News Release

News Release
November 5, 2014
PeptiDream Inc
http://www.peptidream.com /
（Ticker Code：4587 TSE Mothers）
Dr. Ron Jackson, MedImmune/AstraZeneca, to Present Recent
Findings on the PeptiDream Collaboration at EuroPeptides 2014
TOKYO, JAPAN – November 5th, 2014 – PeptiDream Inc, a public Tokyo-based
biopharmaceutical company (“PeptiDream”)(Tokyo:4587) announced today that Dr. Ron
Jackson, Principal Scientist, at MedImmune, the biologics arm of AstraZeneca, will be
presenting some of the recent findings from the PeptiDream-AstraZeneca collaboration
targeting Kras, entitled “Successful Strategies for Optimising Design and Validation of
Macrocyclic and Constrained Peptides” at EuroPeptides, November 17th-19th, Berlin,
Germany.
Kras is one of the most frequently mutated oncogenes in cancer, and represents a
promising therapeutic target, but has been stubbornly intractable. Dr. Jackson will report on
ongoing optimization efforts between the companies on macrocyclic peptides identified at
PeptiDream.
The macrocyclic/constrained peptides identified by PeptiDream, in
collaboration with AstraZeneca, are the first reported cyclic peptide binders to Ras, and hit
novel binding sites, and are highly potent in the inhibition of Kras in cancer cells, validating
that PeptiDream’s macrocylic peptides can penetrate cells and inhibit previously intractable
intracellular targets. Further optimization and development of the lead candidates are
currently ongoing.
EuroPeptides 2014 Website
http://www.informa-ls.com/event/Peptides2014
[Comments from Patrick Reid, CSO and Keiichi Masuya, COO, of PeptiDream Inc]
“The results presented by Dr. Jackson validate the power of our PDPS technology to identify
macrocyclic/constrained peptides that can potently inhibit previously intractable/undruggable
targets, such as Kras. We greatly look forward to continuing their development toward the
clinic.”
<About PeptiDream Inc.>
PeptiDream Inc. is a public (Tokyo Stock Exchange Mothers 4587) biopharmaceutical
company founded in 2006 employing our proprietary Peptide Discovery Platform
System(PDPS) , a state-of-the-art highly versatile peptide generation and selection
platform which enables the production of highly diverse (trillions) non-standard peptide
libraries with high efficiency, for the discovery and development of best-in-class and
first-in-class peptide-based therapeutics. PeptiDream aspires to be a world leader in
the discovery and development of novel highly functional peptide therapeutics to
address unmet medical needs and improve the quality of life of patients worldwide. For
further information please visit www.peptidream.com
Enquiries:
PeptiDream Inc.
Patrick C Reid +81-3-5790-9991 (Tokyo)
EMAIL: p-reid@peptidream.com
Derivation of Cyclic Peptides Targeting Ras using
PD (Ribosome) Display
K-Rras G12V_GTP
Switch 2
Switch 1
2VH5
Aim
To isolate cyclic peptides
blocking Ras function at:
Switch 1 Ras/Raf
Or
Switch 2 Nucleotide
Exchange
1
Cyclic Peptides from PD Display
U
C
A
G
MePhe
Ser
Tyr
ClTrp
OPEN
U
Stop
Leu
Re-assigned
Genetic Code
MeTyr
His
C
Arg
MeGly
A
MeNle
Asn
ClAcX
Cys
Val
G
Arg
Ser
Ser
Arg
MeAla
Asp
Gly
Gly
U
C
A
G
U
C
A
G
U
C
A
G
U
C
A
G
 Incorporation of essentially any non-canonical
amino acid
 Acylation of tRNA, catalysed by a ribozyme
 N-terminal substitution with chloroacetyl amino
acids to give thioether cyclised peptides by
reaction with cysteine
 N-methyl amino acids can be included to reduce
hydrogen bond donors
2
3
Identification of Inhibitory Peptides for K-Ras
 Peptides identified with IC50 3nM direct from library
 Next steps:
– Define inhibition of Ras/Raf interaction or nucleotide exchange
– Proceed to cell-based functional assays
Jon Tart, AstraZeneca
4
Optimisation of Cyclic Peptide based on XRay Crystal Structures
 First reported cyclic peptide direct binders to Ras
 Novel binding sites
 Optimisation for biochemical activity and cell potency
 Optimise by display/design – truncation, minimisation of
hydrogen bond donors (N-methyl amino acids) and
charge
Chris Phillips, Mike Waring, AstraZeneca
5