Kazia Presents Further Paxalisib Data At Sno, Confirming Earlier Positive Safety And Efficacy Signals In Glioblastoma

SYDNEY,Nov. 18,2020 -- Kazia Therapeutics Limited (ASX: KZA; NASDAQ: KZIA),an Australian oncology-focused biotechnology company,is pleased to share a summary of new paxalisib data presented at the Society for Neuro-Oncology (SNO) Annual Meeting,which is being held virtually from 19-21 November 2020.

Key Points

New interim analysis of paxalisib phase II study in glioblastoma (NCT03522298) is highly consistent with prior data

Median progression-free survival (PFS) of 8.4 months reported on this analysis (versus 5.3 months for temozolomide,the existing standard of care)

Median overall survival (OS) of 17.5 months reported (versus 12.7 months for temozolomide)

First substantial presentation of safety data at a 60mg dose shows profile very similar to prior experience,with the most common toxicities including rash,stomatitis (mouth ulcers),and hyperglycemia (high blood sugar),consistent with other PI3K and mTOR inhibitors

Phase I study in DIPG (NCT03696355) shows paediatric maximum tolerated dose (MTD) of 27 mg/m2,with safety profile and pharmacokinetics similar to adult data

Kazia CEO,Dr James Garner,commented,"this is very reassuring data from the glioblastoma study,confirming our earlier results with the data now much more mature. In studies such as this,volatility is the enemy of dependability. From the very first efficacy data we reported from this study,in November 2019,through the ASCO and AACR presentations in June 2020,to today's latest analysis,the PFS and OS figures have remained extremely stable as the study has progressed. This gives us a great deal of confidence that what we are seeing is representative and reliable."

He added,"we expect this study to conclude in the first half of calendar 2021,but it has already provided useful information to guide the development of paxalisib. We have moved into the operational phase of the GBM AGILE pivotal study,and we expect that study to now be the primary focus of our work in glioblastoma from this point forward."

The poster presentation is available for download via the Kazia website at:-

https://www.kaziatherapeutics.com/researchpipeline/paxalisib

Summary of Paxalisib Data in Comparison to Temozolomide (existing standard of care)

Temozolomide[1]

(FDA-approved treatment)

Paxalisib

(interim phase II data)

Progression-Free Survival (PFS)

5.3 months

8.4 months

Overall Survival (OS)

12.7 months

17.5 months

Professor Patrick Wen,the first author on the poster,commented "as this study has matured,we have seen encouraging results that are very stable over successive analyses,and very consistent with prior clinical experience in this drug. Paxalisib is now moving into the GBM AGILE study in glioblastoma,and we expect this to provide definitive data regarding the drug's potential use in this disease and,if successful,a basis for regulatory approval. There remains a profound need for new treatments in glioblastoma,and paxalisib has proven to be an exciting potential candidate."

Initial Data from St Jude Study of Paxalisib in DIPG and Diffuse Midline Gliomas

Dr Christopher Tinkle,lead investigator for the SJPI3K study of paxalisib in DIPG and diffuse midline glioma (NCT03696355),gave an invited oral presentation on interim results from that study.

The SJPI3K study is a first-in-paediatric study,designed to establish the safety and pharmacokinetics of paxalisib in children,and to explore potential early signals of efficacy in this patient population.

The study recruited 27 patients,ranging from 3 to 16 years of age. Four patients discontinued participation prior to receiving a first dose of paxalisib,generally due to disease progression. At the time of analysis,five patients remain on paxalisib treatment,and several patients remain in post-treatment follow-up.

The paediatric maximum tolerated dose (MTD) was determined to be 27 mg/m2. The dose-limiting toxicities (DLTs) included hyperglycaemia,oral mucositis,and rash,which are entirely consistent with the adult experience.

The pharmacokinetics of the drug,a term which describes the concentration of the drug in plasma over time,was very consistent with the adult experience. The study found no meaningful difference between administration of intact capsules and administration via opening of capsules and sprinkling of contents onto a food carrier.

The study has not at this stage shown a clear survival benefit for paxalisib in comparison to historical controls. In terms of PFS,the proportion of patients alive and progression-free at six months (PFS6) was 96%,which compares favourably to an historical control of 58%[2]. However,the authors note that PFS can be a complex endpoint to interpret in DIPG trials due to the confounding effect of incidental radiological changes associated with radiation therapy.

Dr Tinkle commented,"my colleagues and I are very pleased with the outcome of this study. We have determined an appropriate dose for future paediatric work,established an acceptable tolerability profile in children,and demonstrated pharmacokinetic equivalence between intact capsule and open and sprinkled administration,which are critical steps in the development of any new drug for paediatric cancer."

He added,"DIPG is an extremely treatment-resistant disease,and no drug has ever shown convincing efficacy as a monotherapy. Our view has always been that the treatment of this disease will consist in combination therapy,and we have shown that paxalisib is eminently suitable to now be evaluated alongside other agents. We look forward to discussing follow-on work that will explore these opportunities and further investigate paxalisib's potential."

Dr Garner commented,"we are grateful to have had the opportunity to collaborate with one of the world's leading paediatric oncology hospitals in this study. The results provide an excellent foundation for the further development of paxalisib in DIPG,and we will be excited to discuss the next phase of work with our collaborators in coming months."

Next Steps

The paxalisib phase II study remains ongoing,with final data expected in 1H CY2021. The paxalisib arm of the GBM AGILE study has moved into an operational phase,and first patient in is expected early in 1Q CY2021.

The St Jude study in DIPG remains ongoing,with final data expected during 1H CY2021.

Investor Conference Call

Kazia is pleased to invite investors to attend a conference call to discuss the results further.

The call will be held on Thursday 19 November 2020 at 12:00pm,Sydney time (AEDT),which is 5pm on Wednesday 18 November 2020 in San Francisco (PST) and 8pm on Wednesday 18 November 2020 in New York (EST).

Participants will need to pre-register for the call via the following link:

https://s1.c-conf.com/diamondpass/10011029-8iqiBr.html

Click the 'Register Now' button and follow the prompts to complete pre-registration. You will then receive a calendar invite with dial in numbers,a passcode and a PIN to dial into the conference call.

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

[2]T Cooney,A Lane,U Bartels,et al. Neuro-Oncology (2017); 19(9):1279-1280