PBYI - NASDAQ

Good afternoon. My name is Rob, and I'll be your conference call operator today. At this time, all participants are in listen-only mode. After the speaker's formal remarks, there will be a question-and-answer session. [Operator Instructions]. As a reminder, this call is being recorded. I would now like to turn the conference over to Mariann Ohanesian, Senior Director of Investor Relations for Puma Biotechnology. You may begin your conference.

Thank you, Rob. Good afternoon, and welcome to Puma's conference call to discuss our financial results for third quarter of 2024. Joining me on the call today are Alan Auerbach, Chief Executive Officer, President and Chairman of the Board of Puma Biotechnology, Maximo Nougues, Chief Financial Officer, and Jeff Ludwig, Chief Commercial Officer. After market closed today, Puma issued a news release detailing the earnings results for the third quarter of 2024. That news release, the slides that Jeff will refer to, and a webcast of this call are accessible via the homepage and investor sections of our website at Pumabiotechnology.com. The webcast and presentation slides will be archived on our website and available for replay for the next 90 days. Today's conference call will include statements about Puma's future expectations, plans, and prospects that constitute forward-looking statements for purposes of federal security slides. Such statements are subject to risks and uncertainties, and actual events and results may differ from those expressed in these forward-looking statements. For a full discussion of these risks and uncertainties, please review our periodic and current reports filed with the SEC from time-to-time, including our annual report on Form 10-K for the year ended December 31, 2023. You are cautioned not to place undue reliance on these forward-looking statements, which would speak only as of the date of this live conference call, November 7, 2024. Puma undertakes no obligation to revise or update any forward-looking statement to reflect the events or circumstances after the date of this call, except as required by law. During today's call, we may refer to certain non-GAAP financial measures that involve adjustments to our GAAP figures. We believe these non-GAAP metrics may be useful to investors as a supplement to, but not as substitutes for, our GAAP financial measures. Please refer to our third quarter 2024 news release for a reconciliation of our GAAP to non-GAAP results. I will now turn the call over to Alan.

Thank you, Mariann, and thank you all for joining our call today. Today, Puma reported total revenue for the third quarter of 2024 of $80.5 million. Total revenue includes product revenue net, which consists entirely of NERLYNX sales, as well as royalties from our sub-licensees. Product revenue net was $56.1 million in the third quarter of 2024, which was an increase from both the $44.4 million reported in Q2, 2024, and the $51.6 million reported in Q3, 2023. Product revenue for the third quarter of 2024 was impacted by approximately $0.6 million of inventory increase at our specialty pharmacies and specialty distributors. Royalty revenue was $24.4 million in the third quarter of 2024, compared to $2.7 million in Q2, 2024, and $4.5 million in Q3, 2023. Royalty revenue in the latest quarter included the expected sales to China by our offshore partner, Pierre Fabre, as we noted in our August forecast of Q3, 2024 results. We reported 2,723 bottles of NERLYNX sold in the third quarter of 2024, an increase of 208 from the 2,515 bottles sold in Q2, 2024. In Q3, 2024, we estimate that inventory increased by about 37 bottles. In Q3, 2024, new prescriptions were up 3%, compared to Q2, 2024, and total prescriptions were essentially flat compared to Q2, 2024. Jeff will provide further details in his comments and slides. I will now provide a clinical review of the quarter, and then Jeff Ludwig will address our additional color on NERLYNX's commercial activities. Maximo Nougues will then follow with highlights of the key components of our financial statements for the third quarter of 2024. As previously discussed, Puma has an ongoing Phase 2 study of our investigational drug, alisertib, to confirm the efficacy of alisertib monotherapy in patients with small cell lung cancer with biomarkers where the aurora kinase pathway plays a role. The goal is to correlate the efficacy in these biomarker subgroups in the ALISCA-Lung1 study to the efficacy that was previously seen in the biomarker subgroups from the randomized trial of Paclitaxel plus alisertib versus Paclitaxel plus placebo that was published in the Journal of Thoracic Oncology in 2020. If the efficacy and biomarker data are comparable from the two studies, the company believes it would represent a potential accelerated approval strategy and would engage FDA to discuss this further. As investors will remember, alisertib was previously tested as a monotherapy in patients with small cell lung cancer, and the results of this trial were published in Lancet Oncology in 2015. In this trial, Alisertib was administered as a monotherapy to patients with small cell lung cancer. The safety results, (n=60) from the trial, showed that 37% of the patients experienced grade 3/4 neutropenia, 7% experienced grade 3/4 drug-related febrile neutropenia, and 22% of the patients discontinued treatment due to adverse events. The efficacy results from an efficacy of valuable population of 48 patients showed that for the 36 chemotherapy-sensitive patients, the objective response rate was 19%, and the PFS was 2.6 months. And for the 12 chemotherapy-resistant or relapsed patients, the objective response rate was 25% with a PFS of 1.7 months. As investors will also remember, Alisertib was also previously tested in a randomized phase 2 trial of Paclitaxel plus Alisertib versus Paclitaxel plus placebo in patients with second-line small cell lung cancer, which was published in the Journal of Thoracic Oncology in 2020. Alisertib was dosed at a different dose than in the monotherapy trial, with Alisertib being administered at 40 mg BID for 3 weeks on days 1 to 3, 8 to 10, and 15 to 17, plus Paclitaxel 60 mg intravenously on days 1, 8, and 15, whereas the comparator arm received placebo plus Paclitaxel 80 mg per meter squared IV on days 1, 8, and 15 in 28-day cycles. The trial also incorporated an extensive biomarker analysis with a pre-specified analysis of c-Myc expression, as well as a retrospective analysis of genetic alterations in ctDNA with clinical outcome. The safety results from the combination arm of the trial showed that 40% of the patients experienced grade 3 or higher neutropenia, with 13% experiencing grade 3 or higher drug-related febrile neutropenia. 16% of the patients discontinued study treatment because of an adverse event, and 38% of the patients had a dose reduction because of an adverse event. The primary endpoint of that trial was progression-free survival, or PFS. For the ITT population, the hazard ratio for PFS was 0.77, with a p-value of 0.113. When using the corrected definition for the stratification of relapse type, the hazard ratio for PFS was 0.71, with a p-value of 0.038. For the patients with chemotherapy-resistant or refractory disease, the hazard ratio was 0.66, with a p-value of 0.037. With respect to the biomarkers that were studied in that trial, for the patients in the trial who were found to be IHC-positive for c-Myc expression, the hazard ratio in the trial was 0.29, with a median PFS for the paclitaxel plus Alisertib arm of 4.64 months, and a median PFS for the paclitaxel plus placebo arm of 2.27 months. Also, for patients with alterations in cell cycle genes, including CDK6, RBL1, RBL2, and RB1, the PFS for the paclitaxel plus Alisertib arm was 3.68 months, while the placebo plus paclitaxel arm was 1.8 months, and the hazard ratio for PFS was 0.395, with a p-value of 0.003. The overall survival for that subgroup of patients was 7.2 months for the Alisertib arm and 4.47 months for the placebo arm, with a hazard ratio of 0.427 and a p-value of 0.00085. When Puma licensed Alisertib, we stated that one of our focuses would have tried to reduce the adverse event profile of the drug, and more specifically, the grade 3/4 neutropenia, by giving prophylactic GCSF with the administration of Alisertib, and this is being instituted in the ALISCA-Lung1 trial. Currently, there are 20 patients enrolled in the ALISCA-Lung1 trial, with several in screening and prescreening. For the first 18 patients who were available for safety, there has been one patient, or 5.6%, with grade 3/4 neutropenia, and one patient, 5.6%, with febrile neutropenia. No patient has discontinued Alisertib due to adverse events, and one patient, or 5.6%, has required a dose hold. Based on the preliminary improved neutropenia and tolerability that is being seen in the trial, and assuming this continues to be seen, the company is considering the potential to increase the dose of Alisertib monotherapy in the trial. Also, assuming this improved neutropenia and tolerability continues to be seen when Alisertib is combined with paclitaxel, the company believes that it may result in better efficacy of the combination of paclitaxel with Alisertib, and that the company may be able to increase the dose of Alisertib that is able to be given with paclitaxel. Of the 18 patients dosed with Alisertib, 16 have had a post-baseline tumor assessment. Of these, 7 had chemotherapy-sensitive disease, which is defined as a relapse more than 90 days, but less than 180 days, after primary treatment, and 9 had chemotherapy-resistant or refractory disease, defined as relapse less than 90 days after primary treatment. In the chemotherapy-sensitive patients, one patient, or 14%, has shown stable disease, and the median PFS has been 1.2 months. In the patients with chemotherapy-resistant or refractory disease, there have been 2 patients, or 22%, with a partial response, and 1 patient, or 11%, with stable disease, and the median PFS has been 1.4 months. As previously mentioned, we are conducting an extensive analysis of the biomarkers that are known to be involved with the aurora kinase pathway activation to see if it correlates with clinical outcome. The two refractory or resistant patients with partial responses did have biomarkers that correlate with the aurora kinase pathway activation, including RB1 mutations and MYC gains. We caution that this is very early data, and we do not have tissue on all the patients enrolled, so the number of patients with biomarker data is too small to be able to draw definitive conclusions on the associations between biomarkers and Alisertib activity. The company believes that the preliminary data from the ALISCA-1 trial is providing a preliminary indication of potentially better activity in patients with chemotherapy-resistant or refractory disease, which is similar to what was seen in the trials published in the Lancet Oncology and the randomized trial that was published in the Journal of Thoracic Oncology. The company plans to continue enrollment in the ALISCA-1 trial and anticipates additional data will be presented at Medical Conferences in 2025. The company also plans to meet with its steering committee for the trial in order to determine the next steps for the drug and the treatment of small cell lung cancer patients. The company will keep investors updated on this as it progresses. Investors will also remember that the company plans to test Alisertib in the ALISCA-1 trial, a Phase II trial of Alisertib in combination with endocrine treatment in patients with chemotherapy-naive, HER2-negative, hormone receptor-positive metastatic breast cancer. Currently, there are three sites that have been activated for the trial, and we anticipate the initiation of the trial in the fourth quarter of 2024. The company will keep investors updated on this as it progresses. As mentioned on prior earnings calls and in response to investor questions, Puma continues to evaluate several drugs to potentially end license that will allow the company to diversify itself and leverage Puma's existing R&D, regulatory, and commercial infrastructure. The company will keep investors updated on this as it progresses. I will now turn the call over to Jeff Ludwig, Puma's Chief Commercial Officer, for a review of our commercial performance during the quarter.

Thanks, Alan. I appreciate it, and thanks to everyone for joining our third quarter earnings call. Before I move into the commercial review, just a reminder that I will be making forward-looking statements. The commercial team is focused on increasing the utilization of NERLYNXs with an emphasis on HER2-positive early-stage breast cancer patients, who are deemed to have a higher risk of reoccurrence. A significant portion of these patients are treated in the community setting and are being seen by a large number of community oncologists. Given this broad distribution of patients, it's very important to look for opportunities to increase share of voice through personal and or non-personal promotion with a focus on trying to engage physicians at the proper time when they are making treatment decisions related to the extended adjuvant setting. HCP call activity increased about 11% quarter-over-quarter and about 17% year over year. Consistent with the last several quarters, the majority of our calls continue to be live interactions, but the team does look for opportunities to leverage virtual calls depending on the situation. In Q3, greater than 80% of our calls were live interactions, which is very similar to what we reported in Q2 of this year. The commercial team is committed to finding ways to utilize our resources more efficiently and effectively. We are evaluating new partners, new data, and new approaches with the goal of improving our impact and ultimately increasing the utilization of NURLINX. Let me now transition to some of the commercial slides, where I will provide some additional specifics around performance. Once I have finished, I will turn the call over to Maximo for a more detailed review of our financial results. Looking at slide 3, slide 3 is an overview of our distribution model, which is broken out into the specialty pharmacy channel and the specialty distributor or in-office dispensing channel. We do see quarterly fluctuations, but the majority of our business continues to flow through the specialty pharmacy channel. In Q3, about 74% of our business passed through the specialty pharmacy channel, which is similar to the 72% we reported during our Q2 earnings call. Moving to slide 4. NURLINX net revenue in Q3 of 2024 was $56.1 million, which represents an increase of $11.7 million from the $44.4 million we reported in Q2 of 2024 and a $4.5 million increase from the $51.6 million we reported in Q3 of 2023. The significant change in quarterly net revenue was primarily driven by four factors. Number one, inventory changes. Number two, higher US ex-factory sales. Number three, increased product supply revenue to our global partners. And four, a lower gross to net adjustment. I will provide some more details around inventory changes and Maximo will provide some additional specifics during his update. In regards to inventory, we estimate that inventory increased by about $600,000 in Q3 of 2024. As a comparison, we estimate that inventory decreased by about $2.3 million in Q2 of 2024 and increased by about $600,000 in Q3 of 2023. Slide 5 shows Q3 2024 ex-factory bottle sales and also provides both a year-over-year and a quarter-over-quarter comparison. In Q3 of 2024, NERLYNX's ex-factory bottle sales were 2,723, which represents an approximate 8% quarter-over-quarter increase and a 5% year-over-year decrease. In regards to inventory impact, we estimate that inventory increased by about 37 bottles in Q3 of 2024. As a comparison, we estimate that inventory decreased by about 132 bottles in Q2 of 2024 and increased by about 32 bottles in Q3 of 2023. Now let me take just a moment to provide some additional metrics and insights into our third quarter performance. In Q3, we saw new patient starts, or NRX, increased by about 3% quarter-over-quarter and about 8% year-over-year. Total prescriptions, or TRX, were flat quarter-over-quarter and down about 8% year-over-year. Overall demand increased by about 1.5% quarter-over-quarter but was down about 5% year-over-year. Enrollments and SD demand are also important factors in looking at our performance. Enrollments are an important leading indicator, as we have discussed previously. As a reminder, enrollments turn into new patient starts. New patient starts turn into refills, which impact demand in subsequent quarters. In Q3, enrollments were down just under 1% quarter-over-quarter and were up approximately 10% year-over-year. As a reminder, and as we mentioned during our Q3 2023 earnings call last year, we did see some enrollment softness last year that largely occurred in the first part of Q3 of 2023. That softness is contributing to this positive year-over-year comparison. SD demand is also an important performance indicator, as there are patients that are treated solely in the SD channel, which means we will never capture an enrollment from this group. SD demand increased 5% quarter-over-quarter and 13% year-over-year. Turning to slide 6, slide 6 highlights the quarterly adoption of dose escalation since NERLYNX's launch. In Q3, approximately 65% of patients started NERLYNX's at a reduced dose. This is similar to the 66% that was reported in Q2 of this year. The benefits of dose escalation to initiate therapy with NERLYNX's continues to be an important part of our commercial messaging. The control trial showed a significant reduction in grade 3 diarrhea and showed improved persistence and compliance when patients were started at a lower dose. We track multiple cohorts of patients and continue to see improved persistence when patients are started at a lower dose. The commercial team continues to explore additional opportunities to better support patients throughout their NERLYNX's therapy. Slide 7 highlights the strategic collaborations we have formed across the globe. In Q3, NERLYNX's received regulatory approval in Algeria in the extended adjuvant setting. In addition, NERLYNX's was launched in both South Africa and the United Arab Emirates, also in the extended adjuvant setting. We really appreciate the excellent work being done by our partners around the globe and look forward to supporting their continued success moving forward. I'd like to wrap up by thanking my Puma colleagues for their unwavering commitment. The team is passionate about making a difference in the lives of patients and their families battling cancer. The commercial team remains focused on finding ways to be more efficient and effective with their resources and also fully committed to balancing the short-term and long-term priorities of Puma and its shareholders. I will now turn the call over to Maximo Nougues for a review of our financial results. Maximo?

Thanks, Jeff. I will begin with a brief summary of our financial results for the third quarter of 2024. Please note that I will make comparisons to Q2 2024, which we believe is a better indication of our progress as a commercial company and year-over-year comparison. For more information, I recommend that you refer to our Q3 thank you, which will be filed today and includes our consolidated financial statements. For the third quarter of 2024, we reported net income based on GAAP of $20.3 million, or $0.41 per share. This compares to net loss in Q2 2024, or $4.5 million, or $0.09 per share. On a non-GAAP basis, which is adjusted to remove the impact of stock-based compensation expense, we reported net income of $22.4 million, or $0.45 per diluted share, for the third quarter of 2024. Gross revenue from NERLYNX was $67.7 million in Q3 2024 and $55.8 million in Q2 2024. Alan mentioned it. Net product revenue from NERLYNX was $56.1 million, an improvement from the $44.4 million reported in Q2 2024. Higher product sales to our global partners of about $7.4 million, higher U.S. demand, and lower gross-to-net adjustment dropped the higher sales versus Q2 2024. Inventory increased by our distributor was approximately $0.6 million in Q3 versus approximately $2.3 million of drawdown in Q2 2024. Loyalty revenue totaled $24.4 million in the third quarter of 2024 compared to $2.7 million in Q2 2024. Our gross-to-net adjustment in Q3 2024 was about 17.1%, compared to the 20.4% gross-to-net adjustment reported in Q2 2024. Cost of sales for Q3 2024 increased to $29.1 million, reflecting the sales of NERLYNX to our China partner and includes $2.4 million for the amortization of intangible assets related to our NERLYNX license. Cost of sales for Q2 2024 was $10.7 million. Going forward, we will continue to recognize amortization of the milestones to the license short, about $2.4 million per quarter as cost of sales. For fiscal year 2024, Puma anticipates that net product revenue for NERLYNX will be in the range of $187 million to $290 million. We also anticipate that our gross-to-net adjustment for the full year 2024 will be between 20.5% and 21.5%, higher than 2023 due to the impact of the Inflation Reduction Act unexpected Medicaid rebates. In addition, for fiscal year 2024, we anticipate receiving royalties from our partners around the world in the range of $34 to $36 million. We expect license revenue in 2024 in the range of $1 million to $2 million. We also expect that net income for the full year will be in the range of $15 million to $17 million. We anticipate that for Q4 2024, NERLYNX net product revenue will be in the range of $46 million to $48 million. We expect Q4 royalties revenues will be in the range of $3.5 million to $5 million, and we anticipate $1 million to $2 million of license revenue. We further estimate that the gross-to-net adjustment in Q4 2024 will be approximately 21% to 22%, and Puma anticipates Q4 net income between $4 million and $6 million. SG&A expenses were $16.8 million in the third quarter of 2024, compared to $25 million for the second quarter of 2024. SG&A expenses included non-cash charges for stock-based compensation of $1.5 million for Q3 2024, up from $1.4 million in Q2 2024. Research and development expenses were $12.5 million in the third quarter of 2024, down from $13.6 million in the second quarter of 2024. R&D expenses included non-cash charges for stock-based compensation of $0.6 million in the third quarter of 2024, unchanged from the second quarter of 2024. On the expense side, Puma anticipates flat to slightly lower operating expenses in 2024 compared to 2023. More specifically, we anticipate SG&A expenses to decrease by 10% to 12% and R&D expenses to increase 11% to 14% year-over-year. In the third quarter of 2024, Puma reported cash burn of approximately $0.1 million. This compares to cash burn of approximately $10.3 million in Q2 2024. Please note that during Q3, we made our second principal loan payment of $11.1 million related to our obligation with Ethereum. As a result of this, our outstanding principal debt balance decreased to approximately $78.1 million. On September 30, 2024, we had approximately $97 million in cash, cash equivalents, and marketable securities versus about $96 million at year-end in 2023. Our accounts receivable balance was $54.6 million. Our accounts receivable terms ranged between 10 days and 68 days, but our sales outstandings are about 48 days. We estimate that as of September 30, 2024, our distribution network maintained approximately three weeks of inventory. Overall, we continue to deploy our financial resources focused on the commercialization of NERLYNX, the development of our services, and controlling our expenses.

Thanks, Maximo. Puma's Senior Management, in cooperation with the Board of Directors, continues to remain focused on NERLYNX sales trends in 2024 and beyond, and recognizes its fiscal responsibility to shareholders to continue to maintain a positive net income. In the fourth quarter of 2021, we implemented a reduction in expenses with the goal of reducing expenses in order to maximize operational cash flows. We believe that the positive net income that was seen in 2023 resulted from these expense reductions. The expense reductions that we have previously performed and continue to perform are also a major contributor to the positive net income that the company achieved in Q3 of 2024 and that the company is guiding for full year 2024. The company remains committed to continuing to achieve this positive net income and will continue to reduce expenses, if needed, to achieve this. We look forward to updating investors on this in the future. There continues to remain a significant unmet need for patients battling breast cancer, lung cancer, and other solid tumors. We at Puma are committed and passionate about finding more effective ways of helping these patients during their journey, and we will continue to strive to achieve that goal. This concludes today's presentation. We will now turn the floor back to the operator for Q&A. Operator?

We will now begin the question and answer session. [Operator Instructions]. Thank you, and your first question comes from the line of Ed White with H.C. Wainwright. Please proceed with your question.

Good afternoon. Thanks for taking my questions, and congratulations on the quarter. Alan and Jeff, I just wanted to get your thoughts on the sales, exceeding expectations. What are you attributing that to when you dig down into it? And then also, how does persistence play into that? As you keep saying that as patients are using the lower doses, they remain on drugs longer. So I just wanted to get your thoughts on how that's playing through in the revenue numbers?

Yeah, Ed, thanks. I appreciate the questions. I would say a couple things in terms of demand numbers. One, as we state over and over, we believe this drug is very promotionally sensitive, and so trying to get the field force in front of more customers on a regular basis continues to be a very key priority for us. And not only is it getting in front of them, but trying to get in front of these customers at the time they're making decisions is also a huge priority for us. And some of the things we're trying to do to make that happen are leveraging claims data to find out what doctors have patients now, looking at NPP when folks are engaging with their NPP, learning more about NERLYNXs. That's obviously a signal to us that they're making decisions. So we're trying to get much better with the data to drive the location of our sales force. I would say, we're also seeing a very nice conversion from enrollments to new patient starts, to commercial new patient starts. The team is following up on any pending or delayed cases, and that is also a big priority for us. You asked lastly about persistence, and we continue to see at any stage along the persistence curve, whether it's first refill, second, third, or fourth, we see about 5% to 10% of more patients on drug at any given time if they started with low dose as opposed to starting at full dose. So that continues to be a big priority for us, and that does drive better overall bottles per patient. Let me know if that's helpful, if you have more questions.

No, that's great. Thank you. And, Alan, thanks for the update on Alisertib. You had mentioned about still looking at other business development opportunities. How should we be thinking about what you're looking at? Are you looking at something, that you can leverage your current sales force and also perhaps use in concert with Alisertib, or how should we be thinking about what you look for?

Yeah, Ed, thanks for the question. Yeah, in terms of looking at assets, we always are ongoing looking at additional assets to bring in. Are we interested in commercial assets that we could leverage our existing sales force and could put us in a position to kind of have that channel teed up, if you will, for Alisertib? Absolutely, that would be something of interest to us. So we're looking across the span, if you will, and there's no question bringing in additional commercial assets we think would make a lot of sense, especially if they could put us in a position to kind of lay the groundwork for Alisertib.

Okay, thanks, Alan, for taking my questions. And if I could just follow-up on one question, as far as China goes when you have that bolus of patients, is that the way we should be thinking of sales into China in 2025 too, that it's going to be lumpy like that?

Yes, Ed, if you look historically at our sales to China, it's always been lumpy, and the reason for that is that we kind of have a sale into the distribution channel, kind of in those kind of lumpy boluses, if you will. So it's always been like that quarterly, and I would anticipate it would probably change. I would anticipate it would not change in 2025.

Okay, thanks for taking my questions.

The next question is coming from the line of Divya Rao with TD Cowen. Please proceed with your questions.

Hi, guys. Thanks for taking my question. I'll add my congrats on the initial data in lung cancer. Just a couple questions on that. Are the two patients that had a PR still on the trial as of the data cut? And then just in terms of expanding the dose or expanding the dose range potentially, do you have to meet with the FDA before looking at increased doses of Alisertib? And then how are you thinking about maybe how many doses you're planning on exploring? Is it just one or are you trying to go or are you trying to do like a sequential dose escalation to figure out kind of where you can get the most efficacy? Thank you.

Yep. Thanks for the questions, Divya. In terms of the two patients who are with the PRs, I apologize I don't have the data in front of me, so I don't know the answer to that question. With regard to the dose, you'll remember that we licensed this drug from Takeda, and they had previously done monotherapy dose escalation at much higher doses. We're currently dosing at 50 milligrams BID for days 1 to 7, and on that schedule I think they went as high as like 100, if I remember correctly, somewhere in that ballpark. So we've got quite a ways to go that the drug has already been tested, so I don't anticipate, we would certainly inform FDA of our decision to do that, but we wouldn't need kind of a separate meeting or like to schedule a type C meeting or something like that for that. I apologize, your last question?

Just in terms of like how many doses you're thinking about exploring and how are you thinking about the data evolving as you figure out how many doses to explore?

Yeah, so remember that, where we saw the initial efficacy in terms of these subgroups, the biomarker subgroups, was in the randomized trial, which was the Paclitaxel-Alisertib against Paclitaxel-plus placebo. We continue to think that, you know, that is the approvable randomized study design. So one issue becomes what do we do as a monotherapy. The other becomes, you know, what do you do in combination with Paclitaxel because again, I'm forecasting forward here, but let's just say for the sake of argument we do indeed decide that there's an accelerated approval pathway available here as a monotherapy. You'd have to have that trial. The FDA rule is you have to have that trial up and running and I believe they want it almost enrolled, so we kind of have to work on both of those. So I think that we're looking at potentially increasing monotherapy dose, but also in, as I mentioned, in the randomized trial that was done, the Paclitaxel plus Alisertib , they only went up to, if I remember correctly, 30 milligrams or 40 milligrams of Alisertib . We would also be looking whether or not you could increase that as well because again, what we really want to do here is get as great of an efficacy signal as we can and no question, if we can in a randomized trial position ourselves such that not only do we see that, but significant survival benefits, that would be to our advantage as well. So I think we want to kind of look at both the monotherapy dose and the combination with Paclitaxel as well.

That's helpful. Thank you.

Our next question is from the line of Gina Wong with Barclays. Please proceed with your question.

Hi. Thank you for taking our question. So this is Jenny [ph] for Gina. So we have a question about ALISCA-Breast 1 cancers interim readout. So could you provide more color about the timeline? I mean, you mentioned, like, in a medical meeting, and then we wonder, like, how many number of patients data you would report. I think last quarter, it got the readout, it's like a fourth quarter of 2024, but why it is postponed to 2025? Also, like, what is the kind of the benchmark for this, like, activity? Thank you.

Okay. So in terms of ALISCA-Breast breast, we haven't started enrolling that trial yet. So once we get enrollment for that we'll have a much better -- a better view of when we'll be able to present data. So obviously, there's two ways of presenting data. One is to do it on a call like this. The other is at a medical meeting. In terms of your second question, we originally said we were going to provide interim data on the ALISCA-Lung trial, sometime in Q4 of 2024. That's what today's update was. Now, in terms of full presentation at a medical meeting, that will be sometime next year. That's we have a steering committee. They will make that decision. In terms of what the benchmark is, again, we're taking a biomarker-driven approach to the development of Alisertib. In the previous monotherapy trial, they didn't do a biomarker analysis, so it's hard to do a comparative view. In the randomized trial, that's where they did do the biomarker analysis, and that's where the signals popped up of having PFS benefits and potentially, I believe, OS benefits in the patients with the c-Myc gains and the RB1 mutations. In terms of our current trial, again, I don't have the data in front of me, but if I remember correctly, there were more patients in the resistant refractory group that had biomarkers that were associated with a raw kinase activity than in the chemotherapy-sensitive group. So I'm hypothesizing that that's why we're seeing that difference in activity. We had previously seen with Alisertib much better activity in the chemotherapy-resistant refractory, and that was both in the monotherapy trial that was done and published in the Lancet Oncology and in the randomized trial in the journal Thoracic Oncology. Again, I don't have the data in front of me, but if I remember this correctly, in the chemotherapy-resistant refractory group in ALISCA-Lung, I believe there was five patients that had RB1 mutations and c-Myc gain, whereas in the chemotherapy-sensitive group, I believe it was only one. Again, I don't have the data in front of me. That's kind of top of my head. So, again, if what we're seeing is two responders out of five that had those biomarkers, I think that puts us in a decent position. But, again, I'm just speculating on that. Obviously, there's no -- they didn't do that in the previous studies. There's nothing to compare to. And to my knowledge, no one has developed a drug looking at the aurora kinase pathway in these biomarkers.

Thank you.

Thank you. This concludes our question-and-answer session. I would like to turn the conference back to Mariann for closing remarks.

Thank you for joining us today. As a reminder, this call may be accessed via replay at Pumabiotechnology.com beginning later today. Have a good evening.