Oryzon Genomics Sa · BME:ORY
Oryzon Genomics Sa — 2017 BIO CEO & Investor Conference
30 slides from Oryzon Genomics Sa's conference presentation, Feb 13, 2017
Slide 1: 2017 BIO CEO & Investor Conference
Py PRESENTATION MADX: ORY sek : 2017 BIO CEO & Investor Conference ~~ * re
Slide 2: Disclaimer
DISCLAMER This document has been prepared by Oryzon Genomics, S.A. exclusively for use during the presentation. Oryzon Genomics, S.A. does not assume liability for this document if it is used with a purpose other than the above. The information and any opinions or statements made in this document ha
Slide 3: Oryzon: clinical stage epigenetics company
MADX: ORY A publicly traded company on the Spanish Stock Exchange A clinical stage biopharmaceutical company developing innovative therapies in the field of Epigenetics A competitive EPIGENETIC Platform with a first program that validates the platform scientifically and clinically Two therapeutic pr
Slide 4: Management team
CARLOS BUESA: CEO PhD in Biochemistry and Molecular Biology. Author of more than thirty papers and patents internationally. In 2000, he founded Oryzon CEO Genomics, and since 2001 he has served as Chief Executive Officer and Chairman of the Board of Directors. He has taken several advanced program
Slide 5: Epigenetics definition
Epigenetics − the study of heritable changes in genome function that occur without a change in DNA sequence These changes mainly occur due to variations in the structure of chromatin that silence or activate whole regions of the chromosome and all the genes that reside in this region These variation
Slide 6: A LSD1 focused company
A LSD1 focused company LSD1 is an enzyme that demethylates histones: specifically mono and dimethylated H3K4 and H3K9 6
Slide 7: ORY-1001: LSD1 target in cancers, licensed to Roche
LSD1 is a target in some cancers Licensed to ROCHE in 2014 LSD1 is a key effector of the differentiation block in MLL leukemia $23M received in 2014-15 $500+M in future MLL Leukemic stem cells are addicted to LSD1 contingent milestones activity Tiered royalties up to ORY-1001 is a highly potent and
Slide 8: Roche license agreement terms
Effective from April 1st, 2014 License of two patent families of the Oryzon IP Portfolio that Oryzon has created in its pioneering research in LSD1 Scope of the collaboration: R&D and commercialization of Oryzon’s LSD1 inhibitor lead agent ORY- 1001 (RG6016) and/or its backup compounds for oncology,
Slide 9: ORY-1001 preliminary data presented at ASH 2016
Preliminary data presented at ASH 2016. Well tolerated and has been administered to 41 patients in total up to a maximum of three cycles. Excellent oral bioavailability in humans and excellent pharmacokinetic parameters Pharmacodynamic biomarkers S100A12, VCAN, ITGAM, LY96, CD86, GPR65, CRISP9, ANXA
Slide 10: Roche Phase I with ORY-1001 in small cell lung cancer
Licensed to ROCHE in 2014 ORY-1001 has demonstrated Biological Proof of Mechanism as a highly active LSD1 inhibitor with strong differentiation-inducing activity in patients with MLL leukemia. It has shown an excellent safety profile in acute leukemia patients, and also displayed excellent oral bioa
Slide 11: ORY-2001: our next growth driver
ORY-2001: OUR NEXT GROWTH DRIVER ENVIRONMENT GENES EXPERIENCE Identical twins (monozygotic) Same DNA with GBA risk mutation Disconcordant for symptoms of Parkinson’s Up to 20 years difference in onset Patient derived iPSCs: Luca Lovrečić, et al., 2013 The Role of Epigenetics in difference in MAO-B l
Slide 12: LSD1 in CNS transcriptional complexes
LSD1 is a key component of different CNS transcriptional complexes interacting with different transcription factors and very often with HDAC1 and HDAC2 In the brain one of these TFs is REST. The LSD1-REST-CoREST-HDAC1/2 repressor complex is involved mainly in controlling developmental programs and m
Slide 13: ORY-2001 pharmacological properties and preclinical proof of concept
Pharmacological Properties Preclinical Proof of Concept Achieved A selective dual LSD1-MAO-B in different animal models of: inhibitor Alzheimer’s Disease Optimal ADMET and PK profiles Huntington’s Disease Crosses efficiently the BBB Multiple Sclerosis Once daily oral bioavailable 2 Additional CNS di
Slide 14: SAMP8 mouse: a model for Alzheimer's disease
SAMP8 mouse: A model for Alzheimer’s Disease Ac Bg 1 (co frontiers in ORIGINAL RESEARCH ARTICLE AGING NEUROSCIENCE 2 1 esiag ODO (Contare ata avatatle at Searze Somat Biochimica et Biophysica Acta oes Nodes and biological processes identified on the basis of ies network analysis in the brain of the
Slide 15: ORY-2001 produces cognitive improvement in SAMP8 animals
2 or 4 months of oral treatment with ORY-2001 produce a marked cognitive improvement in SAMP8 animals measured by NORT memory tests 9 studies in the last 5 years +150 animals tested Other +readouts in animal models of MS, HD, PD and other human CNS disorders N= 57 N= 12 N= 22 ORY2001 ORY-2001 restor
Slide 16: Cross over experiment: memory function restored
ongoing Cross over Experiment Treatment Month 6 7 Code SAMR1 Vehicle Vehicle 0+0 SAMP8 Vehicle Vehicle 0+0 SAMP8 ORY-2001 ORY-2001 1+1 SAMP8 ORY-2001 Vehicle 1+0 SAMP8 Vehicle ORY-2001 0+1 The drug restored memory function after the deficit had developed The delayed start cohort (0+1) experienced th
Slide 17: Effect driven by LSD1 with additive MAOB component
The effect is driven by LSD1 but there is an additive / synergistic effect provided by the MAOB component ORY-2001 provides a dose dependent protective effect in the medium-term memory of mice, compared to age-matched SAMP8 mice 17
Slide 18: How LSD1-8a works
LSD1-8a KO mice (Zibetti et al, Wang et al) o Neuronal differentiation ↓, Neurite extension ↓ Shelly Berger: ACSS2 deficit leads to o Long Term Memory ↓ memory defect and defect in up- o Induction of Egr ↓, Fos ↓, Npas4 ↓, Arc ↓ regulation of similar gene set How LSD1-8a works? Rat cortical neuron d
Slide 19: Gene expression signature in SAMP8 treated animals
SAMP8 0.96 mg/kg SAMP8 3.20 mg/kg SAMP8 0.96 mg/kg SAMP8 3.20 mg/kg SAMP8 Vehicle SAMP8 Vehicle SAMR1 SAMR1 Genes located in Inflammation -0,1843 -0,68 -1,27 -3,9245 -0,0994 -1,65 -1,64 -1,6714 -0,0339 -0,04 0,00 -3,6929 -0,2165 -1,59 -1,36 -1,6245 -0,025 -0,0715 0,18 -0,06 0,11 0,05 -3,4794 -2,805
Slide 20: S100A9 downregulation improves memory in AD mouse models
S100A9 downregulation improves memory in different AD Tg mice models S100A9 has been involved in the A-Beta deposition dynamics CT-Tg mice S100a9 markedly increased in cortex and Mutant APP(V717I) hippocampus, memory impairment CT100 (London mutation) (Ha et al., 2010) Tg2576 mice S100a9 upregulated
Slide 21: ORY-2001 downregulates S100A9 in SAMP8 hippocampus
ORY-2001 downregulates S100A9 in the Hc of SAMP8 animals Complexes of S100A8 and S100A9 (S100A8/A9) are expressed and released at inflammatory sites A correlation between serum levels of S100A8/A9 and disease activity has been observed in many inflammatory disorders Quinoline-3-carboxamides (Q compo
Slide 22: Model for multiple sclerosis
Model for multiple sclerosis o C57BL/6 mice immunized s.c. with 100 g of MOG35–55 emulsified in CFA containing 4 mg/ml M. tuberculosis H37 RA and i.p. injections of 200 ng of pertussis toxin on days 0 and 2 Treatment after onset of EAE symptoms (d11) during 2 weeks with o ORY-2001 p.o.; ORY-LSD1 p.
Slide 23: ORY-2001 mechanism in multiple sclerosis
ORY-2001 S100A9 TLR APC Peripheral immune + S100A9 T system IL-12/23 Treg Th B Disease S100A9 Disease Autoreactive Th1 and Th17 amplification initiation migration BBB permeability S100A9 Reactivation, expansion, TLR + APC cytokine secretion Central B T Th1 nervous system Th17 IgG autoantibodies MΦ C
Slide 24: Phase I study with healthy volunteers
A Phase I study with 88 healthy volunteers, young and elderly Single Ascending Dose (SAD): all cohorts were safe. No hematological effects nor any other relevant/significant side effects observed in any cohort Additional arm to determine CSF ORY-2001 levels after a single dose Multiple Ascending Dos
Slide 25: ORY-2001 expected to be ready for Phase II in 2H-2017
ORY-2001 expected to be ready for Phase II in 2H-2017 The Phase I in healthy volunteers enables us to go for Phase IIs in different indications The company envisages to perform three different Phase IIs in AD, MS and HD 2015 2016 2017 3Q2015 4Q2015 1Q2016 2Q2016 3Q2016 4Q2016 1H2017 2H2017 CMC / 4W
Slide 26: Corporate strategy: epigenetics momentum, IP and first in class assets
Corporate Strategy: Epigenetics Momentum, IP & First in Class Clinical Assets Epigenetics is an emerging field with high interest from Pharma (select acquisitions: Roche/Tensha; Celgene/Acetylon; Merck/OncoEthix) and from Specialized Investors (Imago, Constellation) High quality science and a broad
Slide 27: Cash balance and financial debt
Cash Balance 28.803.492 Short-term financial assets 5.598.006 Cash and Equivalents 23.205.486 Financial Debt 23.698.609 New Financial bank loans in 2016 Long-term Debts 19.098.559 Short-term debts 4.600.050 15,750 Mio € Net Balance 5.104.884 2,68% Average Interest Rate 27
Slide 28: Shareholders distribution
TOP 10 ORYZON SHAREHOLDER by January 2nd 2017 NAJETI CAPITAL SA 7.017.799 24,65% % Shareholders distribution TAMARA MAES 3.742.530 13,15% CARLOS MANUEL BUESA 3.742.530 13,15% Reference Shareholder INVERSIONES COSTEX S.L. 1.854.723 6,52% 29% JOSE MARIA ECHARRI 1.026.928 3,61% Oryzon Genomics (Own 55%
Slide 29: Milestones and anticipated news flow 2017-2018
2014 Transformational deal with Roche ($21M) on ORY-1001 CONSOLIDATION PERIOD 2015-16 Public in Europe ($36M raised June-2015-June 2016 ) ORY-1001: Clinical Data Presented at ASH-2016 Second Asset (ORY-2001 in clinic development) ORY-1001: LEAD CANCER ASSET FPI in Phase I SCLC by Roche 1Q 2017 • Pha
Slide 30: Thank you very much
THANK YOU VERY MUCH! CARLOS BUESA C.E.O. & Presiden cbuesa@oryzon EMILI TORRELL ANNA K.BARAN BDO IR Director etorrell@oryzon.com abaran@oryzon.com