ACTINOGEN MEDICAL LIMITED — Call Transcript 2018

May 27, 2018

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ASX ANNOUNCEMENT

Actinogen Medical Investor Conference Call

Sydney, 28 May 2018: Actinogen Medical ASX: ACW (‘ACW’ or ‘the Company’) will be hosting an investor conference call on Wednesday the 30[th] of May at 10:30am Australian Eastern Standard Time.

The call will include discussion on the Company’s lead compound, Xanamem, and the good progress the Company is making with XanADu, our Phase II trial in Alzheimer’s disease. Also, we will review the recent announcements on the XanADu Interim Analysis, as well as the $15m placement with three major institutional investors, which was led by the US based Biotechnology Value Fund, L.P. (BVF).

An Investor Presentation is attached, which may be referred to during the Conference Call.

The call will be hosted by Actinogen Medical CEO, Dr Bill Ketelbey , who will be joined by Chairman, Dr Geoff Brooke, and Advisory Board members Professor Craig Ritchie, Professor Colin Masters and Professor Jeffrey Cummings.

Details to join the conference can be found below. The Company will be inviting participants to ask questions during the call and in addition, questions can be submitted beforehand via email to: info@actinogen.com.au.

To join the conference call, please use the below details:

Conference ID: 2657738 – ID number when joining the call

Australian participant dial-in	Participant toll:	+61 2 8038 5221
	Participant toll-free:	1800 123 296
International toll-free dial-in	Canada	1855 5616 766
Toll-free dial-in numbers for each country are listed.	China	4001 203 085
For countries not listed, dial the Australian Participant toll number+61 2 8038 5221	Hong Kong	800 908 865
	India	1800 3010 6141
	Japan	0120 477 087
	New Zealand	0800 452 782
	Singapore	800 616 2288
	United Kingdom	0808 234 0757
	United States	1855 293 1544
To ask a question, participants will need to dial	“*1” (star, 1) on their	telephone keypad

-ENDS-

Actinogen Medical Media Enquires Dr. Bill Ketelbey Zena Chamas CEO & Managing Director Media & Capital Partners P: +61 2 8964 7401 M: +61 434 153 055 E: bill.ketelbey@actinogen.com.au E: zena.chamas@mcpartners.com.au @BillKetelbey

About Actinogen Medical

Actinogen Medical (ASX: ACW) is an ASX-listed biotech company focused on innovative approaches to treating cognitive decline that occurs in chronic neurodegenerative and metabolic diseases. Actinogen Medical is developing Xanamem a promising new therapy for Alzheimer’s disease, a condition with a multibillion dollar market potential. In the US alone, the cost of managing Alzheimer’s disease is estimated to be US$250bn and is set to increase to US$2tn by 2050, outstripping the treatment costs of all other diseases. Alzheimer’s disease is now the leading cause of death in the UK and second only to ischaemic heart disease in Australia

About Xanamem™

Xanamem’s novel mechanism of action sets it apart from other Alzheimer’s treatments. It works by blocking the excess production of cortisol - the stress hormone – through the inhibition of the 11β-HSD1 enzyme in the brain. This enzyme is highly concentrated in the hippocampus and frontal cortex, the areas of the brain most affected by Alzheimer’s disease. There is a strong association between chronic stress and excess cortisol that leads to changes in the brain affecting memory, and to the development of amyloid plaques and neural death – all hallmarks of Alzheimer’s disease.

About XanADu

XanADu is a Phase II double-blind, 12-week, randomised, placebo-controlled study to assess the safety, tolerability and efficacy of Xanamem in subjects with mild dementia due to Alzheimer’s disease. XanADu, will enrol 174 patients at 20 research sites across Australia, the UK and the USA. The trial is registered on www.clinicaltrials.gov with the identifier: NCT02727699, where more details on the trial can be found, including the study design, patient eligibility criteria and the locations of the study sites.

Actinogen Medical encourages all current investors to go paperless by registering their details with the designated registry service provider, Link Market Services.

Alzheimer Treatment Needs a New Approach – Xanamem™ May/June 2018

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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).

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Xanamem™ - novel approach to Alzheimer Dementia

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Actinogen Medical (ASX:ACW)

• Developing Xanamem for the treatment of Alzheimer's disease (AD) and cortisol associated cognitive impairment

• Xanamem, a novel differentiated mechanism of action: prevents the production of excess brain cortisol

S T O C K M E T R I C S[*]

Pending completion of the Placement of 300,000,000 shares (Tranche 1 and 2) and the Share Purchase Plan (SPP)

L A R G E S T H O L D E R S

• Persistently raised cortisol in the brain is associated with the development and progression of AD

• First-in-class, brain penetrant, orally active, inhibitor of 11βHSD1 enzyme, reducing conversion of cortisone to cortisol

Pending completion of the Placement of 300,000,000 shares (Tranche 1 and 2) and the Share Purchase Plan (SPP)

• Biotechnology Value Fund, L.P.

• Platinum Investment Management Limited

• Edinburgh Technology Fund Limited

• Australian Ethical Investment

• JK Nominees

• Experienced board and management; expert clinical and scientific advisory board

• Sunset Capital Management

• Warambi Sarl

• BNP Paribas Nominees

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Interim Analysis – recommendation to continue trial without modification

• Interim Analysis undertaken by independent Data Safety Monitoring Board (DSMB)

• • Safety and efficacy data reviewed

• Conducted on data from first 50 evaluable XanADu trial patients. Additional 37 patients’ safety data also included in the analysis

• No treatment related serious adverse events

• Recommendation affirms the positive benefit-risk safety profile of Xanamem 10mg daily

• Supports progression of study as planned

• Underpins further development in other indications

Announced 23 May 2018

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Substantial Institutional investment in Actinogen Recognises potential and endorses strategy

• Positive interim analysis catalyses significant $15M investment through Placement

• Leading investors enter register:

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• USA specialist biotech investor Biotechnology Value Fund L.P.

• Australian institutions Platinum Investments Management and Australian Ethical Investments

• Strong endorsement - Placement price represents an 13.4% premium to the 5-day VWAP

• BVF cornerstones Placement to become the largest shareholder with a 19.9% holding

• Funding to advance Company's development plan through additional Xanamem studies. Focus on enhancing the dataset for Xanamem, adding substantial value to ongoing partnering discussions

  • Announced 23 May 2018

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New Xanamem studies – funded through May ‘18 capital raising: Enhancing value, broadening scope, enhancing data-set

• New funding to advance Company's development plan

• Focus on enhancing the data-set for Xanamem, broadening scope of use and adding substantial value to asset

• Target engagement study – will help define optimum dose

• Safety studies with higher doses

• Additional standard toxicology studies required by regulators (in all drug development)

• New indications

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6 Xanamem™ - novel approach to Alzheimer Dementia

Cortisol inhibition improves cognition – Key Factor in 2014 Acquisition Two 2004 pilot studies concluded that inhibiting cortisol production in the brain with carbenoxolone improves cognitive function in healthy elderly men & type 2 diabetics – this established Edinburgh Uni hypothesis

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VERBAL FLUENCY – Study 1 VERBAL MEMORY – Study 2
P=0.006 P=0.005
Mean SD Mean SD
Placebo 40.6 12.4 Placebo 55.2 8
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 3 times Study 2 = 12 type 2 diabetics (m=9; f=3) Age 52-70 (Mean Age = 60 ± 4.9) receiving 100mg carbenoxolone
daily compared to placebo for 4 weeks, in a double-blind randomised crossover study. 3 times daily compared to placebo for 6 weeks, in a double-blind randomised crossover study.
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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 Source: Sandeep et al., 2004 PNAS (vol. 101, no. 17) 6734-6739

Xanamem™ - novel approach to Alzheimer Dementia

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Robust Animal Data with new candidate - Key Factor in 2014 Acquisition

Symptomatic and disease modifying effects in mouse models – AUD $25 million invested pre acquisition

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Cognition: treatment 28 days Amyloid Clearance: treatment 28 days
P=0.004 P=0.01
Control 43 ± 21 Control 38 ± 3
Treatment Treatment
Treatment 172 ± 28 Treatment 22 ± 5
p=0.004 p=0.01
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
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Significant improvement in cognition after only 28 days treatment, continuing out to 41 weeks

UE2316 in Tg2576 rodent model of Alzheimer’s disease. Source: Sooy, et al., 2015. Endocrinology 156 (12) 4592-4603

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8 Xanamem™ - novel approach to Alzheimer Dementia

Xanamem

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Xanamem

• 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

• Planning ongoing for additional clinical indications

• Composition of matter IP coverage ≥ 2031, patents granted in all major markets

• ~

• XanADu Alzheimer's trial fully funded following completion of A$5.3 million capital raise in November 2017

• A range of additional studies adequately funded following completion of ~ $17 million capital raising in May 2018

• Webster et al. , 2017, British J Pharmacol 174:396-408

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Cortisol: a validated biomarker and target for AD

Cortisol and Alzheimer’s

• Recent independent studies support the association between cortisol and AD development and progression[1-5]

• Cognitive impairment in patients with neuroendocrine dysfunction[6-9 ]

• Compelling evidence provided by the Australian Imaging, Biomarker & Lifestyle Study of Ageing (AIBL) study (2017)[5 ]

• Subjects with higher plasma cortisol at much greater risk of developing AD

• Accelerated effect of Αβ+ on decline in global cognition, episodic memory and attention

Xanamem

• Data presented at four major international medical congresses in 2016 – AAIC Toronto; CTAD San Diego; ICE Beijing; MMC Lisbon

• Pre-clinical and Phase I data published[10-11]

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MEAN CSF CORTISOL LEVELS

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0.7
0.6 p<0.001
0.5
0.4
0.3
0.2
0.1
0
Cognitive Normal MCI Other MCI AD AD dementia
Popp et al, 2015
CSF cortisol (μg/dl)
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[1] Geerlings et al., 2015, Neurology 85: 1-8; [2] Lehallier et al ., 2016, JAMA Neurology 73(2), 203-212; [3] Popp et al. , 2015, Neurobiol. Aging 36:601–607; [4] Ennis et al., 2017, Neurology 88(4):371-378; [5] Pietrzak et al. , 2017, Biol Psychiatry: Cognitive Neuroscience and Neuroimagery, 2:45-52; [6] Lupien et al., 2009, Nat Rev Neurosci 10:434–445; [7] Starkman et al., 1999, Biol Psychiatry 46: 1595–1602; [8] Lupien et al., 1998, Nat Neurosci 1:69–73; [9] MacLullich et al., 2005, Psychoneuroendocrinology 30:505–515; [10] Sooy et al ., 2015. Endocrinology 156(12):4592-4603; [11] Webster et al. , 2017, British J Pharmacol 174:396-408.

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Cortisol, cognitive decline and AD: a growing body of literature

Recent relevant reviews:

PUBMED:"CORTISOL AND COGNITION"

• Cortisol: Mediator of association between Alzheimer's disease and diabetes mellitus? (Notarianni, 2017 , Psychoneuroendocrinology )

• Unified theory of Alzheimer's disease (UTAD): implications for prevention and curative therapy . (Nehls 2016 , J Mol Psychiatry )

• Is Dysregulation of the HPA-Axis a Core Pathophysiology Mediating Co-Morbid Depression in Neurodegenerative Diseases? (Du and Pang, 2015 ; Front Psychiatry )

• The impact of stress and glucocorticoids on memory. (Tatomir et al . 2014 ; Clujul Med. )

• Contribution of glucocorticoids and glucocorticoid receptors to the regulation of neurodegenerative processes. (Vyas and Maatouk, 2013 ; CNS Neurol Disord Drug Targets )

• Stress-induced cytokines and neuronal dysfunction in Alzheimer's disease. (Ricci et al., 2012; J. Alzheimer’s Dis. )

• Local amplification of glucocorticoids in the aging brain and impaired spatial memory (Yau and Seckl, 2012; Front. Aging Neuroscience )

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140
120
100
80
60
40
20
0
1950 1960 1970 1980 1990 2000 2010 2020
PUBMED: "CORTISOL AND ALZHEIMER'S"
25
20
15
10
5
0
1980 1985 1990 1995 2000 2005 2010 2015 2020
Number of publications
Number of publications
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Xanamem pipeline of indications, back-up compounds*

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• P R E C L I N I C A L P H A S E I P H A S E I I

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Alzheimer’s disease

Diabetes Cognitive Impairment & other diseases with possible cortisol induced Cognitive Impairment

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Post Traumatic Stress Disorder

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Post Myocardial Infarction

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• Back-up compounds to Xanamem, licenced from Edinburgh University

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XanADu – Phase II Trial

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XanADu – Xanamem in Alzheimer's disease

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Phase II double blind, randomised, placebo-controlled study to assess the efficacy and safety of Xanamem in participants with mild Alzheimer's disease*

• 101 patients enrolled (58% of total study cohort) and more than 68 patients already completed study

• On track for last patient enrolled in Q4 2018 and top line results in Q2 2019

• Interim Analysis on first 50 evaluable patients - DSMB recommends continuing XanADu without modification

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Xanamem treatment course 174 12 weeks Mild Alzheimer’s patients Trial conducted at 20 sites in Xanamem 10mg daily

for 12 weeks vs placebo AUS, USA and UK

Primary and secondary endpoints are standard and experimental cognitive outcome measures used in Alzheimer's research: ADASCog14, ADCOMS, CDR-SOB, MMSE, RAVLT, NTB-ED

Registered on Clinicaltrials.gov: NCT02727699

⃰⃰ As at 25 May 2018

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Investment potential

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Commercially experienced, globally recognised

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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
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Peer comparison

What big pharma companies are paying for acquisition of drug developers in the Alzheimer’s space

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2000
1800
1600
1400 X
1200
1000
800 X
600 X
400
200
0
PH I PH II PH III
V A L U E U S $ M I L L I O N S
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Xanamem™ in closing ………….

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Summary

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A huge market with a significant unmet medical need

Xanamem

• Differentiated, with a novel mechanism of action

• Small molecule - oral

• High quality development plan and regulatory review

• Solid IP out to at least 2031

• Potential utility in other neurological indications

XanADu

• Fully funded to completion of XanADu

• Additional studies funded with May 2018 capital raise

• Interim Analysis – continue study without modification

• On track for last patient enrolled before end 2018

• 101 patients enrolled (58% of total); 68 already completed

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Substantial independent support for cortisol/Alzheimer's hypothesis

Highly experienced Board

Growing interest in Xanamem from pharma partners

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A compelling investment opportunity

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Dr. Bill Ketelbey CEO & Managing Director ☏ Main: +61 2 8964 7401 ✉Email: bill.ketelbey@actinogen.com.au www.actinogen.com.au

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Appendix

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Xanamem journey of discovery
11β-HSD1 is highly
expressed in
Xanamem data
regions important Carbenoxolone is
for cognition shown to enhance published
cognitive function Webster et al.,
in elderly men and 2017
11β-HSD1 type II diabetics First First Xanamem XanADu
discoveredenzyme Sandeep et al., 2004 patent filed humanstudy blood brain crosses Top Line results
barrier Q2 19
11β-HSD1
XanADu
knockout mice
ACW acquires FDA IND
related cognitive are protected against age-dysfunction Development of selective 11β-HSD1 development commencesXanamem Xanamemrights to Approval XanADulast patient Subject InXanADu Last
inhibitors that in Q4 18
cross the blood
brain barrier
PHASE I PHASE II
CANDIDATE
NON-CLINICAL
OPTIMISATION
wellcome [trust] funded Actinogen investor funded
1970 1990 2001 2004 2007 2009 2011 2013 2014 2015 2016 2017 2018 2019
XanADu First Subject In
Diabetes Cognition Phase II
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Recent comparable deals

Assets with Alzheimer’s disease as the lead indication or key indication

Licensee/acquirer	Licensor/acquired	Year	Candidate(s)	Phase	Deal Value (US$M)	Upfront (US$M)
Takeda	Denali	2018	ATV platform, three programs	Pre-clinical	~$1,000	$150
AbbVie	Voyager	2017	AAV anti-tau antibodies	Pre-clinical	$1,109	$69
Biogen	BMS	2017	BMS-986168	Ph 1	$710	$300
Allergan	Heptares	2016	Three M1/M4 agonists	Ph I	$3,340	$125
Janssen	AC immune	2015	ACI-35	Ph Ib	$509	Undisclosed
Merck	Bionomics	2014	BNC-375	pre-clinical	$526	$20
Eli Lilly	AstraZeneca	2014	AZD3293	Ph I	$500	$50
Iperian	BMS	2014	IPN007	pre-clinical	$725	$175
Otsuka	Lundbeck	2013	Idalopirdine	Ph II	$825	$150
Janssen	Orion	2013	ORM-12741	Ph IIa	Undisclosed	$31

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24 Xanamem™ - novel approach to Alzheimer Dementia