Investor Presentation Paul Rennie, CEO & MD April 2018 Disclaimer This document, together with any information communicated by Paradigm Biopharmaceuticals Ltd (known as Paradigm, Paradigm Biopharma or the Company), in any presentation or discussion relating to this document (collectively, Information) is confidential, and has been prepared by the Company on the condition that it is for the exclusive information and use of the recipient. The Information is proprietary to Paradigm and may not be disclosed to any third party or used for any other purpose without the prior written consent of the Company. The Information is based upon management forecasts and reflects prevailing conditions, which are accordingly subject to change. In preparing the Information, the Company has relied upon and assumed, without independent verification, the accuracy and completeness of all information available from public sources, or which was otherwise reviewed by it. In addition, the analyses are not and do not purport to be appraisals of the assets, stock or business of the Company. Even when the Information contains a kind of appraisal, it should be considered preliminary, suitable only for the purpose described herein and should not be disclosed or otherwise used without the prior written consent of Paradigm. The Information is provided on the understanding that unanticipated events and circumstances may occur which may have significant valuation and other effects. 2 Investor Presentation November 2017 Corporate Overview Financial information Paradigm Biopharmaceuticals Ltd is an ASX-listed biopharmaceutical company focused on finding new clinical indications for an already approved drug. Paradigm is repurposing PPS for a number of applications with a focus on treatment of arthritis, respiratory and cardiovascular indications giving us multiple shots on goal Share price (21-March-18) A$0.30 Number of shares 120.6m Market capitalisation A$36m Cash (31-Dec-17) no debt
~A$6.0m Enterprise value A$30m Experienced Board and management Investment proposition for finding new clinical indications for an already approved drug; Saves time, save money, less clinical and manufacturing risk Top shareholders1,2 Shares (m) % 21.5 21.1% MJGD Nominees (technology vendor) 6.9 6.8% Other Board and management 7.1 7.0% Irwin Biotech (technology vendor) 6.3 6.2% Paul Rennie (Managing Director) Phase 2 catalysts Q4 CY2018 Note: 1. Blue shading represents Board and management holdings 2. MJGD Nominees and Irwin Biotech are select vendors of Xosoma, which was acquired by Paradigm prior to listing 3 Investor Presentation
November 2017 Drug Repurposing Strategy Much lower cost, accelerated timeline, lower risk and with higher rates of success Lower cost: average development cost of ~US$30-50m compared to US$1.3bn for de novo development 1 Faster: FDA 505(b)(2) pathway leveraging previous clinical efforts, which accelerates the development timeline Lower risk: safety already established so less chance of failure (safety issues account for 30% of clinical failures 1) Higher success rates: 25% chance of successful commercialisation compared to 10% for de-novo drugs 1 Repurposed drugs have the same potential to reach blockbuster drug status as de novo drugs Standard clinical development1,2 10-17 year process Discovery & pharmacology 2 3 years Preclinical testing Phase I clinical trials 5 6 years Phase II clinical trials Phase III clinical trials 2 6 years Regulatory approval 1 2 years Paradigms drug repurposing timeline Often only 1 pivotal Phase II trial Can use RWE open label case studies 1 pivotal Phase III trial for each indication Regulatory approval
3-5 year process to approval 1 year 1 2 years 1 2 years Source: 1. Khanaoure A, Chuki P & De Sousa A (2014) 2. Ashurn T & Thor K (2004) 4 Investor Presentation November 2017 Board and Management High quality Board and management, with top-tier pharmaceutical experience Board and management are renowned leaders in the biopharmaceutical industry, having held senior management positions with top ASX-listed companies, CSL (CSL.ASX) and Mesoblast (MSB.ASX) Extensive experience bringing biopharmaceutical products from clinical development to commercialisation Board and management 5 Graeme Kaufman Non-executive Chairman Broad experience in development and commercialisation of pharmaceutical drugs, previously CFO at CSL, executive VP of Mesoblast and Chairman of Bionomics (BNO) Christopher Fullerton Non-executive Director Chartered Accounting and investment banking expertise, previously Non-executive Chairman of Bionomics and Cordlife (now Life Corporation (LFC.ASX)) Paul Rennie Managing Director Extensive experience in drug development and commercialisation, previously COO & Executive VP, New Product Development of Mesoblast Dr Ravi Krishnan Chief Scientific Officer Significant experience in experimental pathology and investigating novel compounds with immune modulatory effects and anti-inflammatory properties John Gaffney Non-executive Director 30+ years experience as a lawyer, previously Director of Patrys
(PAB.ASX) Kevin Hollingsworth CFO & Company Secretary Previously CFO and Co-Sec of Mesoblast and Patrys (PAB.ASX) Investor Presentation November 2017 Osteoarthritis with Bone Marrow Lesions TGA Special Access Scheme Real World Evidence 45 patients treated All patients (median age of 57.5 years - range 31 to 84 years) had pain and failed current standard of care - analgesics, NSAIDs or corticosteroids. At six weeks after the initiation of PPS treatment: Pain 38 out of 45 patients (84.4%) showed a reduction in pain; Function 38 out 45 patients (84.4%) showed an improvement in knee function; Patient A MRI Pre PPS Treatment Pre treatment Scores High NRS Pain Score = 8 Lysholm Score: 37 (Poor knee function) BME Lesions Joint Space Effusions 6 Investor Presentation Patient A MRI Post PPS Treatment Post Treatment Results Complete resolution of BME lesions and effusions Pain NRS = 0 (pain resolved) Lysholm Score: 65 (Fair knee function) November 2017 Osteoarthritis with Bone Marrow Lesions Osteoarthritis - A blockbuster indication with no effective treatments Osteoarthritis and bone marrow lesions BML are commonly associated with OA and have been linked to early onset of OA and joint cartilage degeneration. 1 BML sustains inflammation and the release of MMPs and ADAMTS-5 enzymes, causing cartilage degeneration
Resolution of the BML, reduces inflammation and promotes joint health Patients treated with PPS have reported statistically significant improvement in pain and function Osteoarthritis is the most common form of arthritis, affecting over 31 million people in the United States, with over 36 million outpatient visits and 750,000 hospitalisations per year. 2 Source: 1. The occurrence and progression of BMLs have been shown to be associated with progression to osteoarthritis and joint pain (Osteoarthritis and Cartilage 2012, 20:1514-1518) and (Rheumatology 2010, 49:2413-9). 2. http://ard.bmj.com/content/annrheumdis/early/2017/07/12/annrheumdis-2017-211396.full.pdf 3. National Institute of Health; Emerging drugs for osteoarthritis; Hunter DJ and Matthews G 16(3): 479491; 2011 September. 4. Ibid. 7 Investor Presentation OA Market Facts: Market of therapeutics to treat OA ~US$5 billion pa Globally3 Cost to US Economy US$128+ billion pa4 AFL Legend Greg Diesel Williams diagnosed with OA, experienced significantly improved pain and function scores post PPS treatment November 2017 TGA-SAS program: 147 OA patients - completed or undergoing PPS treatment for BML LBP; 6; 3.92% OP; 5; 3.27% Hip; 5; 3.27% Hand-wrist; 2; 1.31% Knee and other musculoskeletal indications
Foot-Ankle; 10; 6.54% Complete data set on 45 patients with knee OA Efficacy: Pain and Function Publication Plan: Conference presentation Knee; 125; 81.70% 8 Investor presentation 16 March 2016 TGA-SAS program: 45 patients with BML treated with PPS for Knee Pain and Function A Paired t-test was used to compare the before and after scores for knee pain (NRS) and knee function (LKS). 10 Pain (NRS) Before-after=3.1 p<0.0001 Paired Profiles for (NRS_Before_Tx, 50% reduction in kneeNRS_After_Tx) pain 8 8 6 6 4 100 100 Mean 80
80 60 60 40 40 20 20 4 2 2 Mean 0 NRS_Before_Tx Before 6.3 9 10 Function (LKS) Before-after=23.5 p<0.0001 Profiles for (LKS__Before_Tx, LKS_After_Tx) 64%Paired improvement in knee function Investor presentation 0 NRS_After_Tx After 3.2 LKS__Before_Tx
Before 47.8 LKS_After_Tx After 71.3 16 March 2016 Osteoarthritis with BML: The Market for PPS (ZILOSUL) ZILOSUL has the potential to fill the current gap in osteoarthritis treatment options There is currently no effective treatment for osteoarthritis and BMLs that treats the underlying pathology of the disease. Current therapies treat the symptoms of osteoarthritis and bone marrow edema lesions but prolonged use results in undesirable side-effects. It is widely accepted that NSAIDs and corticosteroids are contraindicated having a detrimental effect on the metabolism of bone and cartilage. Opioids are widely misused globally as patients form serious addictions whilst mitigating pain. 1 ZILOSUL treats the underlying pathology of osteoarthritis by reducing inflammation, resolving the bone marrow edema lesions and down regulating cartilage degrading enzymes (MMPs and ADAMTS-5). (ZILOSUL) NSAID (ibuprofen etc) Opioid (oxycodone etc) Corticosteroid / Cortisone Joint Replacement Treats the symptoms of OA (pain & function) Treats underlying pathology
No undesirable side-effects Non-addictive Anti-inflammatory Non-Surgical 1. https://www.drugabuse.gov/news-events/news-releases/2017/07/pain-relief-most-reported-reason-misuse-opioid-pain-relievers 10 Investor Presentation November 2017 OA with BML: Clinical Timeline Comprehensive clinical pathway to commercialisation OA/BMEL case study published in peer reviewed scientific journal Successful completion of the Phase 2a open label clinical trial Trial demonstrated the safety, tolerability and efficacy of ZILOSUL in patients with a bone marrow edema lesions from a recent ACL (acute knee) injury 45 additional patients treated under the TGA SAS scheme. Very positive clinical signals from BML patients with
osteoarthritis (OA) Over 50% recruited for Phase 2b placebo controlled (100 patient) clinical trial for BML with OA Results due Q4 CY2018 Plan to undertake pilot studies in BML patients with rheumatoid arthritis (RA) 2017 Clinical development timeline Q1 Q2 Q3 2018 Q4 Q1 Q2 Q3 2019 Q4 Q1 Q2 Q3 Q4 Phase 2a open label clinical trial with BMEL in ACL (n=10) Peer Review publication of OA/BMEL case study Osteoarthritis / BMEL Pivotal Phase 2b clinical trial (n=100) Proceed to partner OA Indication with big Pharma Note: 1. Closed label, randomised, double blind, placebo controlled trial expected to commence in Q42017, expected to be completed in 12-18 months after commencement 11 Investor Presentation November 2017 Viral Arthritis Alphavirus
No approved treatment for severely debilitating viral infection Viral Arthritis Alphavirus infections result in the clinical symptoms of joint and muscle pain, fever and joint inflammation. Ross River Virus (RRV) and Chikungunya (CHIKV) are mosquitotransmitted arthritogenic alpha viruses that cause epidemics of severe musculoskeletal disease in many countries. No effective treatment, with sufferers left incapacitated Symptoms can persist for a number of years Ross River Virus & Chikungunya Virus Paradigm acquired the patent from the Institute for Glycomics research at Griffith University. The patent claims the use of PPS to treat alphaviruses, including Ross River Virus (RRV) and Chikungunya Virus (CHIKV). Potential interest from the US Department of Defense to codevelop for treating CHIKV 12 Investor Presentation Chikungunya cases ,USA November 2017 Viral Arthritis: Clinical Timeline Potential to gain Orphan status, resulting in fast-tracked clinical development Pre-clinical studies have been conducted by the Institute of Glycomics at Griffith University. The results suggested that: PPS significantly alleviated the severity of disease and reduced both the inflammatory response and the loss of articular cartilage; PPS has the potential to treat both acute and chronic symptoms associated with mosquito transmitted alphavirus infections (Ross River virus (RRV) and chikungunya virus (CHIKV); There currently is no effective disease modifying treatment for RRV or CHIKV. 30 patients with RRV-arthralgia (joint pain) already treated with PPS under the TGA Special Access Scheme demonstrating tolerability and potential clinical effects Phase 2 Clinical Trial PPS to treat RRV and CHIKV Queensland Government have provided a A$300,000 grant for Ross River research Paradigm to embark on two Phase 2 clinical trial to develop PPS for the treatment of RRV-and CHIKV-induced arthritis and arthralgia Potential for Fast-Track /Breakthrough/Accelerated Approval 2017 Clinical development timeline Proof of concept study under SAS (n=30) Q1 Q2 Q3 2018 Q4 Q1
Q2 Q3 2019 Q4 Q1 Q2 Q3 Q4 Completed CY2016 Design and Ethics approval for Phase II Trial Phase 2 Clinical Trial Ross River Plan for a Phase 2 Clinical Trial - Chikungunya 13 Investor Presentation November 2017 Broad Product Pipeline 14 Investor Presentation November 2017 Clinical Pipeline Paradigm hosts a deep clinical pipeline Indication(s) Clinical Status Market Size IL-1RA Peptide Inflammatory bowel disease (IBD) Cancer-related cachexia Ulcerative colitis
Crohn's disease Safety and efficacy confirmed in Phase 1/2 clinical trial (n:26) Cardiovascular Heat Failure Demonstrated beneficial effects in an established preclinical heart failure model US$18+ Billion2 Hay Fever COPD Allergic Asthma Pre-clinical safety and efficacy in guinea pig model Safety confirmed in Phase 1b clinical trial (n:18) Paradigm to reassess Phase 2b clinical trial (n:40) US$11+ Billion Respiratory 15 Investor Presentation Inflammatory Bowel Disease Medicines predicted to reach US$9.3 Billion1 October 2017 IP Protection Multi-faceted IP protection increases barriers to entry for potential competitors Valuable patent portfolio Paradigm has patent protection because it is using PPS for new indications Minimum life on patents is 2030 and beyond for more recent patents - i.e. 2035 Patents granted for specific indications BMEL BMEL patent patent granted
granted in in USA USA EU EU patents patents granted granted for for respiratory respiratory diseases diseases incl. incl. AR, AR, allergic allergic asthma asthma (AA) (AA) & & chronic chronic obstructive obstructive pulmonary pulmonary disease disease (COPD) (COPD) and and IP1510 IP1510 (IL-1RA) (IL-1RA) Established regulatory exclusivity and trademarks BMEL BMEL patent patent granted granted in in Japan Japan ++ other other Asia Asia Patent applications for Ross River virus and Chikungunya virus Global patent for Heart Failure indication Assessing additional patent applications Secure manufacturing and supply Exclusive 20 year supply agreement with bene PharmaChem1 bene pharmaChem makes the only FDA-approved form of PPS
Patents Patents granted granted for for BMEL BMEL and and respiratory diseases respiratory diseases in in Australia, Australia, China, China, and and New New Zealand Zealand Manufacturing methods are a well kept trade secret Reduces risks associated with manufacturing and supply Note: 1. bene pharmaChem is a private company located in Germany and manufactures the only officially approved and clinically tested medicinal PPS in the USA, Europe and Australia 16 Investor Presentation November 2017 Peer Comparison Attractive investment given low risk development and large market opportunity Paradigm appears undervalued compared to similar stage, drug repurposing peers given its platform for successful development, secure industrial scale manufacturing and the size of its addressable markets Peer Ticker and exchange MVP.ASX Market cap Clinical stage of key Addressable market (A$m) Rationale product size 428 Developing new markets and applications Commercialisation US$1.5bn+ for Penthrox, recent focus on respiratory
diseases, significant manufacturing IP SPL.ASX 444 Commercialising an old technology of Phase III & US$3bn+ synthetic branching polymers (dendrimers), commercialisation with lead product VivaGel in Phase III trials AXSM.NASDAQ 83 Developing novel therapies for the Phase III US$2.5bn+2 management of central nervous system disorders, focusing on treatment of BMEL VRP.LN 285 Focused on commercialising an old Phase I/II(a) US$12bn+3 compound for respiratory diseases, with dual inhibition of key enzymes PAR.ASX 34 Focused on the clinical development of PPS Multiple Phase II(a) US$37bn+4 as a multi-target treatment for complex conditions, such as BMEL/OA, AV & AR Source: Bloomberg, company filings 1. 2. 3. 4. 17 Market data as at 20 March 2018, exchange rates of AUDGBP 0.55 and AUDUSD 0.77 Based on BMEL addressable market size, excludes CRPS addressable market due to lack of available information and thus likely understates true market size Only includes the market size for COPD which is US$12b+, excludes market sizes for other respiratory disease indications Includes AR market US$11bn+ and OA/BMEL market US$8bn+ & $0.5bn for viral arthritis ,excludes COPD addressable market size of US$12bn+ and Asthma addressable market size of US$15bn+ and Heart failure Figures between 2014 & 2016 - Statins $13.2bn (Research and Markets - Global Statin Market 2015-2016), Clopidogrel bisulphate $1.8bn, Beta-blockers $1.55bn, Ace inhibitors 0.47bn, Aspirin $0.54bn, Vitamin K antagonist $0.5bn ( www.pharmacompass.com) Investor Presentation November 2017 Share Price Catalysts Upcoming milestones should drive strong shareholder returns
ACL/BMEL OA/BMEL Phase 2 trials Additional OA with BML RWE results Complete Phase 2b placebo controlled OA clinical trial (100 patients) with trial results Read Out targeted for end CY2018 Additional high Profile sporting identities (such as Andrew Walker, Carlton) treated with PPS under SAS program ALPHAVIRUSES Phase 2 Trials Completion of RRv Phase 2a clinical trial (24 patients) Results Read Out Q3 CY2018 Potential to partner with US DoD on CHIKV treatments and trials Initiation of CHIKV Phase 2a clinical trial Reformulation into oral administration IL-1RA Peptide Auto-immune, oncology Partner with big Pharma 18 cancer cachexia Progress pilot human clinical trials (TBD) HAY FEVER Analysis of Phase 2 results and determine reformulation Explore formulations for COPD and Allergic Asthma Potential to JV or co-fund future development CORPORATE OPPORTUNITIES Potential partners Demonstrated interest from major pharmaceuticals companies in treatments for OA, BMEL, Respiratory, Heart Failure and Alpha Virus & IL-1 RA peptide Partnership with world-class manufacturers EXPANSION Market share Investor Presentation
Expansion of BMEL market into OA and other joint pain indications Progress and potentially partner IL-1RA peptide Progress Alphavirus and Heart Failure Develop new IP and corporate opportunities in new indications November 2017 Contacts Office Level 2, 517 Flinders Lane, Melbourne, VIC, 3000 [email protected] Managing Director & CEO Paul Rennie - [email protected] Chief Scientific Officer Dr Ravi Krishnan [email protected] Corporate Advisor Baker Young Stockbrokers Ltd Dirk van Dissel [email protected] Analyst Baker Young Stockbrokers Ltd Alastair Murray [email protected] 19 Investor Presentation November 2017
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