AbGn-107, an ADC Targets Gastrointestinal Tumors

Transcription

1 AbGn-107, an ADC Targets Gastrointestinal Tumors For a Healthier Life Presented by Ron Lin Feb. 22, 2016 All Rights reserved AbGenomics International Inc El Camino Real, Suite 200, Los Altos, CA

2 Company Overview Principal office in San Francisco Bay Area, CA and Research Center in Taipei Taiwan. Two proprietary therapeutic platforms: First-in-class MAbs for inflammatory and autoimmune diseases Antibody-drug-conjugates (ADC) for cancers 2

3 Cancer Inflammator y disease Product Pipeline Product Indication Preclinical IND enabling Phase I Phase II Phase III Neihulizumab AbGn-168H TNF-Inhibitor Refractory Psoriatic Arthritis Phase-2b to commence In Q4, 17 Neihulizumab AbGn-168H TNF-Inhibitor Refractory Ulcerative Colitis Phase 2a to commence in Q3, 17 Neihulizumab AbGn-168H Steroid Refractory - Acute GvHD Phase 1 to commence in Q3, 17 AbGn-107 (ADC) Gastric, Pancreatic & Colorectal Cancers Phase 1 In advanced GI cancer patients AbGn-110 (ADC) Breast Cancer AbGn-108 (ADC) Lung & Ovarian Cancers A Growing Pipeline of Innovative Drug Candidates for Immune-Mediated Inflammation and Cancer Therapies 3

4 AbGn-107 An ADC that consists of a glyco-variant of CD71-specific antibody and a clinical tested potent tubulin inhibitor through a novel cleavable hydrophilic self-immolative linker. 4

5 Safety Profile of the Target Targeting Ab does not bind to normal tissues (36 Organs tested) except the apical/lumen surface of GI and a few secretary ducts which is considered less accessible to circulating antibody. 5

6 Safety Evaluation of the Target (1) Target Tissues (apical/lumen surface) GI tract mucosa epithelial cells Liver (bile duct) Pancreas (duct) Salivary Gland (duct) Tonsil (squamous cells) Thymus (corpuscle cells) Breast (duct) Lung (Bronchiolar) Clinical tested ADCs known with the same or similar target tissues On-target toxicity observed in clinical studies 7 clinical tested ADCs No on-target toxicity was reported on these sites with the ADCs tested in 2 clinical tested ADCs clinic. 4 clinical tested 5 clinical tested ADCs 4 clinical tested ADCs 2 clinical tested ADCs 7 clinical tested ADCs 5 clinical tested ADCs Skin (sweat gland) 4 clinical tested ADCs 6

7 Safety Evaluation of the Target (2) Target Tissues (apical/lumen surface) Kidney (tubular epi) Cervix (squamous cells) Eye (corneal/conjitival) Urinary transitional epithelia (urothelial) Prostate (glandular epi) Testis (seminiferous tub) Fallopian Tube Uterus (Endometrial gland) Pituitary (epi part) Adrenal (cortical cell) Thyroid (follicular epi) Cerebellum (meangle cells) Clinical tested ADCs known with the same or similar target tissues 4 clinical tested ADCs 3 clinical tested ADCs 1 clinical tested ADCs 4 clinical tested ADCs 3 clinical tested ADCs 4 clinical tested ADCs 3 clinical tested ADCs 5 clinical tested ADCs 3 clinical tested ADCs 2 clinical tested ADCs 3 clinical tested ADCs 1 clinical tested ADCs On-target toxicity in clinical studies No on-target toxicity was reported on these sites with the ADCs listed here. 7

8 Internalization of Targeting Ab 4, 4 hr 37, 4 hr Cancer cell: Panc 02.03; Green: FITC-labeled AbGn Cancer cell: Panc 02.03; Blue: DAPI for nuclear staining; Green: FITC-labeled AbGn Red: LysoTracker 37, 0.5 hr 37, 0.5 hr 8

9 Better Option for Solid Tumors w. Heterogeneous Ag Expression 5-fold more efficient release the payload than vc-pab-mmae more efficient bystander effect than vc- PAB-MMAE 9

10 High Prevalence of Ag Expression in Epithelial Tumors In particular, high expression in adenocarcinoma of GI tract: Gastric cancer : 40-50% Pancreatic cancer: 40-55% Colorectal cancer: 30-60% In vitro diagnostic IHC developed for patients identification 1.25 µg/ml ABG (IRS=12) GEJ tumor high expression (10X) 1.25 µg/ml ABG (IRS=3) GEJ tumor (10X) 1.25 µg/ml ABG (IRS=0) GEJ tumor (10X) 2017/2/15 AbGenomics Confidential 10

11 Superior Efficacy of AbGn-107 Comparative efficacy study vs S.G. linkerpayload Established SU human pancreatic tumor xenograft (medium level expression of antigen) Established SUN-16 - human stomach tumor xenograft SU86.86 Established Xenograft AbGn-107 eradicated large Pancreatic and Colorectal Xenograft Tumors 11

12 Tolerability in Non-Human Primates Only Transient and Reversible Neutropenia. No Sign of Thrombocytopenia No Liver Toxicity 12

13 Dose Reference of ADCs ADC Class ADCs Containing DM-1 ADCs Containing DM4 ADCs Containing MMAE ADCs Containing PBDs Highest Non-Severely Toxic Dose in Monkey (mg/kg) Maximum Tolerated & Efficacious Dose in Cancer Patients (mg/kg) to to to (DAR 2, site-specific) 0.3 AbG s ADCs 6 (DAR 2, site-specific) 2-4 (DAR 2.5) Base on estimation: (0.4 to 1.5) Better therapeutic window Main References: Saber, H and Leighton, J.K. Regulatory Toxicology Pharmacology 71 (3), 444, 2015; Lansita et al, Pharmaceutical Research, July

14 Phase-I Clinical Trial (ongoing) Dose escalation phase advanced colorectal, Pancreatic, and stomach cancer patients. Dose expansion phase (optimal dose) use companion diagnostics to select 8 to 10 antigen positive patients in each group of gastric, pancreatic, and colorectal cancer patients. Up to 54 patients in US. 14

15 Forward-Looking Statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of Statements including words such as "believes," "expects," "anticipates," "intends," "estimates," "plan," "will," "may," "look forward," "intend," "guidance," "future" or similar expressions are forward-looking statements. Because these statements reflect AbG's current views, expectations and beliefs concerning future events, these forward-looking statements involve risks and uncertainties. Although AbG believes that these forward-looking statements and information are based upon reasonable assumptions and expectations, the audience should not place undue reliance on them, or any other forward-looking statements or information in this presentation. Audience should note that many factors could affect AbG's future progress and financial results and could cause AbG's actual results to differ materially from those expressed in forwardlooking statements contained in this presentation. The forward-looking statements in this presentation are qualified by risk factors. These are factors that, individually or in the aggregate, could cause AbG's actual results to differ materially from expected and historical results. AbG assumes no obligation to publicly update any forward-looking statements, whether as a result of new information, future developments or otherwise, except as may be required under applicable securities law. This document is provided for informational purposes only and is neither an offer to purchase nor a solicitation of an offer to sell shares of AbG. 15