Quest Pharmatech Inc. · TSXV:QPT
Quest Pharmatech — AmrutBio — Investor Presentation (January 2016)
22 slides from Quest Pharmatech's investor presentation, January 2016
Slide 1: One-two Punch to Deadly Pancreatic Cancer: Targeted Therapy with Mab AR9.6 and ACP 2127
One-two Punch to Deadly Pancreatic Cancer: Targeted Therapy with Mab AR9.6 and Rapamycin Analogue ACP 2127 Jan 2016
Slide 2: AmrutBio Overview
AmrutBio Overview • A subsidiary of Quest PharmaTech, a publicly traded (QPT-TSXV), Canadian pharmaceutical company • Lead product (Mab AR9.6) under development is for a novel target for cancer therapy discovered at University of Nebraska Medical Center; Target: truncated O-glycans on MUC16 • Second
Slide 3: AmrutBio Overview Continued
AmrutBio Overview Continued • Combinatorial approach for optimal efficacy • Diversified Product Pipeline with two proprietary technologies • Experienced management and scientific team • Access to academic and clinical expertise • Funding required for product development and clinical trials
Slide 4: Management and Scientific Team
Management and Scientific Team • Madi R. Madiyalakan Ph.D, Successful public company CEO, 25 + years Oncology experience • Tony Hollingsworth Ph.D, Chief Scientific Officer, Professor, UNMC • Selvaraj Naicker Ph.D, Chief Chemist • Prakash Radhakrishnan Ph.D, Director of R & D, Research Assistant Pro
Slide 5: Company Directors
Company Directors • Lorne Meikle, B.Econ • Ian McConnan, FCA • Eric Shi, Ph.D. • Shawn Lu, MBA • Madi Madiyalakan, Ph.D.
Slide 6: Pancreatic cancer: A problem
Pancreatic cancer: A problem Overall survival for resected patients with pancreatic cancer (MSKCC surgical database: 1983 – 2005, n =985) (PDA has a five year Survival of only ~6% - Saif, 2013) 100 Stage IA (n=28) 80 IB (n=155) IIA (n=190) Percent survival IIB (n=597) 60 IV (n=15) 40 20 0 12 24 36 4
Slide 7: First Punch: Mab AR9.6
First Punch: Mab AR9.6 Binds to truncated O-glycans on MUC16 mucin (PCT patent pending) Mucins are expressed by most adenocarcinomas Biomarkers CA19-9 and CA125 are mucins Most other longstanding biomarkers for cancer (CEA, AFP, others) are glycoproteins Pathologists consider mucin expression to be
Slide 8: Aberrant glycoforms of MUC16 create biologically active compounds that contribute to tumor aggressiveness
Aberrant glycoforms of MUC16 create biologically active compounds that contribute to tumor aggressiveness MUC16 is a membrane bound, heavily glycosylated cell surface glycoprotein, expressed in certain normal cells; however, its expression is often upregluated in malignant tumors that also produce
Slide 9: Mab AR9.6 Treatment: T3M4 Cells tumor growth and metastasis
Mab AR9.6 Treatment: T3M4 Cells tumor growth and metastasis (A) (B) T3M4 wildtype Tumor metastasis (C) T3M4 KO Tumor metastasis p=0.01 We examined the in vivo therapeutic efficacy of AR9.6 mAb in an orthotopic pancreas tumor model system. T3M4 wildtype and SC cells tumor bearing animals (n=15/group)
Slide 10: Central Hypothesis
Central Hypothesis We hypothesize that differential glycosylation of MUC16 creates novel ligands for growth factor receptors and integrin complexes, and their interactions facilitate constitutive activation of autocrine and paracrine oncogenic cell signaling pathways, which results in enhanced malig
Slide 11: Summary
Summary Our results demonstrate that aberrant expression of Tn/ STn epitopes on the MUC16/CA125 mucin glycoproteins expose EGF-like and other regions of the protein cores that bind to growth factor receptors (ErbB2), and integrin (α2β1) complexes, which induce activation of oncogenic signaling casc
Slide 12: Cyclin Dependent Kinases (CDK)
Cyclin Dependent Kinases (CDK) • Play a crucial role in the processes of transcription, mRNA processing and cellular differentiation • can be targeted in order to prevent proliferation of cancer cells • Inhibition of these kinases has shown induction of apoptosis especially in cancer cells
Slide 13: mTOR Pathway (2nd Control)
mTOR Pathway (2nd Control) • The mammalian TOR (mTOR) pathway is a key regulator of cell growth and proliferation • increasing evidence suggests that its deregulation is associated with human diseases, including cancer and diabetes • mTOR exists in two multiprotein complexes mTORC1 and mTORC2 • mTOR
Slide 14: ACP2127
ACP2127 • ACP 2127 is a novel immunomodulator with anti-cancer properties targeted to inhibit CDK functionality and prevent the growth of cancer cells. • More than 40 compounds were synthesized and screened against various human cancer cell line and 3 drug candidates have been selected for further d
Slide 15: ACP2127 Cell Cycle Inhibition
ACP2127 Cell Cycle Inhibition ACP2127 G2 M G1 S R p1 p21 6 p27 CDK2 CDK4 CDK6 Cyclin E Cyclin D R P P P RB SP P HA SE E AS ABL RB HDAC PH E2F-1 E2F-1 1 G DP-1 DP-1 OFF ON
Slide 16: ACP2127
ACP2127 • Inhibition of growth of various cancer cell- lines. • Cell-cycle analysis using western blot of various cancer cell lysates confirms G1-S block and apoptosis. • Induces cancer cells apoptosis at low concentration (50 μM) • Inhibition of the mTOR PI3K-AKT pathway
Slide 17: ACP2127: Dual Cell Cycle CDK and mTor Inhibitor
ACP2127 Dual Cell Cycle CDK and mTor Inhibitor • Multi-functional potential irreversible inhibitor combining the effect of CDK inhibitor p21 and also through additionally inhibiting mTOR in the PI3K-AKT Pathway • Dual target activity enhance efficacy • Effective Cancer targets: Pancreatic, colon, le
Slide 18: Applications for ACP2127
Applications for ACP2127 Therapeutic potential of CDK inhibitors Cardiovascular diseases Viral infections Artherosclerosis -Restenosis Cardiac hyp Cancers Antitumour chemotherapy —_._ ~3ty -Alzheimers's disease A -Parkinson's disease ~~ -Niemann-pick disease type C -Amyotrophic lateral sclerosis -St
Slide 19: Competitions (CDK Inhibitors)
Competitions (CDK Inhibitors) Name of Drug Indications Status Dinaciclib (SCH727965) Breast, NSCLC, chronic Lymphocytic Phase 3 study in CLL initiated in 2012 Leukemia refractory chronic lymphocytic leukemiarefractory chronic lymphocytic leukemia Palbociclib (PD-0332991) Breast Cancer Phase II trial
Slide 20: Competition (mTor Inhibitors)
Competition (mTor Inhibitors) Name of Drug Indications Status TORISEL Renal cell carcinoma, glioblastoma Approved for treatment of advanced renal cell (Temsirolimus, CCI-779) multiforme, carcinoma in 2007 lymphoma, breast and lung cancer Afinitor Kidney cancer, breast cancer, Approved for Advanced k
Slide 21: Competitive Advantage of ACP2127
Competitive Advantage of ACP2127 ACP2127 is the only drug candidate in development that targets simultaneously two cell cycle regulatory checkpoints for optimal efficacy • p21 through CDK inhibition • p13k/AKT through mTOR inhibition
Slide 22: Summary
Summary AR9.6 mAb EGF MUC16 MUC16 HER2 JAK2 Treatment of cancer cells with AR9.6mAb binds to α2 β1 FAK / ILK MUC16 and blocks the activation of growth factor PI3K receptors and thereby inhibit phosphorylation of Akt, which leads to reduced cell proliferation, in T308 p p S473 vivo tumor growth and m