Announcement PDF Antisense Therapeutics Limited Appendix 4E Preliminary Final Report Year Ended 30 June 2016 Antisense Therapeutics Limited 41 095 060 745 30 June 2016 (Previous corresponding year: 30 June 2015) Name of entity ABN Year Ended Results for Announcement to the Market The results of Antisense Therapeutics Limited for the Year Ended 30 June 2016 are as follows: Revenues Profit after tax attributable to members Net profit for the period attributable to members down down down 71.09% to 455.69% to 455.69% to 1,132,102 (2,514,443) (2,514,443) Explanation of Results The Company reported a loss for the full-year ended 30 June 2016 of $2,514,443 (30 June 2015: $706,918). The loss is after fully expensing all research and development costs. For further details relating to the current period’s results, refer to the Operations Report contained within this document. Dividends No dividends have been paid or declared by the Company since the beginning of the current reporting period. No dividends were paid for the previous reporting period. Net Tangible Assets Per Share Net tangible assets ($) Shares (No.) Net tangible assets per share (cents) Basic earnings/ (loss) per share Diluted earnings/ (loss) per share 2016 4,577,156 176,512,483 2.59 2015 7,091,598 176,512,483 4.02 2016 (1.43) (1.43) 2015 0.45 0.45 Status of Audit of Accounts The Appendix 4E is based on accounts which have been audited. The audit report is included within the financial report which accompanies this Appendix 4E. Antisense Therapeutics Limited ABN 41 095 060 745 Annual financial report for the Year Ended 30 June 2016 Contents to Annual Report Operations Report 1 Intellectual Property Report 6 Directors' Report 9 Auditor Independence Declaration 26 Corporate Governance 27 Statement of Profit or Loss and Other Comprehensive Income 34 Statement of Financial Position 35 Statement of Changes in Equity 36 Statement of Cash Flows 37 Notes to the Financial Statements 38 Directors' Declaration 62 Independent Auditor's Report 63 Corporate Information 65 Operations Report Overview of Company's Activities Antisense Therapeutics Limited (“the Company” or “Antisense Therapeutics”) continued its focus on advancing its antisense oligonucleotide products under development. The following report on operations details the research and development activities undertaken by the Company in the period. Antisense Therapeutics’ Mission Antisense Therapeutics’ mission is to develop and commercialise novel antisense therapeutics in-licensed from Isis Pharmaceuticals Inc (Isis), world leaders in antisense drug discovery and development. The Company’s Research and Development activities are focused on developing its pipeline of 2nd generation antisense drugs for diseases where there is a significant and acknowledged unmet medical need and where the antisense technology has the potential to provide compounds with competitive advantages over existing therapies or drugs in development for those diseases. Antisense Technology Antisense technology prevents the production of proteins involved in disease processes, which results in a therapeutic benefit to patients. Proteins are fundamental components of all living cells and include many types of molecules, such as enzymes, hormones and antibodies, necessary for carrying out the body’s functions. The overproduction or abnormal production of proteins is implicated or associated with many diseases. Antisense prevents undesirable protein production in disease. Antisense drugs are small (12-21 nucleotides) pieces of DNA or RNA that are chemically modified to create drugs. Conventional medicines typically bring about their desired therapeutic effect by binding to a target protein directly, to interfere with the action of the disease causing protein. Antisense drugs on the other hand, are rationally designed to bind to a specific messenger RNA sequence with extraordinary precision and thereby block or stop the production of the disease causing protein in the first instance. Ionis Strategic Partnership A fundamental element of the Antisense Therapeutics strategy is its access to leading antisense technology derived from its strategic partnership with Ionis, a relationship that has been operating for over 15 years. Using its proprietary antisense technology, Ionis has created a large pipeline of first-in-class or best-in-class drugs, with over a dozen drugs in mid- to late-stage development. Ionis has several partnerships with major pharmaceutical companies, including drug development collaborations with GSK, Roche, Bayer and Biogen. In 2013 Ionis gained US FDA approval of the world’s first systemically administered antisense drug mipomersen (KYNAMROTM). The collaboration with Ionis provides Antisense Therapeutics with access to Ionis’ antisense intellectual property, and development expertise to support development and commercialisation of the Company’s pipeline of antisense drugs. ATL1103 for Acromegaly, Diabetic Retinopathy and Nephropathy and Cancer ATL1103 is a second generation antisense drug designed to block growth hormone receptor (GHr) expression thereby reducing levels of the hormone insulin‐like growth factor‐I (IGF‐I) in the blood and is a potential treatment for diseases associated with excessive growth hormone action. By inhibiting GHr production, ATL1103 in turn reduces IGF‐I levels in the blood (serum). There are a number of diseases that are associated with excess GH and IGF‐I action. These diseases include acromegaly, an abnormal growth disorder of organs, face, hands and feet; diabetic retinopathy, a common disease of the eye and a major cause of blindness; diabetic nephropathy, a common disease of the kidney and major cause of kidney failure, and certain forms of cancer. ATL1103 is in clinical development as a treatment for acromegaly. Normalizing serum IGF‐I levels is the therapeutic goal in the treatment of acromegaly and reducing the effects of IGF‐I has a potential role in the treatment of diabetic retinopathy, nephropathy and certain forms of cancer. The Company conducted a successful Phase II trial of ATL1103 with the trial having met its primary efficacy endpoint by showing a statistically significant average reduction in sIGF-1 levels. The Company is presently conducting a high dose study of ATL1103 in adult patients with acromegaly in Australia. Antisense Therapeutics Limited 1 Operations Report (continued) In May 2015 the Company entered into an exclusive license agreement with Strongbridge Biopharma plc (formerly Cortendo AB). The agreement provided Strongbridge with development and commercialization rights to ATL1103 for endocrinology applications. Progress On 9 September the Company announced that dosing had commenced in its ATL1103 higher dose study with two patients having received their initial dose of ATL1103 at one of the Australian clinical trial sites. On 9th March 2016 the Company announced that Strongbridge had advised the Company of its intention to return ATL1103 to Antisense Therapeutics to enable Strongbridge to prioritise their resources and development work on other areas of their endocrine portfolio. On 9th May the Company provided an update on the ATL1103 higher dose study advising that dosing of three patients had been completed. Antisense Therapeutics reported that the patients had received all 26 doses of ATL1103 and that two patients had completed their 8 week follow up period. There were no reports of any serious adverse events related to dosing with ATL1103. The principal investigator of the study, Dr David Torpy, an endocrinologist at the Royal Adelaide Hospital, requested that the 3rd patient continue dosing with ATL1103 as they had responded well to treatment with ATL1103. A protocol amendment to the study was approved by the Adelaide Hospital Ethics Committee for ongoing dosing of this patient for an additional 12 weeks. ATL also advised that it anticipated submitting an amendment to the study protocol for approval to conduct an interim analysis on all 3 patients who had completed the initial 13 weeks of dosing. The interim analysis would assess the change (percentage reduction) from each of the 3 patient’s baseline (start of the study) sIGF-I levels to their levels post dosing. On 29th April the Company advised that it had reached an agreement with Strongbridge on the terms of the termination of the License Agreement for ATL1103. Under the Deed of Settlement, Termination and Transfer Strongbridge in return for the release of all obligations and potential liabilities under the License Agreement paid A$1million. Additionally all 15,025,075 shares owned by SB will be returned to the Company and in due course, cancelled in accordance with the Corporations Act procedures. As part of the termination agreement, Strongbridge also agreed to transfer to ANP: all of the nonGMP and GMP ATL1103 drug compound in Strongbridge’s possession; all data, reports, records, materials and information resulting from Strongbridge’s development activities; and all of its right, title and interest in and to all applications and approvals, including orphan drug designation, with respect to ATL1103. On 12th May Antisense Therapeutics announced that the US Food and Drug Administration (FDA) had granted Orphan Drug designation to the Company’s drug ATL1103 for treatment of Acromegaly. Orphan drug designation is granted by the FDA to drugs intended for the safe and effective treatment of rare diseases that affect fewer than 200,000 people in the U.S. The FDA provides incentives for companies to develop products for rare diseases which may include tax credits towards the cost of clinical trials, waiver of US prescription drug filing fees and orphan product exclusivity upon marketing authorisation, which means that the FDA may not approve any other applications to market the same drug for the same indication for seven years. On 28th June the Company announced that the European Commission had granted orphan medicinal product designation for the Company’s drug ATL1103 for the treatment of Acromegaly in the European Union (EU). The approval was based on the recommendation of a positive opinion from the European Medicines Agency (EMA) Committee for Orphan Medicinal Products (COMP). The COMP assessed the scientific documentation for ATL1103 against the criteria for orphan designation, with the COMP stating in their opinion that ATL1103 ”….will be of significant benefit to those affected by that condition”. Orphan designation in the EU enables sponsors to benefit from a number of incentives, including 10 years of market exclusivity once the medicine is on the market. During that exclusivity period, the EMA and the EU Member states shall not accept another application for a marketing authorization, for the same therapeutic indication, in respect of a similar medicinal product. Other benefits relate to assistance in developing clinical protocols, reduced fees, and access to the EU-funded research grants. Events After Balance Date On 27th July the Company announced that positive results were achieved from the Interim Analysis of ATL1103 Higher Dose Study in 3 acromegaly patients. Patients were dosed with ATL1103 at 300 mg twice weekly, capped at a weekly dose of 6 mg/kg. Antisense Therapeutics Limited 2 Operations Report (continued) sIGF-I levels were reduced in all 3 patients by an average of 18.6% (P = 0.06*) at week 14 (one week past the last dose which is the primary efficacy endpoint in the trial) and an average of 26.7% at week 13 being the last week of dosing (P = 0.04*). Normalisation of sIGF-I was achieved in one patient who received the highest dose per kg of bodyweight (6 mg/kg). This was consistent with the previous Phase II study of ATL1103 where patients who received more drug per kg of bodyweight had greater reductions in their sIGF-I. Reductions of sIGF-I to < 1.3 X ULN was achieved in the other two patients who had larger body weights (over 100kgs) and therefore received relatively lower doses of ATL1103 on a mg per kg basis (5.5 and 5.8 mg/kg/week) suggesting a therapeutic benefit in these 2 patients. ATL1103 appeared to be well-tolerated at the higher mg doses tested in the trial. No patient withdrew from the study and there were no serious adverse events reported. Mild injection site reactions - ISRs (redness, bruising, swelling and itching) were the most common adverse event reported, though these ISRs were of lesser severity and incidence when compared to the previous Phase II trial following the use of ISR mitigation strategies (e.g. icing of the injection site pre and post dosing and use of nanoneedles) recommended by Ionis. An elevated creatine kinase level had also been reported as adverse without apparent clinical sequelae. On 13th July the Company reported that advancements had been made in expanding the intellectual property (IP) portfolio protecting ATL1103. These advancements included both the grant of US patent 9,371,350 (14/137,852) entitled “Modulation of Growth Hormone Receptor Expression and insulin like growth factor expression” and NZ patent 629004 entitled “Combination Therapy comprising a growth hormone variant and an oligonucleotide targeted to the growth hormone receptor.” What is Acromegaly? Acromegaly is a serious chronic life threatening disease triggered by excess secretion of growth hormone (GH) by benign pituitary tumours. Oversupply of GH over stimulates liver, fat and kidney cells, through their GH receptors, to produce excess levels of Insulin-Like Growth Factor-I (IGF-I) in the blood manifesting in abnormal growth of the face, hands and feet, and enlargement of body organs including liver, kidney and heart. The primary treatments for acromegaly are to surgically remove the pituitary gland and/or drug therapy to normalize GH and serum IGF-I levels. In North America and Europe there are approximately 85,000 diagnosed acromegaly patients with about half requiring drug therapy. ATL1102 for Multiple Sclerosis (MS) ATL1102 is a second generation antisense inhibitor of CD49d, the alpha subunit of VLA-4 (Very Late Antigen-4). In inflammation, white blood cells (leukocytes) move out of the bloodstream into the inflamed tissue, for example, the Central Nervous System (CNS) in MS, and the lung airways in asthma. In MS, the inhibition of VLA-4 prevents white blood cells from entering the CNS, thereby reducing the severity of the disease and slowing its progression. VLA-4 is a clinically validated target in the treatment of MS. Antisense inhibition of VLA-4 has demonstrated positive effects in a number of animal models of inflammatory disease including MS. ATL1102 was shown to be highly effective in reducing MS lesions in a Phase IIa clinical trial in MS patients. The Phase IIa clinical trial data on ATL1102 has been published in the medical Journal Neurology (Limmroth et al, Neurology, 2014 Nov 11: 83(20: 1780-8). The Company previously reported that the US Food and Drug Administration (FDA) had responded affirmatively to the Company’s plan to submit a U.S. Investigational New Drug (IND) application for initiation of longer term Phase IIb human trials of ATL1102 for the treatment of MS and that supportive guidance had been obtained from the agency’s Pre-IND assessment of the development strategy for ATL1102, including potential design(s) for a Phase IIb study in MS patients. The Company also previously reported that it had signed a global agreement with innovative expanded access provider myTomorrows (Amsterdam, The Netherlands) to implement an Early Access Program (EAP) for ATL1102 for the potential treatment of MS patients who have no other treatment options in Europe. Progress In July 2015 the Company advised that it was exploring a number of value adding opportunities for ATL1102, including partnering for further clinical development in MS. The Company stated that in consultation with Destum Partners who are assisting Antisense Therapeutics in managing the partnering process for ATL1102, the Company is continuing to seek to partner ATL1102 but with increasing focus on ATL1102’s potential application in treating secondary progressive SP-MS where there is a high unmet medical need with few treatment options available and therefore may provide both increased and broader commercial appeal for ATL1102. Antisense Therapeutics Limited 3 Operations Report (continued) On 12th October the Company provided an update on the EAP advising that it had executed an agreement for the manufacture of an initial quantity of new ATL1102 drug compound with the new ATL1102 compound to be formulated into injectable product for potential use in the EAP. On 8th December the Company advised that the data from the testing of ATL1102 in an animal cancer research study would be presented at The American Society of Hematology (ASH) 57th Annual Meeting in Orlando Florida. The data from this pilot animal study, conducted at the Children’s Hospital Los Angeles (CHLA), showed that ATL1102, led to the rapid mobilization of acute myeloid leukemia (AML) cells to the peripheral blood in mice that had been engrafted with human AML cells. A new provisional patent application incorporating this data and covering ATL1102’s potential application in AML and other leukemias was filed by the Company. On 17th June the Company advised of its intention to submit an Investigational New Drug (IND) application for a Phase IIb trial in SP-MS patients with the Food and Drug Administration (FDA) by end 3’Q’2016 and that in parallel, the Company was actively pursuing potential non-dilutive funding sources and other development opportunities for Antisense Therapeutics to conduct the Phase IIb trial in the event the Company determines this to be the best path forward. In order to potentially help ATL access such grant funding, the Company advised it had executed an agreement with consulting firm FreeMind which specialises in assisting life science organisations secure non-dilutive funding from US Federal Agencies and Private Foundations. The Company also reported on the drug manufacture of ATL1102 for potential use in the EAP and that the compound had been manufactured and formulation of this material into injectable product was complete and undergoing testing to confirm it is ready for human clinical use. Antisense Therapeutics also advised that as a first step towards activating the EAP the Company was proposing to undertake a small investigative study of ATL1102 in relapsing SP-MS patients in Germany with Professor Volker Limmroth (Cologne City Hospital, Department of Neurology, Germany) and that with FreeMind’s assistance, the Company would also pursue potential grant funding for this study. What is Multiple Sclerosis? Multiple Sclerosis (MS) is a life-long, chronic disease that progressively destroys the central nervous system (CNS). It affects approximately 400,000 people in North America and more than 1 million worldwide and the current market for MS drugs is estimated at more than USD$12 billion. It is a disease that affects more women than men, with onset typically occurring between 20 and 40 years of age. Symptoms of MS may include vision problems, loss of balance, numbness, difficulty walking and paralysis. In Australia MS affects over 15,000 people and worldwide MS may affect more than one million people. ATL1102 for Asthma The Company has previously reported encouraging results achieved in an animal model of asthma with the inhaled form of an antisense compound targeting the VLA-4 molecule. Experimental studies showed that the delivery of an antisense drug against VLA-4 via inhalation to the lung significantly suppressed the key asthma indicators in allergen sensitized mice at very low inhaled doses, pointing to the potential application of ATL1102 as an inhaled treatment for asthma. The Company has conducted successful animal studies using inhaled ATL1102. Further development for the inhaled asthma application of ATL1102 would be undertaken with a partner. ATL1101 for Prostate Cancer ATL1101 is an antisense inhibitor of insulin like growth factor 1 receptor (IGF-Ir). IGF-Ir is one of the best known of a family of cell signalling molecules that are referred to as “anti-apoptotic”. These molecules prolong cell survival by inhibiting programmed cell death (apoptosis). Inhibition of cell survival molecules like IGF-Ir can render tumour cells more susceptible to cell death with cytotoxic (cell death inducing) drugs. Similar “chemosensitiser” therapeutic approaches targeting the IGF-Ir are under investigation in several large pharmaceutical companies, lending support to Antisense Theapeutic’s antisense-based strategy against the same target. In animal studies ATL1101 demonstrated its effectiveness in suppressing human prostate cancer tumour growth in mouse models of human prostate cancer and this data has been published (Furukawa J et al Prostate 2010 1:70(2): 2006-18). The Company has previously undertaken certain toxicology studies on ATL1101 that would potentially position the drug to move into a clinical study in patients with prostate cancer. Further clinical development of ATL1101 would be undertaken with a partner. R&D Tax Incentive During the year the Company received from the ATO a payment of $706,327 in relation to R&D expenditure incurred in the 30 June 2016 financial year. Antisense Therapeutics Limited 4 Operations Report (continued) Financial Position At 30 June 2016, the Company had cash reserves of $4,800,718 (2015: $6,829,605). Events After The Balance Sheet Date No matters or circumstances have arisen since the end of the reporting period, not otherwise disclosed in this report, which significantly affected, or may significantly affect, the operations of the Company, the result of those operations, or the state of affairs of the Company in subsequent financial periods. Antisense Therapeutics Limited 5 Intellectual Property Report Antisense Therapeutics currently has 9 patent families with 75 patents registered and 19 patent applications pending covering its three antisense drugs ATL1101, ATL1102, and ATL1103 and their applications. Antisense Therapeutics has also licensed from Isis Pharmaceuticals, 19 Isis proprietary patents and applications directed to the antisense drug platform together with rights to 11 other Isis manufacturing patent families. Since reporting on the status of the Company’s intellectual property portfolio in the 2015 Annual Report the Company has expanded its patent portfolio as follows: • • • A key US patent and a key European patent have been issued and registered; • US patent 9,371,530 covering ATL1103 and other antisense to human GHr reduction of GH Binding Protein, the soluble form of the GHr has been granted; • European 11194098.8 covering ATL1103 and other antisense to GHr reduction of sIGF-I has been granted and registered in 10 European countries; and • NZ patent 629004 covering ATL1103 used in combination with GHr antagonist Somavert has been granted to 2033. The International application PCT/Au2014/000613 has been filed to cover the use of ATL1103 used in combinations with somatostatin agonists to 2034; and Australian patent application 2011301712 has been accepted and US continuation application 15/046352 has been filed covering the use of ATL1102 reduction of circulating immune cells for the treatment of immunological disease to 2031. The progress outlined above has added significant value to an already extensive intellectual property portfolio. Key patents have been granted for all of the compounds in Antisense Therapeutics’ product pipeline that underpin Antisense Therapeutics commercialisation plans for its antisense drugs. Patent application or Country Patent No. ATL1103 Patent Portfolio ** USA 7,803,781 USA 8,299,039 USA 8,637,484 International Australia Canada Europe*** Europe*** Denmark Finland France Germany Italy Spain Sweden Switzerland The Netherlands United Kingdom Japan PCT/US2004/005896 2,004,217,508 2,517,101 04715642.7 11194098.7 Divisional of 04715642.7 Japan New Zealand USA USA USA USA 2006-508878 Divisional of 2006-508878 542,595 7,846,906 8,623,836 9,371,530 Continuation filed International Australian Canada PCT/AU2013/000095 2,013,214,698 2,863,499 Current Status Expiry Patent Registered Patent Registered Patent Registered National Phase applications Patent Registered Patent Registered Under Examination 2025* 2024* 2024* 2024* 2,024 2024* Regional Phase - granted Patent Registered 2024* Patent Registered 2024* Patent Registered 2024* Patent Registered 2024* Patent Registered 2024* Patent Registered 2024* Patent Registered 2024* Patent Registered 2024* Patent Registered 2024* Patent Registered 2024* Patent Registered 2024* Under Examination Patent Registered Patent Registered Patent Registered Patent Registered Filed National Phase Applications Under Examination Under Examination Antisense Therapeutics Limited 2024* 2024* 2024* 2024* 2024* 2024* 2,033 2,033 6 Intellectual Property Report (continued) Europe Japan New Zealand USA 13743020.3 2014-555044 629,004 14/376390 15/007,0011 Divisional USA filed International PCT/AU2014/000613 Australian 2,014,280,847 Canada 2,918,787 Europe 14810926.7 Japan 2016-518801 New Zealand 715,825 USA 14/897896 ATL1102 Patent Portfolio ** USA US 5968 826 USA US 6258 790 International PCT/US99/18796 Australia AU 759938 Canada 2,345,209 Japan 2000-574727 Japan 2006-000258 Europe EP1123414 Denmark DK/EP1123414 Finland EP(FI)1123414 France EP(FR)1123414 Germany DE69934998.2-08 Italy IT40051BE2007 Spain ES2279632 Sweden SE99942290.0 United Kingdom EP(UK)1123414 ATL1102 MS Patent Portfolio ** International Australia Canada Europe*** Denmark Finland France Germany Italy Spain Sweden Switzerland The Netherlands United Kingdom Europe*** Japan PCT/US2009/003760 AU 2009271678 2,728,562 09798248.2 Under Examination Under Examination Patent Registered Under Examination 2,033 2,033 2,033 2,033 Filed International Phase Filed Filed Filed Filed Filed Filed 2,033 2,034 2,034 2,034 2,034 2,034 2,034 Patent Registered 2018 ** Patent Registered 2018*/** National Phase applications Patent Registered 2019 * Patent Registered 2,019 Patent Registered 2019 * Patent Registered 2019 * Regional Phase - granted 2019 * Patent Registered 2019 * Patent Registered 2019 * Patent Registered 2019 * Patent Registered 2019 * Patent Registered 2019 * Patent Registered 2019 * Patent Registered 2019 * Patent Registered 2019 * National Phase applications Patent Registered 2029* Under Examination 2,029 Regional Phase - granted Patent Registered 2029* Patent Registered 2029* Patent Registered 2029* Patent Registered 2029* Patent Registered 2029* Patent Registered 2029* Patent Registered 2029* Patent Registered 2029* Patent Registered 2029* Patent Registered 2029* Under Examination 2029* Under Examination 2029* Divisional of 09798248.2 2011-516297 2014-208153 (Divisional Japan of 2011-5516297) Under Examination 2029* USA 8,415,314 Patent Registered 2029* USA 8,759,314 Patent Registered 2029* ATL1102 Methods of reducing circulating leukocytes / Methods of mobilizing AML cells**** Australia 2,011,301,712 Accepted 2031* Antisense Therapeutics Limited 7 Intellectual Property Report (continued) Canada 2,811,228 15/046352 (Continuation USA of 13/823101) Proviional**** 2,015,904,547 ATL1102 Inhaled Asthma Patent Portfolio ** International Australia Canada Europe Denmark Finland France Germany Italy Spain Sweden United Kingdom PCT AU 2005/001634 AU 2005327506 CA 2,584,614 EP1809302 DK/EP1809302T3 EP(FI)1809302 EP(FR)1809302 DE 60 2005 035 821.8 IT73129 BE/2012 ES2392449 SE1809302T3 EP(UK)1809302 Japan JP 2007-535071 New Zealand NZ 554277 USA US 8,765,700 ATL1101 Patent Portfolio ** International Australia Canada Europe Denmark Finland France Germany Italy Spain Sweden United Kingdom Japan New Zealand USA USA USA USA PCT/AU2004/00160 2,004,210,882 2,515,484 EP1597366 DK/EP1597366 EP(FI)1597366 EP(FR)1597366 DE1597366 IT1597366 ES1597366 SE1597366 EP(UK)1597366 4,753,863 541,637 US7468356 US8217017 9,084,770 US14/731203 (continuation of US12/578,471) Re-instated 2031* Filed Filed 2031* 2036* National Phase applications Patent Registered 2025* Under Examination 2,025 Regional Phase - granted Patent Registered 2025* Patent Registered 2025* Patent Registered 2025* Patent Registered 2025* Patent Registered 2025* Patent Registered 2025* Patent Registered 2025* Patent Registered 2025* Relying on data Abandoned exclusivity Patent Registered 2,025 Patent Registered 2028* National Phase applications Patent Registered Patent Registered 2024 * 2,024 Patent Registered Patent Registered Patent Registered Patent Registered Patent Registered Patent Registered Patent Registered Patent Registered Patent Registered Patent Registered Patent Registered Patent Registered Patent Registered 2024* 2024* 2024* 2024* 2024* 2024* 2024* 2024* 2024* 2,024 2025* 2025* 2,029 Under Examination 2,029 * Potential for up to 5 year extensions to the patent term once the product is a registered drug. ** ATL1101, ATL1102, ATL1103 are also protected internationally by other Isis proprietary antisense technology patents and applications to which Antisense Therapeutics has world-wide license including US7015315 to 2023. Antisense technology patents are potentially extendible for up to 5 years to 2028 in the US. *** Designates all member states of European patent countries including all extension states. Antisense Therapeutics Limited 8 Directors' report Directors The Board of Directors of Antisense Therapeutics Limited present their report on the consolidated entity (referred to hereafter as ‘the Company’) consisting of Antisense Therapeutics Limited and the entities it controlled at the end of, or during, the Year Ended 30 June 2016. In order to comply with the provisions of the Corporations Act 2001, the Board of Directors report as