A major public health concern
Need effective vaccines to prevent HSV-driven disease
HSV-2 infectionsrecurrent herpes
severe disease
intermediate
asymptomatic
3.2 billion
~100 million
HSV-1 and/or HSV-2
Scope of Herpes Problem
Team RVx
William Halford, PhD
Joshua Geltz, PhD
Ashley Mihalich, MS
Agustin Fernandez III
Aziz Friedrich
Why was RVx founded?
• The current standard of care delivered to herpes
patients is inadequate.
• 100 million people suffer with chronic herpetic disease.
Too often, antiviral drugs do not alleviate symptoms.
• Patients live in fear of transmitting herpes to others.
• Approaches doctors use to manage herpes
today were proposed 40 years ago.
• HSV-2 subunit vaccines (1976) main approach in 2016
• acyclovir-based drugs (1977) main approach in 2016
• HSV antibody-capture ELISA (1977) common approach in 2000s
Why is herpes an
unsolved problem?
Theoretical Problem for Scientists
1970s-era solutions offered before HSV’s complex biology understood.
Practical Problem for Patients
• Herpes diagnostic tests error-prone
• HSV-2 vaccines all have failed in U.S. trials
• Acyclovir-derived antivirals marginally effective
Why is herpes an
unsolved problem?
How do RVx’s Technologies Compare?
RVx’s technologies are 50 - 100x more effective
This is the difference between:
• success based on 21st-century technology
vs
• failure based on outdated technology
• RVx’s Mission
• RVx’s Technology: a suite of 21st Century Solutions
1. Better Diagnostic Tests HSV ABVIC Test
Real Herpes Solutions
• RVx’s Mission
• RVx’s Technology: a suite of 21st Century Solutions
1. Better Diagnostic Tests HSV ABVIC Test
2. Better Preventative Vaccines Profavax HSV-2
Real Herpes Solutions
HSV-2 Subunit Vaccines:
30 years of failures
Assumption 1. HSV-2 genital herpes causes cervical cancer.
• Proven wrong by 1983
Assumption 2. DNA-free glycoprotein vaccine will prevent herpes.
• Prediction has failed in 8 clinical trials spanning 28 years
Failed clinical trials of HSV-2 glycoprotein subunit vaccines
• Mertz, et al, 1990 • Straus, et al, 1994 • Straus, et al, 1997
• Corey, et al, 1999 • Stanberry, et al, 2002 • Belshe, et al, 2012
• Vaxfectin Trial (2015) • GEN-003 Trial (2016)
DNA-free HSV subunit vaccine (1976)
Antigenic B- and T-cell
Breadth Cooperation
HSV-2 Subunit Vaccines:
limited Antigenic Breadth
% of HSV-2 proteins present in vaccine
Subunit vaccines
(>40,000 trial participants) Ag Breadth
• Herpevac = gD 0.8%
• GEN-003 = gD + ICP4 2%
• Vical = gD + UL46 3%
• Admedus = HSV-2 peptides 2%
• Agenus HerpV = 32 T-cell peptides 3%
Whole HSV-2 ICP0 - virus vaccines
(0 trial participants) Ag Breadth
• ProfavaxHSV-2 vaccine (ICP0-) 99.3%
ProfavaxHSV-2 : 50 to 100x
more Antigenic Breadth
Does Antigenic Breadth matter?
Total virus-specific antibody
liveProfavax HSV-2
vaccine
HSV-2 gDsubunitvaccine
vs
naïvesurvival: 0 / 5
gD-2survival: 1 / 4
0NLSsurvival: 5 / 5
naïvesurvival: 0 / 5
gD-2survival: 1 / 4
0NLSsurvival: 5 / 5
Halford, et al, 2010
Halford, et al, 2011
Halford, et al, 2013
Halford, 2014
Geltz, et al, 2015
Halford, et al, 2015Profavax HSV-2
vaccine
HSV-2 gD+
alum/MPL
vs
Does Antigenic Breadth matter?
Protection against herpes
RVx: 21st Century Tools
Live HSV ICP0- vaccines2010 Patent 2014 Patent
Halford, et al, 2006
Halford, 2007
Halford, et al, 2010
Halford, et al, 2011
Halford, et al, 2013
Halford, 2014
Geltz, et al, 2015
Halford, et al, 2015
Royer, et al, 2016
• RVx’s Mission
• RVx’s Technology: a suite of 21st Century Solutions
1. Better Diagnostic Tests HSV ABVIC Test
2. Better Preventative Vaccines Profavax HSV-2
3. Better Herpes Treatment? Theravax HSV-2
Real Herpes Solutions
Prophylactic valacyclovir:
standard of care for 20 yrs
Promise: Acyclovir is potent HSV inhibitor in the lab (300 mM)
Problem: Limited bioavailability in vivo (~1 mM)
• Slightly more soluble acyclovir-like drugs developed by 1990s
- valacyclovir - penciclovir - famciclovir
Bottom line on prophylactic valacyclovir:
• has not slowed the epidemic spread of genital herpes
• does not alleviate all herpes symptoms for all patients
• annual revenues $2 billion per year
Acyclic guanosine inhibits HSV DNA synthesis (1977)
Would a therapeutic HSV-2 vaccine
be more effective?
Therapeutic HSV-2 subunit vaccines:
• Weakness: HSV-2 subunit vaccines lack antigenic breadth
Live TheravaxHSV-2 vaccine to manage GH?
• 50-fold increase in antigenic breadth
• 100x more protective than gD-2 vaccines in animal models
TheravaxHSV-2 Vaccine Trial:
Experimental Design
• 20 pre-screened participants flown to St Kitts in two groups:
Group 1 (n=10) 3 shots of TheravaxHSV-2 (March - June, 2016)
Group 2 (n=10) 3 shots of TheravaxHSV-2 (June - August, 2016)
• At each visit: Blood drawn
Intradermal immunization in calf with 150 x 106 infectious units
Follow-up 2 days later with Administering Physician
Luisa Veloz, MDSt Kitts Trial Site
• 20 participants received 2 or 3 shots of TheravaxHSV-2
Shot 1(Day 2)
Shot 2(Day 42)
Shot 3(Day 72)
TheravaxHSV-2 Vaccine Trial:
Vaccination Site Reactions
• 20 participants received 2 or 3 shots of TheravaxHSV-2
TheravaxHSV-2 Vaccine Trial:
Safety & Tolerability
(n=10) (n=10)
TheravaxHSV-2 Vaccine Trial:
Participant-Reported Efficacy
• 17 participants completed 3 shot-vaccination series
Yes,Definitely
Yes,Partly
No
TheravaxHSV-2 Trial: Pre- vs
Pre-Vax Symptomatic Days
Herpes
neuralgia
HSV-2 GHMenstrual
HSV-2 OBs
HSV-1 GH
He
rpe
s S
ym
pto
ma
tic
Da
ys
per
mo
nth
pre-vax + antivirals
TheravaxHSV-2 Trial: Pre- vs
Post-Vax Symptomatic Days
Herpes
neuralgia
HSV-2 GHMenstrual
HSV-2 OBs
HSV-1 GH
pre-vax + antivirals
post-TheravaxHSV-2p = 0.000005
He
rpe
s S
ym
pto
ma
tic
Da
ys
per
mo
nth
TheravaxHSV-2 Trial: Pre- vs
Post-Vax Symptomatic Days
Herpes
neuralgia
HSV-1 GH
pre-vax + antivirals
post-TheravaxHSV-2
He
rpe
s S
ym
pto
ma
tic
Da
ys
per
mo
nth
HSV-2 GHMenstrual
HSV-2 OBs
p = 0.000005
TheravaxHSV-2 Trial: CE-27
Vaccination Site Reactions
Shot 1(Day 2)
Shot 2(Day 42)
Shot 3(Day 72)
60 cm 2
40 cm 29 cm 2
Conclusion
Genital herpes is an infinitely solvable problem.
1970s-era herpes treatments are not working.
RVx’s 21st century solutions are 50 - 100x more effective.
Financial Upside
for Investors
RVx Technology Annual Revenue Potential
• HSV ABVIC Test $0.1 - 1 billion per year
Quest Diagnostics generated $7.5 billion revenue in 2015
• TheravaxHSV-2 Vaccine over $5 billion per year
Global HSV Treatment Market $4.8 billion per year in 2017
• ProfavaxHSV-2 Vaccine over $10 billion per year
market for ProfavaxHSV-2 is 10x greater than any herpes treatment