BPH ENERGY LTD — Investor Presentation 2013

Oct 10, 2013

==> picture [271 x 99] intentionally omitted <==

11 October 2013

Companies Announcement Office ASX Limited Exchange Centre Level 4, 20 Bridge Street Sydney, NSW 2000

Cortical Dynamics Ltd – Cortical Dynamics Presents Results of Clinical Trial at Anesthesiology 2013 in San Francisco

Please find attached an operational update from BPH Energy Ltd ( ASX: BPH ) investee company Cortical Dynamics Ltd.

Yours sincerely,

==> picture [115 x 34] intentionally omitted <==

Deborah Ambrosini Director and Company Secretary

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

==> picture [214 x 86] intentionally omitted <==

11 October 2013

BPH Energy Limited 14 View Street North Perth, WA 6006

Cortical Dynamics Presents Results of Clinical Trial at Anesthesiology 2013 – San Francisco

Cortical Dynamics Ltd (“ Cortical ”) will be presenting the Brain Anesthesia Response (“ BAR ”) monitor’s previously announced clinical trial results at the American Society of Anesthesiologists annual meeting in San Francisco (ANESTHESIOLOGY 2013) incorporating recent further analyses of the clinical data.

The trial conducted at St Vincent’s Hospital in Melbourne was a 25 person product validation designed to evaluate the BAR monitor’s ability to distinguish between two different doses of the widely used intravenous analgesic fentanyl, in addition to assessing the immunity of the BAR monitor to a range of intra-operative mechanical and electrical artifacts known to complicate the EEG measurement of anaesthetic action.

The presentation entitled, ‘The Brain Anaesthesia Response Monitor During Cardiac Surgery: A Double-Blind RCT With Fentanyl’ will be presented by Cortical’s principle scientist, Dr Mehrnaz Shoushtarian. The presentation is scheduled to occur on Sunday 13[th] October 2013 from 8:00 am to 9:30 am Pacific Standard time.

About the BAR Monitor

The BAR monitoring system measures a patient’s brain electrical activity, the electroencephalogram (EEG), in order to indicate how deeply anaesthetised a patient is during an operation via an adhesive sensor applied to the forehead. The BAR monitor is designed to assist anaesthetists and intensive care staff in ensuring patients do not wake unexpectedly, as well as reducing the incidence of side effects associated with the anaesthetic.

The BAR monitor improves on currently used EEG monitors by utilising advances in understanding of how the brain’s electrical activity is produced, and how it is affected by anaesthetic and sedative drugs. The BAR’s unique physiological approach is aimed at independently monitoring the hypnotic and analgesic states associated with anaesthesia, a feature no known existing EEG based depth-of-anaesthesia monitor is able to achieve. Objectively monitoring of hypnotic and analgesic state may lead to improved anaesthetic and surgical outcomes, by reducing recovery times and minimising drug costs.

Cortical Dynamics Ltd

ACN 107 557 620 PO box 317, North Perth, WA, 6906 14 View Street, North Perth, Western Australia T: + 61 8 6467 9525 F: +61 8 9328 8733 contact@corticaldynamics.com www.corticaldynamics.com

==> picture [214 x 86] intentionally omitted <==

In 2012 Cortical completed its first human clinical trial using the BAR monitoring system which was conducted at St Vincent’s Hospital, Melbourne.

Cortical has developed an extensive patent portfolio encapsulating the BAR monitoring system and its physiologically based algorithms, with a total of thirteen patents granted throughout Australia, New Zealand, the United States, Japan and the People’s Republic of China.

About Cortical Dynamics

Cortical Dynamics Ltd is a medical technology company that was established in 2004 to commercialise intellectual property relating to brain function monitoring developed by Professor David Liley and his scientific team at Melbourne’s Swinburne University of Technology.

Cortical Dynamics Ltd

ACN 107 557 620 PO box 317, North Perth, WA, 6906 14 View Street, North Perth, Western Australia T: + 61 8 6467 9525 F: +61 8 9328 8733

contact@corticaldynamics.com www.corticaldynamics.com

The Brain Anaesthesia Response Monitor During Cardiac Surgery: a Double-Blind RCT with Fentanyl

Mehrnaz Shoushtarian, Desmond P McGlade, Louis Delacretaz, David TJ Liley

Cortical Dynamics Ltd, Perth, Australia St. Vincent’s Hospital, Melbourne, Australia

==> picture [143 x 61] intentionally omitted <==

==> picture [172 x 114] intentionally omitted <==

==> picture [86 x 66] intentionally omitted <==

Disclosure

• This study was supported by funding from Cortical Dynamics Ltd.

• Mehrnaz Shoushtarian, Louis Delacretaz and David Liley are employed by Cortical Dynamics Ltd., Australia.

==> picture [97 x 42] intentionally omitted <==

==> picture [57 x 44] intentionally omitted <==

Introduction

==> picture [300 x 186] intentionally omitted <==

• All current EEG based depth of anaesthesia monitors use QEEG, MLAEP, or a combination, to select features which best correlate with clinical endpoints

• All current measures are heuristically derived

Kuizenga et al. (1998), Br. J. Anaesth.

==> picture [97 x 42] intentionally omitted <==

==> picture [57 x 44] intentionally omitted <==

BAR Monitor Liley Model

==> picture [294 x 22] intentionally omitted <==

Passive electrical properties and reversal potentials

==> picture [318 x 27] intentionally omitted <==

Transmitter kinetics, intra-cortical connectivity and cable delays

==> picture [309 x 43] intentionally omitted <==

Conduction delays and cortico-cortical connectivity

==> picture [96 x 41] intentionally omitted <==

==> picture [58 x 44] intentionally omitted <==

BAR Monitor Liley Model

==> picture [350 x 267] intentionally omitted <==

==> picture [96 x 41] intentionally omitted <==

==> picture [58 x 44] intentionally omitted <==

BAR Monitor Liley Model

==> picture [185 x 280] intentionally omitted <==

==> picture [96 x 41] intentionally omitted <==

==> picture [85 x 51] intentionally omitted <==

• Cortical State (CS): Resonant state of cortex

• Cortical Input (CI): Input to cortex

==> picture [58 x 44] intentionally omitted <==

Hypotheses

• CI would differentiate between two patient groups receiving different doses of fentanyl

• In the presence of propofol, CS would correlate well with the Bispectral Index (BIS™)

==> picture [96 x 41] intentionally omitted <==

==> picture [58 x 44] intentionally omitted <==

Methods

==> picture [699 x 293] intentionally omitted <==

----- Start of picture text ----- Recruitment and Randomisation 25 patients primary CABG low risk factorsFentanyl Low Dose 12 g/kg total (8 g/kg + 4 g/kg)Fentanyl Moderate Dose 24 g/kg total (16 g/kg + 8 g/kg)Premedication Lorazepam 2 mg, Oxycontin 10 mgPreoperative Preparation BAR and BIS Sensors appliedIV, Arterial and Pulmonary Artery Catheters insertedMidazolam 0.5 mg to maintain OAA/S 4 (mild sedation only)Induction and Maintenance Propofol 1 mg/kg over 60 seconds then 6 mg/kg/h, titrated to BIS 40‐60Following Induction Fentanyl Dose 1, Pancuronium 0.12 mg/kg; intubate after 3 minutesPrior to Skin Incision Fentanyl Dose 2Haemodynamic Management Vasoactive agents used to maintain SBP 100‐140 mmHg and HR 45‐90----- End of picture text -----

Methods

Patient Fentanyl (1st dose) Fentanyl Skin preparation Pancuromium (2[nd] dose) incision Time (s) t tFENT2‐180(s) FENT2 Induction Maintenance Propofol Propofol

==> picture [96 x 42] intentionally omitted <==

==> picture [57 x 44] intentionally omitted <==

Methods Fentanyl (1st dose) Pancuromium Induction Propofol • Correlations between BIS and CS following induction

==> picture [96 x 42] intentionally omitted <==

Time (s)

==> picture [57 x 44] intentionally omitted <==

Methods

Fentanyl Skin (2[nd] dose) incision

==> picture [256 x 44] intentionally omitted <==

t FENT2

tFENT2‐180(s)

Time (s)

• Relative difference in BIS, CI and CS at time of skin incision and 3 minutes before calculated

==> picture [96 x 42] intentionally omitted <==

==> picture [57 x 44] intentionally omitted <==

Results

• Following induction, a significant correlation between CS and BIS was found.

• Prediction probability:

  • �� = 0.721, SE = 0.014

==> picture [97 x 42] intentionally omitted <==

==> picture [321 x 247] intentionally omitted <==

----- Start of picture text ----- 100��0.618,90 ��0.00180706050403030 40 50 60 70 80 90 100BISCS (arb. units)----- End of picture text -----

==> picture [58 x 44] intentionally omitted <==

Results

==> picture [678 x 314] intentionally omitted <==

----- Start of picture text ----- BIS100100 t=160s��0.851, ��0.001 80806060404055 60 65 70 75 80 85 20 40 60 80 100 120 140 160 180 200BISCS100 10090 9080807070��0.325, ��0. 219 60 t=106s60 5090 92 94 96 98 100BIS 400 20 40 60 80 100 120 140 160 180 200Time (s)CS (arb. units)Induction LOR FENT1CS (arb. units)ORL----- End of picture text -----

Results

==> picture [97 x 42] intentionally omitted <==

==> picture [301 x 284] intentionally omitted <==

----- Start of picture text ----- CI4.2Skin4 incisio n3.8FENT23.6CCS5045403530BIS5040301800 1900 2000 2100 2200 2300Time (s)VArb. units----- End of picture text -----

==> picture [58 x 44] intentionally omitted <==

Results

• The relative change in CI was greater in the FLD group compared with the FMD group

  • ( F (1, 18) = 10.7, P = .004).

• BIS and CS showed no significant difference between the groups.

==> picture [97 x 42] intentionally omitted <==

==> picture [227 x 231] intentionally omitted <==

----- Start of picture text ----- 0.1FMDFLD0.050-0.05-0.1CI CS BISChange in index following fentanyl (2nd dose)----- End of picture text -----

==> picture [58 x 44] intentionally omitted <==

Conclusion

• The fall in CS following anaesthesia induction with propofol showed significant correlation with BIS and is indicative of its utility as a monitor of hypnosis.

• • The ability of the CI index to differentiate the two study groups according to fentanyl dose indicates that the BAR Monitor be useful in the titration of may intraoperative

• opioid analgesic agents.

==> picture [97 x 42] intentionally omitted <==

==> picture [57 x 44] intentionally omitted <==