00:04 Good afternoon, my name is Alexandra, and I will be your conference call 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. [Operator Instructions] As a reminder, this call is being recorded. 00:38 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.

00:47 Thank you, Alex. Good afternoon, and welcome to Puma's conference call to discuss our financial results for the fourth 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. 01:09 After market closed today, Puma issued a news release detailing fourth 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. 01:37 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 events and results may differ from those expressed in these forward-looking statements. 01:57 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, 2021. 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, March 3, 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. 02:36 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 fourth quarter 2021 news release for a reconciliation of our GAAP to non-GAAP results. 03:00 I will now turn the call over to Alan.

03:03 Thank you, Mariann and thank you all for joining our call today. Today Puma reported total revenue for the fourth quarter of 2021, a $55.4 million. Total revenue includes product revenue, net which consists entirely of NERLYNX sales, as well as license fees and royalties from our sub-licensees. Product revenue net was $51 million in the fourth quarter of 2021, which represents increases from the $43.4 million in product revenue net reported in the third quarter of 2021 and $50 million in product revenue net reported in Q4 of 2020. 03:45 Product revenue for the fourth quarter included approximately $5 million of inventory build at our specialty pharmacies and specialty distributors. Royalty revenue was $2.9 million in the fourth quarter of 2021 versus $2.8 million in Q3 2021 and $2.6 million in Q4 2020. License revenue was $1.5 million in Q4 2021. We reported 3,454 bottles of NERLYNX sold in the fourth quarter of 2021, an increase from the 2,947 bottles sold in Q3 2021. 04:23 Bottles sold in the quarter included an estimated 345 bottles, representing inventory stocking at our specialty pharmacies and specialty distributors as mentioned earlier. New prescriptions were down 8% in Q4, compared to Q3, while total prescriptions were down 2.8%. Bottles sold through our specialty distributor network which we often refer to as our in-office network were up 2.6% in Q4, compared to Q3. Jeff will provide further details in his comments and slides. 04:55 I will now provide a clinical review of the quarter and then Jeff Ludwig will add additional color on NERLYNX commercial activities, Maximo Nougues will follow with highlights of the key components of our financial statements for the fourth quarter of 2021. As we have mentioned on prior calls, Puma has an ongoing basket trial of neratinib in HER2…

09:36 Hey, thanks, Alan. Appreciate it and thanks to everyone for joining our fourth quarter earnings call. Before, I move into the commercial review, just a reminder that I will be making forward-looking statements. Commercially, we remain focused on three areas: number one, leveraging the evolving positive clinical data for NERLYNX; two, engaging and educating patients to ask for NERLYNX; and three, increasing our impact to field force execution and evolution. It is great to see progress being made to help support women battling breast cancer overall, but this market clearly remains under penetrated and more must be done and we clearly believe that NERLYNX can play a bigger role in helping patients throughout their journey. 10:21 We were happy to announce in Q4 that NERLYNX was included in two important NCCN Clinical Practice Guideline Updates for the treatment of breast cancer. The first update added NERLYNX to the body of the guidelines for the treatment of adjuvant HER2 positive breast cancer under the heading useful in certain circumstances. Previously NERLYNX was included as a footnote only. The updated guidelines recommends considering extended adjuvant neratinib for patients with HR positive, HER-2 positive disease with a perceived high risk of reoccurrence. 10:51 The second update involved inclusion of dose escalation as an approach to improve the tolerability of neratinib in the treatment of adjuvant HER-2 positive breast cancer. These NCCN updates are important as many institutions practices and clinicians’ references guidelines in the treatment decisions. As highlighted on our Q3 earnings call, we implemented some important organizational changes in Q4. These changes were implemented based on the evolving oncology marketplace and were designed 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 overall ownership…

17:47 Thanks, Jeff. I will begin with a brief summary of our financial results for the fourth quarter of 2021. Please note that I will make comparisons to Q3 2021, which we believe it's 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 2021 10-K which we will be filed today and includes our Consolidated Financial Statements. 18:17 For the fourth quarter of 2021, we reported net income based on GAAP of $4.2 million or $0.10 per basic and diluted share. This compares to our Q3 2021 net loss of $44.7 million or $1.09 per share. On a non-GAAP basis, which is adjusted to remove the impact of stock-based compensation expense, we reported net income of $8.4 million or $0.21 per basic and diluted share for the fourth quarter of 2021. 18:56 Gross revenue from NERLYNX sales was $64.5 million in Q4 2021 versus $53.8 million in Q3 21. Alan mentioned it, net product revenue from NERLYNX sales was $51 million compared to the $43.4 million we reported in the third quarter of 2021. We believe that Q4 net sales included approximately $5 million of inventory buying from our distributors. Royalty revenue totaled $2.9 million in the fourth quarter of 2021 versus $2.8 million in Q3 2021. 19:38 Our gross net adjustment in Q4 2021 was about 21%, an increase from the 19.4% gross to net adjustment in Q3 2021. The increase was driven mainly by higher Medicaid rebate, higher co-pay and higher interest participation in government pricing. Cost of sales for Q4 2021 was $11.9 million including $2 million for the amortization of intangible assets related to our neratinib license. Cost of sales for Q3 2021 was $10.3 million. Going forward, we will continue to…

25:14 Thanks, Maximo. The COVID-19 pandemic has continued to present commercial challenges to Puma, as even with the vaccinations that have been administered in 2021, we still are noting that various to commercial access are still in place. We are hopeful that with COVID cases declining, these varies will reduce in the future, which should improve the ability of our commercial team to access and interact with health care providers to increase their awareness of the NERLYNX data. 25:41 We also recognize the uncertainty as to why an access to health care providers improve and we are remaining conservative in our outlook for improvements and access for this year. Puma’s senior management in cooperation with the Board of Directors continues to remain focused on improving NERLYNX 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 operational cash flows. The company remains committed to protecting these operational cash flows and we'll continue to reduce expenses if needed to achieve this. We look forward to updating investors on this in the future. 26:22 There continues to remain a significant unmet need for patients battling breast cancer, lung cancer and other solid tumors, we at Puma our 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. 26:39 This concludes today's presentation. We will now turn the floor back to the operator for Q&A. Operator?

26:46 We will now begin the question-and-answer session. [Operator Instructions] Your first question comes from Ed White with H.C. Wainwright. Please proceed with your question.

27:15 Good afternoon. Thanks for taking my questions. So, regarding the sales force, is the sales force right sized now and maybe if you can give us a little bit more information on virtual sales calls versus in person calls in the fourth quarter? How that compares to the third quarter and what you're seeing so far in 2022?

27:40 Hi, Ed. Let me answer your second question and then I'll have Jeff answer the first one. In terms of the virtual calls versus live, it's running about 50-50, about half of the calls are in person half of being done virtually. We haven't really seen that change a whole lot yet. We're hopeful it will change more during the year. In terms of the size of the sales force Jeff is going to comment please.

28:04 Yeah. Sure, happy to. And I believe we've got the right size for the opportunity here. As I mentioned, we made this change, certainly not just to maximize resources, but to really capitalize or right sized for the change in the oncology marketplace. There are more and more customers that have gone to virtual or preferred virtual including some continued accounts that are not accessible. So, it has allowed us to reduce our footprint, but ultimately, we feel still be able to cover the vast majority of our business. And I know this question was asked on the last call as well, we will pay very close attention to this product. This is promotionally sensitive. If we come to the point where we cannot get in front of the right customers to improve our business, we will make a business case and adjust that appropriately. But right now, we feel very good about the size and is part of that structure we put all elements of our sales force, our CNEs, our clinical nurse educators, our clinical specialists or sales reps and our strategic account managers under a local leadership team, so they can make right decisions in a quick efficient and hopefully rapid fashion. So, we feel good about it.

29:16 Thanks. You mentioned if the distribution networks at the year-end about five weeks of inventory are there, what do you expect to see throughout 2022 more like the four weeks of inventory stocking?

29:33 Yeah. So, we always see in the four quarter an inventory buy in and that's something we've seen every year. Our anticipation is and Maximo commented this in his comments, we saw the inventory buy in which was roughly 345 bottles in Q4. We're expecting to see that burn down in Q1. And so, because of that burn down, it's going to impact our Q1 sales and we see that trend if you look at the figure we put up, we see that trend every time. Our current expectation is that inventory will remain flat Q3 to Q4, -- I'm sorry, Q2 and Q3 and then come back up in Q4 again, as you get the inventory buying again.

30:16 Okay. Great. Thanks, Alan. That's what I was looking for. And then just sticking a bit more about strategy and business development. How -- are you looking at any potential targets now, or are you looking at anything perhaps early stage products or late-stage products or even currently marketed products that you can use leverage your sales reps to obtain value. I just wanted to get your thoughts on your BD development? Thanks.

30:49 Yeah. Thanks for asking, Ed. We've always been evaluating additional drugs to in-license. We tend to be more of a product centric company and that of technology centric one meaning, we're not likely to get involved in any platform that requires a big preclinical R&D investments. The company is a, what's called an NRDL. So, in our research development only, do we feel there are early stage clinical assets that could be developed, I think that's a fair assumption. Certainly, as we are going to have a lot of operating cash flows this year, assuming, we hit our numbers, and all the numbers come in and we think they're going to in our expenses stay where they are, or go down and investing that cash flow in other assets certainly would it make sense as a way to contribute value to stockholders. Obviously, we would be very picky and we would not look for something that would have a negative impact on those cash flows.

31:55 Great. Thanks, Alan for taking my questions.

32:01 Sure.

32:04 Your next question comes from Yigal Nochomovitz with Citi. Please proceed with your question.

32:09 Hi. This is Carly on for Yigal. Thanks so much for taking our questions. We were just hoping you could go into a bit more detail on the discussion you had with the FDA last quarter on the path forward for HER2 mutated breast cancer. I guess given the FDA had previously requested the amendment to SUMMIT to isolate the effect of neratinib in the randomized stage one portion. I was just curious why you now believe the FDA could potentially require another study -- another randomized study here? Thank you.

32:43 Yeah. Thanks, Carly. The randomization they required was to randomize the patients to either neratinib plus Herceptin plus fulvestrant versus Herceptin fulvestrant versus fulvestrant alone. Those would not be considered the standard of care, if you will, for that industry and it was only seven patients. I think that if they do require us to do a randomized trial, I would expect it would probably be where we have to throw in something that represents the current standard of care for ER positive patients, which will probably be something of a physician's choice type of thing, so you're correct. The purpose of the randomization was to isolate the effects of neratinib but I don't think -- number one, I don't think only seven patients would be a standard of care. But more importantly, I don't know that fulvestrant alone would be a standard of care in that setting either, so I think that's where the -- if the FDA requires one that would be probably the hypothesis as to why.

33:46 Okay. Got it. Thank you for taking the question.

33:52 Your next question comes from Marc Frahm with Cowen. Please proceed with your question.

34:00 Thanks for taking my question. You just answered what was going to be first one on breast question, maybe just a similar question on kind of what that randomized trial would look like on the lung cancer side for those discussions later in the year and kind of what the expectations are there?

34:16 Yeah. Hi, Marc. I don't know the answer to what it would look like, my assumption would be. So, we would probably be looking at patients with EGFR exon 18 mutated lung cancer. There would be patients who already had an EGFR tyrosine kinase inhibitor. So again, if they will take a single-arm trial then that will be the way to proceed if they need a randomized trial. I would assume it against there in a Pierre. I don't know until we talk to them and again these are both small indications. So, it would if again if they want a single-arm trial, we can certainly look at what the ROI on that would be, if they want to randomized one, we would need to look at what the ROI is given the market opportunity and certainly at the time that we take in the money we take to do that. Again, we want to protect our operational cash flows. It's very important to us to do that. And so, it's obviously that's the decision, we need to make.

35:15 Okay. That makes sense. And then maybe there is any updates you can provide on the T790M patent cases and prosecuting that pattern?

35:28 Yeah. So, Marc regarding the T790M IP that Puma has, as I'm sure you can imagine the topic you're discussing in the very sensitive legal matter, and so there's not really how much we can comment on.

35:43 Okay. Fair enough. Thank you.

35:45 Your next question comes from Geoff Meacham with Bank of America. Please proceed with your question.

35:53 Hi. This is Alex on for Geoff. Thank you for taking my question. Can you provide any color on why the Phase II data from the SUMMIT trial of neratinib and typical cancer patients with HER2 mutations was pushed from the first half to the second half? Thank you.

36:08 Yes. In terms of the data for neratinib in HER2 mutated cervical cancer and moving it from first half to the second half. We did not -- it get data together in time to submit it to SGO, which would be the conference we were looking for. So therefore, we're going to be the next conference we were able to do it at is in the second half.

36:31 All right. Thank you.

36:33 If I remember off the top of my head. It's the ahead. I think we were shooting for ESMO for that one. It's really just a timing issue we couldn't get it done for the FGL deadline.

36:47Thank you. Our next question comes from the line of Gena Wang with Barclays. Please proceed with your question.

36:53 Hi. Thanks for taking our questions. This is Tom (ph) for Gena. We just wanted to ask about -- we have two questions and first one about lung metrics and can you just remind us about current complaint rate and implementation of the profit treatment for diarrhea, is there any change? And my second question is thinking about the growth opportunity in 2022, how much cost of impact do you expect from the recent guidance update as well as the China reimbursement program?

37:25 Yeah. I'm sorry can you repeat those questions. We didn't hear it quite well. So, if you can speak up a little bit greatly appreciate that, please.

37:33 Sure. So, the first question is about, can you remind us about the current compliance rate and profit treatment for diarrhea, is there any change there and also other metrics if you can have more color on that front? The second question is about I think about the revenue growth opportunity in 2022, how much positive influence from recent NCCN guidance update as well as China reimbursement program.

38:07 So in terms of the compliance rate, if you will, the main diarrhea prophylaxis that we're looking at is the use of the dose escalation, as Jeff put in his slide, we have seen that increased quarter-over-quarter. We would expect that that would continue as we increase awareness of it. And as you mentioned, it's in the NCCN guidelines as well. And regarding the how much influence the NCCN guidelines will have on revenue going forward, we are certainly hopeful that the improvements of the guidelines adding relative to the body will have a positive influence. And in terms of the China that's going to be a very major influence on our numbers positively. The market for HER2 positive breast cancer in China is probably 2 times to 3 times in terms of number of patients, what it is in the U.S. and certainly being added to the NRDL, which means that the government is reimbursing it. It's a wonderful thing for patients and obviously we’ll have a very positive impact on our numbers. So, as you heard in our guidance, we're expecting a very big ramp-up in our royalties and that is -- all of our partners are showing growth, which is wonderful. And then in Europe, we're showing good growth, et cetera, but the big jump up is the China revenue there.

39:31Maybe, did you mention the compliance rate, the current compliance rate there any change there?

39:42 When you say compliance rates, can you clarify.

39:46 Like patient when they started and stay on the payment?

39:53 So let me try to address that. We do measure cohorts of patients, really by quarter. And as you look at and we do expect as the adoption of dose escalation continues. You'll see a lower discontinuation rate and hopefully an extension of overall length of therapy. The bulk of our patients have come on therapy on dose escalation in the last six months to nine months. So, we don't have a full assessment of that yet, but I can tell you that feedback from customers is very positive around dose escalation, it's easier for patients, easier for nurses and easier for customers and we've got pretty strong podium support from some of our KOLs about implementing dose escalation as well.

40:35 Thank you.

40:39 Thank you. This concludes our question-and-answer session. I would like to turn the conference back over to Mariann for closing remarks.

40:47 Thank you all for joining us today. As a reminder, this call may be accessed via replay of the webcast at pumabiotechnology.com beginning later today. Have a good evening.

41:01 Ladies and gentlemen, thank you for participating in today's conference call. This concludes our program. Everyone have a great day. You may now disconnect.