The DN30 antibody

"Novel Therapeutic Agent for the treatment of a tumor and/or metastasis"

hOA-DN30

  • Patent of hOA-DN30 submitted by the end of September 2018
  • Proven effective innovation of the humanized antibody compared to DN30:
  • Higher anticancer efficacy on xenopatients
  • Better PK profile
  • Better PD profile

A UNIQUE MECHANISM OF ACTION

hOA-DN30

hOA-DN30 removes the MET protein from the cancer cell surface

hOA-DN30 generates a ‘decoy’ MET

DN30-1
DN30-2

Potent induction of MET shedding increases cleaved MET in the extracellular environment and decreases intact MET on cancer cell surface (instead of simply blocking ligand binding)

The cleaved MET (‘decoy’) in the extracellular environment:

  1. sponges and neutralizes excess HGF
  2. binds to intact MET receptors still present on the cell surface, rendering them inactive.

hOA-DN30 inhibits growth of MET-addicted gastric carcinoma cells (GTL16)

OVERCOMING RESISTANCE:
THE ‘FLARE’ EFFECT

DN30-3
DN30-4

When MET is physically removed from the cancer cell surface via hOA-DN30-induced ’shedding’, the internal signaling cascade is disrupted and cell-growth is inhibited.

“Withdrawal of chemical inhibitors prompts MET phosphorylation to levels higher than those displayed at steady-state. This then generates a 'rebound' effect pushing quiescent cancer cells back into the cycle.“

Pupo E, et al. Cancer Res 2016;76:5019–29

DN30 IMPROVEMENT: HUMANIZED ANTIBODY

hOA-DN30

hOA-DN30 Antitumor efficacy

Response to ‘single-arm’ humanized DN30 by a human gastric carcinoma

hOA-DN30 PK profile

PHARMACOKINETIC PROFILE

DN30-5

GTL-16 (MET-addicted) transplanted in NOD SCID mice treated with the indicated dose 3x/week, i.v., for 15 days

Analysis of DN30 antibody plasma concentrations upon intravenous delivery in mice shows a favorable pharmacokinetic profile.

hOA-DN30

1

Highly target specific

2

High in vivo efficacy, wide therapeutic window and good tolerability in vivo (in-house studies)

3

Good stability and half-life

4

Availability of a Non-invasive Diagnostic tool
To be used as a biomarker to identify potential responsive patients - e.g. those displaying MET amplification

ORPHAN DRUG DESIGNATION for RARE and/or BIOMARKER IDENTIFIED TUMORS*

hOA-DN30

Frequency of MET point mutations across cancer subtypes

frequency-600

* Biomarker Identified Tumors: MET positive cancers – incidence: TBD (*)Tsigkos et al. Orphanet Journal of Rare Diseases 2014, 9:13

The incidence of patients with mutated or amplified MET is within the definition of rare disease

Cancer Subtypes and Mutations

23. Uterine Endometrioid Carcinoma
22. Uterine Serous Carcinoma/Uterine Papillary Serous Carcinoma/
21. Uveal Melanoma
20. Oropharynx Squamous Cell Carcinoma
19. Oral Cavity Squamous Cell Carcinoma
18. Adenoid Cystic Carcinoma
17. Angiosarcoma
16. Lung Squamous Cell Carcinoma
15. Bladder Urothelial Carcinoma
14. Upper Tract Urothelial Carcinoma
13. Lung Adenocarcinoma
12. Head and Neck Squamous Cell Carcinoma
11. Anaplastic Astrocytoma
10. Mucinous Adenocarcinoma of the Colon and Rectum
09. Large Cell Neuroendocrine Carcinoma
08. Cutaneous Squamous Cell Carcinoma
07. Cancer of Unknown Primary
06. Small Bowel Cancer
05. Small Cell Lung Cancer
04. Cutaneous Melanoma
03. Melanoma of Unknown Primary
02. Anaplastic Oligodendroglioma
01. Papillary Renal Cell Carcinoma