“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

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

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

GTU Enhances Expression in Muscle and Skin

In Vivo

0,0E+00

5,0E+06

1,0E+07

1,5E+07

2,0E+07

GTU6K14 E2 knockout control K14 regular

rlu mean

4

FVB strain

1,0E+03

1,0E+04

1,0E+05

1,0E+06

1,0E+07

GTU6CMV regular CMV

rlu median

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)

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Primate Data: Antigen Expression in Draining Lymph Nodes

MultiHIV i.d. + EP

p24 + CD1aDay 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

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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

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

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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

1010

FIT Biotech’s Novel Therapeutic HIV Vaccine (GTU-MultiHIV-B)

REV NEF TAT GAG EPITOPES

CMV10 E2 BS

MultiHIV-B

RSV LTR

BPV1 E2

GTU-MultiHIV-B8803 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

Randomized Placebo-Controlled Phase IIa Trial

11

Weeks -4 0 1 4 5 12 13 16 40 64 76 80 84 88

108Final

evaluation

N=20 IMN=20 IDN=10 IMN=10 ID

Treatment-naive

FIT-06 IM (1mg), ID (0.5 mg) FIT-06 IM (2mg), ID(1mg)Placebo IM & ID

Primary endpoints: safety & immunogenicitySecondary endpoints: pVL, CD4 cell countsEnrollment characteristics:

- Age 29 yrs (range: 18-40 yrs). - Plasma viral load > 38000 copies/ml

- CD4 cells/ µl > 500- C clade infected- Treatment-naive South Africans

HIV-Specific CD4 and CD8 T-Cell Responses Increase Following Vaccination

Data 1

0.0

0.5

1.0

1.5

2.0

2.5

% o

f Ag

spec

ific

CD4

T ce

lls

Data 1

0

2

4

6

8

% o

f Ag

spec

ific

CD8

T ce

llsP = 0.0014 P = 0.010

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

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1313

Average Changes in Plasma Viral Load and CD4 Cell Counts after 108 Weeks

Comparison Estimate log(VL) P-valueFIT vs. Placebo -0.31 0.012ID: FIT vs. Placebo -0.16 0.257IM: FIT vs. Placebo -0.47 0.001

Comparison Estimate (cells/uL)

P-value

FIT vs. Placebo +45 0.068ID: FIT vs. Placebo +18 0.514IM: FIT vs. Placebo +72 0.013

Average Change in Plasma Viral Load (after 108 weeks)

Average Change in CD4 Cell Counts (after 108 weeks)

ID=IntradermalIM=Intramuscular

Change from Baseline in Viral Load for Patients with Viral Load ≤4.5 at Baseline

Confidential14

Population ComparisonOverall

difference (weeks 1-

108)

During initial

immunization (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 -0.38p = 0.019 - - -

FIT IM vs Placebo

-0.56p = 0.003

-0.54p = 0.005

-0.60p = 0.002

-0.61p = 0.009

FIT ID vs Placebo

-0.19p = 0.265

-0.34p = 0.067

-0.19p = 0.315

-0.18p = 0.419

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• 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