1. Development of Innovative Medicines
in Russian Academic Institutes.
The Experience of Nonprofit Partnership “Orchemed”
Prof. Sergey Bachurin, corresponding-member of
Russian Academy of Sciences

2. Examples of innovative drug-
candidates developed in the institutes
of Russian Academy of Sciences

3. Zelinsky Institute RAS Harvard Medical
School
Chemical synthesis of conjugated vaccine against Staphylococcus aureus
D-Glucosamine
HO
O 28 Chemical steps: Protective efficacy against
HO
HO O,N-functionalization, the infection of mice with
H2N OH
Introducing of spacer groups, methicillin-resistant
HO
O
glycosylation reactions, Staphylococcus aureus
HO O
HO O Removal of blocking groups. (MRSA) strain
H 2 N HO O
HO O
H 2N H O O
HO O
H 2 N HO O
HO O
H 2N HO O
Oligosaccharide HO O
H 2N H O O
ligand L
Conjugated vaccine
HO O
H 2 N HO O
Survival (mice)
HO O
H 2N H O
Without vaccine
HO O
H 2 N HO O
HO O SH
H 2N
Protein-
carrier (dTT)
Conjugated vaccine
Collaboration: Zelinsky Institute, RAS (chemical synthesis) and Harvard Medical School (bacteriology)
Marina Gening, T. Maira, A. Kropec, D. Skurnik, Y. Tsvetkov, N. Nifantiev*, G. Pier* «Synthetic β(16)-linked N-acetylated and non-
acetylated oligoglucosamines to produce conjugate vaccines for bacterial pathogens» Infect. Immun., 78 (2009) 764-772.

4. Institute of Physiologically Active Compounds RAS and
Institute of Normal Physiology RAMS
Development of new generation of memory-enhancers
and neuroprotectors
70
3D-docking of binary AMPA-receptor modulators Restoration of weak or lost 60
* *
memory in animal models
50
Avoidance %
O
40
30
R2
N
N 20
O O 10
R1
Binary ligand of AMPA-receptor 0
Saline 5 min pre 5 min post 4h post
modulation site
Retention
Training test
0 24
hours
Wild-type Symptomatic TG TG + IP-0012
Novel neuroprotective
agents developed, which
block proteinopathy in
different animal models
of neurodegeneration
(TDP-43 protein and
gamma-synuclein
transgenic animals)
Contractual work with Bayer AG, Pfizer, AC Immune (Switzerland)

5. Novosibirsk Institute Institute of Problem of Institute of Physiologically Institute of Organic
of Organic Chemistry RAS Chemical Physics, RAS, Active Compounds, RAS Chemistry, RAS, Ufa
(both from Chernogolovka, Moscow region)
Development of novel generation of drugs on
the basis of natural and synthetic nanosupports
OH O O
Clathrates of pharmacones with nano-matrixes HO
O O
O HO
of plant origin – the new approach for O
HO OH
HO
OH
O
increasing efficacy, bioavalability and HO
O
OH
OH O
O
OH
decreasing toxicity of known drugs O O HO OH
HO
«Symvaglysin» clathrate of simvastatin with glycyrrhyzic acid (GA)– new cholesterol-
lowering agent (with ED reduced in 3 times).
Clathrate of GA with allapenine – new safe anti-arrythmic more active and less toxic
than medicine Allapenine, IOC Ufa (The above agents are approved for clinical trials)
Original complexes of C60-fullerene and soluble polymers with known medicines
(developed in IPCP and IPAC RAS) showed significantly improved pharmacological
profile of these medicines.

6. Institute of Organic Synthesis (IOS,
Ekaterinburg, Ural Branch RAS)
Development and manufacture of highly-requested
medicines for Russian pharma market
ANTI-VIRAL AGENT «TRIAZAVERIN»:
LISOMUSTIN laboratory to the market
a new anti-cancer
agent Produced and
NO
certified more than
20 000 capsule
H
N N COOH
Cl
O NH2
NO
H
N N COOH
Cl
O NH2
O OH
F
PEFLOXACIN N
O
N
N
H3C
Highly efficient CH 3
antibacterials in series of
fluoroquinolones with broad
spectrum of biological activity.
Broad spectrum of anti-virus activity (human and
Technology of its production is
chicken influenza, PC-infection, vernal
developed
encephalitis, etc).
Clinical trials are under completion.

7. To consolidate the researches of academic institutes in the field of drug
discovery the Nonprofit Partnership “OrCheMed” (Organic-Chemistry for
Medicine) of more than 10 leading academic institutes was founded in 2005.
It unites scientific and innovative potential
of about 3000 scientists.
730 including 200 including
470 scientific personnel 110 scientific personnel
INEOS RAS IPAC RAS
700 including (Moscow) (Chernogolovka)
300 scientific 1200 including > 600
personnel IOC RAS
Ins.Probl.
Chem. Phys. RAS scientific personnel
(Москва) (Chernogolovka)
200 including Ins.Org. Synth. Ins.Org.Phys.
130 scientific Ural Branch RAS Chem. RAS 450 including 250
personnel (Ekaterinburg) (Kazan) scientific personnel
IBOC RAS
Ins.Org.Chem.
800 including (Moscow) RAS (UFA)
200 including
380 scientific 130 scientific personnel
personnel Ins.Chem. Novosibirsk Inst.
RAS (Rep. Komi) Org.Chem.RAS
180 including 450 including
130 scientific personnel 250 scientific personnel
MISSION:
•Analyzing of chemical compounds libraries, developed in different institutes.
•Organizing of virtual and biological screening of chemical compounds libraries.
•Providing the pharmacological and marketing expertise for hit-compounds developed in the
institutes.
•Foundation of novel start-up companies;
•Development of nascent IP from consortium members through project funding and licensing.

8. Modern centers for preclinical trials in the
Russian Academy of Sciences.
Center for preclinical
trials in Chernogolovka
Siberian Center for
animal genetic
Laboratory for
Bioscreening
models
(Puschino Branch of the (Novosibirsk)
Institute of Bioorganic
Chemistry)
• In vivo screening of active compounds
• Toxicological and safety study of lead-
compounds.
• The full-cycle of preclinical trials

9. “Traditional” Drug Discovery Strategy
«Nature Rev.Drug Disc.» 2004-2007
Drug discovery (R&D)
Synthesis of Screening Hit-
new Compounds Lead-
(computational
compounds and bio- optimization Compounds
screening) optimization
Pre-Clinical
Trials (GLP)
appr. 1 000 000 comp. (1000 comp.) (100 comp.)
Drug-candidates
Appr. 15 years (10)
About US$ 1BL
1 PHASE
(60-70% success)
3 PHASE 2 PHASE
(40-60% success) (25-40% success)
1 DRUG CLINICAL TRIALS
ON THE MARKET

10. “Orchemed” as a “catalyst” of drug discovery process in
academician institutes
NP “OrCheMed”
Synthesis of Screening Hit-
new Compounds Lead-
(computational Centers for
compounds and bio- optimization Compounds
screening) optimization preclinical trials
Pre-Clinical
Trials (GLP)
appr. 1 000 000 comp. (1000 comp.) (100 comp.)
Drug-candidates
(10)
Medicinal chemistry approaches decrease time and
cost of R&D stages
1 PHASE
(60-70% success)
3 PHASE 2 PHASE
(40-60% success) (25-40% success)
CLINICAL TRIALS
“Orchemed” should cover the “Nishe” of accumulation of chemical libraries
datebases and selection and commercialization of hit- and lead-compounds

11. Project portfolio
 Antiviral drug BG-122 (INEOS RAS)
 Anticoagulant LS-27 (IOS UrB RAS)
 Antineurodegenerative drug RU-32 (IPAC RAS)
 Antiinflammatory drugs (Yaroslavl SU)
 Antiparkinson drugs (IOC Novosibirsk) Portfolio:
 Cardiovascular drug Dibornol (IC Syktyvkar)
>50 projects in
 Antitumor drugs (IOS, IPCP)
actual
 Advanced drug delivery systems (IPAC, INEOS,
pharmacological
IPCP) areas
 etc.
www.orchemed.com
+7 (496) 524-2563

12. Recognized academic expert group
• Invited experts for State Duma, government, mass media, etc.
• Official codevelopers of Strategy of Development of Pharmaceutical
Industry of Russian Federation in 2008-2020 (Pharma-2020)
• Expert evaluation of work projects for business groups
• Initiator of strategic national projects, such as National bioscreening
network
• Strategic partnership with Russian innovative (bio)pharmaceutical
companies, biopharmclusters, etc.
Presentation of Orchemed Participation in State Duma
initiative Project ”National Presentation of Orchemed Committee Workshop
Bioscreening Network” Projects to Minister E.Nabiulina
in State Duma www.orchemed.com
and ROSNANO Head A.Chubajs
+7 (496) 524-2563

13. Model of commercialization
IP rights Business partners
Institutes NP Orchemed
of RAS Royalties from • Binnopharm
license agreements
One of the biggest GMP
start-up companies
Startup-5 manufacturers in Russia
Venture funds Startup-4
capital • Biopharmacluster
(e.g., Russian Startup-3
investments Startup-2 BioCity
venture company)
Startup-1
or • Maxwell Biotech
out-licensing
Pharmaceutical • International fund of
companies technology and
Investment
• Obninsk pharmcluster
“Park of active
Typical distribution of molecules”
shares in start-up:
• and many other
Scientists-developers – 75% scientific and business
organizations in Russia
NP Orchemed – 25%
www.orchemed.com
and former USSR
+7 (496) 524-2563

14. National Bioscreening Centers Network, NBCN
(Project, developed jointly by RAS, RAMS, MSU and NP Orchemed)
The main goals of the project (2010-2012):
1. Development and launch an integrated infrastructure of biological screening in
Russia for providing discovery of novel innovative medicines.
2. Development of series (30-50) of highly efficient lead-compounds for the most
requested fields of medicine and launch of 3-4 innovative drugs on Russian
pharma market at 2020.
Proposed Structure of NBCN

15. Thank you for your attention!

17. The most fundamental and lasting subject
of synthesis is not production of new compounds,
but production of properties.
George S. Hammond. Norris Award Lecture, 1968
Drug Discovery – One of the Most Requested Field of Chemistry
- In 2007, the global pharmaceutical market grew to US$712 billion (what is about 80% of
Global Oil Market).
- Year-on-year the global pharmaceutical market increased to 10.7% in 2007, largely as a
result of strong sales for new innovative products and high market growth in emerging
pharmaceutical markets such as China, India and Russia.
- It is expected that the global pharmaceutical market is forecast to grow to US$929 billion in
2012. The report “Pharmaceutical Market Trends, 2008 - 2012”
According to the “Strategy of the development of Russian pharmaceutical
industry till 2020”, approved by the Russian Government it is expected that
about 30% of all drugs in Russian Pharma Market will be new innovative
medicines.
Therefore one of the main line of activity of Russian Academy of Science is
the provision of fundamental scientific background for the development of
novel promising drug-candidates.

18. Nonprofit partnership
of chemical institutes of RAS
«Orchemed»
(Organic Chemistry for Medicine).
General information
Established in 2005
The legal status: nonprofit partnership
Founders: Institutes of RAS
Management:
Scientific Board (Chairman – Acad. N.S. Zefirov),
Board of experts (Chairman – Corr. Member of RAS S.O. Bachurin),
Director (K.V. Balakin, PhD, DSc)
Institutes-members: 11 institutes of RAS: Institute of Physiologically Active Compounds,
Institute of Problem of Chemical Physics, Institute of Organic Chemistry, Institute of
Elementorganic Compounds, Institute of Bioorganic Chemistry (all from Moscow area),
Institute of Organic and Physical Chemistry (Kazan), Institute of Chemistry (Syktyvkar),
Institute of Organic Chemistry (Ufa), Institute of Organic Synthesis (Ekaterinburg),
Institute of Organic Chemistry (Novosibirsk), Institute of Chemistry of Solutions (Ivanovo)
www.orchemed.com
+7 (496) 524-2563

19. Features
Orchemed – Russian biggest
cooperative academic initiative in the field of drug O O
N
O
discovery and development
HN HN N HN S
N N N
N
O N O N O N
Complete cycle of preclinical innovative drug Pirenzepine
N
Zolenzepine
N
Telenzepine
N
(Boehringer Ingelheim) (Byk Gulden) (Byk Gulden)
discovery
From virtual screening to preclinical animal studies
Portfolio of innovative projects
More than 50 projects in actual therapeutic areas
Focus on innovative developments
Distinctive feature of academic projects
Orchemed’s Mission: To identify and promote
prospective technologies developed in Russian
academic institutes, and pave the way to effective
technology transfer to national and global www.orchemed.com
pharmaceutical industry +7 (496) 524-2563

20. Drug Discovery: as a rate-limiting step
in Drug Development
In vivo testing and
HTP-screening
systems preclinical trials
of lead-compounds
O
“Weak
O
N
Link” ! Animal
Video camera
N
Water pool Hidden
N O (rat)
N
N
+
F
F
Platform
CH3 F
N
N
N
N
Focused chemical
N N N
N O
N
CH3
N N O
S H3C
libraries
N CH3
Chemical
O N
O
S N S N
N
N
N
compounds
Drug-candidates
N N N
N
N N
Cl
libraries
N N
S
S N N N
O
N OH
O
N H3C O N
N N OH N
O N O O
Optimization of hit- and
O
+
N
CH3
lead- compounds
Virtual
prescreening

21. National Bioscreening Centers Network, NBCN
(Project, developed by NP Orchemed jointly with RAS)
Ufa
The main goals of the project (2010-2012):
Development and launching an integrated infrastructure of biological
screening in Russia for providing discovery of novel innovative medicines
Development of series (30-50) of highly efficient lead-compounds for the
most requested fields of medicine as a potential innovative drugs on
Russian market at 2020.