Puma Biotechnology at H.C. Wainwright Conference: Strategic Growth and Development

On Monday, 08 September 2025, Puma Biotechnology (NASDAQ:PBYI) presented at the H.C. Wainwright 27th Annual Global Investment Conference, highlighting its strategic developments. The company showcased both the promising financial growth of its key drug, NERLYNX, and the potential of its clinical pipeline, while also addressing challenges in drug tolerability and market competition.

Key Takeaways

• Puma Biotechnology reported a 10.8% year-over-year increase in NERLYNX net revenue for Q2 2025.
• The company maintains a strong cash position of $96 million, with no public fundraising since 2016.
• Ongoing phase 2 trials for alisertib show promising early results, focusing on biomarker-defined patient populations.
• NERLYNX's market strategy includes a dose reduction to improve drug tolerability.
• Future guidance anticipates continued revenue growth and profitability in 2025.

Financial Results

• Q2 2025 Net Revenue: NERLYNX net revenue reached $49.2 million, up from $44.4 million in Q2 2024.
• Sales Volume: 2,608 bottles of NERLYNX were sold, marking a 3.7% increase year-over-year.
• Q3 2025 Guidance: Expected NERLYNX revenues are between $46 million and $48 million, with royalties projected at $2 million to $3 million.
• Full Year 2025 Guidance: Anticipated NERLYNX sales range from $192 million to $198 million, and net income is projected between $23 million and $28 million.
• Cash Position: As of the last quarter, Puma holds $96 million in cash and marketable securities.

Operational Updates

• NERLYNX: A dose reduction strategy is implemented for 71% of patients to enhance tolerability, addressing GI toxicity concerns. The drug targets both U.S. and EU markets, with significant patient populations in each region.
• Alisertib: Phase 2 trials are underway for both breast and lung cancer, with enrollment rates exceeding expectations. The trials aim to identify biomarker correlates for treatment response.
• IP Portfolio: Key patents for NERLYNX and alisertib are secured until 2030 and 2029, respectively, ensuring market exclusivity.

Future Outlook

• Clinical Trials: Interim data for the Alysca breast and lung trials are expected by late 2025 or early 2026, focusing on biomarker-directed development.
• Strategic Focus: Puma Biotechnology is committed to advancing biomarker-defined programs and refining clinical trial enrollment criteria based on initial biomarker data.

Conclusion

For further details, readers are encouraged to refer to the full transcript of the conference call.

Full transcript - H.C. Wainwright 27th Annual Global Investment Conference:

Alan H. Auerbach, CEO and President, Puma Biotechnology: Good afternoon, everyone, and welcome to the Puma Biotechnology presentation. Just a reminder, I'm going to be making forward-looking statements. On this slide, you can see Puma's product pipeline. We have our drug NERLYNX, also known as neratinib, which is currently FDA-approved, as well as in other countries for the extended adjuvant treatment of HER2-positive breast cancer. It's also approved for HER2-positive metastatic breast cancer. We also have the drug alisertib, which is an Aurora kinase A inhibitor that we currently have in phase 2 testing, both in hormone receptor-positive, HER2-negative metastatic breast cancer, and in small cell lung cancer. First, to talk about our commercial capabilities, we currently sell the drug NERLYNX in the United States, and you can see we sell it through two channels. This is referred to as our specialty pharmacy channel. There we go, our specialty pharmacy channel and our specialty distribution network.

Our specialty pharmacy channel, that is where a physical prescription is written, and it is filled by one of these pharmacies seen. In the specialty distributor network, this is where the drug is actually given to the patient at the physician's office rather than through a traditional pharmacy. On this slide, you can see our sales are reported in Q2 of 2025. As you can see on the slide, in the second quarter of 2025, we showed $49.2 million in net revenue. That was an increase from the $44.4 million in the previous year. Looking at it sequentially, the $49.2 million in Q2 was an increase from the $43.1 million that was seen in Q1 of 2025. From an X Factor perspective, there were 2,608 bottles sold in Q2 of 2025.

That was an increase from the 2,515 in Q2 of 2024, and also an increase from the 2,338 in Q1 of 2025. One of the main side effects we see with NERLYNX is that there tends to be a GI toxicity that takes place, a grade 3 diarrhea. This tends to be a first cycle effect, and there's a taxafull access of that mechanism. By the second cycle and going forward, that side effect gets reduced. We have found that by starting with a reduced dose of the drug and titrating up in the first month, there's a way of overcoming that. We've been tracking that from a commercial perspective. We first got the data on this in Q2 of 2019, and that's where you'll see you start to saw the first tick up in this happening. We then got it in the label in Q3 of 2021.

That's where you've seen the jump up here. In the most recent quarter, we saw about 71% of the patients starting at this reduced dose, and we've definitely heard feedback from the field that this has done a wonderful job of improving the tolerability of the drug. Outside the U.S., we sell the drug through our partners. You can see on this slide all the partners we have worldwide. That's Specialised Therapeutics in Australia, Medison in Israel, Knight Therapeutics in Canada, Pint Pharma in Latin America, Pierre Fabre in Europe, China, and the MENA region, Bixink in South Korea, and then we also have our partner Erkim in Russia and CIS. In all of these countries, they sell the drug, and we get a royalty back. You can see on the slide all the launches that have occurred.

In terms of the market for the drug, in the U.S., there's about 28,300 patients with early stage HER2-positive breast cancer. Our label includes both hormone receptor-positive and hormone receptor-negative patients. However, in the NCCN guidelines, they recommend the drug only in HR-positive, early stage, high risk, which is defined as those with no pathological complete response, and that's about 6,000 patients. In the EU, our label is limited just to HR-positive disease. There's 37,000 patients in the EU with early stage HER2-positive breast cancer, and about 65% to 70% of those have HR-positive disease. Here you can see our guidance for the third quarter and for full year 2025.

Our guidance for Q3 is for NERLYNX revenues of between $46 million to $48 million, royalties of $2 million to $3 million, net income of $2 million to $4 million, and gross to net in the range of 22.5% to 23.5%. For the full year, we're expecting $192 million to $198 million in NERLYNX sales, $20 million to $24 million in royalty, $23 million to $28 million in net income, and a full year gross to net of 21.5% to 22%. We also have NERLYNX in a current phase one trial combining the drug with T-DXd, also known as ENHERTU. We've seen preclinically that NERLYNX enhanced the tumor regressions with ENHERTU in HER2 and HER2 mutant breast cancer PDXs. There was interim data on this presented at the AACR meeting in 2025. As you can see, the red are the patients with HER2 mutations.

The solid blue are those with IHC HER2-positive 3+. We're very pleased to see these regressions. It was quite intriguing to see the pancreatic regressions, as ENHERTU single agent has not shown many regressions there. We'll end up seeing more data on this next year. To move now to alisertib. Alisertib is an Aurora kinase A inhibitor. It has both single-agent and combination activity in a number of solid tumors, including hormone receptor-positive, triple negative breast, small cell lung cancer, and head and neck cancer. We've seen a lot of single-agent activity with the drug in hematological malignancies as well, including PTCL and NHL. We licensed this drug from Takeda, and prior to us licensing it, it had a very well-characterized safety profile with about 1,300 patients treated across 22 company-sponsored trials. From a preclinical perspective, there's a synthetic lethality between Aurora kinase A and RB1.

More specifically, cancers that have a hypersensitive spindle assembly checkpoint tend to depend on Aurora kinase A for mitotic exit and survival. Because of that, when you inhibit Aurora kinase A, you end up getting stalled mitosis. As you can see, the activity is seen on the slide. Also, Aurora kinase A and MYC preclinically are known to co-regulate each other. This shows the existence of a positive feedback loop. Because of that, when you inhibit Aurora kinase A, you end up also causing apoptosis. To talk more about the development in breast cancer, previously, there was a single-arm trial run of alisertib monotherapy in solid tumors. They tested across all breast cancer, as you can see on the slide, and that included hormone receptor-positive, HER2-negative, HER2-positive, and triple negative.

To focus just on the hormone receptor-positive, HER2-negative, in this study, this was dosing at 50 milligrams BID days one to seven with a two-week off period. There was a 23% objective response rate seen and a PFS of 7.9 months. Here you can see the waterfall plot from that trial. The red bars represent the triple negatives, the blue HR-positive, HER2-negative, and the green HER2-positive. As you can see, very nice tumor regression seen in the HER2-negative HR-positives. On this slide, you can see the side effect profile that was seen. Because of the fact that the drug tends to inhibit spindle formation, you end up seeing a lot of the cytopenias like neutropenia, like leukopenia, and like anemia. Those were the main ones that were seen. There was also a randomized study that was run by the Translational Breast Cancer Research Consortium.

This was alisertib plus fulvestrant versus alisertib alone. As you can see on the right-hand side, the activity seen was alisertib alone, 19.6% response rate, alisertib plus fulvestrant, 20%, and the median PFS 5.6 for alisertib alone, 5.4 for alisertib plus fulvestrant. This was a slightly different dosing regimen. This was alisertib 50 milligrams BID days one to three, eight to ten, and 15 to 17 on a 28-day cycle. On the safety side, again, the cytopenias were the main ones that were seen, similar to what we've seen previously, with the main one being the neutropenias that were seen. There was also a randomized study that was run of paclitaxel plus alisertib versus paclitaxel alone, again in positive, HER2-negative metastatic breast cancer. As you can see on the right-hand side here, the PFS showed a hazard ratio of 0.56 with a P-value of 0.005.

The PFS was 10.2 months in the alisertib paclitaxel arm and 7.1 months in the paclitaxel alone arm. On the bottom of the slide, as you can see, there was a trend toward positive median OS. However, this did not hit statistical significance. Very interestingly, in the trial in the patients that were previously treated with palbociclib, so treated with a CDK4/6 inhibitor, there was a much larger increase in the magnitude of the PFS benefit. In those patients, the PFS benefit was 13.9 months versus 5.6 for the paclitaxel alisertib arm against paclitaxel alone, with a hazard ratio of 0.58 and also a much stronger CBR rate as well. From a preclinical perspective, we see that both RB1 loss and MYC upregulation are known to be seen preclinically in palbociclib-resistant HR positive breast cancer cell lines.

As was previously shown, alisertib has selective activity in tumors that have RB1 loss and with MYC upregulation. Clinically, this would make sense for why we saw that better activity in the palbociclib-treated patients. Currently, we have an ongoing study of alisertib, which we refer to as Alysca breast. This is a phase 2 dose optimization trial. We're taking patients who have received CDK4/6 inhibitors and endocrine therapy, and they've received at least two prior lines of endocrine therapy. This is in the third line endocrine setting. We're dosing in three arms: 50 milligrams BID, 40 milligrams BID, and 30 milligrams BID up to 150 patients. In the trial, we're looking at ORR, overall response rate, duration of response, disease control rate, and PFS.

When we first bought alisertib, one of the things that we looked at was the development of the drug in biomarker-sensitive populations and in a biomarker-descript population. That is clearly what we're going to be looking for in this trial as well. As we've publicly disclosed, this trial is enrolling well ahead of expectations. As we've said on the call, it's enrolling about 2x the rate we thought it would, which we find to be very encouraging. We're hoping to have interim data from this either in the fourth quarter of this year or the first half of 2026. To move now to the development in small cell lung cancer. There was a phase 2 trial run of alisertib monotherapy in all solid tumors, and this included patients with small cell lung cancer.

As you can see, in all the patients with small cell lung cancer, there was a 21% response rate with a PFS of 2.1 months. In the chemotherapy-sensitive patients, this was a 19% response rate with a PFS of 2.6 months. In the chemotherapy-resistant or relapsed, a 25% response rate with a PFS of 1.7 months. This is the waterfall plot that was seen in the trial. The light blue are the chemotherapy-sensitive patients. The red are the chemotherapy-refractory or resistant. This was a side effect profile seen. The main side effects seen here are the cytopenias, the neutropenia, the anemia, and the leukopenia. There was also a randomized phase 2 run of the trial, which was paclitaxel plus alisertib versus paclitaxel placebo in second line small cell lung cancer.

This randomized patients to alisertib 40 milligrams BID for three weeks, dosing on days 1 to 3, 8 to 10, and 15 to 17, plus paclitaxel at 60 milligrams per meter squared on days 1, 8, and 15. The control arm was placebo plus paclitaxel given at 80 milligrams per meter squared on days 1, 8, and 15 in a 28-day cycle. Very importantly, they did a very extensive biomarker analysis in this trial, and I'll be sharing that data shortly. In the ITT population, you can see there was a hazard ratio seen of 0.77, which did not hit statistical significance. In this trial, they originally randomized patients depending on sensitive and resistance from time of administration of chemotherapy. That is not the, I'm sorry, from time of response. That is not the standard definition that is used. It is usually time from completion of chemotherapy.

This was then corrected in a later analysis, and using the corrected hazard ratio, it was 0.71 with a P-value of 0.038. On the OS side, using either the original definition or corrected, did not have a statistically significant hazard ratio. As I mentioned, there was a very extensive biomarker analysis that was done in patients that were found to be positive for MYC expression. There was a statistically significant PFS benefit seen. That was a PFS benefit of 4.64 in the paclitaxel alisertib arm, 2.27 in the placebo paclitaxel with a hazard ratio of 0.29. As you can see, that's a tight confidence interval as well. That's below one. They also looked at cell cycle mutations and specifically RB1. The specific categorization was patients with CDK6, RBL1, RBL2, or RB1. The large majority of them were RB1 loss of function mutations.

As you can see in that, the PFS was 3.68 in the paclitaxel alisertib arm, 1.8 in the placebo paclitaxel, and the OS was 7.2 in the paclitaxel alisertib and 4.47 in the paclitaxel placebo. Both a PFS and OS benefit in the mutant population were observed. From a side effect perspective, again, the cytopenias were the main ones that were seen. That included the neutropenia, which stood out, as well as the anemia and the thrombocytopenia. We currently have an ongoing study, which we call the 4201 or the Alysca lung study. We originally started at 50 milligrams BID one to seven on a 21-day cycle, so days one to seven with two weeks off. As we've disclosed on our quarterly conference calls, we were seeing a PK that was lower than we expected and a bit lower than the IC50 level.

In this trial, we're giving a primary prophylaxis with GCSF, which has not been done before, and we are definitely seeing a great decrease in the neutropenia rates because of it. Because of that, it's allowing us to now dose higher, so we're now dosing at 60 milligrams BID. We think this will get more patients above the IC50 level, and hopefully, if that is seen to be safe, we can dose up to 70 milligrams and higher. In prior phase one trials, they've dosed as high as 100 milligrams, so we think we've got some room to be able to move up here, assuming we can see the same safety profile. Again, we are looking at this trial as a primary endpoint to look at biomarker correlates for the responses of either ORR, DOR, DCR, or PFS.

We would be looking to do a biomarker-defined development program for this, similar to what we're doing in positive breast. Our goal is to do a parallel clinical and biomarker development. The idea here is to look at the initial biomarkers in the 4201 and the ALISCA lung study, see which biomarkers we select best for in terms of activity, and then amend the trial so we are just enrolling with that biomarker. Again, we're also doing the assay development on the validation side so we can do a prospective CDX development as well. From an IP perspective, the IP for NERLYNX is quite strong. The composition of matter patent is issued and expires in 2030. This was extended by Hatch-Waxman in November 2021. We also have patents on the use of treatment cancer, which goes out to 2025. There are two polymorph patents, which go out to 2028.

There is a combination with capecitabine out to 2031, and then a use specifically in our marketed indication of extended adjuvant breast in 2030. For alisertib, the composition of matter expires in 2029. Use in proliferative diseases 2032, use in small cell lung cancer 2033, and treatment of breast in 2034. We've got additional patents, but we're filing and prosecuting on this, and all of these patents have the ability to be extended for up to five years through Hatch-Waxman extension. We also have IP on a related area, which is the EGFR T790M area. This has issued claims in Europe and the United States. There was a marketed drug, which is the AstraZeneca drug Tagrisso, which we believed infringed on this. We filed opposition against this. We had a jury trial that found that the patents were valid and were being infringed by AstraZeneca.

We were awarded $107.5 million in damages for acts of infringement. A judge, unfortunately, ruled that the patents were invalid for lacking enablement and an adequate written description in August of 2024, and we filed an appeal in September 2024. To go through our milestones for the company, as you can see, the ones checked are the ones we've already accomplished. We're expecting to have interim data from the ALISCA breast, as I mentioned, either in the fourth quarter of this year or the first half of 2026, and interim data from our ALISCA lung trial, which is the small cell lung cancer one in Q4 of 2025. From a management perspective, I act as CEO and President of the company. Maximo F. Nougues is our Financial Officer. Doug Hunt is our Chief Scientific Officer on the interim basis, as well as the Head of Regulatory Medical Affairs and Pharmacovigilance.

Heather Bleibers is our Senior Vice President of Marketing, and Roger Storms is our Head of Sales. Here you can see the Board of Directors of the company. The board has a very extensive background, including backgrounds on the clinical side, regulatory, finance, as well as commercial. From a financial perspective, we currently trade on the NASDAQ under the ticker PBYI. As of the last quarter, our cash and marketable securities was $96 million. Our net income was $5.9 million in the last quarter, and our cash earned was $2.9 million. We haven't raised money publicly since 2016. The two exceptions to that are in 2022, there were two private placements done. The first one was done to me and Athyrium Capital, who is our lender, and the second one just done to me. Our issued and outstanding is 50.4 million. I'll just close with the company highlights.

NERLYNX is the first HER2-positive drug approved by the FDA for the extended adjuvant treatment of early stage HER2-positive breast cancer in patients who've received prior trastuzumab. It's also the first HER2-directed tyrosine kinase inhibitor approved both in the early stage and the metastatic. In the U.S., we've got full rights from a commercial perspective to NERLYNX, which we believe is where the value for the shareholders lies. We've got clinical activity with our development stage asset alisertib in hormone receptor-positive, HER2-negative breast, triple negative breast, and small cell lung cancer, and the potential for a very novel biomarker-directed development and commercial opportunity with alisertib. I thank everyone for coming, and I assume I have time for questions. Yes, any questions?

Unidentified speaker: There are no questions. Thank you so much for the presentation. We really appreciate you, Alan, and Puma coming and presenting at our conference and the time and effort that goes into it. Thank you so much.

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