CARTHERICS The Future of Cancer Treatment Our strategy October 2019 The future of cancer treatment. Combining stem cells and immunotherapy. Strictly confidential and proprietary to Cartherics Pty Ltd.
Cartherics Pty Ltd 2 § Founded 2015 § Laboratories and offices at Monash Health Translation Precinct, Melbourne, Australia § Series A financing AU$5M completed late 2015 § Series B Financing AU$5M (plus an optional AU$1.3M) § Federal and State Grants AU$3.5M § Company operations commenced January 2016. The future of cancer treatment. Combining stem cells and immunotherapy. Strictly confidential and proprietary to Cartherics Pty Ltd.
Preparing for two Phase I/II Autologous Clinical Trials 3 1. Cutaneous T Cell Lymphoma § Product CTH-001 (anti-TAG-72 CAR-T cells) 2. Relapsed Ovarian Cancer § Product CTH-004 (anti-TAG-72; + gene k/o CAR-T cells) The future of cancer treatment. Combining stem cells and immunotherapy. Strictly confidential and proprietary to Cartherics Pty Ltd.
Initial cancer target: TAG-72 4 § Glycoprotein found on the surface of many types of cancer cells, including breast, colon, gastric, lung, pancreatic and ovarian cancers (+ T Cell Lymphoma) § Human tissue distribution studies have shown >95% of serous and >85% of clear cell ovarian cancers are TAG-72 positive o Expression levels increase in malignant disease. The future of cancer treatment. Combining stem cells and immunotherapy. Strictly confidential and proprietary to Cartherics Pty Ltd.
Killing human ovarian cancer xenografts in NSG mice : CTH-001 (anti 5 TAG-72) Tumor wt Control T cells CTH-001 • Ovcar 3 Tumors grown to 100m 3 ; • TAG72 CAR-T cells injected 3 times, 5 days apart; • Control mice given non-transduced T cells; Normalised to • All controls had to be culled by 40 days; baseline • TAG 72 CAR-T cells showed strong Control T cells CTH-001 reduction in tumor size to 70 days ctly Confidential The future of cancer treatment. Combining stem cells and immunotherapy. Strictly confidential and proprietary to Cartherics Pty Ltd.
Killing human ovarian cancer xenografts in NSG mice : CTH-004 (anti 6 TAG-72 + gene K/O) Control T cells Control T cells 600 600 550 NT 550 Seq3 TAG72 + 1 dose of DGKaz KO at day 85 Seq3 TAG72 + 1 dose of Seq3 TAG72 at day 85 500 500 DGKaz KO NT 450 Seq3 TAG72 450 DGKaz KO CTH-001 400 400 350 Tumour Mean mm 3 350 Tumour Mean mm 3 CTH-001 300 300 250 250 200 200 150 150 100 100 CTH-004 50 CTH-004 50 CTH-004 0 0 -10 0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 -10 0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 Days post CAR-T Days post CAR-T The future of cancer treatment. Combining stem cells and immunotherapy. Strictly confidential and proprietary to Cartherics Pty Ltd.
Histology of human tumours and remnants 7 OVCAR3 - CTH-004 100 days hCD3+ CAR-T cells TAG-72 – brown stain OVCAR3 - Non Transduced 30 days The future of cancer treatment. Combining stem cells and immunotherapy. Strictly confidential and proprietary to Cartherics Pty Ltd.
T cell lymphomas express elevated TAG-72 8 § There is a strong precedent for treatment of lymphomas with CAR-T cells § A significant proportion (>40%) of patients with T cell lymphoma (TCL) show elevated levels of circulating TAG-72+ T cells o Cartherics’ CTH-001 cells kill these T cells - see next slide § There are very few therapeutic options available for these patients § Cartherics to study Cartherics CTH-001 as an autologous therapy for TCL. The future of cancer treatment. Combining stem cells and immunotherapy. Strictly confidential and proprietary to Cartherics Pty Ltd.
Tag-72+ Cutaneous T Cell Lymphoma (CTCL) patients: CTH-001 9 D o n o r 1 C A R : C T C L P B M C s a s ta rg e ts F re q u e n c y o f C D 3 + /T A G -7 2 + c e lls * * 1 5 5 0 C D 3 + /T A G -7 2 + c e lls 1 0 (% v ia b le ) CTH-001 killing 4 0 5 M e a n ± S E M (% v ia b le ) 3 0 0 T c e lls (n o C A R ) T A G -7 2 C A R (3 ) 2 0 1 0 **p < 0 .0 1 D o n o r 1 C A R : J u rk a ts a s ta rg e ts 0 6 0 H D C T C L C D 3 + /T A G -7 2 + c e lls (n = 1 5 ) (n = 4 9 ) 4 0 (% v ia b le ) 50 *p= 0.0259 CTCL 2 0 CTH-001 killing HD 40 Population frequency (% of CD3+) 0 30 T A G -7 2 C A R (3 ) T c e lls (n o C A R ) n.s 20 CAR-T killing TAG-72+ cells 10 0 AG-72+ AG-72+ CD4+ CD8+ The future of cancer treatment. Combining stem cells and immunotherapy. Strictly confidential and proprietary to Cartherics Pty Ltd.
Off-the-shelf – Allogeneic cancer therapy 10 Umbilical Cord Blood Donors HLA haplotype iPSCs The future of cancer treatment. Combining stem cells and immunotherapy. Strictly confidential and proprietary to Cartherics Pty Ltd.
Cartherics is also preparing for …. 11 § ‘first in human’ Phase I/II Allogeneic CAR-NK cell clinical trial, Product CTH-401; relapsed ovarian cancer, and § product developed through Federal Government CRC-P Grant of AU$3 Million to Cartherics, Mesoblast, Cell Therapies, Monash University and Hudson Institute of Medical Research. The future of cancer treatment. Combining stem cells and immunotherapy. Strictly confidential and proprietary to Cartherics Pty Ltd.
iPSC to NK method of manufacture 12 iPSC iNK iNK HE progenitor Phase 1 Phase 3 Phase 4 Phase 2 iPSC iNK Progenitor HE development iNK Maturation mTesR1 Media A Media B Media C Media D Day-1 Day0 Day3 Day8 Day22 Day30 Overview § Total time: 30 days § Method designed on patterning cell development that mimics natural NK development in the body § Focus on xeno-free, scalable, molecularly-defined and clinically translatable systems § ~150,000 iNK cells per iPSC The future of cancer treatment. Combining stem cells and immunotherapy. Strictly confidential and proprietary to Cartherics Pty Ltd.
iNK Cytotoxic function on ovarian cancer cells in vitro 13 Legend Ovarian cancer Ovarian cancer Cancer alone Cancer alone in basal media Cancer alone in NK media NK from healthy donor Cord-derived NK iPSC-derived NK (method#1) iPSC-derived NK (method#2) 10 Target cells alone Normalised cell index 8 Non-transfected iNK How to read the graphs? (Average ± SD) 6 Cancer growth/survival GFP iNK (unsorted) cell index CTH-403 (unsorted) (TAG-72 CAR iNK) 4 Cancer killing 2 Time 0 10 20 30 40 -2 Time from addition of effector cells (h) Take home message: 1. iPSC derived NK cells kill ovarian cancer in vitro 2. iPSC-NK cells function similar to normal NKS 3. TAG-72 CAR iNK increases killing of ovarian cancer The future of cancer treatment. Combining stem cells and immunotherapy. Strictly confidential and proprietary to Cartherics Pty Ltd.
Company relationships 14 § Mesoblast - CRC partner § Cell Therapies (Peter Mac) - CRC partner, Manufacturing partner § ToolGen - Partnership for gene editing § PanCella - Partnership for Immuno-cloaking and Fail-safe technology § Berry Genomics – Genomics partnership. The future of cancer treatment. Combining stem cells and immunotherapy. Strictly confidential and proprietary to Cartherics Pty Ltd.
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