DGAP-News: AiCuris Anti-infective Cures GmbH: Two Recent Publications on Pritelivir Confirm the Potency of the Novel AiCuris Anti-Herpes Simplex Virus Drug

DGAP-News: AiCuris Anti-infective Cures GmbH / Key word(s): Scientific
AiCuris Anti-infective Cures GmbH: Two Recent Publications on Pritelivir
Confirm the Potency of the Novel AiCuris Anti-Herpes Simplex Virus Drug

23.06.2016 / 09:00
The issuer is solely responsible for the content of this announcement.


Two Recent Publications on Pritelivir Confirm the Potency of the Novel
AiCuris Anti-Herpes Simplex Virus Drug

– Clinical data published in the peer-reviewed “Journal of Infectious
Diseases” showed no evidence of resistance in HSV-2 sequences obtained
from genital swabs collected during a phase II trial

– Pritelivir clinical phase II data were used for the development of a
mathematical model to optimize dose selection for clinical trials
published in the renowned journal “Science Translational Medicine”

Wuppertal, Germany, June 23, 2016 – AiCuris Anti-infective Cures GmbH, a
leading company in the discovery and development of drugs against
infectious diseases, announced today the publication of results assessing
molecular signals of drug resistance over 28 days of therapy; this was a
secondary objective from a recent phase II dose finding study with
pritelivir. The peer-reviewed article titled: “No evidence of resistance of
HSV-2 to pritelivir following four weeks of daily therapy” was prepared in
collaboration with Dr. Paul Edlefsen and colleagues at the Fred Hutchinson
Cancer Research Center and University of Washington, Seattle, Washington,
USA, and will be published in the July issue of “The Journal of Infectious

Pritelivir belongs to a new class of antiviral compounds, the helicase-
primase inhibitors, being developed to treat herpes simplex virus type 1
(HSV-1) and type 2 (HSV-2) infections. Oral pritelivir has successfully
completed a phase II clinical trial in 156 participants with genital HSV-2
infections showing reduced viral shedding and genital lesions. The
mentioned peer-reviewed article reports the results of a secondary
objective of this clinical study. It specifically assesses the emergence of
mutations consistent with helicase-primase inhibitor resistance in people
receiving pritelivir for daily treatment of genital HSV-2 infections, even
at suboptimal doses.

Importantly, no changes in HSV-2 sequence occurred during treatment in the
individual patients and no emergence of resistance mediating mutations was
observed. Overall, only few mutations relative to the consensus sequence
were found and these observed variations were considered to be reflective
of pre-existing HSV-2 diversity among the trial participants.

Link to published article:

“The prevalence of HSV-2 infections in the general population ranges from
10% to 60% worldwide. HSV-2 infections can lead to genital herpes, which
typically causes painful ulcers. Infections can also be unrecognized,
meaning that infected individuals, with or without symptoms, can shed HSV
and so can infect sexual partners,” said Dr. Holger Zimmermann, CEO of
AiCuris. “These publications show, once again, that pritelivir is proving
to be an exceptional approach to herpes treatment. With its novel mode of
action and no evidence of resistance to pritelivir, we are confident that
this small molecule therapy could become an important option to treat HSV
infections,” he added.

Using data from the same clinical phase II dose finding trial, the renowned
journal “Science Translational Medicine” published an article in February
2016 titled “Mathematical modeling of herpes simplex virus-2 suppression
with pritelivir predicts trial outcomes.” In this article, again in
collaboration with the Fred Hutchinson Cancer Research Center as well as
with ICPD (Institute for Clinical Pharmacodynamics, Latham, New York, USA),
Dr. Joshua Schiffer et al. introduced a mathematical model to optimize dose
selection for clinical trials by combining for the first time population
pharmacokinetics with a previously established model of viral pathogenesis
in genital HSV infection to simulate the efficacy of a compound.

The mathematical simulation was able to model viral shedding kinetics in
the five treatment groups and thus to predict the trial outcome. Moreover,
it confirmed that based on its innovative mode of action and its long half-
live, pritelivir can effectively and dose-dependently decrease viral
replication by decreasing shedding episode frequency, duration, and viral
load. In addition, the model indicates that besides inhibiting replication
in epithelial cells, pritelivir seems also to inhibit the virus directly in
the neuron.

Link to published article: http://stm.sciencemag.org/content/8/324/324ra15.

About Pritelivir
Pritelivir is an innovative, highly active and specific inhibitor of herpes
simplex virus (HSV). As a compound derived from a novel chemical class
(thiazolylamides), pritelivir is active against both types of herpes
simplex virus (HSV-1 and HSV-2) causing labial and genital herpes,
respectively, and retains activity against viruses which have become
resistant to marketed drugs. Pritelivir has a mode of action that is
distinct from other antiviral agents currently in use for treating HSV
infections (i.e., the nucleoside analogues acyclovir and its prodrug
valacyclovir as well as famciclovir, the prodrug of penciclovir). Whereas
nucleoside analogs terminate ongoing DNA chain elongation through
inhibition of viral DNA polymerase, pritelivir prevents de novo synthesis
of virus DNA through inhibition of the helicase-primase complex. In
addition, it does not require activation within an HSV infected cell by
viral thymidine kinase and is therefore also protective to uninfected

Currently the company runs two clinical development programs with
pritelivir. The most advanced program, pritelivir (oral), showed
superiority against standard treatment valacyclovir in a clinical phase II
trial in patients with genital HSV-2 infection. Pritelivir (topical),
designed for the treatment of recurrent labial herpes (mainly HSV-1), just
entered phase I clinical testing.

About HSV
Herpes simplex viruses (HSV) are widespread in the human population
(seroprevalence up to 100%, depending on geographic area and
subpopulation), and are divided into herpes simplex virus type 1 (HSV-1)
and type 2 (HSV-2). Infections lead to lifelong persistence of the virus,
with frequent and sometimes painful recurrences. While HSV-1 predominantly
causes oral lesions (cold sores), HSV-2 manifests in the genital region and
is mainly sexually transmitted. In immunocompromised patients, HSV can lead
to serious complications. In the immune competent, the negative stigma
associated with genital herpes and visible facial lesions might cause
psychological distress.

About AiCuris Anti-infective Cures GmbH
AiCuris was founded in 2006 as a spin-off from Bayer and focuses on the
discovery and development of drugs against infectious diseases. Majority
investor is the SANTO Holding. The company is developing drugs for the
treatment of viruses such as human cytomegalovirus (HCMV), herpes simplex
virus (HSV), hepatitis B virus (HBV), and adenoviruses. In the field of
antibacterials, AiCuris is concentrating on the search for innovative
treatment options for life-threatening (multi)resistant hospital-treated
pathogens. In 2012, AiCuris signed a license agreement with Merck & Co
(MSD) which attracted significant attention being one of the largest
agreements of this kind in the European biotech industry. The agreement
covers the development of novel drug candidates against HCMV. Letermovir,
the most advanced compound, is currently in phase III clinical trials in
patients undergoing bone marrow transplantation.

                                  Media Relations
AiCuris Anti-infective Cures      MC Services AG
Katja Woestenhemke                Anne Hennecke
Friedrich-Ebert-Str. 475/Geb.     Kaiser-Friedrich-Ring 5
42117 Wuppertal                   40545 Düsseldorf

Phone      +49 202 317 63 0       Phone    +49 211 529 252 22
Fax          +49 202 317 63 1601  Fax        +49 211 529 252 29
Email      business@aicuris.com   Email     anne.hennecke@mc-services.eu
Web        www.aicuris.com        Web       www.mc-services.eu


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