World Vaccine Congress Washington: Antibody persistence of a single-dose live-attenuated chikungunya virus vaccine in adults

Antibody persistence of a single-doselive-attenuated chikungunya virus vaccine (VLA1553) in adults.

World Vaccine Congress, Washington 03-Apr-2024

Susanne Eder-Lingelbach

VP Clinical Development

Valneva

A leading specialty vaccine company

Focused on vaccines that make a difference

Proven, Integrated Expertise: Three in-house vaccine approvals; three proprietary commercialized travel vaccines

Focused R&D: Advancing first-, only- or best-in-class vaccine candidates; Experience across multiple vaccine platforms

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• Indications differ by country - Please refer to Product / Prescribing Information (PI) / Medication Guide approved in your respective countries for complete information, incl. dosing, safety and age groups in which this vaccine is licensed, ETEC = Enterotoxigenic Escherichia coli (E. Coli) bacterium

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Chikungunya: A Major Public Health Threat

Mosquito-transmitted disease with potentially debilitating consequences

	▪	Chikungunya virus (CHIKV) is transmitted by Aedes mosquitoes1
	▪	Acute chikungunya, seen in up to 97% of those infected, typically presents with
		sudden onset of high fever and joint pain.1
	▪	Often causes large, explosive outbreaks, affecting one-third to three-quarters of
		the population1; difficult to predict next outbreaks2
Aedes aegypti	▪	High burden of disease: outbreaks can have substantial health-economic impact;
		infection can progress to severe chronic symptoms in many patients4
	▪	Outbreaks have occurred in Asia, Africa and across Latin America1 with the
		potential for it to happen in the U.S. and Europe2,4; recent outbreak in Paraguay5
		with PAHO issuing an epidemiological alert for the Americas6
	▪	Returning infected travelers can trigger local transmission in areas where
		relevant mosquitoes are established (e.g. Southern U.S./Europe)2
Aedes albopictus

1. Staples et al. CDC Yellow Book 2020, Chapter 4 . 2. Bettis et al, PLOS Neglected Tropical Diseases 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; 5 PAHO provides guidance to countries in response to increased chikungunya cases; 6 Epidemiological Alert: Chikungunya increase in the Region of the Americas

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High Acute Morbidity: Can Lead to Chronic Incapacitation

Lasting months to years in a high proportion of patients

Acute Phase

(up to 97% )1

• Symptoms typically begin 3-7 days after being bitten by an infected mosquito1
• • Fever and joint pain / joint inflammation, other systemic manifestations1-4
  • Joint symptoms are typically severe and can be debilitating1
• Viremia for 5-10 days2,3
• Acute symptoms typically resolve in 7-10 days1
• Sub-acutepost-viremic state (6-21 days) can occur3,4
• • Persistent articular symptoms
  • Tenosynovitis and bursitis

Chronic Phase

(~43% of cases)5

• Long-termsuffering differs per study:6-8
• • A study showed that 57% of patients are still somewhat affected by the disease after 2.5 years6
  • However, up to 78.6% of cases may have persistent muscle and joint symptoms at 27.5 months7
  • The CDC Yellow Book reports a range from 5 to 80% of patients with persistent joint pains, as well as prolonged tiredness, for months or years after their illness8

Chikungunya means "to become contorted" in Kimakonde, describing sufferers' stooped appearance

1. Staples et al. CDC Yellow Book 2020, Chapter 4. 2. Rudolph KE et al. Am J Trop Med Hyg. 2014;90:882-891. 3 Suhrbier A et al. Nat Rev Rheumatol. 2012;8:420-429. 4. Stalkowsky F et al. PLoS one 2009;4:e7603-e7603. 5 Paixao ES, et al. Trans R Soc Trop Med Hyg. 2018;112(7):301-316. 6 Doran C, et al. PLoS Negl Trop Dis. 2022;16(3):e0010142. 7 Essackjee K, et al. Postgrad Med J. 2013;89(1054):440-447. 8 Centers for Disease Control and Prevention (CDC). Chikungunya CDC Yellow Book 2024. Available at: https://wwwnc.cdc.gov/travel/yellowbook/2024/infections-diseases/chikungunya. Accessed: October 2023.

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Chronic Chikungunya Negatively Impacts Quality of Life

Persistent rheumatologic disease

Post-CHIKV rheumatism	Effect of arthritis/	Joints typically involved	Impact on
2 forms	polyarthritis	by polyarthritis5	life activities1-4
Mechanical musculoskeletal	Long-term joint pain1-3	⚫	Hands	⚫	Standing up
		Knees		Walking/mobility
disorders	Stiffness after immobility1-3	⚫	⚫
	⚫	Wrists	⚫	Using hands
Chronic inflammatory arthritis	Can be triggered by change	⚫	Ankles	⚫	Self-care
in temperature and physical effort4	⚫	Shoulders	⚫	Daily/leisure activities

Carpitis and thumb arthritis (left) -	Two years after CHIKV infection: Intense arthritis	Symmetrical inflammatory
Multiple tenosynovitis of fingers and wrist (right)1	of metacarpophalangeal joints and wrist5	polyarthritis3

CHIKV = chikungunya virus.

1. Simon F, et al. Medicine. 2007;86:123-137. 2. Tritsch S, et al. J Rheum. 2020;47:1267-1274. 3. Mohan A, et al. Indian J Dermatol. 2010;55:54-63. 4. Schilte C, et al. PLOS Negl Trop Dis. 2013;7:e2137. 5. Amaral J, et al. Viruses. 2019;11:289.

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Chikungunya: A Global Threat

Chikungunya virus has been identified in >110 countries on all continents except Antarctica1

Countries with current outbreaks or evidence of chikungunya virus transmission

among people within the last 5 years2

• Chikungunya virus (CHIKV) was first identified in Tanzania in 19521
• Over the following ~50 years CHIKV was geographically isolated and caused occasional outbreaks in Africa and Asia1
• CHIKV has since spread rapidly and been identified in over 110 countries throughout the world1
• It is estimated that over three quarters of the world's population live in areas

at-risk of CHIKV transmission3

*Does not include countries or territories where only imported cases have been documented (see reference 3 for imported cases in Europe).

1. WHO CHIGV factsheet. Available at https://www.who.int/news-room/fact-sheets/detail/chikungunya. Accessed: March 2024. 2. CDC Chikungunya Virus Disease Information. Available at: https://www.cdc.gov/chikungunya/geo/index.html. Accessed: March 2024. 3. Puntasecca CJ, et al. PLoS Negl Trop Dis. 2021; 15(3): e0009055.

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VLA1553 at a Glance

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

CHIKV VLA1553

• Live-attenuated, single dose, i.m., lyophilized
• Based on La Reunion strain of East Central South African genotype
• Attenuation by reverse genetics, large deletion within the non-structuralnsP3 protein

Regulatory Milestones

• Approved by the FDA (November 2023)
• Additional filings under review by EMA, Health Canada and Anvisa (Brazil)

Development Status - FDA Approved, Preparing Phase 4

• Pivotal Phase 3 Trial: Primary Endpoint (Seroresponse
  Rate) met
• Lot-to-Lotconsistency Trial: Primary Endpoint met
• Antibody persistence trial ongoing: positive 24 months data
• Adolescents trial in Brazil ongoing: positive Day 29 data

Target Populations & Geographic Reach

• Non-endemic countries: Travelers / Military / Outbreak preparedness in U.S., EU, CAN1
• Endemic use: Partnered with CEPI and Instituto Butantan, technology transfer

1 https://www.cdc.gov/vaccines/acip/recommendations.html

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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 unfeasible in a pre-licensuresetting1

• Unpredictable and short-lived outbreaks
• Logistical boundaries
• Acceptable timeframes and cost barriers

In the U.S., chikungunya vaccines can be licensed following the "accelerated approval" pathway

• Other regulators also agreed to licensure based on serological endpoints

FDA-agreed surrogate endpoint: "Seroresponse Rate"

1 VRBPAC Meeting, Nov 2019.

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Evidence Supporting the Serological Endpoint

After transfer of human post-vaccination sera, neutralizing antibodies conferred sterilizing immunity in non-human primates

A non-human primate (NHP) model was used to determine a surrogate of protection

• The NHP model mimics many aspects of human disease

Experimental Set-Up1:

• Sera from human vaccinees at varying titer levels were transferred to NHP's
• Animals challenged with wild-type chikungunya virus, monitored for fever and viremia

Results1:

• No fever in any of the NHP's who received human post-vaccination serum
• No live, replicating virus detected
• All animals had strongly reduced, some undetectable, viral RNA load, depending on titer
• • Determined pre-challenge titer resulting in sterilizing immunity in NHPs - very conservative approach: seroresponse defined as µPRNT50≥150

Further evidence1:

Protective titer determined in a prospective seroepidemiological trial in the Philippines translated into a µPRNT50

of ~49

1 Roques P, et al. JCI Insight. 2022;7(14):e160173. doi: 10.1172/jci.insight.160173.

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