Bilex Pharma is pleased to announce that BLX-NIPAH01, our investigational mRNA vaccine candidate against Nipah virus, has demonstrated complete protection in preclinical challenge studies. This significant milestone advances our efforts to develop a vaccine against this deadly emerging pathogen with pandemic potential.
Addressing a Serious Emerging Threat
Nipah virus is a zoonotic pathogen that causes severe disease in humans, with mortality rates ranging from 40% to 75% in documented outbreaks. First identified in 1999 during an outbreak in Malaysia and Singapore, the virus has caused subsequent outbreaks in Bangladesh and India, with the most recent outbreak occurring in Kerala, India, in 2023.
“Nipah virus represents one of the most concerning emerging infectious disease threats due to its high mortality rate, documented human-to-human transmission, and potential for broader geographic spread,” said Dr. Andras Ottlik, CEO and Director of Bilex Pharma. “Despite this significant threat, no vaccines or specific treatments are currently approved for Nipah virus infection.”
Comprehensive Preclinical Evaluation
The recently completed studies evaluated BLX-NIPAH01 in multiple animal models, culminating in challenge studies conducted at a Biosafety Level 4 (BSL-4) facility in collaboration with international research partners.
Non-Human Primate Challenge Study
The most advanced evaluation tested the vaccine’s protective efficacy in non-human primates (cynomolgus macaques), considered the gold standard model for Nipah virus infection:
- Study Design: Twelve animals were randomized to receive either two doses of BLX-NIPAH01 (n=8) or placebo (n=4), followed by challenge with a lethal dose of Nipah virus Bangladesh strain 42 days after the first vaccination
- Survival Results: All vaccinated animals (100%) survived through the 56-day post-challenge observation period, while all placebo animals developed severe disease and reached humane endpoints by day 15 post-challenge
- Disease Prevention: Vaccinated animals showed no clinical signs of disease, and viral RNA was undetectable in blood and throat swabs throughout the study
- Tissue Analysis: Post-mortem examination of placebo animals revealed typical Nipah virus pathology in multiple organs, while vaccinated animals sacrificed at study termination showed no evidence of infection or pathology
“These results are extremely encouraging, demonstrating that BLX-NIPAH01 provided complete protection against lethal Nipah virus challenge in a highly relevant animal model,” explained Dr. Eleanor Harrington, Chief Scientific Officer at Bilex Pharma. “The absence of detectable viral replication in vaccinated animals suggests the potential for preventing not only disease but also transmission.”
Hamster Model Findings
Prior to the non-human primate study, the vaccine was evaluated in the Syrian golden hamster model:
- Dose-Response Assessment: Different dose levels were tested, with strong protection observed across multiple dosing regimens
- Single-Dose Efficacy: Importantly, significant protection (80%) was achieved with a single dose, suggesting potential utility in outbreak response scenarios
- Cross-Protection: The vaccine, based on the Bangladesh strain, also provided protection against challenge with the Malaysia strain, demonstrating cross-protection against different Nipah virus genotypes
“The robust protection observed in two different animal models provides compelling evidence of BLX-NIPAH01’s potential,” noted Dr. Sophia Chen, Chief Medical Officer at Bilex Pharma. “The demonstration of cross-protection against different viral strains is particularly important for a pathogen with documented genetic diversity.”
Innovative mRNA Vaccine Design
BLX-NIPAH01 utilizes Bilex Pharma’s proprietary mRNA platform to deliver the genetic instructions for two key Nipah virus proteins:
- Glycoprotein (G): Critical for virus attachment to host cells and a primary target for neutralizing antibodies
- Fusion Protein (F): Essential for viral entry and another important antibody target
“Our vaccine design targets the two major surface proteins of Nipah virus, generating robust immune responses against both,” explained Dr. Harrington. “Additionally, we optimized the mRNA sequences and protein conformations to maximize immunogenicity while ensuring safety.”
The vaccine employs Bilex Pharma’s BiLipid™ delivery system, previously highlighted in the company’s Nature Biotechnology publication for its enhanced thermostability and efficient cellular delivery.
Comprehensive Immune Response
Detailed immunological analyses revealed that BLX-NIPAH01 induced robust and multifaceted immune responses considered crucial for protection:
- Strong Neutralizing Antibodies: High titers of neutralizing antibodies were detected after the second dose, with levels correlating with protection
- Cellular Immunity: The vaccine induced strong T-cell responses against both G and F proteins, including CD8+ responses likely important for clearing infected cells
- Durability: Immune responses remained robust through the six-month observation period of the immunogenicity studies
- Rapid Response: Following challenge, vaccinated animals demonstrated rapid anamnestic responses, with neutralizing antibody titers increasing substantially within one week
“The balanced immune response, including both strong antibody and T-cell components, likely contributes to the complete protection observed in our studies,” said Dr. James Wilson, Director of Emerging Virus Immunology at Bilex Pharma. “This comprehensive immunity is particularly important for controlling a pathogen like Nipah virus that can infect multiple organs.”
Part of Project RESPOND
BLX-NIPAH01 is a key component of Bilex Pharma’s Project RESPOND, the company’s pandemic preparedness platform focused on developing vaccines against pathogens with epidemic and pandemic potential.
“The impressive results with our Nipah vaccine candidate demonstrate the potential of our rapid-response mRNA platform to address emerging viral threats,” said Dr. Ottlik. “The speed with which we advanced from initial design to demonstration of protection highlights the advantages of this technology for pandemic preparedness.”
The program has received funding support from the Coalition for Epidemic Preparedness Innovations (CEPI), which has identified Nipah virus as one of its priority pathogens for vaccine development.
Manufacturing and Thermostability Advantages
In parallel with efficacy studies, Bilex Pharma has made significant progress on manufacturing and formulation aspects critical for deploying the vaccine in regions where Nipah virus outbreaks occur:
- Scalable Manufacturing Process: The established production process can be readily scaled to produce millions of doses if needed
- Enhanced Thermostability: The vaccine demonstrated stability for at least one month at 2-8°C and seven days at ambient temperature (25°C)
- Lyophilization Potential: Initial studies of freeze-dried formulations show promise for creating a product that could be stored at higher temperatures for extended periods
“From the beginning, we designed this vaccine with implementation in endemic regions in mind,” explained Dr. Robert Jenkins, Vice President of Manufacturing at Bilex Pharma. “The thermostability profile is particularly important given the limited cold chain infrastructure in areas where Nipah outbreaks have occurred.”
Pathway to Clinical Development
Based on these promising preclinical results, Bilex Pharma is accelerating preparations for first-in-human clinical trials:
- Regulatory Engagement: Pre-IND (Investigational New Drug) meetings with regulatory authorities are scheduled for Q1 2024
- cGMP Manufacturing: Production of clinical trial material will commence in Q2 2024 at the company’s Manchester facility
- Phase 1 Clinical Trial: Expected to begin in Q3 2024, evaluating safety and immunogenicity in healthy adults
- Clinical Development Plan: A comprehensive development strategy is being finalized in consultation with regulators and global health organizations
“We’re committed to advancing this vaccine candidate into clinical development as rapidly as possible,” said Dr. Chen. “Given the severity of Nipah virus disease and the lack of medical countermeasures, we’re exploring various regulatory pathways that could accelerate availability in the event of an outbreak.”
Collaboration with Global Health Partners
The development of BLX-NIPAH01 has benefited from collaboration with multiple international partners:
- Coalition for Epidemic Preparedness Innovations (CEPI): Providing funding support and strategic guidance
- National Institute of Allergy and Infectious Diseases (NIAID): Conducting BSL-4 challenge studies through established facilities
- Duke-NUS Medical School, Singapore: Contributing expertise in Nipah virus immunology and diagnostic assays
- WHO R&D Blueprint: Alignment with international frameworks for priority pathogen research
“Addressing the threat of Nipah virus requires coordinated international effort,” noted Dr. Ottlik. “We’re grateful for the support of our partners and look forward to continuing these collaborations as we advance BLX-NIPAH01 toward clinical evaluation.”
Potential Public Health Impact
While Nipah virus outbreaks have been geographically limited to date, the development of an effective vaccine has significant public health implications:
- Outbreak Response Tool: A vaccine could be deployed to contain outbreaks, protecting healthcare workers, contacts of infected individuals, and affected communities
- Protection for High-Risk Populations: Individuals with occupational exposure to the virus’s animal reservoirs (primarily bats and pigs) could be preemptively vaccinated
- Pandemic Prevention: Given Nipah virus’s pandemic potential, a vaccine represents a crucial preparedness measure that could prevent a wider epidemic
- Platform Validation: Success with the Nipah vaccine further validates Bilex Pharma’s mRNA platform for addressing other emerging threats
“The devastating impact of the COVID-19 pandemic has underscored the importance of developing vaccines against emerging pathogens before they cause global crises,” said Dr. Ottlik. “Our Nipah vaccine program exemplifies this proactive approach to pandemic preparedness.”
Looking Forward
Following these successful preclinical studies, Bilex Pharma is committed to advancing BLX-NIPAH01 through clinical development while continuing to optimize the vaccine for potential deployment in endemic regions.
“These remarkable preclinical results represent an important milestone in our efforts to address one of the world’s most concerning emerging pathogens,” concluded Dr. Ottlik. “While significant work remains to bring this vaccine to clinical use, the 100% protection observed in these rigorous studies provides strong encouragement that we’re on the right path.”
About Bilex Pharma
Bilex Pharma is a UK-based biotechnology company dedicated to advancing human health through groundbreaking research and innovative vaccine development. Our mission is to protect communities worldwide by combating infectious diseases and emerging health threats with safe, effective, and accessible vaccines.
About Nipah Virus
Nipah virus is a zoonotic pathogen belonging to the Paramyxoviridae family. It primarily circulates in fruit bats (Pteropus species) and can be transmitted to humans through direct contact with infected animals or consumption of contaminated food products. Human-to-human transmission has been documented, particularly in healthcare settings. Nipah virus infection typically causes acute encephalitis with symptoms including fever, headache, dizziness, and altered consciousness, progressing to coma in severe cases. The case fatality rate ranges from 40% to 75%. No vaccines or specific treatments are currently approved for Nipah virus infection.