Kazia Therapeutics Limited (ASX: KZA; NASDAQ: KZIA), an Australian 
oncology-focused biotechnology company, is pleased to share a poster 
presentation of interim data from the ongoing phase II study of paxalisib 
(formerly GDC-0084) in glioblastoma, the most common and most aggressive form 
of primary brain cancer. Top-line data from this interim analysis was 
previously announced to ASX on 7 April 2020.

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Key Points

- Analysis of Stage 1 of the study (n=9) shows median overall survival (OS) of 
17.7 months. This compares very favourably with temozolomide, the existing 
standard of care, which has a reported median OS of 12.7 months in this patient 
population 
- Progression-free survival (PFS) in Stage 1 was 8.4 months, which represents a 
clinically material advantage over the 5.3 months associated with temozolomide 
- The longest-treated patient remains on therapy and progression-free some 19 
months after diagnosis 
- Safety profile is consistent with prior clinical experience. Rash, mucositis, 
and hyperglycemia are the most common toxicities, and 60mg, once daily, orally, 
was confirmed as the maximum tolerated dose (MTD)

Professor Patrick Wen from Dana-Farber Cancer Institute, who was the lead 
author on the poster presentation, commented, "These are encouraging early 
signals. We anticipate paxalisib will move into a pivotal study later this year 
and look forward to reviewing further data as it emerges."

Kazia CEO, Dr James Garner, added, "We are pleased to be able to share these 
extremely promising data with clinicians and partners, albeit in the novel 
forum of a virtual academic meeting. As we have previously said, the gold 
standard for any new cancer drug is the ability to extend life, and we are 
seeing evidence from this study that paxalisib may achieve this very 
challenging goal. We expect to begin recruitment to the international GBM AGILE 
pivotal study in the second half of this year. In the meantime, we expect 
several further data read-outs over the next two quarters."

Summary of Paxalisib Data in Comparison to Temozolomide (existing standard of 
care)
 
                                      Temozolomide              Paxalisib
                                      (FDA-approved treatment)  (Stage 1 of 
Phase II Study)
 
Progression-Free Survival (PFS)
Measures ability of a drug to slow 
growth of a tumour                    5.3 months                8.4 months

Overall Survival (OS)
Measures ability of a drug to 
prolong life                          12.7 months               17.7 months
 
ASCO Conference

The American Society of Clinical Oncology Annual Meeting is one of the premier 
scientific conferences in the world for research and treatment of cancer. It is 
typically attended by more than 30,000 clinicians, researchers, industry 
executives, and patient advocates. In 2020, the meeting is being conducted in a 
virtual format due to the ongoing COVID-19 pandemic.

The Kazia data is presented in Abstract 2550 (NCT03522298). In addition to 
Kazia's paxalisib poster, abstracts are being presented by the Global Coalition 
for Adaptive Research on the GBM AGILE clinical trial (Abstract TPS2579; 
NCT03970447), and by the Alliance for Clinical Trials in Oncology on their 
genomically-guided study in brain metastases (Abstract TPS2573;  NCT03994796), 
in which paxalisib is one of three participating drug candidates.

The Kazia poster is available for download via the Kazia website at 
https://kaziatherapeutics.com/researchpipeline/publicationspresentations

Background 

The reported overall survival (OS) figure of 17.7 months represents a strong 
signal of clinical efficacy. The existing, FDA-approved standard of care, 
temozolomide, is associated with an OS of 12.7 months in this patient 
population[1]. Comparison between different studies is always imprecise, but 
the magnitude of the numerical difference provides powerful evidence that 
treatment with paxalisib may extend life in this patient group.

The reported progression-free survival (PFS) figure of 8.4 months compares 
favourably with the PFS of 5.3 months that is associated with temozolomide in 
this patient population. In April 2020, Kazia reported an interim analysis 
showing a PFS of 8.5 months in the overall study population (n=30). This poster 
only reports the first stage of the study (n=9), and the figure in this part of 
the study was 8.4 months.

Before losing patent protection, temozolomide achieved peak sales in excess of 
US$ 1 billion per annum, which provides an indication of the commercial 
opportunity associated with a new treatment for glioblastoma.

The Kazia study is being conducted in newly-diagnosed glioblastoma patients, 
following surgery and radiotherapy. Only those patients with an unmethylated 
MGMT promotor have been recruited. This genetic marker renders patients 
effectively resistant to temozolomide and is present in approximately 
two-thirds of patients.

Thirty patients were enrolled to this study, comprising 9 in Stage 1, and 21 in 
Stage 2. Data reported here are provisional figures from Stage 1 (for OS) and 
from the entire study population (for PFS), but may change as ongoing patients 
proceed through the study. The study has been conducted at leading centers of 
excellence in the United States.

The safety of paxalisib remained broadly consistent with prior experience, with 
hyperglycaemia (raised blood sugar), oral mucositis (mouth ulcers), and 
low-grade rash among the most common drug-related toxicities.

In addition to this phase II study in glioblastoma, four other studies are 
underway with paxalisib in different forms of brain cancer, and it is 
anticipated that several of these will provide initial efficacy data during CY 
2020.

Investors are referred to Kazia's announcement of 7 April 2020 for further 
discussion of these results.

Next Steps

The phase II study remains ongoing, with approximately half of the total 
enrolled patient population still receiving drug at the time of analysis and a 
number of additional patients still in follow-up. Kazia expects to complete the 
study in 1H CY2021.

Kazia had previously had an abstract accepted the AACR Annual Meeting, which 
had originally been scheduled for April 2020. This meeting has now been 
rescheduled to several virtual meetings, and Kazia will present a poster at the 
'AACR Virtual Annual Meeting II' on 22-24 June 2020. 

[1] ME Hegi, A-C Desirens, T Gorlia, et al. N Engl J Med (2005); 352:997-1003 

SOURCE: Kazia Therapeutics Ltd