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Puma Biotechnology - Earnings Call - Q1 2025

May 8, 2025

Executive Summary

  • Q1 2025 total revenue was $46.0M (+5.0% y/y) and GAAP EPS was $0.06, with non-GAAP adjusted EPS of $0.10; management highlighted “better than expected net income” and guided to continued profitability for FY25.
  • Revenue and EPS exceeded Wall Street consensus: revenue $46.0M vs $44.6M, EPS $0.10 vs -$0.02; demand strength offset seasonal inventory drawdown and higher gross-to-net, producing a headline beat on both metrics (values retrieved from S&P Global).
  • FY2025 guidance maintained: net product revenue $192–$198M, royalties $20–$24M, net income $23–$28M, gross-to-net 20.5%–21.5%; Q2 net product revenue guided to $48–$50M and net income $4–$6M.
  • Call focus: inventory normalization (-$4.7M), dose-escalation adoption (~72%), stronger SD channel demand, Medicare Part D redesign tailwinds, and alisertib program updates with protocol amendment to increase dosing in SCLC.
  • Near-term stock catalysts: revenue/EPS beats vs consensus, inventory normalization into Q2, Medicare tailwinds, additional alisertib interim data in H2 2025, and partnership expansion (Er-Kim distribution).

What Went Well and What Went Wrong

  • What Went Well

    • Revenue and EPS beat consensus; non-GAAP EPS $0.10 vs -$0.02 consensus; revenue $46.0M vs $44.6M (values retrieved from S&P Global). CEO: “We are pleased to report better than expected net income”.
    • Commercial execution: ~72% dose-escalation starts supporting persistence/compliance; SD channel demand up ~4% q/q and ~14% y/y.
    • Clinical momentum: encouraging neratinib + T-DXd signals (PRs across HER2-altered tumors; pancreatic regression observed) and alisertib programs enrolling ahead of expectations; Phase II portion opened March 2025.

  • What Went Wrong

    • Seasonal inventory drawdown reduced net product revenue by ~$4.7M and bottles by ~251; TRx down ~9% q/q and demand down ~6% q/q.
    • Gross-to-net headwind: Q1 gross-to-net ~20.8% vs 18.2% in Q4, dampening net revenue conversion.
    • China royalties softer near term due to regulatory transitions; Q1 royalty revenue $2.9M vs $4.7M in Q4.
View the full earnings report

Transcript

Operator (participant)

Good afternoon. My name is Sherry, and I will be your conference call operator today. At this time, all participants are in a listen-only mode. After the speaker's formal remarks, there will be a question-and-answer session. If you would like to ask a question during that time, simply press the star key, then the number one on your telephone keypad. If you would like to withdraw your questions, please press star two. If you should require operator assistance during the conference, please press star zero. 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. Thank you. You may begin your conference.

Mariann Ohanesian (Senior Director of Investor Relations)

Thank you, Sherry. Good afternoon and welcome to Puma's Conference Call to discuss our earnings results for the first quarter of 2025. 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, Jeff Ludwig, Chief Commercial Officer, Heather Blaber, Vice President of Marketing, and Roger Storms, Vice President of Sales. After the close today, Puma issued a news release detailing earnings results for the first quarter of 2025. 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 securities laws. 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, 2024. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this live conference call, May 8, 2025. Puma undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference 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 a substitute for, our GAAP financial measures. Please refer to our first quarter 2025 earnings release for a reconciliation of our GAAP to non-GAAP results. I will now turn the call over to Alan.

Alan Auerbach (CEO, President and Chairman of the Board)

Thank you, Mariann, and thank you all for joining our call today. Today, Puma reported total revenue for the first quarter of 2025 of $46.0 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 $43.1 million in the first quarter of 2025, a decline from the $54.4 million reported in Q4 2024, and an increase from the $40.3 million reported in Q1 of 2024. Product revenue for the first quarter of 2025 was impacted by approximately $4.7 million of inventory decrease at our specialty pharmacies and specialty distributors. Royalty revenue was $2.9 million in the first quarter of 2025, compared to $4.7 million in Q4 2024 and $3.5 million in Q1 2024.

We reported 2,338 bottles of NERLYNX sold in the first quarter of 2025, a decrease of 626 from the 2,964 bottles sold in Q4 2024. In Q1 2025, we estimate that inventory decreased by 251 bottles. In Q1 2025, new prescriptions, or NRx, were up approximately 6% compared to Q4 2024, and total prescriptions were down approximately 9% compared to Q4 2024. Jeff will provide further details in his comments and slides. I will now provide a clinical review of the quarter. Jeff Ludwig, as well as Heather Blaber and Roger Storms, will add additional color on NERLYNX commercial activities. Maximo Nougues will follow with highlights of the key components of our financial statements for the first quarter of 2025.

At the recent American Association for Cancer Research, or AACR, annual meeting, interim data from an ongoing phase one trial, which is NCT05372, that is sponsored by the National Cancer Institute, evaluating the combination of daratinib and fam-trastuzumab deruxtecan, or in HER2, in patients with metastatic solid tumors was presented. The phase one data includes patients with metastatic solid tumors harboring HER2 overexpression, IHC3+, IRB2 amplifications, or activating HER2 mutations. In the poster presentation, 20 patients received study treatment. Dose level one had seven patients. Dose level two had four patients. Dose level three had nine patients. The most common treatment emergent adverse events of any grade included nausea, N equals 15 or 75%, diarrhea, N equals 15 or 75%, fatigue, N equals 13 or 65%, and hypokalemia, N equals 11 or 55%.

Grade three treatment emergent adverse events that occurred in more than two patients included anemia, N equals 6 or 30%, diarrhea, N equals 4 or 20%, and hypokalemia, N equals 3 or 15%. The only grade four treatment-related adverse event was neutropenia that occurred in one patient, which was 5%. One DLT, which was acute kidney injury, was observed at dose level one. No DLTs were observed at dose level two, and one DLT was observed, which was fatigue, leading to early discontinuation at dose level three. Three patients developed grade one pneumonitis, or interstitial lung disease, ILD. Two patients at dose level one and one at dose level three. The proportion of reported treatment emergent adverse events was lower at higher doses.

Of the 15 response-available patients by RECIST, four patients had a partial response, including patients with gastroesophageal, which was N equal 2, and it was one HER2-positive IHC3+ and one HER2 mutated. Pancreatic, which was one patient who was an IHC3+, and ovarian, which was one patient who was also a 3+, and the ovarian was a confirmed response. Most notably, three of five patients with advanced pancreatic cancer were observed to have tumor regression. One PR for 13 cycles, which is ongoing, and two with stable disease, consisting of one patient with a 29.4% tumor regression for nine cycles and one patient with a 13.3% regression for eight cycles. Dose level three, which consisted of trastuzumab deruxtecan at 5.4 mg per kg and neratinib about 120 mg in week one, 160 in week two, and 240 in week three and onward, was selected as the recommended phase two dose.

Part two of the study, which consists of a pharmacodynamic evaluation of trastuzumab deruxtecan with neratinib in 12 patients, opened to enrollment in March of 2025. Patients with advanced solid tumor and HER2 amplification or overexpression or HER2 mutation will be enrolled. We look forward to updated data from this trial to be presented likely in 2026. In addition, Puma currently has two ongoing phase two studies of our investigational drug alisertib, the ALISKA Breast I trial, which is a phase two trial of alisertib in combination with endocrine treatment in patients with HER2 negative, hormone receptor positive, metastatic breast cancer, and ALISKA Lung I, which is a phase two study looking at the efficacy of alisertib monotherapy in patients with small cell lung cancer.

As a reminder, the ALISKA Breast I trial investigates alisertib in combination with endocrine treatment, which consists of either anastrozole, exemestane, letrozole, fulvestrant, or tamoxifen in patients with HER2 negative, hormone receptor positive, metastatic breast cancer. Patients must be chemotherapy naive, have been previously treated with CDK4/6 inhibitors, and received at least two prior lines of endocrine therapy in the recurrent or metastatic setting to be eligible for the trial. Patients are being dosed with alisertib given at either 30 mg, 40 mg, or 50 mg twice daily, BID, on days one to three, eight to ten, and 15 to 17 on a 28-day cycle, in combination with the endocrine therapy of the investigator's choice. Patients must not have been previously treated with the endocrine treatment in the metastatic setting that is being given in combination with alisertib in the trial.

Primary efficacy endpoints will include objective response rate, duration of response, disease control rate, and progression-free survival. As a secondary objective, the company will be evaluating each of these efficacy endpoints within biomarker subgroups in order to determine whether any biomarker subgroup correlates with better efficacy, as has been seen in the preclinical and clinical studies in other cancers, including breast cancer and small cell lung cancer. The company will then look to focus the future clinical development of alisertib in combination with endocrine for patients with HER2 negative, hormone receptor positive breast cancer in patients with these biomarkers. The trial was initiated in late November 2024. There are currently 26 sites in the U.S. and 12 sites in Europe that have been activated for the trial, and the trial is enrolling ahead of expectations.

There are currently 28 patients enrolled in the trial, one expected to be enrolled this week, and six additional patients in screening. We are looking to have interim data from this trial later in 2025. With respect to the ALISKA Lung study, as discussed in the last conference call, the company believes that the data obtained to date from the ALISKA Lung I trial is providing a preliminary indication of potentially better activity in patients with biomarkers where the urokinase pathway plays a role. The most recent analysis of the pharmacokinetic data from the ALISKA Lung I trial suggests that we are seeing a lower PK of alisertib in the ALISKA Lung trial compared to the previous phase II study of alisertib monotherapy in small cell lung cancer patients that was published in Lancet Oncology.

The company is in the process of amending the protocol to increase the dose of alisertib from 50 mg to 60 mg, which the company believes will increase the PK of the drug to levels closer to what was seen in the prior phase two trial. The company looks to have additional interim data from this trial later in 2025. As mentioned on prior earnings calls and in response to investor questions, Puma continues to evaluate several drugs to potentially in-license or acquire that would 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 review of our commercial performance during the quarter.

Jeffrey Ludwig (Chief Commercial Officer)

Thanks, Alan. Appreciate it. Thanks to everyone for joining our first quarter earnings call. Before I move into the commercial review, just a reminder that I will be making forward-looking statements. The commercial team remains focused on expanding the utilization of NERLYNX with a primary emphasis on patients who are at increased risk of recurrence. The marketing team has recently revised the core sales aid aligned with this strategy. In addition, the team has continued their emphasis on improving clinical education and engagement through non-personal promotion and developed a new patient resource brochure designed to improve persistence and compliance throughout a patient's NERLYNX therapy. The sales team is working very hard on expanding overall HCP reach and frequency with an emphasis on increasing engagement when treatment decisions are being made.

In Q1 of 2025, call activity was flat year over year and down about 2% quarter over quarter, driven by an increased number of vacancies. We expect that trend to improve as these vacancies are filled. Heather Blaber, our VP of Marketing, and Roger Storms, our VP of Sales, have joined us during this call and will add some additional details in a few moments. Let me now transition to some of the commercial slides where I will provide some additional specifics around performance. Slide three is an illustration of our distribution model, which is broken out into the specialty pharmacy channel and the specialty distributor or in-office dispensing channel. In regards to the overall distribution of our business, in Q1 of 2025, about 67% of our business was purchased through the SP channel, and the remaining 33% was purchased through the SD channel.

We are seeing some stronger growth in the SD channel driven by two main factors. Number one, increased sales in the GPO segment, and two, some increasing 340B purchasing. Turning to slide four, NERLYNX net revenue in Q1 of 2025 was $43.1 million, which represents a decline of about $11.3 million from the $54.4 million we reported in Q4 of 2024, and an increase of $2.8 million from the $40.3 million we reported in Q1 of 2024. The significant change in quarterly revenue was driven largely by anticipated seasonal inventory changes and higher gross and net expenses in a prior quarter. I will provide some more details around inventory changes, and Maximo will provide some additional specifics around gross and net expenses during his update. In Q1 of 2025, we estimate that inventory decreased by about $4.7 million.

As a comparator, we estimate that inventory increased by about $3.7 million in Q4 of 2024 and decreased by about $2 million in Q1 of 2024. On slide five, slide five shows Q1 2025 NERLYNX bottle sales and also provides a year-over-year and a quarter-over-quarter comparison. In Q1 of 2025, NERLYNX bottle sales were 2,338, which represents an approximate 21% decrease quarter-over-quarter and a 3% decrease year-over-year. It is typical for us to see inventory increase in Q4 and then subsequently decline in Q1. Similar to the prior slide, let me specifically call out the inventory changes from a bottle perspective. In Q1 of 2025, we estimate that inventory decreased by 251 bottles. As a comparator, we estimate that inventory increased by 204 bottles in Q4 of 2024 and decreased by 120 bottles in Q1 of 2024.

Let me take a moment to provide some additional metrics regarding our first quarter performance, and then I'll turn the call over to Heather and Roger to share their insights into sales and marketing. In Q1, we saw enrollments increase about 6% quarter-over-quarter but decline about 8% year-over-year. We have seen some continued enrollment softness in April, which we are monitoring very closely. New patient starts or NRx followed a similar pattern, growing about 6% quarter-over-quarter but declining about 7% year-over-year. Turning to total prescriptions or TRX, we saw a TRX decline of about 9% quarter-over-quarter and a decline of about 3% year-over-year. Finally, let me share some specifics around demand. In Q1, we saw demand decline about 6% quarter-over-quarter but increase about 2% year-over-year.

As mentioned earlier, we have seen stronger demand growth in the SD channel, where we saw SD demand grow about 4% quarter-over-quarter and about 14% year-over-year. Let me now turn the call over to Heather and Roger for some additional insights. Why don't we start with Heather Blaber, our VP of Marketing? Heather, the floor is yours.

Heather Blaber (VP of Marketing)

Thanks, Jeff. I appreciate the opportunity to be on this call and share some more insights into the marketing strategy and execution. As Jeff mentioned earlier, the marketing team is focused on increasing the utilization of NERLYNX with a focus on patients who are at continued risk of recurrence. We recently conducted several focus groups with community oncologists to better understand patient risk factors that are most concerning to physicians and to garner feedback on some more recent publications regarding the overall risk of recurrence. We have utilized those insights to update and revise our core sales aid and messaging with the goal of engaging physicians on a broader set of patients where the risk of recurrence is high and where we believe that NERLYNX can play an important role in helping to reduce that risk.

In addition to revising the core sales aid and messaging, we have also recently rolled out a new patient education resource designed to better support our patients throughout their recommended course of NERLYNX therapy. This educational resource will be provided to patients on a monthly basis as they receive their refills. Lastly, I know Jeff mentioned our goal of expanding the overall share of voice. The marketing team works very closely with our field leadership team to increase the engagement with oncologists through our non-personal promotion, both branded and unbranded messaging. Our non-personal promotion efforts target a very broad group of oncologists, and we are continually evaluating new partners and new approaches that will enhance these efforts.

I know our sales team is also heavily focused on increasing engagements with healthcare providers, so now I would like to take the opportunity to turn it over to our Vice President of Sales, Roger Storms, to provide some additional insights and perspective. Roger.

Roger Storms (VP of Sales)

Thanks, Heather. I also appreciate the opportunity to participate on the call and share my perspective. I joined Puma in December of last year, so I'm still relatively new, but I'm very excited to be here and passionate about finding ways to better support HER2-positive breast cancer patients. My focus is on executional excellence and expanding overall share of voice. As previously mentioned, our Q1 call activity was flat year-over-year and down about 2% quarter-over-quarter, driven by a higher vacancy rate. My expectation is that we will see an increase in our overall reach and frequency, driven by a reduction in these vacancies, as well as better overall execution. I'm happy to say that we've made good progress on our openings and have brought in strong talent with both breast cancer experience and established relationships with key customers.

In regards to executional excellence, we are focused on helping our sales reps get in front of more customers with the goal of increasing engagement when clinical decisions are being made. We're utilizing claims data, non-personal promotion feedback, and piloting predictive analytics to help our teams prioritize their time and maximize their impact. Early feedback on the new marketing core sales aid has been positive and allows my team to discuss a broad group of patients, which is aligned with our goal of increasing the utilization of NERLYNX.

Jeffrey Ludwig (Chief Commercial Officer)

Thanks, Roger, and thanks, Heather, for providing additional specifics and insights. Let me wrap up with just a few more slides, then I'll turn the call over to Maximo for a more detailed financial review. Turning to slide six, slide six highlights the quarterly adoption of dose escalation since NERLYNX's launch. In Q1, approximately 72% of patients started NERLYNX at a reduced dose. This is similar to the 74% we reported in Q4 of 2024. Continued messaging and adoption of dose escalation remains an important commercial priority. Patients who are started on NERLYNX utilizing dose escalation have better persistence and compliance. We believe dose escalation, coupled with the new patient education resource Heather discussed, will give patients better support throughout their NERLYNX therapy and ultimately help them reduce the risk of recurrence. Slide seven highlights the strategic collaborations we have formed across the globe.

In Q1 of 2025, NERLYNX was launched in Libya in the extended adjuvant setting, and we signed a distribution agreement with Ircam for select countries in Eastern Europe and Central Asia. We really appreciate the excellent work being done by our partners around the globe and look forward to supporting their continued success moving forward. Let me wrap up by thanking the entire Puma team once again for the continued passion and commitment for helping patients and their families battling breast cancer. This disease can have devastating effects, and we know more can be done and more needs to be done. I'll now turn the call over to Maximo for a review of our full financial results. Maximo?

Maximo Nougues (CFO)

Thanks, Jeff. I will begin with a brief summary of our financial results for the first quarter of 2025. Please note that I will make comparisons to Q4 2024, which we believe is a better indication of our progress as a commercial company than year-over-year comparisons. For more information, I recommend that you refer to our first quarter 2025 10Q, which we'll refile today and includes our consolidated financial statements. For the first quarter of 2025, we reported net income based on GAAP of $3 million or $0.06 per share. This compares to net income in Q4 2024 of $19.3 million or $0.39 per share. In the fourth quarter of 2024, we released a portion of our valuation allowance, resulting in a non-cash deferred income tax benefit of $7.1 million.

The valuation allowance was established to offset our deferred tax assets, which are primarily related to our historical losses. This significantly increased our net income. On a non-GAAP basis, which is adjusted to remove the impact of stock-based compensation expense, we reported net income of $5 million or $0.10 per basic undiluted share for the first quarter of 2025. Gross revenue from NERLYNX sales was $54.4 million in Q1 2025 and $66.5 million in Q4 2024. Alan mentioned it. Net product revenue from NERLYNX sales was $43.1 million, a decrease from the $54.4 million reported in Q4 2024. The lower net revenue was driven mostly by the seasonality of inventory fluctuation and higher gross-to-net expenses than prior quarter. Inventory drawdown by our distributors was approximately $4.7 million in Q1 versus an increase of approximately $3.7 million in Q4 2024.

Royalty revenue totaled $2.9 million in the first quarter of 2025 compared to $4.7 million in Q4 2024. Our gross-to-net adjustment in Q1 2025 was about 20.8% compared to the 18.2% gross-to-net adjustment reported in Q4 2024. Cost of sales for Q1 2025 declined to $10.6 million and includes $2.4 million for the amortization of intangible assets related to our neratinib license. Cost of sales for Q4 2024 was $13.9 million. Going forward, we will continue to recognize amortization of our milestones to the license source, about $2.4 million per quarter, as cost of sales. For fiscal year 2025, Puma anticipates that net neratinib product revenue will be in the range of $192 million-$198 million. We also anticipate that our gross-to-net adjustment for the full year 2025 will be between 20.5% and 21.5%.

In addition, for fiscal year 2025, we anticipate receiving royalties from our partners around the world in the range of $20 million-$24 million, lower than 2024 due to fewer shipments expected to China as our partner works through regulatory transitions during the first several quarters of 2025. We do not expect license revenue in 2025. We also expect that net income for the full year will be in the range of $23 million-$28 million. We are not forecasting any potential release of any additional tax asset valuation allowance in our net income estimate at this time. However, this will be evaluated on an ongoing basis. We will continue to keep investors updated on these as it progresses.

At this time, we do not believe that tariffs imposed or proposed to be imposed by the U.S., particularly with other countries, will have a material impact on our product cost or results of operations. However, shifting trade policies in the U.S. and other countries have been rapidly evolving and are difficult to predict. As a point of reference, our manufacturing product cost accounts for a mid to high single-digit percentage of our total cost of goods sold. We anticipate that for Q2 2025, NERLYNX product revenue net will be in the range of $48 million-$50 million. Also, we expect Q2 royalty revenue will be in the range of $2 million-$3 million and no license revenue. We further estimate that the gross-to-net adjustment in Q2 2025 will be approximately 20%-21.5%. Puma anticipates Q2 net income between $4 million and $6 million.

SG&A expenses were $17.6 million in the first quarter of 2025 compared to $16.6 million in the fourth quarter of 2024. SG&A expenses included non-cash charges for stock-based compensation of $1.2 million for Q1 and $1.3 million for Q4 2024. Research and development expenses were $13.8 million in the first quarter of 2025, a decrease from $15.2 million in the fourth quarter of 2024. R&D expenses included non-cash charges for stock-based compensation of $0.8 million in the first quarter of 2025 compared to $0.5 million in the fourth quarter of 2024. On the expense side, Puma anticipates flat to slightly lower total operating expenses in 2025 compared to 2024. More specifically, we anticipate SG&A expenses to decrease by 5-10% and R&D expenses to increase by 10-15% year-over-year. In the first quarter of 2025, Puma reported cash burn of approximately $7.8 million.

This compares to cash earned of approximately $4.3 million in Q4 2024. Please note that during Q1, we made our fourth principal loan payment of $11.1 million related to our obligation with Aeteria. As a result of this, our total outstanding principal debt balance decreased to approximately $56 million. On March 31st, 2025, we had approximately $93 million in cash, cash equivalents, and marketable securities versus about $101 million at year-end in 2024. Our accounts receivable balance was $25.2 million. Our accounts receivable terms ranged between 10-68 days, while our day sales outstanding are about 50 days. We estimate that as of March 31st, 2025, our distribution network maintained approximately three weeks of inventory. Overall, we continue to deploy our financial resources to focus on the commercialization of NERLYNX, the development of alisertib, and controlling our expenses.

Alan Auerbach (CEO, President and Chairman of the Board)

Thanks, Maximo. Puma Senior Management, in cooperation with the Board of Directors, continues to remain focused on NERLYNX sales trends in 2025 and beyond and recognizes its fiscal responsibility to the shareholders to continue to maintain positive net income. We believe that the positive net income that was seen in fiscal years 2023 and 2024 resulted from the financial discipline across the company over the last few years. 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 Q1 2025 and the company is guiding to for full year 2025. 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 medical need for patients battling breast cancer, lung cancer, and other solid tumors. We at Puma are committed and passionate about finding more effective ways at 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?

Operator (participant)

Thank you. We will now begin the question-and-answer session. If you wish to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. If you wish to withdraw your request, please press star two. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment while we pull for questions. Our first question is from Divya Rao with Cowen & Company. Please proceed.

Divya Rao (Analyst)

Hi, Alan. Thanks for taking my questions. This is Divya on for Mark. I just had two questions on alisertib. One, I guess, could you talk about where the alisertib IP is held? Is it in Ireland? Is it in the U.S.? Also, manufacturing. The comments that you made, was that just related to NERLYNX manufacturing, or is that similar for alisertib as well? I have a second question.

Alan Auerbach (CEO, President and Chairman of the Board)

Hi, Divya. Thank you for the question. In terms of the IP, we actually have a license to the IP from Takeda. I need to get back to you on where it is physically located. The origin of alisertib is that it was originally developed by Millennium, which was here in the United States. I'm assuming that's where it is, but I don't have that information in front of me. Let me get back to you on that. It's a great question. I just don't have the information in front of me.

Divya Rao (Analyst)

Sure. No worries.

Alan Auerbach (CEO, President and Chairman of the Board)

Now, on the manufacturing, I believe it is mostly done in the U.S., if I'm remembering this correctly, currently. Now, obviously, we're not at commercial scale, and we obviously will take into account tariffs and future tariffs and things like that in the future. I believe right now, my remembrance of this is that we're doing it all in the U.S.

Divya Rao (Analyst)

Okay. That's helpful. Thank you.

Alan Auerbach (CEO, President and Chairman of the Board)

Did you have another question on the IP? I kind of cut you off there. I apologize.

Divya Rao (Analyst)

Oh, no worries. No worries. I think you answered it. Thank you.

Alan Auerbach (CEO, President and Chairman of the Board)

Thank you.

Operator (participant)

Our next question is from Gina Wong with Barclays. Please proceed.

Karen Wong (AP Analyst)

Hi. This is Khun Wong on behalf of Gina Wong from Barclays. We have a few questions. For alisertib, lung cancer phase two trial, you just mentioned the protocol amendment for dose increase. Could you confirm whether the interim data readout will still be later this year? In addition to the PK data, how did the response data look like based on the current dose? Second question is for the NERLYNX phase one data presented at AACR 2025. Some tumor types, like pancreatic cancer, showed a better response than others. How would you select a tumor type moving forward? What magnitude of PFS improvement is expected based on the response data? Lastly, we would like to ask your view on the impact from the Medicare Part D redesign and also the new CBER Director and the potential impact on the drug approval path. Thank you.

Alan Auerbach (CEO, President and Chairman of the Board)

Let me handle the first two. With regard to the small cell lung cancer, we are amending the protocol to go from 50 to 60 milligrams. In the prior monotherapy trials of alisertib, if I remember correctly, they went up as high as 100 milligrams. I think we're assuming we're going to be okay to go up to 60. I don't have the data in front of me in terms of what we would expect in terms of obviously, we haven't dosed the patients at that level yet, so I don't have the data in front of me in terms of what we'd expect in terms of changes in response rates and things like that. In terms of the biomarkers, again, I don't have the data in front of me. We did definitely see better activity in the patients where the aurora kinases pathway played a role.

We would expect we would probably see something similar to that at the higher doses as well. We still are planning to have data later this year. Obviously, the quicker we can get the amendment done and enrolled patients, the more patients at 60 milligrams we can have. I can't really speculate on that right now. With regard to the NERLYNX phase I, you are correct that we did tend to see more activity in the combination of neratinib with Enhertu. The reasons for that is mechanistically based, which is that neratinib, being an irreversible HER2 inhibitor, it internalizes the HER2 receptor. Because of that, if you have an ADC, the perception is what you're doing is you're bringing more of the ADC into the cell. That may be why we are seeing in tumor types where you historically have not seen much activity with Enhertu, like pancreatic.

We're seeing the better activity with the combination. Not clear what we would expect. I think we need more data to be able to say what we expect in terms of ORR, PFS, etc. There is no question. We are extremely encouraged by it. My understanding is that they've had quite a lot of interest in enrollment since we've opened the new cohorts. I think we'll probably have some more data on that to talk about later this year. I think my understanding is they're looking to present it publicly at a scientific conference probably in the first half of 2026, is my recollection. In terms of your commentary on the FDA, that's CBER. We go through CDER. Not a whole lot we can really add in value. If you can repeat your question on the Medicare, please.

Karen Wong (AP Analyst)

Yeah. So your view on the impact from Medicare Part D redesign in 2026 to 2027?

Alan Auerbach (CEO, President and Chairman of the Board)

In terms of you're talking about the Medicare redesign that was part of the IRA. Is that what you're asking about?

Divya Rao (Analyst)

Yes.

Alan Auerbach (CEO, President and Chairman of the Board)

Yeah. Yeah, great question. We've been paying attention to that. What we've seen from the IRA portion is that copay for patients have actually declined somewhat in 2025, and we expect them to decline in 2026 as well. We've actually seen an increase in the percentage of our business going through Medicare and a subsequent slight decrease in that going to free goods. It's actually been helpful to us, and it's made it slightly more affordable for patients to get on and stay on NERLYNX. Does that answer your question, or?

Divya Rao (Analyst)

Yes.

Alan Auerbach (CEO, President and Chairman of the Board)

Yeah. Thank you.

Divya Rao (Analyst)

Yes. Thank you.

Operator (participant)

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

Mariann Ohanesian (Senior Director of Investor Relations)

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

Operator (participant)

Ladies and gentlemen, thank you for participating in today's conference call. This concludes our program. Everybody have a great day. You may now disconnect.

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