William Halford, PhD

RVx, Chief Science Officer

21st Century Herpes Solutions

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

• RVx’s Mission

• RVx’s Technology: a suite of 21st Century Solutions

Real Herpes Solutions

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• failure based on outdated technology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

TheravaxHSV-2 Trial:

CE-27 HSV Western Blots

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