On January 29, 2021 Kazia Therapeutics Limited (ASX: KZA; NASDAQ: KZIA), an Australian oncology-focused biotechnology company, reported an update on the ongoing development of its product candidates for the quarter ending 31 December 2020 (Press release, Kazia Therapeutics, JAN 29, 2021, View Source [SID1234574406]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Key Points
GBM AGILE pivotal study opened to recruitment for the paxalisib arm, placing the drug on a direct path to commercialisation
Completion of an AU$ 25 million financing round in October 2020 leaves the company well-funded to commence GBM AGILE pivotal study; initial one-off start-up fee of US$ 5 million paid on execution
New clinical collaboration launched with Pacific Pediatric Neuro-Oncology Consortium (PNOC) to investigate paxalisib as combination therapy in DIPG
Interim analysis of paxalisib phase II study in glioblastoma presented at Society for Neuro-Oncology (SNO) Annual Meeting, directionally confirming earlier results
Interim analysis of paxalisib phase I study in DIPG presented at SNO Annual Meeting, showing favourable safety and tolerability
Final top-line data from Cantrixil phase I study in ovarian cancer released; definitive study publication in draft
Kazia CEO, Dr James Garner, commented, "the December quarter has been defined by two critical achievements: a financing round that will substantially fund the GBM AGILE pivotal study for paxalisib, and the subsequent commencement of recruitment to that study. We are now, in common parlance, a ‘phase III company’, with our lead program on a direct path to a potential FDA approval, and that elevation in status is beginning to be reflected in a much broader and deeper level of investor engagement."
Commencement of GBM AGILE Pivotal Study
On 16 October 2020, immediately following a successful $25 million financing round, Kazia executed a definitive agreement with the Global Coalition for Adaptive Research (GCAR) to execute the paxalisib arm of the GBM AGILE pivotal study (NCT03970447). Positive data from this study is expected to support the registration of paxalisib as a new therapeutic for glioblastoma.
GBM AGILE has been established by leading clinicians and researchers in the glioblastoma field to expedite the approval of promising new therapies for the disease. It is an adaptive study, in which the number of patients recruited is constantly adjusted according to emerging data. Through this and other efficiencies, GBM AGILE lowers the cost of developing a new drug in glioblastoma by a very substantial margin, while still providing gold-standard clinical data to support registration.
GBM AGILE is currently active at 35 sites in the United States and will shortly be opening in Canada. Expansion to EU and China is expected during CY2021.
Successful Capital Raise Provides AU$ 25 Million in New Funding
As noted in the company’s previous Appendix 4C, on 1 October 2020, Kazia launched a one-for-three accelerated non-renounceable entitlement offer to raise approximately $25 million, before fees. The transaction was fully underwritten by Bell Potter Securities Limited.
The accelerated institutional component closed on 2 October 2020, raising approximately $16.4 million from institutional investors, representing approximately a 70% take-up. The retail component closed on 20 October 2020, raising a further $8.8 million, with approximately 32% take-up.
This financing leaves the company well-funded to implement the GBM AGILE pivotal study.
New Study in DIPG
On 10 December 2020, Kazia announced that it had signed a Letter of Intent (LOI) with the Pacific Pediatric Neuro-Oncology Consortium (PNOC) to include paxalisib in a new clinical trial of multiple therapies in combination for patients with DIPG and other diffuse midline gliomas (DMGs).
The PNOC study will also include ONC-201 (Oncoceutics, Inc) and panobinostat (SecuraBio, Inc) and will explore treatments in various combinations using an adaptive design.
Of note, the PNOC study has built off an extensive body of laboratory research undertaken by Associate Professor Matt Dun at the Hunter Medical Research Institute in Newcastle, NSW. The Dun laboratory research is expected to be published in a peer-reviewed academic journal during 1H CY2021.
Kazia’s participation in the PNOC study incurs no direct cost to Kazia, beyond provision of study drug and administrative support. Implementation is subject to approval by FDA and relevant institutional review boards, and to execution of a definitive agreement between Kazia and the University of California, San Francisco (UCSF) on behalf of PNOC.
Interim Data from Phase II Study in Glioblastoma & Phase I Study in DIPG
Kazia reported new interim data from the ongoing phase II study of paxalisib in glioblastoma (NCT03522298) at the Society for Neuro-Oncology (SNO) Annual Meeting in November 2020.
The interim analysis of all patients in the study (n=30) showed a progression-free survival (PFS) of 8.4 months, and an overall survival (OS) of 17.5 months. These numbers compare favourably with the historical control: corresponding figures of 5.3 months and 12.7 months, respectively, are reported with temozolomide, the only FDA-approved standard of care in newly diagnosed glioblastoma.
At the same meeting, Dr Chris Tinkle and colleagues gave an oral presentation on interim data from their ongoing phase I study of paxalisib as monotherapy in patients with DIPG and DMGs (NCT03696355). The study had recruited 27 patients and reported generally favourable safety and tolerability with paxalisib, having determined a maximum tolerated dose (MTD) in children of 27 mg/m2.
There was not, at the time of analysis, a clear signal of efficacy, which was unsurprising given that the primary focus of the study was safety and tolerability. However, the authors reported a progression-free survival at 6 months (PFS6) of 96%, which compares favourably to an historical control of 58%.
Final Top-Line Data from Cantrixil Phase I Study in Ovarian Cancer
On 9 December 2020, Kazia reported top-line final data from the completed phase I study of Cantrixil (TRX-E-002-1) in advanced ovarian cancer. In total, 25 patients were recruited at hospitals in the United States and Australia. An MTD of 5 mg/kg was determined, with the key side effects being abdominal pain and gastro-intestinal symptoms.
Among 16 evaluable patients, one patient demonstrated a complete response (CR) according to RECIST criteria, and two patients demonstrated partial responses (PRs), making an overall response rate (ORR) of 19%.
Kazia is currently working alongside the investigators to produce a manuscript for submission to a peer-reviewed academic journal.
Receipt of $1.02 million R&D Tax Rebate
On 14 December 2020, Kazia received $1.02 million via the Australian R&D Tax Rebate scheme.
Completion of Unmarketable Parcel Share Sale Facility
As announced to ASX on 2 November 2020, Kazia launched an unmarketable parcel share sale facility in which parcels of less than AU$ 500 in value could be resumed and re-sold, with the benefits accruing to the holder.
This facility closed as planned on 18 December 2020, with 243,784 shares being purchased from shareholders and sold on market for an average price of $1.37 per share. The proceeds from the sale of these shares is to be distributed to those shareholders during the first week of February 2021. As a result of the facility, a total of 1,860 shareholders have left the register, and a number of other shareholders took the opportunity to consolidate their holdings.
Impact of COVID-19
The company has no revisions to its prior guidance concerning COVID-19, but envisages a systematic review with investigators during 1Q CY2021. At present, there is limited operational impact, but Kazia continues to monitor the situation closely.
As noted in the accompanying Appendix 4C, the company’s cash position as at 31 December 2020 was AU$ 19.366 million. The company invested AU$10 million in research and development activities during 2Q FY2021, including an initial one-off fee of US$ 5M (~AU$ 6.5M) to commence the GBM AGILE pivotal study, and incurred G&A expenses of AU$ 0.5 million.
On the basis of cash at 31 December 2020 and expenditure during the quarter, the Appendix 4C reflects 1.92 quarters of available funding. However, as noted above, the company incurred substantial one-off payments in 2Q FY2021 associated with commencement of the GBM AGILE pivotal study for paxalisib. As a result, expenditure in this quarter is unrepresentative of ongoing spend.