Kazia Therapeutics Limited (KZIA) Earnings Call Transcript & Summary

Okay. Good morning, everybody. I think we have most people who are going to join us have joined, but there may be a few more to come. Having said that, I welcome you to Kazia Therapeutics Annual General Meeting. My name is Bryce Carmine, and I'm the Chairman of Kazia Therapeutics. As the time is now 10 a.m. in Sydney and a quorum is present, I formally declare the 2024 Annual General Meeting of Kazia Therapeutics Limited open. As set out in the Notice of Meeting, the Annual General Meeting is being held as a fully virtual meeting. We are joined today by CEO, John Friend; along with my fellow nonexecutive directors, Steven Coffey, Ebru Davidson and Bob Apple. I welcome all attendees to the meeting. Please note that only shareholders and proxy holders are able to ask questions and vote at the meeting. For shareholders and proxy holders who wish to ask a question, you can then submit those online, and we will respond to them later in the meeting. You should direct those questions as much as you can to John Friend, and then he will pass the answers if any others are required to answer them. Before we move to the formal business of the meeting, I would like to make some general observations about where Kazia is at the moment. As many of you can relate, the past financial year was marked by persistent market challenges, leading to funding and operational pressures across the global biotech sector. The XBI, the biotech index in the U.S., has been consistently under pressure since reaching its peak in February 2021. And sadly 2025 has been no exception with further erosion beginning from November of '24. Despite these hurdles, Kazia has remained strategically focused on raising capital as the opportunity presented and directing it towards advancing our 2 key assets, paxalisib and EVT801. John will review the appropriate steps that have been taken in his presentation over the past 12 months. Despite these hurdles -- sorry. I'm sorry, I missed. I jumped a paragraph. Since June of 2023, we have worked to strengthen the Board of your company with the addition of Ebru Davidson, who brings a legal background plus Board biotech experience. More recently, Bob Apple has joined the Kazia Board, bringing significant U.S.-based biotech executive experience and deep industry knowledge. On the clinical development front, paxalisib continued to deliver promising results with strong data being released from a number of trials. Most notably, in July 2024, immediately after the reporting period, we announced results from GBM-AGILE, a Phase II/III study by the Global Coalition of Adaptive Research, GCAR, in other words. We were encouraged to see that paxalisib showed a clinically meaningful 54% improvement compared to standard-of-care treatment for overall survival in newly diagnosed unmethylated patients with glioblastoma. We were disappointed. This level of clinical activity shown in 2 studies was not viewed by the FDA as meaningful enough in this devastating disease with few treatment options. We are actively talking to potential partners, however, who could pursue an appropriate regulatory trial requested by the FDA. Towards the end of 2024 calendar year, we announced the first -- a world-first phase in clinical trial, evaluating the combination of paxalisib and immunotherapy in patients with advanced breast cancer. This is an exciting development for paxalisib program and further strengthens our partnership with the clinical team in Brisbane at QIMR Berghofer, a world-leading research institute based in Australia. We look forward to providing results and regular updates on this open-label trial in the months ahead. Our EVT801 clinical program also made some important strides in financial year 2024 with the completion of Phase I of our EVT801 clinical trial in solid tumors. In May of 2024, we announced that both primary and secondary endpoints of the trial were met with the drug showing encouraging clinical activities, especially in patients with advanced ovarian cancer. We are now focused on planning a Phase II study in advanced ovarian cancer patients while simultaneously seeking potential partners for the program. In closing, I'd like to thank the Board and the wider Kazia team for their passion and dedication as we reach clinical milestones under challenging macroeconomic conditions. Our vision remains unchanged. We're committed to addressing unmet urgent medical needs in cancer care by developing innovative medicines benefiting patients around the world. I would also like to thank you, our shareholders. Your ongoing support of Kazia made it possible for us to continue the work we do. The clinical results provide clear evidence that our 2 assets are worthy of further development. Your Kazia team is committed to enhancing the value of your portfolio by delivering further clinically meaningful advances -- advancements and continuously identifying and assessing strategic opportunities with both our current assets. I would now like to welcome CEO, John -- Dr. John Friend, to provide a more detailed overview of the key milestones for the financial year. Thank you. John?

Thank you, Bryce. Good evening, afternoon and morning to everyone attending our 2024 Annual General Meeting. Again, I'd like to thank you for taking time out of your evening or day as the case may be for joining us. Unfortunately, the timing of this meeting was pushed to May, but we have every intention of getting back on schedule for our 2025 AGM meeting before the end of this year. Rather than highlighting what we've executed on during the fiscal year 2024, I'm going to focus most of our time providing an update as to what the team has accomplished and working on since then. For those interested in more specifics of the fiscal year 2024, please take a look at the 20-F that was filed with the SEC in November of 2024 or the annual report that was finalized in February of this year. Our standard forward-looking statements. As you know, both of Kazia's clinical-stage assets are unique, highly specific targeted drugs with promising data across a number of high unmet needs oncology indications. The development and clinical trials to evaluate the safety and efficacy of paxalisib have been focused on its inherent ability to cross the blood-brain barrier. Up until this year, all of paxalisib's trials have enrolled adult and pediatric patients with primary or secondary brain cancer. I'll discuss our exciting rationale and recent entrants into other solid tumor indications in a few minutes. Our second oncology asset is a highly specific small molecule VEGFR3 inhibitor called EVT801. Preclinical studies have shown EVT801 to be active against a broad range of cancers and has demonstrated evidence of synergy with several immuno-oncology agents. The Phase I study was completed, and preliminary clinical data was presented late last year in 2024. We'll review this data in subsequent slides. Over 2024 and the first quarter of 2025, many of the listed trials have completed or nearing completion. In adult brain cancer, GBM-AGILE study was completed, results to be discussed later, and we anticipate the investigator-initiated trial with Weill Cornell to evaluate paxalisib in combination [indiscernible] and a ketogenic diet will complete enrollment in 2025 with preliminary results presented in 2026. We've recently announced that paxalisib will be evaluated in a very unique genomically guided glioblastoma adaptive platform clinical trial, also known 5G. This trial, which I can say is fully funded by not-for-profit foundations and charities, will enroll patients with PI3K pathway mutations and treat them daily with paxalisib. In terms of pediatric brain cancer, we've been informed by PNOC, the sponsor of the PNOC022 study last weekend, that the additional clinical data analyses will be completed in June or July of this year, and we hope to present that data later on in 2025. As you may recall, we announced last year a very encouraging overall survival data from that study, the PNOC022 study, in newly diagnosed and recurrent children with diffuse midline glioma, or DIPG, treated with both paxalisib and ONC201. Within the brain metastasis development pillar, 2 studies, the Memorial Sloan Kettering and the Dana-Farber Cancer Institute trials, were completed and data presented throughout the year in 2024. I'll discuss the primary and secondary analyses for GBM-AGILE study now. As you know, GBM-AGILE is adaptive Phase II/III global trial designed to screen and characterize the response of glioblastoma patients to novel investigative agents. A total of 313 newly diagnosed unmethylated, or NDU patients, and recurrent glioblastoma patients being treated at top U.S. and Canadian cancer hospitals were randomized in Stage I to either paxalisib or the standard-of-care current -- concurrent control arm from March of 2021 to May of 2022. This is an important distinction in that the cumulative control arm included patients who were enrolled from July of 2019, which was the GBM-AGILE study start date until May of 2022. We believe [indiscernible] is the concurrent control arm who were treated at the same time as the paxalisib-treated patients. Based on preliminary interim analysis, the high bar for graduation to Stage II was not met, and patients continued to receive paxalisib or temozolomide, the concurrent standard of care, for up to 12 months. For the primary analysis, the median overall survival was 14.77 months for paxalisib, treated with -- treated NDU, or newly diagnosed patients, versus 13.84 months for the cumulative standard of care, newly diagnosed unmethylated patients. For our prespecified secondary analysis you see in the subsequent columns, in the NDU patients, median overall survival was 15.54 months in the paxalisib arm versus 11.89 months in the concurrent standard of care arm. As you see, moving left to right, in the other sensitivity analyses or other prespecified secondary analyses, you see very similar results of 15.54 months with paxalisib-treated patients versus 11.7 months with the concurrent standard of care. Again, as the slide depicts, all 3 prespecified secondary overall survival analyses were highly consistent with approximately a 4-month survival benefit observed in patients with paxalisib. For full disclosure, an efficacy signal was not detected in patients with recurrent disease or recurrent glioblastoma with paxalisib compared to standard of care. Based on these results and the totality of the data from completed paxalisib clinical studies, Kazia requested a meeting with the FDA to discuss potential clinical and regulatory path forward. Following the discussion in December of 2024, Kazia announced that the FDA's current position is that data of overall survival would generally not be appropriate for accelerated approval, but could be considered to support a standard traditional approval. The agency further commented that the secondary endpoint overall survival data from the GBM-AGILE study are supportive and informative for designing and executing a pivotal registrational study in pursuit of a standard approval. Furthermore, Kazia aligned with the FDA on key aspects of the design of our proposed registrational pivotal Phase III study, including patient population, primary endpoint and the comparator arm to be used. Specifically, the study will be a randomized, controlled study of paxalisib versus standard of care, temozolomide, in patients with newly diagnosed unmethylated glioblastoma to determine overall survival as well as other parameters of clinical efficacy, safety and tolerability. Approximately 366 patients will be enrolled over 14 months in the study with a 1:1 treatment ratio between paxalisib and temozolomide. We anticipate engaging roughly 50 clinical sites across the globe, including North America, U.K., Europe, Asia Pacific for this study. The Kazia team is exploring various bids from contract research organizations, or CROs, in parallel to discussions, as you heard from Bryce, with strategic partners as well as cooperative groups to participate or fully fund the trial. We'll now transition our work out -- transition the presentation to our work outside of neuro-oncology, in particular, and specifically advanced breast cancer. Announced in December of 2022, Kazia and QIMR Berghofer initiated a collaboration to explore the impact of paxalisib and other PI3K inhibitors in combination with immunotherapy drugs like pembrolizumab or olaparib. The lead investigator shown here, Dr. Sudha Rao, had a hypothesis that PI3K inhibitors could modulate not just tumor cancer cells, but also the environment in and around the tumor and possibly improve our own tumor-fighting cells, such as T cells and B cells. In addition to the preclinical findings listed on the slide, we are pleasantly surprised to learn that these effects were only observed when both PI3K and mTOR were inhibited. Drugs that inhibit only PI3K or mTOR did not have these similar effects in these studies performed. We continue to collaborate with Dr. Rao and her team to further delineate this novel mechanism of action in preclinical models as well as in patient tumor samples in particular, exploring patients in earlier stage triple-negative breast such as Stage IIb and Stage III. Kazia will continue to provide updates through abstracts, presentations and manuscripts in peer-reviewed journals throughout 2025 and beyond. In January, we announced the regulatory approval and launch of a clinical trial evaluating a combination of paxalisib and immunotherapy in patients with advanced breast cancer. The ABC-Pax, or advanced breast cancer paxalisib study, will assess the safety and efficacy of paxalisib in combination with KEYTRUDA, pembrolizumab, or LYNPARZA, olaparib, in women with advanced breast cancer, in particular, triple-negative breast. ABC-Pax is a multicenter open-label Phase Ib study enrolling 24 patients who received this combination therapy for up to 12 months. Another key objective of this study is to assess paxalisib's effect on circulating tumor cells, dormant cancer stem cells and the overall body's innate immune system, including T cells, B cells, natural killer cells, et cetera. Currently, the study is open and actively screening patients at the Royal Brisbane and Women's Hospital, Gold Coast University Hospital and Sunshine Coast University Hospital in Queensland, Australia, with plans to open up an additional 4 sites or more in Australia. As an open-label trial, we anticipate providing clinical updates throughout 2025. Moving on to EVT801. As mentioned, EVT is a highly selective small molecule VEGFR3 inhibitor that targets tumor angiogenesis, meaning it inhibits the formation of new blood vessels, in particular, lymph vessels in tumors. It's being developed in a variety of solid tumors, including ovarian, renal, colon, pancreatic, soft tissue sarcoma, hepatocellular carcinoma. Again, in preclinical studies, EVT801 has shown antitumor effects in various tumor models by inhibiting tumor angiogenesis, reducing hypoxia and decreasing immunosuppressive cytokines inflammatory markers and cells. The Phase I study scheme and preliminary results are shown here on this slide. A total of 26 patients received EVT801 across 6 dosing cohorts, ranging from 50 milligrams daily to 500-milligram twice a day. In general, EVT801 was well tolerated across all doses with the majority of toxicities being mild to moderate and transient in nature. 11 different cancer types, including colon, renal cell and pancreatic, were enrolled in the study with advanced ovarian cancer being the most prevalent with 11 patients. These 11 patients were highly pretreated with an average age of 67 years and a median time from initial diagnosis of 9 years. The preliminary data here as well as other was accepted and presented at the 15th Biennial Ovarian Cancer Research Symposium in Seattle that occurred in September of 2024. In November of 2024, the last patient completed the follow-up survival visit in this study. We anticipate receiving the final data from the Phase I study shortly and have plans to present the final data as well as a number of exploratory analysis later this year at an international medical congress. In addition to speaking with scientific thought leaders in the ovarian cancer therapeutic arena, we're initiating a process to explore alternatives for EVT801, which include finding a strategic partner with resources to continue the clinical development of EVT801. Given the positive data and commercial potential for EVT801, we believe this is a rare opportunity for our partner. And in conclusion with one final slide. In summary, we have streamlined our pipeline with several clinical trials completing their targeted enrollment. Glioblastoma and diffuse midline glioma, or DIPG, remain our most advanced programs, and we will continue to update our shareholders with the progress in all significant catalysts. We're extremely excited about our recently launched Australian-focused clinical trial for advanced breast cancer. Again, this trial is based on highly reproducible preclinical data that has generated a family of novel intellectual property that should provide exclusivity well into 2045. In spite of political, economic and regulatory challenges facing all micro-cap biotech companies, the team at Kazia Therapeutics continues to push the development of paxalisib and EVT801 forward. We'll be providing a financial update as per Australian corporation and regulation shortly, maximizing non-dilutive funding, such as government or not-for-profit grants, example, Michael J. Fox that we announced recently; legacy asset IP sales, Cantrixil, as well; and the developmental milestones. An example of this would be continuing to support our partner, Sovargen, in terms of their first patients dosed in their clinical trial, which we expect ideally by the end of this year, resulting in significant 7-digit clinical milestone. These will all remain a priority for continued funding through 2025. We will, of course, remain opportunistic during discussions with strategic regional and global biotech and pharmaceutical companies, and we'll update our shareholders accordingly. Thank you again for your time. And at the end of the formal section with Bryce, we can take some additional questions. I believe we'll have -- we should have some time for that. So with that in mind, I'll turn it back over to you, Bryce, for the next section.

Thank you, John. We now move to the formal agenda as set out in the notice of meeting sent to all shareholders. Shareholders will be given an opportunity to ask questions in relation to the resolution and generally in relation to the company's business and management. [Operator Instructions] We will endeavor to respond to as many questions as possible today. Voting today will be conducted by way of a poll, and I will shortly open voting. I appoint [ Glenn Rogers ] of Computershare Investor Services Proprietary Limited as the returning officer. If you are eligible to vote, once voting opens, press the Vote icon in the Computershare platform to activate your voting option. To cast your vote, simply select one of the options. There is no need to present send or enter. Your vote is automatically recorded. You can change your vote at any time until I declare the voting closed. I now declare voting open. By way of notice, I intend to cast all undirected votes for which I hold a valid proxy as Chairman in favor of the resolution in today's meeting. I now move to the formal business of the meeting. The first item of business is to receive and consider the annual report of the company and its controlled entities for the year ended 30th of June 2024, which includes the financial report and the directors' and auditors' reports. The annual report is for consideration, but not the subject of a resolution. Copies of the annual report were sent to all shareholders who requested it, and it is available on the company website. Are there any comments or questions on the reports from the shareholders? If there are, again, submit them in the questions, and John will respond to them later. Thank you. We'll now move to the resolution. We have one resolution to vote on today. The resolution, together with the proxy votes received, are shown on your screen. Can we get those on the screen?

Yes, sorry. Apologies. There you go, Bryce.

The resolution is for the election of Mr. Robert Apple, who was appointed as a Nonexecutive Director on 18th of January 2024 to fill a casual vacancy. In accordance with the company's constitution, Bob Apple retires at the conclusion of this Annual General Meeting, and being eligible, stands for reelection. Bob has more than 25 years of senior leadership experience in the pharmaceutical industry, including 16 years with Antares Pharma Inc. as Senior Vice President, Chief Financial Officer and Corporate Secretary, before going on to become President and Chief Executive Officer from 2016 until its acquisition by Halozyme Therapeutics in 2022. Does anybody have any questions or comments? If they do, please record them in the chat box, and John will read those during the appropriate point.

I don't see any questions at this point in time, Bryce.

Okay. So if there are questions then at this point in time, please do raise them and place them in the chat box.

No questions regarding that. I do see one question regarding clinical that we'll address at the end. So happy to address that question once we get through the election process.

Okay. Based on that, I will put the resolution to the meeting that Mr. Robert Apple, who retires in accordance with clause 20.6 of the company's constitution, being eligible, be elected as a director of the company. Please record your vote through the Computershare platform. Seeing everybody has concluded, that now concludes the formal resolution. Please ensure that you have registered your vote for the resolution before I close the poll. [Voting]

I now declare the poll closed.

Are there any further questions?

I saw one, Bryce. Let me get to it. Let me read it. Yes. So a question came in asking about the DIPG study and an update. That was -- I did mention the DIPG study, that's the PNOC -- P-N-O-C -- 0-22 study. This is enrolling both newly diagnosed and recurrent DIPG, or diffuse midline glioma patients. So they -- PNOC, the sponsor of this study -- have not been enrolling new patients while they've been undergoing these recent analyses. Some of these analysis include pharmacogenomic and -- mostly pharmacogenomic but also some imaging reanalysis looking for response rates. They are heavily engaged in these analyses and expect to have been completed in June or July. I just got this update fresh off the press last weekend. So that's when I would expect we should have some updates there and hopefully see some additional -- those analyses presented later this year at some neuro-oncology based meetings, which there are only a few out there. But yes, we would hope to see this data presented as well as updates on those established patients, which we still have several patients who have been receiving -- who've been on study drug, i.e., paxalisib, for several years now. So I would hope to see some updated overall survival analysis and Kaplan-Meier curves toward the end of this year as well.

Are there any further questions, John?

Not right now. I will just pause maybe a second just to make sure I haven't missed anything. I don't see anything. So here's a question that just came through in terms of milestone payments from Sincere. Based -- so Sincere is the Chinese-based biotech, large biotech company who had in-licensed the rights to paxalisib -- sorry, the rights to paxalisib for China, Macau and Taiwan. We've been working with them now for some time. The agreement, the next clinical milestone, the next significant clinical milestone would be based off of their first enrollment in a trial. And right now, we're still in discussions about what that trial would look like, whether a GBM or potentially joining in our breast cancer evaluations. Question asking about any acquisition talks. As I mentioned, any strategic announcements, significant acquisitions, mergers, those sorts of things, would have to be released. So at this time, we wouldn't be announcing any significant movements in terms of mergers, acquisitions, divestitures, et cetera, without significant -- unless these things were fully moved on and ready for disclosure.

Maybe, John, I'll just make a comment on that point. What is important to note is in meetings, scientific meetings and business meetings that occur across the industry around the world, there are always conversations taking place with other companies, whether they be small, medium or large. And that's an ongoing process for any company such as us to maintain a degree of dialogue with those especially who would be prospective acquirers or licensors.

Thanks, Bryce. We'll give it another minute. One additional comment about exploring partnerships, promising partnerships that can be shared. Again, as Bryce clearly delineated just a second ago, this is an ongoing business development. There's an ongoing ever living sort of discussions that we have in terms of partnerships. We wouldn't disclose how many that we're undergoing now and -- until it was something meaningful from a legal perspective that we would need to disclose. I see Elissa was also -- our Corporate Secretary, is also checking any messages, and she's -- she forwarded me one that I addressed, and I don't see any others at this point in time, Bryce.

Okay. Then I think we can draw this meeting to a close. The poll, as required, will be declared on our website, and you can view the results on our website. But at this point, I would declare the meeting closed, and the results will be published as I just indicated. We thank you for attending, and we thank you for your ongoing support of Kazia, and we will keep you informed and updated as key events happen throughout the ongoing months ahead. Thank you very much for joining. And we look forward to seeing you in the future. Take care. Bye now.