Candidate: MRT5500

Type: mRNA vaccine based on Translate Bio’s proprietary MRT™ platform it acquired from Shire in 2017.

2021 Status: Announcing first-quarter results on April 28, Sanofi re-stated that results from the Phase I/II trial of MRT5500 are expected in the third quarter–while adding that the company has begun preclinical studies to evaluate additional mRNA candidates against emerging SARS-CoV-2 variants.

Sanofi Chief Financial Officer Jean-Baptiste de Chatillon acknowledged to analysts that MRT5500 and another Sanofi COVID-19 vaccine candidate, the adjuvanted recombinant protein-based SP0253, were “quite behind” in development, but added: “With the evolution of the pandemic, they could find a place.”

Sanofi and Translate Bio said March 12 that they had launched their Phase I/II trial for MRT5500. The randomized, double blind, and placebo-controlled trial is designed to evaluate the vaccine candidate’s safety, tolerability, and immune response. The companies expect interim results from the trial in the third quarter.

A total of 415 healthy adults 18 years of age and older are expected to be enrolled in the trial across 13 investigational sites. Clinical trial participants will receive one dose of MRT5500, or two doses 21 days apart. Three different dose levels will be investigated (15µg, 45µg or 135µg).

A joint development team is working to improve the temperature stability of the mRNA vaccine candidate by targeting a -20°C storage temperature for late-stage clinical trials and at launch. Efforts are also underway to enable the product to be stable at routine refrigerator temperature (2-8°C), Sanofi and Translate Bio said.

Preclinical studies will continue over the next several months to evaluate whether MRT5500, as well as additional mRNA vaccine candidates, will induce neutralizing antibodies against the emerging SARS-CoV-2 variants.

2020 Status: Sanofi and Translate Bio said October 15 that MRT5500 induced potent neutralizing antibodies against SARS-CoV-2 in preclinical studies whose results were detailed in a preprint posted on bioRxiv. MRT5500 was shown to induce dose-dependent levels of binding antibodies and neutralizing antibodies specific to the SARS-CoV-2 spike protein in mice that received dose levels of 0.2, 1, 5 and 10 µg per dose using a two-dose vaccination schedule, administered three weeks apart.

According to the companies, 100% seroconversion was seen at all dose levels after one administration, with a further increase in titers was observed following a second administration. Across all dose levels, neutralizing antibody titers were seen in mice that received the two-dose regimen. In the 5 µg and 10 µg dose groups, titers were detected after one administration of MRT5500 and were more pronounced after the second administration.

In non-human primates, a majority developed neutralizing antibodies reactive to the SARS-CoV-2 spike protein in NHPs after the first dose at levels of 15, 45 and 135 µg per dose under a two-administration vaccination schedule, three weeks apart. Potency of MRT5500 was assessed via pseudovirus neutralization and micro-neutralization. Antibody titers were further enhanced after a second administration with 100% of NHPs reaching levels significantly higher than those from human convalescent sera by day 35.

A Phase I/II clinical trial of MRT5500 is expected to begin in the fourth quarter of 2020, Sanofi and Translate Bio said.

In June, Sanofi and Translate Bio said they expanded their two-year-old collaboration to develop mRNA vaccines for infectious diseases, with the phama giant nearly tripling to more than $2.3 billion its potential payout to Translate Bio, and the companies increasing from five to seven the maximum number they plan to develop under that partnership.

The additional vaccines will consist of candidates against COVID-19 and influenza. Sanofi and Translate Bio said their COVID-19 collaboration, which began in March, has progressed to evaluating multiple vaccine candidates in vivo for immunogenicity and neutralizing antibody activity, with the goal of supporting the selection of a lead candidate.

“We have more than one RNA construct,” Translate Bio CEO Ronald C. Renaud Jr. told GEN in May in an interview about the company’s progress in developing a COVID-19 vaccine candidate. “Our lead one is, it should be no surprise, it’s the prefusion Spike glycoprotein. That’s what we’re focused on as our lead program, but it’s safe to say that we’re also looking at additional constructs that address some interesting epitopes.

The companies aim to launch a first-in-human clinical trial of the COVID-19 vaccine in the fourth quarter.

Under their expanded agreement, Sanofi agreed to pay Translate Bio a total $425 million upfront, consisting of $300 million cash and a private placement common stock investment of $125 million based on a share price of $25.59, representing a 50% premium to the 20-day moving average share price prior to signing. Sanofi also agreed to pay Translate Bio up to $1.94 billion in payments tied to achieving development, regulatory, manufacturing, and commercialization milestones—including $450 million that Sanofi agreed to pay when the companies launched their up-to-$805 million-plus collaboration in June 2018.

The potential milestones and other payments including approximately $360 million that Translate Bio anticipates receiving over the length of the agreement, inclusive of COVID-19 vaccine development milestones.

Investors signaled approval of the expanded partnership with a stock buying surge that shares of Translate Bio up 47% to $23.87 per share as of the close of trading 4 p.m., from $16.24 on June 22.

Sanofi CEO Paul Hudson told analysts on the company’s quarterly conference call April 24 that the companies are targeting Q4 2020 for the start of initial clinical studies, aiming for approval in late 2021: “We’re scaling up from a current capacity up to 360 million doses by H1 2021.” That scale-up, Hudson said, will entail going from 100 gram single-batch production with its clinical-stage mRNA therapeutics platform to 250 gram batches, “and it is assumed that towards the end of the year, beginning of the year, we go kilogram batches. And that would allow us to significantly upscale to hundreds of millions of doses.”

Investors responded with a buying surge that sent Translate Bio’s shares surging 41% over two trading days, to $14.52 on April 27 from $10.31 on April 23.

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.

 


COVID-19: 300 Candidates and Counting

To navigate through the >300 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:

FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.

DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data.

KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.

TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.

GEN has also tagged the most common treatment types:

● ANTIVIRAL
● VAX
● ANTIBODY
● RNA