It felt natural for Alain Maiore and Sebastian Amigorena to bring in Michel Sadelain as a co-founder of Mnemo Therapeutics. A CAR-T pioneer, Sadelain had been involved as an advisor since the early days — enthusiastic about Amigorena’s work in a genetic knockout that could enhance T cell memory and a new class of potential targets he’s discovered — and could introduce some well-known technologies to the toolbox. So they got the initial cash from Sofinnova Partners to plant roots in Paris and New York in early 2019; within a few months, they began to see more clearly just what the antigen discovery platform might unlock.
“Then Michel said there’s something I haven’t told you guys,” Maiore, a serial entrepreneur and former VC, recalled.
The star Memorial Sloan Kettering researcher and Juno co-founder, as it turned out, had been working on a booster strategy for CAR-T cells — a secretive technology that Mnemo managed to wrangle an exclusive license for. From there, they went on to recruit Isabelle Rivière, MSK’s cell therapy manufacturing lead, and Justin Eyquem, Sadelain’s former postdoc, on board.
The result is a company that houses a range of T cell engineering technologies, including the Suv39h1 knockout that Amigorena was initially working on, in addition to a target identification engine and a plan to keep CMC manufacturing in-house from early-stage research all the way through commercialization. And it’s now got $90 million (€75 million) to kick off a two-year march toward the clinic.
“I would say each one of these technologies could technically be an independent company,” said CSO François Gaudet. “Some of them I think have the chance to be transformational technologies. But when you mix them together, you can get even more.”
Testing these tools one by one and teasing out how they add to or complement each other is crucial considering Mnemo’s ultimate goal. The issues with the first generation of CAR-Ts are well documented: They only work for liquid tumors but not solid ones, the manufacturing process is expensive and cumbersome, and new safety concerns are already emerging.
But instead of standing by one approach, the biotech wants to stay agnostic about the modality and be ready to lend a critical hand wherever the breakthroughs come. No single holy grail will fix all the problems, Maiore suggested. Depending on the patient profile and indication, autologous, allogeneic and in vivo cell therapies could all have their place.
That’s why the CEO is fairly certain Mnemo will conduct its first clinical trial in solid tumors with an autologous CAR-T directed at a known target, while starting off the hematologic work with an allogeneic construct. Every six months, they will review the data and prepare to reprioritize the portfolio based on the results.
“The only way to select your target is to try it,” he said. “And so we want to be in a position to try as many targets as possible, so that eventually we are able to pick the best one to get into the clinic.”
And they are certain they will have their hands full with epigenetic antigens, or E-antigens, which are not your classical neoantigens, Maiore noted, but complexes or proteins that arise from dysregulation in epigenetic mechanisms, resulting in the translation of elements that shouldn’t be translated in normal cells. Not only are they immunogenic, Amigorena’s team at the Institut Curie found these antigens were also recurrent and highly specific to cancer.
It all makes for a coveted headstart in one of the most-watched races across biopharma, as investors lavish on a diverse suite of ways to tinker immune cells such that they can unleash an attack on cancer. Casdin Capital joined Sofinnova in leading the round; Redmile, Emerson Collective and Alexandria Venture Investments chipped in.
Yet the 28-strong team at Mnemo is also well aware of the challenges that remain.
Most recently, Carl June, Oz Azam and their team at Tmunity sounded the alarm on lethal cases of neurotoxicity that derailed their clinical trial for a prostate cancer CAR-T — a move Maiore said the field should be “grateful” for.
He is convinced there will be solutions. Mnemo’s answer to those safety questions will be a mix of animal models that are ultra sensitive to toxicity, more conservative clinical designs and technological tweaks.
“We are doing a lot of thinking and we’ve been quiet since day 1 because we really wanted to think this through,” he said. “And looking forward, we will let the science do the talking.”