Interview – Biothera primed for investor validation

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Biothera might be anything but a typical oncology player, but its persistence in demonstrating the value of adding its Imprime PGG technology to standard cancer treatments was rewarded with a late-breaking abstract at the recent Esmo congress.

Now the private US group is embarking on a “significant financing round from one of world’s leading life sciences investors”, its chairman and president, Dan Conners, told EP Vantage during the meeting in Madrid. Whether this results in a tightening of the business focus, or indeed an even more drastic event, are probably nice problems to have.

It might come as a surprise that since its creation in 1997 Biothera has operated a dual model combining a functional foods business with pharmaceuticals. It is not clear whether one unit effectively funds the other, but Mr Conners says around $180m has been raised from individual angel investors.

Both divisions are centred on Imprime PGG, an extract from a proprietary yeast strain, whose key intellectual property is upheld by a complex manufacturing system. Imprime PGG, the company claims, can prime the body’s innate immune system to attack pathogens it normally would not.

Biothera carried out numerous single-arm oncology trials before embarking on a combination of Imprime PGG and Erbitux in NSCLC, a phase II randomised trial that demonstrated a significant increase in objective response rate – at least when assessed by the investigator, if not by independent central review.

But Erbitux was abandoned in lung cancer, making this setting a no-go. Undeterred, Biothera designed a similar trial with Avastin instead of Erbitux, and it was this open-label randomised study that the Esmo late-breaker highlighted.

In the 92-patient trial the addition of Imprime PGG to Avastin gave a 60.4% objective response rate versus 43.5% with Avastin and chemo alone. Although the study was 90% powered to detect an ORR improvement from 30% to 50% this result failed to hit statistical significance, but the 4.5-month survival increase in such a small trial was a “dramatic increase”, says Biothera’s chief medical officer, Ada Braun.

How it works

Imprime PGG is infused intravenously before the standard-of-care antibody is administered the same day, and the theory behind it is ingenious.

To destroy a pathogen, neutrophils need two triggers: so-called “complement” – soluble blood proteins – bound to the target cell, plus a beta-glucan. The trouble is that while beta-glucans are present in yeast – hence the swift natural eradication of fungal infections by the innate system – they are not found in cancer cells.

“Imprime PGG provides the missing beta-glucan moiety that the tumour cell lacks to enable it to be recognised by the innate system,” says Ms Braun. These beta-glucans bind to complement receptors on neutrophils, effectively priming them to attack tumour cells already coated in complement.

Mr Conners adds: “We’ve tricked neutrophils into now seeing a cancer cell as a fungal or yeast infection.”

In addition to the Erbitux and Avastin lung cancer studies, Biothera has undertaken a third randomised trial – a phase III open-label study called Primus, in 795 KRAS wild-type colorectal cancer patients. Mr Conners will not say which indication is the potential lead for Imprime PGG, but “multiple appropriate phase III studies” are planned.

“We are the only company that has an agent in phase III that works on the innate immune system,” says Ms Braun. Innate Pharma’s lead project, lirilumab, is an anti-KIR antibody that aims to activate natural killer cells in the innate immune system, but at present is in phase II.

A separate issue is Biothera’s functional foods business, through which the soluble beta-glucan is marketed as Wellmune WGP as a health supplement.

It is not clear how profitable this is, nor how it might fit into Biothera’s fund-raising plans; investors might, for instance, specifically want to fund the oncology applications, which they might see as a more lucrative, higher-margin opportunity.

A trade sale or IPO on the strength of oncology would get around any such issues and, Mr Conners says, “We are exploring options on the public markets.” Given the market cycle he probably needs to strike while the iron is hot.

Trial ID Trial name
NCT00874848 (Erbitux trial)
NCT00874107 (Avastin trial)
NCT01309126 Primus

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

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