My talk on PEGS Boston 2016 April 29, 2016

1. APRIL 29, 2016
PEGS, BOSTON
DISCOVERY AND CHARACTERIZATION OF
A HIGH POTENCY ANTI-INFLAMMATORY
TRISPECIFIC TNF⍺/IL-17A/IL-17F INHIBITOR

2. AUTHORS
S. AGEEV
A. ULITIN
E. ZUBAREVA
I. USTUGOV
D. KORZHAVIN
E. LOMKOVA
V. SOLOVJEV
E. SOFRONOVA
V. EKIMOVA
A. ALEXANDROV
A. KARABELSKY
Y. BASOVSKIY
V. USATOVA
T. CHERNOVSKAYA
E. MOROZOVA
A. GRACHEV
R. IVANOV
D. MOROZOV
PRESENTER:
PAVEL YAKOVLEV
APRIL 29, 2016
PEGS, BOSTON

3. APRIL 29, 2016
PEGS, BOSTON
BCD 121
OctetRED96 measurement demonstrated that BCD 121
is capable to simultaneous non-completitive IL-17A
and TNF ligand binding.
Blue lines — added 1 mkg/ml TNFa
Red and green — without TNFa

4. APRIL 29, 2016
PEGS, BOSTON
YEAR 2012

5. APRIL 29, 2016
PEGS, BOSTON
YEAR 2012
SAINT-PETERSBURG

6. APRIL 29, 2016
PEGS, BOSTON
YEAR 2012
SAINT-PETERSBURG MOSCOW

7. APRIL 29, 2016
PEGS, BOSTON
YEAR 2012
SAINT-PETERSBURG MOSCOW
PHAGE DISPLAY

8. APRIL 29, 2016
PEGS, BOSTON
YEAR 2012
SAINT-PETERSBURG MOSCOW
PHAGE DISPLAY 454 SEQUENCING SYSTEMS

9. APRIL 29, 2016
PEGS, BOSTON
YEAR 2012
SAINT-PETERSBURG MOSCOW
PHAGE DISPLAY 454 SEQUENCING SYSTEMS
IL17A

10. APRIL 29, 2016
PEGS, BOSTON
454 SEQUENCING SYSTEMS

11. APRIL 29, 2016
PEGS, BOSTON
ANTIBODY ANNOTATION
V/D/J GENES
FR/CDR
SOMATIC
MUTATIONS
GERMLINE FAMILIES

12. APRIL 29, 2016
PEGS, BOSTON
PATTERN MINING
FR1 CDR1 FR2 CDR2 FR3
QVQLVQSGAEVKKPGASVKVSCKASGYTFT G--YYMH WVRQAPGQGLEWMG WINP--NSGGTNYAQKFQG RVTMTRDTSISTAYMELSRLRSDDTAVYYCAR
QVQLVQSGAEVKKPGASVKVSCKASGYTFT S--YAMH WVRQAPGQRLEWMG WINA--GNGNTKYSQKFQG RVTITRDTSASTAYMELSSLRSEDTAVYYCAR
QVQLVQSGAEVKKPGASVKVSCKASGYTFT S--YDIN WVRQATGQGLEWMG WMNP--NSGNTGYAQKFQG RVTMTRNTSISTAYMELSSLRSEDTAVYYCAR
QVQLVQSGAEVKKPGASVKVSCKASGYTFT S--YGIS WVRQAPGQGLEWMG WISA--YNGNTNYAQKLQG RVTMTTDTSTSTAYMELRSLRSDDTAVYYCAR
QVQLVQSGAEVKKPGASVKVSCKVSGYTLT E--LSMH WVRQAPGKGLEWMG GFDP--EDGETIYAQKFQG RVTMTEDTSTDTAYMELSSLRSEDTAVYYCAT
QMQLVQSGAEVKKTGSSVKVSCKASGYTFT Y--RYLH WVRQAPGQALEWMG WITP--FNGNTNYAQKFQD RVTITRDRSMSTAYMELSSLRSEDTAMYYCAR
QVQLVQSGAEVKKPGASVKVSCKASGYTFT S--YYMH WVRQAPGQGLEWMG IINP--SGGSTSYAQKFQG RVTMTRDTSTSTVYMELSSLRSEDTAVYYCAR
QMQLVQSGPEVKKPGTSVKVSCKASGFTFT S--SAVQ WVRQARGQRLEWIG WIVV--GSGNTNYAQKFQE RVTITRDMSTSTAYMELSSLRSEDTAVYYCAA
QVQLVQSGAEVKKPGSSVKVSCKASGGTFS S--YAIS WVRQAPGQGLEWMG GIIP--IFGTANYAQKFQG RVTITADESTSTAYMELSSLRSEDTAVYYCAR
QVQLVQSGAEVKKPGSSVKVSCKASGGTFS S--YAIS WVRQAPGQGLEWMG GIIP--IFGTANYAQKFQG RVTITADKSTSTAYMELSSLRSEDTAVYYCAR
EVQLVQSGAEVKKPGATVKISCKVSGYTFT D--YYMH WVQQAPGKGLEWMG LVDP--EDGETIYAEKFQG RVTITADTSTDTAYMELSSLRSEDTAVYYCAT
QITLKESGPTLVKPTQTLTLTCTFSGFSLS TSGVGVG WIRQPPGKALEWLA LIY---WNDDKRYSPSLKS RLTITKDTSKNQVVLTMTNMDPVDTATYYCAHR
QVTLKESGPVLVKPTETLTLTCTVSGFSLS NARMGVS WIRQPPGKALEWLA HIF---SNDEKSYSTSLKS RLTISKDTSKSQVVLTMTNMDPVDTATYYCARI
QVTLKESGPALVKPTQTLTLTCTFSGFSLS TSGMRVS WIRQPPGKALEWLA RID---WDDDKFYSTSLKT RLTISKDTSKNQVVLTMTNMDPVDTATYYCARI
EVQLVESGGGLVQPGGSLRLSCAASGFTFS S--YWMS WVRQAPGKGLEWVA NIKQ--DGSEKYYVDSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYCAR
EVQLVESGGGLVQPGRSLRLSCAASGFTFD D--YAMH WVRQAPGKGLEWVS GISW--NSGSIGYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTALYYCAKD
QVQLVESGGGLVKPGGSLRLSCAASGFTFS D--YYMS WIRQAPGKGLEWVS YISS--SGSTIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYCAR
EVQLVESGGGLVQPGGSLRLSCAASGFTFS S--YDMH WVRQATGKGLEWVS AIG---TAGDTYYPGSVKG RFTISRENAKNSLYLQMNSLRAGDTAVYYCAR
EVQLVESGGGLVKPGGSLRLSCAASGFTFS N--AWMS WVRQAPGKGLEWVG RIKSKTDGGTTDYAAPVKG RFTISRDDSKNTLYLQMNSLKTEDTAVYYCTT
EVQLVESGGGVVRPGGSLRLSCAASGFTFD D--YGMS WVRQAPGKGLEWVS GINW--NGGSTGYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTALYHCAR
EVQLVESGGGLVKPGGSLRLSCAASGFTFS S--YSMN WVRQAPGKGLEWVS SISS--SSSYIYYADSVKG RFTISRDNAKNSLYLQMNSLRAEDTAVYYCAR
EVQLLESGGGLVQPGGSLRLSCAASGFTFS S--YAMS WVRQAPGKGLEWVS AISG--SGGSTYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAK

13. PATTERN MATCHING
S
S
S A
M
S
A
S
V T Y
Y
A
A A
S
V
Q
S
Y
T
S S
P
G
S Y
R
R
V
Y
L
E
I
L
P
D
F
A
F
G
S
A
A
C
S
W
V
R
Q
S
V
W
R
F
T
A
C
Y
Y
W
G
Q
A

14. PATTERN MATCHING
S
S
F P
M
G
G
G
G A H
Y
E
N D
F
V
K
W
N
I
G G
F
S
Y S
G
T
D
Y
R
Y
G
T
D
F
T
L
W
F
R
Q
A
V
F
R
F
A
A
C
Y
Y
W
G
Q
T

15. APRIL 29, 2016
PEGS, BOSTON
ALIGNMENT-BASED ANNOTATION
5’ V
3’ J

16. APRIL 29, 2016
PEGS, BOSTON
ALIGNMENT-BASED ANNOTATION
5’ V
3’ J3’ J
3’ J

17. APRIL 29, 2016
PEGS, BOSTON
ALIGNMENT-BASED ANNOTATION
5’ V
3’ J
3’ J 3’ J
3’ J
3’ J
5’ V 5’ V

18. APRIL 29, 2016
PEGS, BOSTON
STRANGE SEQUENCES

19. APRIL 29, 2016
PEGS, BOSTON
STRANGE SEQUENCES
VH3 family

20. APRIL 29, 2016
PEGS, BOSTON
STRANGE SEQUENCES
VH3 family
Unnormal FR2

21. APRIL 29, 2016
PEGS, BOSTON
STRANGE SEQUENCES
VH3 family
Unnormal FR2
Some unusual mutations in FR3

22. APRIL 29, 2016
PEGS, BOSTON
STRANGE SEQUENCES
VH3 family
Unnormal FR2
Some unusual mutations in FR3
Enlarged CDR3

23. APRIL 29, 2016
PEGS, BOSTON
VHH

24. APRIL 29, 2016
PEGS, BOSTON
LEAD OPTIMIZATION PLAN
Make a classic Fv
Humanize heavy chain

25. APRIL 29, 2016
PEGS, BOSTON
PAIRING VHH
VL
VH

26. APRIL 29, 2016
PEGS, BOSTON
HUMANIZATION

27. APRIL 29, 2016
PEGS, BOSTON
HUMANIZATION

28. APRIL 29, 2016
PEGS, BOSTON
HUMANIZATION

29. APRIL 29, 2016
PEGS, BOSTON
HUMANIZATION

30. AFFINITY MATURATION
Δ Affinity

31. APRIL 29, 2016
PEGS, BOSTON
BCD 085
ANTI-IL17
Development Preclinical Studies I Phase II Phase III Phase Registration
✓

32. APRIL 29, 2016
PEGS, BOSTON
AUTOMATIC
PIPELINE

33. APRIL 29, 2016
PEGS, BOSTON
ANTI-TNF⍺
TNF⍺
VH
VL

34. APRIL 29, 2016
PEGS, BOSTON
CONSTRUCTION OF TRISPECIFIC

35. APRIL 29, 2016
PEGS, BOSTON
CONSTRUCTION OF TRISPECIFIC

36. APRIL 29, 2016
PEGS, BOSTON
CONSTRUCTION OF TRISPECIFIC

37. APRIL 29, 2016
PEGS, BOSTON
BACK TO VHH
VL VH

38. APRIL 29, 2016
PEGS, BOSTON
BACK TO VHH
VL VH

39. APRIL 29, 2016
PEGS, BOSTON
BACK TO VHH
45T
44G

40. APRIL 29, 2016
PEGS, BOSTON
BCD 085 VHH
VHH
IL17a

41. APRIL 29, 2016
PEGS, BOSTON
BCD 121
CH
VH
CL
VL
VHH

42. APRIL 29, 2016
PEGS, BOSTON
QUESTIONS?
YAKOVLEV@BIOCAD.RU