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“ The therapeutic effect of FIT- 06, GTU®-Multi-HIVB DNA vaccine, observed in HIV-1 infected people. Results of a Phase II trial”. Prof. Mart Ustav SVP,

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Presentation on theme: "“ The therapeutic effect of FIT- 06, GTU®-Multi-HIVB DNA vaccine, observed in HIV-1 infected people. Results of a Phase II trial”. Prof. Mart Ustav SVP,"— Presentation transcript:

1 “ The therapeutic effect of FIT- 06, GTU®-Multi-HIVB DNA vaccine, observed in HIV-1 infected people. Results of a Phase II trial”. Prof. Mart Ustav SVP, CSO

2 FIT Biotech Ltd. Private Company, founded in 1995 Based in Tampere, Finland cGMP manufacturing facility GTU ® - Gene Transport Unit - Proprietary vector platform technology Solid IP covering GTU ® globally 2

3 Novel DNA plasmid based GTU ® Vector Properties Safe –Non-replicating, non-integrating DNA plasmid –Multiple injections possible Effective –Episomal anchoring and segregation-partitioning enhancement –Higher # cells transfected, and high expression level of gene of interest Solid IP position

4 GTU Enhances Expression in Muscle and Skin In Vivo 4

5 Preclinical Studies with GTU ® Vectors Expression studies –Superior expression of antigen in GTU versus conventional vectors - comparative data from mice, swine and non-human primates –Lower amount of DNA needed Preclinical immunogenicity studies in non-human primates (Martinon et.al., 2009, Human Gene Therapy) 5

6 Primate Data: Antigen Expression in Draining Lymph Nodes MultiHIV i.d. + EP p24CD1a p24 + CD1a Day 8 post injection Macaque study published 2009 in Human Gene Therapy Plasmid delivered intradermally into keratinocytes Found antigen in draining lymph nodes This is evidence of cross- presentation 6

7 Conclusions from NHP Studies AuxoGTU ® -MultiHIV B plasmid induces strong anti-HIV cell-mediated immune response Induces polyfunctional (IFNg + IL-2) T-cells Induces long lasting HIV specific T-cells (> 3 years) The response is strongly dependent on the delivery method 77

8 Therapeutic HIV Vaccine for Functional Cure Immunological support for HIV infected individuals –Lowers plasma viral load Reduces sexual and mother-to-child transmission –Restores functional CD4 cells Delays development of AIDS Early therapeutic intervention in HIV infected individuals –Reduces side effects caused by ART –Reduces drug induced resistant mutations 8

9 9 GTU ® MultiHIV Vaccine: Six Target Genes A fusion protein representing 6 different HIV-1 genes The antigen sequences are derived either from the specific isolate or are deduced from the HIV1 consensus (A, B, C) and phylogenetic ancester (FGH) sequences Maximal representation by in tandem arrayed epitope-rich regions Codon optimization for maximal expression and inclusion of immuno-stimulatory sequences Preclinical studies - mice,swine, NHP

10 10 FIT Biotech’s Novel Therapeutic HIV Vaccine (GTU  -MultiHIV-B) REV NEF TAT GAG EPITOPES CMV 10 E2 BS MultiHIV-B RSV LTR BPV1 E2 GTU  -MultiHIV-B 8803 bps GTU  DNA technology is unique because it allows: - Long-term expression of gene of interest - Less DNA needed per immunisation - E2 BPV segregation/partitioning function

11 Randomized Placebo-Controlled Phase IIa Trial 11 Weeks Final evaluation N=20 IM N=20 ID N=10 IM N=10 ID Treatment-naive FIT-06 IM (1mg), ID (0.5 mg) FIT-06 IM (2mg), ID(1mg) Placebo IM & ID Primary endpoints: safety & immunogenicity Secondary endpoints: pVL, CD4 cell counts Enrollment characteristics: - Age 29 yrs (range: yrs). - Plasma viral load > copies/ml - CD4 cells/ µl > C clade infected - Treatment-naive South Africans

12 HIV-Specific CD4 and CD8 T-Cell Responses Increase Following Vaccination % of Ag specific CD4 T cells % of Ag specific CD8 T cells P = P = Additional Relevant Data: Responses to Gag-B and/or Gag-C at V11 (week 76) and/or V13 (week 84) were observed: - CD4 response observed in 83% of participants - CD8 response observed in 67% of participants - CD4 and CD8 response observed in 55% of participants An increase of antigen-specific CD4 and CD8 T cells secreting TNFα was observed 12

13 13 Average Changes in Plasma Viral Load and CD4 Cell Counts after 108 Weeks ComparisonEstimate log(VL)P-value FIT vs. Placebo ID: FIT vs. Placebo IM: FIT vs. Placebo ComparisonEstimate (cells/uL)P-value FIT vs. Placebo ID: FIT vs. Placebo IM: FIT vs. Placebo Average Change in Plasma Viral Load (after 108 weeks) Average Change in CD4 Cell Counts (after 108 weeks) ID=Intradermal IM=Intramuscular

14 Change from Baseline in Viral Load for Patients with Viral Load ≤4.5 at Baseline Confidential14 PopulationComparison Overall difference (weeks 1-108) During initial immunizatio n (weeks 1- 12) After initial immunization (weeks 16-76) During additional immunization (weeks 80-84) Excluding patients with very high baseline log viral load (>4.5 excluded) (N=45) FIT vs Placebo p = FIT IM vs Placebo p = p = p = p = FIT ID vs Placebo p = p = p = p = 0.419

15 15 FIT Biotech GTU DNA vaccine is safe and well tolerated in HIV infected individuals FIT Biotech has demonstrated clinically relevant effects on the two major markers of functional cure GTU DNA vaccine favourably increases CD4 cell counts in untreated, chronically infected individuals When compared to placebo, IM immunization had a significant impact on decreasing pVL for at least 27 months of study follow up Enhanced effect on pVL in subjects with favorable HLA allele type [B*5703] The results obtained are with a B-Han-2 isolate clade vaccine Key Clinical Results


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