Full Press Release Details
Corporate Overview January 2025 NASDAQ: KZIA | X: @KaziaTx
Forward Looking Statements This presentation contains forward -looking
statements, which can generally be identified as such by the use of words such as "may," "will," "estimate," "future," "forward," "anticipate," "plan,"
"expect," "explore," "potential" or other similar words. Any statement describing Kazia's future plans, strategies, intentions, expectations, objectives, goals or prospects, and other statements that are not
historical facts, are also forward-looking statements, including, but not limited to, statements regarding: the timing for interim or final results and data related to Kazia's clinical and preclinical trials, or third-party trials evaluating
Kazia's product candidates, timing and plans with respect to enrolment of patients in Kazia's clinical and preclinical programs, the potential benefits of paxalisib and EVT801, the potential results of combination studies of paxalisib
and other collaborations, timing for any regulatory submissions or discussions with regulatory agencies, the potential market opportunity for paxalisib and EVT801, and Kazia's strategy and plans with respect to its business and programs. Such
statements are based on Kazia's expectations and projections about future events and future trends affecting its business and are subject to certain risks and uncertainties that could cause actual results to differ materially from those
anticipated in the forward-looking statements, including risks and uncertainties: associated with clinical and preclinical trials and product development, the risk that interim data may not be reflective of final data, related to regulatory
approvals, and related to the impact of global economic conditions, including disruptions in the banking industry. These and other risks and uncertainties are described more fully in Kazia's Annual Report, filed on Form 20-F with the SEC, and
in subsequent filings with the SEC. Kazia undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise, except as required under applicable law. You should not place
undue reliance on these forward-looking statements, which apply only as of the date of this presentation. Certain information contained in this presentation and statements made orally during this presentation relate to or are based on studies,
publications, surveys and other data obtained from third-party sources and our own internal estimates and research. While we believe these third-party studies, publications, surveys and other data to be reliable as of the date of this presentation,
it has not independently verified, and makes no representations as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, no independent source has evaluated the reasonableness or
accuracy of our internal estimates or research and no reliance should be made on any information or statements made in this presentation relating to or based on such internal estimates and research. 1
Company Overview A late-clinical-stage oncology drug development company
Corporate Highlights Licensing-driven business model Paxalisib EVT801 focused on high quality, differentiated clinical-stage assets sourced from Genentech (Paxalisib) and Sanofi / Brain-penetrant pan-PI3K / mTOR inhibitor Selective VEGFR3 inhibitor
Evotec (EVT801) Well-validated class with five current FDA-approved Designed to avoid off-target toxicity of older, non- therapies selective angiokinase inhibitors Only brain-penetrant PI3K inhibitor in development
Primarily targets lymphangiogenesis Lean virtual pharma model, with ~75% of cashflows applied directly to In development for multiple brain cancers Completed phase 1 for advanced solid tumors clinical trials Clinical trials ongoing in brain
metastases, childhood Preliminary data from adaptive, biomarker study at 2 brain cancer, glioblastoma, IDH-mutant glioma, and leading cancer sites in France presented at 2024 AACR primary CNS lymphoma Ovarian Cancer Research Symposium
Potential opportunities for non-dilutive Unique asset being evaluated in multiple trials Potential use in multiple solid tumor types income via additional partnering Multiple signals of clinical activity across several Potential
indications include: ovarian cancer, renal cell activity cancer types carcinoma, liver cancer, colon cancer, and sarcoma Fast Track, Orphan Drug, and Rare Pediatric Disease Designations from US FDA Rich potential commercial opportunity
Potential combination with immunotherapy Delisted from Australian Securities Glioblastoma alone sized at US$ 1.5 billion per annum Strong evidence of synergy in preclinical data supports Exchange (ASX) in Nov 2023; now
Commercial licensee in place for China potential of monotherapy or combination use solely listed on NASDAQ (KZIA) Licensee for intractable seizures in rare CNS diseases Advanced breast cancer trial launched 1Q CY2025 Phase 1 final data
anticipated CY2025 2
Pipeline - Two Differentiated Assets CY2025 positive clinical data
updates driving strong interest in oncology community licensed from: Paxalisib Investigational, small molecule, potent, brain-penetrant inhibitor of PI3K / mTOR Preclinical PHASE 1 PHASE 2 PHASE 3 MARKET Anticipated Collaborators / Sponsors Further
Glioblastoma & IDH-mutant glioma Update 3 studies Common primary brain cancer CY25 Further DIPG/Advanced Solid Tumors Update 3 studies Childhood brain cancer CY25 Further AT/RT Update Childhood brain cancer CY25 Further Data Brain Metastases 3
studies CY25 Cancer that spreads to brain from elsewhere Initial Data Primary CNS Lymphoma 1 study CY25 Form of non-Hodgkin's lymphoma Study Cancers Outside the CNS Launch 1 study Advanced Breast Cancer 1QCY25 licensed from: EVT801
Investigational, small molecule, highly specific inhibitor of VEGFR3 Final Data Advanced Solid Tumors CY25 Patients w/ highly treatment-resistant cancer IDH: Isocitrate dehydrogenase, DIPG: Diffuse Intrinsic Pontine Glioma, AT/RT: Atypical Teratoid
Rhabdoid Tumor, CNS: central nervous system, TNBC: triple negative breast cancer, VEGFR3: vascular endothelial growth factor receptor 3 3
Paxalisib Mechanism of Action Only brain-penetrant drug in development
within the dual PI3K/mTOR inhibitor class Paxalisib is the only brain-penetrant 1 The PI3K pathway is activated in 2 Five PI3K inhibitors have already 3 been approved by FDA dual PI3K/mTOR inhibitor in many forms of cancer development
Chronic lymphocytic Only 2% of small-molecule Glioblastoma 90% leukemia drugs are brain-penetrant Follicular lymphoma Breast 80% Follicular lymphoma Lung 75% Chronic lymphocytic leukemia Follicular lymphoma
Endometrial 60% Breast cancer Ovarian 60% Not able to cross blood-brain barrier Follicular lymphoma Able to cross blood-brain barrier Prostate 45% Source: Data on file 4
Paxalisib - Development History Growing Body of Clinical Evidence
Demonstrating Activity in GBM 2012-2015 February 2018 August 2019 7 January 2021 1 August 2022 Genentech Phase 1 clinical GDC-0084 awarded GDC-0084 becomes GBM AGILE Kazia provides progress paxalisib' with the granting pivotal study
update on the GBM study in 47 patients with Orphan Drug Designation of an International Non- commences Agile Pivotal Study advanced, high-grade by the US FDA in Proprietary Name (INN) by recruiting glioma. Study demonstrated glioblastoma the World
Health paxalisib arm a favourable safety profile Paxalisib does not and provided efficacy Organisation progress from stage 1 signals to stage 2 Patients enrolled in the first stage of the paxalisib arm to continue on treatment as per protocol, and
in follow-up until final data 10 July 2024 GBM AGILE Phase 2/3 trial data showed clinically meaningful improvement in a prespecified secondary analysis for overall survival in paxalisib-treated, newly diagnosed unmethylated March 2018 3 December
2021 patients with glioblastoma August 2020 2016 Early 2000's Kazia in-licenses Kazia commences Phase 2 study of paxalisib Paxalisib granted Genentech develops GDC-0084 from mono-therapy in 30 company-sponsored Breakthrough GDC-0084 as a
potential new Genentech following newly-diagnosed GBM Phase 2 clinical study Designation by the therapeutic for glioblastoma deep due diligence patients (NDU) provides of GDC-0084 as a first US FDA for which included Phase efficacy data with mOS of
line therapy in patients glioblastoma 1 study and animal 15.7 months with glioblastoma data 5
Glioblastoma Background & Market potential 6
Glioblastoma Overview The most aggressive malignant brain cancer Lung
Any age, No clear No clear but most improvement in cause common in prognosis for Breast or strong risk 60s 20 years factors 14 million cancer cases per annum Colon Five-year 3-4 months survival Prostate 3 - 5% Stomach Survival, (breast cancer:
if untreated 90%) Glioblastoma Multiforme 133,000 cases per annum worldwide "Even a few months increase in overall survival makes a huge difference for my patients, so efficacy of an GBM treatment market size approved therapeutic makes the
largest impact." (2022) US$ 1.5 billion US Neuro-Oncologist Source: Data on file. Market research performed 2021 7
Primary Market Research Outcomes Physicians indicated a 2-month minimum
and 12-month optimum increase in efficacy for newly diagnosed unmethylated GBM treatments, but adoption would be high regardless Key Takeaway Due to the high unmet need for a more efficacious therapy for Newly Diagnosed Unmethylated (NDU)
GBM patients, physicians indicated high adoption rates if Product X (paxalisib)* is approved by the FDA and achieved their suggested minimum mOS improvement of 2-3 months for newly diagnosed unmethylated GBM patients Source: Data on file.
Company-sponsored market research performed in 2021 * There is no guarantee that the Paxalisib data generated to date will support an FDA approval for commercial use 8
GBM AGILE study data - Primary and secondary analysis
Paxalisib and GBM-Agile International, multi-center, adaptive, phase
2/3 study evaluating promising therapeutics in patients with glioblastoma Completed Key Points Regorafenib Negative outcome Bayer (Sep 2022) A platform study', sponsored by GCAR run independently of Final Top Line 3 Paxalisib
Data individual companies, Kazia Therapeutics Economies of July 2024 designed to expedite the scale due to 2 approval of new drugs for multiple Completed VAL-083 glioblastoma Comparison participating Negative outcome Kintara Therapeutics against a
(Oct 2023) drugs allows for Multiple drugs are evaluated common control large site pool, in parallel, saving time and Ongoing arm reduces robust study Troriluzole Joined study in Jan money overall subject infrastructure, Biohaven
Pharmaceuticals 2022 numbers, saving and reduced cost time and cost Not a winner-takes-all' Ongoing (no arm vs. arm VT1021 approach: multiple drugs can Joined study in Jan comparison) Vigeo Therapeutics 2022 succeed
Cutting-edge adaptive Shared Control Arm design' avoids redundant recruitment, expediting path to market Adaptive study design limits Primary endpoint is overall 1 4 number of subjects required to survival (OS), the gold
demonstrate efficacy, eliminating standard' for approval of redundancy new cancer drugs GCAR: Global Coalition for Adaptive Research 10 Randomization
Paxalisib & GBM-Agile Study schema; Paxalisib arm (n=154) enrolled
Newly Diagnosed Unmethylated GBM patients (NDU) and Recurrent GBM patients Paxalisib Paxalisib stage 1 stage 2 Evaluate for graduation Evaluate for futility Study completed Paxalisib 12 months after enrolment stops last patient enrolled Time
adjusted controls (20 months) Concurrent controls (14 months) March 2021 July 2019 May 2022 May 2023 Cumulative control arm Important notes: The cumulative control arm is a combination of concurrent control patients and the "Time
adjusted control" patients that were enrolled in the study before the Paxalisib arm joined the study Bayesian Primary Analysis uses data from the cumulative control arm, while Prespecified Secondary Analysis uses data from the
concurrent control arm (i.e.. Compares paxalisib data with standard of care) All patients (Paxalisib, concurrent control, and cumulative control) were censored on May 2023 if still alive 11
Paxalisib & GBM-Agile Concurrent Control versus Cumulative Control
Cumulative controls: Patients randomized to control from the start of the entire GBM AGILE study (June 2019) to the date the last patient was randomized to paxalisib. Cumulative control patients are censored one year after the last patient was
enrolled in paxalisib arm (May 2023) Concurrent controls: Patients randomized to the control arm from the date of inclusion of paxalisib (April 2021) onto the study until the date the last patient was randomized to paxalisib. Concurrent control
patients are censored one year after the last patient was enrolled in paxalisib arm (May 2023) 12
Paxalisib and GBM-Agile Summary of OS in NDU Patients: Primary and
Secondary Analyses Prespecified Secondary OS analysis Primary OS analysis Main analysis Sensitivity analysis I Sensitivity analysis II Bayesian piecewise Frequentist methods and Frequentist methods and Frequentist methods and Method exponential
model standard Kaplan-Meier standard Kaplan-Meier standard Kaplan-Meier curve curve curve ITT ITT ITT ITT Population Paxalisib: 54 Paxalisib: 54 Paxalisib: 54 Paxalisib: 54 Number for Cumulative control: 75 Concurrent control: 46 Concurrent control:
46 Concurrent control: 46 analysis Paxalisib: 14.77 Paxalisib: 15.54 Paxalisib: 15.54 Paxalisib: 14.39 Median OS Cumulative control: Concurrent control: 11.89 Concurrent control: 11.70 Concurrent control: 11.89 13.84 0.89 (0.54, 1.38) 0.76 (0.45,
1.26) 0.67 (0.40, 1.13) 0.73 (0.45, 1.18) Hazard ratio 24% hazard reduction 33% hazard reduction 27% hazard reduction Important notes: Although the primary OS analysis did not meet statistical significance compared to the cumulative control arm, the
prespecified OS analyses were consistent with an encouraging 30% hazard ratio reduction An efficacy signal was not detected in the recurrent disease population [median OS of 9.69 months for concurrent SOC (n=113) versus 8.05 months for paxalisib
(n=100)] Source: Data on file 13
Paxalisib and GBM-Agile Treatment Emergent Adverse Events (TEAE) NDU
Patients Common Adverse Events Summary TEAEs reported by 20% of patients Concurrent In the paxalisib arm, the most frequently Paxalisib SOC: Preferred Term (N=52) (N=44) reported treatment emergent adverse Patients with any TEAE 50 (
96) 40 ( 91) events (TEAEs) were hyperglycemia Hyperglycemia 34 ( 65) 5 ( 11) Fatigue 31 ( 60) 21 ( 48) (65%); fatigue (60%); lymphocyte count Lymphocyte Count Decreased 26 ( 50) 8 ( 18) decreased (50%); white blood cell count White Blood Cell Count
Decreased 21 ( 40) 4 ( 9) Nausea 20 ( 38) 19 ( 43) decreased (40%), nausea (38%); Decreased Appetite 19 ( 37) 7 ( 16) decreased appetite and diarrhea (37% Diarrhea 19 ( 37) 2 ( 5) each); stomatitis (33%); constipation, Stomatitis 17 ( 33) 0 ( 0)
Constipation 16 ( 31) 17 ( 39) platelet count decreased, and rash Platelet Count Decreased 16 ( 31) 5 ( 11) maculopapular (31% each) Rash Maculo-Papular 16 ( 31) 1 ( 2) Alanine Aminotransferase Increased 15 ( 29) 4 ( 9) In the concurrent
standard of care (SOC) Neutrophil Count Decreased 15 ( 29) 7 ( 16) arm, the most frequently reported TEAEs Headache 13 ( 25) 6 ( 14) Alopecia 12 ( 23) 5 ( 11) were fatigue (48%), nausea (43%), Seizure 12 ( 23) 8 ( 18) constipation (39%), and
vomiting (25%) Anemia 11 ( 21) 5 ( 11) Aspartate Aminotransferase Increased 11 ( 21) 2 ( 5) Vomiting 11 ( 21) 11 ( 25) 14 Source: Data on file
Recap and next steps for Paxalisib in glioblastoma 15
Paxalisib in Glioblastoma Phase 2 Clinical Study Encouraging median OS
(mOS) in Newly Diagnosed Unmethylated GBM patients Overall Survival (OS) (n=30) Median OS: 15.7 months (11.1-19.1) Historical mOS for existing therapy: 12.7 months (Hegi et al. 2005) Note: Figures for existing therapy are for temozolomide, per Hegi
et al. (2005); No head-to-head studies have been published 16
Paxalisib in Glioblastoma Phase 2 Clinical Study Encouraging safety
profile Number of Patients at Any Dose (n=30) Experiencing AEs Possibly' or Likely' Related to Paxalisib (affecting 10% of patients) Term Gr 1 Gr 2 Gr 3 Gr 4 Total (%) Fatigue 3 13 2 18 (60%) Stomatitis 4 7 3 14
(47%) Decreased appetite 6 6 1 13 (43%) Hyperglycemia 3 1 6 2 12 (40%) Nausea 4 6 1 11 (37%) Rash, maculo-popular 1 1 7 9 (30%) Diarrhea 7 1 8 (27%) Vomiting 4 2 1 7 (23%) Rash 2 4 1 7 (23%) Neutrophils decreased 3 3 1 7 (23%) Platelets decreased 6
1 7 (23%) Weight decreased 5 2 7 (23%) Lymphocytes decreased 2 3 5 (17%) Dehydration 4 1 5 (17%) Dysgeusia 4 4 (13%) Cholesterol increased 4 4 (13%) ALT increased 1 2 3 (10%) Triglycerides increased 1 2 3 (10%) Malaise 2 1 3 (10%) 17
Paxalisib in Glioblastoma Consistent median Overall Survival data in
two studies of NDU glioblastoma patients Standard of Care data GBM AGILE study (left) Compelling Paxalisib data in NDU patients and STUPP historical controls (right) in NDU when compared to SOC patients Paxalisib in Paxalisib in Concurrent SOC STUPP
historical Kazia sponsored control GBM Agile GBM Agile phase 2 study (n=54) (N/A) (n=46) (n=30) Median OS: 12.7 Median OS: 15.54 Median OS: 15.7 Median OS: 11.9 months months* months* months *GBM Agile; Prespecified secondary analysis of median
Paxalisib in Newly Diagnosed Unmethylated GBM Next Steps 19
Childhood Brain Cancers 20
Paxalisib in Childhood Brain Cancer High unmet need especially in
patients with diffuse midline gliomas (DMGs) Brain cancer is the most common Brain cancer represents about one Prognosis of childhood brain 1 2 3 malignancy of childhood third of childhood cancer deaths cancer, especially DMGs, has improved little
in recent decades Source: CBTRUS; CDC; Ages 0-14 shown; Adamson PC, CA Cancer J Clin. 2015;65:212-220 21
Summary of Paxalisib in Childhood Brain Cancer Kazia is actively