Slide title. Deborah O NeilO. February 23 rd, t: f:

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1 Deborah O NeilO February 23 rd, 2011

2 The Business Based in Aberdeen Key biologics & anti-infectives infectives cluster Founded 2004 Design & develop novel anti-infectives infectives Peptide therapeutics Target poorly served antifungal & antibacterial indications Lead product completed phase IIa clinical development 2010

3 R&D Programmes

4 Technology Platform Third generation antimicrobial peptides First cousins of endogenous antimicrobial peptides (AMP): Ideal therapeutic targets perhaps But not druggable NovaBiotics has taken AMP apart & re-built them to generate a new class of AMP Biology, not chemistry led; rational drug design

5 The Approach Apply synthetic AMP as therapeutics to replace/enhance endogenous AMP Endogenous AMP form the cornerstone of eukaryotic/prokaryotic immunity Central to first line antimicrobial defence...etc. (pleiotropic effects) Susceptibility to infection from a failure in this system or inability to deploy it Epithelial/keratinocyte derived AMP (β-( defensins, cathelicidins) Neutrophil derived AMP (α-defensins( defensins)

6 AMP Therapeutics: Benefits Known/predicted mode of action (MOA) Microbicidal (fungicidal) Membrane perturbation & lysis Inhibition of germ-tube formation MOA minimises or negates the risk of acquired resistance Targeted specifically to microbial (fungal) versus host cell membranes Attractive safety/toxicological profile Hydrophilic compounds Formulation/delivery flexibility

7 150 proprietary/patented peptides >250 microbes assessed for susceptibility NovaBiotics AMP retain only the positive features of endogenous AMP Comprise the same core cationic amino acids Simpler in structure & smaller in size Technology Platform Clinical isolates of Gram-positive & Gram-negative aerobic & anaerobic bacteria, dermatophytes, yeasts & moulds (susceptible & resistant to conventional antimicrobials) Enhanced activity, specificity, stability, bioavailability Selected by tailored proprietary assay systems Expert technical team & resources in-house

8 The Lead Onychomycosis (fungal nail infection) provides an attractive topical first indication $5 bn,, poorly served global market 12% of the worlds population are affected only 4 licensed products currently available safety/tox tox issues, efficacy rates of 6-38%, 6 used for weeks Endogenous AMP facilitate antimicrobial protection within the skin & nails NovaBiotics has replicated this with a synthetic AMP selected for delivery through the nail: Fungicidal activity, charge, size & stability

9 The Lead Novexatin /NP213 Patented clinical stage API Topical (brush-on) treatment for nail fungus HN H 2 N NH 2 H N NH NH HN O O N H O NH H 2 N H N O O NH H N O NH H N H N O H 2 N N H NH N H NH 2 NH Novexatin proven thus far to be safer & more effective than a limited competition Penetrates the nail but not skin Remains bioavailable and fungicidal within the nail Clears infection within 28 days (versus weeks) A comprehensive preclinical and clinical data package HN HN NH 2 HN HN NH 2

10 Novexatin Novexatin penetrates full thickness nail & remains bioavailable within as a fungicidal peptide against Trichophyton spp

11 Novexatin clinical development: Onychomycosis Day 0 Day 180 Novexatin (28 days) Mycologically negative Vehicle only (28 days) Mycologically positive

12 Novexatin clinical development: Onychomycosis Example of clinical/pd data acquired patient SID Day 0 mycological status Day 29 mycological status Culture -ve Culture +ve+ Visible hyphae DTM colour change No hyphae visible

13 Clinical Improvement Throughout the Trial Period Slide title Novexatin Clinical development: Onychomycosis Clinical and Mycological Day 180 Assessment % Patients Reporting Improvement in Nail Appearance Mild infection Novexatin Placebo

14 Novamycin Candidiasis/candidaemia remains a poorly served & increasingly prevalent clinical problem Expanding population of at-risk individuals Novamycin has potential application in OPC as well as systemic anti-candida applications Novamycin also has utility in non-candida infections Aspergillosis, cryptococcosis etc. Preclinical development underway & anticipated to be in clinic 2011/2012

15 Novamycin /NP339 Novamycin Patented candidacidal peptide (linear, 2 kda) ) with common molecular architecture to Novexatin Active against all Candida spp & other clinically relevant & antifungal yeasts & moulds No resistance development (>65 cycles) Equally effective against metabolically active & inactive Candida spp & rapidly fungicidal (<30 min) C. albicans biofilm eradication/prevention pk profiling to establish optimal dosing regime/delivery Promising initial acute tox & in vivo efficacy data in two models of acute, disseminated C. albicans infection

16 Novamycin Growth (OD530) Activity of Novamycin Against C. albicans in vitro Concentration (µg/ml) Dose-dependent candidacidal activity of Novamycin in vitro against C. albicans SC5314 Novamycin = a peptide with small molecule potency

17 Novamycin Activity of Novamycin Against C. albicans in vitro Novamycin rapidly kills Candida spp in vitro with an MIC 100 of 1-2 µg/ml The fungicidal mechanism of action and rapid time of kill of Novamycin demonstrated by flow cytometric analysis of C. albicans SC5314

18 Novamycin Candidacidal Activity of Novamycin in an in vivo Model of Acute Candidiasis Mean CFU/g Kidney Weight Control Novamycin Amphotericin B Efficacy of a single dose of Novamycin (1 mg/kg) demonstrated in a murine model of disseminated C. albicans infection versus amphotericin B (5 mg/kg)

19 Novamycin Novamycin Retains Activity in Saliva Growth (OD 530 ) Nystatin Novamycin Concentration (μg/ml) Efficacy in saliva suggests application of Novamycin in OPC

20 Novamycin Activity (in vitro) of Novamycin Against Non-Candida Fungal Pathogens Growth (OD 530 ) Concentration (µg/ml) Growth (OD530) Concentration (µg/ml) Activity against A. fumigatis Activity against C. neoformans

21 NP432 Bactericidal peptide NM001 Mucolytic/antibacterial Antibacterials Programme Active against Gram-negative& Gram-positive organisms Respiratory, systemic & dermal infections Gram-negative infections associated with cystic fibrosis a priority indication Biofilm eradication & prevention In vivo tolerability demonstrated & reduction of bacterial burden in lung Pseudomonas aeruginosa infection model

22 NP432 Activity of NP432 versus P. aeruginosa 57833C Growth (OD 625 ) Concentration(µg/ml) The antibacterial peptide NP432 demonstrates potent activity (24 h) against clinical isolates of Pseudomonas spp.

23 NP432 NP432 is a Potent Disrupter of Bacterial Biofilms Impact of NP432 on biofilms of clinically relevant Staphylococcus assessed using live/dead stain microscopy (live organisms green/dead organisms red)

24 NM001 NM001 prevents Bacterial Biofilm formation T=0 h T=0 h T=17 h NM001 2 mg/ml Little or no established biofilm Control Thick mucus biofilm Impact of NM001 P. aeruginosa biofilm formation assessed using the BioFlux system

25 NM001 NM001 as a Combination Therapy P. aeruginosa Tobramycin TOB + NM001 S. aureus Growth (OD625) Concentration (µg/ml) S. aureus NM001 demonstrates additivity or synergy when applied in combination (against Gram-positive & Gram-negative bacteria) with NovaBiotics novel AMP or conventional antibiotic therapies

26 Summary Peptides provide the ideal molecular platform for building novel antimicrobials For the same reasons that their endogenous counterparts are vital to natural immunity Mode of action (specificity only to microbes) Lack/minimal risk of resistance in target pathogens Clinical validation of NovaBiotics novel class of anti-infectives infectives Application in acute & chronic disease Novexatin versus Novamycin & pipeline

27 Summary Rationally designed, synthetic AMP provide a potential solution to the unmet need for more effective & safer antimicrobials Antifungals & antibacterials Where chemistry led-approaches have failed; e.g. ability to penetrate nail barrier differentiate subtleties of fungal and mammalian cell wall component better toxicity profiles Even in the most challenging of infections primary care/community acquired nosocomial

28 Emma Brown Cedric Charrier Vanessa Duncan Derry Mercer Lorna Miller Krissie Millar Jennifer Robertson Shaun Robertson Shane Smith Colin Stewart Linda Turvey Slide title Neil Gow Donna McCallum Carol Munro The Team

29 Deborah O NeilO February 23 rd, 2011 deborah@novabiotics.co.uk