Core Insights - Kazia Therapeutics has announced preclinical and translational data supporting NDL2, a first-in-class protein degrader targeting nuclear PD-L1, which is linked to immunotherapy resistance and metastatic progression [1][3][11] Group 1: Mechanism and Efficacy - NDL2 targets a newly discovered intracellular PD-L1 species that drives immune evasion and resistance to checkpoint inhibitors, differentiating itself from existing PD-1/PD-L1 antibodies [3][5] - In preclinical models of triple-negative breast cancer (TNBC), NDL2 reduced primary tumor volume by 49% as a monotherapy and by 73% in combination with anti-PD-1 therapy, with a 50% reduction in lung metastases in the combination setting [4][9] - NDL2 treatment led to a shift towards a less aggressive tumor state and enhanced anti-tumor immune response, including increased CD8+ T-cell infiltration and reduced markers of T-cell exhaustion [8][9] Group 2: Clinical Development and Strategic Positioning - Kazia plans to initiate first-in-human clinical trials for NDL2 in 2027, focusing on immunotherapy-refractory solid tumors where PD-L1 biology and resistance are well established [13][14] - The company is advancing IND-enabling studies and will present data at an oncology-focused scientific meeting in the second quarter of 2026 [14][15] - The strategic focus on protein degradation aligns with industry trends, as large pharmaceutical companies are increasingly investing in degrader technologies to tackle therapeutic resistance [10][16] Group 3: Translational Evidence and Biomarkers - Research indicates that nuclear PD-L1 is enriched in resistant and metastatic tumors, including TNBC, melanoma, non-small cell lung cancer (NSCLC), and colorectal cancer [6][7] - Longitudinal liquid biopsy analysis showed that reductions in nuclear PD-L1 could serve as an early predictive biomarker of treatment benefit [7]

Core Insights - Kazia Therapeutics provided a clinical update on its Phase 1b study evaluating paxalisib in combination with pembrolizumab and chemotherapy for late-stage metastatic triple-negative breast cancer (TNBC) [1] Clinical Highlights - The Phase 1b trial is a multi-center, open-label, randomized study initiated in June 2025, focusing on the safety, tolerability, and preliminary clinical activity of paxalisib in advanced breast cancer patients [4] - Three patients with metastatic TNBC have shown meaningful clinical responses, including two partial responses and one confirmed complete metabolic response [2][9] Patient Responses - Patient 1, a 61-year-old female, achieved a partial response after nine cycles of treatment with paxalisib, pembrolizumab, and chemotherapy [5] - Patient 2, a 47-year-old female, demonstrated a partial response with complete resolution of a target lung lesion after three treatment cycles [6] - Patient 3, a 44-year-old female, achieved a confirmed complete metabolic response after re-treatment with paxalisib and pembrolizumab [7] Safety and Tolerability - Paxalisib has been generally well tolerated, with approximately 75% of adverse events assessed as unlikely or unrelated to the drug [8] - Most adverse events were mild to moderate, with only one case of Grade 1 hyperglycemia reported [8] Future Plans - Kazia plans to activate two additional clinical sites by April 2026 and aims to enroll twelve TNBC patients by the end of 2026, with topline data expected in early 2027 [9] - The company is also exploring paxalisib in other breast cancer populations, including earlier-stage TNBC and hormone receptor-positive, HER2-negative breast cancer [10] Executive Commentary - Dr. John Friend, CEO of Kazia Therapeutics, expressed optimism about the preliminary results, highlighting the rarity of confirmed complete responses in metastatic TNBC and the potential of paxalisib to enhance existing immunotherapy regimens [11]

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 private placement of approximately $50 million in shares and prefunded warrants, priced at $5 per ADS, with each ADS representing 500 ordinary shares [1] - The net proceeds are expected to be around $46.5 million, which will be utilized for the clinical development of paxalisib, advancing the PD-L1 degrader program, and general corporate purposes [2] - The company anticipates that the net proceeds from the PIPE, along with existing cash, will extend its cash runway into the second half of 2028 [3] Clinical Developments - Kazia Therapeutics reported an initial immune-complete response in a patient with stage IV triple-negative breast cancer treated with paxalisib, pembrolizumab, and standard chemotherapy under an FDA-authorized protocol [3] - After approximately three months of treatment, a PET/CT scan indicated that all previously identified lesions had completely resolved metabolically in the same patient [4] Stock Performance and Predictions - The average 1-year price target for Kazia Therapeutics shares is $20.0, indicating an expected upside of 104.12% [5] - No analysts have bearish recommendations for Kazia Therapeutics, while one analyst has a bullish rating [6] - As of the last check, KZIA stock is up 10.49% at $10.11 [6]

Energy Sector - Constellation secured a $1 billion loan from the U.S. Department of Energy to advance its Crane Clean Energy Center, which aims to bring 835 MW of new baseload nuclear power online [2][3] - The funding is part of the Energy Dominance Financing Program and is expected to lower Constellation's cost of capital, supporting infrastructure for the digital economy and increasing power capacity for AI workloads [3][4] Technology Sector - Adobe announced its acquisition of Semrush for $12.00 per share, valuing the company at approximately $1.9 billion, marking a significant move in digital marketing [10][20] - The acquisition aims to enhance Adobe's customer experience orchestration capabilities in the context of generative AI, addressing challenges in brand visibility and engagement [11][12] Oncology Sector - Kazia Therapeutics reported a patient with stage IV triple-negative breast cancer achieved an initial immune-complete response under an expanded-access protocol, a notable outcome given the low response rates in such cases [6][7] - The company highlighted its plans for upcoming presentations and progress in its drug development pipeline, including a request for a Type C meeting with the FDA [9]

Core Insights - Kazia Therapeutics Limited (NASDAQ: KZIA) shares surged 51.74% in after-hours trading to $8.74 following the release of promising clinical data on metastatic triple-negative breast cancer (TNBC) [1][2] Clinical Data - A patient with stage IV TNBC achieved an immune-complete response under an FDA-approved single-patient expanded access protocol, combining paxalisib with pembrolizumab (Keytruda) and standard chemotherapy [2] - After three months of treatment, a PET/CT scan indicated that all previously identified lesions had completely resolved metabolically, with the patient's tumor burden reduced by 86% after just three weeks of treatment [3] Rare Clinical Outcome - Complete responses in stage IV metastatic TNBC are extremely rare, and the initial complete response observed is considered an encouraging clinical finding by the CEO of Kazia Therapeutics [4] Upcoming Scientific Presentations - Kazia announced acceptance of two presentations at the 2025 San Antonio Breast Cancer Symposium, focusing on a Phase 1b study of paxalisib combined with olaparib or pembrolizumab/chemotherapy, and liquid biopsy tracking of PI3K-mTOR residual disease signatures in metastatic breast cancer [5] Nasdaq Compliance Concerns - Kazia Therapeutics received a staff determination letter from Nasdaq indicating it did not meet the $35 million minimum Market Value of Listed Securities requirement by the Nov. 10 deadline, and plans to request a hearing to address this issue [6] Stock Performance - Year-to-date, Kazia Therapeutics has fallen 34.02%, but has risen 58.24% over the past six months, with a market capitalization of $9.56 million and shares trading between $2.86 and $30.05 over the past year [7] - The stock closed at $5.76, down 5.29% in the regular session, but has a positive price trend across all time frames according to Benzinga Edge Stock Rankings [8]

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].