Kazia Therapeutics Ltd · NASDAQ:KZIA
Kazia Therapeutics — Technical Presentation (June 2022)
27 slides from Kazia Therapeutics's technical presentation, Jun 23, 2022
Slide 1: Paxalisib in Childhood Brain Cancer Educational Webinar
Paxalisib in Childhood Brain Cancer Educational Webinar 22 June 2022 ASX: KZA | NASDAQ: KZIA | Twitter: @KaziaTx
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains forward-looking statements within the meaning of the safe-harbor provisions of the Private Securities Litigation Reform Act of 1995. Such statements involve substantial risks and uncertainties, not all of which may be known at the time. All state
Slide 3: Webinar speakers
Dr James Garner Associate Professor Matt Dun Dr John Friend Chief Medical Officer Chief Executive Officer Group Leader, Cancer Research Signalling Group Kazia Therapeutics Limited Hunter Medical Research Institute Kazia Therapeutics Limited University of Newcastle, Australia 2
Slide 4: Agenda
Agenda • Strategic considerations in development of drugs for childhood brain cancer Dr James Garner • Emerging data for paxalisib in DIPG Associate Professor Matt Dun • Emerging data for paxalisib in AT/RT Dr John Friend • Overview of Kazia’s childhood brain cancer program Dr John Friend • Closing
Slide 5: Agenda
Agenda • Strategic considerations in development of drugs for childhood brain cancer Dr James Garner • Emerging data for paxalisib in DIPG Associate Professor Matt Dun • Emerging data for paxalisib in AT/RT Dr John Friend • Overview of Kazia’s childhood brain cancer program Dr John Friend • Closing
Slide 6: Childhood brain cancer is a critical element of the paxalisib development program
Childhood brain cancer is emerging as a critical element of the paxalisib development program licensed from: Paxalisib Small molecule, highly potent, brain-penetrant inhibitor of PI3K / mTOR PRECLIN. PHASE 1 PHASE 2 PHASE 3 MARKET Glioblastoma Most common primary brain cancer DIPG Highly aggressive
Slide 7: Brain cancer is the most common malignancy of childhood
Brain cancer is the most common malignancy of childhood, representing about one third of childhood cancer deaths Average Annual Age-Adjusted Incidence Mortality (cases / 100,000 people; 2014-2018) (estimated absolute number of cases in US; 2020) 7 Others, 134 5.85 6 Lymphoma, 15 Brain & Other CNS, 4
Slide 8: Prognosis of childhood brain cancer has improved little in recent decades
Prognosis of childhood brain cancer, especially DMGs, has improved little in recent decades 100% FDA-Approved Drug Therapies 1960 Diffuse Midline Nil Gliomas 2000 Atypical Teratoid / Nil Rhabdoid Tumors Medulloblastoma Nil 50% 0% Acute Acute Non-Hodgkins Wilms Brain Stem Lymphoblastic Myeloid Lympho
Slide 9: Childhood brain cancer comprises a diverse range of pathologies
Childhood brain cancer comprises a diverse range of pathologies Average Annual Number of Cases, US 5,095 2,917 100% Others Germ Cell Tumors 90% Medulloblastoma Embryonal Non- 80% Tumors Malignant 70% Atypical Rhabdoid / Teratoid Tumors (AT/RT) 60% 50% 40% Glioma Diffuse Midline Gliomas (DMGs) (inclu
Slide 10: Childhood cancers are becoming an area of focus for the pharmaceutical industry
Childhood cancers are becoming an area of focus for the pharmaceutical industry Pediatric Cancer Drug Approvals by FDA, 2010-2020 R/R AML CML / Ph+ ALL SEGA R/R B-ALL R/R B-ALL CML Trk+ Tumors Sarcoma 2011 2020 Neuroblastoma Lymphoma CML / Ph+ ALL Trk+ Tumors Thyroid Ca Neurofibroma Melanoma 9
Slide 11: Regulatory agencies encourage and increasingly require paediatric development
Regulatory agencies encourage and, increasingly, require paediatric development FDA Best Pharmaceuticals for Children • Allows FDA to request sponsors to provide pediatric data, but fulfilment is Act (2002) voluntary • 6 month patent extension for drugs completing PSP successfully FDA Pediatric Rese
Slide 12: Agenda
Agenda • Strategic considerations in development of drugs for childhood brain cancer Dr James Garner • Emerging data for paxalisib in DIPG Associate Professor Matt Dun • Emerging data for paxalisib in AT/RT Dr John Friend • Overview of Kazia’s childhood brain cancer program Dr John Friend • Closing
Slide 13: What is DIPG?
What is DIPG? • Most aggressive paediatric cancer with median overall survival of ~9-11 months and no long term survivors • Located in the pontine region of the brain, which is responsible for life-essential functions, including cardiac and respiratory control • Current treatment is radiotherapy, wh
Slide 14: DIPG is genetically heterogenous
DIPG is genetically heterogenous • 80-90% of DIPG cases harbour a lysine-to- methionine (K-to-M) mutation in histone 3 (H3) at amino acid 27 (H3K27M), and this may be considered the defining genetic alteration of DIPG • Additional mutations are necessary to drive glioma formation: Proliferative gene
Slide 15: ONC201 has shown promise as a single agent in DIPG compassionate use
ONC201 has shown promise as a single agent in DIPG compassionate use experience Apparent extension of overall …but different tumours have …and PI3K / AKT signalling survival in comparison to widely varying sensitivity to seems to be a primary resistance mechanism historical controls… ONC201… Overall
Slide 16: Combination of ONC201 and paxalisib appears synergistic
Combination of ONC201 and paxalisib appears synergistic Addition of paxalisib rescues ONC201 from pAKT activation 15
Slide 17: Clinical cases from compassionate use corroborate laboratory data
Clinical cases from compassionate use experience corroborate laboratory data Patient 1 Patient 2 • Commenced ON201 + paxalisib immediately following • Commenced ONC201 + paxalisib following re-irradiation radiotherapy after diagnosis • At 5 months, MRI showed continued regression of • Tumour size ha
Slide 18: A phase II trial is underway to evaluate ONC201 and paxalisib
A phase II clinical trial is underway to formally evaluate the combination of ONC201 and paxalisib • Phase II interventional study, Newly-Diagnosed DMGs sponsored by the Pacific Pediatric Neuro-Oncology Consortium ONC201 + (PNOC) Post-Radiotherapy paxalisib • Up to 216 participants in multi- arm ada
Slide 19: Agenda
Agenda • Strategic considerations in development of drugs for childhood brain cancer Dr James Garner • Emerging data for paxalisib in DIPG Associate Professor Matt Dun • Emerging data for paxalisib in AT/RT Dr John Friend • Overview of Kazia’s childhood brain cancer program Dr John Friend • Closing
Slide 20: Atypical Teratoid / Rhabdoid Tumor (AT/RT)
Atypical Teratoid / Rhabdoid Tumor (AT/RT) • Atypical Teratoid Rhabdoid Tumors are the most common malignant brain tumors of infancy – Occurs in the cerebellum or brainstem – Usually develops by age three but can occur in older children – Presenting symptoms include • Issues with balance/coordinatio
Slide 21: Collaboration with Johns Hopkins University for Pediatric Brain Cancers
Kazia Therapeutics Announces Collaboration with Johns Hopkins University For Pediatric Brain Cancers • Lead researcher – Jeffrey Rubens, MD – Assistant Professor of Pediatrics & Oncology – Sidney Kimmel Cancer Center, Johns Hopkins University • Objective – Establish efficacy of Paxalisib in AT/RT an
Slide 22: Preclinical Data Presented at 2022 AACR and ISPNO Meetings
Kazia Therapeutics Announces Preclinical Data Presented at 2022 AACR and ISPNO Meetings Paxalisib monotherapy slows tumor growth and extends survival in mice bearing AT/RT orthotopic xenograft tumors CHLA06 BT12 100 100 Control Control Paxalisib Paxalisib 75 75 50 50 25 25 0 0 0 10 20 30 40 50 0 20
Slide 23: Preclinical Data Presented at AACR and ISPNO Meetings (continued)
Kazia Therapeutics Announces Preclinical Data Presented at 2022 AACR and ISPNO Meetings (continued) Combination of Paxalisib with DAY101 synergizes to slow AT/RT cell growth Paxalisib combines with RG2833 to disrupt cell cycle regulation and expression of stem cell factors CDK1 LIN28A 1.5 1.5 1.0 1.
Slide 24: Agenda
Agenda • Strategic considerations in development of drugs for childhood brain cancer Dr James Garner • Emerging data for paxalisib in DIPG Associate Professor Matt Dun • Emerging data for paxalisib in AT/RT Dr John Friend • Overview of Kazia’s childhood brain cancer program Dr John Friend • Closing
Slide 25: Kazia has interest in at least three forms of childhood brain cancer
Kazia has interest in at least three forms of childhood brain cancer Others Diffuse Midline Gliomas Atypical Teratoid / (Medulloblastoma & HGG) (DMG, DIPG) Rhabdoid Tumors (AT/RT) Preclinical Positive preclinical data in Positive preclinical data as combination with ONC201 Research monotherapy and i
Slide 26: Agenda
Agenda • Strategic considerations in development of drugs for childhood brain cancer Dr James Garner • Emerging data for paxalisib in DIPG Associate Professor Matt Dun • Emerging data for paxalisib in AT/RT Dr John Friend • Overview of Kazia’s childhood brain cancer program Dr John Friend • Closing
Slide 27: www.kaziatherapeutics.com
www.kaziatherapeutics.com [email protected] 26
Kazia Therapeutics — Technical Presentation (June 2022) on 6ix