EP Vantage Interview - Symphogen awaits proof of concept as funding secured

With a headline-grabbing €100m ($137m) of private financing secured, Symphogen is now powering towards the next crucial milestone – proof-of-concept data. By the end of the year two phase II trials should report on the Danish antibody specialist’s most advanced products, created by the novel platform technologies that helped attract such significant funding.

Kirsten Drejer, Symphogen's chief executive, tells EP Vantage that the majority of the new investment will be ploughed into oncology, where the company is working on antibody mixtures against existing targets, hoping to show much improved efficacy. The anti-EGFR products Erbitux and Vectibix are the first in Symphogen’s sights; positive data will help to justify Europe’s largest ever financing of a private biotech.

Validation

SYM004 is the company’s most advanced oncology project, currently undergoing phase I dose escalation trials which should yield data in the coming months. A phase IIa is planned for the spring, in metastatic colorectal cancer patients.

The product is a recombinant polyclonal antibody, a composition of antibodies that bind to different sites on the same antigen. In the case of SYM004, two antibodies bind to two, non-overlapping epitopes on the EGF receptor. This prompts aggregation of the receptors on the surface of the cell, which get internalised and broken down inside.

“So in essence you see total removal of the receptor from the cancer cell surface,” Ms Drejer says. “I believe what is happening is that the cancer cell sees this as something very un-physiological and needs to internalise and degrade the complex.”

Removing the receptor terminally interrupts the EGFR signalling pathway, which is involved in the growth and proliferation of tumours. Pre-clinical data suggests SYM004 will have greater efficacy and similar side effects to monoclonal antibodies like Erbitux and Vectibix, which solely work by blocking the receptor. Phase IIa data will hopefully provide crucial clinical validation.

Mimic nature

Ms Drejer says Symphogen’s approach is based in an attempt to mimic both the specifity and diversity of nature’s way of treating disease. Current antibodies provide the former but not the latter; combinations of antibodies could provide an answer to the lack of diversity, or at least an improved solution.

The broad applicability of Symphogen’s platforms – which allow the discovery, selection and manufacture of these polyclonal antibodies – was largely responsible for attracting such a big funding round, Ms Drejer says.

“We have developed a unique mechanism of action which can be translated to other receptors, not just EGFR, that is why investors were keen to support us with a large amount,” she says.

Following behind ‘004 are several other earlier stage products, including SYM005, against the Her2 receptor.

“We have made a pool of antibodies against a number of extremely relevant targets, so we’re in a position now where we want to pick new combination products,” she says.

Flexibility

Monoclonal antibodies generated $27.5bn in revenues last year in cancer indications, a figure that is set to grow by 24% by 2016, according to EvaluatePharma. It is easy to see why Symphogen decided to switch its research focus into this area; initially the company was looking at infectious disease targets and blood products.

A few of these legacy products remain, including the company’s most advanced candidate SYM001, intended as an alternative to existing hyperimmune immunoglobulins used to treat idiopathic thrombocytopenic purpura (ITP). Phase II data will be available at the end of the year and a partner is being sought; Swedish Orphan Biovitrum handed its rights back earlier this year.

Symphogen is also keen to find a partner for SYM004, although Ms Drejer acknowledges that more extensive phase II data might be required to convince interested parties that the product can be better than existing anti-EGFR therapies.

The fundraising certainly gives the company the means to do just this; progress further with trials and add more value before having to seek a deal.

Out of the ordinary

Antibodies remain a hot area of research and it is perhaps not surprising that a novel approach like Symphogen’s can attract such significant sums of money. However, this was not a typical venture capital round, and Symphogen is not a classic VC-backed company; this financing was the sixth time funds have been raised since the company was founded in 2000.

Symphogen has been around for long enough that more traditional funds might be looking for an exit by now. The fresh €100m - €108m had been raised in previous five rounds – will last another four to five years, meaning some shareholders could end up being around for 15 years.

A look at the investors helps explain why they may be happier to wait than traditional VCs: the lead investor was Novo A/S, the huge Danish foundation which has been with Symphogen since the beginning, and a new investor is The Danish Pension Fund PKA.

This does not mean they will not be looking for rich returns and a clear exit. But they may be happier to wait for it.

“As we get a more mature pipeline we can decide whether to go public or become a cash generating biopharma company, but at least we have freedom to operate from a position of strength rather than constantly chasing new money,” Ms Drejer says.

A position that many of Symphogen’s rivals will envy.

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