06.05.20110 Dr. Agnieszka Turowska Warsaw, 2015 Spin-off in practice German experience from Polish...

06.05.2011

1

Dr. Agnieszka Turowska

Warsaw, 2015

Spin-off in practiceGerman experience from Polish perspective

• 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.€

The German Biotechnology Sector 2014

source: Report: The German Biotechnology Sector 2014, biotechnologie.de

• 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

Drug development process

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

Founded in

2006

Employees 10

Further Indications

• Atopic Dermatitis

• Ulcerative Colitis

Location Marburg, Germany

• Psoriasis

• COPD

DNAzymes as therapeutic agents

DNAzyme specifically binds to target mRNA1 DNAzyme cleaves GATA-3 mRNA2

Decomposition of cleavage products; DNAzyme continues cleavage activity3

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

Source: Barnes P. JCI 118 (2008): 3546-3556.

• GATA-3 plays a central role in the

allergic inflammatory response

• Orchestrates a wide range of Th2-

mediated cytokines, in particular IL-

4, 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)

Homburg et al. ``Safety and tolerability of a novel inhaled GATA3 mRNA targeting DNAzyme in patients with TH2-driven 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)

• 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

Key development milestones for biotech spin-off company

• 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

Preclinical program

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

• GMP (Good Manufacturing Practice) certified manufacturing

• Stability studies (min. 6 months)

• Certified Packaging

• Transport & distribution

Investigational Medical Product (IMP)

• Preclinical programm


• Investigetional Medical Product (IMP)







Primary goal: safety & tolerabilty (20-80 subjects, weeks to months)

Clinical Trial Overview

First in class First in manI a: safety & tolerability [single dose, healthy subjects]I b: safety & tolerability [multiple doses, healthy subjects]I c: safety & tolerability [single dose, patients]

First in classII a: explorative POC study [multiple dose, patients]II b. Proof of concept study [multiple ascending dose, patients]


Primary goal: efficacy & safety (30 -200 patients, months to years)

• The number and design of clinical trials may vary depending on country and regulatory agency









quality requirements

value risk

Is it realistic for academic spin-off to place the drug on the market?

• 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

Evaluation criteria

• 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)

Summary

Thank you

06.05.20110 Dr. Agnieszka Turowska Warsaw, 2015 Spin-off in practice German experience from Polish...

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