Post on 13-Jul-2018
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Karolinska Development Helsinki, 10 April 2014
Key Learnings from the Karolinska Development Concept Michael Sundström, VP Discovery Research
My Background
• Training @ Uppsala & KI
• Pharmaceutical Industry (9) Pharmacia, Sweden and Italy
• Small & Large Biotech (2) Actar & Biovitrum
• Public Private Partnership (5) University of Oxford, SGC
• University Research Center (5) University of Copenhagen, CPR
• Investment Company, Biotech (3) Karolinska Development; & KDEx
The Essential Proteins Background:
There are ~20,000 unique genes/proteins in human
Proteins constitute the ‘machinery of life’, carrying out a multitude of functions, such as movement, signalling and metabolism
Modifications of unique proteins generate a large number of variants (post translational modifications, splicing, degradation …)
Interactions and expression regulation, makes the combinatorial opportunities enormous ….
In addition:
The vast majority of all drugs, modulate the functions of proteins or are proteins directly
... and there is a gigantic knowledge gap concerning protein function
The Scale - a Conservative Estimate
Post-translational Modifications of proteins
(PTMs)
>10 fold increase ~100,000 validated 3 million sites available P most common
Alternative Splicing and functional SNPs
~5 fold increase Splicing 11,500 validated, likely for 16,000 genes SNPs 2 millions in coding regions 12,000 validated at protein level
~ 20,300 unique Human Genes
Genome
Proteome > 1,000,000
Human Protein Variants ΔFunction
Wikström & Sundström, Bioforum Europe 2010
The (un)Targeted Cancer Kinome From Fedorov et al, 2010 - Nature Chem Biol
“we also highlight kinases identified by RNAi as potential targets that are specifically required for growth and survival of the cancer type with a defined genetic background (bars in red) and statistically relevant driver mutations identified by large-scale sequencing efforts (bars in magenta)”
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Karolinska Development in Summary
Exclusive access to medical innovations from top ranked academic institutions
Large ownership and active management of the portfolio – management team with strong track record
Large portfolio – 28 projects – 20 pharmaceutical and 8 technology projects - 18 in clinical trials
Significant progress and strong focus on business development activities has enabled us to begin making valuable deals
Continued rich news flow with clinical data expected in 2014 and 2015 to prepare for more exits
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Management Team
Dr. Torbjörn Bjerke CEO
Dr. Terje Kalland CSO
Christian Tange CFO
Business Development Otto Skolling VP Business Development Previous: Novozymes, Siemens Life Support, Pharmacia & Upjohn
R&D Team Dr. Gunilla Ekström VP Operations Previous: Orexo, AstraZeneca
IPR Ann-Sofie Sternås VP IPR Previous: Pharmacia, AstraZeneca
Dr. Tomas Odergren VP Clinical Development Previous: AstraZeneca
Michael Sundström VP Discovery Research Previous: Pharmacia, Novo Nordisk Foundation Center for Protein Research, Structural Genomics Consortium at Oxford University
Previous: President & CEO, Orexo AB President & CEO, Biolipox AB EVP R&D, ALK-Abello AS Director Pharmacology, AstraZeneca Visiting scientist, Genentech Inc Board member: Topotarget AS, NeuroSearch AS, DBV Technologies SpA Founder Action Pharma AS, Founder TXP Pharma Gmbh
Previous: SVP, Novo Nordisk AS CSO, Biovitrum AB Head, Oncology Research, Pharmacia Corp Board member: Arts Biologics AS, CBIO LLC, Innate Pharma SpA, Dako AS, Accuro Immunology AB
Previous: Advisor Private Equity CFO CMC Biologics Founder & CEO, Neecos Finance Manager, Haburi.com Financial Controller, Warner Lambert Controller, Max Bank Controller, Skandia
IR & Business Analysis Benjamin Nordin IRO Previous: Kaupthing Bank, JP Nordiska, Karolinska Institutet
Legal Ulf Richenberg General Counsel Previous: Esselte, Vattenfall, Scribona, Stokab Finance Michael Owens Chief Controller Previous: Arthur Andersen & Co, Ernst & Young, Vitamex AB
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Exclusive Access to Innovation and a Clear Route to Exit
EXCLUSIVE AGREEMENT Karolinska Institutet • One of the top ranked medical universities in the world
and one of Europe’s largest
• Around 1,500 scientists, >2,000 MD/PhD students publishing > 4,000 peer reviewed scientific publications annually
• Karolinska Development has an exclusive Deal Flow Agreement with the TTO of Karolinska Institutet - KIAB
COLLABORATION AGREEMENTS • Mayo Clinic, USA • Ospedale San Raffaele, Italy • Medical University in Graz, Austria • Several major Nordic Universities
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Validated target, intervention point Hit compound
– Interacts with target – No obvious liabilities – Suitable chemical starting point
Lead compound – Modulates target function – Selective over anti-targets – Characterized for druggability – Represents series of similar compounds
Candidate drug – Extensive profiling, meeting TPP criteria
Search Learn Confirm
Exlporatory Lead Opt Pre-Clin Dev Phase I Phase II Phase III
Safety study • 20 – 80 people
Safety study • Identify side effects • Measure effectiveness • Often 100 – 300 people
Measure effectiveness • Monitor side effects • >1000 people
Where We Focus
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• Great science, novelty, true innovation • Through collaborator: access to know-how, network & tools
• Established Mechanism of Action • Target dependent effects • Feasibility (e.g. druggable target class) • Defined and validated disease link
• Medical need and defined patient population • Differentiation/benefits vs. existing treatment • Clinical development & regulatory path • Intellectual property rights
Scientific and Technical Considerations
Academia
• Karolinska Institutet • Leading Nordic and EU based • US/Canada • Drug Discovery Organizations
Unsolicited Proposals
Commercial
• Conferences • Networking Events • Cooperation with similar
organizations
200-250 per year
Project Flow – Primary Sources
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Process
Initial Review Science/technology based
~15%
In-House Second Opinion
~85%
No
OK by R&D Team
CDA Based Review
External
Opinion(s)
Due Diligence
Including
formalities
Investment Proposal
BoD
1%
Project Flow – Distribution (2013)
Cancer
CNS
Inflammation
Infectious Diseases
Womens Health
Other TA
MedTech
Medtech
Lead Discovery
Lead Opt
Potential CD
40% from Biotech companies 60% from Universities
20% from Sweden 60% from EU 10% US 10% ROW
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Most Common Reasons for a No
Technical: • Pre-clinical data not supportive of claims • Unclear Mechanism of Action • Sub-optimal compound properties • Intellectual Property Rights • Clinical and/or Regulatory hurdles Business • Outside KD priority areas • Unclear medical need or lack of specified target population • Competitive landscape (too much; too little) • Business plan/proposition • Valuation • Management team
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Accepted Projects
Have:
• Strong scientific foundation • Defined Mechanism of Action • Technical feasibility • Indication with clear medical need & differentiation • Defined patient population (e.g. genetic, stage, biomarkers) • Supportive pre-clinical data with (prototype) compound • Favourable IPR or possibility to generate • Defined clinical path forward • Strong management team • Identified future potential partners
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New Potential Treatment for Endometriosis
Status
Forendo Pharma is based on research from University of Turku, Finland and incudes leading academic professionals in endocrinology
Efficacy demonstrated in preclinical models A candidate drug has been selected for further
preclinical development and Phase I The company is also pursuing a project targeting
patients with low testosterone levels – efficacy demonstrated in Phase II with fispemifene
Market Overview
In endometriosis, cells from the lining of the uterus (endometrium) grows in the abdominal cavity causing infertility and pain
The disease affects up to 10% of women in fertile age Endometriosis treatment includes surgery – often
multiple procedures, pain management and hormonal treatment
No treatment available today cures the disease and endometriosis therefore has a profound health economic impact
Company: Forendo Pharma Oy
Active ingredient: Small molecule
Primary indication: Endometriosis
Current Phase: Preclinical
Sources: Medtrack, Giudice & Kao, Lancet 2004
Ownership: 21%
HSD17B1 enzyme leverages tissue estradiol level up to 10x from systemic level
Estrone (E1) •low activity
HO
OH
HO
O
Estradiol (E2) •Highly active
HSD17B1
HSD17B2
• Expressed in: – Endometrium, endometriosis – Breast , most breast cancers – Uterine fibroids – Present in ovary with other HSDs and aromatase
• HSD17B2 eliminates estradiol
Endometriosis model in marmoset monkeys best surrogate for the human disease
Detection of blood flow using color doppler
Endometriotic lesions on the peritoneal surface of uterus and bladder
Endometriotic lesions show strong HSD17B1 and a decreased HSD17B2 expression like the human disease (Einspanier et al. 2006) Animals show pain related behavior (Arnold & Einspanier 2013) Disease responds to human endometriosis therapies
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Innovative Approach to Cranioplasty
Status OssDsign Cranio PSI is a novel bioceramic implant for
skull surgery Early clinical data for OssDsign Cranio PSI are very
promising PET/CG imaging has confirmed that bone grows on the
ceramic material Registration certificate from the Swedish Medical
Product Agency for the cranial implant has been received Clinical trial ongoing with OssDsign Cranio PSI
Market Overview Complications in connection to cranioplasty multiplies
total treatment costs each time
OssDsign’s approach is applicable in other indications such as trauma to large bones
The market for bone replacement products was worth EUR 1bn in 2012
Ownership: 26%
Company: OssDsign AB
Product: OssDsign Cranio PSI
Primary indication: Cranioplasty
Current Phase: Product
At 6 months Post-op