AiCuris: 10 years of successful R&D in anti-infective therapy · AiCuris at a Glance The Powerhouse for Anti -Infectives Foundation Spin-out from Bayer’s Antiinfective research

AiCuris: 10 years of successful R&D in anti-infective therapy

BIO Europe Cologne, Germany; 08 November 2016

AiCuris: The Powerhouse for Anti-Infectives

“Committed to making the difference”

AiCuris at a Glance The Powerhouse for Anti-Infectives

Foundation Spin-out from Bayer’s Antiinfective research in March 2006. Built up with 21 Bayer experts – today 55 employees

Approach Development of resistance-breaking antiviral & antibacterial agents with new mode-of-actions and/or from new chemical classes

Projects / Products - addressing high medical need Antivirals (HCMV, HSV, HBV, Adenovirus) and Hospital Antibiotics Lead candidate Letermovir (prophylaxis and treatment of HCMV) licensed to Merck & Co (MSD), currently in clinical Phase 3

3 AiCuris - BioEurope 2016

Achievements in Research & Development

AiCuris’ research activities in Virology and Bacteriology resulted in several new development candidates

AiCuris’ development activities Currently 5 projects in Phase 1 2 compounds achieved proof of concept and successfully completed dose-range-finding

in Phase 2 1 compound reached Phase 3 clinical testing (cooperation with MSD)


Indication Program Discovery Preclinical Phase I Phase II Phase III

HCMV Human cytomegalovirus

Letermovir (AIC246) [Licensed to Merck&Co (MSD)]

AIC476

AIC387

AIC813 [Licensed to Merck&Co (MSD)]

HSV Herpes simplex virus Pritelivir (AIC316), oral

Pritelivir (AIC316), topical

Autoimmune diseases AIC284

HBV Hepatitis B virus AIC649

Research

Adenovirus Research

Hospital antibiotic AIC499 [supported by IMI]

Research

Research

AiCuris – R&D Pipeline


Gram-negative Resistance Breaker (AIC499) Superior Drug with Blockbuster Potential

Indication Multidrug resistant (MDR) Gram-negative infections caused by a broad range of bacterial species incl. P. aeruginosa and Enterobacteriaceae

Mode of action Resistance-breaking β-lactam for broad empiric use in combination antibiotic with β-lactamase inhibitor (BLI)

Status of development Advanced Preclinical development

Next events Start clinical Phase 1 expected end 2016

USPs Hospital-treated

Gram-negative bacteria, expected market volume (2021) $3.8B

No approved drug with comparable MDR coverage so far

Premium pricing due to high unmet medical needs in life-threatening situations


AIC499 + BLI allows to treat a vast proportion of infections caused by Gram-negative wild-type and MDR pathogens

Enterobac-teriaceae wt strains

ESBL strains

AmpC strains

KPC strains

OXA-48 strains

NDM strains

P. aerugi-nosa wt

P. aerugi-nosa MDR

strains

Acineto-bacter wt strains

A. bau-mannii

MDR strains

meropenem

imipenem

piperacillin + tazobactam

ceftazidime

ceftazidime + avibactam

aztreonam

aztreonam + avibactam

AIC499

AIC499 + tazobactam

excellent coverage (>90%)

good coverage (70% - 89%)

partial coverage (30% - 69%)

no coverage (<29%)

BLI combination data was not determined

AIC499 profile – Pathogen Coverage


Pritelivir (AIC316) A Perfect Protection against Herpes Simplex Virus

Mode of action: Inhibition of HSV helicase-primase

Indication: HSV infections in immune suppressed patients (“last resort”), treatment and suppression of recurrent genital and labial herpes

Status of development: In preparation for clinical Phase 2 for “Last Resort” In preparation for clinical Phase 2 for “Labial herpes”

Next events Start Phase 2 for “Last Resort” in immunocompromised

patients Start Phase 2 for labial herpes

USPs Novel mode of action Protection of

uninfected cells


Pritelivir A Perfect Protection Against HSV

Cells protected for >24 h due to long half-life

no activation required

Present drugs do not cover sufficient exposure for continuous control of HSV

Viral enzyme (TK) needs to be present for activation of nucleosides

Highly effective suppression of recurrent episodes, shedding and transmission

No protection of uninfected cells Perfect protection

HSV


2.4

5.2

1.7

5.4

0

1

2

3

4

5

6

Pritelivir Valacyclovir Pritelivir Valacyclovir

Shed

ding

rate

(%)

Shedding rate

*** *** 1.9

3.9

1.1

4

00.5

11.5

22.5

33.5

44.5

Pritelivir Valacyclovir Pritelivir Valacyclovir

Lesi

on r

ate

(%)

Lesion rate

*** ***

ITT PP *** p<0.0001

Not shown: log HSV DNA, shedding AUC, as well as number of subjects reporting pain was significantly lower under pritelivir than under valacyclovir

Pritelivir superior to valacyclovir in primary and secondary endpoints

Pritelivir - AIC316-01-II-01 Phase 2 Pritelivir vs. Valtrex™


Indication HCMV infections in cases of immune incompetency, deficiency or immunosuppressed patients (e.g. transplant patients)

Mode of action Antiviral drug, inhibition of HCMV viral terminase

Status of development Met primary endpoint in Phase 3 efficacy / safety study

for prevention of HCMV infection in bone-marrow-transplant recipients (conducted by Merck & Co.)

Orphan drug status in EU and the US, FDA Fast Track Designation

Letermovir (AIC246) New Treatment Approach against HCMV

USPs Novel mechanism

of action Good oral

bioavailability and lack of toxicity


Partnering Track Record Breakthrough Alliance Award 2013 by Deloitte Recap

AiCuris and Merck & Co, USA Enter Exclusive Worldwide License Agreement for Investigational Portfolio Targeting Human Cytomegalovirus

Letermovir, first-in-class small molecule candidate against the Human Cytomegalovirus (HCMV) plus back-up project

Upfront payment €110 m Milestone payments

€332.5 m Royalties on worldwide

sales Option to co-promote in

selected countries

Biggest licensing deal of a German biotech company

Awarded „Deal of the Year“ 2013 with prestigious Deloitte Recap Breakthrough Alliance Award

Asset The deal structure Highlights


Summary – 10 years of AiCuris A Company with Proven Track Record in R&D

The Powerhouse for Anti-Infectives

Scientists and experts in all focus research fields and for all pre-clinical and clinical development activities

Proven track record as PoC company Current pipeline comprises

advanced projects originating from own in-house research

Multiple new research and development projects since foundation in 2006

Global network of experts, partners and service providers

In addition to in-house R&D, focused scouting activities towards identification of: New interesting targets/MoAs for

antivirals and antibacterials Potential joint development partners

and in-licensing opportunities Opportunities to expand our pipeline

and business


AiCuris: 10 years of successful R&D in anti-infective therapy

BIO Europe Cologne, Germany; 08 November 2016

Documents

AiCuris: 10 years of successful R&D in anti-infective therapy · AiCuris at a Glance The Powerhouse for Anti -Infectives Foundation Spin-out from Bayer’s Antiinfective research