PEV7 - Pevion Biotech AG

PEV7 key advantages
First-in-class opportunity
Identification of main virulence
factor as prime target antigen
(proprietary, recombinant
protein)
Pioneering approach to
mucosal immunity: two galenic
forms for mucosal (intravaginal)
and i.m. route of application
Clinically and market validated
carrier & adjuvant system for
high-quality B cell responses to
subunit antigens
Scalable, GMP compliant
manufacturing process
Unrecognized disease
burden
“I have been battling this for over
15 years. Maintenance fluconazole
no longer works. I have
done everything out there.”
(aged 44, USA)
“You can’t concentrate [on your
work], because it is itching so
strongly.” (aged 37, Switzerland)
“This has really affected my self
esteem and confidence. Really
got me down. And no one is
getting to the bottom of it.”
(aged 31, UK)
“Needless to say it has ruined my
life and still is.” (aged 35, UK)
J U L Y 2 0 1 1
PEV7
Therapeutic vaccine against RVVC
Recurrent vulvovaginal candidiasis (RVVC), also known as chronic recurrent
thrush, is a largely unrecognized but highly debilitating condition, which affects
5% of adult women worldwide. Cure rates of RVVC with available antifungal
drug therapy remain disappointing and there is no prophylactic treatment
available.
A therapeutic vaccine has the potential to break new ground: the prevention of
recurrencies which no drug can provide. Pevion is developing a state-of-the-art
therapeutic vaccine based on a proprietary protein antigen, a key virulence
factor of Candida, presented on the surface of virosomes. PEV7 achieved
excellent results in preclinical studies and has generated already positive
Phase I interim data.
M E D I C A L N E E D
One out of twenty adult women suffer from recurrent vulvovaginal candidiasis
(RVVC), which is defined as four or more acute episodes of symptomatic VCC
within a year. Candida albicans is the predominant species causing 80-95% of
cases. Symptoms are vulvovaginal inflammation, burning, soreness, abnormal
vaginal discharge, severe itching, discomfort, and pain.
At present, there is no satisfactory treatment for RVVC available. The acute
condition usually responds to treatment with antifungal drugs of the azoleclass.
Clinical practice guidelines recommend an induction therapy with a
topical or oral azole for 10-14 days, followed by a maintenance suppressive
regimen for at least 6 months (e.g. oral fluconazole once per week). More than
90% of patients are well controlled while on maintenance therapy, but upon
cessation, the recurrence rate is 40-50% within a few months. Long-term
protection for these patients does not exist. In addition, anti-fungal drugs have
significant adverse effects including local irritation and pain, hepatotoxicity,
interactions with some contraceptives and oral hypoglycemic agents, and
supposed teratogenicity of some therapies (limitation of use during pregnancy
and breast feeding).
The quality of life of RVVC patients is strongly impacted, both physically and
psychologically, with suffering over many years and no perspective for
amelioration or cure. The disease represents a permanent mind occupation
and incessant stress. It impedes social activities and impacts the performance
at work. Moreover, it is an embarrasing issue and very difficult or impossible to
talk about, in particular in front of employers, colleagues and friends. It also
severely affects partner/relationships, and over time, leads to desperation or
even depression. Therefore, alternative, more sustainable treatment options
are urgently needed.
M A R K E T O P P O R T U N I T Y
RVVC offers a first-in-class opportunity for a therapeutic vaccine. Pevion has
conducted a thorough primary market research confirming high prevalence
and incidence rates as well as the high unmet medical need. Despite the wide
spread of the disease, the public awareness of RVVC is relatively low, due to
the taboo character of the topic. Consequently, there is little competition on
the development of a vaccine against RVVC and Pevion has a clear head start
with the first vaccine in the clinics.

2
Yeast fungus Candida albicans
PEV7 vaccine with recombinant
protein antigen presented on the
surface of virosomes
V A C C I N E P R O F I L E
PEV7 is a state-of-the-art therapeutic vaccine against recurrent vulvovaginal
candidiasis (RVVC) caused by the pathogenic form of Candida albicans
indicated for women with a history of RVVC. The vaccine candidate uses a
proprietary, recombinant Sap2 protein antigen, one of the main Candida
albicans virulence factors, presented on the surface of virosomes. PEV7 is being
developed in two galenic forms, one for standard intramuscular injection and
one for intravaginal application (capsules).
R A T I O N A L E F O R V A C C I N E D E S I G N
Immunological mechanisms functioning at the vaginal mucosa are still a topic
of intense research and much of what is known comes from animal rather than
human data. Candida-specific cell-mediated immunity has for a long time been
considered the major host defense mechanism against mucosal candida
infections. However, recent studies have demonstrated the important role of
humoral immunity in protection against mucosal candidiasis. More generally,
mucosal antibodies, both secreted IgA and transudated IgG, are highly
important for immunity against pathogens that enter via mucosal surfaces,
since they can act early on during the infection cycle. In the genital tract, IgA
and IgG are equally important and according to preclinical observations, anticandida
IgA and IgG antibodies bind to candida species, thereby reducing
their ability to adhere to epithelial cells and thus preventing the tissue
penetration phase. Based on this knowledge, the goal of Pevion’s candida
vaccine is to elicit a strong protective antibody response that prevents
recurrence.
Recent research also demonstrated that mucosal immunization or a
combination of intramuscular and mucosal immunization can be more efficient
than intramuscular immunization alone. This concept is currently being clinically
validated by two virosomal vaccines. Notably, the candida vaccine PEV7 and
furthermore a HIV vaccine of Pevion’s licensee Mymetics, which demonstrated
good safety and immunogenicity in human at both low and high dose. For the
candida vaccine, Pevion has developed a formulation for intravaginal mucosal
application (capsules), which would also be more convenient for the patient.
Pevion exclusively in-licensed a recombinant Sap2 protein antigen from the
Istituto Superiore di Sanità in Rome (Italy). Sap2 has been identified as a main
virulence factor and represents a prime vaccine target. The use of a protein
antigen requires a suitable carrier and adjuvant system, and Pevion’s virosome
technology is the optimal choice for this purpose.
P R E C L I N I C A L R E S U L T S
In summary, key findings from animal studies are as follows:
Rats immunized with PEV7 showed a rapid fungal clearance from vaginal
fluid, when challenged with pathogenic Candida albicans, in particular during
the first days, which are the most burdening in terms of disease symptoms
The protective efficacy of PEV7 was dose-dependent
PEV7 elicited robust antibody levels in vaginal fluid of both IgA and IgG
specific for the native target protein
Intranasal, sublingual, and vaginal routes of administration resulted in
comparable protection
Toxicity studies in rats, rabbits, and minipigs showed no abnormalities and
merely very mild local irritation
Preclinical studies clearly demonstrated that intravaginal administration of
PEV7 generated a solid immune response to the native antigen target in the
vagina and at the same time leads to very rapid elimination of candida
infection. Both antibody isotypes, IgA and IgG, which are essential for mucosal
immunity, were present in vaginal fluid of immunized animals. Furthermore, it
has been proven that the virosome-based component enhances both
immunogenicity and the protective effect of the antigen.

3
Rapid fungal clearance during
critical first days of infection.
Rats were immunized with the
Candida vaccine PEV7 and then
challenged with pathogenic
Candida albicans. In immunized
rats the pathogen was rapidly
cleared from vaginal fluid (>40 %
reduction of CFU after only 1 day
versus 5 % in unvaccinated animals
(neg control); complete clearance
after 13 days versus 55 % reduction
in unvaccinated animals).
Preliminary Phase I data
show immunogenicity in
human even at low dose
Pevion Biotech AG
Worblentalstrasse 32
3063 Ittigen
Switzerland
Phone +41 31 550 44 44
Fax +41 31 550 44 45
info@pevion.com
www.pevion.com
C L I N I C A L D E V E L O P M E N T
PEV7 has entered a clinical Phase I study in February 2010, which is designed to
evaluate the safety and tolerability of the vaccine as primary endpoint.
Immunogenicity will be evaluated as secondary endpoint. The study will enroll
48 healthy women of childbearing age. Half of the volunteers will receive
intramuscular injections, while the other half will receive capsules, administered
intravaginally.
Positive preliminary data from the first study group that received the vaccine
intramuscularly at a low dose have already been obtained. The results
demonstrated that PEV7 is safe and well tolerated in all subjects and elicits an
immune response even at low dose.
I P S I T U A T I O N
Pevion has a complete patent portfolio regarding virosomes covering all
aspects and applications of the virosome technology platform. In addition,
Pevion holds exclusive patent rights to the recombinant candida antigen and
its use in vaccine formulations. Pevion has full freedom to operate for PEV7.
S E L E C T E D R E F E R E N C E S
Vulvovaginal candidosis. Sobel JD. Lancet 369 (9577): 1961-71 (2007). Review
Anticandidal immunity and vaginitis: novel opportunities for immune
intervention. Cassone A, De Bernardis F, Santoni G. Infect Immun. 75(10): 4675-
86 (2007). Review
Candida albicans secreted aspartyl proteinases in virulence and pathogenesis.
Naglik JR, Challacombe SJ, Hube B. Microbiol Mol Biol Rev. 67(3): 400-28
(2003). Review
Evidence that members of the secretory aspartyl proteinase gene family, in
particular SAP2, are virulence factors for Candida vaginitis. De Bernardis F,
Arancia S, Morelli L, Hube B, Sanglard D, Schafer W, and Cassone A. J Infect.
Dis. 179:201-208 (1999).
Immunization with HIV-1 gp41 subunit virosomes induces mucosal antibodies
protecting nonhuman primates against vaginal SHIV challenges. Bomsel M,
Tudor D, Drillet AS, Alfsen A, Ganor Y, Roger MG, Mouz N, Amacker M,
Chalifour A, Diomede L, Devillier G, Cong Z, Wei Q, Gao H, Qin C, Yang GB,
Zurbriggen R, Lopalco L, Fleury S. Immunity 34(2): 269-80 (2011).
C O N T A C T
To request further information, please contact:
Julian Wagner, PhD, Business Development
info@pevion.com, Tel: +41 31 550 44 44