Our strategy October 2019 The future of cancer treatment. Combining - - PowerPoint PPT Presentation

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Our strategy October 2019 The future of cancer treatment. Combining - - PowerPoint PPT Presentation

Jan 10, 2024 30 likes •171 views

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

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The future of cancer treatment. Combining stem cells and immunotherapy. Strictly confidential and proprietary to Cartherics Pty Ltd.

CARTHERICS

The Future of Cancer Treatment

October 2019

Our strategy

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The future of cancer treatment. Combining stem cells and immunotherapy. Strictly confidential and proprietary to Cartherics Pty Ltd.

Cartherics Pty Ltd

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§ 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.

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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

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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)

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The future of cancer treatment. Combining stem cells and immunotherapy. Strictly confidential and proprietary to Cartherics Pty Ltd.

Initial cancer target: TAG-72

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§ 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

  • Expression levels increase in malignant disease.
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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 TAG-72)

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Tumor wt Normalised to baseline

  • Ovcar 3 Tumors grown to 100m3;
  • TAG72 CAR-T cells injected 3

times, 5 days apart;

  • Control mice given non-transduced

T cells;

  • All controls had to be culled by 40 days;
  • TAG 72 CAR-T cells showed strong

reduction in tumor size to 70 days ctly Confidential

Control T cells Control T cells CTH-001 CTH-001

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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 TAG-72 + gene K/O)

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  • 10
10 20 30 40 50 60 70 80 90 100 110 120 130 140 50 100 150 200 250 300 350 400 450 500 550 600 Days post CAR-T Tumour Mean mm3 NT Seq3 TAG72 DGKaz KO
  • 10
10 20 30 40 50 60 70 80 90 100 110 120 130 140 50 100 150 200 250 300 350 400 450 500 550 600 Days post CAR-T Tumour Mean mm3 NT Seq3 TAG72 + 1 dose of DGKaz KO at day 85 Seq3 TAG72 + 1 dose of Seq3 TAG72 at day 85 DGKaz KO

CTH-004 CTH-001 Control T cells CTH-004 CTH-004 CTH-001 Control T cells

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The future of cancer treatment. Combining stem cells and immunotherapy. Strictly confidential and proprietary to Cartherics Pty Ltd.

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Histology of human tumours and remnants

hCD3+ CAR-T cells TAG-72 – brown stain OVCAR3 - CTH-004 100 days OVCAR3 - Non Transduced 30 days

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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

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§ 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

  • 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.

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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

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CTH-001 killing CTH-001 killing AG-72+ AG-72+ 10 20 30 40 50

Population frequency (% of CD3+)

CTCL HD

*p= 0.0259 n.s

H D (n = 1 5 ) C T C L (n = 4 9 ) 1 0 2 0 3 0 4 0 5 0

F re q u e n c y o f C D 3 + /T A G -7 2 + c e lls (% v ia b le ) M e a n ± S E M

* *

**p < 0 .0 1

T c e lls (n o C A R ) T A G -7 2 C A R (3 ) 5 1 0 1 5 D o n o r 1 C A R : C T C L P B M C s a s ta rg e ts C D 3 + /T A G -7 2 + c e lls (% v ia b le ) T c e lls (n o C A R ) T A G -7 2 C A R (3 ) 2 0 4 0 6 0 D o n o r 1 C A R : J u rk a ts a s ta rg e ts C D 3 + /T A G -7 2 + c e lls (% v ia b le )

CAR-T killing TAG-72+ cells

CD4+ CD8+

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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 HLA haplotype iPSCs Umbilical Cord Blood Donors

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The future of cancer treatment. Combining stem cells and immunotherapy. Strictly confidential and proprietary to Cartherics Pty Ltd.

Cartherics is also preparing for ….

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§ ‘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.

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The future of cancer treatment. Combining stem cells and immunotherapy. Strictly confidential and proprietary to Cartherics Pty Ltd.

iPSC to NK method of manufacture

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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

iPSC HE iNK

progenitor

iNK

mTesR1

Media B

Media A

Day0 Day8 Day22 Day30 Day-1 Day3 Media C Media D

iPSC HE development iNK Progenitor iNK Maturation

Phase 1 Phase 2 Phase 3 Phase 4
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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

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10 20 30 40

  • 2

2 4 6 8 10

Time from addition of effector cells (h) Normalised cell index (Average ± SD) Target cells alone CTH-403 (unsorted) Non-transfected iNK GFP iNK (unsorted)

Take home message:

How to read the graphs? Cancer growth/survival Cancer killing cell index Time

  • 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

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)

Legend (TAG-72 CAR iNK)

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The future of cancer treatment. Combining stem cells and immunotherapy. Strictly confidential and proprietary to Cartherics Pty Ltd.

Company relationships

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§ 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.