Dr Derry K Mercer Principal Scientist NovaBiotics Ltd. Antimicrobial peptides as the next generation of anti-infectives
Slide title
Dr Derry K Mercer Principal Scientist NovaBiotics Ltd
Antimicrobial peptides as the next generation of anti-infectives t: +44 1224 71137...
Candidiasis, candidaemia, Aspergillosis Gram –ve and +ve bacterial infections
www.novabiotics.co.uk
Slide title Technology platform Potential solution to the current & future unmet need for new antimicrobials
• Antifungal & antibacterial peptides (AMP) – First line of body’s defense
• Re-engineered a new class of antimicrobials against this template • Clinical potential in difficult to treat diseases where traditional small molecule chemistry is failing – – – –
Potent, synthetic derivatives of natural AMP Microbicidal (kill) mode of action Low/no toxicity No resistance development
• Global market for anti-infectives worth >$80bn t: +44 1224 711377 f: +44 1224 711370
www.novabiotics.co.uk
Slide titleAMPs Deconstructed First Generation AMP Innate immunity AMPs
Identify antimicrobial regions
Remove immunomodulatory regions
Remove cytotoxic regions
Modify residues to improve efficacy Second Generation AMP t: +44 1224 711377 f: +44 1224 711370
Remove/replace immunomodulatory residues Introduce novel residues to improve efficacy and other active moeities Formulate to improve in vivo efficacy and bioavailability Third/Fourth Generation AMPs t: +44 1224 711377 f: +44 1224 711370
www.novabiotics.co.uk
Novexatin®
Slide titleLead product candidate • Topical treatment for nail fungus, partnered with Taro for further clinical development & commercialization
• First product to address both the infectious & cosmetic issues of onychomycosis – Outperforms the competition
• Unique, first-in-class features of Novexatin® include: – Fungicidal, penetrates nail – Maintains therapeutic activity in nail for > 1 year
– Time to treat: 28 days •
Nail fungus affects 12% of the global population - >$6bn global market by 2022 t: +44 1224 711377 f: +44 1224 711370
www.novabiotics.co.uk
Lynovex®
Slide title Therapy for cystic fibrosis • Global market for CF worth $4.59bn (2017) • Lynovex also relevant for COPD & other chronic respiratory diseases • Small molecule
• Novel dual mucolytic and antibacterial agent • Orphan drug status for the treatment of CF
• Outperforms current ‘gold standard’
t: +44 1224 711377 f: +44 1224 711370
www.novabiotics.co.uk
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Lynovex® Therapy for cystic fibrosis
• Adjunct therapy to currently employed CF treatments – Synergizes with CF antibiotics to potentiate their effects
• Already approved for use in an unrelated, orphan indication - drug re-purposing – Discussions underway with license holders re: commercial collaboration – Phase IIa clinical trial (CF patients) for oral form anticipated to commence Q2/2014 – Developing inhaled form of Lynovex in parallel t: +44 1224 711377 f: +44 1224 711370
• Active against Aspergillus and Cryptococcus – Common molecular architecture to Novexatin – Membranolytic mechanism of action
• Positive in vivo data in clinically predictive models • Early commercial discussions underway re: women’s health applications • Major therapeutic USPs over existing antifungals – outperforms other drug classes • Global market worth $5.7bn (2014) for systemic mycoses t: +44 1224 711377 f: +44 1224 711370
www.novabiotics.co.uk
Novarifyn®
Slide titledifferentiated antibacterials Highly • First in class bactericidal peptides • Rapidly kill even multi-drug resistant, clinically & economically significant pathogens • High potency against Gram -ve & Gram +ve targets • No toxicity/wide therapeutic window in vitro and in vivo • Efficacious & well tolerated in in vivo models of infection • Global market for antibiotics worth $45bn (2013) t: +44 1224 711377 f: +44 1224 711370
Application and spreading of Test Item Fungal inoculum
Nutrient-free agar plate
t: +44 1224 711377 f: +44 1224 711370
Inert support
www.novabiotics.co.uk
t: +44 1224 711377 f: +44 1224 711370 A m
N ov ex at
40 00 (2
8
8
(2
d)
d)
in (2 8 or d) o 5% lo fin A e m (2 or 8 ol d) of Sc in ho e (1 ll 8% 80 Pe C d) r f ic ec lo t pi N ro ai 8% lP x O en C la ic m lo in pi e ro (2 x 8 O d) la m in e (6 0 d) Ex ci lo r( 28 d)
5%
10 %
Pe g
er
at
W
Growth (cfu/ml)
Slide title Versus the Competition
1.0×10 6
1.0×10 5
1.0×10 4
1.0×10 3
1.0×10 2 Limit of detection
1.0×10 1
1.0×10 0
www.novabiotics.co.uk
Slide title Long-term efficacy CFU recovered (%)
150 125 Novexatin®
28 d treatment
100
Untreated control nails disintegrate
75
New control nails infected with T. rubrum
50
Nails re-infected with T. rubrum
25 0 0
All nails infected
1
2
3 4 Time (Months)
5
6
An application period of 28 days treats for 12 months t: +44 1224 711377 f: +44 1224 711370
www.novabiotics.co.uk
12
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Novexatin®
Dead fungal hyphae
Live fungal hyphae
Novexatin-treated, 14 d
Itraconazole-treated, 14 d
Novexatin® penetrates the nail and kills fungus. t: +44 1224 711377 f: +44 1224 711370
www.novabiotics.co.uk
Slide titlePhase IIa Trial Summary • Despite limitations/restrictions, clear evidence of efficacy was obtained from the Phase IIa safety study • Data demonstrated evidence of clinical and also combined clinical & mycological improvement • Improvement more obvious in patients with mild to moderate infection • All data would have been statistically significant – >80% confidence limit by two-tailed non-parametric analyses if using sample sizes planned for the Phase IIb study t: +44 1224 711377 f: +44 1224 711370
www.novabiotics.co.uk
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Lynovex®
• Orphan drug candidate • First in class, highly differentiated approach to tackling cystic fibrosis – Mucoactive – Antibacterial & antifungal – Antibiofilm
• Tri-functionality, two routes of delivery – Oral & aerosol
• Adjunct therapy for use alongside existing CF antibiotics Repurposing one orphan drug (cysteamine for cystinosis) for another orphan indication t: +44 1224 711377 f: +44 1224 711370
Lynovex® has approximately double the mucolytic activity of currently marketed products t: +44 1224 711377 f: +44 1224 711370
www.novabiotics.co.uk
Slide titleAntimicrobial Activity
*
‘eradication’
~4 log reduction ~1 log reduction
~3 log reduction
t: +44 1224 711377 f: +44 1224 711370
www.novabiotics.co.uk
Slide titleAntimicrobial Activity Antimicrobial activity of CF panel antibiotics in combination with Lynovex® Reversal of antibiotic resistance, synergy (S)& additivity (A) Lynovex Synergy (S) or additivity (A) observed with P. aeruginosa
Colistin
Ciprofloxacin
Tobramycin
Gentamicin
strain
Antibiotic Resistance
Pa01
ColR
S
-
S
S
Pa14
ColR
S
A
A
A
Pa058
ColR CipR
A
A
A
A
TobR Pa57388A
ColR
S
A
S
S
Pa57388D
ColR GentR
S
A
S
S
t: +44 1224 711377 f: +44 1224 711370
www.novabiotics.co.uk
Slide title
Lynovex What Next?
• Phase IIa study will commence in Q2/2014 – 12-15 adult CF patients – Open label study – Orally available cysteamine bitartrate
• Oral (capsule) form for exacerbations • Develop inhaled form for maintenance – Adults & paediatric patients
• Goal: A first-in-class, front-line adjunct therapy for long-term treatment & management of CF Potential for significant clinical benefit & impact on quality of life if ex vivo data translates through to the clinic t: +44 1224 711377 f: +44 1224 711370
www.novabiotics.co.uk
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Summary
• Leading edge science combined with validated product & technology platform through global licensing deal with Taro Pharmaceuticals Inc. • Attractive mix of clinical stage product candidates, pipeline programmes & platform technology • Novel therapeutics with significant/blockbuster potential – – – –
Fungal nail infection: >$6bn1 Cystic fibrosis: $4.59bn2 Deep tissue & bloodstream fungal infections: $5.7bn3 Antibacterials: £45bn4
t: +44 1224 711377 f: +44 1224 711370
www.novabiotics.co.uk
Slide title
Summary
• Initiate Phase IIb clinical trial of Novexatin® • Complete Phase IIa clinical trial of Lynovex ® • Initiate Phase I trial of Novamycin ®
• Extend pre-clinical/in vivo testing of Novarifyn ® • Continue pipeline development t: +44 1224 711377 f: +44 1224 711370
