Core Viewpoint - Kazia Therapeutics Limited plans to hold a follow-up Type C meeting with the U.S. FDA to discuss overall survival findings in newly diagnosed glioblastoma patients treated with paxalisib and to seek feedback on a potential regulatory pathway aligned with the FDA's Project FrontRunner initiative [1][2]. Regulatory Strategy - The company aims to engage the FDA to determine if the overall survival data from newly diagnosed glioblastoma patients treated with paxalisib can support a conditional approval pathway [2]. - Kazia intends to propose the initiation of a post-approval, randomized Phase 3 confirmatory study prior to submitting the New Drug Application (NDA), ensuring alignment with the FDA's emphasis on overall survival as a primary endpoint [2][5]. Project FrontRunner Initiative - Project FrontRunner is an FDA initiative encouraging earlier approval of cancer drugs for advanced or metastatic diseases, rather than only for patients who have exhausted treatment options [3]. - Kazia plans to reference Project FrontRunner principles in its Type C briefing package, including an overall survival-driven confirmatory study plan for newly diagnosed glioblastoma [4]. Clinical Data - In a prespecified secondary analysis, the median overall survival for newly diagnosed unmethylated glioblastoma patients treated with paxalisib was reported as 15.54 months, compared to 11.89 months for the standard of care [4]. - The company emphasizes the importance of overall survival as a meaningful endpoint for patients and clinicians in the context of glioblastoma treatment [2][5]. Company Background - Kazia Therapeutics is an oncology-focused drug development company based in Sydney, Australia, with paxalisib as its lead program, targeting multiple forms of cancer [7]. - Paxalisib has undergone ten clinical trials and has received various designations from the FDA, including Orphan Drug Designation and Fast Track Designation for glioblastoma [7][8].

Core Insights - Kazia Therapeutics Limited reported an 86% reduction in tumor burden in a single patient with triple-negative breast cancer (TNBC) after three weeks of treatment with a combination of immunotherapy, chemotherapy, and the investigational drug paxalisib [1][2][3] Company Overview - Kazia Therapeutics is an oncology-focused drug development company based in Sydney, Australia, primarily developing paxalisib, a pan-PI3K/mTOR inhibitor [5] - The company has conducted multiple clinical trials involving paxalisib, including a completed Phase 2/3 study in glioblastoma and ongoing trials in advanced breast cancer and other cancers [5] Clinical Trial Information - Kazia is conducting a multi-centered Phase 1b study in Australia to evaluate the safety and preliminary anti-tumor activity of paxalisib in combination with Keytruda® and chemotherapy for advanced breast cancer, including TNBC [4] - The ongoing trial aims to assess the effects on circulating tumor cells and cluster dynamics to understand how paxalisib may enhance immunotherapy responsiveness [4] Patient Case Details - The patient treated under the expanded-access protocol was a 40+ year old female diagnosed with TNBC in April 2023, who had no residual cancer after initial treatments but later developed metastatic disease [2] - The treatment regimen included immunotherapy, chemotherapy, and paxalisib, leading to significant tumor regression [2][3]

Core Insights - Kazia Therapeutics Limited is participating in a fully funded Australian Medical Research Future Fund project aimed at improving treatment for diffuse midline glioma (DMG) through an AI-enabled clinical decision-making platform [1][2][3] Project Overview - The initiative, named DMG-ADAPTS, will last three years and focus on optimizing the sequencing and timing of targeted therapies for DMG, which is a severe pediatric cancer with a median survival of less than one year [2][3] - DMG accounts for up to 25% of childhood brain cancer deaths, highlighting the urgent need for effective treatments [3] Kazia's Role - Kazia will provide its investigational drug paxalisib, a dual PI3K/mTOR inhibitor, which is currently being evaluated in multiple clinical studies for various brain cancers [4][5] - Positive signals have been reported in the PNOC 022 study, indicating encouraging activity of paxalisib in pediatric brain cancer [4] Strategic Importance - The project aims to integrate AI with precision therapies to potentially revolutionize the management of aggressive tumors like DMG and DIPG [5][7] - Kazia's involvement underscores its commitment to innovative solutions for pediatric cancers, leveraging global research excellence [5][6] Future Directions - The project will also focus on developing a cloud-based AI platform that integrates multiomics and profiling to guide individualized therapy decisions in real time [7] - Establishing non-invasive biomarkers to anticipate resistance and inform timely therapeutic transitions is a key goal of the initiative [7]

Table of Contents As filed with the Securities and Exchange Commission on September 30, 2025 Registration No. 333- UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM F-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 KAZIA THERAPEUTICS LIMITED (Exact name of Registrant as specified in its charter) (State or other jurisdiction of incorporation or organization) If any of the securities being registered on this Form are to be offered on a delayed or continuous basis pursuant ...

Core Insights - Kazia Therapeutics Limited announced new findings from a collaborative research program indicating that paxalisib, an investigational PI3K–mTOR inhibitor, significantly reduces circulating tumor cells (CTCs) in Stage IV HER2-positive metastatic breast cancer patients [2][3] Company Overview - Kazia Therapeutics is an oncology-focused drug development company based in Sydney, Australia, with a lead program centered on paxalisib, which targets multiple forms of cancer [5] - The company has been developing paxalisib since it was licensed from Genentech in late 2016, and it has been involved in ten clinical trials for various cancers [5] Research Findings - In an ex vivo study, paxalisib monotherapy achieved a complete (100%) disruption of CTC clusters containing three or more cells, which are associated with metastasis and poor prognosis [2][6] - The results extend the understanding of paxalisib's potential beyond triple-negative breast cancer into HER2-positive disease, highlighting its ability to disrupt CTC clusters [3][6] - The findings complement ongoing Phase 1b trials in Stage IV triple-negative breast cancer, where significant reductions in CTCs and clusters have been observed [3] Future Directions - Detailed datasets regarding metastatic signatures and disrupted progenitor populations in Stage IV HER2-positive breast cancer have been submitted for presentation at an upcoming global oncology meeting in 2025 [4]

Group 1 - Kazia Therapeutics Limited has entered into a securities purchase agreement for a private placement of equity securities, raising approximately $2.0 million [1][2] - The securities in the PIPE are priced at a 5% premium to the closing price of Kazia's ADSs on July 31, 2025, and the transaction is expected to close on August 4, 2025 [1][2] - The net proceeds from the PIPE will be used to support the clinical development of lead programs, including paxalisib and EVT801, as well as for general corporate purposes [2][3] Group 2 - The CEO of Kazia Therapeutics expressed gratitude for investor support and highlighted the importance of the additional capital for advancing clinical-stage assets [3] - The securities sold in this PIPE are not registered under the Securities Act of 1933 and will require a shelf registration statement to be filed with the SEC within 60 days of closing [3][4] - Kazia Therapeutics is focused on developing innovative oncology treatments, with lead programs targeting brain cancer and advanced solid tumors [6]

Core Insights - Kazia Therapeutics has announced preliminary results from its Phase 1b trial involving Paxalisib, pembrolizumab, and standard chemotherapy, showing promising outcomes in a patient with metastatic triple-negative breast cancer [1][5][6] Patient Profile - The trial's first patient is a 61-year-old female diagnosed with metastatic triple-negative breast cancer, specifically localized to the left upper lobe of the lung [3] Clinical Significance of Patient Data - Circulating tumor cell (CTC) clusters are critical in metastasis and are associated with poor prognosis; they can resist apoptosis and evade immune detection [4] - The combination treatment of Paxalisib and immunotherapy resulted in a rapid reduction of both CTC numbers and clusters, which is not typically observed with chemotherapy or immunotherapy alone [5][6] Mechanistic Insights - The early data aligns with preclinical findings that suggest Paxalisib disrupts both single CTCs and multicellular clusters, indicating a mechanistic synergy [2][5] Next Steps - The company plans to explore the relationship between CTC kinetics and radiographic responses, continue patient enrollment, and conduct a comprehensive analysis of the immune microenvironment and CTC kinetics [7] - The investigational regimen includes Paxalisib, pembrolizumab, and chemotherapy, with results showing over 50% reduction in total CTC count and a notable decrease in CTC clusters [7] Company Overview - Kazia Therapeutics is an oncology-focused drug development company based in Sydney, Australia, with its lead program being Paxalisib, which targets the PI3K/Akt/mTOR pathway for various cancers [9]

Core Insights - Kazia Therapeutics Limited announced transformative preclinical research on paxalisib, highlighting its potential in treating triple-negative breast cancer (TNBC) [1][2] - The research indicates paxalisib can reprogram the tumor microenvironment and enhance immune response, showing synergy with immune checkpoint inhibitors [2][6] - The publication of this research supports the ongoing Phase 1b clinical trial of paxalisib in advanced breast cancer [4] Preclinical Research Findings - Conducted by Professor Sudha Rao at QIMR Berghofer Medical Research Institute, the study shows paxalisib's ability to remodel the TNBC tumor microenvironment, increasing CD4+ and CD8+ T cell infiltration and activation [2][6] - The combination of paxalisib with KEYTRUDA® (pembrolizumab) demonstrated significant antitumor activity, leading to robust tumor regression and prolonged survival in preclinical models [6] Clinical Development - Kazia has initiated a Phase 1b trial evaluating paxalisib in combination with checkpoint inhibitors and chemotherapy for advanced breast cancer, marking a significant step in clinical translation [5] - The company has previously conducted ten clinical trials for paxalisib, primarily focused on brain cancers, and is now expanding its application to solid tumors [5] Regulatory Designations - Paxalisib has received multiple designations from the FDA, including Orphan Drug Designation and Fast Track Designation for glioblastoma and other conditions, indicating its potential therapeutic value [5] Company Overview - Kazia Therapeutics is an oncology-focused drug development company based in Sydney, Australia, with a lead program centered on paxalisib, a PI3K/Akt/mTOR pathway inhibitor [5]

Core Insights - Kazia Therapeutics has initiated a Phase 1b clinical trial for paxalisib, targeting advanced breast cancer, marking a significant step in expanding its application beyond brain cancer [1][3] - The trial will evaluate paxalisib in combination with established therapies like olaparib and pembrolizumab, focusing on safety, tolerability, and preliminary efficacy [2][6] Study Design - The trial is a multi-center, open-label, randomized study with two treatment arms: Arm A will assess paxalisib with olaparib, while Arm B will combine paxalisib with pembrolizumab and standard chemotherapy [2][6] - Participants will undergo deep biomarker profiling to support future development and assess early clinical activity signals [2] Strategic Significance - The integration of paxalisib into combination regimens is part of Kazia's strategy to enhance value through differentiated science and collaborations [5] - The trial aims to provide insights into how paxalisib may enhance the effectiveness of immune checkpoint inhibitors and DNA repair-targeted therapies [6] Company Background - Kazia Therapeutics is an oncology-focused biotechnology company based in Sydney, Australia, with a lead program centered on paxalisib, a dual PI3K/mTOR inhibitor [5][7] - The company has previously conducted multiple clinical trials for paxalisib, including studies in glioblastoma and other brain cancers, with several trials showing promising interim data [7]

Core Insights - Kazia Therapeutics Limited has made significant advancements in its clinical programs and corporate strategy, particularly with its lead drug paxalisib, which is being evaluated for multiple cancer types [2][3] Pipeline - Paxalisib - The company received a research grant from The Michael J. Fox Foundation to explore paxalisib's potential as a treatment for Parkinson's disease, funding preclinical studies at The Hebrew University of Jerusalem [4] - A clinical trial has been launched to evaluate the combination of paxalisib with immunotherapy in patients with advanced breast cancer, specifically targeting triple-negative breast cancer [4] - Kazia has aligned with the FDA on the design of a pivotal phase 3 study for paxalisib in glioblastoma, which will enroll approximately 366 patients and compare paxalisib to standard of care [8] Pipeline - EVT801 - The last patient follow-up in a Phase 1 study of EVT801 for advanced solid tumors was completed, with final data expected in Q2 2025 [6] Corporate Developments - Kazia raised $3 million in capital during Q1 2025, including $1 million in non-dilutive funding [2][3] - The company received a notification from Nasdaq regarding its Market Value of Listed Securities falling below $35 million, with a compliance period until November 10, 2025 [9] - Kazia executed a reverse ADS split to maintain compliance with Nasdaq's minimum bid price requirement [9] - The company sold all intellectual property rights to Cantrixil for $1 million, as Vivesto decided not to pursue its development in ovarian cancer [9] - CEO Dr. John Friend purchased 8,000 ADSs at a split-adjusted price of $4.2465 per ADS [9]