Alzheimers Treatment Needs a New Approach Xanamem Bill Ketelbey - PowerPoint PPT Presentation

Alzheimer’s Treatment Needs a New Approach – Xanamem™ Bill Ketelbey – September 2018 Singapore

Disclaimer This presentation has been prepared by Actinogen Medical Limited. (“Actinogen” or the “Company”) based on information available to it as at the date of this presentation. The information in this presentation is provided in summary form and does not contain all information necessary to make an investment decision. This presentation does not constitute an offer, invitation, solicitation or recommendation with respect to the purchase or sale of any security in Actinogen, nor does it constitute financial product advice or take into account any individual’s investment objectives, taxation situation, financial situation or needs. An investor must not act on the basis of any matter contained in this presentation but must make its own assessment of Actinogen and conduct its own investigations. Before making an investment decision, investors should consider the appropriateness of the information having regard to their own objectives, financial situation and needs, and seek legal, taxation and financial advice appropriate to their jurisdiction and circumstances. Actinogen is not licensed to provide financial product advice in respect of its securities or any other financial products. Cooling off rights do not apply to the acquisition of Actinogen securities. Although reasonable care has been taken to ensure that the facts stated in this presentation are accurate and that the opinions expressed are fair and reasonable, no representation or warranty, express or implied, is made as to the fairness, accuracy, completeness or correctness of the information, opinions and conclusions contained in this presentation. To the maximum extent permitted by law, none of Actinogen its officers, directors, employees and agents, nor any other person, accepts any responsibility and liability for the content of this presentation including, without limitation, any liability arising from fault or negligence, for any loss arising from the use of or reliance on any of the information contained in this presentation or otherwise arising in connection with it. The information presented in this presentation is subject to change without notice and Actinogen does not have any responsibility or obligation to inform you of any matter arising or coming to their notice, after the date of this presentation, which may affect any matter referred to in this presentation. The distribution of this presentation may be restricted by law and you should observe any such restrictions. This presentation contains certain forward looking statements that are based on the Company’s management’s beliefs, assumptions and expectations and on information currently available to management. Such forward looking statements involve known and unknown risks, uncertainties, and other factors which may cause the actual results or performance of Actinogen to be materially different from the results or performance expressed or implied by such forward looking statements. Such forward looking statements are based on numerous assumptions regarding the Company’s present and future business strategies and the political and economic environment in which Actinogen will operate in the future, which are subject to change without notice. Past performance is not necessarily a guide to future performance and no representation or warranty is made as to the likelihood of achievement or reasonableness of any forward looking statements or other forecast. To the full extent permitted by law, Actinogen and its directors, officers, employees, advisers, agents and intermediaries disclaim any obligation or undertaking to release any updates or revisions to information to reflect any change in any of the information contained in this presentation (including, but not limited to, any assumptions or expectations set out in the presentation). 2 Xanamem™ - novel approach to Alzheimer’s dementia

Actinogen Medical (ASX:ACW) In May 2018, Actinogen raised • Xanamem, Actinogen’s lead compound, in S T O C K M E T R I C S * $16.5m via an institutional development for the treatment of Alzheimer's A S X C O D E A C W placement and SPP that saw disease (AD) and cortisol-associated cognitive Market Capitalisation $63.1m leading US biotech investor, BVF impairment Enterprise Value $53.1m Partners LP take a 19.9% holding 52-week High/Low $0.039-$0.066 and leading Australia-based • Xanamem, a novel differentiated mechanism Top 20 Shareholdings 61% institutional investors Australian of action: prevents the production of excess Ethical and Platinum Asset brain cortisol Management join the register. T O P 1 0 H O L D E R S Rank Name % • Persistently raised cortisol in the brain is 1 HSBC Custody Nominees 24.34% associated with the development and 2 National Nominees Ltd 4.49% progression of AD 3 Edinburgh Technology Fund Limited 4.43% 4 JK Nominees Pty Ltd 3.68% • First-in-class, brain penetrant, orally active, 5 Citicorp Nominees 2.12% inhibitor of 11βHSD1 enzyme, reducing 6 CS Fourth Nominees 2.04% conversion of cortisone to cortisol 7 Warambi Sari 2.01% 8 BNP Paribas Nominees Pty Ltd 1.93% • Experienced board and management; expert 9 Mr Martin Rogers 1.84% clinical and scientific advisory boards 10 Sunset Capital Management Pty Ltd 1.84% 3 Xanamem™ - novel approach to Alzheimer’s dementia

Commercially experienced, globally recognised Board of Directors Xanamem Clinical Advisory Board Dr. Geoff Brooke Dr. Bill Ketelbey Dr. Jason Loveridge Dr. George Morstyn Prof. Craig Ritchie Prof. Colin Masters Prof. Jeffrey Cummings Chairman CEO & MD Non-Executive Director Non-Executive Director Chair 4 Xanamem™ - novel approach to Alzheimer’s dementia

A foundation of cutting edge research and translation Scientific Advisory Board Prof Brian Walker Prof Scott Webster Prof Jonathan Seckl Pro-Vice-Chancellor Professor of Medicines Discovery Vice Principal Research Strategy and University of Edinburgh University of Edinburgh Resources University of Newcastle Combining deep understanding of endocrinology, 11 β HSD1 and drug discovery • • Conducted seminal research linking cortisol with cognitive decline • Actively engaged in the progress and development of Xanamem Xanamem™ - novel approach to Alzheimer’s dementia 5

Human pilot studies (2004) - Cortisol inhibition improves cognition Inhibiting cortisol production in the brain with carbenoxolone improves cognitive function in healthy elderly men & type 2 diabetics VERBAL FLUENCY – Study 1* VERBAL MEMORY – Study 2** P=0.006 P=0.005 Mean SD Mean SD 40.6 12.4 55.2 8 Placebo Placebo Treatment 44.2 10.6 Treatment 58.8 5.2 0 10 20 30 40 50 60 70 0 10 20 30 40 50 60 70 * Study 1 = 10 healthy subjects Age 55-75 (Mean Age = 65.5 ± 5.5) receiving 100mg carbenoxolone **Study 2 = 12 type 2 diabetics (m=9; f=3) Age 52-70 (Mean Age = 60 ± 4.9) receiving 100mg 3 times daily compared to placebo for 4 weeks, in a double-blind randomised crossover study. carbenoxolone 3 times daily compared to placebo for 6 weeks, in a double-blind randomised crossover study. Significant improvement in verbal fluency and verbal memory after only 4 and 6 weeks treatment 11β -Hydroxysteroid dehydrogenase inhibition improves cognition function in healthy elderly men and type 2 diabetics Sandeep et al., 2004 PNAS (vol. 101, no. 17) 6734-6739 6 Xanamem™ - novel approach to Alzheimer’s dementia

Robust animal data with new candidate Symptomatic and disease modifying effects in mouse models – AUD $25 million invested pre-licensing by ACW COGNITION: treatment 28 days AMYLOID CLEARANCE: treatment 28 days P=0.004 P=0.01 43 ± 21 38 Control Control ± 3 Treatment Treatment 172 ± 28 22 Treatment ± 5 Treatment p=0.01 p=0.004 0 50 100 150 200 250 0 10 20 30 40 50 Latency to enter dark compartment (seconds) Number of Plaques / brain area (total) Mean ± SEM Mean ± SEM Significant improvement in cognition after only 28 days treatment, continuing out to 41 weeks UE2316 in Tg2576 rodent model of Alzheimer’s disease . Sooy, et al., 2015. Endocrinology 156 (12) 4592-4603 7 Xanamem™ - novel approach to Alzheimer’s dementia

Xanamem 8 Xanamem™ - novel approach to Alzheimer’s dementia

Mechanism of action Inhibition of 11 β HSD1, reducing brain cortisol production 9 Xanamem™ for Alzheimer’s disease CONFIDENTIAL

Xanamem • Actinogen’s lead compound • A novel, first in class, potent, orally bioavailable, brain-penetrant, 11βHSD1 inhibitor 1 • Differentiated mechanism of action: blocking cortisol production in the brain • Symptomatic and disease modifying effects in vivo 1 • Well-tolerated – dosed >100 patients/subjects: acceptable clinical safety, toxicity and PK/PD profile 1 • Effective human brain concentrations demonstrated 1 • XanADu – phase II clinical study underway, dosing subjects with mild AD dementia in USA, UK, AU • Fully funded following completion of ~A$5.3 million capital raise in Nov 2017. • Planning ongoing for additional studies and clinical indications • A range of additional studies adequately funded following completion of ~$16.5 million capital raising in May-July 2018 • Composition of matter IP coverage ≥ 2031, patents granted in all major markets 1. Webster et al ., 2017, British J Pharmacol 174:396-408 10 Xanamem™ - novel approach to Alzheimer’s dementia