PUMA BIOTECHNOLOGY INC H.C. Wainwright 28th Annual Global Investment Conference

Great. Thank you. I want to welcome everyone to the Puma Biotechnology presentation. Just a reminder, I'll be making forward-looking statements. On this slide, you can see the product pipeline for the company. We have our drug NERLYNX, also known as neratinib, which is FDA approved and on the market both in the U.S. as well as ex-U.S. in a number of indications, including extended adjuvant, HER2-positive breast cancer, and HER2-positive metastatic breast cancer. We also have our pipeline drug, alisertib, which is an Aurora kinase A inhibitor, which we have in phase II trials, known as the ALISCA-Breast and ALISCA-Lung trials, which is in ER-positive, HER2-negative breast cancer and small cell lung cancer. To talk first about our marketed drug, NERLYNX is sold in the U.S. through Puma, through its own sales force.

We sell the drug through two networks, as you can see on the screen. The first one is the specialty pharmacy network. The other one is what we call the specialty distribution network. In the specialty pharmacy network, this is where there's a physical prescription for the drug written, and it's provided by one of these pharmacies here, and then that's how it's delivered to the patient. In the specialty distribution network, this is also called our in-office dispensing, and this is where there's no prescription written. This is just given to the patient in the physician's office. On this slide, you can see the revenue that we most recently reported for NERLYNX in the U.S. Our Q2 2026 revenue was $53.6 million. That compares very favorably to the $49.2 million in the prior year. Also looking at the comparison from Q1, again, Q2 2026 was $53.6 million.

That was $42.2 million in Q1 of 2026. We're very pleased to see that type of growth. Looking at the ex-factory bottles, we had 2,929 sold in Q2 of 2026. That compares to 2,608 in the same quarter prior year and to 2,328 in Q1 of 2026. From a pure U.S. demand perspective. Good. Thank you. Again, commercial demand 2,986 in Q2 of 2026. That compares favorably to 2,693 in Q2 of 2025 and to 2,786 in Q1 of 2026. Outside the United States, we sell the drug through partners who sell the drug for us and then pay us back a royalty. On this slide, you can see the partners that we have. In Australia, Southeast Asia, our partner is Specialized Therapeutics. In Israel, it's Medison Pharma. In Canada, it's Knight Therapeutics Inc. Latin America is Pint Pharma. South Korea is Bixink Therapeutics. Russia, CIS is Er-Kim. In Europe, Greater China, and other parts of Asia, we work with Pierre Fabre.

Here you can see our guidance for the third quarter. Our current guidance is for $54 million-$56 million in U.S. revenues from NERLYNX, and total revenue $56 million-$59 million. You can also see that our full year income, we recently raised our guidance to $205 million-$209 million for NERLYNX for the U.S. for the year. That is a raise, as you can see on the slide. Also on the net income line, we are expecting $17 million-$20 million in net income. That is also a raise from our prior guidance. Also with neratinib, there is an ongoing phase I trial that is being run by the NCI. Neratinib is an irreversible pan-HER inhibitor. When you combine it with an ADC, it ends up bringing more of an ADC into the cell preclinically.

We saw preclinical synergy, as you can see on the slide, when we combined the drug with T-DXd, also known as ENHERTU. As you can see, you saw a very nice synergy here when you did that. This data was reported at AACR last year. This is the interim data from the phase I clinical trial. This was done in tumors that were either HER2 mutated or HER2 3+ IHC. As you can see, we saw some very nice dramatic declines here. This was in a GE junction, this in esophageal, this one in a pancreatic, this one in ovarian. This trial is continuing, and I believe we are expecting data from this next year to be presented at a scientific conference. To move now to alisertib. Alisertib is an aurora kinase A inhibitor.

Prior to Puma licensing the drug, it had been tested in about 1,300 patients across 22 company-sponsored trials from the prior sponsor. It has shown single agent and activity in combination with other agents in a number of different tumor types, including hormone receptor-positive breast cancer, triple-negative breast cancer, small cell lung cancer, and head and neck cancer. It also has been extensively tested in hematological malignancies, including PTCL and NHL. From a mechanistic perspective, aurora kinase A and c-MYC tend to co-regulate each other. As you can see on the slide, aurora kinase A and c-MYC transcriptionally upregulate each other. So there is a positive feedback loop. More specifically, c-MYC upregulates cyclin D2, CDK4, and cyclin E, which creates a complex formation and therefore you get phosphorylation, which leads to cell proliferation. By inhibiting aurora kinase A, you are also inhibiting c-MYC, which can lead to apoptosis.

To move now to the clinical development of the drug in breast cancer. We have an ongoing trial we call ALISCA-Breast1, where we are testing three different doses of alisertib. 30 milligrams, 40 milligrams, and 50 milligrams BID in combination with endocrine therapy. This is as a third-line agent. These patients have all seen prior CDK4/6, and then also seen another line of endocrine before entering this trial. We announced the interim data from this on our second quarter earnings call. As you can see, this is the breakdown of the patients. As you can see, the large majority of these patients were third line, some of them even more extensive, fourth or fifth.

From a side effect profile, because of the mechanism of the drug, the main side effect that has been seen with alisertib in clinical testing has been neutropenia, and specifically grade 3/4 neutropenia. Before Puma licensed the drug, there was a trial called TBCRC 041, which tested alisertib as a single agent or with fulvestrant in ER-positive breast cancer. You can see the side effect profile, which is shown here, which showed about a 41%-42% grade 3/4 neutropenia. In ALISCA-Breast, we saw a much lower rate, which we were pleased to see. Get that to work. At the highest dose, 50 milligrams, which is equivalent to what was previous, only a 26.9% rate, and then lower rates at the lower doses.

In terms of the clinical benefits, on a best response basis, we saw a response rate of about 18.4% in the 50-milligram arm and 20% in the 40-milligram arm, and about 5% in the 30 milligram. Here you can see the progression-free survival. Both the 40 and the 50 milligram in the intent to treat population showed a roughly 5.5 month PFS. That is very similar to what was seen in TBCRC 041. The 30 milligram showed about a 2-month PFS. One of the things that was very important to us to look at is knowing the mechanism of action of the drug being an aurora kinase A inhibitor. We were looking whether or not there are selective patients that, because of activation of the aurora kinase A pathway, would respond better to the drug.

MYC, as I mentioned, tends to co-regulate and be transcriptionally upregulated with aurora kinase. We felt that MYC was one to study, and we did so very extensively. In this slide, you can see on an intent to treat basis, the patients with a higher MYC copy number, so copy number greater than 2, had a 7.29 month PFS, whereas the ones with a copy number equal to 2 had a 2-month PFS. There we go. We also looked at the percent of cells that were c-MYC positive, looking at the cohort of 11%-100% or 0%-10%. As you can see in the 40-milligram arm, the patients that were 11%-100% c-MYC positive had a PFS of 5.75 months, and the 50-milligram group, 9.3 months. We also looked at the typical subgroups that are known in ER-positive breast cancer. ESR1 is obviously one of those.

We are very pleased to see that in the patients who had ESR1 mutations in the 40-milligram group, the PFS was 3.7 months. In the 50-milligram group, 9.3 months. Also looking at the PIK3CA mutations in the PIK3CA wild-type patients. In the 40-milligram group the PFS was 5.65 months. In the 50-milligram group, as you can see, the PFS has yet to be reached. Obviously, we need to follow these patients out much further. Interestingly, when we looked at the group that was both PIK3CA wild-type and ESR1 mutated, in the 40-milligram group it was a PFS of 4.86. When we looked at the 50-milligram group, as you can see on the slide, none of the patients have yet progressed. Obviously, that is very encouraging to see, but we need to follow the patients out further to get a longer-term duration.

One of the things that we were very interested in is why we were seeing this type of activity in this ESR1 mutated and PIK3CA wild-type group. What we noted was that when we looked at the percent positive c-MYC cells and the ones who had this 11%-100%, we were seeing that both looking at it through tissue DNA and through ctDNA, we were seeing a much higher percentage of these patients having a higher percent of c-MYC positive cells. For whatever reason, we're seeing an enrichment of c-MYC in these patient subgroups, and we think that might select them for being the ones most likely to respond to alisertib. Our plan is we started the enrollment of ALISCA-Breast.

Now that we've got the interim data, we're now just focusing on both the 40 and 50-milligram population and specifically looking at the biomarkers of interest. The plan we have is once we understand what the biomarkers are, to do a parallel assay development of an assay and look to specifically amend the trial just for the patients with that biomarker-defined population and focus on that in a phase III trial. Our expected milestones is, we announced on our recent call, we've expanded the enrollment in the 40 and 50 milligram cohorts, and we're doing that as we speak. Specifically, we're going to be looking at the PIK3CA wild type and the ESR1 mutant, where we saw the best activity in the interim cut. There'll be additional interim data from this trial presented in the fourth quarter of 2026.