DUBLIN – Sanofi SA is investing €80 million (US$90.8 million) in Biontech AG as part of an extension of an existing alliance to develop synthetic mRNA-based cancer immunotherapies. Mainz, Germany-based Biontech will spend that cash – and a lot more besides – on a shared clinical development program, having exercised an option to co-develop with Paris-based Sanofi the lead candidate therapy from the five-product deal.
"We wanted a little bit of the action from the co-development arena," Biontech's chief operating officer, Sean Marett, told BioWorld.
The as-yet-unnamed therapeutic is currently entering a phase I trial in patients with solid tumors.
It comprises a mix of synthetic mRNA molecules that collectively encode a cocktail of pro-inflammatory cytokines. It will be injected directly into patients' tumors in order to elicit a memory T-cell response that will, the partners hope, enable patients' immune systems to mount a sustained response against both local and distal tumors. "The tumor will be expressing the cytokines encoded by the mRNA," Marett said. "The idea is to get the tumor to do the heavy lifting."
The companies are not disclosing the identity of the cytokines employed in the therapeutic at this point. "We did a lot of work optimizing which cytokines to put into the mixture," Marett said. How they work in concert is not completely understood. "I don't think we can say definitively we optimize based on synergy. We optimize based on effect," he said.
The original alliance between Sanofi and Biontech, which entailed $60 million in up-front and near-term payments, as well as up to $300 million in per-product milestones, dates back to 2015. It is one of a clutch of significant programs entering the clinic in the coming year, including Biontech's first CAR T therapy, which is in development for solid tumor applications. The company is not yet disclosing the target involved. "It's one of our proprietary antigens," Marett said.
Also on the starting grid is an immuno-oncology program emerging from its alliance with Copenhagen, Denmark-based Genmab A/S to develop bispecific Duobody antibodies against antigens selected by Biontech. "We're expecting the fruits of that to go into the clinic this year as well," Marett said. It could, he added, represent a new mode of action in immune checkpoint modulation.
Sanofi is the second big pharma company to invest in Biontech, following Pfizer Inc.'s acquisition of equity as part of a $120 million initial down payment on an mRNA-based vaccine against influenza virus. That deal has a further $305 million attached in milestone payments. (See BioWorld, Aug. 17, 2018.)
More fundraising ahead
Given Biontech's large appetite for cash, another more substantial fundraising is still on the cards. "Inevitably, one option is to look at financing through more traditional routes," Marett said. "We can look at whether to do another private round or whether to do an IPO."
The company, which disclosed a $270 million crossover round 12 months ago, has raised north of $1.15 billion in either equity investment or payments from partners. But with about 1,000 staffers – it claims to be Europe's largest privately held biopharma firm – and extensive development and co-development commitments, its carrying costs are high.
Its most obvious peer, Cambridge, Mass.-based Moderna Inc., raised $604 million in December, in Nasdaq's largest-ever biotech IPO. It has in total raised more than $3.2 billion in equity finance and payments from partners. Another mRNA contender that looms large is Tübingen, Germany-based Curevac AG, which has raised $420 million in equity finance since its formation in 2000. Curevac hit the skids two years ago, when a prostate cancer vaccine failed to deliver in a phase IIb trial. The key issues facing all developers of mRNA-based vaccines and therapeutics include stability, efficient delivery across the plasma membrane, and avoidance of unwanted immune effects. All of those parameters have to be successfully managed before any therapeutic strategy can be assessed in terms of efficacy.
The next 12 to 18 months will have a significant bearing on Biontech's prospects, as several key clinical trials start to deliver efficacy data. Those include a phase I study in melanoma of Lipo-Merit, a tetravalent cancer vaccine based on its Fixvac technology, which comprises a combination of mRNAs designed to elicit immune responses against shared tumor antigens. Also in the mix is a trial of a dual vaccination strategy in triple-negative breast cancer, which targets both shared antigens that are commonly expressed across the general patient population and antigens that are unique to each individual patient. An extensive study of RO-719847, a personalized cancer vaccine targeting patients' individual neoepitopes, which it is developing with the Genentech arm of Basel, Switzerland-based Roche Holding AG, is due to read out in 2020.