BPH ENERGY LTD — Investor Presentation 2015

Nov 25, 2015

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26 November 2015

Companies Announcements Office Australian Securities Exchange Limited 10[th] Floor, 20 Bridge Street SYDNEY NSW 2000

Dear Sir/Madam,

Cortical Dynamics Poster Presentation at American Society of Anesthetists Conference 2015

Please find attached an update from BPH Energy Ltd (ASX: BPH) investee company Cortical Dynamics Ltd. BPH Energy currently holds 3.89% of Cortical Dynamics but has the option to increase its holding to in excess of 10% through the conversion of its secured loan.

Yours Sincerely

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Deborah Ambrosini Company Secretary

BPH Energy Limited ACN 095 912 002 PO Box 317, North Perth, Western Australia 6906 14 View Street, North Perth, Western Australia 6006 admin@biopharmica.com.au www.biopharmica.com.au

T: +61 8 9328 8366 F: +61 8 9328 8733

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26 November 2015

Companies Announcements Office Australian Securities Exchange Limited 10[th] Floor, 20 Bond Street SYDNEY NSW 2000

Dear Sir/Madam,

Cortical Dynamics Poster Presentation at American Society of Anesthetists Annual Meeting

Cortical Dynamics Ltd (“ Cortica l”), is pleased to provide a copy of the poster entitled “Comparisons of EEG measures of Hypnosis and Anti-Nociception in Response to Stimuli During Propofol Remifentanil Anesthesia” that was recently presented at the 2015 Annual Meeting of the American Society of Anesthesiologists in San Diego (please see attached).

The paper was presented by Mr Marko Sahinovic who was one of the co-authors on this paper with Cortical’s principal research scientist Dr Mehrnaz Shoushtarian.

Yours Sincerely

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David Breeze Executive Director

About Cortical

Cortical is an Australian based medical device technology company that has developed a next generation Brain Function Monitor. The company is focused on commercialising the intellectual property developed at Swinburne University. The core-product the Brain Anaesthesia Response (BAR) monitor has been developed with the objective of better detecting the effect of anaesthetic agents on brain activity, aiding anaesthetists in keeping patients optimally anaesthetised.

The BAR monitor improves on currently used electroencephalogram (EEG) technologies by incorporating the latest advances in our understanding of how the brain’s rhythmic electrical activity, the

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

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electroencephalogram (EEG), is produced. The approach used is fundamentally different from all other devices currently available in the market in that its underlying algorithm produces EEG indexes which are directly related to the physiological state of the patient’s brain.

The global brain monitoring market in 2012 was valued at $1.08 billion and is poised to grow at a CAGR of 8.6% to reach $1.63 billion by 2017. The global brain monitoring devices market is broadly segmented into three categories based on its product, application, and end-user. Fueling market growth is the various technological advancements which are leading to high functionality, lower costs, ease of operation, and miniaturization of devices.

Initial marketing in will focus on TIVA (Total Intravenous Anaesthesia), a method of inducing and maintaining general anaesthesia without the use of any inhalation agent. This is becoming more widely accepted, particularly in Western Europe.

Cortical's technology has a versatility that goes beyond depth of anaesthesia and may be applied to other EEG based markets, such as Neuro-diagnostic, drug discovery, drug evaluation and the emerging Brain Computer Interface (BCI) market.

There are considerable opportunities offered by subsequent expansion of the company’s core technology through developing the product to carry out additional functions including neuro-diagnostics of changes in brain and memory functions to provide early warning of degenerative diseases, pain response and tranquiliser monitoring for trauma patients in intensive care units.

The BAR monitor is protected by five patent families in multiple jurisdictions worldwide consisting 16 granted patents.

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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

Comparisons of EEG Measures of Hypnosis and Anti-Nociception in Response to Stimuli During Propofol Remifentanil Anesthesia M.M. Sahinovic, M.D.[1] , M. Shoushtarian, Ph.D.[2] , A.R. Absalom, M.D.[1] , A. Kalmar, M.D.[1] , H. Vereecke, M.D.[1] , D. Liley, M.B.[3] , M.M.R.F. Struys, M.D.[1] 1. University Medical Center Groningen, Groningen, Netherlands, 2. Cortical Dynamics Ltd., Melbourne, Australia, 3. Swinburne University of Technology, Hawthorn, Australia Methods Results Introduction & Aims In a previously published study[2] patients were randomly assigned to Median CI, CCS, CVI and BIS values during the 9 time periods are shown in Hypnosis and analgesia constitute two important components of receive different combinations of hypnosis (propofol administered by fig. 3. Before stimulation, at P1, neither individual nor combinations of anesthesia. Nociception induced responses during anesthesia result closed loop to reach BIS target 50 or 70) and anti-nociception (target measures could differentiate responders from non-responders as both from inadequately inhibited ascending sensory signals. Current effect-site remifentanil concentrations of 0, 2, 4 or 6 ng/ml). Raw EEG groups seem visually intertwined (fig 4a and 4b). After the application of electroencephalogram (EEG) derived measures do not provide accurate was recorded. After a 17.5 min stabilisation period, at t = 0 in Fig. 1, an the OAA/S (P2) distinction between responders and non-responders information on this sub-cortical activity. The neurophysiology-based OAA/S (Observer’s Assessment of Alertness/Sedation; fig 2) was improved but only in the combined measures plane (CCS/CI and BIS/CVI) as EEG measures Cortical Input (CI) and Composite Cortical State (CCS) performed. Thereafter, from t = 60 to 90 sec, a tetanic stimulus (100 Hz, shown in fig 4b and 4c. K-means classification showed that CI and CCS have been shown to be differentially influenced by analgesic and 60 mA) was applied. The CCS, CI, BIS and CVI were calculated from the hypnotic medications respectively,[1] and thus could function as combined have higher sensitivity (75.8% vs 42%, P=0.006) and specificity EEG for the period -20 sec until +230 sec. (52% vs 24%, P = 0.0159) than CVI and BIS combined in differentiating independent analgesia and hypnosis drug effect monitors. For the current study we calculated the median values of these responders from non-responders (Fig. 4). Using these EEG derived measures to optimize anesthetic drug dosing parameters during 9 time periods (P1 to P9 in Fig 1) before and after before and during noxious stimulation could maximize patient safety the application of the OAA/S and tetanic stimulus. and improve operating conditions while minimizing adverse effects. Score Res onsiveness p 5 Res onds readil to name s oken in normal tone p y p In the current study we aimed to evaluate how well: 4 Lethar ic res onse to name s oken in normal tone * * * * • g p p * * * * * * The individual EEG derived measures (BIS, CVI, CI, CCS) and 3 Responds only after name is called loudly and/or repeatedly * • Combinations thereof (BIS/CVI versus CCS/CI) 2 Res onds onl after mild roddin or shakin p y p g g measured before stimulation and after the administration of a test 1 Responds only after painful trapezius squeeze stimulus (OAA/S) could separate patients responsive and non- 0 No response after painful trapezius squeeze * * * * * * responsive to a subsequent tetanic stimulation. * * * * Fig.2 The Observer’s Assessment of Alertness/Sedation scale (OAA/S) Fig.3 Mean (SD) EEG measures (a) CCS, (b) CI, Fig.4 CCS/ CI and BIS/CVI used in combination. Patients were classified as responsive if the OAA/S was >=1 and/or (c) BIS and (d) CVI of the different remifentanil (a) and (b) show measures at P1 (baseline) and P1 P2 P3 P4 P5 P6 P7 P8 P9 there was a purposeful response to the tetanic stimulus, otherwise groups across the time periods. Significant (c) and (d) at P2 (after OAA/S stimulus). *differences shown are between P1 (baseline) they were classified as non-responsive. Prediction probability’s were and other time points (P<0.05, ** P<0.01). calculated for individual measures (data not shown). Scatterplots were constructed to visually judge the ability of individual and combined Conclusion Tetanic measures to distinguish responders from non-responders.(Fig.4) K- OAA/S Stimulus (30 sec) 1. Individual parameters and combinations of parameters, measured before before means classification was used to quantify this. Fig.1 Timeline of study period (seconds). Median value of CCS, CS, a stimulus, are all poor predictors of subsequent response to stimulus. References . after BIS and CVI during each of 9 time periods (P1 to P9) was calculated 2. The combination of CCS and CI, measured after the OAA/S stimulation, better 1. Liley et al. Anesthesiology 113 (2):292-304 t = 0 represents the start of the OAA/S observation

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Median CI, CCS, CVI and BIS values during the 9 time periods are shown in
fig. 3. Before stimulation, at P1, neither individual nor combinations of
measures could differentiate responders from non-responders as both
groups seem visually intertwined (fig 4a and 4b). After the application of
the OAA/S (P2) distinction between responders and non-responders
improved but only in the combined measures plane (CCS/CI and BIS/CVI) as
shown in fig 4b and 4c. K-means classification showed that CI and CCS
combined have higher sensitivity (75.8% vs 42%, P=0.006) and specificity
(52% vs 24%, P = 0.0159) than CVI and BIS combined in differentiating
responders from non-responders (Fig. 4).
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Fig.4 CCS/ CI and BIS/CVI used in combination. (a) and (b) show measures at P1 (baseline) and (c) and (d) at P2 (after OAA/S stimulus).

1. Individual parameters and combinations of parameters, measured before before a stimulus, are all poor predictors of subsequent response to stimulus. 2. The combination of CCS and CI, measured after the OAA/S stimulation, better separates responders from non-responders than BIS and CVI, & individual parameters.

References 1. Liley et al. Anesthesiology 113 (2):292-304 2. Sahinovic et al. Anesth Analg 119 (2):288-301