The mRNA developer Moderna Therapeutics’ huge success at raising money has yet to be matched by similar victories in the clinic. While its chief executive, Stéphane Bancel, admits that progress has been slower than some had hoped, he maintains that the company is still on track. “We wanted to do it right and safely. We tried to not rush,” he tells EP Vantage.
The group has also not been rushed into going public, a highly anticipated move given its $5bn valuation. Moderna needs more data, Mr Bancel concedes, but this could be coming soon. “When we have rare disease data in humans is when we go out.” Its lead rare disease candidate, mRNA-3704, is set to enter the clinic in 2018, so results, and therefore an IPO, could realistically be a couple of years away.
Meanwhile, impatient investors might be somewhat reassured by a new deal with Astrazeneca – Moderna’s third with the big pharma, covering a heart failure candidate encoding relaxin.
The deal is structured differently from most early-stage agreements, in which the smaller partner usually receives “a bit of cash up front and then a 10% royalty or whatever”, Mr Bancel says. “Astra is going to pay for phase I and II, and then it’s a 50:50 profit share. We prefer these kinds of deals. We’re not looking for short-term cash, seeing as we still have a billion on the balance sheet – we’re shooting for long-term value.”
However, like much of the group’s pipeline the molecule concerned is still early stage: it is not expected to go into human trials until 2019.
And there is another reason to be cautious. Targeting relaxin has not gone smoothly, Novartis’s serelaxin being a notable phase III failure this year (Serelaxin setback puts focus on Entresto, March 22, 2017).
Moderna believes that its new candidate, AZD7970, might have advantages over serelaxin. Firstly, the former could be more convenient as it is delivered via a five-minute bolus injection, versus a 48-hour IV infusion for serelaxin. Secondly, AZD7970 leads to an extended period of protein expression, contrasting with what Moderna believes is "the very short half-life of the native relaxin-2 peptide”. It will be a while before these claims are put to the test.
The companies plan to dose AZD7970 once monthly – the project employs Moderna’s new N2GL delivery formulation, developed in-house, which is designed to allow repeated administration of mRNA-based therapies.
This could be a big step forward for Moderna. Its previous delivery technology had a long half-life and did not allow for repeat dosing, because of tissue accumulation.
N2GL is cleared from tissue more quickly so could be safer for the repeat dosing necessary to get into rare diseases, something the company has made much of in the past.
It has not all been plain sailing. In July Alexion returned rights to a rare disease pipeline comprising 10 projects, including a candidate for Crigler-Najjar syndrome type 1 (CN1). This disease is still an area of interest, Moderna says, but MMA is now the priority.
Meanwhile other projects previously covered by the Alexion tie-up could be accelerated. “We’re kind of reshuffling the whole deck of cards to reprioritise,” says Mr Bancel. “Some of the things they owned via the deal we think are more exciting than the things we were working on.”
The number-one priority for Moderna over the next 12-18 months is rare diseases in the liver, he adds. “What you’re going to see next year is massive expansion of the pipeline – we have half a dozen projects we’re working on right now.”
Show us the data
This is all well and good, but one criticism of Moderna is that data are thin on the ground – and September’s pipeline update did little to address this.
The group’s most advanced candidate – under another deal with Astra – is mRNA AZD-8601, a cardiovascular disease project encoding VEGF-A, which is set to go into phase II after what the companies deemed a phase I success. But the groups came under fire for not releasing details of how much VEGF-A protein was produced in the study.
Mr Bancel says that he cannot give more information, as the companies are “trying to protect a good publication in a good journal”, but he adds: “It worked beautifully.”
Another question mark over Moderna is its company culture. When asked about reports of staff retention issues, Mr Bancel says: “It’s not made for everybody – it’s a mission-driven company, a pretty intense place; we expect people to do great science.”
Scientific success will be vital if Moderna is to transfer its private valuation onto the public markets. Mr Bancel insists that by not floating too early – like some of the Crispr companies, for example – Moderna has been able to invest properly in its platform and pipeline.
But he concedes: “I cannot try to convince people it’s going to work until I have data.” Promises have got Moderna this far – it will need solid evidence to get to the next stage.