Kazia Annual Report 2022

22 DIRECTORS’ REPORT Broad Clinical Program Ongoing Sponsor Phase Indication Registration PAXALISIB Global Coalition for Adaptive Research II/III Glioblastoma NCT03970447 Weill Cornell Medicine II Glioblastoma (with ketogenesis) NCT05183204 Alliance for Clinical Trials in Oncology II Brain metastases NCT03994796 Dana-Farber Cancer Institute II Breast cancer brain metastases (with Herceptin) NCT03765983 Dana-Farber Cancer Institute II Primary CNS Iymphoma NCT04906096 Pacific Pediatric Neuro-Oncology Consortium II DIPG (childhood brain cancer) NCT05009992 ST Jude Children’s Research Hospital I DIPG NCT03696355 Memorial Sloan Kettering Cancer Center I Brain metastases (with radiotherapy) NCT04192981 EVT801 Kazia Therapeutics I Advanced solid tumours NCT05114668 Research and development report Paxalisib The company’s lead development candidate is paxalisib (formerly known as GDC-0084), a small molecule, brain-penetrant inhibitor of the PI3K / Akt / mTor pathway, that is being developed as a potential therapy for glioblastoma (GBM), the most common and most aggressive form of primary brain tumour in adults, as well as other forms of brain cancer. Paxalisib is orally administered and is presented in a 15mg capsule formulation. The development candidate is the subject of IND 112,608 with the US FDA. Paxalisib Genentech Early Development Paxalisib was developed by Genentech, Inc (South San Francisco, California). Genentech has completed an extensive preclinical development program that provided convincing validation for paxalisib as a potential drug for brain cancer. Genentech also completed a phase I clinical trial in 47 patients with advanced recurrent grade III and grade IV glioma. The most common adverse events were oral mucositis and hyperglycemia. Per RANO criteria, 40% of patients exhibited a best observable response of stable disease, and 26% demonstrated a metabolic partial response on FDG-PET. Paxalisib Worldwide Exclusive License and Intellectual Property The company entered into a worldwide exclusive license for the asset in October 2016. Under the terms of the exclusive license agreement with Genentech, Kazia has the right to develop and commercialise the drug in all indications. Genentech is eligible to receive milestone income on commercialisation of the asset and royalties on net sales in any indication. Genentech has no right to direct the development of paxalisib, no right of approval for Kazia to sub-license, and no right of first refusal. Paxalisib is the subject of granted or pending composition-of-matter patents in all key territories. In general, the expiry of these patents is in December 2031. However, the company expects that it will be able to secure patent term extensions in the most substantial markets, including US, EU, China, Japan, and Korea, and that these extensions will provide effective protection until 2036. In addition, the company has recently received notice of grant for a patent protecting the manufacturing process associated with paxalisib, and this will provide an additional layer of protection in relevant territories until 2036. The development candidate was granted the International Non-Proprietary Name (INN) ‘paxalisib’ by the World Health Organisation in December 2019. This was confirmed as the United States Adopted Name (USAN) by the USAN Council in April 2020. Paxalisib Regulatory Activity Paxalisib was granted orphan drug designation (ODD) by FDA for glioblastoma in February 2018, and for the broader indication of glioma in August 2020. The development candidate also received Fast Track designation (FTD) for glioblastoma in August 2020, and Rare Pediatric Disease Designation (RPDD) for diffuse midline gliomas in August 2020. In addition, paxalisib was granted ODD by the US FDA for AT/RT, a rare pediatric brain cancer in June 2022 and RPDD in early July. Collectively, these special designations provide paxalisib with enhanced access to FDA, a waiver of PDUFA fees, a period of data exclusivity and, in the specific case of RPDD, the potential to secure a pediatric Priority Review Voucher (pPRV) should paxalisib be approved in either of these indications.

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