Puma Biotechnology Inc

Good afternoon. My name is Taryn, 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 1 on your telephone keypad. If you would like to withdraw your question, simply press the number 1 again. If you should require operator assistance during the conference, you may press star 0. As a reminder, this call is being recorded. I would now like to turn the conference call over to Marianne Ohannesson, Senior Director of IR for PUMA Biotechnology. You may begin your conference.

Thank you, Taryn. Good afternoon and welcome to PUMA's conference call to discuss our financial results for the first quarter of 2022. Joining me on the call today are Alan Auerbach, Chief Executive Officer, President and Chairman of the Board of PUMA Biotechnology, Maximo Noguez, Chief Financial Officer, and Jeff Ludwig, Chief Commercial Officer. After market closed today, PUMA issued a news release detailing first quarter 2022 financial results. 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 at and available for replay for the next 90 days. Today's conference call will include statements about the company'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 national 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, 2021. Your caution not to place undue reliance on these forward-looking statements, which speak only as of the date of this live conference call, May 5, 2022. The company 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 also 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 2022 news release for a reconciliation of our GAAP to non-GAAP results. I will now turn the call over to Alan.

Thank you, Mary Ann, and thank you all for joining our call today. Today, PUMA reported total revenue for the first quarter of 2022 of $45.7 million. Total revenue includes product revenue net, which consists entirely of Neuralink sales, as well as license fees and royalties from our stub licensees. Product revenue net was $40.7 million in the first quarter of 2022, which represents a decline as expected from the $51.0 million in product revenue reported in the fourth quarter of 2021 and $45.8 million in product revenue reported in Q1 2021. Product revenue for the first quarter of 2022 included approximately $4.3 million of inventory drawdown at our specialty pharmacies and specialty distributors. Royalty revenue was $5 million in the first quarter of 2022, an increase from $2.9 million in Q4 2021 and $2.4 million in Q1 2021. We recorded no license revenue in the latest quarter. We reported 2,680 bottles of Neuralink sold in the first quarter of 2022, a decline from the 3,454 bottles sold in Q4 of 2021. As we noted on last quarter's call, bottles sold in the fourth quarter included an estimated 345 bottles representing inventory stocking at our specialty pharmacies and specialty distributors. We estimate that the inventory stocking decreased by approximately 282 bottles, in Q1 of 2022. In Q1 2022, new prescriptions were up approximately 17% compared to Q4, while total prescriptions were down approximately 1.7%. 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 add additional color on near-links commercial activities. Maximo Nuguez will follow with highlights of the key components of our financial statements for the first quarter of 2022. As we have mentioned in our prior calls, PUMA has an ongoing basket trial of neratinib and HER2-mutated cancers referred to as a summit trial. In the fourth quarter of 2021, PUMA met with the FDA to discuss the regulatory path for neratinib in patients with hormone receptor-positive HER2-negative breast cancer who have a HER2 mutation. Investors will remember that Based on the meeting with the FDA in the fourth quarter of 2019, this arm of the summit trial was modified such that patients were randomized to receive either fulvestrant alone, fulvestrant plus trastuzumab, or the combination of neratinib plus fulvestrant plus trastuzumab. Under the initial Simon 2 stage design, each of the three arms enrolled seven patients during stage 1. If no patient in a given arm responded, that arm was closed to further enrollment. If in the first stage one or more patients responded, the arm was then expanded up to 18 patients. If less than four patients in the expanded arm responded, that arm was closed to further enrollment. If more than four patients responded, the arm was expanded to 30 patients. As was previously disclosed to investors and was presented at the San Antonio Breast Cancer Symposium in 2021, for the first seven patients who were treated in the Fulvestrant alone arm of the trial, no patients achieved a response. In the seven patients who were treated with fulvestrant plus trastuzumab arm of the trial, no patients achieved a response. In the first seven patients who were treated in the neratinib plus fulvestrant plus trastuzumab arm of the trial, one or more responses were seen, and therefore the criteria was met to expand to stage two of the Simon 2 stage design. That arm of the trial was expanded to further enrollment, and an additional 18 patients have been enrolled with combination of neratinib plus fulvestrin plus trastuzumab. Enrollment to this arm has been stopped while we analyze the additional data. At the meeting with the FDA in the fourth quarter of 2021, the data from the seven patients randomized to each of the three arms was shared with the FDA. PUMA also told the FDA that they had an additional 18 patients who had been treated with the combination of neratinib plus fulvestrin plus trastuzumab and the data from these 18 patients could be shared with the FDA in 2022. PUMA plans to submit to FDA in the second half of 2022 and schedule a meeting to discuss the regulatory path for NRAD in this indication. PUMA anticipates that the FDA will either allow the company to file for accelerated approval based on the existing single arm data or may require additional data or may require a separate randomized trial for this indication. If a randomized trial is required, the company will make a decision as to whether or not to proceed based on the time and cost of the trial versus the potential market opportunity. Additional data from this cohort will be presented at the American Society of Clinical Oncology annual meeting in June of 2022. PRUMA will also plan to present data at the ASCO annual meeting from the cohort of patients in the summit with HER2-mutated biliary tract cancer who were treated with neratinib. PUMA will continue to update investors on the status of this as it progresses. As investors are also aware, in November 2020, we announced interim data from another cohort of the summit trial, more specifically the cohort of patients with metastatic non-smell cell lung cancer with epidermal growth factor, or EGFR, exon 18 mutations who have been previously treated with an EGFR-targeted tyrosine kinase inhibitor. As was shown in the data that was presented, there were four responses out of 11 patients, and therefore the criteria had been met to proceed to stage two of the Simon two-stage design and enroll 30 patients. There are currently 31 patients enrolled in this arm of the trial, and we anticipate that we will have additional data from this cohort to report in the second half of 2022. Once we receive this data, we plan to meet with the FDA to discuss the regulatory path for this indication. PUMA anticipates that the FDA will either allow the company to file for accelerated approval based on the single-arm data or may require additional data or a separate randomized trial for this indication. If a randomized trial is required, the company will make a decision whether or not to proceed based on the time and cost of the trial versus the potential market opportunity. Enrollment to this arm of the trial has been halted while we analyze the current data and wait for regulatory guidance. As mentioned on the last earnings call, PUMA is also evaluating several drugs to potentially in-license that would allow the company to diversify itself and leverage PUMA's existing R&D, regulatory, and commercial infrastructure. PUMA will continue to update investors on the status of 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. Appreciate it. And 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. Now, let me start by reinforcing our commitment and our passion about helping patients in their battle with breast cancer. We believe that Nerlings can play a key role in both early-stage disease to prevent reoccurrence after adjuvant trastuzumab-based therapy, as well as in metastatic disease. Commercially, we remain focused on three areas. Number one, leveraging and communicating the evolving positive clinical data of Neuralinks. Number two, engaging and educating patients about the risks and benefits of Neuralinks. And three, increasing our impact through field force execution and evolution. Now, I'm happy to see progress being made on all three fronts. We saw steady increases in our call activity in Q1 as access increased in parts of the country, and our sales team became more comfortable in their new geographies following our Q4 reorganization. Over 60% of our calls made in Q1 were live versus virtual, and we saw a steady increase in live calls versus virtual calls throughout the quarter. Now, the ebb and flow of COVID has been hard to predict, but we are hopeful this trend will continue. In addition, we increased our outreach to patients in various advocacy groups, adjusted our personal and non-personal promotional mix, and stayed focused on communicating the clinical benefits of Neuralinks, including the previously announced updates to the NCCN clinical practice guidelines for the treatment of breast cancer. This market remains under-penetrated, and we are committed to doing more to help support women battling breast cancer. With that high-level update, let me transition to some of the U.S. commercial slides. Once I've finished my remarks, I will turn to call over to Maximo for a more detailed review of our financial results. On slide three, you see that our distribution model has not changed. We have two channels that provide Neuralinks to patients. We refer to these as our specialty pharmacy channel and our specialty distributor channel or in-office dispensing channel. The majority of our business continues to flow through the specialty pharmacy channel, In Q1, approximately 81% of our business went through this channel, with the remaining 19% of the business flowing through the specialty distributor channel. This is slightly different than the 76% specialty pharmacy and 24% specialty distributor mix that we reported in our Q4 earnings call. This change is driven by a larger percent drawdown in the SD channel, as well as some SD demand softness that occurred in Q1. Slide 4 shows U.S. quarterly net sales of Neuralink since FDA approval. As Alan noted, our net product sales were $40.7 million in the first quarter of 2022. This is a decrease from the $50.1 million we reported in Q4 of 2021. This change is being driven by an estimated $5 million build that occurred in Q4 of 21 and a subsequent inventory drawdown of approximately $4.3 million that occurred in Q1 of 2022. This pattern of inventory build in a fourth quarter followed by a subsequent inventory reduction in Q1 is common and has been seen in prior years as shown on the slide. Slide five shows the bottles of Neuralink sold by quarter since launch. Please note this slide shows ex-factory bottles sold so it represents sales into our specialty pharmacy and specialty distribution channel and not end user demand. We sold 2,680 bottles of Nerlinks in Q1 of 2022, which is a decrease of 774 bottles from our Q4 2021 bottle sales of 3,454. The majority of this decrease was a direct result of the inventory build that occurred in Q4 and the subsequent inventory drawdown in Q1 of 2022. Now, let me provide some additional insight into the business. New prescriptions or new patient starts are a very important leading indicator for our business. These new patient starts turn into refills, which will influence subsequent quarters in terms of total bottles sold. As highlighted in previous earnings calls, we tend to see a decline in new patient starts in the fourth quarter with a subsequent increase in the first quarter of the following year due to some patients deciding to delay starting on their links until after the Q4 holidays. This pattern did play out. We previously highlighted that new patient starts declined by about 8% in Q4 of last year, which was a smaller decline than we had seen in the last several years, but nonetheless still a decline. This decline impacted our total bottle sales in Q1 of 2022. As importantly, we did see new patient starts grow by about 17% in Q1, which should benefit us in subsequent quarters as well. In regard to free drug, we continue to see an increase in the number of patients qualifying for free drug through our patient assistance program, which is being driven largely by an increase in Medicare patients who cannot cover the cost of their copay and are unable to obtain financial assistance due to the limited availability of copay support from the foundations. As previously reported, we were excited to have dose escalation added to our label in late June of last year for both our extended adjuvant indication as well as our metastatic indication. In addition, we were very pleased that NCCN updated their 2022 clinical practice guidelines for breast cancer to include dose escalation in early stage breast cancer. As you can see on slide six, we did see an increase in the adoption of dose escalation in the first quarter where almost 62% of patients were started on Neuralynx at a lower dose. Dose escalation can clearly benefit patients by significantly reducing the amount of grade three diarrhea and reducing overall discontinuations. We continue to highlight these benefits and are committed to seeing this adoption continue to grow. Now on slide seven, you see the highlights of our strategic collaborations that we have formed across the globe with the goal of making Nearlinks available to more patients around the world. We are pleased with our global partners and the progress being made. In Q1 of 2022, we saw regulatory approval in Mexico for the extended adjuvant indication, and Neuralynx was officially launched in both Ireland and South Korea. I highlighted in our Q4 earnings call that Neuralynx was added to China's National Reimbursement Drug List, or NRDL, for 2022. NRDL approval is an important milestone. The early feedback has been positive, and we're excited to see access increase in China for women battling early-stage breast cancer. Now, just to wrap up, PUMA was founded on a commitment to making a difference in the lives of patients and their families battling breast cancer. I want to thank the commercial team for their continued passion and commitment to making such a difference. We know more has to be done, and we're not going to stop until we achieve that goal. I will now turn the call over to Maximo for a review of our financial results. Maximo?

Thanks, Jeff. I will begin with a brief summary of our financial results for the first quarter of 2022. Please note that I will make comparisons to Q4 2021, which we believe is a better indication of our progress as a commercial company and year-over-year comparisons. For more information, I recommend that you refer to our Q1 2022 10-Q, which will be filed today and includes our consolidated financial statements. In the first quarter of 2022, we reported a net loss based on GAAP of $3.4 million, or $0.08 per basic undiluted share. This compares to a Q4 2021 net income of $4.2 million, or $0.10 per share. On a non-GAAP basis, which is adjusted to remove the impact of stock-based compensation expense, we reported a net loss of $0.3 million, or $0.01 per basic undiluted share. for the first quarter of 2022. Gross revenue from Netlink sales was $51.5 million in Q1 2022 versus $64.5 million in Q4 2021. As Alan mentioned, net product revenue from Netlink sales was $40.7 million compared to the $51 million we reported in the fourth quarter of 2021. We believe that Q1 net sales included approximately $4.3 million of inventory drawdown from our distributors. Project revenue totaled $5 million in the first quarter of 2022, an increase from $2.9 million in Q4 2021. Our gross to net adjustment in Q1 2022 was 21%, black from the gross to net adjustment in Q4 2021. Increases to coverage gap and co-pay charges were offset by decreases in Medicaid expenses to keep our quarter-over-quarter gross-to-net flat. Cost of sales for Q1 2022 was $10.8 million, including $2 million for the amortization of intangible assets related to our Neratinib license. Cost of sales for Q4 2021 was $11.9 million. Going forward, we will continue to recognize amortization of milestones to the last resort for about $2 million per quarter as cost of sales. For fiscal year 2022, PUMA reiterates its previous guidance that net product revenue will be in the range of $180 to $190 million. We also anticipate that our gross net adjustments for the full year 2022 will be between 21% and 22%, slightly better than our prior guidance. Furthermore, for fiscal year 2022, we continue to anticipate receiving royalties from our partners around the world in the range of $27 to $34 million, and we don't expect licensed revenue in 2022. We recognize there continues to be a great deal of uncertainty regarding the impact of COVID-19. and this may continue to negatively impact our sales, royalties, and license revenue. We anticipate that for Q2 2022, Nearlink's net sales will be in the range of $44 to $47 million. We also anticipate Q2 royalty revenues will be in the range of $7 to $9 million. We estimate that the gross to net adjustment in Q2 2022 will be approximately 20% to 21%. PUMA anticipates the net income in Q2 of 2022 will be slightly positive. SG&A expenses were $20.4 million in the first quarter of 2022, compared to $22.5 million in Q4 2021. SG&A expenses included non-cash charges for stock-based compensation of $2.2 million for the first quarter of 2022, compared to $2.4 million for Q4 2021. Research and development expenses were 15.2 million in the first quarter of 2022, compared to 14.2 million for Q4 2021. R&D expenses included non-cash charges for stock-based compensation of 0.9 million in the first quarter, compared to 1.8 million for Q4 2021. In the first quarter of 2022, PUMA reported cash burn of 17 million, compared to cash burn of 5.4 million in Q4 2021. In Q1 2022, we made a payment of $27.1 million related to our class action lawsuit and executed a private placement for $10 million. As a result of cost containment actions across the company implemented in the fourth quarter of 2021, PUMA continues to expect lower operating expenses in 2022 compared to 2021. More specifically, We anticipate SG&A expenses to be down approximately 15% to 20%, and R&D expenses to be down 10% to 15% year over year. At March 31, 2021, we had $73.9 million in cash, cash equivalents, and marketable securities. Our accounts receivables balance was $27 million. Our accounts receivable terms range between 10 and 68 days, while our day sales and standings are about 47 days. We estimate that as of March 31st, 2022, our distribution network maintained approximately four weeks of inventory. Overall, we continue to deploy our financial resources to focus on the advancement of Neratinib through ongoing clinical trials and the commercialization of Nerlix.

Thanks, Maximo. During 2020 and 2021, the COVID-19 pandemic presented significant commercial challenges to PUMA and presented significant barriers to commercial access for PUMA's commercial team. We are hopeful that with COVID cases declining and vaccination and booster rates increasing, these barriers will reduce in the future, which should improve the ability of our commercial team to access and interact with healthcare providers to increase their awareness of the Neuralink's data. We also recognize the uncertainty as to when access to health care providers will improve, and we are remaining conservative in our outlooks for improvements in access for this year. PUMA senior management, in cooperation with the board of directors, continues to remain focused on improving near-link sales in 2022 and beyond. In the fourth quarter of 2021, we implemented a reduction in expenses with the goal of reducing expenses in order to maximize operating cash flows. The company remains committed to protecting these operational cash flows 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 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?

Thank you. We will now begin the question and answer session. If you wish to ask a question, please press star 1 on your telephone keypad at this time. A confirmation tone will indicate your line is in the question queue. If you wish to withdraw your request, please press the number 1. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. Again, if you do have a question or comment, you may press star 1 on your telephone keypad at this time. We'll take our first question from Ed White with HC Wainwright. Please go ahead.

Good afternoon. Thanks for taking my question. Just a couple of questions on the Salesforce. You had mentioned that 60% of your calls are live Can you give us some background about what the change has been over the last quarter? And perhaps, did you see a change from January to March?

Ed, sure, happy to do that. The short answer to both is yes. We saw a larger percent of live calls in Q1 versus Q4, so we saw improvement there. January was slightly better than December, but February and March we saw fairly significant and steady improvement on live versus virtual. So we've seen that trend continue actually throughout the quarter.

And do you have any data showing that live is better than virtual as far as account penetration is concerned?

So I've seen a couple of things. Feedback from the field certainly is that the live interactions are deemed to be more valuable. We've also seen market research from ZS that says the sort of fatigue of virtual calls across the industry has started to weigh in. And so we qualitatively and quantitatively believe that live calls are better. It's giving us more time in front of customers as well.

And, Ed, if I can add to that, I think the other aspect with live calls is that, you know, oftentimes the rep is going into a practice that's got multiple physicians and, you know, multiple ACPs there as well as, you know, nurses and other things. When they're live, they get the opportunity to interact with, you know, lots of people, whereas on a virtual call it's just going to be one-on-one with, you know, the health care provider, the nurse, or something like that. So in a live situation, you know, we kind of refer to it as the total office call, being able to speak to as many people in the office as possible. You obviously have more of an opportunity for that.

Okay, thanks, Alan. And last question, just you had mentioned that the distribution network is sitting at on about four weeks of inventory currently. Do you expect that to remain stable or should we see a change perhaps, you know, down to three or up to five at some point?

Ed, we do see some fluctuations in our inventory levels, but that level is about normal. We don't expect it to be significantly different than that. As we mentioned in the call, we saw a fairly significant inventory build in the fourth quarter. We subsequently saw that decline largely early on in the first quarter, and it's now, for the most part, stabilized week over week. So we think that's a fairly good inventory estimate at this time.

Yes, to put a few more numbers behind it, in the fourth quarter we said that the inventory build was about 345 bottles. We saw that work down by 282 bottles in Q1, so they're still a little bit there, you know, still in there, not huge, looks like around 50 or 60 bottles or so. My anticipation would be that that might get slowly worked down over Q2 and Q3. And then again, you know, in Q4 we would expect to see an inventory build like we see every year. So that would be kind of what I would expect for the future quarters.

Thanks. And if I could sneak in one last question, can you make any comments on duration that the patients are staying on drug? You know, how is it looking for the number of bottles per patient?

And we do track duration of therapy. And what you see with Neuralynx is that first refill is really important. If we can get patients through that first refill, that first, you know, second month on drug, into that second month on drug, the discontinuation rates drop off, which is what we're trying to achieve here. We certainly believe that with the increase of dose escalation, we will see more second fills or the first refill. The bulk of our patients on dose escalation, as you look at our slide, really has occurred in the last three, six, nine months. We see that bolus above 50%. We are tracking those cohorts. I don't have any updated data to quantify that yet. But what I can tell you is in dealing with customers, the feedback from customers on dose escalation is that it's much easier for patients, much easier for the practice, much easier for physicians. We've also seen that physicians that adopt dose escalation are more likely to treat additional patients with NeurLynx as well. Hopefully that helps some. That does.

Thanks so much for taking my questions. You're welcome.

We'll take our next question from Yagal in the home events with Siddhi. Please go ahead.

Hi, team. This is Ashok Mubarak on for Yagal. Thanks for taking my question. I apologize if I missed this in your prepared remarks, hopping between calls, but can you help level set for your upcoming ASCO data for the summit cohorts, maybe any color on how many patients, level of detail, level of follow-up that you'll present for both the her two mutant breast and biliary tract cancer presentations?

Yeah, so in terms of the HER2 mutant breast, I believe it would be the additional 18 patients that have been enrolled since we last updated. And then on the biliary, I apologize, I don't remember the number off the top of my head, but it would be the full cohort that will be presented. Okay, great. In terms of the data, I would expect to see the standard response rates, PFS, and things like that.

Okay. Then maybe I'll sneak in one more follow-up. I know you've been weighing FDA discussions related to the potential for accelerated approval in HER2 immune breast and EGFR exon 18 lung. Do you have any updated thoughts on how you've been weighing that ROI in terms of maybe the need to run additional studies. I'm just curious what your latest thoughts are.

Well, yeah, I think we have, you know, all seen that the FDA seems to be a little more reticent to allow accelerated approvals on single-arm data. You know, they just had the recent panel, you know, the ODEC panel discussion on that whole topic. And so, you know, I think there's certainly risk to that, given the way the FDA appears to be communicating things. We obviously won't know until we speak with them and until we analyze all the data as well. So, you know, we really don't know. Now, in terms of kind of the, you know, risk benefit and ROI of doing that, You know, if we're going to start a randomized trial in, you know, 2003, assuming the full three years for that trial to go forward, you know, you're talking about probably, you know, 2026, getting that data for an approval in 2027, and our composition of matter patent expires in 2030. So that would be the calculations we would be using to determine the ROI on that.

Okay. Thanks for all the color.

We'll take our next question from Divya Rao with Cowan & Company. The floor is yours.

Good afternoon. This is Divya on for Mark. Thanks for taking our question. I just have two. One is on the commercial side, but do you have a sense for the sort of breakdown in terms of payer distribution between the commercial and maybe government or Medicare-based plans? And then Just another question on just the revenue breakdown based on your guidance. It looks like for the first half of the year, we're looking at like about $87 million at the upper end, and then about an 18% increase in H-2. Do you have any color on kind of the assumptions you're making for that increase in H-2? It would be helpful. Thank you.

Hey, thanks for the questions. I'll take the first question you had on payer mix. And obviously our payer mix does fluctuate, but let me give you a general color. We have about 65% of our business is commercial payers. I would say about 23% or so, 24% is government, Medicare, Medicaid, VADOD. And then we do have certainly about 10% or so that is either other or uninsured that does not include any acknowledgement of insurance coverage.

And then on the second question, which is the revenue breakdown of You know, our assumption is that you will see, you know, slight growth, you know, in terms of the Q2 to Q3 with the bulk of that growth being Q3 to Q4. Okay.

That's helpful. Thank you.

And then, as we mentioned, you know, we're expecting to be, you know, slightly net income positive in Q2. Okay.

And for our next question, we'll move to Jeff Meacham with Bank of America. Please proceed.

Hi, this is Alex Hammond on for Jeff Meacham. Thank you for taking our question. Can you talk about your expectations from the cohort 4B and 4C of the Phase II trial of the combination of Capsula plus Neurotinib in patients with HER2-positive breast cancer and brain metastases who have been previously treated with Capsula? Thank you so much.

So this is on TBCRC22, which is our trial of neratinib in patients with brain mets. So as you correctly point out, there are two cohorts. One of them is neratinib plus Quetzala in patients who are Quetzala-naive. The other is neratinib plus Cadsila in patients who have already seen Cadsila. So this is going to be very interesting data because it's going to be very applicable to the current treatment paradigm for HER2-positive breast cancer with brain mets because, you know, you are certainly seeing patients who have previously seen Cadsila either in the adjuvant setting or in the metastatic setting and then have brain mets. And then you're also seeing patients where they did not have Quetzila, either adjuvant or metastatic, and perhaps got to Kaiser as their first treatment, and therefore they're Quetzila-naive. So our expectation would be that we would see, you know, I don't remember the number of patients off the top of my head. I'm guessing it's somewhere around 20, 25-ish. where we would see, you know, the response rates and PFS in both of those cohorts. I do believe we will see patients who have previously been treated with Tukaiza as well. So I think it's going to be very, you know, real-world applicable. And, you know, remember that neratinib is in the NCCN guidelines for brain mets. So if, indeed, the data is positive, we would have the opportunity to potentially submit it to the NCCN for inclusion. which would allow physicians, you know, to be able to utilize it if they so wished.

Thank you. And for our next question, we'll turn the floor over to Gina Wong with Barclays. You may proceed.

Hi, this is Sheldon for Gina. Thanks for taking our question. Maybe one on the Exxon 18 mutation, not a lung cancer cohort that's expected in second half this year. You mentioned that you have 31 patients enrolled. Could you comment on how many of those patients have passed TKI failure? I suppose that would be the ultimate cohort that will support the FDA approval, right?

Correct. From a registrational perspective, we would be focusing on the patients who have already seen an EGFR TKI. The exon 18 mutations, when they're naive to an EGFR TKI, tend to be responsive to a, you know, first-line TKI. And that can be the first-generation drugs, so, you know, gefitinib and erlotinib, or it can be the second-generation drugs like afatinib and osomertinib. My understanding is I think those 30 patients, the large majority of them have already seen a TKI because that was where we had focused the development of the drug. So I would envision that the large majority of them have indeed failed an EGFR TKI.

Got it. Thanks.

This concludes our question and answer session. I would now like to turn the conference back to Mary Ann for closing remarks.

Thank you 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.

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