2024-05-14

What specific cancer types are CureVac targeting with their oncology strategy and how does CureVac's mRNA technology differ from traditional cancer vaccines?

Over the last decade, therapeutic cancer vaccines have deployed cancer cell proteins to train the immune system to recognize and attack tumors. While most phase III studies have not shown significant benefit for patients at the time, we are now seeing a renewed interest in therapeutic cancer vaccines based on mRNA technology. Cancer cells should be recognized by the immune system as “foreign” in the same way the immune system recognizes pathogens. With mRNA vaccines, we have the opportunity to overcome the immune system’s tolerance by encoding antigens that are specific to cancer cells in patients. When an mRNA vaccine is taken up by immune cells, as well as other cells in the body, they are instructed to present the cancer antigens encoded by the mRNA to other immune cells. With that, the immune cells are activated and now trained to identify cancer cells as malignant and destroy them. For our cancer vaccine approach, we leverage proprietary and cutting-edge technologies for antigen discovery as well as our clinically validated second-generation mRNA backbone, which targets improved intracellular mRNA translation for early and strong immune responses.

We currently have a Phase 1 study underway with our cancer vaccine candidate, CVBGM, which is evaluating safety and tolerability in patients with glioblastoma after surgical resection. The candidate encodes for known tumor-associated antigens linked to glioblastoma. Our first data readout from this trial is expected in the second half of 2024. Additionally, we recently announced a collaboration with The University of Texas MD Anderson Cancer Center to jointly develop cancer vaccine candidates in hematological and solid tumor indications. With CureVac’s end-to-end capabilities for antigen discovery and mRNA vaccine design and MD Anderson’s experience in cancer drug development and clinical research, this collaboration is an ideal match for cancer vaccine progress and innovation.

Could you detail the scientific insights that led to the development of the mRNA-based Avian Influenza vaccine and what were the main findings from the phase 2 studies for the Seasonal Influenza vaccine?

As in our oncology programs, we recently leveraged our second-generation mRNA backbone in infectious diseases to encode a relevant avian flu antigen. There has been increased focus on the H5N1 avian influenza, which is considered a potential future pandemic threat, known to sporadically cross species from its original bird host to other animal hosts and humans. Together with our partner GSK, we develop an investigational avian flu pre-pandemic vaccine candidate, which encodes an influenza A H5-antigen. A combined Phase 1/2 study was initiated in April 2024. Just before starting this study, we reported promising interim Phase 2 data in seasonal influenza, also developed in collaboration with GSK, which further confirmed that our proprietary mRNA platform elicits strong overall antibody titers at well-tolerated dose levels.

How does CureVac's mRNA vaccine address the evolving challenges posed by COVID-19 variants?

One of the major benefits of mRNA technology is its speed and flexibility. By exchanging the coding region of the mRNA construct, we can very quickly and easily adjust vaccines to the most relevant strains and latest standard of care. The technology is also very well suited to design multivalent as well as combination vaccines by including more than one mRNA construct per vaccine that have the potential to protect against more than one variant or more than one disease with a single vaccine.

Earlier in 2024, we announced positive interim results from our Phase 2 COVID-19 clinical trial, which confirmed competitive immune responses at lower doses and a favorable tolerability profile in a direct head-to-head comparison with a licensed bivalent mRNA-based comparator vaccine. As COVID-19 strains evolve, we will be able to adapt our clinical vaccine candidates to healthcare needs.

What specific patient populations are you targeting with your mRNA-based therapies for the best outcomes?

With various programs in our pipeline, including infectious disease and oncology, our aim is to have broad impact across different patient populations. However, there is one common thread for all the indications we are targeting: we are trying to address significant unmet medical need. In infectious disease, the unmet need is focused on alleviating a pandemic situation or, with seasonal flu, reducing deaths and severe illnesses every year. In oncology, while there has been great progress in treating many different types of cancer, there still exists a tremendous treatment gap for many others. At CureVac, we know that a one-size-fits all approach to addressing cancer is not the only answer. That’s why we are taking two different approaches in how we plan to design cancer vaccines. Broadly, we aim to develop off-the-shelf cancer vaccines across different indications that share common tumor-specific antigens. But we also aim to take a more personalized approach with patients who might not respond to broad treatment, leveraging their individual tumor profile to develop a vaccine specifically for them.

What are the primary technical challenges in developing mRNA-based therapeutics for non-infectious diseases and how does CureVac ensure the stability and efficacy of mRNA drugs for therapeutic use?

Looking beyond infectious diseases to the next major opportunity for mRNA technology in oncology, the field of immunotherapy has significantly advanced with the progression of new technologies, such as next-generation sequencing, to extract detailed genomic data from patient samples. Over the last decade, ‘conventional’ immuno-oncology approaches have focused on the exome, the protein-coding part of the genome, which represents only about 1.5% of the total genetic information. More recently, breakthrough developments in sequencing capacity and the advent of whole genome sequencing have enabled the extraction of vastly larger amounts of data that today allows us to utilize the remaining 98.5% of genetic information. In view of extracting such genetic information from tumor cells, we believe this is where the bulk of the immunogenicity resides.

We brought these technologies in house with the acquisition of Frame Cancer Therapeutics in 2022. We apply whole-genome-sequencing for every patient sample combined with short and long-read RNA sequencing to map the full genomic inventory of the tested tumor cells. Downstream of the sequencing, proprietary bioinformatics integrate all the data to retrieve the exact changes in the DNA of the tumor cells compared to healthy cells. Correlation of this data with changes in the RNA transcription of the tumor results in entirely new and potentially antigenic tumor antigens that we plan to test as targets for a portfolio of new cancer vaccine candidates. These new antigens are not only entirely foreign to the body but are also uniquely expressed in the tumor and not in healthy tissue. In their foreignness, these constructs are expected to raise stronger immune responses than antigens derived from exome-based conventional approaches.

We are confident that our mRNA platform offers significant potential to provide solutions for people and patients in indications with high unmet medical needs. To improve the efficacy of our mRNA constructs, our emphasis is on high intracellular expression and protein output , which we believe can lead to more effective treatments at low and well-tolerated doses. Additionally, we have achieved promising stability with next-generation formulations, which offers the potential to overcome a yet significant hurdle in mRNA therapeutics. While challenges remain, such as the need for robust therapeutic and preclinical models for proof of concept, we are committed to pushing the boundaries of innovation in mRNA technology.

What advancements do you anticipate in delivering mRNA-based drugs and vaccines to patients?

We’ve covered the potential for mRNA drugs to address cancer indications and infectious disease, but I would also like to highlight its potential for areas beyond that. For example, it can help to produce therapeutic proteins in the body to account for a lack of a certain protein. There are so many diseases, especially in the rare category, that are caused by a lack of a specific protein or dysfunctional proteins. There is ample potential for mRNA therapeutics to have impact in this area, giving the body the tools it needs to make the right proteins and function correctly. We also believe there is room for improvement, particularly in the design of mRNA vaccines and therapeutics, e.g. improved mRNA delivery, which will be needed to further advance the technology’s precision, power and safety. But there is time. CureVac has been advancing mRNA technology for more than 20 years and we are still only at the beginning of realizing the potential benefits for patients.