Transcript Truly Novel Anti-Infectives MGB Biopharma – Delivering True Novelty

Bringing True Novelty to the
Anti-Infectives Space
New Class of Antibacterials Based on
a Completely New Mechanism of Action
Biotrinity
13th May 2014
Truly Novel Anti-Infectives
MGB Biopharma – Delivering True Novelty
• Developing a truly novel class of drugs for infectious diseases
based on the University of Strathclyde’s DNA Minor Groove
Binder (MGB) Technology
• This platform provides an opportunity to develop various
compounds against bacteria, viruses, fungi and parasites with a
completely new mode of action which are distinct from the
antimicrobial drugs used in clinical practice today
• MGB-BP-3 is the first compound from this platform, with strong
activity against Gram-positive pathogens, ready to progress into
clinical development
• Founded in April 2010 – HQ in Glasgow, Scotland - and funded by
an Angel syndicate and the Scottish Co-Investment Fund
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Truly Novel Anti-Infectives
The First Novel Mode of Action For Decades
• MGBs bind A-T or G-C rich
sequences within the minor
groove of bacterial DNA in a
sequence and conformationspecific fashion
• Interferes with transcription
factors and alters the
microorganism’s regulation
• Does not inhibit bacterial
DNA replication
Binding of MGB-BP-4 compound to the
DNA minor groove; NMR-derived structure
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Truly Novel Anti-Infectives
Novel Anti-Infectives Platform
Discovery
Hit-to-Lead
Lead
Optimisation
Preclinical
Phase I
Phase II
MGB-BP-3 C. diff oral
MGB-BP-3 MRSA etc. IV
MGB-BP-3 topical
Gram-negative
Anti-fungal
Anti-viral
Anti-parasitic
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Truly Novel Anti-Infectives
MGB-BP-3 – Our Lead Molecule
• Oral formulation for C. difficile infections – IND ready
(endorsed by MHRA to progress into a phase I study)
• I.V. formulation targeting a broad range of Gram +ve
pathogens - clinic-ready in 2015
• Topical formulation – feasibility testing
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Truly Novel Anti-Infectives
MGB-BP-3 oral formulation
Activity of MGB-BP-3 against Clostridium difficile compared to vancomycin
Graph plotting log10 reduction of viable cells against time on
exposure to x2, x4 and x8 the MIC of MGB-BP3 and vancomycin
against C. difficile isolate ATCC 700057
Graph plotting log10 reduction of viable cells against time on
exposure to x2, x4 and x8 the MIC of MGB-BP3 and vancomycin
against C. difficile isolate NCTC13366 (NAP1/027)
MGB-BP3 x2
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MGB-BP3, all
concentrations
MGB-BP3 x8
6
MGB-BP3 x2
6
12
2
18
6
24
Time(h)
Control
Control
0
0
Vancomycin x8
4
log10 reduction
2
log10 reduction
Control
Vancomycin x4
Vancomycin x8
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Vancomycin x4
Vancomycin x8
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Vancomycin x4
MGB-BP3 x8
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Vancomycin x2
Vancomycin x2
MGB-BP3 x4
Vancomycin x2
log10 reduction
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MGB-BP3 x4
6
-2
Graph plotting log10 reduction of viable cells against time on
exposure to x2, x4 and x8 the MIC of MGB-BP3 and vancomycin
against C. difficile isolate 113703-13
8
12
18
24
2
0
6
Time(h)
12
18
24
Time(h)
-2
-2
-4
-4
-4
Superior activity against C. diff in comparison to vancomycin
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Truly Novel Anti-Infectives
MGB-BP-3 intravenous formulation
• Under development for the treatment of hospital acquired
systemic Gram-positive infections (susceptible and resistant
Staphylococcus, Streptococcus and Enterococcus)
• MGB-BP-3 lyophilised as a glutarate salt
• Reconstituted with WFI and 5%dextrose
• Acute tolerability study in mouse confirmed MTD of 100mg/kg
(anticipated human dose 7-15mg/kg)
• Pharmacokinetic profile supported bolus and continuous
intravenous administration
• In vivo activity confirmed in mouse infection models
• Manufacturing optimisation and scaling up ongoing
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Truly Novel Anti-Infectives
MGB-BP-3 further development
2014
MGB-BP-3 C diff Phase I
1 Optimisation and GMP manufacturing 4kg
2 Clinical Batch Manufacture (Encap)
3 Stability (Encap)
Project 1
4 IMPD - MHRA CTA Submission
5 Packaging and labelling (Almac)
6 Phase I SAD & MAD
Q1
Q2
2015
Q3
Q4
Q1
Q2
2016
Q3
Q4
Q1
Q2
MGB-BP-3 Intravenous formulation up to IND-Ready
1 PK infusion study in rats
2 Single Dose DRF Study in the Rat
Project 2 3 Animal infection models (thigh and sepsis)
4 PK/PD in vivo assessment (Strept&Staph)
5 Metabolism (radiolabelled in rats)
6 GMP tox batch production (Aptuit)
7 Stability (Aptuit)
8 Safety pharmacology (CNS, CV and Resp)
Project 3
9 Micronucleus study (rats)
10 General toxicity (14-day rat/dog studies)
11 MHRA pre-IND meeting
MGB-BP-3 Topical formulation feasibility study (Medpharm)
1 Formulation as a topical dosage form
Project 4
2 Efficacy against S aureus
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Truly Novel Anti-Infectives