Chikungunya: Phase 3 Clinical Development of a Single-shot Live-Attenuated Vaccine (Presentation at the American Society of Tropical Medicine & Hygiene)

Chikungunya: Phase 3 clinical development of a single-shotlive-attenuated vaccine candidate

American Society of Tropical Medicine & Hygiene

Vera Bürger

Director Clinical Strategy, Project Lead Chikungunya Vaccine Development

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Chikungunya: Phase 3 clinical development of a single-shotlive-attenuated vaccine candidate VLA1553 - ASTMH

November 1, 2022

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Chikungunya: a major public health threat

Mosquito-transmitted disease with potentially debilitating consequences

Aedes aegypti

Aedes albopictus

• Chikungunya virus (CHIKV) is transmitted by Aedes mosquitoes1
• Often causes large, explosive outbreaks with high attack rates, affecting one-third to three-quarters of the population1; difficult to predict next outbreaks2
• Outbreaks have occurred in Asia, Africa and across Latin America1 with the potential for it to happen in the U.S. and Europe2,4
• Highest areas of risk of infection for travelers include the Americas, parts of Africa, and Southeast Asia3
• Returning infected travelers can trigger local transmission in areas where relevant mosquitoes are established (e.g. Southern U.S./Europe)2
• High burden of disease: outbreaks can have substantial health-economic impact; infection can progress to severe chronic symptoms in many patients4

No cure; treatment is symptomatic and supportive only

Without a vaccine, prevention is limited to protection

against mosquito bites and vector control

1. Staples et al. CDC Yellow Book 2020, Chapter 4 . 2. Bettis et al. PLOS Neglected Tropical Diseases 2022;16(1): e0010069. 3. Lindsey et al Am J Trop Med Hyg. 2018;98(1):192-197.doi:10.4269/ajtmh.17-0668 4. Silva LA et al. J Clin Invest. 2017 Mar 1;127(3):737-749.

Chikungunya: Phase 3 clinical development of a single-shotlive-attenuated vaccine candidate VLA1553 - ASTMH

November 1, 2022

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VLA1553 at a Glance

Live-attenuated CHIKV vaccine candidate targeting long-lasting immunity with a single shot

Vaccine Candidate VLA1553

• Live-attenuated CHIKV vaccine candidate, single dose, i.m., lyophilized
• Based on La Reunion strain of East Central South African genotype
• Attenuation by reverse genetics, 60aa deletion within the non-structural nsP3 protein

Regulatory Milestones

• FDA: Fast Track and Breakthrough designations granted
• • Rolling submission of Biologics License Application (BLA) commenced in Aug 2022
• EMA: PRIME designation 2020
• Investigational vaccine candidate, not approved for use in any jurisdiction

Development Status

• Pivotal Phase 3 Trial: Primary Endpoint (Seroresponse Rate) met
• Lot-to-Lotconsistency Trial: Primary Endpoint met
• Antibody persistence trial ongoing
• Adolescents trial in Brazil ongoing

Target Populations & Geographic Reach

• Non-endemic countries: Travelers / Military / Outbreak preparedness in US, EU, CAN
• Endemic use: Partnered with CEPI and Instituto Butantan, technology transfer

Chikungunya: Phase 3 clinical development of a single-shotlive-attenuated vaccine candidate VLA1553 - ASTMH

November 1, 2022

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Licensure Pathway for Chikungunya Vaccines Accelerated approval pathway agreed with regulators for chikungunya vaccines

• Classical efficacy studies for chikungunya vaccines are considered unfeasible1,2
• • Unpredictable and short-lived outbreaks
  • Logistical boundaries
  • Acceptable timeframes & cost barriers
• In the US, chikungunya vaccines can be licensed following the
  "accelerated approval" pathway
• • Other regulators also agreed to licensure based on serological endpoints
• FDA-agreedsurrogate endpoint "Seroresponse Rate":
• • Rate of subjects achieving a neutralizing antibody titer of ≥150 in a µPRNT50 assay2

1 VRBPAC Meeting, Nov 2019. 2 Bettis et al, PLoS Negl Trop Dis 16(1): e0010069

2 Roques P, et al. Effectiveness of CHIKV vaccine VLA1553 demonstrated by passive transfer of human sera. JCI Insight. 2022 Jul 22;7(14):e160173. doi: 10.1172/jci.insight.160173.

PMID: 35700051; PMCID: PMC9431671.

Chikungunya: Phase 3 clinical development of a single-shotlive-attenuated vaccine candidate VLA1553 - ASTMH

November 1, 2022

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