Kazia Therapeutics Ltd · NASDAQ:KZIA
Kazia Therapeutics — Investor Presentation (June 2023)
39 slides from Kazia Therapeutics's investor presentation, Jun 26, 2023
Slide 1: A Diversified Oncology Drug Development Company
A Diversified Oncology Drug Development Company June 2023 ASX: KZA | NASDAQ: KZIA | Twitter: @KaziaTx
Slide 2: Forward-Looking Statements
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 describ
Slide 3: Company Overview
Company Overview A late-clinical-stage oncology drug development company Paxalisib EVT801 Company is dual-listed on NASDAQ (KZIA) and ASX (KZA) with market cap around US$ 27 million Brain-penetrant pan-PI3K / mTOR inhibitor Selective VEGFR3 inhibitor • Well-validated class with five FDA-approved the
Slide 4: Pipeline – Two Differentiated Assets
Pipeline – Two Differentiated Assets Lead asset provides a ‘pipeline in a molecule’ licensed from: Paxalisib Investigational, small molecule, potent, brain-penetrant inhibitor of PI3K / mTOR Preclinical PHASE 1 PHASE 2 PHASE 3 MARKET Anticipated Final Data Glioblastoma & IDH-mutant glioma 3 studies
Slide 5: History
Paxalisib History Asset licensed from Genentech in 2016 Kazia commences phase I clinical Kazia commences phase II Positive final data from phase II trial in diffuse midline glioma clinical trials in brain metastases glioblastoma study • Partnership with St Jude • Partnerships with leading US • Basis
Slide 6: CY2023 Milestones and Newsflow
CY2023 Milestones and Newsflow Multiple catalysts across two clinical programs Preclinical data for paxalisib in melanoma presented at AACR (2023) 1H CY2023 ü Preclinical data for paxalisib in DMG/DIPG & AT/RT presented at AACR (2023) 1H CY2023 ü Preliminary data from Kazia’s EVT801 phase I trial pr
Slide 7: Mechanism of Action
Paxalisib Mechanism of Action Only brain-penetrant drug in development within the PI3K inhibitor class 1 2 3 The PI3K pathway is activated in Five PI3K inhibitors have already Paxalisib is the only brain- been approved by FDA penetrant PI3K inhibitor many forms of cancer • Chronic lymphocytic Only 2
Slide 8: Glioblastoma
Glioblastoma 7
Slide 9: Glioblastoma: High unmet need, especially in MGMT unmethylated patients
Paxalisib in Glioblastoma High unmet need, especially in ‘MGMT unmethylated’ patients Standard of Care Debulking surgery Radiotherapy + Temozolomide (‘Stupp where possible temozolomide maintenance therapy Regimen’) 6 weeks 4w 6 x 28-day cycles Methylated MGMT Status ~35% of patients respond to temoz
Slide 10: Glioblastoma: Phase II PFS and OS
Paxalisib in Glioblastoma Phase II study suggests encouraging PFS and OS in context of current treatment landscape Progression-Free Survival (PFS) Overall Survival (OS) (n=30) (n=30) Median PFS: 8.6 months (6.6-11.0) Median OS: 15.7 months (11.1-19.1) Comparator figure for existing therapy: 5.3 mont
Slide 11: Glioblastoma: Phase II safety profile
Paxalisib in Glioblastoma Safety profile in Phase II study is favorable for a drug in advanced cancer 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
Slide 12: Glioblastoma: GBM AGILE adaptive multi-drug study
Paxalisib in Glioblastoma Adaptive multi-drug study, GBM AGILE, is ongoing Key Points Completed Regorafenib Negative outcome Bayer (Sep 22) • A ‘platform study’, sponsored by GCAR run independently of individual 3 Ongoing Paxalisib companies, designed to expedite the No graduation to Stage Kazia The
Slide 13: Glioblastoma: GBM AGILE interim analysis may have been premature
Paxalisib in Glioblastoma We believe GBM AGILE’s interim analysis may have been premature OVERALL STUDY DESIGN up to 150 patients 50 patients Stage 1 (‘Exploratory’) Stage 2 (‘Confirmatory’) Full FDA Approval Blinded Graduation Analysis POTENTIAL CONTRIBUTORY FACTORS TO PAXALISIB GRADUATION RESULT G
Slide 14: Glioblastoma: Cornell low-insulin study
Paxalisib in Glioblastoma Cornell study to investigate if low-insulin state enhances paxalisib activity OVERALL STUDY DESIGN Rationale of conducting the study • As with most PI3K inhibitors, Newly-diagnosed GBM hyperglycemia is a key toxicity (unmethylated MGMT) Ongoing Paxalisib + metformin Study a
Slide 15: Grade 2/3 IDH-Mutant Glioma: LUMOS Clinical Study
Paxalisib in Grade 2/3 IDH-Mutant Glioma LUMOS 2 Clinical Study • LUMOS2 is a prospective, multi-center, open-label, multi-arm, phase II, biomarker-directed, signal-seeking, umbrella clinical trial sponsored by University of Sydney – Adults with progressive grade 2/3, IDH-mutant glioma at recurrence
Slide 16: Childhood brain cancers
Childhood brain cancers 15
Slide 17: Summary of Paxalisib in Childhood Brain Cancer
Summary of Paxalisib in Childhood Brain Cancer Kazia has interest in at least three forms of childhood brain cancer Advanced Childhood Cancer Diffuse Midline Gliomas (DMG, Atypical Teratoid / (PI3K/mTOR activated) DIPG) Rhabdoid Tumors (AT/RT) Positive preclinical data as Positive preclinical data i
Slide 18: Childhood Brain Cancer: High unmet need
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 third Prognosis of childhood brain cancer, 1 2 3 malignancy of childhood of childhood cancer deaths especially DMGs, has im
Slide 19: Diffuse Midline Gliomas: Phase I trial in children
Paxalisib in Diffuse Midline Gliomas Phase I trial (St. Jude Children study) showed paxalisib was generally well tolerated in children OVERALL STUDY DESIGN Results from Phase I trial ✓ MTD of paxalisib has been established Newly diagnosed H3K27-mutant Newly-diagnosed DIPG DMG ✓ Paxalisib exhibited a
Slide 20: Diffuse Midline Gliomas: ONC201 and paxalisib synergy
Paxalisib in Diffuse Midline Gliomas Combination of ONC201 and paxalisib appeared synergistic in preclinical model The in vivo xenograft model demonstrated extended Addition of paxalisib rescued ONC201 from pAKT survival with the addition of paxalisib activation Jackson, et al. ONC201 in combination
Slide 21: Diffuse Midline Gliomas: PNOC022 study
Paxalisib in Diffuse Midline Gliomas Multi-arm, global site study, PNOC022, is underway OVERALL STUDY DESIGN Single agent in target validation Combination therapy in Three different cohorts and/or radiation phase maintenance phase TV: ONC201 Day -1 ONC201 once weekly + paxalisib Newly-diagnosed DMG
Slide 22: Diffuse Midline Gliomas: Compassionate use case studies
Paxalisib in Diffuse Midline Gliomas Case studies from compassionate use suggest activity Patient 1 Patient 2 • Commenced ONC201 + paxalisib immediately • Commenced ONC201 + paxalisib following following re-irradiation radiotherapy after diagnosis • At 5 months, MRI showed continued regression of •
Slide 23: Childhood Brain Cancer: OPTIMISE phase II study
Paxalisib in Childhood Brain Cancer Australian phase II study, OPTIMISE, anticipated enrollment in 2H 2023 The trial explores paxalisib in combination with existing chemotherapy agents for the treatment of children with high-risk malignancies, including (but not confined to) brain tumors 100 patient
Slide 24: Atypical Teratoid / Rhabdoid Tumor: Monotherapy activity
Paxalisib in Atypical Teratoid / Rhabdoid Tumor Monotherapy showed activity in vivo models Paxalisib monotherapy slowed tumor growth and extended survival High unmet need in mice bearing AT/RT orthotopic xenograft tumors BT12 CHLA06 • Atypical Teratoid /Rhabdoid Tumors 100 100 Control Control (AT/RT
Slide 25: Brain metastases
Brain metastases 24
Slide 26: Summary of Brain Metastases Clinical Studies Underway
Summary of Brain Metastases Clinical Studies Underway Registration Indication Phase N Status Sponsor Secondary (Metastatic) Brain Cancer Brain Metastases NCT04192981 I Up to 36 Recruiting (combination with radiotherapy) Breast Cancer Brain Metastases NCT03765983 II Up to 47 Recruiting (combination w
Slide 27: Brain Metastasis: PI3K pathway mutations
Paxalisib in Brain Metastasis PI3K pathway mutations are common in brain metastases and associated with a worse prognosis No Yes PIK3CA mutation Yes No CNS failure after SRS CNS failure after WBRT +PIK3CA mutations at 1 yr –PIK3CA mutations at 1 yr CNS failure after 48 (26-67) 30 (21-40) WBRT, % (95
Slide 28: Brain Metastasis: Phase I interim analysis
Paxalisib in Brain Metastasis Phase I trial’s interim analysis showed encouraging clinical activity of paxalisib in combination with radiation therapy OVERALL STUDY DESIGN Additional 12 patients 12 patients enrolled (9 evaluable, 3 did not complete protocol treatment) Stage 2 (‘Confirmatory’) Stage
Slide 29: Brain Metastasis: Phase II with trastuzumab
Paxalisib in Brain Metastasis Phase II trial to evaluate efficacy with trastuzumab in BCBM patients OVERALL STUDY DESIGN Rationale of conducting the study • The PI3K/Akt/mTOR is an Cohort A: Single-arm, two-stage important pathway in HER2- (~37 patients) positive breast cancer brain Ongoing Treatmen
Slide 30: Brain Metastasis: Genomically guided phase II study
Paxalisib in Brain Metastasis Genomically guided phase II study of multiple therapies in patients with brain metastases Rationale of conducting the study Abemaciclib • Approximately 30% of patients Eli Lilly Completed Breast cancer CDK mutation Graduation to Stage 2 with metastatic cancer develop br
Slide 31: Primary CNS lymphoma
Primary CNS lymphoma 30
Slide 32: Primary CNS lymphoma: Phase II trial
Paxalisib in Primary CNS lymphoma Phase II trial to evaluate safety and efficacy of paxalisib in PCNSL Preliminary results anticipated 2H23 OVERALL STUDY DESIGN Rationale of conducting the study • PCNSL is a subtype of lymphoma Ongoing 25 patients with recurrent Treatment: paxalisib Last patient in
Slide 33: Other solid tumors
Other solid tumors 32
Slide 34: Metastatic Melanoma: In vivo single agent activity
Paxalisib in Metastatic Melanoma Paxalisib showed potent single agent activity in an in vivo melanoma model Tumor Volume (Activity) Animal Weight (Tolerability) Survival (Efficacy) Source: AACR 2023 abstracts 33
Slide 35: Metastatic Melanoma: Potential in refractory melanoma
Paxalisib in Metastatic Melanoma Paxalisib showed potential as therapeutic strategy in refractory melanoma Paxalisib blocked proliferation in vitro (cell confluence assay) Unmet need • Melanoma is the 5th most common cancer for men & women in the U.S. • Approximately 50% of all melanomas harbor an a
Slide 36: Potential Paths to Registration
Paxalisib – Potential Paths to Registration Multiple opportunities to become a marketed product Diffuse Midline Gliomas Initial data from • Potential path to accelerated approval via phase II study ongoing phase II study with ONC201 • Existing Rare Pediatric Disease Designation 3Q CY2023 creates pos
Slide 37: Second Drug in Clinical Trials: EVT801
Second Drug in Clinical Trials EVT801 has potential in a wide range of cancers Future Phase II Future Pivotal Explore EVT801 as Study Study an anti-angiogenic therapy, likely in Monotherapy Monotherapy tumours that express high ONGOING One or more solid One or more solid VEGFR3 Phase I Study tumours
Slide 38: Board and Management Team
Board and Management Team Extensive experience in drug development Board of Directors Management Team Scientific Advisory Board Iain Ross Priscilla Brastianos, MD Dr John Friend Chairman of the Board Chief Executive Officer Bryce Carmine Karen Krumeich John de Groot, MD Independent Director Chief Fi
Slide 39: www.kaziatherapeutics.com [email protected]
www.kaziatherapeutics.com [email protected]
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