Translate Bio Announces Publication of Preclinical Results of COVID-19 mRNA Vaccine Candidate MRT5500 in npj Vaccines
-- Multiple antigen constructs, including the construct used in MRT5500, induced potent neutralizing antibodies against SARS-CoV-2 in preclinical studies in multiple species --
-- Efficacy demonstrated in Syrian Golden Hamster challenge model under single and two-dose vaccination regimens of MRT5500 --
-- MRT5500 developed under a collaboration agreement with
The publication outlines the main findings of the preclinical studies as follows:
Intracellular trafficking of mRNA-encoded target antigens demonstrated mutation dependence within the spike glycoprotein.
- Various constructs were evaluated across a number of studies to select a lead candidate including evaluation of expression and intracellular trafficking in vitro, as well as immunogenicity in mice and non-human primates (NHPs). The data demonstrated intracellular trafficking is construct dependent with unique trafficking observed when the expressed antigen contains furin-cleavage site mutations. These mutations can help define immunogenic responses as determined in both mouse and non-human primate studies measuring neutralizing antibody titers against SARS-CoV-2.
- In mice, MRT5500 (0.2, 1, 5 and 10 µg) induced dose-dependent binding antibodies and neutralizing antibodies specific to the SARS-CoV-2 spike (S) glycoprotein; neutralizing antibody titers were detected after one dose of MRT5500 in higher dose groups (5 µg, 10 µg), and were enhanced after a second dose at day 21.
- In NHPs, MRT5500 (15, 45 and 135 µg) induced antibodies reactive to recombinant S [protein] in nearly all NHPs; neutralizing antibody titers were detected after one dose of MRT5500 and were enhanced after a second dose at day 35. In NHPs, neutralizing antibody titers reached levels higher than those from human convalescent sera.
MRT5500 demonstrated protection against viral infection and disease progression.
- Syrian golden hamsters were immunized with MRT5500 (0.15, 1.5, 4.5 and 13.5 µg dose levels) with either a single immunization, or two administrations 21 days apart. MRT5500 demonstrated the ability to induce both humoral and cell-mediated antiviral responses and confer protection against a virus challenge in hamsters with all dose regimens, except the single 0.15 µg dose. Vaccination further resulted in protection from lung pathology and clearance of virus from the lungs as determined through viral subgenomic RNA measurements, thus supporting the further development of MRT5500 as a clinical candidate.
Data from MRT5500 indicated a low risk of vaccine-associated enhanced respiratory disease.
- Immunization with MRT5500 induced TH1-biased responses in both mice and NHPs.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include, but are not limited to, those regarding: the plans to report interim results from the Phase 1/2 clinical trial of MRT5500 in the third quarter of 2021; the potential ability of MRT5500 to elicit a robust immune response; the potential for MRT5500 to be a promising COVID-19 vaccine candidate and play a role in protecting people against COVID-19; the expected benefits of Translate Bio’s collaboration with Sanofi; Translate Bio’s beliefs regarding the broad applicability of its technology; and Translate Bio’s plans, strategies and prospects for its business, including its lead development programs and continued development of mRNA vaccines for the treatment of infectious diseases. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “forward,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from current expectations and beliefs, including but not limited to: the current and potential future impacts of the COVID-19 pandemic on Translate Bio’s business, financial condition, operations and liquidity; Translate Bio’s ability to advance the development of its platform and programs, including without limitation its vaccine development program generally and MRT5500 specifically, under the timelines it projects, demonstrate the requisite safety and efficacy of its product candidates and replicate in clinical trials any positive findings from preclinical studies; the successful advancement of the collaboration agreement between
Source: Translate Bio, Inc.