BriLife (IIBR-100) Vaccine Description
The Brilife (IIBR-100) viral vector vaccine candidate contains a recombinant vesicular stomatitis virus (VSV), an animal virus that does not cause disease in humans. Brilife (VSV ΔG) takes the VSV and genetically engineers it to express the spike protein of the SARS-CoV-2 betacoronavirus on its envelope.
In addition, the spike protein was replaced with that of SARS-CoV-2, resulting in rapid and potent induction of neutralizing antibodies against the SARS-CoV-2 coronavirus. BriLife presents the entire spike protein complex of the coronavirus to the body's immune system and can simultaneously present multiple variants of the spike protein. The human body recognizes the spike protein expressed on the envelope and develops an immunological response.
The Brilife vaccine differs from other COVID-19 vaccines by presenting the entire COVID-19 spike protein to the body's immune system. In addition, it is a self-propagating, live-virus vaccine that may be updated to address new variants of COVID-19 more rapidly than some other vaccine platforms.
Israel completed the vaccination of 240 patients in a phase 2/3 clinical trial on November 16, 2021. The immunologic response was such that vaccinated patients were given "green passports" and were not required to be immunized with mRNA vaccines. Serologic testing of a sample of those patients demonstrated neutralizing antibody levels against the Delta variant comparable to those generated against the wild-type virus. Hungary will be the first European Nation to host a clinical trial site for the registrational phase 2b/3 trial of the BriLife COVID-19 vaccine.
In its collaboration with NRx, the Israel Institute for Biological Research (IIBR) confirmed it would provide technical assistance while receiving customary royalty and milestone payments for its intellectual property. In addition, NRx has committed to supplying all required doses of the vaccine for the population of Israel.
NRx (Nasdaq: NRXP) draws upon more than 300 years of collective, scientific, and drug-development experience to bring improved health to patients. The NRx board of directors includes Dr. Sherry Glied, former US Assistant Secretary for Health, Daniel E. Troy, JD, former Chief Counsel of the US FDA, Chaim Hurvitz, former director of Teva and President of the Teva International Group, and General H.R. McMaster, Ph.D., the 26th United States National Security Advisor.
BriLife (IIBR-100) Vaccine History
NRx was awarded worldwide development and commercialization rights to Israel's BriLife™ vaccine by Israel's Ministry of Defense on behalf of the Israel Institute for Biological Research. NRx established a subsidiary company at the invitation of the Luxembourg Ministry of Economy and has initiated the manufacturing scale-up process for the BriLife vaccine in partnership with a contract manufacturing partner in the Brussels region. The Company aims to manufacture the first GMP batch of BriLife at a million-dose scale by June 2022.
The Israel Institute for Biological research (IIBR) was established in 1952 as a governmental research institute founded by scientists from the IDF Science Corps and academic organizations under Isreal's Prime Minister's Office. IIBR is located in the city of Ness Ziona, Israel.
BriLife (IIBR-100) Vaccine Cell Line
BriLife (IIBR-100) Vaccine uses the following cell lines: Design and Development of BriLife (IIBR-100): BHK hamster cells, Vero monkey cells; Production: Vero Monkey Cells; Confirmatory Lab Tests: Plaque reduction; immunofluorescence, Vero monkey cells.
BriLife (IIBR-100) Vaccine Indication
Brilife (IIBR-100) is indicated to prevent COVID-19 infection with the new coronavirus known as SARS-CoV-2. However, no pediatric, oncology or pregnancy vaccine efficacy has been disclosed. Moreover, the vaccine has been demonstrated to evolve in the same manner as the SARS-CoV-2 virus evolves, thus potentially generating immunity against future variants.
BriLife (IIBR-100) Vaccine Dosage
The Company reported in the third quarter of 2021, Israel completed the vaccination of 240 patients at the final strength of 10 per dose. Israeli media reported that local health authorities notified participants in the BriLife vaccine trial who received the highest dose vaccine and did not need a third booster dose. Their protection remained high six months after getting a second dose. Participants who received lower doses of the BriLife vaccine have been advised to get a booster vaccination with Pfizer or Moderna shots, as those lower dosages do not appear to offer sufficient long-term protection.
NanoPass MicronJet™ Intradermal Injection System
The Israel Ministry of Health recently approved a study investigating the NanoPass MicronJet™ intradermal injection system for the BriLife vaccine. The NanoPass system, invented in Israel, uses a patented microneedle system to deliver the vaccine into the skin with minimal discomfort. This approach is especially promising for the BriLife vaccine because it binds to angiotensin-converting enzyme two receptors, which are present in significantly larger quantities in human skin cells than in muscle cells where traditional vaccines are injected. In addition, early data with other vaccines suggests that intradermal delivery of BriLife may result in a more robust immune response at substantially lower vaccine dosing.
January 14, 2022 - During the 2022 H.C. Wainwright BioConnect Virtual Conference, NRx identified the plans to move forward with a clinical trial of the BriLife investigational vaccine for COVID-19 as a heterologous booster for those already vaccinated with mRNA vaccines. There is reason to believe that a viral vector vaccine that binds to cells that express angiotensin-converting enzyme 2 receptors, such as the BriLife investigational vaccine, has the potential to create true mucosal immunity and provide a different type of immunity than the mRNA vaccines.
December 15, 2021 - NRx Pharmaceuticals announced that Nasdaq had added the Company to the Nasdaq Biotechnology Index effective December 20, 2021.
November 16, 2021 - NRx Pharmaceuticals announced a Net loss for the three months ended September 30, 2021, was $20.8 million, or $0.40 per share. And NRx confirmed it is in discussions with BNP Paribas Luxembourg, led by the bank's Head of Global Trade Solutions, to establish a € 150 million financing arrangement to support the BriLife vaccine.
August 24, 2021 - NRx Pharmaceuticals (Nasdaq: NRXP) announced it had completed its previously announced private placement. The gross proceeds from the private placement were $30 million before deducting placement agent fees and other offering expenses.
BriLife (IIBR-100) Vaccine News
January 11, 2022 - NRx Pharmaceuticals confirmed the Israel Ministry of Health has approved the first-in-human trial of intradermal BriLife vaccination with the objective of enhancing immune response. And based on the preliminary findings, NRx is designing a phase 2b/3 study of the BriLife vaccine as a booster to protect against COVID-19 variants of concern including the Omicron variant. Patients in the study in Israel and elsewhere will be fully vaccinated with mRNA vaccines.
December 9, 2021 - The Company announced Hungary would be the first European Nation to host a clinical trial site for the registrational phase 2b/3 clinical trial of the BriLife COVID-19 vaccine. In addition, NRx has been invited to submit a pediatric trial protocol that may include both injected and nasal spray administration of the vaccine. Regulatory clearance for the BriLife trial is expected by the end of 2021.
December 6, 2021 - NRx Pharmaceuticals was advised that the independent Data Safety Monitoring Board overseeing the phase 2 trial of the viral vector BriLife vaccine has concluded its safety analysis. A formal report is expected in the coming days. Based on the input received, NRx is proceeding with its plans to initiate a phase 2b/3 registration trial of BriLife. The BriLife 002 phase 2b/3 trial is expected to commence in Israel and the Nation of Georgia, with European and North American countries to be added once the initial phase 2b volunteers have been vaccinated.
November 29, 2021 - The JPost reported Israel's Institute for Biological Research is examining the SARS-CoV-2 Omicron virus variant in its national safety laboratories at the request of the Health Ministry.
November 26, 2021 - NRx Pharmaceuticals today notes' blood (Sera) from an initial sample of eleven phase 2/3 clinical trial participants demonstrated effective neutralizing antibodies against the original "wild-type" coronavirus and was tested for antibodies to the Delta variant. Of the eleven tested samples, ten neutralized the Delta variant.
November 24, 2021 - A non-peer-reviewed study concluded: We show that sera from BriLife® vaccinees maintain neutralization capacity against alpha, beta, gamma, and delta SARS-CoV-2 variants.
November 16, 2021 - The Company confirmed Israel completed the vaccination of 240 patients with the BriLife vaccine at the ten-dose level. The immunologic response was such that vaccinated patients were given "green passports" and were not required to be vaccinated with mRNA vaccines. In addition, serologic testing of a sample of those patients demonstrated neutralizing antibody levels against the Delta variant comparable to the neutralizing antibody levels generated against the wild-type virus. And NRx obtained advice from the WHO, and the EMA in designing a Phase 2b/3 registration trial targeted to commence in December 2021.
November 14, 2021 - Research conducted by the Israel Institute of Biological Research has shown that the Brilife vaccine is effective against the SARS-CoV-2 coronavirus Delta variant, The Jerusalem Post has confirmed.
November 5, 2021 - NRx agreed to a tech transfer and scale-up contract with an advanced viral vector, contract research, and manufacturing organization in the Luxembourg region to advance the BriLife vaccine from its current research scale platform to a scalable, adherent cell viral vector manufacturing platform that conforms to Good Manufacturing Practices and other regulatory requirements.
October 3, 2021 - In an interview with The Jerusalem Post, the father of Israel's BriLife coronavirus vaccine, Prof. Shmuel Shapira, predicted that when the country's vaccine is ready, "it will be better" than what its citizens have today.
September 18, 2021 - JPost reported the BriLife vaccine clinical trial was closed, according to Eytan Ben-Ami, head of early phase clinical trials at Sheba Medical Center. However, the data from the trial of more than 700 people should be analyzed in October 2021 - Phase 2b/3 Trial of VSV-ΔG SARS-CoV-2 Vaccine (BRILIFE) Against Approved Comparator Vaccine. (BRILIFE002).
September 10, 2021 - NRX Pharmaceuticals, Inc. Form S-1 (Form 8-K) relevant excerpts - The BriLife vaccine has demonstrated a statistically significant increase in COVID-neutralizing antibody - a sign of immunity to SARS-CoV-2 - compared to placebo in Phase 2a trials conducted in Israel and is currently completing Phase 2b dose-ranging trials in Israel and Georgia.'
September 8, 2021 - NRx Pharmaceuticals to Participate in H.C. Wainwright 23rd Annual Global Investment Conference on September 13-15, 2021.
September 1, 2021 - Local media reported Tamir Pardo, a former head of the Mossad, joined the board of directors of NeuroRX, which plans to bring the BriLife COVID-19 vaccine to market.
August 23, 2021 - NRx announced today Israeli media reported 230 volunteers who received the highest dosage of the Brilife vaccine, developed by the Israel Institute for Biological Research were notified that they did not need a third dose of the vaccine as their protection remained high, six months after getting a second dose. Participants in the High Dose BriLife Investigational Vaccine Trial who received lower doses of the BriLife vaccine have been advised to get a booster vaccination with either Pfizer or Moderna vaccines, as those lower dosages do not appear to offer sufficient long-term protection.
August 9, 2021 - NRx Pharmaceuticals announced it is initiating a phase 2b dose-confirmatory clinical trial of the BriLife™ vaccine against COVID-19 in the Nation of Georgia. The purpose of the study is to confirm the vaccine's ability to generate an immune response against the COVID-19 Delta variant before entering phase 3 trials in multiple nations. The phase 2b program will also incorporate a potential intradermal vaccination option where a small quantity of vaccine is placed into the skin instead of a traditional needle injection into a muscle.
July 12, 2021 - NRx Pharmaceuticals (Nasdaq: NRXP), a clinical-stage pharmaceutical company, announced today that it had signed a Memorandum Of Understanding with the Government of Israel to license exclusive worldwide development, manufacturing, and marketing rights to a novel Coronavirus vaccine developed by the Israel Institute for Biological Research. NRx has Arranged for Rapid Phase 2b/3 Testing in Israel, the Nation of Georgia, and Ukraine with Support of the National Governments, Health Ministries, and Cromos, LLC.
May 4, 2021 - Haaretz reported that Israel's Biological Research is considering restarting its ongoing clinical trial. According to sources, it became apparent from the first and second phases of the clinical trials on the two-shot Israeli BriLife vaccine that it would be possible to forgo the second shot if patients were given a higher dose in a single injection. As a result, the Nes Tziona-based institute plans to move its clinical trials from Israel to Argentina.
April 22, 2021 - The Jerusalem Post reported the Phase II trial for the experimental BriLife vaccine paused for two months while scientists prepared a higher dose of the vaccine.
December 29, 2020 - The Phase II trial for Israel's Brilife vaccine got underway at Sheba Medical Center.
November 27, 2020 - Hadassah-University Medical Center and Sheba Medical Center reported that they had administered the Brilife coronavirus vaccine candidate to 80 volunteers, thus completing the Phase I clinical trial.
November 14, 2020 - Hadassah-University Medical Center has vaccinated 23 people against the novel coronavirus using the Israel Institute for Biological Research's coronavirus vaccine candidate Brilife, the hospital said Friday. "All 23 participants in their 20s to 50s have had the vaccine in the last two weeks and are feeling well," said Prof. Yossi Karko, director of the Center for Clinical Research at Hadassah. "They have not suffered from any unusual side effects or medical problems following the vaccine, other than temporary sensitivity at the site of injection – as expected."
November 8, 2020 - Four women selected to participate in the human trial of "Brilife," the Israeli Institute for Biological Research's coronavirus vaccine, were vaccinated at Hadassah University Medical Center in Jerusalem Ein Kerem. All four women were in their 20s - 30s and had been medically tested and found suitable to participate in the trial.
November 1, 2020 - The human trial of Brilife, its coronavirus vaccine candidate, launched by injecting two people – one at Hadassah-University Medical Center in Jerusalem's Ein Kerem and one at Sheba Medical Center at Tel Hashomer.
October 26, 2020 - Testing the BriLife vaccine developed at Israel Institute for Biological Research on healthy volunteers has begun at Hadassah and Sheba medical centers.
October 20, 2020 - Israel names its coronavirus vaccine candidate: Brilife.
June 21, 2020 - ISRAEL21c reported that a single dose of the IIBR's recombinant VSV-∆G-spike vaccine "results in rapid and potent induction of neutralizing antibodies against SARS-CoV-2" in Syrian golden hamsters in a successful preclinical trial. It was also tested successfully in mice, rabbits, and pigs, paving the way to human trials.
BriLife (IIBR-100) Vaccine Clinical Trials
BriLife (IIBR-100) continues in clinical trials. The Phase IIb/3, prospective, randomized, comparator-controlled, observer-blind, multi-center non-inferiority study was last updated in September 2021. Subjects will receive two intramuscular (IM) injections of the IIBR-100 (prime-boost) separated by 28 days consisting of 1 ml replicating viral rVSV SARS-CoV-2-S vaccine or active comparator. The injection will be performed on Day 0 and Day 28±2d in the deltoid muscle and followed through 12 months post-last vaccination.