BPH ENERGY LTD — Investor Presentation 2012

Oct 23, 2012

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24 October 2012

ASX Market Announcements Australian Securities Exchange Limited 10[th] Floor, 20 Bond Street SYNDEY NSW 2000

Dr Robin Scaife to Present at National Melanoma Conference

BPH Energy Limited (ASX: BPH ) investee company Molecular Discovery Systems Limited (“ MDS” ) is pleased to provide a copy of Dr Robin Scaife’s presentation that he will present today at the inaugural National Melanoma Conference hosted by the Scott Kirkbride Melanoma Research Centre (SKMRC). SKMRC supports research that is aimed at providing breakthroughs for improved diagnosis and treatment of melanomas.

Dr Scaife was awarded an SKMRC Discovery Research Grant in 2011 to use the highcontent imaging analysis platform at MDS to screen new drug-like molecules for inhibitors of melanoma cell survival and proliferation.

MDS is continuing to invest in the discovery of new oncology drug candidates via its inhouse screening program.

Yours sincerely,

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David Breeze Chairman

For Further Information

David Breeze david@bphenergy.com.au Chairman tel: +61 (0) 8 9328 8366

BPH Energy Limited ACN 95 912 002 PO Box 317, North Perth, Western Australia 6906 14 View Street, North Perth, Western Australia 6006 admin@bphenergy.com.au www.bphenergy.com.au T: +61 8 9328 8366 F: +61 8 9328 8733

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Background:

MDS :

MDS has core expertise in high-content and high-throughput imaging and analysis. Central to the MDS drug screening platform is a semi-automated cellular imaging and analysis facility that provides access to complex drug targets. BPH Energy has a 20% residual interest in MDS after the spin-off of MDS in 2010. BPH Energy is working towards a listing of MDS on the Australian Securities Exchange.

BPH Energy Limited ACN 95 912 002 PO Box 317, North Perth, Western Australia 6906 14 View Street, North Perth, Western Australia 6006 admin@bphenergy.com.au www.bphenergy.com.au T: +61 8 9328 8366 F: +61 8 9328 8733

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Robin M. Scaife

Molecular Discovery Systems (BPH Energy) WAIMR "Screening for new oncology drug candidates by imaging of molecular and cellular targets"

Oncogene and non-oncogene screening

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+
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Inhibition of growth signal

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23h 23.5h
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Induction of cell death

Molecular Targets and Drugs

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(Volasertib)
Hanahan and Weinberg, Cell 2011
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Schlabach et al., Science (2008)
Jones et al., Science (2008)
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Melanoma Oncogenic Signaling

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Rapamycin
17/20 mTOR inhibitors =
Pyrimidine or Quinolines
Accessible Chemistry Space
LY294002
Drugs
Structural
+ -
Diversity
Enamine Drug
collectioSpace
n
Pharmacological
Diversity
Karbowniczek et al., JID (2008) Anti-phospho S6
Romeo et al., Oncogene 2012
Anti-phospho S6
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S6 Phosphorylation Screen

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Control Rapamycin Hit
P-S6
p53
Z=0.68
Rapamycin
7
6
5
4 Re-test
Hit
3
2
1
0
1 1… 1… 1… 1… 1… 1… 1… 1… 1… 1… 2… 2… 2… 2… 2… 2… 2… 2… 2… 3… 3… 3… 3… 3… 3… 3…
12 23 34 45 56 67 78 89
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Hits + _
P-S6
P-GSK-3
-Tb
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Induction of Cell Death

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Annexin-V/GFP-H2B
475nm segmentation
MCF7
535nm segmentation
MCF12
MCF7
/
MCF12
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Selective Induction of Cell Death

~2/10,000 compounds

~50/10,000 compounds

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Selective inhibition Non-selective inhibition
MCF12 MCF7 MCF12 MCF7
2500 2000
2000
1500
t0 t0
1500
t48 1000 t48
1000
6d 5d
500
500
0 0
F3 C12 Ave F3 C12 Ave H11 Tx Ave H11 Tx Ave
Cell #
Cell #
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Inhibition of Cytokinesis

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39
t0
t60 min H2B-GFP
39
* * * * * *
• • • • • • • • • •
t0
* *
* * [ ] * [ ] *
• • • • • •
t60 min
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Actin and Endocytosis

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Eggart et al. , PLoS, (2004) Aurora B
Binucleines Tritc-phalloidin//Hoescht
DMSO 39
Swinholide,
Jasplakinolide
F-Actin
Rhodblocks
Castoreno et al., NCB (2010)
Dynamin
(Joshi et al .,Mol Cancer 2011)
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Tritc-phalloidin//Hoescht
DMSO 39
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Inhibition of Mitosis

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Smith and Chircop (2012)
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Clathrin
Royle et al., Foraker and Brodsky
Nature 2005 JCB 2012
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CKAP5/ch-TOG

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Supplementary Table 12 | Agents that disrupt mitosis: limited activity to date

Aurora Polo KSP1	Compound	Company	Comment

Komlodi-Pastzor et al., NRCO (2011)

Taxol Resistance

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Perez, The Oncologist (1998)
30-60%
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Dumontet and Jordan NRDD (2010)

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Shi et al., 2008
Arrest
Death
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Death
Exit
Time
HeLa
Death signal Arrest signal
PC3
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Taxol Synthetic Lethality

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Mitotic Death
23h 23.5h
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Moore et al., Cell (2010)
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Whitehurst et al., Nature (2007)
siRNA screen
V-ATPase
inhibition
Taxol+
RTA203
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200
No Tx
150
100
50
0
1 2 3 4 DMSO 5
200
GI50 [Tx]
150
100
50
0
1 2 3 4 5
DMSO
Cell #
Cell #
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Selective Targeting of Microtubules

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-Tb/P-AU
DMSO 113
Aneja et al. Cancer Res
(2006)
-Tubulin/Hoescht
DMSO Tx
Noc Noc DMSO
113 Nsc
Noc 49 Noc 113
Hoescht
/
-Tubulin
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New Cellular Targets

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-Tb/P-AU -Tb
83 KSPi
1.5
74
1
Tx Death
Tx+74
0.5
0 Exit
-Tb/CREST/Hoescht
Time
Tx+74 Tx
Death signal Arrest signal
Cell # Mitosis
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Induction of Death Signal

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263
KSPi
Tx
KSPi+263
Tx+263
Shi et al., (2011)
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Domingo-Domenech et al., Cancer Cell (2012)
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Rachel Ramsdale (PMCC)

Bruno Meloni (CNND)

Brian Gabrielli (UQ)

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MCF12
Neurons
GFP-H2B
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SKMRC (WAIMR) Chemical Library