Dr Olga Pleguezuelos CSO and Project Manager at SEEK
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Dr Olga Pleguezuelos CSO and Project Manager at SEEK
Imutex Limited,
Limited formed in
2016, is a joint venture
between SEEK Group and
hVIVO to accelerate the
development of a Mosquito
Vaccine (AGS-
(AGS-v) and Broad-
Broad-
Spectrum Influenza Vaccine
(FLU-
(FLU-v).
SEEK and hVIVO each have
in excess of 15 years
experience in the fields of
immunology, infectious
diseases, vaccines, clinical
trials and human models.
Imutex Limited 8 April 2018 2No risk of Absence of
genetic infectious
integration or material
recombination. Ability to exclude
regions associated with
Cost effective large toxicity or autoimmune
scale purification recognition
Easy
characterization by Amplify conserved and
well established immune regions in
analytical protein
techniques
Freeze drying avoids
(HPLC/MS)
cold-chain during
storage and transport• Aim: rapid identification of conserved immunoreactive
antigens.
• Epitope prediction: T cell reactive epitopes predicted using
16 different parameters to assess reactivity including
crystallography, charges, Van der Waals forces,
shapes, length and chemical interactions.
• Peptide selection based on:
• conservation (>70%)
• multiple predicted T cell epitopes for several
human HLAs
• approxDisease burden: (~1 billion
cases of flu, ~3–5 million
cases of severe illness and
Complex 300K–500K deaths annually
manufacturing,
manufacturing worldwide) Economic
limited number of burden: lost work
doses available, force and
only those at risk strained health
are vaccinated. system.
Influenza virus is
Ineffective antiviral highly variable
treatment due to requiring
development of development of a
resistance. Low efficacy when new vaccine
circulating strains and annually.
annually
vaccine strains are not
matched
Imutex Limited 8 April 2018 6Universal Vaccine Goals
• Provides cross-protection against broad range of influenza
strains.
• Decreases symptomatology.
• Reduces hospitalisations.
• Remains the same year after year allowing all year round
manufacturing.
• Less complex and cost-effective manufacturing so larger
population can be vaccinated.
Imutex Limited 8 April 2018 7 FLU-v is composed of an equimolar
mix of 4 peptides (FLU-5, FLU-7,
FLU-8N, FLU-10) which cover
conserved T cell reactive regions
in M1, M2 and NP influenza proteins.
A dose of 500ug contains 50nmol of each peptide in a sterile
glass vial (no excipients).
The final product is a lyophilised sterile mix that will need
reconstitution prior subcutaneous injection (either as
emulsion in oily adjuvant (Montanide ISA-51, Seppic) or as a
non adjuvanted suspension. A phase I (N=32) and phase Ib (N=48) showed FLU-v was safe and
well tolerated.
tolerated
A single dose of FLU-v induced specific dose dependent cellular
immunity in humans.
humans
Vaccination with a single dose of adjuvanted FLU-v followed by
challenge with live influenza H3N2 strain resulted in reduction of
viral titre and clinical symptom score that correlated with IFNγ
production.
cross-reactivity in vitro to
The immune response to FLU-v showed cross-
different influenza strains (A/Swine H1N1, A/Duck H3N8 and
A/New Caledonia H1N1).
Results published in Vaccine (2012) 30: 4655– 4660, Clinical and Vaccine
Immunology (2015)22: 828-835 and Clinical and Vaccine Immunology
(2015) 22:949-956Imutex Limited 8 April 2018 10
Imutex Limited 8 April 2018 11
Imutex Limited 8 April 2018 12
EU funded, UNISEC Consortium
A randomised, double-blind, placebo-controlled, single-
centre phase IIb trial (healthy adults 18-60)
Treatment arms:
◦ 1 dose FLU-v adjuvanted (n=74)
◦ 2 doses FLU-v non-adjuvanted 21 days apart (n=74)
◦ 1 dose Adjuvanted Placebo (n=37)
◦ 2 doses Non-adjuvanted placebo (n=37)
Trial Locations: Clinical Site: Isala, Zwolle, The
Netherlands, External Laboratories: RKI (Germany), NIPH
(Norway), UMCG (The Netherlands) 5 visits:
◦ Visit 1(day -7 to day-2): screening
◦ Visit 2 (day 0): randomisation, baseline blood sample and
vaccination 1
◦ Visit 3 (day 21): vaccination 2 & review of AEs after
vaccination 1.
◦ Visit 4 (day 42): review of AEs after vaccination 2 and post-
vaccination blood sample 1
◦ Visit 5 (day 180): post-vaccination blood sample 2
Influenza follow up from 1st Dec 2016-31 March 2017: Daily
online symptom questionnaire followed by swab after sudden
onset of at least one respiratory and one systemic symptom.
Imutex Limited 8 April 2018 14 Immunogenicity: To evaluate the cellular immune responses
at 42 and 180 days as the change in level of TH1 cytokine
production from baseline (day 0) following FLU-v vaccination,
given as a suspension or as emulsion (adjuvanted), compared
to placebo (Flow Cytometry and ELISA).
Safety:
◦ To evaluate the incidence of solicited AEs in all groups until
21 days after the last dosing of study vaccine.
◦ To evaluate the incidence and nature of unsolicited AEs and
SAEs in all subjects during the whole study period. (Primary)
Imutex Limited 8 April 2018 15 To compare the effects of FLU-v with placebo, given as a
suspension or emulsion (adjuvanted) on immune responses
as measured using TH2 cytokines (Flow Cytometry)
To evaluate the IgG and IgM antibody responses specific to
FLU-v at 42 and 180 days from baseline following vaccination
(ELISA)
Imutex Limited 8 April 2018 16 To assess the effect of previous influenza vaccinations on the
immunogenicity of FLU-v.
To evaluate the efficacy of FLU-v vaccine in the reduction of
the incidence of RT-PCR confirmed influenza A and/or B
infection in all subjects during the influenza season 2016-
2017.
To evaluate the efficacy of FLU-v vaccine in the reduction of
symptom scores using diary entries and a scoring system
among RT-PCR confirmed influenza A and/or B confirmed
infections during the influenza season 2016-2017.
To measure the titer of IgG subclasses in antibody responder
samples to determine their functional role.
To determine whether immune response to FLU-v is able to
cross-recognise five different influenza strains
(IFNg+Granzyme B ELISPOT)
Imutex Limited 8 April 2018 17 Most common injection related AEs are mild to moderate in
severity and include haematoma, heat, swelling, redness,
pain, itching and induration at the site of injection.
SAEs: Vaccine unrelated as determined by PI, study doctor,
medical monitor and pharmacovigilance:
◦ Abdominal Hernia surgery: resolved
◦ Surgery for skiing shoulder fracture: resolved
◦ Surgery for myocardial infarction: resolved
◦ Hospitalisation for alcohol abuse and depression: resolved
Imutex Limited 8 April 2018 18 Intention to treat: all randomised subjects independently of
vaccine administration. N=175
Full Analysis Set: 2 immunisations, blood samples in
prevaccination and at least 1 post-vaccination timepoint.
N=167
Per Protocol: 2 immunisations, blood samples for all 3 time
points, no major Protocol Deviations. N=152
Safety Population: any subject that received at least one
immunisation. N=175
Protocol deviations: 111
Imutex Limited 8 April 2018 19 Partial Blinded-Data was analysed to determine the quality of
the data and the robustness of the statistical methods used
The analysis of some samples was repeated
Rules for sample acceptance under discussion and to be
implemented in version 2 of the Statistical Analysis Plan
Unblinding planned for 19th February
Statistical Analysis completed by (TBC by Eelko’s team)
Data report completed by 31st March
Imutex Limited 8 April 2018 20Imutex Limited 8 April 2018 21
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