On October 30, 2020 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 30 September 2020 (Press release, Kazia Therapeutics, OCT 30, 2020, View Source [SID1234569471]).
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Key Points
Paxalisib granted special designations by US FDA: Rare Pediatric Disease Designation in DIPG, Orphan Designation in glioma, and Fast Track Designation in glioblastoma
New clinical collaboration launched with Dana-Farber Cancer Institute: a phase II study in primary CNS lymphoma, led by Dr Lakshmi Nayak
Post-period: completion of a ~$25 million financing round and execution of definitive agreement with GCAR to commence GBM AGILE pivotal study
Kazia CEO, Dr James Garner, commented, "the September quarter has been highly productive: we have launched a new clinical study, and we have seen important recognition by FDA of the drug’s potential in several forms of brain cancer. These achievements leave us ideally positioned as we now transition into the GBM AGILE pivotal study in glioblastoma. The remainder of this year, and the year ahead, are likely to be rich in data read-outs and in operational progress, as we see paxalisib move rapidly towards commercialization."
FDA Special Designations Awarded
In August 2020, Kazia received Rare Pediatric Disease Designation (RPDD) from the US FDA for paxalisib in the treatment of diffuse intrinsic pontine glioma (DIPG). RPDD is designed to support and encourage the development of drugs for rare childhood illnesses. The key benefit of it the program is that it allows for the sponsor company to receive a priority review voucher (PRV) at the time of an application for marketing authorization in the paediatric disease. The PRV can be sold to another company and used for any new drug, and such transactions have historically commanded prices between US$ 68 and 350 million.
Also in August 2020, Kazia received Fast Track Designation (FTD) from the US FDA for paxalisib in the treatment of glioblastoma. FTD is designed to expedite development of pharmaceutical products which demonstrate the potential to address unmet medical needs in serious or life-threatening conditions. It provides Kazia with substantially enhanced access to FDA, including the ability to submit a ‘rolling NDA’, in which components of the new drug application can be filed as they become available, increasing efficiency and reducing risk in the approval process.
In addition, and also in August 2020, Kazia received Orphan Drug Designation (ODD) from the US FDA for paxalisib in the treatment of glioma. This encompasses both DIPG and glioblastoma. The company previously received ODD for the narrower indication of glioblastoma in February 2018. ODD provides access to certain grant funding, a waiver of PDUFA fees at the time of NDA submission (currently approximately US$ 3 million per indication), and a period of data exclusivity which augments the patent protection.
The achievement of these milestones leaves the paxalisib program well-optimised from a regulatory standpoint:-
Glioblastoma
DIPG
Orphan Drug Designation February 2018 August 2020
Fast Track Designation August 2020
Rare Pediatric Disease Designation n/a August 2020
New Phase II Study in Primary CNS Lymphoma
In September 2020, Kazia launched a new clinical collaboration with Dana Farber Cancer Institute. Under the terms of the collaboration, Dr Lakshmi Nayak will lead a phase II investigator-initiated clinical trial in primary CNS lymphoma. Dr Nayak is an extensively published clinical researcher in this field, and Dana Farber has a world-leading specialist unit for treatment and research of this disease. Primary CNS lymphoma is a form of brain cancer that affects approximately 1,500 patients per annum in the United States. It is considered a high-potential target for paxalisib, since three of the four FDA-approved PI3K inhibitors are used to treat forms of lymphoma outside the central nervous system.
Broad Clinical Trial Program on Track
Sponsor
Phase
Indication
Registration
Kazia Therapeutics
II
Glioblastoma
NCT03522298
Alliance for Clinical Trials in Oncology
II
Brain metastases
NCT03994796
Dana-Farber Cancer Institute
II
Breast cancer brain metastases
(with Herceptin)
NCT03765983
Dana-Farber Cancer Institute
II
Primary CNS lymphoma
TBD
St Jude Children’s Research Hospital
DIPG (childhood brain cancer)
NCT03696355
Memorial Sloan Kettering Cancer Center
Brain metastases
(with radiotherapy)
NCT04192981
Post-Period Events – Successful Capital Raise
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 $8.8 million, with approximately 32% take-up.
This financing leaves the company well-funded to execute the GBM AGILE pivotal study.
Post-Period Events – GBM AGILE Moves into Operational Phase
On 16 October 2020, the company executed a definitive agreement with the Global Coalition for Adaptive Research (GCAR) to commence paxalisib’s participation in the GBM AGILE pivotal study in glioblastoma.
GBM AGILE is an international, multi-drug platform study, designed to expedite the approval of new medicines for glioblastoma. It is run independently of any individual company, under the leadership of some of the world’s premier experts in the field. The study is already ongoing, with thirty sites in the United States and Canada participating, and the first drug is Bayer’s Stivarga (regorafenib). Paxalisib will be the second drug to enter the study. First patient in to the paxalisib arm is expected to occur in early Q1 CY2021.
Impact of COVID-19
The company has no revisions to its prior guidance concerning COVID-19. At present, there is limited operational impact, but Kazia continues to monitor the situation closely.
Financial Update
As noted in the accompanying Appendix 4C, the company’s cash position as at 30 September 2020 was AU$ 6.5 million. The company invested AU$ 1.6 million in research and development activities during 1Q FY2021, and incurred G&A expenses of AU$ 0.6 million.
On the basis of cash at 30 September 2020 and expenditure during the quarter, the Appendix 4C reflects almost three quarters of available funding. However, immediately post-period, the company executed a fully underwritten capital raise which yielded approximately $25 million in new capital, before fees. As a consequence, the company’s operations are well-funded for the foreseeable future.
Upcoming Milestones
The key milestones for the next two quarters are as follows:-
Additional interim data from the ongoing phase II study of paxalisib in glioblastoma (November 2020 – SNO Annual Meeting)
Initial interim data from the ongoing phase I study of paxalisib in DIPG at St Jude Children’s Research Hospital (November 2020 – SNO Meeting)
Initial interim data from the ongoing phase II study in breast cancer brain metastases at Dana-Farber Cancer Institute (precise timing remains uncertain due to COVID-related disruption of conference schedules)
Top-line final data from the completed phase I study of Cantrixil in ovarian cancer
First patient in (FPI) to GBM AGILE registration study for paxalisib in glioblastoma (planned for each Q1 CY2021 in order to avoid Christmas and New Year period)
These milestones are indicative and may be subject to change.