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mRNA Cancer Vaccines Score CureVac $105M in Financing

By Cormac Sheridan
Staff Writer

CureVac GmbH closed what will in all likelihood go down as the largest private equity round in European biotechnology this year, an €80 million (US$104.9 million) investment from dievini Hopp BioTech Holding GmbH & Co. KG, which will enable it to take forward two mRNA-based therapeutic cancer vaccines, in clinical development for prostate cancer and non-small-cell lung cancer (NSCLC).

The deal is both a major endorsement of CureVac's RNActive platform technology and a marker of dievini Hopp's distinctive investment strategy, in terms of its appetite for risk and its patience. (See story in this issue.)

Tuebingen, Germany-based CureVac plans to move its prostate cancer vaccine, CV9103, into a European Phase IIb trial shortly, but a readout will not be available until 2016 or 2017, CEO Ingmar Hoerr, told BioWorld International. "You lose efficacy data, you lose statistical data if you go any faster," he said. The company will reveal further details of the planned study in the coming months.

Walldorf, Germany-based dievini Hopp, which now holds more than 80 percent of its equity, is fully aligned on the investment horizon.

"In oncology, you have to go for overall survival. If you don't go for a late-stage diseases, then you have to accept certain timelines, of course," CureVac chairman and managing director of dievini Hopp, Friedrich von Bohlen, told BioWorld International. The mechanism by which immunotherapies work impose their own timelines. "You throw in a chemo, and you have an effect the next day. With a vaccine, you have an effect only months later."

The hope is that the effect is more durable than what is all too often seen with chemotherapeutics.

CureVac also plans to move its NSCLC vaccine, CV9201, into a smaller-scale mechanism-of-action study, in order to gain more data about how it elicits an immune response. "Immunotherapy is not only [about] going for overall survival data. It's very important to know the mode of action," Hoerr said.

The investment comes in the wake of positive clinical data from early stage trials of both CV9103 and NSCLC vaccine CV9201 . "To me, it was very interesting to see we had a universal vaccine platform, which can encode any antigen we want," Hoerr said. "On this platform, we can build a lot of other vaccines as well, using other antigens."

Vaccines based on the mRNActive technology comprise several naked mRNA molecules, each of which encodes an antigen of interest. They are administered separately via intradermal injection and are taken up by dendritic cells, which then express the antigens and present them to the immune system.

CureVac has developed methods for modifying mRNA sequences to improve their stability and boost their translation levels. It also has developed a process for formulating mRNA molecules with protamine, a histone-like protein obtained from the sperm of salmon, which acts as an immunostimulatory adjuvant.

CV9103 comprises four individual mRNA molecules, which encode PSA (prostate-specific antigen), PSCA (prostate stem cell antigen), PSMA (prostate-specific membrane antigen) and STEAP1 (six transmembrane epithelial antigene of the prostate 1), respectively.

In an open-label Phase I/IIa trial in 44 patients with castrate-resistant prostate cancer and rising levels of PSA, CV9103 elicited an immune response against at least one antigen in 79 percent of the patients, and against more than one antigen in 58 percent of the responding patients. Similarly, in a Phase I/IIa trial of CV9201 in 46 patients, 65 percent mounted an immune response against at least one of the five antigens present in the vaccine, and two-thirds of the responders recognized two or more antigens.

"They were really better than our expectations, in regard to the number of patients who showed a response to at least one antigen," Hoerr said.

The data were sufficiently strong to persuade dievini Hopp to take the plunge. "When patients have an immune response against two or more antigens that you provide in the vaccine, then there are strong hints that you will also see a clinical response," von Bohlen said. "With all these data we have so far, we're pretty optimistic that CureVac will deliver strong Phase IIb and later on strong Phase III data in oncology."

Seattle-based Dendreon Corp.'s autologous cell therapy for prostate cancer Provenge (sipuleucel-T) was the first therapeutic cancer vaccine to gain approval, but its commercial performance has not matched expectations, owing to its high price and difficult logistics.

Bavarian Nordic A/S, of Kvistgaard, Denmark, began a Phase III trial of its cancer vaccine Prostvac – a sequentially dosed combination of two different Poxviruses, each of which encodes PSA plus three immune enhancing co-stimulatory molecules – in November 2011. (See BioWorld International, Nov. 23, 2011.)