Table of Contents As filed with the Securities and Exchange Commission on December 19, 2025 Registration No. 333-290598 UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 Amendment No. 1 to 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) (Primary Standard Industrial Classification Code Number) Australia 2834 Not applicable (I.R ...

Table of Contents As filed with the Securities and Exchange Commission on December 19, 2025 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) Registration No. 333- UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM F-1 Australia 2834 Not applicable (Primary Standard Industrial Classification Code Number) Three International Towers Le ...

Core Insights - Kazia Therapeutics announced promising data from the 2025 San Antonio Breast Cancer Symposium, highlighting the efficacy of paxalisib in treating HER2-positive metastatic breast cancer and triple-negative breast cancer (TNBC) [1][2]. Group 1: Clinical Findings - The first patient in the TNBC Phase 1b trial showed a 76% reduction in tumor volume and significant decreases in circulating tumor cells (CTC) and clusters [1]. - Paxalisib demonstrated a 42% reduction in single CTCs and a 78% reduction in CTC clusters, including large clusters associated with metastatic progression [6]. - Early biomarker data indicated that paxalisib has measurable biological activity after just one treatment cycle [5]. Group 2: Mechanistic Insights - Paxalisib disrupts aggressive CTC clusters and reverses resistance pathways, enhancing immune response by revitalizing exhausted T- and B-cell populations [2][8]. - The drug targets mesenchymal, metastatic, and epigenetically resistant CTC clusters, which are key drivers of metastasis [11]. - There is evidence of epigenetic reprogramming of CTCs towards less aggressive phenotypes, confirmed through digital pathology [7]. Group 3: Broader Implications - The findings suggest that paxalisib's effects are relevant across multiple breast cancer subtypes, not just TNBC, indicating a potential for broader therapeutic applications [9]. - Kazia's research points to a unifying biology across breast cancer subtypes, suggesting that paxalisib could address unmet needs in current treatment paradigms [9]. - The company is exploring combination therapies with pembrolizumab and PARP inhibitors, which may enhance treatment efficacy in various breast cancer contexts [12].

Core Insights - Kazia Therapeutics Limited announced a significant clinical milestone with a patient suffering from stage IV triple-negative breast cancer (TNBC) achieving an initial immune-complete response (iCR) after treatment with paxalisib, pembrolizumab (Keytruda®), and standard chemotherapy [1][5]. Clinical Developments - The patient experienced an 86% reduction in tumor burden after three weeks of treatment, with a PET/CT scan showing complete metabolic resolution of all previously identified lesions after approximately three months [2]. - Complete responses in stage IV metastatic TNBC are rare, with pembrolizumab monotherapy showing complete response rates of only 0.6–4% in previous studies [3]. - The initial iCR observed in this case is considered a highly unusual event, suggesting enhanced biological activity of the combination regimen [4]. Future Plans and Presentations - Kazia will present findings related to paxalisib and its NDL2 programs at the upcoming Brisbane Cancer Conference on November 27-28, 2025, and at the San Antonio Breast Cancer Symposium from December 10-14, 2025 [6][7]. - The company is advancing its NDL2 PD-L1 degrader program towards IND-enabling studies anticipated in early 2026, aiming to address resistance mechanisms in immuno-oncology [10]. - Kazia plans to request a Type C meeting with the FDA to discuss overall survival findings from clinical studies involving paxalisib in glioblastoma, aligning with the Project FrontRunner framework [11]. Regulatory and Compliance Updates - Kazia received a notice from Nasdaq regarding non-compliance with the Market Value of Listed Securities requirement, with a deadline to regain compliance by November 10, 2025 [12]. - Following the deadline, Kazia received a staff determination letter indicating non-compliance, but intends to request a hearing to address the situation [13].

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]