BIOLOGICS
the modified mRNA has three distinct features: first, the formulation and modifications of the mRNA lead to increased stability; second, translatability ensures strong antigen expression; and, third, the technology gives enhanced immune-stimulatory activity. It is important to note that natural mRNA is prone to hydrolysis by ubiquitous ribonucleases leading to instability and rapid degradation.
“The mRNA modifications of RNActive support both antigen expression and immune stimulation mediated by Toll-like receptor 7 and 8 (TLR7, TLR8) and, importantly, is HLA independent, which is not the case for peptide-based vaccines. In addition, RNActive vaccines do not activate the regulatory T cells (Treg) that are responsible for intra-tumoral immune suppression which has hindered the effectiveness of cancer immunotherapy for decades,” he says.
Drug candidate clinical progress CureVac has successfully completed an open-label Phase 1/2a clinical study to test the safety and tolerability of its drug candidate CV9103 in patients with castration-resistant prostate carcinoma and rising PSA levels. CV9103 is composed of four different RNActive molecules encoding four different prostate cancer-specific antigens. The company plans to initiate a randomised Phase 2b clinical study in prostate cancer evaluating overall survival, with data expected in 2017.
The second drug candidate, CV9202, has been shown to be safe, well tolerated and biologically active, producing a robust, balanced immune response to all antigens in a Phase 1/2a study in patients with stage III or IV non-small-cell lung cancer (NSCLC). CV9201 is composed of five different RNActive molecules encoding for antigens that are frequently overexpressed in non-small cell lung cancer. In addition, the company will continue the NSCLC programme with a second clinical study currently being planned.
Development through partnerships “Strategic alliances and partnerships are important to us,” says Hoerr. “We are looking for partnerships for our first-in-class mRNA vaccines and adjuvants with pharmaceutical and biotechnology companies and academia. Last year, Sanofi Pasteur, In-Cell Art and CureVac formed a collaboration in a $33.1 million project, in which we may receive a double-digit million dollar funding in an option
36 sp2 Inter-Active September/October 2012
deal to further strengthen our RNActive technology. “We had been in contact with Sanofi Pasteur for some time, and they contacted us immediately after DARPA announced the funding call at the end of November 2010. We received notice of the funding from DARPA at the end of March 2011. “CureVac will discover, design, optimise and manufacture the mRNAs, and perform initial immunogenicity testing and certain challenge experiments. With our extensive knowledge in the GMP production of RNA and through our production facility, the company is endeavouring to demonstrate the flexibility and universal applicability of the RNActive platform.” Sanofi Pasteur will run extended safety and immunogenicity studies in vivo and in vitro. In particular, the company will apply VaxDesign’s MIMIC system to test the vaccine candidates in a ‘human-like’ in vitro setting. Furthermore, Sanofi Pasteur will perform challenge experiments in relevant animal models. In- Cell-Art will develop nanoparticle carrier molecules to potentially further protect the mRNA and enhance its immunogenicity effect by delivering it to the right place. Separate from this collaboration, Sanofi
Pasteur and CureVac have signed an option agreement for a collaborative project for the development of RNActive vaccines for specific pathogens. This agreement consists of several predefined pathogens. Once Sanofi Pasteur exclusively licenses a pathogen, it will pay CureVac an upfront payment for each one. The upfront and milestone payment for each single pathogen could be up to €101.5 million in addition to tiered royalties on sales of RNActive vaccines if Sanofi Pasteur develops a prophylactic or a therapeutic vaccine against such pathogen. The upfront and milestone payment for each pathogen could be up to €150.5 million in addition to tiered royalties on sales of RNActive vaccines if Sanofi Pasteur develops both a prophylactic and a therapeutic vaccine.
Further opportunities “To our knowledge there is no other commercial approach using mRNA for direct intradermal application for therapeutic or prophylactic vaccination,” says Hoerr. “Other approaches are using mRNA to be loaded ex vivo on dendritic cells for stimulating antigen- specific responses. There are also reports of naked mRNA being injected into lymph nodes directly in vivo in animal studies. There are also reports on the use of viral-derived self- replicating RNA (‘replicons’) as vaccines and there have recently been first reports on using mRNA for re-programming cells or as
Meet Ingmar Hoerr of CureVac
Ingmar Hoerr is a co-founder and the CEO of CureVac. During his scientific career, he laid the foundation of CureVac’s unique RNA-based technology platform, RNActive, enabling the development of a new class of cancer vaccines. With a background in both biology and business management, he decided to set up CureVac in order to advance his findings to their full therapeutic and commercial potential. His scientific track record includes work in the laboratories of Professor Günther Jung and Professor Hans- Georg Rammensee, renowned scientists in organic chemistry and immunology, respectively. Hoerr also completed one year of field studies on leprosy and HIV in collaboration with the World Health Organization (WHO) at Madurai Kamaraj University in India. He received his PhD in biology from Tübingen University in 1999, and a MBA from Danube University in Krems, Austria in 2001.
replacement therapy.
“Immunotherapy continues to be a promising approach, especially in oncology; it seems to be the most natural and patient- friendly treatment option for cancer alongside traditional methods such as surgery, radiation and chemotherapy. Additionally, the field of prophlylactic immunotherapy is emerging, requiring safe and effective vaccines that are easy to manufacture and administer, that are well tolerated, and that potentially avoid the need for exogenous adjuvants.
mRNA is a molecule made by nature, and it becomes more and more clear that mRNAs and mRNA-vaccines could have a huge impact to fight against cancer and pathogens.
Further information CureVac GmbH Paul-Ehrlich-Strasse 15 72076 Tübingen Germany Tel: +49 70 719 20530 Fax: +49 70 719 205311
Internet links Email:
info@curevac.com Web:
www.curevac.com
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44