by lower personnel expenses. Lastly, other operating expenses increased year on year due to the impairment of one production line within our GMP-four production facility, which was initially planned and set up for commercial large scale production and canopy scaled down to provide products for clinical production, in alignment with Q of X. Refocus on R and D. Financial results increased by €3,700,000,000 to €5,200,000 in the fourth quarter of twenty twenty four. And decreased by €1,000,000,000 to €13,200,000 for the twelve months of 2024 compared to the same periods in 2023. The decrease was mainly driven by lower interest income on cash investments. For the fourth quarter, pretax loss was €38,600,000 For the full year, profit was a hundred and €90,900,000. This compares to pretax losses in the same periods of 2023. With this, I'd like to reinforce that key strategic decisions made to conserve resources throughout 2024 have had positive impact moving us into a position of strength, as we work toward key milestones and continue to reshape what's possible in medicine. I now hand hand the call back to Alexander for today's key messages.

Thank you, Axel, and thank you all for your attention. The fourth quarter of twenty twenty four closed out a year of remarkable change for CureVac. The potential of mRNA to transform medicines is enormous, and our agility as an organization and ability to pivot has enabled us to further build upon that potential and unlock new areas in which mRNA technology make a meaningful impact for patients. Financially, we closed the fourth quarter twenty twenty four with cash position of €482,000,000 providing us with a solid expected financial runway into 2028. This gives us the stability needed to continue to drive innovation. We are making great progress in oncology around are off the shelf and personalized precision immunotherapies, And with encouraging results for our lead candidate in glioblastoma, are eager to show continued progress with an anticipated Part B readout, as well as advancements of our off to shelf program in squamous non small cell lung cancers.

In infectious diseases, we are quickly moving forward with the Upec Vec vaccine in urinary tract infections, eager to make a new medical breakthrough in an indication where greater metamorphosis.

We continue in 2025 with our focus on high value mRNA opportunities, from a wealth finance position and supported by strong strategic partnerships and a broad IP portfolio. With that, I conclude our presentation and open the floor for your questions.

Thank you. If you would like to ask a question, please press 1 on your telephone keypad. A confirmation tone will indicate your line would like to remove your question from the queue. And for participant choosing speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment while we poll for questions. Our first question is from Alex Stranahan with Bank of America. Please proceed.

Hey, guys. Thanks for taking our question.

And congrats on the progress, to close twenty four. Two two questions from us. Maybe first, actually, both are on the squamous program. You know, the the use of the antigens outside of the exome is is pretty unique to this program.

What would you say that maybe the early signs you'd point folks to in the the first in human clinical readout is as evidence that including these antigens is maybe having a preferential effect on activity and is it safe to say that the first patient dose in the second half of this year would set you up to maybe a mid or second half 26 readout. From the phase one. Didn't didn't see this on your catalyst slide in your prepared remarks. Thank you.

Okay. Very interesting. So so I I didn't quite get the last part of the question, but I'll start with the first part. So in with our antigen discovery class, platform, especially for off the shelf antigens, we usually run them through an extensive set of validation assays. Where we basically look, whether the antigen is selected, especially the novel ones outside the exons, whether they are expressed on the tumor, whether they are not expressed on healthy tissues, whether human T cells or immune cells can recognize them, and whether basically they are presented via MHC complexes, and whether they basically lead to tumor cell killing. And we have a, you know, internally company defined algorithm with very clearly set criteria to when we say an antigen passes the selection criteria or not. And based on all of the preclinical experiments we have done, with these novel antigens, we remain optimistic that we would see, basically, strong immune responses to this quite novel and again also very foreign proteins in cancer patients. There is right now no clinical evidence right, because we said this is the first time we're ever testing for these novel antigens in cancer patients. But there was also preclinical evidence from other groups in cancer animal models showing that when you vaccinate animals, this was a colon cancer model.

When you vaccinate animals who have a colorectal cancer, with the vaccine against these novel antigens that you see cancer regression. So there's preclinical evidence from other set that supporting us. Our own. Again, experiments have suggested that these antigens are mutagenic. And that's why we are taking them into the clinic. Would you mind repeating the second part of the question? I'm sorry, I didn't quite understand it. Because you said something about the dosing of the first and what that means, or what indication that would give.

Yeah. No. Just more in terms of data readout time, obviously, pace of enrollment. It's probably the biggest swing factor here, but I just didn't see a a data catalyst on I think it was slide 14. Of your prepared We we want to be a bit cautious here. Right? Because, it's a first in human study. And and we have to do the dose escalation, of course, with a quite broad dose, dose limiting toxicity window. And and that's why we sort of, like, have our internal projections, but right now do not feel comfortable to share them because you never know. We wanna see, like you said, wanna see how recruitment goes in the first cohort and then maybe at the next update. We can give better projections when you will see the first data next year. But you can you know, you you probably can know that we will do everything to to speed up get recruitment, you know, on track or even faster, and then, of course, analyze the data as quickly as possible.

Got it. Thank you.

Our next question is from Manny Fulihar with Leerink. Please proceed.

Hey, guys. You have Ryan on for Mani. Thanks for taking our question. Just hoping you could provide a bit more detail on what you see as the regulatory path for the CVG VM asset? You know, have you had conversations with regulators at this point on steps to approval and what that would look like? And then, I guess, to pivot off of that, do you see the recent changes that the FDA influencing any prior conversations that you guys have had?

Thanks. Maybe I can start with the second one, and then Miriam, can comment on the regulatory path. On your question on whether we seen any impact yet, with the FDA, So far, not for our program. You know, we the IND cleared for us squamous program on time and with with any major surprises. So no negative impact on that so far, but, you know, we all understand it's quite a fluid fluid situation with everything that going on. But so far, at least in our own programs, we have not seen any negative impact Mary, if you wanna comment on GBM potential regulatory path, and how to move forward with the program.

Maybe one point to add. We also interacted with FDA on our UPC program, and it was the same. Right? We don't see any impact. We get responses quickly. Same quality, unbiased, absolutely no changes compared to the past. For CD GBM, right, as said, if the data from phase one and the extension cohort show meaningful clinical activity, then and and we would go for phase two. Of course, we would do as a next step, I'm discussing. Again, this is all just under discussion, a randomized phase two with an appropriate comparator arm and an appropriate endpoint And we haven't yet had any discussions with regulatory authorities, so far because we wanted to await more data from phase one knowing that this is a high risk population. And and and we sort of, like, wanted to have more confidence that we will you know, have point indications that we go forward.

Great. Thank you.

Our next question is from Roger Song with Jefferies. Please proceed.

Thanks for that day and then taking on question.

A couple of questions. Maybe the first one related to the GBM. Given the Part b data gonna be second half, and then you will have you will make go forward decision. So just curious to what is the criteria to make that decision. And then on the squamous non small cell lung cancer, this you know, the multi complex antigen selection is very interesting. Just curious, given you say ninety five percent of the patient, they have a one plus antigen, fifty percent have four plus. Just curious in your preclinical model, do you see the difference when you have the model only have one versus four plus you see the difference on the activity, antitumor activity. The last part of the question is the regarding your cash runway guidance. Into 2028. Just you know, can you give us some color around how much operation is included in this cash runway guidance given you have a couple ongoing pipeline and then you new new new pipeline upcoming, like the GBM squamous cell and then UTI. And then it it this attachment will include all the phase one, phase two. Implant. Thank you.

So Miriam, three questions. One on GBM. I guess, where the bar is or how we would assess you know, go, no go decisions, and the one on squamous on the number of antigens, we see differences, and then maybe one for axial on the cash runway.

Okay. Okay. I'll start with the GBM question. And so, yes, we we have set a basic a high threshold for for GBM. Basically would expect to see in our population a median over survival of fifteen months or longer to say give a go or also an overall response rate of about twenty percent. If we would see that in our population, that would give us confidence to say, look. This could look promising. And and and, potentially warrants an investment into a phase two. Regarding your your question on coverage, for this claimant program, which is I think it's a really interesting question. But I have to tell you that the animal models do not allow us to actually investigate how clinical efficacy in those animals would look like if they have a response to two antigens or four antigens. The animal models actually In our animal models, we can not vaccinate against the targets we use to vaccinate human beings. Right? Because we have to vaccinate for murine. Antigens, and that's why no animal model would give you the answer to this. And the question you asked is is this sort of, like, million dollar question. Right?

Do you do we need to have a broad immune response against multiple antigens to achieve maximum clinical efficacy? Or a deep and strong responses to few antigens that are the right ones enough to give you clinical efficacy. And based on the data from others, not our own, we have seen some promising data We are basically in, immune responses against on average four antigens, [indiscernible] In other trials, it suggested that two antigens are enough So we don't really know the answer, but we would say based on all of our knowledge that some kind of diversity in terms of immune response would be good. And so hopefully, again, we would see responses to two more or more of those antigens that would then translate into clinical efficacy. So I cannot really give you an answer to the question because that's a $1,000,000 question. That we have to address in our clinical trials in the future.

Yeah. In terms of the cash runway into 2028, so what I can tell you is is that we also wanna be a little bit cautious here, but what I can tell you is is that the current for the current core program, meaning, you know, our ID in for, you know, a clinical start in 2026 as well as our oncology programs, GBM and squamous non small cell lung cancer. As well as our personalized cancer vaccine, you know, the clinical phases are included. But always please remember that, you know, some of these clinical phases are also after the cash out. Yeah. So so everything, of course, is planned as the clinical pipeline, is developed and planned for. But, you know, not all phase one and phase twos are prior to, the the potential cash out. Got it. Answers your question?

No.

That answers. Thank you.

Our next question is from Ali Mural with UBS. Please proceed.

Hi. This is Jasmine on for Ali. Thanks so much for taking our question. Wanted to ask about your latest strategy on collaboration. So, you across oncology and the non respiratory disease programs, what's your latest thinking about where you would want to potentially partner versus keep developing yourself? Thanks.

That's a good I I think in general, what we tried to do this year is really focus CureVac and what we are really good at, which is mostly technology innovation, research, and I would say early development, Of course, we have a few collaborations already in place as the one with GSK. For the rest respiratory infectious disease program. We have a collaboration in place as well with MD Anderson Cancer Center, our next generation shared off the shelf cancer vaccines, I think in general, as Axel just outlined, I think we are in a position from a financial perspective, but also from a capability and manufacturing perspective to run the early clinical trials. Phase ones, and maybe depending on the indication also, two. But I think the goal, especially for the larger PAs, such as oncology, would be clearly to partner then the late stage development program. With somebody that has real muscle in the field that really has the means to develop it more broadly and then eventually also commercialize worldwide.

Great. Thank you.

Our next question is from Roy Buchanan with Citizens. Please proceed.

Hey. Thanks for taking the questions. I had a few on the European patent proceedings. I guess, you give a sense of the timelines for the infringement hearing and possibly the assuming that's positive, the damage proceedings for the, six six eight and seven five five that was just upheld as valid. And then does Pfizer BioNTech do they have a chance to appeal the validity decision for six six eight? And then can you give a little bit of more detail on that subject to amendments comment in the slide 14, I think or six. Sorry.

Thanks.

Sure. I mean, we highlight kind of the key overarching time lines on on slide six. Of the presentation. The kind of next milestones are is we have further European patent office hearing for a second, polyA patent, the seven seventy five patent, which takes place [indiscernible] And then, as it's a bifurcated process, should that validity be confirmed as well, it goes back to the infringement court, in this case, it's the infringement court in Dusseldorf, where the hearing is scheduled for July 1, and as I mentioned, it includes the 6s8 and if the validity is confirmed as well, the seven seventy five, Paulier patent.

Then yes, there is an opportunity for the opposing partner to appeal but if infringement is confirmed, then validity has been confirmed prior would nevertheless start at least the damages process. In Europe, which don't copy exactly this, but my understanding is can take up to a year. To be [indiscernible] In The US, of course, it's different. In The US, you have one legal case which will start in September 8 this year, and in US you have one process that covers validity, infringement, as well as damages at the same time.

Okay. Great. I have a question. Yeah. I'm just curious. This subject to amendments comment on the Yeah. So the amendment was mostly related to the length of the poly A tail, I. E, the number of adenine nucleotides that were that were included It's quite technical, but I think we don't believe that this amendment will weaken our infringement position. I think that's the key point.

Okay. Great. And then maybe just throwing one on the the Genmab collaboration that was terminated. Can you just give us the crux of why that was terminated and what stage it got to? Thanks.

Well, I think it the the question was with the Gemmap and Gemmap collaboration. I So I think it was dormant for quite some time. It didn't lead it didn't really lead to anything. So also in our interest to really focus on the most promising programs. I think we terminated the program in kind of mutual mutual agreement.

Okay. Thank you. Our next question is from Jonathan Miller with Evercore ISI. Please proceed.

Hi, guys. Thanks for taking the question, and and congrats on the recent progress Maybe I'll start with one on the non small cell program. Obviously, you, like others, are are trying to develop this primarily in early stage setting. But, of course, the phase one is in later stage patients' metastatic patients. So I just I'd love to get a sense for what you're hoping to see in that phase one data that would move you to early stage setting? Do you need to see, efficacy signs of early efficacy in metastatic setting beyond maybe immune engagement or T cell induction, for instance, do you need to see increases in ORR or increases in PFS? To drive you to the early stage setting, or or would safety and immune engagement be sufficient to make that decision?

And then and then secondly, maybe on on the IP case, but I'll I'll I'll let you answer cancer first, please.

Okay. No. It's a great question. So as we said, right, we do believe that the precision immunotherapies will work in earlier cancer settings. Because the immune system is functioning and you have, less tumor burden to control it. And so with that, basically, our criteria and and primary objectives for the the phase one trial in squamous non small cell lung cancer would be to see immune responses against the encoded antigen. So that would be sort of like a primary hurdle. If c see then, of course, clinical activity, that would be most encouraging. But we also, basically really want to test this treatment in earlier stages of cancer because we have seen with other programs of sort of like similar platform that in advanced metastatic stages of of cancer, these immunotherapies do not work that well. So immune response is our primary target to see. That we see strong immune responses against the encoded antigens. And that would be encouraging and all we want to see because we would then sort of like do an expansion cohort in earlier settings. And from there, then look for clinical activity signals in the earlier cancer settings that would then determine whether we go for phase two and beyond in that setting.

Does that answer your question? Because we Yeah.

Absolutely.

Absolutely. I guess, one more then on that. On the novel ex exome antigens, I'd be really curious to see more of that preclinical data, more of that antigen development data. Do you have plans in the near term to discuss that antigen selection process more to to get deeper into the contribution of those X exome novel antigens to immune engagement and and efficacy?

So we're discussing that we would like to discuss and disclose more. We have to see when is what possible. It's super exciting, and I know everybody's interested. Right? There are some, let's say, internal checks we have to take before we go public and share all the all the data around that.

Okay. Makes sense.

On the IP front, the poly a patent that was just held up in the EPO this is this the same set of IP that was struck down in The UK court last year? I believe it was, end of last year.

And so can you discuss maybe some of the differences between those two cases and and whether we should be reading through from some prior hours that they brought in.

To the potential for the patents in The US court? [indiscernible] this is quite a complex question, and maybe we can do a follow-up call of this. But, I mean, The UK situation is different. The assessment is different. I mean and just the fact that you know, the German validity court came to a different conclusion, I think, highlights some of these differently. But John, very happy to set up a follow on call with our IT team, you know, to go more into the details.

Alright. Fair enough. I look forward to that. Our next question is from Chiara Manatroni with Chem ten. Please proceed.

Hello, team. Thanks a lot for taking my question. This is Cure. I'm on behalf of Susango four thousand. Congratulation with the progress. I was wondering on the glioblastoma program, how should we think about the translation of immunogenicity data to tumor responses? And then I was curious to know for the next indication for the Charlotte antigen vaccine. How do you usually go about selecting indication besides, let's say, having a common expression of the antigen on these tumors? Okay. So I start with the GBM question. So I we we have shared at the congresses that in that first part a of the trial, those escalation part of the trial where we were able to analyze 13 patients We also saw in in in seven patients who entered the trial with a residual tumor mass, we saw one partial response. Unfortunately, we couldn't unfortunately, this patient didn't have enough material to do the immune immunoassessment. That's why it's hard to correlate. But normally, coming to your question, if we see immune responses, we would like to, of course, see a translation into a tumor growth control or clinical, overall response. But it it's it's not happening in all cases, right, because we know that sometimes immunotherapy just controls the tumor growth and and can keep the tumor stable, but still by doing so can prolong over survival.

So why, again, it would be highly encouraging with any of our precision immunotherapy treatments if we see more clinical responses, the real benchmark to make a decision gono go is based on overall survival. [indiscernible] you don't have tumor shrinkage, you can still have tumor growth control. And with that prolonged overall survival. Does that answer your question? Yes. Very clear. Thank you. On okay. On GBM. And then the selecting indications.

So in our antigen discovery approach, we sort of like screen antigens and then run them through our algorithms using, like, everybody else, Our but our unique proprietary sort of, like, select and ranking criteria. And only for antigens when they sort of like pass we would basically pick them and and and and consider them to be encoded on one of our candidates.

What we usually do is then [indiscernible] a year or so ago a strategic therapeutic area strategy where we looked across different cancer types, a ton of cancer types, had certain criteria in terms of are these cancers responding to immunotherapy, Is there a high unmet medical need, competitive landscape? Commercial case, and so on and sort of, like, prioritize the cancer cases? And then in those highly prioritized or higher ranked cancer indications, we drove antigen discovery activities that then led the identification of potential antigens that we ran through our algorithm and then came up with the antigens. And of course, as you can imagine, when you look at all cancer types, lung cancer comes up as the number one priority often.

Highly responding to immunotherapy, and that's where basically basically some of our antigen discovery efforts initially focused on lung cancer, but also on others. But we prioritized this program for the reasons I mentioned.

So I I hope this is much bigger Okay. Good. Yes. Absolutely. Thank you.

Our final question is from Starr with Goldman Sachs. Please proceed.

Hi. This is Max on behalf of Roger and Sharma.

Thank you for taking my question. The first one is about r and d. How do you expect, cost to progress through 2025 given your clinical development plans?

And the second question is about the lung cancer trial. Do you plan to check how the response rate could change after patients receive the vaccine? Because I believe the first treatment is supposed to be pembro or pembro combined with chemo.

Then you you inject patients with the with the vaccine just curious how the the clinical trial design is for that part.

Okay. So maybe I start with the second question because I have a question or clarifying question for your first one. So in our phase one trial, again, we select patients with metastatic disease who are on pembro maintenance. These patients usually with lung cancer, very few will have complete response, they will have some sort of, like, residual tumor that is stable under febrolizumab motor therapy. And we are adding the vaccine.

And again, what we would look at is immune responses. And we will also monitor, clinical efficacy. So if we do see a partial response or a tumor shrinkage by adding the we will definitely measure that and also report that. We'll look at progression free survival duration of response, other sort of, like, endpoint driven parameters in that setting. But basically, patients come in, ask stable under pembrolizumab, and we are adding the vaccine. And from that moment on, we will measure or will have regular tumor measurements to see the impact of adding the vaccine.

Got it. K? And and then for your first question, r and d cost, can you please repeat? Because I wasn't sure what you were asking. Question was on r and d spend twenty 5 moving forward. Don't know if you wanna comment if you wanna comment in detail. Maxwell. I I I think there is you know, as I said earlier, there are there are two two things maybe to this equation. I said earlier to another analyst that we included our core pipeline, into, also the early clinical phases into the cash runway Of course, very important to recognize is that as you know, we came from a transformation in 2024 and we continue [indiscernible] we continue to you know, try to you know, have more efficiency, more cost efficiency, and reduce our overall expenses And that, of course, applied. And and on the other side, as you know, you know, we move this company being more of a biotech pipeline company, meaning that we focus very much on our you know, from a cost r and d cost perspective on our pipeline programs, So there, of course, we try to be as efficient and focused as possible.

I don't know if that answers your question.

Got it. Sorry. Can I slip in another question? I noticed that one of your charts showed declining mRNA integrity at 25 degrees?

Celsius.

Could you talk about that? I think it's a slide 13.

Yes. Okay. So you're talking about our proprietary l and p wherein the data on slide 13. Right? [indiscernible] right, RNA and trajectory.

And on the left side, right, where basically, the the data then I guess your question is about the blue line, where free dried RNA integrity decreased to something around 58 60%. Is that the the question? [indiscernible] Yeah. [indiscernible] Right? This is still with its specifications. If you look at integrity and and and and and where the specifications are with regulators, And and so that's why this is encouraging because remember, this is at room temperature. MRNA at room temperature And and after a year at room temperature, it's still terms of integrity within the specifications agreed with regulators today. Got it.

Alright. Thank you. It's it's We have reached the end of our question. Question and answer session. I would like to turn the conference back over to Sarah for closing remarks.

Thank you. With this, we would like 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.

Thank you. The conference has concluded. You may now disconnect.