Transcript presentation_Turowska

Spin-off in practice
German experience from Polish
perspective
Dr. Agnieszka Turowska
Warsaw, 2015
0 06.05.2011
The German Biotechnology Sector 2014
• Number of companies dedicated to biotechnology: 570 (incl. 13 start ups)
• Number of employees in dedicated biotechnology companies 16.950
• Over 90 drugs in clinical trial testing
• R&D expenditure of dedicated biotechnology companies 899 Mio.€
source: Report: The German Biotechnology Sector 2014, biotechnologie.de
Drug development process
• 10-15 years for a drug to travel from the research lab to the patient.
• 1 to 3 billion euros is the cost of a new drug development from the
research lab to the patient
• 1 in 10 000 active substances tested in research lab will be placed
on the market
source: Report: The German Biotechnology Sector 2014, biotechnologie.de
sterna biologicals GmbH - Company Overview
Objective
Development of novel DNAzyme-based therapies for chronic
inflammatory diseases
Lead
Product
SB010 for moderate and severe Th2-driven asthma
Further
Indications
• Atopic Dermatitis
• Psoriasis
• Ulcerative Colitis
• COPD
Founded in
2006
Location
Marburg, Germany
Employees
10
DNAzymes as therapeutic agents
1
DNAzyme specifically binds to target mRNA
3
Decomposition of cleavage products; DNAzyme continues cleavage activity
2
DNAzyme cleaves GATA-3 mRNA
Reduced mRNA levels resulting in
decrease of translated protein
with subsequent biological
consequences
GATA-3 is the Master Transcription Factor
in Th2-driven Inflammatory Diseases
• GATA-3 plays a central role in the
allergic inflammatory response
• Orchestrates a wide range of Th2mediated cytokines, in particular IL4, IL-5, IL-9, and IL-13
• Recent evidence that GATA-3 is also
expressed directly in Mast cells,
Epithelial cells, and Eosinophils
further supports central role of
GATA-3
• By targeting GATA-3 directly, SB010
impacts multiple Th2-dependent
downstream pathways (“broad
spectrum“ approach)
Source: Barnes P. JCI 118 (2008): 3546-3556.
Homburg et al. ``Safety and tolerability of a novel inhaled GATA3 mRNA targeting DNAzyme in patients with TH2driven asthma`` J Allergy Clin Immunol (2015)
Turowska et al. ``Biodistribution of the GATA-3-specific DNAzyme hgd40 after inhalative exposure in mice, rats and
dogs." Toxicol Appl Pharmacol (2013)
Fuhst et al. ``Toxicity profile of the GATA-3-specific DNAzyme hgd40 after inhalation exposure." Pulm Pharmacol
Ther. (2013)
Dicke et al. "Absence of unspecific innate immune cell activation by GATA-3-specific DNAzymes." Nucleic Acid Ther
(2012)
Sel et al. "Effective prevention and therapy of experimental asthma using a GATA-3 specific DNAzyme." JACI (2008)
Schmidts et al. " Protective effect of drug delivery systems against the enzymatic degradation of dermally applied
DNAzyme." Int J Pharm (2011)
Schmidts et al. " Development of drug delivery systems for the dermal application of therapeutic DNAzymes." Int J
Pharm (2012)
Key development milestones for biotech
spin-off company
• Preclinical program
• Toxicology and local tolerability studies
• Investigational Medical Product (IMP)
• Phase I clinical trial
• Phase II clinical trial
• Phase III clinical trial
• Phase IV clinical trial
Preclinical program
• To know and understand the pathogenesis of the disease
• To identify crucial pathways and interfere with them by appling a drug molecule
• To demonstrate specificity of the molecule (target regulation)
• To proof efficacy in in vitro and in vivo animal model(s)
• To determine optimal and minimal effective dose
• To determine optimal application regimen
• To evaluate uptake, kinetics and distribution
• To investigate potential off-target effects
• To develop analytical method of drug detection
• Time: 1-3 years, outsourcing vs internal development
Key development milestones for biotech
spin-off company
• Preclinical program
• Toxicology and local tolerability studies
• Investigational Medical Product (IMP)
• Phase I clinical trial
• Phase II clinical trial
• Phase III clinical trial
• Phase IV clinical trial
Toxicological program
on the example of SB010 for asthma treatment
Toxicological program
on the example of SB010 for asthma treatment
• Certified Good Laboratory Practice (GLP) Facility
• Parallel vs. sequential proceeding (risk/benefit ratio)
• The number and design of toxicology studies may differ depending
on country and regulatory agency
• Time: 1-3 years
Key development milestones for biotech
spin-off company
• Preclinical program
• Toxicology and local tolerability studies
• Investigational Medical Product (IMP)
• Phase I clinical trial
• Phase II clinical trial
• Phase III clinical trial
• Phase IV clinical trial
Investigational Medical Product (IMP)
• GMP (Good Manufacturing Practice) certified
manufacturing
• Stability studies (min. 6 months)
• Certified Packaging
• Transport & distribution
Key development milestones for biotech
spin-off company
• Preclinical programm
• Toxicology and local tolerability studies
• Investigetional Medical Product (IMP)
• Phase I clinical trial
• Phase II clinical trial
• Phase III clinical trial
• Phase IV clinical trial
Clinical Trial Overview
• Phase I clinical trial
Primary goal: safety & tolerabilty (20-80 subjects, weeks to months)
First in class First in man
I a: safety & tolerability
I b: safety & tolerability
I c: safety & tolerability
[single dose, healthy subjects]
[multiple doses, healthy subjects]
[single dose, patients]
• Phase II clinical trial
Primary goal: efficacy & safety (30 -200 patients, months to years)
First in class
II a: explorative POC study
II b. Proof of concept study
[multiple dose, patients]
[multiple ascending dose, patients]
• The number and design of clinical trials may vary depending on country
and regulatory agency
Key development milestones for biotech
spin-off company
• Preclinical program
• Toxicology and local tolerability studies
• Investigational Medical Product (IMP)
• Phase I clinical trial
• Phase II clinical trial
• Phase III clinical trial
• Phase IV clinical trial
value
risk
quality
requirements
Is it realistic for academic spin-off to place the drug on the market?
Evaluation criteria
• Scientific publications
• Conference presentations & posters
• Reports from preclinical and toxicological studies a including raw data
• Documents submitted to regulatory agencies: Investigator´s Brochure (IB),
clinical trial protocol, Investigational Medical Product Dossier (IMPD)
• Audit reports of the external collaborators
• SOP (Standard Operating Procedure)
process overview
Summary
• The goal & destination of academic spin-off should be defined
at the beginning based on: human resources, financial status,
potential of research facility
• Interaction with business partners is inscribed in the nature of
academic spin-off
• Therefore, quality standards required by business partners
have to be fullfilled (or exceeded!) in order to ensure
collaboration and secure seed financing
• Meeting quality standards in practice means that the structure
of academic spin-off should be carefully designed (professional
writer & quality control, GLP)
Thank you