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: [email protected] 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