A messenger with punch

TṺBINGEN, Germany—CureVac, a clinical-stage biopharmaceutical company developing a new class of therapies and vaccines based on messenger RNA (mRNA), has entered into a collaboration and licensing agreement to develop an mRNA-based influenza vaccine. The deal will see CureVac team up with Crucell Holland BV, a member of the Janssen Pharmaceuticals group. “Strategic alliances and partnerships are important to CureVac, and CureVac is always looking for deals with pharmaceutical and biotechnology companies and academia. Recent discussions have led to the collaboration and licensing agreement with Janssen Pharmaceuticals,” states Dr. Ingmar Hoerr, CEO of CureVac.

Under the deal, CureVac will develop optimized RNActive vaccines based on Crucell's antigen sequences, which will be tested in several models. So far, RNActive vaccines based on CureVac's technology platform have shown better efficacy and safety in many clinical trials compared to other vaccines. Last year, for example, in-vivo data published by CureVac and the Friedrich-Loeffler Institute online in Nature Biotechnology reportedly showed that mRNA vaccines induced balanced, long-lived and protective immunity to influenza A virus infections in various animal models. It was also shown that the production of RNActive vaccines is highly flexible. Thus, RNActive vaccines could theoretically be rapidly supplied for a variety of virus strains and subtypes identified in response to pandemic scenarios.

At that time, Hoerr noted that, “The findings and results from a very fruitful collaboration with our colleagues from the renowned Friedrich-Loeffler Institute underscore the medical potential of mRNA beyond cancer immunotherapy and validate the capacity of our RNActive vaccines to prevent infectious diseases. The synthetic nature of our RNActive vaccines reduces production time dramatically and allows for sequence-matched vaccines that can be produced quickly and reliably in a scalable process. Additionally, our vaccines can be stored at room temperature, thereby avoiding the cold-chain—in contrast to all other vaccines on the market—and making worldwide distribution of our vaccines logistically and financially attractive.”

In order to develop new and effective mRNA vaccines, CureVac is combining both the antigenic and adjuvant properties of mRNAs. RNActive vaccines consist of modified and formulated mRNA with three distinct features: strong antigen expression, increased stability and enhanced immune-stimulatory activity. Furthermore, compared to conventional methods, the RNActive technology provides faster generation of vaccines. The human immune system recognizes the RNA as “foreign” nucleic acids, Hoerr notes, and this stimulates the mammalian innate immune system—the non-specific immune system—through activation of Toll-like receptors (TLRs).

 “Therefore, RNActive vaccines also have self-adjuvanting properties: They induce a robust expression of the antigenic target protein and provide, at the same time, a strong danger signal leading to activation of different pattern recognition receptors (e.g. TLR7, TLR8). Thus, RNActive vaccines and immunotherapies stimulate the adaptive and innate immune systems optimally and lead to a balanced humoral as well as T-cell-mediated immune response. This includes antibody-producing B-lymphocytes, cytotoxic T-cells, memory T-cells and helper T-cells,” he states.

In ongoing development work not included in the Janssen deal, CureVac is also developing RNAdjuvant, a RNA-based adjuvant composed of single-stranded non-coding RNA. RNAdjuvant has shown in preclinical trials that it may increase the efficacy of a large number of different vaccines, and could therefore be combined with protein- and peptide-based vaccines, presumably without any toxic side effects. The company has successfully completed Phase I/IIa studies with its RNActive cancer vaccines in prostate cancer and non-small-cell lung cancer. Results so far have shown that mRNA-based products are safe and capable of inducing balanced immune responses. In addition to developing its own pipeline, CureVac is collaborating with Sanofi Pasteur and In-Cell-Art on a $33.1 million project co-funded by the Defense Advanced Research Projects Agency for the development of prophylactic vaccines in infectious diseases utilizing its RNActive technology platform.