Antisense Therapeutics Limited announced that it intends to conduct a double-blind, placebo controlled six month dosing trial of ATL1102 followed by a six month open label phase (collectively the `Phase IIb' trial) in non-ambulant
boys with Duchenne's Muscular Dystrophy (DMD). The primary endpoint of PUL2.0 will be assessed after six months of treatment (versus 12 months in the Phase IIb/III study). This follows the Company's previous announcement on 13th July 2022 advising the re-evaluation of its clinical plans for ATL1102 in DMD to focus on the most effective deployment of existing cash reserves and to reduce upfront capital requirements. The Phase IIb study aims to enrol and randomize 45 non-ambulant boys with DMD. Following the initial six-month regimen of either placebo, 25 mg or 50 mg once weekly, participants will be invited into a further six-month open label follow-up treatment period in which all boys will be on active treatment (25 or 50mg). This additional time period will be used to demonstrate longevity of response as well as collect additional safety data and facilitate streamlining and de-risking of a Phase III study, the most expensive phase of the drug's development (i.e., may reduce the number of dosing arms). It is the Company's view that if results from the Phase IIb proved to be highly successful, it would then engage with Regulatory Agencies in relation to obtaining an accelerated approval for the unmet medical need of non-ambulant DMD patients. The Phase IIb trial design is modelled on the Phase IIb/III study outlined in Company's Paediatric Investigation Plan (PIP) (refer to following presentation for details on the Phase IIb trial design) and agreed by the European Medicines Agency (EMA) and The Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. The Phase IIb/III clinical trial application submitted in Germany (BfArM) is undergoing evaluation. With the regulatory focus now directed to submission of the Phase IIb trial applications, no additional Phase IIb/III trial submissions are planned at this time. The Company had previously announced that the next clinical milestone following Phase IIb/III trial initiation would have been a planned futility analysis after the first approximately 48 patients had completed their 6 months of dosing. This was to be a blinded analysis of the data by the Data Safety Monitoring Board and the outcome communicated as either a go or no-go decision to continue dosing as per protocol. No statistically analysed efficacy data would have been available at that time for reporting to the market. The revised trial design now to be conducted brings forward the definitive reporting of unblinded and statistically analysed trial data following the completion of the initial randomized blinded six-month dosing period. The Company believes that if successful, positive data from a controlled trial of ATL1102 in DMD patients could add substantial value to the program and, based on previous external feedback, garner serious partnering interest at an earlier point in the development program than previously anticipated. The revised trial design has allowed for the opportunity to incorporate Australian sites alongside key trial centres in Europe. This provides the important benefit of continuity of working with Australian investigators who were involved in the conduct of the previous successful Phase II clinical trial of ATL1102 in DMD. The addition of Australian trial sites is expected to facilitate a significantly greater proportion of the trial costs as being eligible for the R&D tax incentive cash rebate, which should have a material impact on reducing the cash requirements for the conduct of the study. The Company is able to leverage preparatory work undertaken for the Phase IIb/III trial including trial site and clinical investigator identification, selection and relationship development, clinical trial protocols and applications. The new strategy allows the Company to confirm drug efficacy through the rigor of the placebo-controlled trial design so as to allow for discussion with regulators for potential fast tracking into registration phase or potential accelerated approval, pending trial outcomes. The Company anticipates the first of the trial sites for the Phase IIb trial to be initiated in this calendar year. Based on current enrolment expectations, the last patient is projected to enter the trial in early 3Q'23 with the blinded phase of the trial to complete once the last patient has finished their six months of dosing. Reporting of the trial results would follow shortly thereafter. These revised clinical plans have substantially reduced the Company's budgeted trial costs, and with the expected additional R&D tax incentive rebates, the Company now estimates that it can fund both the Company and the trial into 4Q'23. The Company will move forward with the study initiation as outlined above. There is an approximately mid-single digit A$m additional future cash requirement to get to the time point of the reporting of trial results and the Company will update the market upon confirmation of the amount of such additional future funding and how it will be sourced.