Interview – BioNTech spreads bets in cancer immunotherapy

Some biotechs could be accused of putting all their eggs in one basket, but this is not a charge that can be levelled at BioNTech. The privately held German company has six subsidiaries, with a mix of lower-margin businesses that are bringing it some early cash, and high-risk, high-reward contenders further down the road. The latter group includes candidates, albeit very early stage, in the hot emerging areas of messenger RNA and immunotherapy.

“We have three revenue and profit streams now: diagnostics, peptides, and GMP manufacturing,” Sean Marett, chief operating officer, tells EP Vantage. On the diagnostic side, BioNTech recently launched its MammaTyper molecular test, which analyses tumour tissue to stratify breast cancer patients. More interesting, however, is its lead therapeutic programme, an mRNA vaccine currently in phase I studies in melanoma.

But the company’s diagnostic capabilities are the key to its success, Mr Marett insists, as they allow it to produce a personalised mRNA product. This is where BioNTech differs from other contenders in the space like Moderna Therapeutics and CureVac, the executive says.

“For every patient, we sequence each patient’s tumour and identify mutated antigens, and select a certain number of mutated antigens to then manufacture for that patient,” he explains. Once delivered, it is hoped that the mRNA will prime the patient’s own immune system to attack the cancer. BioNTech has proven that the concept works in mice in a study published in Nature in April.

Mr Marett concedes that this personalised approach could make its mRNA product very expensive – but adds that manufacturing costs are something BioNTech is working on. He did not say what price the company is targeting, but believes reducing costs to a reasonable level is “highly achievable”.

Modified mRNA

mRNA’s instability has made delivery problematic in the past, but BioNTech claims to have got around this by making “a number of modifications to the mRNA construct that allow, first of all, a much greater stability to the mRNA and, secondly, a greater expression once it’s in the target cell,” the COO says. In this regard it might fall foul of Moderna, which makes the bold claim of holding the patents for any mRNA modifications.

Notwithstanding these potential issues, delivery itself, to the dendritic cells in the lymph nodes, is “pretty simple,” according to Mr Marett – the lymph nodes are located using ultrasound and the mRNA injected directly under local anaesthetic. “The dendritic cells take the mRNA up within two minutes and then it’s expressed and processed naturally.”

BioNTech is testing both naked mRNA and mRNA delivered in a proprietary lipid nanoparticle formulation in humans. “It’s just a question of which one will drive efficacy the furthest,” says Mr Marett. “We’re exploring both at the moment to see which we will take forward.”

As for why the company is targeting melanoma initially, “it’s a useful model for demonstrating immunogenicity very quickly. If you see effects in melanoma, you know that you are having an immunological effect”. But while it could give BioNTech proof of concept, it is also a legitimate target in its own right, he adds, with an unmet need. Mr Marett points out that while melanoma is a competitive market, new PD-1/PD-L1 inhibitors only produce a response rate of 10-20%.

BioNTech has also just started a phase I study using a systemic application of its mRNA vaccine in triple-negative breast cancer.

Immunotherapies

Earlier in development, the company has preclinical immunotherapy programmes using both engineered T cell receptors (TCRs) and chimaeric antigen receptors (CARs). In the former, it has signed up Eli Lilly, but further details are scant – Mr Marett did not disclose what tumour antigens or even which cancers the companies are targeting (Better late than never: Lilly joins immuno-oncology chase, May 12, 2015).

In CAR-T, he did say that BioNTech would probably be looking at ovarian cancer, but was similarly reticent to divulge more information. The company is not looking for partners in this area until it has progressed to a later stage of development.

In yet another shot on goal, BioNTech is also working with Genmab on bispecific immunostimulatory antibodies, in a deal signed in May worth $10m up front. The company, which has seen substantial private investment to date from among others the Strüngemann brothers and MIG fund, is clearly raising its profile in the sector – possibly ahead of an IPO. Mr Marett admits that the company will need to raise more funds at some point, but did not say if it has plans to go public soon. 

The issue for the German company is not, therefore, finding new candidates – but rather staying focused enough to get one or more of them to market.

To contact the writer of this story email Madeleine Armstrong in London at [email protected] or follow @medtech_ma on Twitter