Kazia Therapeutics Limited operates as an oncology-focused biotechnology company.
The company has a portfolio of development candidates, diversified across various technologies, with the potential to yield agents in a range of oncology indications.
Paxalisib
The company’s lead development candidate is paxalisib, a small molecule, brain-penetrant inhibitor of the phosphoinositide-3-kinase (PI3K)/Akt/mammalian target of rapamycin mTor pathway, which is being developed as a potential therapy for...
Kazia Therapeutics Limited operates as an oncology-focused biotechnology company.
The company has a portfolio of development candidates, diversified across various technologies, with the potential to yield agents in a range of oncology indications.
Paxalisib
The company’s lead development candidate is paxalisib, a small molecule, brain-penetrant inhibitor of the phosphoinositide-3-kinase (PI3K)/Akt/mammalian target of rapamycin mTor pathway, which is being developed as a potential therapy for glioblastoma (GBM), a common 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 investigational new drug application 112,608 with the U.S. Food and Drug Administration (FDA).
Paxalisib was developed by Genentech, Inc (South San Francisco, California) and the company entered into a worldwide exclusive license for the asset in October 2016. Prior to this transaction, Genentech had completed a preclinical development program that provided validation for paxalisib as a potential drug for brain cancer. Genentech also completed a phase I clinical trial in patients with advanced recurrent grade III and grade IV glioma (NCT01547546).
The development candidate was granted the International Non-Proprietary Name ‘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 is a potent and selective inhibitor of all four isoforms of phosphoinositide-3-kinase (PI3K) and a moderate inhibitor of the mammalian target of rapamycin (mTOR). Paxalisib, by contrast, inhibits a biochemical control signal, and is therefore associated with a different resistance and toxicity profile.
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 focuses that it would be able to secure patent term extensions in the majority substantial markets, including the U.S., European Union, China, Japan, and Korea, and that these extensions would provide protection until 2036. In addition, the company has received notice of grant for a patent protecting the manufacturing process associated with paxalisib, and this would provide an additional layer of protection in relevant territories until 2036.
Paxalisib was granted orphan drug designation by FDA for glioblastoma in February 2018, and for the major indication of glioma in August 2020. The development candidate also received Fast Track designation for glioblastoma in August 2020, and Rare Pediatric Disease Designation (RPDD) for diffuse midline gliomas in August 2020. Collectively, these special designations provide paxalisib with improved access to FDA, a waiver of the Prescription Drug User Fee Act fees, a period of data exclusivity and, in the specific case of RPDD, the potential to secure a pediatric Priority Review Voucher should paxalisib be approved in this indication.
Phase II Clinical Trial in Newly Diagnosed Glioblastoma with Unmethylated MGMT Status (NCT03522298)
A company-sponsored phase II study of paxalisib in newly diagnosed patients with unmethylated MGMT promotor status (NCT03522298) remains ongoing. In November 2020, an interim analysis was presented at the Society for Neuro-Oncology (SNO) Annual Meeting. In April 2021, the company presented additional interim data focusing on pharmacokinetics at the American Association for Cancer Research Annual Meeting. This data supported 60mg as the go-forward dose, and suggested no significant food effect, allowing for both fed and fasted administration in future studies.
In May 2021, the last patient in the phase II study experienced disease progression and came off study drug, after some 2.3 years of treatment. The study is in survival follow-up, with final data expected by end of CY2021.
Phase II/III Clinical Trial in Glioblastoma (GBM AGILE) (NCT03970447)
Paxalisib commenced recruitment to GBM AGILE (NCT03970447), a phase II/III adaptive clinical trial in glioblastoma, in January 2021. GBM AGILE is sponsored by the Global Coalition for Adaptive Research, a U.S.-based 501(3) non-profit organization dedicated to advancing the development of new therapies via the application of statistical methodologies. The study is a platform study, or master protocol study, in which multiple experimental agents are evaluated in parallel, and are compared against a shared control arm. GBM AGILE uses an adaptive Bayesian statistical design to ensure that the number of patients required to reach a definitive answer are enrolled. Paxalisib is participating in the first and third of these groups but would not examine patients with methylated MGMT promotor status in this study.
As of 30 June 2021, three experimental agents are enrolling patients in GBM AGILE: Bayer’s regorafenib, the company’s paxalisib, and VAL-083, manufactured by Kintara Therapeutics. The study has screened various patients, and various study sites are open to the paxalisib arm, with expected to open during 2H CY2021.
GBM AGILE is intended to serve as the registration study for paxalisib in glioblastoma. The study has been designed with registrational intent, and FDA has indicated that it considers the study suitable for this purpose.
Phase II Study in Glioblastoma in Combination with Ketogenesis
In June 2021, the company entered into an agreement with the Joan & Sanford I Weill Medical College of Cornell University in New York, NY, known as Weill Cornell Medicine, for an investigator-initiated phase II clinical trial combining paxalisib with ketogenesis in patients with newly-diagnosed and recurrent glioblastoma. In addition to the general interest in ketogenic diets as a potential adjunct to treatment for various forms of cancer, research by Professor Lew Cantley and colleagues has demonstrated the potential for insulin to antagonise PI3K inhibition. Administering a PI3K inhibitor in the context of minimal insulin secretion should allow the drug to achieve its full potential, and a combination of ketogenic diet and metformin would be used in this study to achieve a hypoinsulinaemic state. The study is focused to commence recruitment during 2H CY2021.
Phase I Study in Diffuse Intrinsic Pontine Glioma (DIPG) (NCT03696355)
An investigator-initiated phase I study of paxalisib in children with DIPG and other diffuse midline gliomas (DMGs) (NCT03696355), sponsored by St Jude Children’s Research Hospital in Memphis, TN, reported initial interim data in an oral presentation at the SNO Annual Meeting in November 2020. The study met its primary focus and determined a maximum tolerated dose for paediatric use of 27 mg/m2. The safety profile and pharmacokinetics were consistent with the adult data. As of 30 June 2021, various patients remain in survival follow-up, and final data is expected during FY2022.
Phase II Study in Diffuse Intrinsic Pontine Glioma (DIPG) (NCT05009992)
In December 2020, the company entered into a letter of intent with the Pacific Pediatric Neuro-Oncology Consortium to execute an investigator-initiated phase II adaptive study of paxalisib in patients with DIPG and other DMGs, a group, which collectively constitutes one of the aggressive childhood cancers. The study would explore paxalisib in combination with ONC-201, a small-molecule investigational new drug, which targets dopamine receptor D2, and which is manufactured by Oncoceutics, Inc, a wholly-owned subsidiary of Chimerix, Inc. The study is expected to commence recruitment in 2H CY2021.
Phase II Study in Primary CNS Lymphoma (PCNSL) (NCT04906096)
In September 2020, the company signed an agreement with Dana-Farber Cancer Institute in Boston, MA, for an investigator-initiated phase II clinical study of paxalisib in patients with primary CNS lymphoma (PCNSL) (NCT04906096). This study commenced recruitment in June 2021. Four of the five FDA-approved PI3K inhibitors are indicated for various forms of lymphoma, so this is considered a high-potential indication for paxalisib. The brain-penetrant qualities of paxalisib make it suitable for investigation in this patient group. The study is expected to run for approximately two years. The study commenced recruitment in June 2021.
Phase I Study in Brain Metastases in Combination with Radiotherapy (NCT04192981)
This study is expected to provide initial interim data during FY2022.
Phase II Study in HER2+ Breast Cancer Brain Metastases in Combination with Trastuzumab (NCT03765983)
This study is expected to provide initial interim data during FY2022.
Phase II Genomically-Guided Study in Brain Metastases (NCT03994796)
The Alliance for Clinical Trials in Oncology is sponsoring a phase II multi-drug study of multiple agents in the treatment of brain metastases from any primary tumour (NCT03994796). The study establishes a genomic profile for patients at entry and then assigns them, on the basis of the predominant mutational profile in their tumour, to receive either abemaciclib (CDK4/6 mutations), entrectanib (ROS/Trk mutations), or paxalisib (PI3K mutations). This study is expected to provide initial interim data during FY2022.
EVT801
The company’s second development candidate is EVT801, a small-molecule selective inhibitor of vascular endothelial growth factor receptor 3. EVT801 was originally discovered by Sanofi SA and was licensed to Evotec SE as part of a major transaction. Evotec conducted a program of preclinical development, which showed compelling evidence of activity in a range of animal models. The drug was licensed to the company in April 2021.
EVT801 is protected by granted or pending composition-of-matter patents in all key territories, with exclusivity generally through to the early 2030s.
The company has initiated work on a phase I clinical trial of EVT801, which would seek to explore both of these mechanisms (inhibition of lymphangiogenesis and modulation of tumour immune micro-environment), as well as provide critical information regarding the safety, tolerability, and pharmacokinetics of the drug. The planned phase I study would be initiated at two trial sites in France and would focus to recruit patients with advanced cancer. The study is expected to commence recruitment by the end of CY2021.
In parallel, the company continues to explore licensing and partnering opportunities with other companies that have the potential to effect further refinements in the scope of its business.
Research and Development
In the year ended year ended June 30, 2021, the company spent a total of A$14.5 million on company-sponsored research and development activities.
History
The company was founded in 1994. The company was incorporated in 1994. It was formerly known as Novogen Limited and changed its name to Kazia Therapeutics Limited in 2017.
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