CureVac Q4 2024 Earnings Call Transcript

Quartr
Provided by Quartr
April 10, 2025

There are 13 speakers on the call.

Operator

Greetings. Welcome to Cureac Fourth Quarter and Full Year twenty twenty four Financial Results and Business Update Call. At this time, all participants are in a listen only mode. A question and answer session will follow the formal presentation. As a reminder, this conference is being recorded.

Operator

It is now my pleasure to introduce Sarah Faki, Vice President, Corporate Communication and Investor Relations. Thank you, Sarah. You may begin.

Speaker 1

Thank you. Good morning, good afternoon, and welcome to our conference call. 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 Zener, Chief Executive Officer of CureVac Miriam Mendila, our Chief Scientific Officer and our Chief Financial Officer, Axel Marcumas.

Speaker 1

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 today, 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.

Speaker 1

These statements involve risks and uncertainties that could cause actual results to differ materially from those projected. Georec 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.

Speaker 1

I will now turn the call over to Alexander.

Speaker 2

Thank you, Sarah. Ladies and gentlemen, good morning, good afternoon to everybody on the 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 to streamline and rightsize 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.

Speaker 2

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 resectable glioblastoma. The phase one study successfully completed enrollment of Part B. The speed of the enrollment underscored the urgent need for new treatment options in this aggressive form of brain cancer, and we are encouraged with 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 milestone with the IND clearance from the US Food and Drug Administration to proceed with phase one.

Speaker 2

We anticipate treating the first patient in the second half of twenty twenty five. Transitioning to infectious diseases, our new licensing agreement with GSK prophylactic vaccines continues to progress. In November, GSK initiated a combined phase 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 and received in the first quarter of twenty twenty five. Additionally, in its full year and fourth quarter earnings report, GSK confirmed that its clinical program for standalone seasonal influenza vaccine is being prepared for phase three.

Speaker 2

Transition to phase three will 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 folio tail six six 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 and the 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.

Speaker 2

Our previously mentioned licensing agreement with GSK signed in July 2024 and valued up to €1,450,000,000 plus royalties, marked a pivotal moment for CureVac. This agreement provides us with significant capital and leverages GSK's expertise in infectious diseases for successful development and commercialization. Importantly, we 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.

Speaker 2

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, in urinary tract infections, which 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 influenza 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.

Speaker 2

On the management side, we welcome two new members to our leadership team, Taminda 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 2025 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 our program for squamous non small cell lung cancer is scheduled to be treated in the second half of this year.

Speaker 2

The clinical development of our new prophylactic vaccine program for UPEG is underway, and we expect to file an IND submission in the second half of this year for a phase one 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 and innovative IP portfolio and anticipate 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 probably remain 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 polyA tailed six sixty eight patent in amended form represents an important step in our ongoing litigation with Pfizer BioNTech.

Speaker 2

This decision supports a pioneering role and significant contributions to mRNA vaccine technology, particularly in the space of COVID-nineteen vaccines. Please 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, the infringement proceedings are displayed.

Speaker 2

For an IP dispute, infringement is decided by the regional court Dusseldorf, as well as potential damages related to all six IP rights at issue. On the right side, validity proceedings are displayed. Validity of our IP rights is heard by different authorities depending on the nature of the IP rights. Validity of the split cell patterns is heard by the EPO. Following the EPO's positive decision on our first split polyA six sixty eight patent last month, a hearing to rule on infringement is scheduled for 07/01/2025.

Speaker 2

And should validity of the second split polyA tail patent also be confirmed by the EPO in a hearing which is scheduled for May 2025, it would also be included in the July 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.

Speaker 3

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 one glioblastoma study with CVGBM, an off the shelf precision immunotherapy encoding eight segments from four known tumor associated antigens with 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 are 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 cvGBM.

Speaker 3

At the recommended one hundred microgram dose for the expansion part of the study, the 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 from our collaboration with MyNeo Therapeutics.

Speaker 3

I will provide more detail on the study later in this presentation. In 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 GSK. In our proprietary non respiratory infectious disease portfolio, our program for prophylactic vaccine against uropathogenic E. Coli bacteria to prevent urinary tract infections is well on track.

Speaker 3

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 nanoparticle with clustering of FIGH 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, and 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 one development. All current candidates of the GSK trials are based on CureVac's proprietary second generation mRNA backbone.

Speaker 3

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, we'll 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, their 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.

Speaker 3

In this complex landscape, we see tremendous opportunity for our mRNA therapeutics to revolutionize 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 and has been clinically validated in phase one and two studies in both infectious diseases and oncology. Second, our proprietary and highly differentiated whole genome based antigen discovery platform.

Speaker 3

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 powerful 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.

Speaker 3

Accordingly, we aim to apply mRNA therapeutics at early stages of cancer in the adjuvant or perioperative setting. We believe by intervening early, we 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.

Speaker 3

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.

Speaker 3

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.

Speaker 3

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.

Speaker 3

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 febrolizumab maintenance therapy for up to twelve months or until disease progression or undue toxicity occurs. In Part A, we 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 optional dose expansion Part B will be conducted.

Speaker 3

The primary endpoints of the phase one study include the incidence of dose limiting 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, aligned with our goal to apply mRNA precision immunotherapies at early stages of cancer. Moving on to infectious diseases on slide 11, let me provide you with a brief overview of the details of the respiratory disease program, which 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 milestone payment for CureVac.

Speaker 3

The program for a pre pandemic vaccine against avian influenza is currently in phase two of the combined phase one two 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 standalone 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, we leverage their expertise in vaccine development and commercialization to bring innovative vaccines based on our mRNA technology to market.

Speaker 3

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.

Speaker 3

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. Prophylactic vaccines often target induction of high antibody titers, and T cell responses only were 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.

Speaker 3

In previously reported, a proprietary LNP system for infectious diseases featuring a PEG free lipid composition that demonstrated strong humoral 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 bespoke 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 at at minus 80 degrees Celsius or minus 112 degrees Fahrenheit as a control.

Speaker 3

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, which provides a strong development path through the end of twenty twenty six.

Speaker 3

On the oncology front, starting with our most advanced Phase I of the SHELD 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 potentially continuing to a Phase II study, which could start in the second half of twenty twenty six. Following FDA clearance of the IND submission, the Phase I 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 Officers' Health 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 expected to start in the second half of twenty twenty six.

Speaker 3

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 one clinical development in the first half of twenty twenty six. Additional discovery work in other non respiratory diseases is ongoing, and we anticipate expanding our pipeline in this area with additional programs in 2025 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.

Speaker 3

I would now like to conclude the portfolio update and hand over to Axel for a review of the financial data.

Speaker 4

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 and innovation. Today, we report a strong cash position of €481,700,000 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 Qovac's intellectual property relating to applicable vaccine programs with no further R and D work obligation our side.

Speaker 4

As such, it was fully recognized as revenue in 2024. Given that under the terms of the new licensing agreement, obligations from prior collaborations relating to R and D services had expired, remaining contract liabilities amounting to €80,400,000 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 one 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% work force reduction was completed by end of twenty twenty four with incurred costs 17% below the allocated budget.

Speaker 4

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 to 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 and COV going forward. Taken together, in 2024 extraordinary payments related to CVN COV, 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 increased from €402,500,000 at the end of twenty twenty three based on the €400,000,000 upfront payment from GSK in August 2024.

Speaker 4

The increase is partially offset by our ongoing R and D activities as well as a total of €137,000,000 1 off payments 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 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 2023. For the full year 2024, operating profit was €177,700,000 compared to an operating loss of €274,200,000 for the same period in 2023.

Speaker 4

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 Q of X 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.

Speaker 4

Third, general and administrative expenses decreased compared to the prior year 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 Qovac's refocus on R and D. Financial results increased by $3.7200000.0 euros 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 €190,900,000.

Speaker 4

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'll now hand the call back to Alexander for today's key messages.

Speaker 2

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 can make a meaningful impact for patients. Financially, we closed the fourth quarter twenty twenty four with a 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.

Speaker 2

We are making great progress in oncology, or off the shelf and personalized precision immunotherapies, And with encouraging results for our lead candidate in glioblastoma, we are eager to show continued progress with an anticipated Part B readout, as well as advancements of our off the shelf program in squamous non small cell lung cancers. In infectious diseases, we are quickly moving forward with the U Pack vaccine in urinary tract infections, eager to make a new medical breakthrough in an indication where great unmet need persists. We continue in 2025 with our focus on high value mRNA opportunities from a well financed 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.

Operator

Thank A confirmation tone will indicate your line is in the question queue. You may press star two if you would like to remove your question from the queue. And for participants using speaker equipment, it may be necessary to pick up your handset Our first question is from Alex Stranahan with Bank of America. Please proceed.

Speaker 5

Hey, guys. Thanks for taking our questions, and congrats on the progress to close 24. Two two questions from us. Maybe first, actually, both are on the squamous program. You know, the the the use of antigens outside of the exome is is pretty unique to this program.

Speaker 5

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

Speaker 2

Okay. Very helpful.

Speaker 3

Thanks. So I didn't quite get the last part of the question, but I'll start with the first part. So with our antigen discovery platform, especially for off the shelf antigens, we usually run them through an extensive set of validation assays where we basically look, whether the antigens is selected, especially the novel ones outside the exomes, 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 to the in in in in cancer patients.

Speaker 3

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 is 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 that's preclinical evidence from other settlers 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?

Speaker 3

I'm sorry. I I didn't quite understand it. Because you said something about the dosing of the first patient and and and and what that mean, or what indication that would give.

Speaker 5

Yeah. No. Just more in terms of data readout time. Obviously, pace of enrollment, is probably the biggest swing factor here, but I just didn't see a data catalyst, on I think it was slide 14, of your prepared

Speaker 3

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, we 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.

Speaker 6

Got it. Thank you.

Operator

Our next question is from Mani Fourekar with Leerink. Please proceed.

Speaker 7

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 CVGBM asset. Have you had conversations with regulators at this point on steps to approval and what that would look like?

Speaker 7

And then I guess just to pivot off of that, do you see the recent changes that the FDA influencing any prior conversations that you guys have had? Thanks.

Speaker 2

Maybe I can start with the second one, and then, Miriam, you can comment on the regulatory path. On your question on whether we've seen any impact yet, with the FDA, so far, not for our program. You know, we have the ID 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's going on. But so far, at least in our own programs, we have not seen any negative impact.

Speaker 2

Miriam, if you wanna comment on GBM potential regulatory path and how to move forward with the program.

Speaker 3

Maybe one point to add. We also interact 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.

Speaker 3

For CD GBM, right, as said, if the data from phase one and the expansion 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 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 have indications as we go forward.

Speaker 7

Great. Thank you.

Operator

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

Speaker 8

Thanks for that day and taking all question. A couple of questions. Maybe the first one related to the GBM. Given the Part B data are 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.

Speaker 8

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 as the model only have a one versus a four plus? You see the difference on the activity, antitumor activity.

Speaker 8

The last part of the question is 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 new new pipeline upcoming, like the GBM, squamous cell and the UTI. And then it it does this pass urine will include all the phase one, phase two implant? Thank you.

Speaker 2

Okay. So Miriam, three questions. One on GBM, I guess where the bar is or how we would assess, you know, gono go decisions, and the one on squamous on the number of antigens and whether we see differences, and then maybe one for axial on the cash runway.

Speaker 3

Okay. Okay. I'll start with the GBM question. And so, yes, we we have set basically a high threshold for for GBM, and basically would expect to see in our population immediate overall survival of fifty months or longer to say give a go or and 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 to a phase two.

Speaker 3

Regarding your, your question on coverage for the squamous 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, or 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.

Speaker 3

And the question you ask is is the 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 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 showed a difference.

Speaker 3

And other trials 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.

Speaker 4

Yeah. In terms of the cash runway into 2028, so what I can tell you is is that and 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 portfolio preparing 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.

Speaker 4

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. It. Answers your question?

Speaker 8

No. That answers. Thank you.

Operator

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

Speaker 9

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 know, across oncology and the non respiratory infectious disease programs, what's your latest thinking about, where you would want to potentially partner versus, keep developing yourselves?

Speaker 9

Thanks.

Speaker 2

That's a good question. I I think in general, what we tried to do this year is really focus CureBag 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 respiratory infectious disease program. We have a collaboration in place as well with MD Anderson Cancer Center on next generation shared off the shelf cancer vaccines. And 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, you know, phase ones and maybe depending on the indication also phase two.

Speaker 2

But I think the goal, especially for the larger TAs such as oncology, would be, clearly to partner then the late stage development program with somebody that has real muscle in the field and really has the means to develop it more broadly and then eventually also commercialize worldwide.

Speaker 9

Great. Thank you.

Operator

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

Speaker 10

Hey, thanks for taking the questions. I had a few on the European patent proceedings. I guess, can you give a sense of the timelines for the infringement hearing and possibly that, 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 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.

Speaker 10

Sorry. Thanks.

Speaker 2

Sure. I mean, we highlight kind of the key overarching timelines on slide six of the presentation. Right? So the kind of next milestones are is we have further European patent office hearing for a second poly A patent, the seven seventy five patent, which takes place May, 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 six S8, and if the validity is confirmed as well, the seven seventy five polyA patent, then, yes, there is an opportunity for the opposing partner to appeal, but if infringement is confirmed and validity has been confirmed prior, that would nevertheless start at least the damages process in Europe, which don't count me exactly this, but my understanding is can take up to a year, to be completed. In The US, of course, it's different.

Speaker 2

In The US, you have one legal case which will start in September 8 this year, and in The US, you have one process that covers validity, infringement, as well as damages at the same time.

Speaker 10

Okay. Great. I question. Yeah. Just curious.

Speaker 10

This subject to amendments comment on the

Speaker 2

Yeah. So the amendment was mostly related to the length of the poly 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.

Speaker 10

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.

Speaker 2

Well, I think it's the the question was with the Genmab and Genmab collaboration. Right? 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 programming kind of mutual mutual agreement.

Speaker 11

Okay. Thank you.

Operator

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

Speaker 6

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 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.

Speaker 6

Do you need to see efficacy signs of early efficacy in metastatic setting beyond maybe immune engagement or 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 let you answer cancer first, please.

Speaker 3

Okay. No. It's a great question. So as we said, right, we do believe that the immunotherapies will work in earlier cancer settings because the immune system is functioning, and you have, less tumor burden to control. And so with that, basically, our criteria and and primary objectives for the phase one trial in squamous non small cell lung cancer would be to see immune responses against the encoded antigen.

Speaker 3

So that would be sort of like a primary hurdle. If we see then, of course, clinical activity, that would be most encouraging. But 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 cancer, these immunotherapies do not work that well. So immune responses are 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 to 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?

Speaker 3

Yeah.

Speaker 6

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 ex exome novel antigens to, immune engagement and and efficacy?

Speaker 3

So so we're discussing that we would like to discuss and disclose more. We we have to see when is what's 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 can go public and share all the all the data around that.

Speaker 6

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 art that they brought in to the potential for the patents in The US Court?

Speaker 2

Maybe, John, 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.

Speaker 6

Alright. Fair enough. I look forward to that.

Operator

Our next question is from Chiara Manatroni with Chemtan. This

Speaker 12

is Chiara. I'm on behalf of, Susan Goldfarthousand. 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 shard antigen vaccine, how do you usually go about selecting indication, besides, let's say, having a common expression of the antigen on these tumors?

Speaker 3

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, dose escalation part of the trial where we were able to analyze 13 patients. We also saw 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, and that's why it's it's hard to correlate.

Speaker 3

But normally coming to your question, if we 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'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, and but still by doing so can prolong overall 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 to make a decision go no go is based on overall survival. Because if you don't have tumor shrinkage, you can still have tumor growth control and with that prolonged overall survival. Does that answer your question?

Speaker 12

Yes. Very clear. Thank you.

Speaker 3

On okay. On GBM. And then the selecting indications. So, you know, 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, selection 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.

Speaker 3

What we usually do is then, in in in oncology, we have, designed 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 to 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 of highly responding to immunotherapy. And that's where basically some of our antigen discovery efforts initially focused on lung cancer, but also on others. But we prioritize this program for the reasons I mentioned.

Speaker 3

So I I hope this is a hard question. Okay. Good.

Speaker 12

Yes. Absolutely. Thank you.

Operator

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

Speaker 11

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?

Speaker 11

And the 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.

Speaker 3

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 a complete response, so they will have some sort of like residual tumor that is stable under pembrolizumab monotherapy, and we are adding the vaccine. And again, what we would look at is immune responses, and we will also monitor, clinical efficacy.

Speaker 3

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

Speaker 11

Got it.

Speaker 3

K? And and then for your first question, r and d cost, can you please repeat? Because I wasn't sure

Speaker 2

what you were asking. Question was on r and d spend 25 moving forward. Don't know if you wanna comment if you wanna comment in detail, Maxwell.

Speaker 4

I I I think there is, you know, as I said earlier, there two things maybe to this equation. As 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 continuously 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.

Speaker 4

I don't know if that answers your question.

Speaker 11

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?

Speaker 11

I think it's slide 13.

Speaker 3

Yes. Okay. So you're talking about our proprietary LNP where I introduced the data on slide 13. Right? And where I showed RNA, right, RNA and regulatory.

Speaker 3

And on the left side, right, where basically the data there I guess your question is about the blue line, where freeze dried RNA integrity decreased to something around 58 60%. Is that the the question? Update on this. So

Speaker 11

Yeah.

Speaker 3

Specific specifications. Right? This is still with the 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.

Speaker 3

MRNA at room temperature. And and after a year at room temperature, it's still, in terms of integrity within the specifications agreed with regulators today.

Speaker 11

Got it. All right. Thank you.

Speaker 4

We

Operator

have reached the end of our question and answer session. I would like to turn the conference back over to Sarah for closing remarks.

Speaker 1

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.

Operator

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

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Earnings Conference Call
CureVac Q4 2024
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