daryono hadi tjahjono - S e k o l a h F a r m a s i - I T B

MK Pengembangan Obat
24 Agustus 2020

Drug Discovery &

Development
Daryono Hadi Tjahjono

Laboratory of Medicinal Chemistry, HPC & Biomolecule Testing

School of Pharmacy, Bandung Institute of Technology
Jl. Ganesha 10, Bandung 40132, Indonesia
e-mail: daryonohadi@fa.itb.ac.id
 daryono hadi tjahjono - S e k o l a h F a r m a s i - I T B

Medicine:
Global spending will reach
nearly $1.5 trillion by 2023

Source: IQVIA, Market Prognosis, Jan 2019

 daryono hadi tjahjono - S e k o l a h F a r m a s i - I T B

Specialty Medicine (Spending & Growth) in Developed Markets

Source: IQVIA, Market Prognosis, Jan 2019

 daryono hadi tjahjono - S e k o l a h F a r m a s i - I T B

Record of 15 New Oncology Therapeutics and One Supportive Care Therapy

(lunched in 2018)

Sources: IQVIA Institute, April 2019

 daryono hadi tjahjono - S e k o l a h F a r m a s i - I T B

Global New Active Substances (NAS)

[available since 1996]
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Global Biologics Spending

Biosimilars’ adoption will expand,
but will remain modest to 2017

Source: IMS Health Thought Leadership, Sept 2013

2019: US$ 387 Bn

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Conventional Drugs →Biopharmaceuticals

MW ca. 18,500 Aspirin MW 180

-Interferon

IgG Monoclonal Antibody

MW ca. 160,000
Fab fragment
rProtective Antigen
 daryono hadi tjahjono - S e k o l a h F a r m a s i - I T B

The ten top-selling biopharmaceutical products in 2009

Sales
Product Company
($ Biln)
Enbrel (etanercept) 6.58 Amgen, Wyeth, Takeda Pharmaceuticals
Remicade (infliximab) 5.93 Centocor (Johnson&Johnson), Schering-
Plough, Mitsubishi Tanabe Pharma
Avastin (bevacizumab) 5.77 Genetech, Chugai, Roche
Rituxan/MabThera (rituximab) 5.65 Genetech, Biogen-IDEC, Roche
Humira (adalimumab) 5.48 Abbott, Eisai
Epogen/Procit/Eprex/ESPO (epoitin alfa) 5.03 Amgen, Ortho, Janssen-Cilagg, Kyowa
Hakko Kirin
Herceptin(trastuzumab) 4.89 Genetech, Chugai, Roche
Lantus (insulin glargine) 4.18 Sanofi-Aventis
Neulasta (pegfilgrastin) 3.35 Amgen
Aranesp/Nespo (darbepoetin alfa) 2.65 Amgen, Kyowa Hakko Kirin
Source: LaMerle Business Intelligence, Barcelona
Source: Gary Walsh, Nature Biotechnology , Volume 28 (9) – September 2010
 daryono hadi tjahjono - S e k o l a h F a r m a s i - I T B

Top 10 Best Selling Biologics of 2014

Expression 2014 Sales
Rank Biologic Company
System ($ Biln)
1 Humira (adalimumab) CHO AbbVie 12.543 billion
Murine Johnson & Johnson
2 Remicade (infliximab) Myeloma and Merck & Co. 9.240 billion
Rituxan (rituximab, MabThera; includes Roche and Biogen
3 CHO 8.678 billion
next generation of Rituxan -Gazyva Idec
4 Enbrel (etanercept) CHO Amgen and Pfizer 8.538 billion
5 Lantus (insulin glargine) E.coli Sanofi 7.279 billion
6 Avastin (bevacizumab) CHO Roche 6.957 billion
7 Herceptin (trastuzumab) CHO Roche 6.793 billion
8 Neulasta/Neupogen (pegfilgrastim) E.coli Amgen and Kyowa 5.857 billion
Hakko Kirin
Prevnar 13/Prevenar 13 and
9 Pfizer 4.464 billion
Prevnar/Prevenar (7-valent)
10 Avonex (interferon beta-1a) CHO Biogen Idec 3.013 billion
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US Share of New Active Substances (NAS)

First Launched on the World Market
 daryono hadi tjahjono - S e k o l a h F a r m a s i - I T B

Drug Discovery and

Development

Lead: chemical compound that has pharmacological or biological activity and

whose chemical structure is used as starting point for chemical modification
in order to improve potency, selectivity, or pharmacokinetic parameters.
 daryono hadi tjahjono - S e k o l a h F a r m a s i - I T B

Drug Discovery and Development

Identify disease

Find a drug effective

against disease protein
Isolate protein (2-5 years)
involved in
disease (2-5 years) Scale-up

Preclinical testing
(1-3 years) Human clinical trials
(2-10 years)

Formulation

FDA approval
(2-3 years)
Lead: chemical compound that has pharmacological or biological activity and
whose chemical structure is used as starting point for chemical modification
in order to improve potency, selectivity, or pharmacokinetic parameters.
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Technology is impacting this process

GENOMICS, PROTEOMICS & BIOPHARM.
Potentially producing many more targets
and “personalized” targets

HIGH THROUGHPUT SCREENING

Identify disease Screening up to 100,000 compounds a
day for activity against a target protein

VIRTUAL SCREENING
Using a computer to
predict activity
Isolate protein
US$ 1,778m
COMBINATORIAL CHEMISTRY
Rapidly producing vast numbers Find drug
of compounds
MOLECULAR MODELING US$ 873m
Computer graphics & models help improve activity
Preclinical testing
IN VITRO & IN SILICO ADME MODELS
Tissue and computer models begin to replace animal testing
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S.M. Paul, et al., Nature Reviews Drug Discovery, 2010, 9(3), 203–214.

Berapa Biaya Riset Rata-rata per Molekul Obat?

+CADD

Classic
(in million US$)
Collective anual R&D spending: US$ 50 billion
Fig : R&D funding model to produce ONE New Molecular Entity (NME)
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Forbes
Pharma & Healthcare |8/11/2013 @ 11:10AM |

How Much Does Pharmaceutical

Innovation Cost? A Look at 100
Companies
R&D spending per New Drug (NME):
Abbort ......... 13,183 ($ Million) [Rp 130 T]
Genentech .... 1,569 ($ Million)
Mylan .............. 254 ($ Million)
OMRIX .................. 15 ($ Million) [Rp 150 M]
Note: based on 10 year R&D spending (100 pharmas)

http://www.forbes.com/sites/matthewherper/2013/08/11/
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Pfizer, Vertex, Eli-Lilly, GlaxoSmithKline, Sanofi:

non-small-cell lung cancer; Hepatitis C; Alzheimer; Antibiotic; Blood thinner
 daryono hadi tjahjono - S e k o l a h F a r m a s i - I T B

Drugs derived from Structure-based Approaches by CADD

Capoten Captopril ACE Hypertension 1981 Bristol-Myers Squibb

Trusopt Dorzolamide Carbonic Glaucoma 1995 Merck

anhydrase
Viracept Nelfinavir HIV protease HIV/ AIDS 1999 Agouron (Pfizer) and Lilly

Tamiflu Oseltamivir Neuraminidase Influenza 1999 Gilead and Roche

Gleevec Imatinib BCR- Abl Chronic 2001 Novartis
myelogenous
leukaemia
Additional examples:
o Many of the atypical antipsychotics
o Cimetidine, (the prototypical H2-receptor antagonist)
o Selective COX-2 inhibitor NSAIDs
o Enfuvirtide (a peptide HIV entry inhibitor)
o Nonbenzodiazepines, like zolpidem and zopiclone
o Raltegravir (an HIV integrase inhibitor)
o SSRIs (selective serotonin reuptake inhibitors; a class of antidepressants)
o Zanamivir (an antiviral drug)
daryono hadi tjahjono - S e k o l a h F a r m a s i - I T B
 daryono hadi tjahjono - S e k o l a h F a r m a s i - I T B

Personalized
Medicines
 daryono hadi tjahjono - S e k o l a h F a r m a s i - I T B

Personalized
Medicines
 daryono hadi tjahjono - S e k o l a h F a r m a s i - I T B

Tugas MK Pengembangan Obat

1. Legislasi dan regulasi obat
2. Clinical trial (menurut FDA) calon obat (untuk small molecule)
3. Kerja obat pada sistem enzim vs sistem reseptor
4. Pro-drug
5. Biosimilar dan produksinya
6. Penemuan dan pengembangan obat HIV
7. Penemuan dan pengembangan obat kanker (ambil 3 kanker utama)
8. Penemuan dan pengembangan obat diabetes
9. Penemuan dan pengembangan vaksin (virus & bakteri/mikroba)
10. Penemuan dan pengembangan vaksin kanker
11. Proses penjaminan produk di fasilitas produksi obat
Link youtube terkait: https://youtu.be/TaJTCVB9shw
daryono hadi tjahjono - S e k o l a h F a r m a s i - I T B

Terima Kasih
Hatur nuhun
 daryono hadi tjahjono - S e k o l a h F a r m a s i - I T B

Lab. Desain Molekul Obat (CADD)

Perangkat lunak yang tersedia:

o Gaussian 09 o AutoDock 4.2
o ADMET Predictor v8.1 o Discovery Studio 2017
o MOE 2014 o VMD
o Amber 12.0 o Marvin
o Gromacs 2016 o Chimera

Hardwares utama: 3 semi-HPC (3 x 10 core)

 daryono hadi tjahjono - S e k o l a h F a r m a s i - I T B

Lab. Sintesis & Instrumen

 daryono hadi tjahjono - S e k o l a h F a r m a s i - I T B

Peralatan lain di Kampus Ganesha

yang bisa di-akses:
o NMR spectrometer
o MS/MS spectroscopy
o LC-MS
o HPC dengan 124 core
o SEM
o TEM