James Jungkue Lee

April, 2012

Binding affinity- mono or avidity

Immunogenicity

Pharmacokinetics (T1/2)

Bio distribution (into tissue)

Multi-targetability (mono-specific versus bi-specific)

Engineerability

Manufactureability Yield

Thermostability

pH stability

Structural stability

2

Antibody

mimetic Scaffold

Molar

mass Example drug Developer

Antibody Immunoglobulin 150kDa Herceptin, retuxan etc Genentech etc

Affibody Z domain of Protein 5 kDa ABY-025 (anti-HER2) Affibody AB (SW)

Affilins Gamma-B crystallin 20kDa

Ubiquitin 10kDa SAPVF2 2801 (Preclinical)/ Cancer/imaging

(Subnanomolar IC50)

SPVF-2801-30/Cancer solid tumor

Scil Protein Pharmas

Affitins Sac7d (from Sulfolobus acidocaldarius) 7kDa

Anticalins Lipocalins 20kDa

Avimers A domains of various membrane

receptors

9-18 kDa C 326 (Stage ?)

Anti-IL-6 avimer

Avidia Amgen

(2006, $380mm)

DARPins Ankyrin repeat motif 10-19kDa MP0112 Phase I (with Allergan)

Anti-VEGFA binder for wet MD, diabetic

macular edema (IC50<10pM, T1/2>6d)

Molecular Partners

Fynomers SH3 domain of Fyn 7kDa

Kunitz domain

peptides

Kunitz domains of various protease

inhibitors

6kDa Ecallantide Dyax

Monobodies

(adnectins)

10th type III domain of fibronectin 10kDa Angiocept(CT-322), VEGF receptor 2 antagonist

for glioblastoma, NSCLC, CRC

Adnexus BMS

(2007, $430mm)

Nanobody Single domain antibody 12-15kDa ALX-0081, against von Willebrand factor, ATN-

103 anti TNF alpha (Phase II)

Ablynx

3

Pipeline

compound Target Stage IC50 T1/2 Host Remarks

Antibody Various Various Marketed subnano Weeks CHO

Affibody ABY-025 HER2 P1 E.Coli Imaging

Affilins SAPVF2 2801 n/a PC E.Coli

Avimer C 326 IL-6 > P2 50 pM E.Coli CD

DARPin MP0112 VEGFA P1/2a <10 pM >6d E.Coli

(>200mg/l) Eye

Kunitz

peptide Ecallantide kallikrein M

Monobody

(Adnectin)

Angiocept

(CT-322)

VEGFR2

(KDF for VEGFA) P2 E.Coli

Nanobody

(sdAb) ALX-0081

von Willebrand

factor P2 E.Coli

4

5

6

7

8

9

Strong binding affinity Non-immunogenicity Engineerability for PK or drug conjugation Molecular properties for manufacturing

Strong intellectual property right

Strategic selection of targets Enough resource allocation (financing and

HR)

10

Affinity?

Pharmacokinetics?

Size of molecule?

Manufacturing yield?

11