“Delivering the Promise of Genetic Medicine and Vaccines”
NAPWA Symposium
6th IAS Meeting
An HIV-based Lentiviral Vector Vaccine
Achieves Functional Cure Post-challenge
in a Subset of Vaccinated Macaques
Dr. Lawrence Michaelis
Chairman and CEO
Rome, July 19th 2011
1
VRX496 Autologous CD4 T Cell Therapy
• 65 patients in several Phase 1 and 2 trials of VRX496
- Infusions found to be safe
- Induces significant CD4 cell increases in a sub-set of HIV-infected
patients. Decreased viral load set point in STI setting.
- Produces mutations in HIV, making the virus less fit to replicate (see
IAS WEPDA0205 Poster Discussion)
• Decision made to secure funding to advance program to Phase 2b
- ACTG agreed to support next trial
- Search for corporate co-development partner
• VRX496 platform provided important insights into next generation
product - HIV vaccine candidate, VRX1273
- Safety
- Design
- Manufacturing
2
General Benefits of Therapeutic HIV Vaccine
•
•
•
•
•
•
•
•
3
Lower viral load
Lower forward transmission
Preserves the CD4 compartments
Extends survival
No toxicities
Low frequency of treatment
Preserve ARV alternatives
Significantly reduce cost
Benefits of Therapeutic HIV Vaccine
•
•
•
•
•
•
•
•
General Benefits
Lower viral load
Lower forward transmission
Preserves the CD4
compartments
Extends survival
No toxicities
Low frequency of treatment
Preserve ARV alternatives
Significantly reduce cost
VIRxSYS’ VRX1273
• Viral load reduction achieved
• CD4 compartments maintained
•
•
•
•
•
Survival advantage demonstrated
No toxicities and reinfusion-safe
Single set of infusions effective
No drug-resistance of HIV expected
Anticipated to be cost effective
• Clade-agnostic. Designed for global
application
4
Benefits of Therapeutic HIV Vaccine
•
•
•
•
•
•
•
•
General Benefits
Lower viral load
Lower forward transmission
Preserves the CD4
compartments
Extends survival
No toxicities
Low frequency of treatment
Preserve ARV alternatives
Significantly reduce cost
VIRxSYS’ VRX1273
• Viral load reduction achieved
• CD4 compartments maintained
•
•
•
•
•
Survival advantage demonstrated
No toxicities and reinfusion-safe
Single set of infusions effective
No drug-resistance of HIV expected
Anticipated to be cost effective
• Clade-agnostic. Designed for global
application
VRX1273 HIV Vaccine – Targeted as a Functional Cure
5
Objectives for VIRxSYS’ VRX1273 HIV Vaccine
• Reduce viral load
• Preserve the CD4 compartments
• Extend survival
* T.C. Friedrich and D.I. Watkins, 2005
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Outstanding Results from the NHP SIV Model
• Vaccine extremely immunogenic
– Unique, high-magnitude CD8 responses to SIV
• Strong protection from extremely high and pathogenic
challenge; 40% of vaccinated monkeys responded favorably:
– Long-term control of viral load, over a 18-months period, down to
undetectable levels
– Complete preservation of the immune compartment: vaccinees are not
immuno-deficient and develop no symptoms of AIDS
– SIV control extends to the immune sanctuaries, with dramatic decrease of
virus in all reservoirs tested
– Improved survival in all vaccinees, even in those that did not truly “respond”
according to the above parameters
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* Please refer to Late-Breaker abstract MOLBPE042: Franck Lemiale et al. “A lentiviral
vector HIV vaccine candidate protects macaques from high dose SIV intrarectal challenge:
vaccine responders achieve functional cure”.
Reduced SIV Provirus in Reservoirs of Vaccinees
Plasma viral load
1.E+04
SIV DNA copies/million cells
1.E+08
SIV RNA copies/ml
1.E+07
1.E+06
1.E+05
1.E+04
1.E+03
1.E+02
SIV DNA copies/million cells
Proviral DNA in
jejunum
9010
1.E+03
1.E+03
1.E+02
1.E+02
1
1
1.E+01
1.E+01
1.E+02
Unvaccinated EC SIV-infected,
deceased
2 LV-vaccinated
2
Unvaccinated EC SIV-infected,
deceased
SIV DNA copies/million cells
LV-vaccinated
1.E+04
1.E+04
1.E+03
1.E+01
1.E+01
Proviral DNA in PBMC
600
8010
9010
LV-vaccinated
Unvaccinated EC SIV-infected,
deceased
Proviral DNA in
lymph nodes
7010
8010
500
6010
7010
5010
400
6010
4010
5010
300
3010
4010
2010
200
3010
1010
2010
100
10
1010
0
10
LV-vaccinated
Unvaccinated EC SIV-infected,
deceased
Averages of 13 NHP deceased of SIVmac251 infection
1
2
3
4
Mamu
Elite Controller (EC)
3 B*08+/B*17+
4
LV-only vaccine responders
Next Steps
• HIV Vaccine Program was presented to the FDA
• Pre-IND meeting successfully completed
•
No challenge to the strategy of using integrating HIV-based lentiviral
vector as vaccine
• Finalized clinical design with help of Medical Advisory Board
• Preparing for IND-enabling studies (Tox/Biodistribution),
analytical assays development and manufacturing scale-up
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Why so Little for Therapeutic Vaccines?
• As for today, no preventive vaccine approach succeeded
• Despites over 20 years of efforts and massive investments
• Furthermore, preventive vaccine does not address the growing
needs of alternative treatments for HIV infected individuals
• Thus one may question why there are insufficient funds available to
develop therapeutic vaccine aimed at functional cure
• Small companies cannot do everything themselves
• Focusing on product development is their mandate
• Advocacy groups are better suited pushing a change in priorities
We need your support for developing a
Functional Cure for HIV
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“Delivering the Promise of Genetic Medicine and Vaccines”
Thank You
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First ; Advantages of a TV
Second: Overview of the monkey study. Emphasize toxicity and all
animals severely infected, no prime, etc.
Third: Results at 6, 12, and 18 months : VL, Survival, immune System,
Proviral DNA, and lymphactics
Fourth: Review our interpretation. “Not aware of other primate studies
with such results, comments from MAB, what we would have with 40%,
lentiviral vector and safety, PV in a therapeutic setting.
Five: Next steps, FDA, Plan on TI in Phase I, More attention for funding
of Functional cures,