haapalinna iddst 2014 handout

Increase of the

Productivity of the

Discovery Process

by Partnering and

Outsourcing Antti Haapalinna,

Ph.D., Adjunct Professor, eMBA

Vice President, Research, R&D,

Orion Corporation ORION PHARMA

12th Annual Congress of International Drug Discovery Science &

Technology, 16-20 November 2014, Suzhou, China Stream 16: Symposium of Drug Discovery R & D Outsourcing Services

Structure

• Orion in brief as background information

• The new role of R&D and process for new products in pharmaceutical industry

• Productivity increase of Orion R&D within 6 years

What has been made?

• Classification of partners

• Partnering and oursoursing models in use

• Need of reliable key metrics to value R&D investment and

boost the future growth of the company

• Conclusions

Orion's R&D: The voice of science and the patient

Building Well-being Is Orion’s Mission

Orion’s own sales organisation’s areas

Sales areas of partners

Orion is a globally operating Finnish company

developing pharmaceuticals and diagnostic

tests – a builder of well-being.

Orion in brief 2013

Net sales EUR 1 007 million

Operating profit EUR 268 million

R&D expenses EUR 101.9 million

Nro of personnel (at end of) 3,519

in Finland 2,816

in other countries 703

Market cap on 11 June 2014 EUR 3,78 billion

Orion Corporation

Innovative treatments worldwide

5

Orion’s own sales organisation’s areas

Sales areas of partners

R&D, new model

and

effect on

productivity

6 R&D, the Voice of Science and the Patient

The new role of internal R&D

7

Search,

combination

and processing

of

knowledge by

internal R&D

Knowledge and IPR

from internal sources

Knowledge and IPR

from external sources

Commercialisation

through internal paths

Commercialisation

through external paths

(from J. Kettunen, S-K Ilomäki, P. Kalliokoski;

Making sense of innovation management, 2008)

Orion partnerships cover the entire R&D value chain of operations - Increasing focus on research collaboration partnerships - Rights for further development and marketing of candidate compounds to Orion (especially in Europe) - Development partnerships are usually sought for clinical phase III at the latest, especially in marketing authorization cases in countries outside Europe - Rewards and risks are shared with partners


30

Active-To-Hit Hit-To-Lead Lead Optimization

CNS B

CNS C

Cardiovascular

Urology

CNS A

Candidate Precandidate

Oncology A

Research projects 2006 = Before candidate

selected for development to IND/CTA

CTA

"R&D: The Voice of Science and the Patient"

9

Pharmaceutical Development pipeline year 2009

Own proprietary animal drug research

Own proprietary drug research

Developed by a partner

Project Indication Preclinical

Clinical phases

Registration

I II III

Histrelin implant (Vantas®) advanced prostate cancer Endo Pharmaceuticals Solutions

Stalevo®, expansion of the indication in the US early stage Parkinson’s disease

Dexmedetomidine (intravenous) for European markets sedative for patients in intensive care

Stalevo®, development for the Japanese market Parkinson’s disease

Easyhaler® combined formulation asthma, COPD

Pharmacology of steroid receptors SARM, prostate cancer

Alfa 2 C receptor pharmacology schizophrenia, Alzheimer

Active-To-Hit Hit-To-Lead Lead Optimization

Candidate Precandidate

Research projects 2014

10

CNS D

CNS A

Oncology E

CNS B

Oncology C

CNS C

Oncology B

Oncology D

CNS G

CNS F

CNS E

CNS H Super generic

Collaaboration (Biologic) for new indication

HIT Finding

CTA

CNS H

CNS I

CNS J


Oncology A

Project Indication Clinical phases

Registration I II III

Easyhaler® budesonide-formoterol Asthma, COPD

Stalevo® for Japanese markets 1) Parkinson’s disease

Easyhaler® salmeterol-fluticasone Asthma, COPD

ORM-12741 (alpha-2c adrenoceptor

antagonist) 2) Alzheimer’s disease

ODM-201 (androgen receptor inhibitor) 3)

Prostate cancer

ODM-103 (more effective COMT inhibitor) Parkinson’s disease

ODM-203 (dual FGFR & VEGFR inhibitor) Cancer

Key pharmaceutical development projects year 2014

11

1) Conducted by partner Novartis

2) In collaboration with Janssen Pharmaceuticals

3) In collaboration with Bayer

IIa

Completed Ongoing

....and 3 projects in nonclinical development for IND/CTA

What has been

made to increase

the number of

projects and

research output?

12 Orion's R&D: The voice of science and the patient

13

Collaborative networks across the R&D value chain

Generics Development and

Product Lifecycle Management

Partnering …and moving further

Late stage

development Early development Research

Partnering and outsourcing

… and moving earlier Partnering

Target

identification and validation

8–24 mth

Hit to Lead

generation

12–24 mth

Lead

optimisation

18–36 mth

Candidate

selection,

preclinical

dev.

12–24 mth

Phase I

12–14 mth

Phase III

18–48 mth

Phase II

12–36 mth


14

Classification of collaborators

Strategic significance/ Technology

low

low

high

high Competence required for product/activity

Competitive bidding, cost efficiency

Collaboration

Availability/ quality

Development of product solutions/ Cost efficiency

Strategic collaboration

Development of competence, technologies, processes, products

>100 partners

20-30 partners

a few partners

Usually; Ample availability / Restricted availability

Public &Private

Partnerships


Orion view on collaboration and networking

opportunities

Scientific

competence - Universities

- Research centres

Drug discovery &

development

competence - Small biotech, Pharma

companies or CROs

Orion

Networking

Collaboration

opportunity

Collaboration

opportunity

Collaboration

opportunity


“R&D -The Voice of Science and the Patient"

FTE agreement; hybrid and

integrated model. On line support

allocated for several research

projects in Orion. In addition also

multiple small tasks outsources on

demand.

Risk sharing hit & lead

finding project

Risk Sharing Project on

pre-candidate/dev.

candidate finding

Univ.

network Several partners and CROs

Partner

&CROs

&CROs

&CROs Partner

Univ.

network

Various kinds of collaboration models in use

Partners (working for several parallel projects)

Internal database

Chemistry

Laboratories

Orion CL

contact

Project groups

Biology

Laboratories

Orion BL

ADME Contact

Info and

compounds

Coded samples (without

structures)

Results

Results

ADME

needs /

compound

Structure- activity

groups

Responsible Chemists

Orion CL

eRoom

Orion BL

eRoom

Info

Structure activity

DB

DATA transfer

by Orion personnel

DATA transfer

by Orion personnel

Info

(FTE)

Info,

Structures

compounds

Example of test and information management

in hybrid and integrated model for novel

compounds


POI Hit to

Lead

Lead

Optimization

Development

for phase 1

TMP Lead

selection

Development

candidate

selection

I-ID I-XX-YY D-XX-YY

Timelines between phases to be recorded: 1) Hit to lead phase (from official start of the project to identification 1st lead structure)

2) identification of Lead molecule: (start of lead optimization process),

3) identification of Pre candidate (broader in vivo efficacy and safety testing) and

4) identification of Drug development candidate (start of the nonclinical developmental work for the CTA)

5) CTA ready

WBS-code logic:

all POIs Specific research project Specific development project

Pre-

candidate

selection

CTA

documentation

ready (Target Molecule Profile)

Guidance and logic in early R&D


• Lead molecule start of lead optimization process

• Active in relevant cell based assay

• Suitable physicochemical (measured) properties

related to the target profile

• Suitable pharmacokinetic properties in vitro and in

vivo related to the target profile efficacy in vivo

• Or appropriate secondary in vitro model to reflect the

potential mechanism of action

• Preliminary in vitro safety parameters evaluated

• Scaffold should not be genotoxic

• Clear patent strategy

• Initial FTO defined

• Preliminary SAR

• Stringent optimization strategy described

• Precandidate • Active in relevant biochemical and/or cell-based

assays with an acceptable pharmacological profile

(specificity, selectivity, and potency)

• Suitable physicochemical (measured) properties

related to the Program Target(s)

• Suitable pharmacokinetic properties in vitro and in

vivo related to the Program Target

• Efficacious in vivo to reflect the proposed

mechanism of action, with demonstrated

pharmacodynamic effect

• Preliminary in vitro and in vivo cardiac safety

parameters shall be acceptable for further

development

• Not genotoxic

• No harmful metabolites have been identified

• Patentable and preliminary freedom to operate (FTO)

ok

• Initial scale up for broader efficacy and safety

evaluation

• Drug Development Candidate • All the properties of the Precandidate but also:

• Patententable as a composition of matter with a clear patent strategy and freedom to operate (FTO) defined

• Initial synthesis scale up for broader efficacy and/or safety studies have been carried out; no major liabilities for

manufacturing or formulation have been identified

• The results from non-GLP in vivo safety pharmacology and toxicology (dosing for two weeks) studies in two species

(e.g., rat & dog) support further development

Definitions (the same for all projects)

19

20

POI Hit to

Lead

Lead

Optimization

Development

for phase 1

TMP Lead

selection

Development

candidate

selection

1) Hit to lead phase (from official start of the project to identification 1st lead structure)

2) identification of Lead molecule: (start of lead optimization process),

3) identification of Pre candidate (broader in vivo efficacy and safety testing) and

4) identification of Drug development candidate (start of the nonclinical developmental work for the CTA)

5) CTA ready

Timelines between phases recorded:

Timelines after 2007 (on average)

Pre-

candidate

selection

CTA

documentation

ready

17,5 8,8 13,0 19,2 Months: 15,7


21

Internal projects Collaboration projects

Time from the start of

the project to the

identification of

Precandidate

36.9 months 38.9 months

Internal FTEs used 39.3 6.1

Average extrenal costs 1 * X € 2.1 * X €

Average total costs 1 * X € 0.65 * X €

Comparison of internal and collaboration projects from

the start to the precandidate identification phase


• Combining resources creates more value

for both parties (win-win)

• Partnerships add new skills and knowledge

to joint projects.

• Possibility to start new projects fast with

flexible resource allocation (within both

companines).

• Partnering eables risk sharing.

22

Why partnering & outsoursing ?


ACT SMART - Agility challenge

23

Thus:

• Pure short term rationalization and cost cutting will

not be the right solution

• Capability of the organization to manage complexity

is important and needs to be continuously improved

• Prioritization and efficiency need to be continuously

improved

• Target setting and measurement as and essential

means to increase overall R&D performance

• Amount of information vs. quality of information !

• “Unused information is waste”


Thank you

for your interest

QA ?

haapalinna iddst 2014 handout

Health & Medicine