Antibodies have transformed the treatment landscape in many diseases, but are time-consuming and expensive to make. "Producing them is a complete pain in the butt," nclick="getInfo('15080'); return false;">Biontech’s chief operating officer, Sean Marett, tells EP Vantage.
The German company believes it has got around the manufacturing issues by developing an mRNA product that stimulates the liver to make its own therapeutic antibodies. It has so far only proven the approach in mice – in a study published today in Nature Medicine – but if it works in humans it could rival traditional production methods, Mr Marett believes.
Of course, nclick="getInfo('15080'); return false;">Biontech still has a long way to go and will now need to take its so-called RiboMABs into the clinic. It is "too early to say" what target or targets the group will evaluate in its first human trials, but Mr Marett highlights claudin-18.2, which featured in the mouse study, as a "promising target". The protein is frequently overexpressed in gastrointestinal and pancreatic tumours.
Other groups are looking at claudin-18.2, including nclick="storyWordlink('Astellas'); return false;">Astellas, which has a phase II monoclonal antibody, nclick="storyWordlink('IMAB362'); return false;">IMAB362, obtained through last year’s purchase of Ganymed. "That gives us some confidence in that this is perceived as a good commercial target," Mr Marett says.
Claudin-6, also used in the mouse study, is another "highly relevant" target, he adds. Again, nclick="storyWordlink('Astellas'); return false;">Astellas is active here, with nclick="storyWordlink('IMAB027'); return false;">IMAB027 in phase II development for ovarian cancer.
Bispecific
But rather than using its mRNA technology to induce patients to produce a MAb, nclick="getInfo('15080'); return false;">Biontechsought to produce bispecific antibodies. In the mouse study these were directed against CD3, a protein present on effector T cells, plus one of three tumour-associated antigens: claudin-6, claudin-18.2 or nclick="storyWordlink('EpCAM'); return false;">EpCAM.
The idea behind this nclick="storyWordlink('"bispecific antibody"'); return false;">bispecific antibody approach – also employed by nclick="getInfo('1006'); return false;">Amgen’s nclick="storyWordlink('Blincyto'); return false;">Blincyto, though this is manufactured in the traditional manner – is to bring T cells into contact with tumour cells, triggering tumour cell destruction.
The early signs suggest that nclick="getInfo('15080'); return false;">Biontech’s project works, at least in mice. "We’ve demonstrated not only that we get what we expect, bispecific antibodies, but also that they had a therapeutic effect on the tumour," Mr Marett says.
In the study, mRNA encoding the bispecific antibodies was delivered intravenously in a nanoparticle lipid formulation. According to Mr Marett, nclick="getInfo...
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