CureVac emerges with €35m cancer vaccine endorsement

It looks like Germany’s CureVac just emerged from stealth mode. Today’s oncology deal with Boehringer Ingelheim comes hot on the heels of July’s tie-up with Sanofi Pasteur, seemingly justifying the faith of venture capitalists who pumped a massive $99m into a series D round in 2012.

Perhaps most surprising is the fact that Boehringer is endorsing not only CureVac’s technology, but also its application as a cancer vaccine – an area notorious for disappointment. The deal focuses on a naked mRNA vaccine through the design of which CureVac thinks it can overcome earlier failures.

The concept is simple enough: deliver mRNA to cells of the immune system, leading to expression of target proteins and triggering an immune response against tumour cells. This is theoretically safer than delivering DNA, which is able to integrate into the host genome and can thus lead to unwanted side effects that are difficult to reverse.

But in practice, although mRNA delivery has been shown to induce significant protein expression, the approach has been hampered by the inherent instability of mRNA and its rapid degeneration in the body.

CureVac, however, claims to have got around this by modifying the mRNA sequence to stabilise the molecule, as well as raising its immunogenicity by complexing it with protamine, a small nuclear protein. This work came from Tübingen University, from which the company was spun out in 2000 (EP Vantage Interview – CureVac hoping for continued support from guardian angel, December 11, 2009).

However, beyond some major VC funding and the backing of one Dietmar Hopp, until recently CureVac had little in terms of hard industry validation. This changed last October, when Johnson & Johnson picked up a licence to an mRNA influenza vaccine, and then two months ago Sanofi Pasteur turned a multi-year pathogen collaboration into a formal commercial agreement.

Raising the stakes

Boehringer raises the stakes further still, handing over €35m ($45m) up front for full rights to CureVac’s CV9202 – a transdermally administered, self-adjuvanting, naked mRNA vaccine coding for six antigens expressed in lung cancer – and agreeing to a further €430m in future milestones plus royalties.

Interestingly, Boehringer is specifically aiming to combine CV9202 with its pan-HER inhibitor Gilotrif, launched last year for NSCLC patients with a specific EGFR mutation. Research in this space is hotting up, with AstraZeneca’s AZD9291 and Clovis Oncology’s rociletinib targeting EGFR-positive patients with a secondary mutation, called T790M.

Combo work is to begin in what Boehringer will at present only call “at least two different lung cancer settings”, while CV9202 plus chemoradiation will be tested in unresectable stage III NSCLC. CureVac has carried out several clinical studies, and CV9202 is at present in a phase I NSCLC trial combined with radiation.

Phase I/II data for CV9201, a version of this project containing mRNA coding for five of the six antigens, were presented at the Asco meeting in 2012, showing a favourable safety profile and induction of immune response in 60% of NSCLC patients. CureVac’s most advanced mRNA application in oncology is CV9104, in a phase II study in metastatic castrate-resistant prostate cancer.

With the failures of Merck KGaA’s Stimuvax, an anti-MUC1 vaccine, and GlaxoSmithKline’s MAGE-A3 very fresh in the memory, the vaccine approach to targeting cancer must be seen as extremely risky.

If delivering mRNA holds the key, and if CureVac really has overcome the problem of mRNA’s instability, then Boehringer might be on to something.

To contact the writer of this story email Jacob Plieth in London at or follow @JacobEPVantage on Twitter

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