Translate Bio CEO Ronald C. Renaud Jr.

Sanofi Pasteur will partner with Translate Bio to develop an mRNA vaccine for preventing COVID-19, the companies said today, through a partnership that builds on a nearly two-year-old collaboration to create mRNA vaccines.

The COVID-19 collaboration—whose value was not disclosed—is intended to combine vaccine expertise and external research networks of Sanofi Pasteur, Sanofi’s vaccines global business unit, with Translate Bio’s mRNA platform, which the companies will apply to discover, design, and manufacture SARS-CoV-2 vaccine candidates.

Translate Bio said it has begun to produce multiple mRNA constructs toward the vaccine, and has established 100 gram single-batch production with its clinical-stage mRNA therapeutics platform. The company is underway with its build-out of dedicated manufacturing space through a contract manufacturing partner to accommodate at least two 250 gram batches per month.

“Ideally, we’d like to get to one construct, but we’ll evaluate multiple constructs until we get to that point,” Translate Bio CEO Ronald C. Renaud Jr. told GEN. “We’d like to take all of these into animal testing as quickly as possible, and then make decisions on where we think the best approach is going forward.”

Sanofi and Translate anticipate getting into animal testing in a matter of weeks, Renaud said. “We have a goal to be in the clinic towards the end of this year, maybe the beginning of next year, but really driving toward the end of this year. That’s all going to be subject to discussions with regulatory authorities. But we’re moving absolutely as quickly as we can.”

Platform acquired from Shire

Through the proprietary MRT™ platform it acquired from Shire in 2017, Translate Bio creates mRNA that encodes functional proteins, and encapsulates the mRNA in a lipid nanoparticle (LNP). When that mRNA is delivered to the target cell, the cell’s own machinery recognizes it and translates it, restoring or augmenting protein function to treat or prevent disease.

“It’s very similar to the way you’d approach other infectious diseases: You take the instructions, if you will, the messenger RNA that would encode for the antigen—in this case, the coronavirus—and then let the body produce that antigen, and then have natural immunity take over,” Renaud said.

“That’s really the goal, and that’s part of the attractiveness of a messenger RNA platform. It’s not a cell-based or a tissue-based or a vector-based approach. This is an approach where you’re using the body’s own cellular machinery to produce the antigen.”

In the case of the COVID-19 partnership, Renaud said, “we will look at multiple constructs, but that will also probably mean multiple LNP candidates as well.”

The COVID-19 program is separate from the five infectious disease programs on which Sanofi and Translate Bio agreed to partner when they launched their up-to-$805 million-plus collaboration in June 2018. The companies have not disclosed the targets of the five infectious disease programs, which Sanofi controls.

“We’re going to continue to focus on those original targets, but also focus the strengths of the collaboration on COVID-19,” Renaud said.

The COVID-19 collaboration comes a day after Translate Bio said it anticipated delays in enrollment, dosing and follow-up in its ongoing Phase I/II clinical trial of its lead clinical program, the cystic fibrosis candidate MRT5005, because of how healthcare institutions have shifted their attention to responding to COVID-19. The company said it will announce “at a later date” when it plans to release an interim data readout of an additional single-ascending dose group and the multiple-ascending dose (MAD) portion of the trial.

Just two weeks ago on March 12, Translate Bio said it anticipated sharing those readouts in the third quarter.

Keeping programs “on track”

Renaud said Translate Bio continues to focus on MRT5005, as well as the Sanofi infectious disease programs, and discovery-phase evaluation of targets in additional pulmonary diseases using the company’s proprietary lung delivery platform.

“To the extent that we can do that in this new environment, where many of us are working from home and what-not, we are pulling out all the stops that we can to make sure everything stays on track,” Renaud said.

He said it’s too soon to say how much Translate Bio’s workforce, now approaching 100 employees, may grow as a result of the Sanofi COVID-19 partnership or other programs: “As things continue to move forward and move down development pathways, we’ll assess our headcount needs at that time and grow as needed.”

The work-from-home environment necessitated by authorities as they respond to the global COVID-19 pandemic hasn’t affected the pace of drug development so far within Translate Bio, Renaud said: “I wouldn’t say it’s slower or faster. It’s just different, in some cases, we’re doing things a little bit more quickly, and a little more effectively. And in some cases, without having everybody under one roof, it takes some time to schedule a meeting or get people online.

“We’re doing the best we can,” Renaud added. “In the lab, we continue to move things forward.”

Founded in 2011 as RaNa Therapeutics, Translate Bio was established with a focus on RNA therapeutics, initially based on an epigenetics-based platform developed by Jeannie T. Lee, MD, PhD, of Harvard Medical School and Massachusetts General Hospital—who won the 2016 Lurie Prize in Biomedical Sciences by the Foundation for the National Institutes of Health (FNIH) for her pioneering work.

In January 2017, RaNa announced that it acquired Shire’s MRT platform for an undisclosed price, and hired the Shire employees who had been working since 2008 on developing the mRNA platform and applying it to programs intended to treat cystic fibrosis and urea cycle disorders.

“In one way it was a building block on top of the RNA intellectual property that we had already been building as a result of the work we were doing at RaNa,” Renaud said in an interview with GEN last year. “But then having a true messenger RNA platform like what was being built inside of Shire took it way beyond the next level, to really putting us at the forefront of building messenger RNA as a therapeutic.”

Multiple COVID-19 efforts

The partnership with Translate Bio marks the latest of several Sanofi efforts to develop COVID-19 treatments, and the second that involves creating a vaccine.

On February 18, Sanofi Pasteur announced a vaccine collaboration with the Biomedical Advanced Research and Development Authority (BARDA) based on Sanofi’s recombinant DNA platform, designed to produce an exact genetic match to proteins found on the surface of the virus, and the company’s previous development work for a SARS vaccine.

Sanofi’s recombinant DNA technology is designed to produce an exact genetic match to proteins found on the surface of the virus. The DNA sequence encoding this antigen would be combined into the DNA of the baculovirus expression platform—the basis of Sanofi’s licensed recombinant influenza product—and used to rapidly produce large quantities of the coronavirus antigen which will be formulated to stimulate the immune system to protect against the virus.

Sanofi is also partnering with Regeneron Pharmaceuticals to develop a new COVID-19 indication for the companies’ marketed arthritis drug Kevzara® (sarilumab). On March 16, the companies said they launched a Phase II/Phase III clinical trial program in the U.S. evaluating Kevzara as a treatment for severe COVID-19 coronavirus infection in up to 400 patients.

The primary Phase II endpoint is reduction of fever and the secondary endpoint is decreased need for supplemental oxygen. Phase III will evaluate improvement in longer-term outcomes including preventing death and reducing the need for mechanical ventilation, supplemental oxygen and/or hospitalization. Regeneron will lead clinical studies in the U.S., while Sanofi will do so overseas.

Kevzara is an interleukin-6 (IL-6) receptor antagonist approved by the FDA in 2017 to treat adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs. Regeneron and Sanofi reason that IL-6 may play a role in driving the overactive inflammatory response in the lungs of patients who are severely or critically ill with COVID-19.

Sanofi’s collaborations with BARDA and Regeneron are two of 60 COVID-19 development programs that were highlighted in a GEN A-List published earlier this month. That list will be updated soon with additional treatments.

“We are committed to leveraging different ways to address the COVID-19 public health crisis by testing treatments, as well as two vaccines using different platforms. We believe the more approaches we explore, the better our likelihood of success in achieving this goal,” stated David Loew, Global Head of Vaccines at Sanofi. “Having sufficient installed capacity will be key to satisfy the strong demand for vaccines we will probably see, and based on the experience we’ve had under the collaboration to date, we believe the Translate Bio mRNA platform could help us meet that need.”

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