Chemomab Therapeutics Ltd. · NASDAQ:CMMB
Chemomab Therapeutics — Anchiano Therapeutics — Investor Presentation (February 2020)
28 slides from Chemomab Therapeutics's investor presentation, Feb 4, 2020
Slide 1: Targeting Genetically-Defined Cancers: Corporate Presentation February 2020
TARGETING GENETICALLY - DEFINED CANCERS Corporate Presentation February 2020
Slide 2: Safe Harbor Statement
Safe Harbor Statement This presentation contains forward - looking statements within the meaning of U.S. federal securities laws and Israeli securities laws that involve risks and uncertainties. These forward - looking statements include, but are not limited to, statements about our market opportuni
Slide 3: We Aim to Develop Transformative Therapies Targeting the Genetic Basis of Cancer
We Aim to Develop Transformative Therapies Targeting the Genetic Basis of Cancer 3 Anchiano Therapeutics (Nasdaq: ANCN) Pan - RAS Program PDE10/ β - catenin Program • We are a small molecule biopharmaceutical oncology company • We are focused on pan - RAS inhibition • Our team has a record of succes
Slide 4: Executive Team
Executive Team Our team has a track record of oncology development 4 Frank G. Haluska, MD, PhD President and Chief Executive Officer Former Harvard Medical faculty, A riad CMO, led global research team and two oncology drug approvals David Kerstein, MD Chief Medical Officer Spearheaded worldwide app
Slide 5: Scientific Advisory Board
Scientific Advisory Board World authorities on the basic and clinical science of targeting signaling pathways 5 Julian Adams, PhD CEO at Gamida Cell, former Head of R&D at Infinity, and SVP of Drug Discovery at Millennium Pharmaceuticals, expert in signal transduction Neal Rosen, MD, PhD Director, C
Slide 6: Pipeline: Focus on pan-RAS inhibitor development
Pipeline 6 Focus on pan - RAS - inhibitor development CORPORATE PRESENTATION |
Slide 7: RAS is the Most Frequently Mutated Oncogene in Human Cancer
Human cancers with >5% RAS mutation frequency • Mutations in the RAS family of genes (KRAS, HRAS and NRAS) are the most frequent oncogenic mutations known and are present in over 30% of all cancer • There is a need and opportunity for agents that target all isoforms of RAS and all activating mutatio
Slide 8: RAS is Central to Malignancy
• RAS resides at the center of the key pathways that transduce signals from the surface of the cell to its interior, resulting in survival, proliferation, or other responses to the cellular environment • Most cancers carry activating mutations in this pathway; such mutations can involve an upstream
Slide 9: Amgen and Mirati Have Successfully Demonstrated KRAS G12C Inhibition in Clinical Trials
9 Amgen and Mirati Have Successfully Demonstrated KRAS G12C Inhibition in Clinical Trials Preclinical data successfully predicted clinical responses with Amgen and Mirati drugs o Data above show that preclinical activity with low nanomolar cellular IC50s against KRAS G12C mutant cell lines, and supp
Slide 10: The Pan-RAS Market Opportunity
The Pan - RAS Market Opportunity 10 * “Total addressable patients” represents the total treatable advanced/metastatic patient population, and does not consider m ark et dynamics (e.g., therapy line, pref. share, market access, etc.) Source: 2019 SEER Data; Garrido et al., Ther Adv Med Oncol , 2017;
Slide 11: Our RAS Inhibitor Discovery Strategy
11 Our RAS Inhibitor Discovery Strategy We screened candidate inhibitors from a custom library of compounds having an indene core, as illustrated at left The primary screen involved high - throughput dose - response experiments utilizing cell lines with mutant RAS (HCT - 116) and wild - type (WT) RA
Slide 12: Characteristics Expected with Direct Pan-RAS Inhibition: Comparison with AMG 510
Characteristics Expected with Direct Pan - RAS Inhibition: Comparison with AMG 510 12 * Data not shown Characteristic ANC 007 AMG 510 Potently inhibits KRAS, NRAS, and HRAS mutant cell lines (across multiple mutations) in monolayer and spheroid cultures Potently inhibits KRAS G12C mutant cell lines
Slide 13: Our Compounds Demonstrate Potent and Selective Pan-RAS Inhibition
Our Compounds Demonstrate Potent and Selective Pan - RAS Inhibition Source: Keeton et al., AACR 2019; Mattox et al. AACR 2019; McConnell et al. AACR 2017; Data on File 13 Mutation Status IC 50 , Cell - based Assay (nM) Cell Line Tumor Origin Genotype KRAS G12C 2.1 Mia PaCa - 2 Pancreatic Mutant RAS
Slide 14: Potent and Selective Pan-RAS Inhibition of Monolayers and Spheroids
Potent and Selective Pan - RAS Inhibition of Monolayers and Spheroids Source: Keeton et al., AACR 2019; Mattox et al. AACR 2019; Data on File 14 A C E B D Growth inhibitory activity in monolayer cultures for ANC 007 is illustrated in Figs. A and B, left, for both colon cancer (A) and pancreatic canc
Slide 15: Potent and Selective Pan-RAS Inhibition in Lung Cancer
Potent and Selective Pan - RAS Inhibition in Lung Cancer Source: Data on File 15 ANC 007 uM B ANC 007 uM A Growth inhibitory activity in monolayer cultures for ANC 007 is illustrated in several lung cancer cell lines with the genoty pes indicated in the figure (A) Activity is similar in spheroid cul
Slide 16: Inhibition of Downstream Signaling Through RAF and PI3K Pathways
Inhibition of Downstream Signaling Through RAF and PI3K Pathways In Vitro and In Vivo 16 Source: Keeton et al., AACR 2019; Mattox et al. AACR 2019 B A Treatment of MIA - PaCa - 2 pancreatic cancer cells with KRAS G12C results in inhibition of signaling of the MAPK pathway as evidenced by inhibition
Slide 17: Induction of Cell Cycle Arrest and Apoptosis
Induction of Cell Cycle Arrest and Apoptosis 17 Source: Keeton et al., AACR 2019; Mattox et al. AACR 2019 ANC 007 selectively induces mitotic (M) arrest of HCT - 116 mutant KRAS tumor cells but not RAS WT HT29 cells (A) ANC 007 also induces apoptosis as evidenced by cleaved caspase 3 (B) ANC 007 nM
Slide 18: Inhibition of GTP Binding to Recombinant KRAS
Inhibition of GTP Binding to Recombinant KRAS Mattox et al. AACR 2019; Data on File 18 The effect of ANC 007 on the binding of GTP to RAS has been tested in several experiments ANC 007 inhibited the GTP loading of recombinant RAS in cell - free biochemical assays (A); when added to nucleotide - free
Slide 19: ANC 007 Exhibits In Vivo Anti-tumor Activity in RAS-driven Tumor Models
Source: Mattox et al. AACR 2019; Data on File 19 Figure : ANC 007 inhibits growth of KRAS mutant HCT - 116 tumor cells in a subcutaneous mouse xenograft model . Athymic nude mice were implanted in the right flank with 10 million tumor cells per mouse . Mice were treated once daily by intratumoral ad
Slide 20: In Vivo Anti-tumor Activity in RAS-driven Tumor Models
In Vivo Anti - tumor Activity in RAS - driven Tumor Models Source: Data on File 20 Day 17 – Tx Start on Day 6 ANC 007 suppressed tumor growth in a CT26 colon tumor mouse xenograft model by subcutaneous delivery Representative control (Left) and MCI - 062 animals (Right) shown in the figure MCI - 062
Slide 21: RAS Inhibitor AMG 510 Stimulates Anti-tumor Immunity
RAS Inhibitor AMG 510 Stimulates Anti - tumor Immunity Source: Canon et al., Nature 2019 21 Data from the KRAS inhibitors presently in the clinic are generating hypotheses that suggest a hallmark of direct RAS inhibition may be enhancement of anti - tumor immunity AMG 510 drives increases in immunog
Slide 22: ANC 007 Stimulates Anti-tumor Immunity Similar to AMG 510
ANC 007 Stimulates Anti - tumor Immunity Similar to AMG 510 Source: Keeton et al., AACR 2019; Mattox et al. AACR 2019 22 In an immune competent mouse tumor model (CT26, colorectal), ANC 007 suppressed tumor growth in association with decreased PD - L1 levels in tumors (figure A, B); decreased PD - 1
Slide 23: Development Timelines
Development Timelines Pan - RAS Preclinical Development • Preclinical program focused on development of clinical lead compound • Anticipate total 12 - 18 months (from Q1 2020) to product candidate nomination, followed by approximately 12 months for IND - enabling studies • Anticipate IND and initiat
Slide 24: PDE10/β-catenin Program Overview
PDE10/ b - catenin Program Overview Source: Li et al., Oncogene, 2015; Data on File 24 Figures : PDE 10 overexpression in colon tumor cells ; inhibition blocks colony formation and B - catenin/ Tcf transcription . A, Differential PDE 10 levels in normal colonocytes (NCM 460 ) and colon tumor cells a
Slide 25: ANC 061 Inhibits Colon Tumorigenesis in the Apc Min Model
ANC 061 Inhibits Colon Tumorigenesis in the Apc Min Model Source: Ward et al., AACR 2019 25 Familial adenomatous polyposis (FAP) is a genetic predisposition to multiple colon adenomas which progress to colon cancer; patients have a mutation in APC and dysregulation of β - catenin ANC 061 inhibits PD
Slide 26: ANC 030 Inhibits Lung Tumorigenesis in A549 Lung Cancer Model
ANC 030 Inhibits Lung Tumorigenesis in A549 Lung Cancer Model Source: Zhu et al. AACR 2019 26 ANC 030 administered orally inhibits tumor growth in an orthotopic lung cancer mouse model without apparent toxicity ANC 030 significantly extends survival in the A549 mouse model from a median 44 to 77 day
Slide 27: Intellectual Property
Intellectual Property Strong IP estate Granted patents cover composition of matter and methods of use in RAS - driven malignancies Patent life through 2034 Sulindac Indene library Initial hit Primary Screen K - Ras mutant HCT116 vs. WT Ras Raf mutant HT29 ~ 1500 compounds ADT - 004 27 CORPORATE PRES
Slide 28: Key Takeaways
E xperienced management has history of successful small molecule targeted therapy development for such programs Data in hand demonstrate pan - RAS nM potency in vitro, inhibition of RAS signaling, inhibition of GTP binding to RAS, in vivo activity, and stimulation of anti - tumor immunity Related co
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