Oncotelic Therapeutics Inc · OTC:OTLC
Oncotelic Therapeutics — Mateon Therapeutics — Pharma Forum 2020
21 slides from Oncotelic Therapeutics's conference presentation, Sep 22, 2020
Slide 1: Building the next generation Biotech
SS —e — —i gt = <1 . ™ ONCOTELIC Building the next generation Biotech TRABEDERSEN-DRUG DEVELOPMENT USING PHOSPHOROTHIOATE ANTISENSE PLATFORM MATEON THERAPEUTICS
Slide 2: Forward-looking Statements
Forward-looking Statements This document contains “forward-looking statements” that involve substantial risks and uncertainties for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, included in thi
Slide 3: The Three Convergents
The Three Convergents — QT “e PointR.a ONCOTELIC Supercom Antisense puting DNA Transcription MATEON THERAPEUTICS
Slide 4: Antisense Oligonucleotide Molecules
ae Antisense Oligonucleotide Molecules ~r + Single stranded (13-25-mer) DNA molecules * Specifically inhibit target protein expression via complementary hybridization to relevant mRNA “PS backbone 5 —,-3° Antisense oligonucleotide -3’ Target mRNA £\ + RNAse H-mediated cleavage of target mRNA DNA/RNA
Slide 5: Antisense as Next Generation Drugs
Antisense as Next Generation Drugs a Inception 1850s to present 1920s to present 1990s to present Size 200-500 >150,000 5,000 to 7,000 Drug Discovery Random screening Focused screening Rationally designed Success Rate Low-~5% Moderate-~50% High-~90% Predictable PK No Yes Yes On Target Safety Target
Slide 6: FDA has approved several ASO
FDA has approved several ASO Fomivirsen: treatment of patients with cytomegalovirus (CMV) retinitis Macugen: age-related macular degeneration (AMD) of the retina Mipomersen: homozygous familial hypercholesterolemia (HOFH) Nusinersen/Spinraza: spinal muscular atrophy. Exondys- Duchenne muscular dystr
Slide 7: Application of Antisense: SARS-CoV-2 Antiviral Agents
XP Ze = — “LN ni ONCOTELIC Application of Antisense SARS-COV-2 ANTIVIRAL AGENTS MATEON THERAPEUTICS
Slide 8: SARS-CoV-2 Target Regions
SARS-COV-2 Target Regions > > 5-UTR: 72 nucleotide-long leader sequence at the 5’ end of SARS-CoV-2. TRS: transcription-regulating sequences (TRSs) mediating the discontinuous transcription of subgenomic viral mRN As (sgRNAs). FS: ORF 1a/1b is translated by way of ribosomal frameshifting into polype
Slide 9: Active SARS-CoV-2 Antisense
ONC ie Active SARS-CoV-2 Antisense = ie > Antiviral activity against SARS-CoV and SARS-CoV-2 for each compound is shown. > Cytotoxicity was observed for TRS1 (53-72), FS (13,458-13,472), and STERM (1-20) MOE. > High antiviral activity was observed with the following compounds: OT-101, STERM (1-20),
Slide 10: Application of Antisense: OT-101 as SARS-CoV-2 Antiviral Agent
— —————— ONCOTELIC Application of Antisense OT-101 AS SARS-COV-2 ANTIVIRAL AGENT MATEON THERAPEUTICS 10
Slide 11: OT-101 is a Nanomolar Inhibitor of SARS-CoV-2 Replication
en Uckun FM, Trieu V. Anna Pul and Cri Car Med..2020; 3(1); o1 -09: = ONC _ > OT-101 was effective against both SARS- CoV and SARS-CoV-2. Moreover, CC50 for OT-101 was calculated to be >1000 ug/mL (the highest concentration tested) indicating that the cellular proliferation was not affected by OT-10
Slide 12: SMAD3 inhibition and SARS-CoV-2 replication
Wei J. et al. Preprint. bioRxiv. 2020;2020.06.16.155101. > Enrichment of sgRNAs targeting the signal transducers SMAD3 and SMAD4 as well as TGF-B superfamily receptor ACVR1B were observed as pro-viral. SIS3, an inhibitor of SMAD3 of the TGF-B pathway, exhibited dose dependent protection from virus-i
Slide 13: TGF-B and EGFR pathway upregulation upon infection
Stukalov A et al. bioRxiv.2020.06.17.156455. —- > Upon virus infection, there was an h sone Boe upregulation of TGF-B and EGFR ~ mo, sag pathways. Specifically, their diffusion can wi “ono, 7 4 analysis revealed the connection £ bce Steen between the binding of ORF8 and ORF3 : aie to TGF-B-associate
Slide 14: Elevated TGF-B in COVID-19
—— Elevated TGF-f in COVID-19 > Elevated TGF-B2 expression among RNAs isolated from the bronchoalveolar lavage (BAL) fluid of COVID-19 patients versus normal controls has been reported [Xiong Y et al. Emerg Microbes Infect. 2020;9(1):761- 770). TGF-B is higher among severe COVID-19 patients. Normal
Slide 15: Impacts of Elevated TGF-B
Impacts of Elevated TGF-B Sin, > TGF-B recruits neutrophils into the site of inflammation laying down neutrophil extracellular traps (NET’s) responsible for capillaritis, fibrin deposition, mucositis in COVID-19 [Barnes BJ et al. J Exp Med. 2020;217(6):e20200652.]. TGF-B inhibits ENaC and causes flu
Slide 16: OT-101: Drug Product - TGF-B2 Antisense
OT-101: Drug Product- TGF-B2 Antisense. ~—— %* Trabedersen (OT-101) is a single-stranded phosphorothioate antisense oligodeoxynucleotide (18-mer) targeting the human TGF-B2 messenger RNA * Ready for registration trials--Over 200 patients treated across 6 clinical trials Potential for breakthrough de
Slide 17: OT-101 inhibits SARS-CoV-1 and SARS-CoV-2 replication
—_—— —————— —S OT-101 inhibits SARS-CoV-1 and SARS-CoV-2 replication— * In collaboration with Dr. Brett Hurst at Utah State University, part of the NIAID Antiviral Testing Consortium * Invitro antiviral activity against SARS-CoV-1 and SARS-CoV-2 in Vero 76 cells. Compound Virus ECs CCeg Sl OT-101 SA
Slide 18: MOA of OT-101: The TGF-B storm
——_ - —antvin! Ce ——MOA of OT-101: The TGF-B storm Antiviral cons _—— <= "Sate OT-101: , viral replication is suppressed, IFNB is induced, and innate and adaptive immune responses suppressed. End result = protection from both viral and immune driven pathologes ie. ARDS and cytokine storm. [1]. Untre
Slide 19: OT-101 Treatment Suppressed IL-6
———_ OT-101 Treatment Suppressed IL-6 19 Cytokine levels of clinical plasma samples of 12 pancreatic cancer patients of the PO01 study of OT-101 in advanced solid tumor patients were measured using the ImmunoSignal cytokine storm assay developed by Eurofins. Nine patients with elevated IL-6 were exa
Slide 20: OT-101: Proposed Phase IIa/III Clinical Trial Design
—_OT-101: Proposed Phase Ila/IIl Clinieal tral desire COVID-19 COVID-19 Patients Phase IIA Trial -part 1- w/o oxygen requirement -part 2- w/ oxygen requirement Phase III N~ 300 2:1 Randomization Size and Indication dependent on phase IIA oz>7 outcome mN-ZOjuoz>x Arm 1 Arm 2 OT-101 Dose: 140 mg/m? on
Slide 21: Thank You
—— eo Mateon/Oncotelic- (MATN)- Pharma Forum 2020/ eas Pharmacology and Toxicology/September 21, 2020 i _ —@ ~i\” NAVIGATOR DATA PIPELINE Large Data Analytics Large Clinical Data High Value Pipeline A MATEON Thank You THERAPEUTICS