Announcement PDF ASX Announcement Recce Delivers Opening R&D Address at 2019 World Antibiotic Resistance Congress Sydney, Australia, 08 November 2019: Recce Pharmaceuticals Ltd (ASX: RCE) (Recce or the Company), developing a new class of synthetic antibiotics, today released its presentation at the World Anti-Microbial Resistance Congress in Washington D.C., 7-8 November 2019. Picture: Chairman Dr Prendergast Dr John Prendergast, Chairman of Recce Pharmaceuticals, today delivered the Opening R&D Address on “How synthetic antibiotic development can change the antibiotic treatment model”. Supporting slides available below. The Company has further been invited to Lead a Panel at the Economist Anti-Microbial Resistance Summit Asia Thursday 5 December 2019 in Singapore and looks forward to updating in due course. Dr Prendergast’s talk will be available in the coming weeks on the company’s website. 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Given the risks and uncertainties that may cause the Company’s actual future results, performance or achievements to be materially different from those expected, planned or intended, recipients should not place undue reliance on these intentions, expectations, future plans, strategy and prospects. The Company does not warrant or represent that the actual results, performance or achievements will be as expected, planned or intended. US DISCLOSURE This document does not constitute any part of any offer to sell, or the solicitation of an offer to buy, any securities in the United States or to, or for the account or benefit of any “US person” as defined in Regulation S under the US Securities Act of 1993 (“Securities Act”). The Company’s shares have not been, and will not be, registered under the Securities Act or the securities laws of any state or other jurisdiction of the United States, and may not be offered or sold in the United States or to any US person without being so registered or pursuant to an exemption from registration including an exemption for qualified institutional buyers. 1 2 3 Brown & Wright, Nature 2016 International Focus to Identify New Antibiotics Common goal - Overcome anti-microbial resistance 4 Primary Synthetic Anti-Bacterial Strategies Antimicrobial Peptides (APs) Antimicrobial Polymers (AMPs) Nanotechnologies AMPs can either display antibacterial activities through its own inherent chemical structure; e.g., quaternary nitrogen groups, halamines and polylysine or can serve as a backbone to improve the potency of existing antibiotics. AMPs’ design traditionally based on the chemical templates provided by Antimicrobial Peptides (APS), a class of peptides of the innate immune system which protects the body from invading pathogens. APs are relatively small in size (10–50 amino acids), amphiphilic with cationic charge. With these physical characteristics, APs accumulate on the cell membranes and form pores on the structure, thus killing the bacteria. With multimodal mechanisms of action, APs can resist acquired resistance by the bacteria. 5 Design Strategies for Novel Antibiotics Type of Antibiotics Delivery Manufacturing modalities costs Toxicity Enzyme Degradation Antimicrobial Peptide – based polymers (APs) Yes High High Yes Antimicrobial Polymers (AMPs) No Low ? No Recce Pharmaceuticals Yes Low Acceptable No THE distinguishing feature of RECCE antibiotics is its unique Mechanism of Action 6 Design Strategies for Novel Antibiotics Antimicrobial Peptides (APs) Antimicrobial Polymers (AMPs) • Many AMPS show significant efficacies against bacteria in vitro but had reduced potency when tested in vivo • Despite their potential, AMP’s application in the clinical setting have been hampered due to several pharmaceutical limitations such as: susceptibility to enzymatic degradation, poor bioavailability and toxicity 7 Natural antibiotics vs synthetic antibiotics All Fungi or Bacteria based ‒ “Penicillin allergy is the most common drug allergy and is reported in up to 15 percent of hospitalized patients” 1 Only as good as what’s found in nature Has always had naturally occurring superbugs, now multiplying out of control! Entirely man-made and designed synthetically with purpose Universal Mechanism of Action - detailed experimentation demonstrates it does not succumb to superbugs. Broad Spectrum capability and maintains its activity even with repeated use! 1 https://www.uptodate.com/contents/choice-of-antibiotics-in-penicillin-allergic-hospitalized-patients/abstract/1 8 RECCE® 327: A New Class of Broad-Spectrum Antimicrobial Polymer to address antibiotic resistant Superbug Crisis Kills Gram +ve & Gram –ve Based on a unique composition – Copolymer bacteria, including their superbug forms - even with of PEPP repeated use. Water soluble over a broad range of pH and essentially Lead indication for treatment of sepsis – a net neutral charge #1 most expensive condition. Qualified Infectious Disease Product designation under GAIN Act. 10 years market exclusivity (post approval). Patented manufacturing, producing to Phase I & II volumes. Fast track (life of regulatory process). 9 Tackling superbugs – RECCE® 327 (video) 10 RECCE® 327 – MoA RECCE® antibiotics are attracted to the bacteria plasma membrane through hydrophobic attraction An interaction occurs within the bacterial plasma membrane proteins via hydrophilic interactions Subsequent constriction of bacterial cell wall and the natural, unique high metabolic pressure in bacteria results in bacterial cell lysis Efficacy is independent of the mutation rate 11 RECCE® 327 Mechanism of Action in practice 00:00 minutes 180 minutes Before application of RECCE® 327, the E.coli bacteria cells are healthy, smooth and intact E. coli bacteria cells (10e6 cfu/ml) having their outer membrane weakened – and bursting from treatment with RECCE® 327 (1000 ppm) 20 minutes After application of RECCE® 327, the E.coli bacteria cell membrane begins to weaken and disrupt Bacteria bursting and now “mopped up” by host immune cells Some bacteria already distended and lysing This is a high-definition electron microscope image generated in February 2017 by Dr Peta Clode and Lyn Kirilak of the Centre for Microscopy, Characterisation and Analysis, University of Western Australia. It was taken to demonstrate RECCE ® 327’s unique mechanism of action 12 RECCE® antibiotics kill at practical speeds Rates of kill of standard bacteria S. aureus E. coli P. aeruginosa S. pyogenes C. difficile 20-60 20-60 3-24 20-60 20-60 minutes minutes hours minutes minutes Rates of kill of Superbugs S. aureus E. coli P. aeruginosa 20-60 20-60 3-24 minutes minutes hours The same kill-rates for standard bacteria and their superbugs 6 All concentrations of bacteria (germ) were 10 cfu/ml Concentration of RECCE antibiotic was 1,000 ppm against all bacteria except P. aeruginosa 2,000 ppm was used against P. aeruginosa 13 RECCE® antibiotics repetitive use 1 Number of repetitive uses before displaying loss of antibiotic activity 1 After repetitive use, the commercial antibiotic loses activity; >25 repeats RECCE® antibiotic DOES NOT 14 RECCE® Antibiotics – Curative study* Three groups of 10 mice were each infected with MRSA (S. aureus superbug) Number of mice that survived Sepsis from S. aureus (superbug) All ten mice treated with RECCE® antibiotic survived Nine mice treated with current antibiotic (Oxacillin) survived Four mice that had no treatment at all, survived Note: Oxacillin was chosen for its known activity against MRSA. It is however a ‘narrow-spectrum’ antibiotic. In a clinical context, where diagnostics cannot immediately determine bacterial type, use in combatting any number of other bacteria, may likely see a less favorable patient outcome… RECCE® 327, with its proven ‘broad-spectrum’ activity, has shown strength against a range of bacteria including superbug forms, delivering rapid kill of deadly germs. * Results from an independent laboratory in USA 15 RECCE® Antibiotics – Preventative study* Controlled study with two groups of mice: Sepsis in mice from Streptococcus pyogenes Blue group represent mice with RECCE® 327 already flowing through blood stream Grey group represent mice with no treatment At 0 hours both groups were introduced with significant S. pyogenes bacterial burden to the blood stream Due to RECCE® 327 already present in a preventative role, introduction of bacteria to the blue group DID NOT lead to established infection Results were monitored at 12th hour (per industry standard) to allow bacterial infection to develop in host After the 12th hour, S. pyogenes appears to be clearing naturally from the blood – WRONG ‒ Bacteria in grey group rapidly colonising in the kidneys – commonly resulting in catastrophic organ failure ‒ NOT in RECCE’s case. Bacteria in blood rapidly killed and unable to establish infection in kidneys * Results from an independent laboratory in USA 16 Toxicity Study* – Beagle Dogs A dose-range-finding and intravenous infusion toxicity study with RECCE® 327 in Beagle Dogs. Dogs administered RECCE® 327 (70mg/kg) over 4-hour IV infusion protocol Compound again well identified in the blood High correlation between dose level and plasma concentration Studies (in-vitro & in-vivo) indicate broad spectrum efficacy at 70mg/kg dose recce.com.au 10 *Results from an independent US laboratory Patents and trademarks Patent portfolio covers all key geographies, manufacturing and modes of use Patent Family 1 Granted Expiry Patent Family 2/3 Expiry Trademarks registered Australia ✓ 2028 ✓ 2035 ✓ USA ✓ 2029 ✓ 2035 ✓ Europe ✓ 2028 ✓ 2035 ✓ Germany ✓ 2028 ✓ 2035 - Spain ✓ 2028 ✓ 2035 - France ✓ 2029 ✓ 2035 - United Kingdom ✓ 2028 ✓ 2035 - Italy ✓ 2028 ✓ 2035 - Sweden ✓ 2028 ✓ 2035 - Japan ✓ 2028 ✓ 2035 ✓ China ✓ 2028 Pending 2035 ✓ Filed Patent Family 1 – granted Unique and highly economical manufacturing process Patent Family 2 – pending Applications (Multi-drug delivery) Patent Family 3 – pending Anti-viral uses Trademarks RECCE® for use on pharmaceutical products and services 18 Manufacturing and Production Wholly owned, automated manufacturing facility in Sydney’s Macquarie Park Raw materials plentiful and CHEAP – few $/KG No expensive waste – 99.9% product yield. Automated manufacture process taking approximately 1 ¼ hours. 500 doses per automated manufacture output in less than 1 hour/run Currently producing in volumes to support planned Phase I & II clinical trials. Facility built to pharmaceutical specification. Packaging and labelling to international ‘tamper-proof’ Snapshot for RECCE® 327 ✓ Efficacy – Performs as a broad spectrum antibiotic – active against Gram-negative, Gram-Positive and drug resistant Superbugs ✓ Safety – Toxicology & Dose Escalation studies in four animal species (2 small, 2 large) - Escalating dose, Maximum dose, Repeat Dosing ✓ Haemolysis – Selective toxicity against bacteria in the bloodstream ✓ Genotox & Mutagenicity cleared – multiple studies confirm does not cause cell mutation ✓ Pharmacokinetics – RECCE® 327 clears rapidly from blood stream after dosing ✓ Allergenicity – Unlike most existing antibiotics, anaphylactic reactions not evident ✓ Mechanism of Action – Unique (MoA) always works, unable to be overcome by bacterial mutation (superbugs) – even with repeated use! ✓ 100% Soluble at all pH’s – 100% soluble at all pH’s – even to the very acidic (low) pH of the stomach ✓ Chemistry, Manufacturing & Controls (CMC) – Established (wholly owned) to human clinical specification (GLP/GMP) ✓ First-in-human applications in preparation 20 RECCE® 327 development program Recce’s technology enjoys the added opportunity of multiple markets and product categories. SEPSIS (IV – S. AUREUS, E. COLI) GASTRITIS (ORAL – H. PYLORI) INTESTINAL (ORAL – E. COLI) Estimated timelines/indications are subject to change in development plans and regulatory requirements/clarifications FIH – First-inhuman *Testing for RECCE ® antibiotic Safety and Efficacy **Date submissions to regulators for permission to market 21 RECCE® 327 recognized as a Qualified Infectious Disease Product Qualified Infectious Disease Product (QIDP) designation is awarded if FDA considers the drug to treat “serious or life-threatening infections, including those caused by an antibacterial or antifungal resistant pathogen.” Legal status awarded under US Generating Antibiotic Incentives Now (GAIN) Act Labeled for fast track designation – speed the FDA’s review process 10 years market exclusivity, starting from the date of New Drug Application approval QIDP designated drugs to treat serious or life-threatening conditions and fill an unmet medical need Anticipated further five-year exclusivity under New Chemical Entity (NCE) policy* 50% loading… *A New Chemical Entity (NCE) can be defined as "a compound which, previously, hasn't been described in scientific literature” Australia’s TGA Special Access Scheme The Special Access Scheme (SAS) refers to arrangements that provide for the import and/or supply of an unapproved therapeutic good for a single patient, on a case by case basis. 3 categories Category A Category C • • Notification of use of specific therapeutic goods; allows certain types of health practitioners to supply therapeutic goods deemed to have an established history of use. Pathway that may be accessed by a prescribing medical practitioner or by a health practitioner acting on behalf of that medical practitioner, for a patient, who is seriously ill with a condition from which death is reasonably likely to occur within a matter of months, or from which premature death is reasonably likely to occur in the absence of early treatment. Category B • Application pathway that can be accessed by health practitioners if patients do not fit the Category A definition. Thank you John Prendergast, Ph. D. Chairman +61 2 8075 4585 recce.com.au References • O’Neill, J. (2016). Tackling drug-resistant infections globally: final report and recommendations. [online] The Review on Antimicrobial Resistance. • World Health Organization. (2019). Report: No Time to Wait: Securing the future from drug-resistant infections. • CDC (2013) Report: Antibiotic Resistance Threats in the United States. • OECD iLibrary. (2018). Stemming the Superbug Tide: Just A Few Dollars More. • Wanted: a reward for antibiotic development. (2018). Nature Biotechnology • Burnside, R. (2019). Spotting Sepsis Sooner. [online] The Pathologist. • ScienceDaily. (2018). Targeting sepsis, the leading cause of ICU deaths, with a nanocarrier-delivered microRNA. • Lim, E., Hollingsworth, K., Aribisala, B., Chen, M., Mathers, J. and Taylor, R. (2011). Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. • Kim, H. and Park, S. (2019). Sepsis: Early Recognition and Optimized Treatment. Tuberculosis and Respiratory Diseases, 82(1), p.6. • Sepsis Alliance. (2017). Sepsis Fact Sheet • O’Brien, J. (2015). Safe Healthcare Blog: The Cost of Sepsis. 26