Puma Biotechnology, Inc.
Q3 2021 Earnings Call Transcript

Published: 4 Nov 2021

[Operator:]

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

[Mariann Ohanesian:]

Thank you, Melinda. Good afternoon, and welcome to Puma's conference call to discuss our financial results for the third quarter of 2021. Joining me on the call today are Alan Auerbach, Chief Executive Officer, President and Chairman of the Board of Puma Biotechnology; Maximo Nougues, Chief Financial Officer; and Jeff Ludwig, Chief Commercial Officer. After market closed today, Puma issued a news release detailing third quarter 2021 financial results. That news release, the slides that Jeff will refer to and a webcast of this call are accessible via the home page and Investors 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 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 actual 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 Securities and Exchange Commission from time to time, including our annual report on Form 10-K for the year ended December 31, 2020. 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, November 4, 2021. 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 third quarter 2021 news release for a reconciliation of our GAAP to non-GAAP results. I will now turn the call over to Alan.

[Alan Auerbach:]

Thank you, Mariann, and thank you all for joining our call today. Today Puma reported total revenue for the third quarter of 2021 of $46.2 million. Total Revenue includes product revenue net, which consists entirely of US NERLYNX sales, as well as license fees and royalties from our sublicensees. Products revenue net was 43.4 million in third quarter of 2021, representing declines from the 48.9 million and product revenue net reported in the second quarter of 2021 and 49.3 million in product revenue reported in Q3 of 2020. Product revenue for the quarter was negatively impacted by approximately $3.5 billion due to inventory reduction at our specialty pharmacies and specialty distributors. Royalty revenue was 2.8 million in the third quarter of 2021 versus 4.3 million in Q2 of 2021 and 1.5 million in Q3 of 2020. During the third quarter of 2021, we continued to experience challenges brought on as a result of the COVID-19 pandemic and the Delta variants. As Jeff will show in his presentation, we are reported 2947 bottles of NERLYNX sold in the third quarter, versus the 3354 bottles sold in Q2 of 2021. Bottle sales in the quarter were negatively impacted by the inventory reduction and our specialty pharmacies and specialty distributors mentioned earlier. Jeff will provide further details in his comments and slides. Due to the access limitations presented by COVID-19 call activity to physicians declined approximately 10.5% in Q3 compared to Q2. New prescriptions were up 2.9% in Q3 compared to Q2, while total prescriptions were down 3.1%. Bottles sold through our specialty distributor network which we also refer to as our in office network were down 11.9% in Q3 Compared to Q2. I will now provide a clinical review of the quarter and then Jeff Ludwig will add additional color on the NERLYNX commercial activities. Maximo Nougues, will follow with highlights of the key components of our financial statements for the third quarter of 2021. As we had mentioned on our prior calls, Puma has an ongoing basket trial of neratinib in HER2 mutated cancers, referred to as the SUMMIT trial. In the fourth quarter of 2019, 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. The purpose of the meeting in 2019 was to discuss the potential to file for accelerated approval on the data from the SUMMIT trial on the patients treated with a combination of the neratinib plus fulvestrant plus trastuzumab. At that meeting, the FDA suggested to modify the SUMMIT trial, in order to better isolate the contribution of neratinib to the efficacy seen in the SUMMIT trial for the patients treated with a combination of neratinib plus fulvestrant plus trastuzumab. In early 2020, the SUMMIT trial was amended such that ER-positive HER2-negative breast cancer patients who have a HER2 mutation were randomized to receive either fulvestrant alone, fulvestrant plus trastuzumab, or the combination of neratinib plus fulvestrant plus trastuzumab. The randomized portion of the trial was designed using Simon 2-stage designed. Each arm of the study initially enrolled seven patients during stage one. If no patient in the given arm responds, that arm will be closed to further enrollment. If in the first stage, one or more patients respond, the arm will then be expanded up to 18 patients. In less than four patients in the extended arm respond that arm will be closed to further enrollment. If four or more patients respond, the arm will be open to enroll additional patients. As was discussed on the second quarter earnings conference call, for the first seven patients who were treated in the fulvestrant alone arm of the trial, no patients received a response. In the seven patients who were treated in the fulvestrant plus trastuzumab arm of the trial, no patients achieved a response. Enrollment to the fulvestrant alone and the fulvestrant plus trastuzumab arms of the trial were therefore paused. During the third quarter Puma convened the study's independent data monitoring committee or IDMC. To review the data from both the singlet and the doublet cohorts. The IDMC recommended closing both the singlet and the doublet cohorts. In the first seven patients who were treated in the 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. This arm of the trial has been expanded to further enrollments. Currently, patients with ER-positive HER2-negative breast cancer who have HER2 mutation are only being enrolled into this triplet arm in SUMMIT, which treats patients with neratinib plus fulvestrant plus trastuzumab. We anticipate that additional data on this will be presented at the San Antonio Breast Cancer Symposium in the fourth quarter of 2021. Puma believes that the data from the randomized portion of the trial has addressed the FDAs request to isolate the contribution of neratinib to the efficacy seen in the SUMMIT trial in the patients treated with a combination of neratinib plus fulvestrant plus trastuzumab. Puma has therefore scheduled a meeting with the FDA this quarter to discuss the data from the randomized portion of the trial and to discuss the potential pathway to file for accelerated approval for the combination of an neratinib plus fulvestrant plus trastuzumab on the data in patients with ER-positive HER2-negative breast cancer who have HER2 mutation and have been treated in the SUMMIT trial. At the FDA meeting in 2019, the FDA agreed that patients treated with the triplet or neratinib plus fulvestrant plus trastuzumab, who enrolled both prior to the amendment in 2020, as well as those enrolled after the amendment would be eligible for inclusion in the efficacy database used to support approval. Puma will continue to update investors on the status of this as it progresses. As investors are also aware, last November, we announced interim data from another cohort in SUMMIT and more specifically, the cohort with metastatic non-small cell lung cancer with epidermal growth factor or EGFR, exon 18 mutations who've been previously treated with an EGFR tyrosine kinase inhibitor. We are continuing to enroll this cohort of patients and anticipate we will have additional data from this cohort to report in the first half of 2022. 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.

[Jeffrey Ludwig:]

Thanks, Alan. Appreciate it. And thanks to everyone for joining our third quarter earnings call. Before I move into the commercial review, just a reminder that I will be making forward-looking statements. In our second quarter earnings call we announced a quarter-over-quarter increase in net sales and ex-factory bottles. Our goal was and still is to deliver consistent quarter-over-quarter growth, which we were not able to achieve in Q3. Our ability to deliver consistent growth was largely based on two key assumptions. Number one, the positive evolving clinical profile of NERLYNX and two, an improvement in call activity and access driven by an increase in vaccinations and the loosening of customer restrictions. As I reflect upon our Q3 performance, I continue to feel very strongly about the evolving clinical data, and its ability to shape and change the risk benefit perceptions of NERLYNX in this underpenetrated market. The assumption that has caused us the biggest challenge is customer access, and overall declining HCP call activity. As Alan mentioned earlier, we saw about a 10% reduction in overall HCP calls in Q3 versus Q2. Now, HCP access and engagement is critical when you're trying to reposition a brand and share new evolving clinical data. Given the importance of this leading indicator, let me provide some additional insight. As I compare our pre-COVID HCP engagement with our current activity, we're still down overall about 40%. We do expect that access caused by COVID restrictions will improve in the future. But given the uncertainty of the pandemic we are focused on increasing HCP activity through both personnel and non-personnel promotion. With that high level update, let me transition to some of the US commercial slides and I will provide some additional insights along the way. Once I have finished my remarks, I will turn the call over to Maximo, who will review the full financial results. Looking at Slide 3, as you may recall, we have two channels that provide NERLYNX 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 flows through the specialty pharmacy channel. More specifically in Q3, approximately 77% of our business went through this channel with the remaining 23% of the business flowing through the specialty distributor channel. This is in line with what we reported into Q2 earnings call as well. Moving to Slide 4. Slide 4 shows US quarterly net sales at NERLYNX since FDA approval. As Alan noted, our net US product sales were $43.4 million in the third quarter of 2021. This is a decrease from the $48.9 million we reported in Q2 of 2021. We clearly do not want to see a decline in quarterly net sales. But I do want to provide a little more insight into this decline. Approximately 3.5 billion or 60% of this decline was due to a reduction in distributor inventory. Moving to Slide 5. Slide 5 shows the bottles of NERLYNX sold by quarter since launch. Please note that 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 2947 bottles of NERLYNX in Q3 of 2021, which is a decrease of 407 bottles from our Q2 2021 bottle sales of 3354. Again, approximately 60% of this decline was from a reduction in distributor inventory. As we look at our overall business, we pay very close attention to our leading indicators. We already talked about HCP call activity, but another key leading indicator is NRx or new patients' starts. These new patients turn into continuing patients and tend to benefit the subsequent quarter in terms of overall results. Looking back a few quarters, we saw an increase in new patient starts in Q1, which helps drive positive growth in Q2. We unfortunately did not sustain that same level of new patient starts in Q2, which impacted the Q3 results which we're discussing now. In focusing specifically on Q3, we did see an increase in new prescriptions of about 3% in Q3, and the commercial team is focused on improving that trend moving forward. As previously reported, we were excited to have dose escalation added to our label in late June for both our extended adjuvant indication as well as our metastatic indication. As you can see, we saw a significant increase in the adoption of dose escalation in the third quarter, where approximately 57% of patients were started or NERLYNX at a lower dose. This is a large increase from the 38.7% of patients were reported in Q2, which we believe is a result of the updated label. We are pleased with the increasing adoption of dose escalation and believe that this increased adoption will improve the overall tolerability of NERLYNX, increase the average length of therapy and ultimately allow more patients to receive the full benefit of NERLYNX. This remains a key commercial priority and we're working to ensure dose escalation is highlighted on pathways, formularies and dosing compendium. Slide 7 highlights these strategic collaborations we have formed across the globe with the goal of making NERLYNX available to more patients around the world. We continue to be pleased with our global partners and the progress being made. In terms of updates, we recently received regulatory approval in South Korea in the extended adjuvant setting, metastatic regulatory approval in Taiwan, and are happy to report that NERLYNX was launched in Peru. In addition, we're watching Mexico and Brazil closely as we are expecting regulatory decisions in the very near future. We are continuing to work very closely with our partners and look forward to future potential launches in additional countries in Europe, Latin America, Asia and the Middle East. Before I turn the call over to Maximo, I wanted to provide some additional updates that are important to our future success. I mentioned earlier that I am happy with the evolving clinical profile of NERLYNX. We have presented or published some important clinical updates over the last year that I've discussed on prior earnings calls. I'm excited to say that we will also have a nice presence at this year's San Antonio Breast Cancer Symposium, where we have nine abstracts that have been accepted. Continuing to present and highlight the evolving clinical profile of NERLYNX is a cornerstone of our strategy. We believe that these clinical updates coupled with the increasing adoption of dose escalation will collectively help us strengthen the risk benefit profile of NERLYNX and allow us to appropriately expand utilization. Lastly, I want to let you know about some important commercial organizational changes that we are implementing. It is clear that the oncology market continues to evolve and that COVID has likely caused additional access restrictions both from an acute and a chronic perspective. Given our inability to drive consistent growth, it does not make sense to maintain the same size and structure. I have taken actions to streamline our commercial organization not only to better align our financial resources, but as importantly, to simplify reporting structures, reduce layers of management and improve ownership and execution at the customer level. We have reduced the number of sales representatives and consequently adjusted the size of our territories to ensure appropriate coverage and to better account for the new hybrid environment which consists of both live and virtual interactions. We have revised our targeting to help our teams better focus our efforts where we'll have the greatest potential impact on patients. And we're building out a core strategic accounts team to better align with our largest customers. Collectively with these changes, I expect to be able to reduce the overall commercial footprint by approximately 40%. These changes will cause some disruption within the organization, but we've worked to appropriately manage vacancies over the last few months to reduce the impact on individuals. These changes are being put in place as we speak, and I look forward to updating you all on future calls as to the impact we are seeing. 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 passion and commitment to making a difference. We know more must be done and we will not stop until we have achieved our goals. I will now turn the call over to Maximo for a review of our financial results.

[Maximo Nougues:]

Thanks, Jeff. I will begin with a brief summary of our financial results for the third quarter of 2021. Please note that I will make comparisons to Q2 2021, 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 10-Q, which will be filed today and include our consolidated financial statements. For the third quarter of 2021, we reported a net loss based on GAAP 44.7 million and $1.09 per share. In Q2 2021, we reported a net loss of 5.1 million. On a non-GAAP basis, which is adjusted to remove the impact of stock based compensation, we reported a net loss of 40.4 million or $0.99 per share for the third quarter of 2021. Gross revenue from NERLYNX sales was 53.8 million in Q3 2021 versus 59.3 million in Q2 2021. As Alan mentioned it, net product revenue from NERLYNX sales was 43.4 million compared to the 48.9 million we reported in the second quarter of 2021. Royalty revenue totaled 2.9 million in the third quarter of 2021 versus 4.3 million in Q2 2021. Our gross net adjustment in Q3 2021 was about 19.4%, an increase from the 17.7% gross net adjustment in Q2 2021. The increase was driven by primarily by higher Medicare rebates. Cost of sales for the Q3 2021 was 10.3 million, including 2 million for the amortization of intangible assets related to our neratinib license. Cost of sales for Q2 2021 was 12 million. Going forward, we will continue to recognize amortization of milestones to the licensor for about 2 million per quarter as cost of sales. For fiscal year 2021, Puma anticipates that the net product revenue will be in the range of 180 million to 182 million, lower than our prior guidance. The reduction to the guidance reflects our expectations for longer than anticipated improvement in access to HCP. We also anticipate that our gross-to-net adjustment in 2021 will be between 19% and 20%. Furthermore, for fiscal year 2021, we anticipate receiving royalties from our partners around the world, in the range of 13 million to 14 million and license revenue in the range of 50 million to 52 million. We recognize there is 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 Q4 2021, NERLYNX net sales will be in the range of 42 million to 44 million. And royalty revenues will be in the range of 3.5 million to 4.5 million. Historically, in Q4 we have seen a decrease in new patient starts, patients choose to delay starting NERLYNX until after the holidays. So we are incorporating this assumption into our Q4 net sales guidance. We anticipate that the gross-to-net adjustment in Q4 2021 will be approximately 19.5% to 20.5%. SG&A expenses were 26.1 million in the third quarter of 2021 compared to 39.4 million for Q2 2021 respectively. SG&A expenses including non-cash charges for stock based compensation of 3 million for the third quarter of 2021 compared to 16.7 million for Q2 2021. Stock based compensation expenses in Q2 2021, included approximately 13.6 million resulting from a modification approved by stockholders to the term of an employee warrant. Research and Development expenses were 18.8 million in the third quarter of 2021 compared to 18.6 million for Q2 2021. R&D expenses, including non-cash charges for stock-based compensation of 1.3 million in the third quarter, compared to 1.5 million for Q2 2021. Other expenses include an increase for our legal accrual of 24.5 million, mostly to reflect the settlement in principle arrived for the class action lawsuit in October, for a total of approximately 54.2 million and an 8.4 million charge related to our debt refinancing in July 2021. In the third quarter of 2021, Puma reported cash burn of around 21.4 million compared to cash burn of 0.1 million in Q2. If we exclude onetime cash flow events that impacted Q3 2021, we would have seen positive cash flow of 0.1 million. As a result of cost containment actions across the company, such as the commercial restructuring that Jeff described, Puma is expecting lower operating expenses in Q4 and ongoing for SG&A as well as in research and development. We ended the third quarter of 2021 with 87.5 million in cash, cash equivalents and marketable securities. Our account receivables balance at September 30 was 23.8 million. Our accounts receivables terms range between 10 and 68 days, while our day sales outstanding are about 48 days. We estimate that as of September 30, 2021, our distribution network maintain approximately three weeks of inventory. Overall, we continue to deploy our financial resources to focus on advancing of neratinib through ongoing clinical trials and the commercialization of NERLYNX.

[Alan Auerbach:]

Thanks, Maximo. The COVID-19 pandemic has continued to present commercial challenges to Puma. However, we are hopeful that with the vaccinations that have been occurring in 2021 and will continue to occur throughout the year, it will reduce these barriers 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 NERLNX data. We also recognize the uncertainty as to when access to healthcare providers will improve, and we are remaining conservative in our outlook for improvement and access for the remainder of the year. Former senior management in cooperation with the Board of Directors continues to remain focused on NERLYNX revenue and sales growth for 2021 and beyond. We look forward to updating investors on this in the future. There continues to remain a significant unmet need for patients battling breast cancer, lung cancer and other solid tumors. We at Puma are committed and passionate about finding more effective ways at helping these patients during their journey, and we will continue to strive to achieve that goal.

[Mariann Ohanesian:]

This concludes today's presentation. We will now turn the floor back to the operator for Q&A. Operator?

[Operator:]

We will now begin the question-and-answer session. Your first question comes from Yigal Nochomovitz with Citi. Proceed with your question.

[Carly Kenselaar:]

Hi, this is Carly on for Yigal. Thank you for taking our questions. We have two questions. First, we're just hoping you could elaborate further on the rationale for sort of restructuring within the commercial organization and sort of how specifically the overall commercial strategy is shifting as a result of these changes. And then the second question is on 2022 and sort of as the pandemic eases, how you're thinking about the revenue trajectory heading into next year. Thanks so much.

[Alan Auerbach:]

Hi, Carly. Thanks for the questions. Jeff, would you like to handle those.

[Jeffrey Ludwig:]

Sure. Let me talk through the restructuring of the organization on the commercial side. We talked a lot about share voice. And let me just talk about share voice in a broader sense, our share voice has not been restricted because of the number of people we have in the field. But it's really been restricted because of the changes in access largely due to COVID. So in our previous structure, we essentially had excess capacity. And regardless of how hard we tried to change and adjust, we were just not able to efficiently use that capacity or those resources. Looking at a little more granular, we definitely see accounts that have restricted access to the industry. And in those cases, as you can guess it typically does not make sense to deploy resources the same way. It's an inefficient utilization of headcount. The continuing trend in oncology has been toward more restrictions versus less restriction. With that said, we do expect access restrictions caused by COVID to improve in the future. But the timing is uncertain. But ultimately, we're going to see some accounts continue to restrict access, others are going to open back up to a more hybrid situation, virtual and live, as you can guess you can be more efficient with resources there. And there'll be something opened up fully. And that's the ones we like. Our new structure should allow us to increase call activity from our current levels. And we believe we can be more effective with better targeting evolve in our evolving clinical data. And also with the reduced layers of management, we think we can execute in a more efficient and effective manner. I will end though by looking at Alan across the table for me that if we get to a position where we're not able to fully engage the customers the way we want from a capacity standpoint, I can make a very simple business case, and we can adapt very, very quickly moving forward.

[Alan Auerbach:]

We're certainly recognizing the challenges for our reps to interact with healthcare providers. And as Jeff had said, if we compare kind of our HCP calls separating with pre-COVID it's down about 40%. So if you want to kind of look at it as a quantitative aspect of the cost per rep that number is down 40%. So what we're kind of doing here is putting our calls per rep back to where it was pre-COVID by just reducing the number of reps. And just is absolutely right, if we see in 2022, that things are opening up and there is a need to add reps and go back to what we have previously, we're happy to do so. It's just we're recognizing the need to be fiscally responsible to the shareholders of the company. And if we see the need to grow, that's fine. It's just given the limited access. It just doesn't make sense to have that infrastructure right now.

[Jeffrey Ludwig:]

Carly, one other comment here, which is, we are building out a strategic accounts, team and capability which we previously really haven't had. And we think it's really important that we'll be able to better align with some of our largest most important customers going forward. And clearly a large potential or large part of the opportunity resides with those customers. So we see that as a better way of moving forward as well.

[Alan Auerbach:]

And then do you want to handle the piece on 2022?

[Jeffrey Ludwig:]

Carla, can you repeat that question? I'm sorry, I missed the second part of that question.

[Carly Kenselaar:]

Yeah. No problem. I was just asking about 2022 and just preliminary thoughts on sort of the revenue trajectory into next year.

[Jeffrey Ludwig:]

So I don't know that we've reduced, we've we publicly stated anything about 2022 revenue expectations. But obviously, I'm hoping that we can put - we can leverage the new data that we have, the evolving clinical data. We're hoping that this new organizational structure will play out to be more efficient and effective. And obviously, we're working very hard to increase our call activity and engagement with customers. The goal is to drive growth, and that's what we're continuing to try to do.

[Alan Auerbach:]

And Carly, in terms of potential new opportunities for revenue. Obviously, the mutations would be one in terms of interesting awareness in those. And the other is we have ongoing trial, which is the TBCRC 022, which is looking at neratinib in patients with brain mets in combination with Kadcyla. We're looking for that data to be presented sometime in the first half of 2022, my guess would be ASCO. And certainly due to the huge unmet medical need, in HER2-positive breast cancer for patients with brain mets and we're already in the NCCN guidelines for brain mets, there's a possibility you're going to see uptake of NERLYNX there.

[Carly Kenselaar:]

Got it. That's helpful. Thank you for taking the question.

[Operator:]

Your next question comes from Marc Frahm with Cowen. Please proceed with your question.

[Marc Frahm:]

Yes, thanks for taking my question. One clarification just on the headcount reductions in the sales force. You said the footprint would be down 40%. Is that just headcounts down 40%? Should we also expect expenses to be 40%? Or kind of one-to-one relationship there or is there a little bit of a disconnect? And then I think also in your comments, you mentioned the OpEx will go down not just for SG&A but also R&D, can you quantify that at all?

[Alan Auerbach:]

Yeah, so in terms of Jeff's comment on the 40%, the headcount would be commercial individuals that he was talking about being down 40%. In terms of the expenses that won't be down 40%. Maximo, do you want to give some guidance on that?

[Maximo Nougues:]

Yeah. Our expectation is quarter-over-quarter. So Q4 versus Q3 expenses will go down 10%, operating expenses in total.

[Alan Auerbach:]

And Marc, so R&D expenses will go down just because we don't have a lot of trials ending, but also, the way our reporting structure is, the way we record expenses, the medical affairs department, which is technically commercial, their expenses get reported through research and development. So although it's a commercial group, just the way it's structured, their expenses come in through research and development.

[Marc Frahm:]

Okay, great. That's helpful. And then I'm guessing there's often some onetime charges in there, should that - is that 10% reduction in Q4 likely to increase a bit more as we get into 2022. And the onetime charges are in the results as well.

[Alan Auerbach:]

We're not aware of any one time charges for 2022. So from an R&D perspective, we had them - we had ones like, Maximo said in the last quarter, the biggest of which was payment to the licensor. We had payment to Pfizer for European approval. That's the main one.

[Marc Frahm:]

Was one time charges associated with the resizing the sales force.

[Alan Auerbach:]

With the restructuring, yeah, Marc.

[Maximo Nougues:]

Yeah. So the onetime charges that we expect is about 1.2 million for the quarter. So that's included in our SG&A.

[Marc Frahm:]

Okay, that that's helpful, and then maybe from a data perspective. Alan, thanks for the review of the design of the HER2 mutation study in breast cancer. And the analysis that was done on the first seven patients within the Simon 2-stage design, is that the exact data set that we will see at San Antonio Breast? Or do we effect a more updated dataset with potentially more follow up on those patients and maybe even some additional patients since this trials continued?

[Alan Auerbach:]

Yeah, that is a good question. I do not know the answer to that right now. Yeah, I apologize. My memory isn't as good as it once was. I recently saw that presentation and I don't - I know it was the seven patients from the triplet arm. And the updated follow up on them. I don't know if we - like the patients enrolled post randomization, I don't know if there'll be part of that. It's a poster presentation. And that's public information but it's a poster presentation. I don't know that - I don't remember if we're going to put in the ones from post randomization. So I apologize I don't have that right now.

[Marc Frahm:]

Okay. No worries, like trials keep track of. Thanks very much for answering the questions.

[Operator:]

Your next question comes from - I apologize, it looks like we have Paul Choi with Goldman Sachs. Please proceed with your question.

[Unidentified Analyst:]

Hi, this is Kate on for Paul. Thank you for taking our questions. We have two of them. First, for the EGFR lung study, what additional data will the FDA require beyond the SUMMIT data to support an accelerated approval? And then second, what sort of feedback have you gotten from physicians regarding the new dose escalation regimen? Thank you.

[Alan Auerbach:]

So let me take the first one. In terms of EGFR lung, we are specifically looking at patients with exon 18 mutated, exon 18 EGFR mutated lung cancer who have already failed, and EGFR TKI. To answer your question, what will the FDA require? I don't think we know the answer to that right now, because we've not had a discussion with them post the data, if you will, to know what they would require. I imagine, I think we have in our milestones that we're going to plan a meeting with the FDA to discuss that. My speculation would be that we have certainly seen a lot of these rare mutations in lung that the FDA has required a single arm trial. I think, if I remember correctly, it's usually around 50 or 100 patients or so. I would assume the data from SUMMIT would suffice for that. So we could just expand it to that. That would be my assumption. I don't have any concrete words from FDA on that. The trial has been enrolling very well, I think we're close to like 30 patients in that arm already. So we're well on our way. I just don't have - I can't give you any feedback, because we even had that specific discussion with the FDA. On your second question on the dose escalation, I will answer and Jeff you can add in. With the universal feedback we have got has been very favorable. They definitely have said that it makes a notable difference in the grade three diarrhea rate, and also the overall tolerability of it. And I would say we continue to hear very, very positive feedback on that. Jeff, would you like to add.

[Jeffrey Ludwig:]

Yeah. Alan, I'll try not to be redundant you. I would say the same thing Kate. We've seen very good feedback from customers. The evidence really is this significant uptick we saw in Q3, and as you can guess, that is a blended number for all of Q3. So we continue to see weekly and monthly, very nice uptick of dose escalation, that data is based off of the control data. And that's why the FDA approved it that showed the greater than 60% reduction in grade three diarrhea and greater than 80% reduction in discontinuations. Customers believe in that data, they're seeing early feedback that is very positive as they treat patients. It's helping the nursing staff as well. And we think ultimately, it will help patient stay on drug and get the full benefit of NERLYNX, which we obviously believe is very important to us.

[Unidentified Analyst:]

Awesome, thank you so much.

[Jeffrey Ludwig:]

Thank you.

[Operator:]

Your next question comes from Geoff Meacham with Bank of America. Please proceed with your question.

[Alex Hammond:]

Hi, this is Alex on for Geoff Meacham. Thank you for taking our question. So our first one is when you look at the commercial access disruptions caused by COVID, how do you see the script potentially recovering once the pandemic subsides? I think it'll be a spike quarter-over-quarter or do you think it'll be maybe something a little bit more gradual? And the second one is any color that you can provide on the global partner launches during the quarter in terms of feedback you've been receiving in the field. So those are my two. Thank you.

[Alan Auerbach:]

Yeah. Jeff would like to answer both those questions?

[Jeffrey Ludwig:]

Sure. Let me give it a shot. So Alex, I think the first comment is, let me be go on record to say that I've been wrong on COVID every step of the way, we've been in the ebbs and flows and spikes along the way. So that's been challenging. But as we've seen COVID across the country, what we see is pockets and spikes, we see some loosening of restrictions some go in the other direction. So everything that we're counting on in our forecast is that we're going to see a slow, steady, hopefully reduction in COVID cases and a slow, steady increase in access. That's what we would count on, we obviously would hope for a much greater spike. But that's just not what we've been seeing as we've monitored over the last 17 months here.

[Alan Auerbach:]

And if I can just add to that real quick, Alex. I think we were optimistic early in 2021 that with vaccinations and COVID numbers dropping that we would start to see access improving. And as Jeff said, we're wrong, we just have not yet seen that. At some juncture, I think we will, it's just very hard to predict when that will be. And Jeff, do you want to answer the one on the global partner?

[Jeffrey Ludwig:]

Yeah, Alex, obviously, we're - as we mentioned in the upfront comments, we're very pleased with the partnership. Our global partners, they're doing a nice job of moving NERLYNX to regulatory approval and launches. We're excited that NERLLYNX was launched in Peru just recently. We expect it to be launched for metastatic in Taiwan soon. And as I stated, we're excited to see what happens in Mexico and Brazil. The initial launches, from the customers on the ground has been positive, there's unmet need across the globe. And we think NERLYNX fills a nice niche unmet need. So we're seeing some nice, slow, steady uptick that is important to us.

[Alan Auerbach:]

Yeah. And Alex, I can add to that. We've been very lucky to have some really great partners. Our largest, which is Pierre Fabre, who's been doing a wonderful job of it, and we've been very pleased with their execution.

[Alex Hammond:]

Great, thank you so much.

[Operator:]

Your next question comes from Gena Wang with Barclays. Please proceed with your question.

[Sheldon Fan:]

Hi, this is Sheldon on for Gena. Thanks for taking our questions. Maybe one on the TBCRC Kadcyla combo data. So this is in brain mets patient population and what type of impulse would you presents? And could you talk about the benchmark and recorded path and also your thoughts on the future of commercial landscaping to this indication given that ran out other drugs in the second and third line also showed pretty strong activity in the CNS. Thanks.

[Alan Auerbach:]

Yeah. Let me take that question. So the TBCRC 022 trial is a trial that originated with Pfizer. When we licensed the drug we took it on and we have expanded it. The trial originally was getting random alone in patients with HER2-positive of metastatic breast cancer that had brain mets. We expanded it to look at the combination with capecitabine which is XELODA. And then we expanded again to look to combination with Kadcyla. The reason we were looking at combination with Kadcyla is that the preclinical data shows that neratinib being an irreversible HER2 inhibitor, ends up increasing internalization of the HER2 receptor. So you end up bringing more of the - when you combine with an ADC you end up bringing more of the ADC inside the cell. And so you have kind of a synergistic effect. We have a trial of that combination, neratinib plus Kadcyla called FB-10, which we reported at ASCO, a 60% response rate, which was much rather we expected, which we believe is a testament to that. In terms of the patients in TBCRC 022. These are all patients with HER2-positive breast cancer with brain mets. It's been - again, it's neratinib with Kadcyla and there are two cohorts of patients. One, are the patients who have previously been treated with Kadcyla. The second is the patients who have not been previously treated with Kadcyla. My understanding from the investigators is it is likely both of those cohorts will be reporting out most likely at ASCO next year. Because of the timing of when the trial has been going, I would expect we would also have a number of patients in the trial who've been treated with some of the newer agents, like in HER2 or Tukysa. In terms of what I would say is the benchmark, you're looking at patients who are late stage failed other existing therapies. There's really no treatment for these patients because other than Tukysa, I don't think there's any drug that actually has HER2-positive metastatic breast cancer with brain mets in their label or even has much data on it. I would say anything north of a 20% response rate, I think would be viewed as encouraging. I don't know that we're looking to go run a large Phase III trial in this indication, but we would certainly look to try to submit it to the NCCN guidelines. As you're aware, neratinib is already in the NCCN guidelines for brain mets. So I think we would look to update those guidelines with this new data.

[Sheldon Fan:]

That's very helpful. Thanks.

[Operator:]

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

[Mariann Ohanesian:]

Thank you for your interest in Puma Biotechnology. As a reminder, this call may be accessed via replay of the webcast at pumabiotechnology.com beginning later today. Have a good evening.

[Operator:]

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