Puma Biotechnology, Inc. (PBYI) Earnings Call Transcript & Summary

All right. Good morning, everyone, from the virtual JPMorgan Healthcare Conference. My name is Cory Kasimov, and it's my pleasure to introduce our next company, Puma Biotechnology, and Chairman and CEO, Alan Auerbach. Please note there will not be a Q&A session following this presentation. So with that, Alan, thanks for being with us here today, and let me turn things over to you.

Great. Thank you very much, Cory. Are we moving to my slides now? So just a reminder, I'm going to be making forward-looking statements. So on Slide 3, you can see our product pipeline with neratinib. As you can see, we have neratinib in many different indications, both marketed ones as well as ones in developments. In terms of marketed indications, the drug is approved in 2 indications, both in HER2-positive breast cancer. One is the extended adjuvant indication, where it's approved as a monotherapy. The other is a metastatic indication, where it's approved as a combination. And that's based on the ExteNET Phase III results as well as the NALA trial. Also in the extended adjuvant, we have a Phase II trial known as CONTROL, where we're looking at ways of reducing the side effect profile of the drug. We, also in the metastatic, have a trial known as FB-10, combining neratinib with Kadcyla, which is also known as T-DM1. We are also looking at neratinib in a specific subgroup of patients with metastatic disease, and that subgroup is those with brain metastases. And that's an ongoing study known as TBCRC 022. Outside of HER2-positive breast cancer, we're also looking at neratinib in HER2-mutated tumors. And that includes HER2-mutated breast cancer, HER2-mutated cervical cancer and exon 18 mutated non-small cell lung cancer. Those are all part of a large trial we refer to as SUMMIT, which is our basket trial, and I'll be going through each one of these trials on the slide in more detail. On Slide 4, we can start talking about the commercial aspects of Puma. So right now, we currently sell NERLYNX, which is neratinib, in the United States using our own commercial sales force. And we sell it through 2 channels. One is the specialty pharmacy network, which you can see on the slide. And there are several pharmacies where a physical prescription is written, and then that is delivered to the patient. And then we also have another channel that we refer to as specialty distributor network, and this is also referred to as the in-office dispensing. And this is where, instead of a prescription being written, the bottle is actually given to patients in the physician's office. On Slide 5, you can see our quarterly revenues for NERLYNX, and this starts from launch in Q3 of 2017 and goes to our most recently reported quarter, which is Q3 of 2020. So as you can see, in Q3 of 2020, we reported $49.3 million in NERLYNX U.S. sales. On our third quarter earnings, our guidance for Q4 was revenues of between $49 million and $51 million, and we are reiterating that guidance again. On Slide 6, you can see our quarterly bottles sold for NERLYNX, and this is, again, starting at launch in Q3 of 2017 and going to the most recently reported quarter, which was Q3 of 2020. As you can see on the slide, in Q3 of 2020, we sold 3,611 bottles of NERLYNX, and there was a slight decline from the 3,728 in Q2 of 2020. As we reported on our call in Q3 of 2020, we've been having some challenges due to COVID and not being able to get into the physician's office to market to them. We have also been hearing from a number of different physicians and health care providers that they're seeing less patients coming into the physician's office, specifically in kind of this extended adjuvant indication due to concerns over COVID. So we've also been impacted by that as well. On Slide 7, one of the ways that we have been able to overcome the side effect profile of the drug is by doing things upfront to try to prevent it. The main side effect profile of NERLYNX is that the drug can cause an upfront severe diarrhea, grade 3 or higher diarrhea. This tends to occur in the first month or 2 that the patient is on the drug. So we did a very large trial known as CONTROL, which I'll talk about in more detail. And one of the ways we found to be very effective in managing that upfront diarrhea was to start with kind of half a dose of the drug and then kind of titrate up in that first month to full dose. So we've been -- we first got the data showing this at ASCO in 2019, which you can see on the slide is Q2 of 2019. And at that point, about 10.7% of the prescriptions being written were using this reduced dose. And then as awareness of it increased, we started to see a higher percentage of it being used. Obviously, with COVID, our ability to increase awareness of this was decreased quite dramatically. So you can notice it started to level off as the COVID impact hit in Q1 of 2020. We are doing a lot from a nonpersonal promotion standpoint to try to increase awareness of this because we do find, and we get feedback that it does help with the tolerability of the drug and decreasing the discontinuation. So this is something we're -- to increase the awareness of this is something that's going to be a major goal of ours in 2021. On Slide 8, you can see our rest-of-the-world partnerships. So as I mentioned, we sell NERLYNX ourselves in the United States. Outside the United States, we have partnerships with a number of other organizations. And you can see those on the slide. In Australia and Southeast Asia, our partner is Specialised Therapeutics; in Israel, Medison; in Canada, Knight Therapeutics; in China, CANbridge; in Latin America, Pint; and then in Europe, the Middle East, North and West Africa, South Africa and Turkey, it's Pierre Fabre; and then in South Korea, it's Bixink. In the large number of these situations, the drug has been approved and already launched, and our partners sell them for us and then pay us back a royalty. Clearly, in 2021, we will see a lot more launches in a number of other countries. So we are optimistic that we're going to see a nice increase in the royalties being paid to us. So on Slide 9, you can see the CONTROL study. This is a Phase II study that we undertook to try to decrease the side effect profile of the drug. So again, NERLYNX causes a grade 3 or higher diarrhea in the first 1 or 2 cycles that the patient is on the drug. So what we first looked at was using antidiarrheal agents like loperamide to see whether or not that could reduce it. And then we tried combining it with other agents like anti-inflammatories or a bile acid sequestrant. And basically, it was testing in the extended adjuvant indication, so testing it for an entire year, and just using this prophylaxis technique for the first cycle or 2. On Slide 10, you can see the way the CONTROL study was designed. The first cohort looked at using loperamide, which is Imodium alone. We then combined it with budesonide and then combined it with colestipol. And then the one on the far right is the one I was referring to earlier, which is a dose escalation. And in this situation, we just do a dose escalation. There's no antidiarrheals that are mandated. They're just used as needed. And this is starting with a low dose of the drug and then titrating it up. On Slide 11, you can see the results of this. And as you can see, so on the right-hand side of the slide, you'll see the results for the ExteNET trial, which basically show the grade 3 diarrhea rate of 40% and 17% of the patients discontinuing the drug due to diarrhea and 26% of them having a dose reduction due to the diarrhea. So as you can see, as we were using different techniques, whether it's the loperamide, the loperamide budesonide, loperamide colestipol or the dose escalation, we were able to nicely reduce the grade 3 diarrhea rates, also decreased the percentage of patients that had diarrhea that led to discontinuation or to a dose reduction. You'll note that in the arm that's the dose escalation, that appeared to be where we got the best results overall. So decreasing the grade 3 diarrhea rate from 40% down to 13%, decreasing the percent of patients discontinuing from 17 down to 3, and discontinue -- and decreasing the number who had a dose reduction from 26 down to 3. This is one of the reasons that we have been trying to increase awareness of this technique. And we've been getting very positive feedback on it, and that's going to be, again, a very key goal for us in 2021. On Slide 12, you can see the number of patients in the U.S. and Europe that have early-stage breast cancer treated with adjuvant treatment. This comes out to about 28,300 patients in the United States and 37,000 in the EU. One point to note is that our label in the United States includes both hormone receptor positive and hormone receptor negative patients, whereas our label in the EU only includes hormone receptor positive patients, which we believe makes up about 65% to 70% of those patients in the EU. On Slide 13, you can see our Phase III NALA trial, and this was our metastatic trial, and this was in third-line or later HER2-positive metastatic breast cancer. Patients were allowed to enter the trial who had asymptomatic CNS mets as well. This was done under an SPA from FDA as well as scientific review from the EMA. Patients were randomized in a 1:1 fashion to get either neratinib with capecitabine, which is also known as Xeloda; or lapatinib with capecitabine. And the co-primary end points were centrally confirmed PFS and overall survival. And there was a number of secondary end points, as you can see on the slide. And the one I'll be talking quite a bit about is this time to intervention for CNS mets. So on Slide 14, you can see the results of the trial. Again, this was in third-line HER2-positive metastatic disease and essentially confirmed PFS hit the primary end point with a hazard ratio of 0.76 and a log rank p-value of 0.0059. As you can see, the curves kind of separated very nicely the more time that went out. Because of the fact that the proportional hazard ratio was violated in this trial, we had prespecified a restricted means analysis. And on Slide 15, you will see that analysis. So the restricted means analysis, which was prespecified, showed that the mean PFS for the neratinib plus capecitabine was 8.8 months, and for the lapatinib capecitabine was 6.6 months, so an improvement of 2.2 months in PFS. And again, the p-value there, 0.0003. On Slide 16, you can see the overall survival for the co-primary end point. The trial did not hit the end point for overall survival. The hazard ratio was 0.88 with log rank p-value of 0.2086. And the improvement from a restricted means perspective, it was an improvement of from 22.2 months to 24 months, so an improvement of roughly 1.7 months. So on Slide 17, as I mentioned, one of the key co-primary end points was time to intervention for CNS mets. And so this was defined as basically any therapeutic intervention for CNS mets. We know that neratinib crosses the blood-brain barrier. So what we are trying to look at in this study was whether or not neratinib would prevent brain mets. So as you can see on the slide, both in terms of the therapeutic interventions, whether they be radiation therapy, surgery, anticancer medications, neratinib showed a reduction in the need for those. And then we also looked at the overall cumulative incidence of brain mets in the trial. And as you can see, there was a nice improvement and a nice reduction in the incidence of brain mets. It was 22.8% in the neratinib arm and 29.2% in the lapatinib bar, and that p-value was 0.043. Interestingly, lapatinib is also known to cross the blood-brain barrier. So it was very nice in this trial because both arms included drugs, HER2-directed drugs, that could actually cross the blood-brain barrier. So the market for third line HER2-positive metastatic breast, it's about 6,400 patients in the U.S. that have third-line metastatic disease and about 4,700 with fourth-line metastatic disease. And that's on Slide 18. Moving now to Slide 19. Another ongoing study we have in the metastatic is the FB-10 study. This is a Phase I/II trial of neratinib with Kadcyla, which is also known as T-DM1. When Kadcyla was first approved, the data was largely in a population that had not seen the current first-line standard of care, which is Perjeta. And data has come out that has shown that the response rate to Kadcyla tends to decrease a bit in patients who have previously been treated with Perjeta. So if I remember the numbers correctly, I believe the response rate with Kadcyla in the metastatic trial that it was proved was somewhere in the 40% range. And if you looked at patients who were previously treated with Perjeta, it was down more in the 20% to 25% range. So we did the FB-10 study, looking at neratinib with Kadcyla, and we mandated that the patients had to have had prior treatment with Perjeta. And we did a dose-ranging study, 120, 160, 200 to 240 with the approved dose of Kadcyla. On Slide 20, you can see the results from this. And this data was presented at ASCO a few years ago, and the study is still ongoing. We saw initially a response rate of 60%, which was -- we are very pleased with. That's higher than either the Kadcyla data in the Perjeta-naive patients or in the Perjeta-treated patients. And we're also very pleased to see a number of CRs as well that had very good duration. So this trial is still ongoing. We're anticipating that an update of that to this trial could be presented sometime in 2021. So on Slide 21, you will see the TBCRC 022 trial. And this is a study that we are doing, looking at neratinib in patients with breast cancer who have tumors that have gone into the brain, also referred to as brain mets. What's very interesting about this trial is that we've had a number of cohorts, looking at both neratinib as a single agent but also in a number of combination therapies as well. The 2 I'll be talking about more is the cohort 3, which is the combining with neratinib with capecitabine and in cohort 4. The data for cohort 3, I will show you shortly. Cohort 4 is ongoing. And I'm anticipating that cohort 4c, which are the patients with progressive CNS mets and have had prior Kadcyla, we're expecting that data to be presented sometime in 2021. This will be the first data looking at neratinib with Kadcyla in patients with brain mets. And there was data at the San Antonio Breast Cancer Meeting this year, showing that a very unique attribute of neratinib is that being an irreversible inhibitor compared to some of the reversals, neratinib causes an increase in internalization of the HER2 receptor. So when you combine it with an ADC like Kadcyla, you end up increasing the intratumoral levels of that ADC. So we'll be seeing the first test of this from a clinical perspective in brain mets with that data. And I would anticipate that sometime in the second half of this year. Cohort 3, which is shown on Slide 22, was testing neratinib with capecitabine in patients with brain mets, and this was in a population of patients that had not had prior lapatinib. And the response rate we've seen was 49%. And as you can see, we have a nice waterfall plot that is shown. And based on this data, as you can see on Slide 23, neratinib is actually in the NCCN guidelines for brain mets. So it's a Category 2A based on the data I just showed you with neratinib and capecitabine. And then we also are in the guidelines under our Category 2B based on another metastatic trial known as NEfERTT, which was a trial that showed that neratinib was able to prevent brain mets in a first-line metastatic setting. So on Slide 24, we have the SUMMIT basket trial. The way this trial was designed is it was designed initially as a tumor-agnostic study, where basically any patient that had an EGFR exon 18 or a HER2 or HER4 mutation was enrolled in the trial. If we got a -- any one of them that kind of hit the first threshold in a Simon's 2-stage, to expand it, we then expanded it to its own separate individual basket. So as you can see on the slide, the 3 baskets that I want to talk more about is the EGFR exon 18 lung, the HER2-mutated cervical and the hormone receptor positive breast. So on Slide 25, to start talking more about the hormone receptor positive breast cohort. So on Slide 26, HER2 mutations in breast tend to occur in estrogen receptor positive breast cancer. And it makes up about 7% to 9% of ER-positive breast cancer. This tends to be mutually exclusive with HER2 amplification. So you don't see tumors that are HER2-positive and HER2-mutated. That's kind of rare that you see that. They tend to be HER2-negative tumors that will -- are also HER2-mutated. When we first started testing neratinib as a single agent, we noted that there was crosstalk that was occurring between the estrogen receptor and the HER2 mutation. And more specifically, as we suppress the HER2 mutation with neratinib, the estrogen receptor increased its transcription. And so it was starting to overexpress itself as a way around the tumor. We started to give fulvestrant so that we could block both the upregulation of the estrogen receptor and the HER2 mutation. And what we are seeing is that a mechanism of resistance to that treatment was that the tumor was now converting from being HER2-negative to HER2-positive. So we then modified the trial to add Herceptin, which is trastuzumab, so that we are blocking the estrogen receptor with fulvestrant, the HER2 mutation with neratinib and then trying to prevent the mechanism of resistance, which was flipping from being HER2-negative to positive using Herceptin. So on Slide 27, the data on this has been very well published. We first published the neratinib monotherapy data in Nature in 2018 and then the monotherapy data as well as the data on neratinib with fulvestrant was published in Cancer Discovery. We also published the most recent data on the neratinib plus Herceptin plus fulvestrant cohort at the San Antonio Breast Cancer Meeting last December. So on Slide 28, you will see the data from that cohort. And as you can see on the slide, we saw a very nice waterfall plot. The large majority of the patients showed tumor regression, a very nice response rate. And very interestingly, we were able to see responses in tumors of various histologies, whether they were lobular or ductal; in patients who had, had prior fulvestrant or had not had prior fulvestrant; in patients who had prior CDK4/6; in patients who did not have prior CDK4/6; and in patients with other co-mutations, like co-mutations in CDH1, PIK3CA, TP53, ERBB3 or ESR1. It was very nice to see this very broad depth of responses, and we are very pleased with the data. On Slide 29, you can also see the swimmer plot, which shows the durations. So as you can see, we saw a number of partial responses as well as 1 CR as well. And the duration has tended to be quite good. And some of these patients going out as much as 135, 140 weeks, many of them going out well over a year. So we're very pleased to see these long durations as these patients tended to be pretty heavily pretreated. A lot of -- I think it was around 75% of these that had prior chemo, and obviously, a lot of them had, had prior -- and multiple endocrine therapies as well. So in third, fourth quarter of 2019, we had gone to the FDA to see what the approval pathway would be for this. And what the FDA asked us to do was to do a Simon 2-stage to better understand the contribution of neratinib to that triplet efficacy. What they asked us to do was to do a randomized trial of one arm being fulvestrant Herceptin neratinib, one arm being Herceptin with fulvestrant and another one being fulvestrant alone. It's a Simon 2-stage, so you have 7 per arm. If you hit 1 response, or 1 or more responses, you expand the basket to a total of 18 patients. If not, you shut down that arm. Enrollment in this was negatively impacted in 2020 due to COVID. It then did pick up again in the third and fourth quarter. So we're very pleased with that. And we should be able to have this trial fully enrolled in the first half of 2021. And that would allow us to get the initial data from this and hopefully to have a meeting to discuss a potential accelerated approval pathway with the FDA sometime in the first half of 2021 as well. To move now to the SUMMIT cervical cancer cohort. In cervical cancer, about 5% of cervical cancer has a HER2 mutation. It tends to be enriched in the adenose and a high occurrence in the HPV-positive tumors. So this is neratinib monotherapy data. This was published in gynecological oncology. And as you can see, we saw a very nice response rate here, and it really didn't matter where the HER2 mutation was located, whether it was extracellular or intracellular, where we're still able to see responses. On Slide 34, you can see the durations, which is the swimmer plot. And again, we saw some very good durations, a number of these ongoing. We will continue to update this data at some time in the future, probably in 2021 as well. So now moving to Slide 35. We can now talk about the EGFR exon 18 lung data. So on Slide 36, EGFR exon 18 mutations have shown themselves preclinically to be very sensitive to neratinib. And so here, you can see the results of the in vitro studies. And on the left, you will notice the comparative effects of neratinib on the EGFR exon 18 cells. This is compared to the other EGFR exon, or the EGFR TKIs that includes first generation ones like gefitinib and erlotinib; the second-generation ones like afatinib and dacomitinib and AZD9291. And as you can see, neratinib tends to have the best preclinical activity in those exon 18 mutations. Moving to Slide 37. Previously, and this was actually prior to Puma licensing neratinib, there was a Phase II trial that had been done of neratinib in an all-comers lung cancer. In that trial, there were 4 patients that had EGFR exon 18 mutations and specifically had the G719X mutation. In that -- of those 4 patients, 3 of them had shown a partial response with a median PFS of 52.7 weeks. So on Slide 38, this was one of the reasons we included this in our basket trial, and we reported the results of the initial results of this basket trial on our earnings call in November of 2020. So these are the results from the first 11 patients in the SUMMIT basket trial who have EGFR exon 18 mutated lung cancer. We had an n of 11 patients, and you can see the breakdown of those patients. Importantly, the group that we're focusing on are the ones who've been treated with a prior tyrosine kinase inhibitor. So as you can see on Slide 38, in the trial, 10 or 91% of those patients have been treated with a prior tyrosine kinase inhibitor. And that included gefitinib erlotinib, osimertinib or afatinib. So on Slide 39, you can see the initial efficacy results that we reported in the TKI-pretreated patients, which is where we're focusing going forward. In those 10 patients, we had a confirmed response rate of 40%, a best response rate of 60% and a median duration of response of 7.5 months and a median PFS of 9.1 months. Enrollment in this trial is continuing, and we'll be reporting results from that sometime in 2021. We're also going to be doing a lot to increase awareness of this data within the lung cancer community, so doing a number of presentations throughout 2021 at lung cancer specific meetings to increase awareness of the data and also help to future the -- to the future enrollment in the trial as well. On Slide 40, you can see both the waterfall plot on the right and the swimmer plot on the left. As you can see, we saw very nice responses, both in patients who had either just a single mutation of G719X or co-mutations with either E709X, S768I or the triple mutations, which was G719C, the S768I and the T790M. In terms of the durations, in terms of the swimmer plot on the left, we're very pleased to see these durations as well. And again, we'll be continuing to update this data at some point in the future. On Slide 41, from a safety perspective, we are actually quite pleased. While, as I mentioned earlier, neratinib is known to have a side effect profile, which is grade 3 diarrhea, in this small cohort of patients, we did not see any incidence of grade 3 diarrhea. Most of the side effects we saw are more of a grade 1, grade 2 type of perspective. On Slide 42, you can see this in a little more detail. So the majority of these patients had a grade 1 diarrhea. There was 1 patient with a grade 2, but we did not see any with a grade 3. Moving to Slide 43. To put this into some perspective, afatinib, which is known as Gilotrif, is actually the only drug that has actually in its label anything with exon 18 mutations. And there's quite a bit of data on afatinib in both TKI-naive and TKI-pretreated patients. As I mentioned, where we're focusing neratinib is in the TKI-pretreated patients. And as you can see for -- on Slide 43, for the G719X mutation, which were the exon 18s, afatinib had a response rate of roughly 10.5%. So obviously, the 40% that we're seeing right now in the SUMMIT trial compares very, very nicely to that. On Slide 44. So the success criteria for the Simon's 2-stage was met for both the first and second stage of the Simon's 2-stage design. So we're continuing enrollment in that second stage. And it's designed to be up to a total of 30 patients. As I mentioned, we'll be presenting additional data from this in the first half of 2021 and then also throughout the year. And at some point in 2021, we would like to schedule a meeting with the FDA to discuss a potential accelerated approval strategy for neratinib in these EGFR exon 18-mutated lung cancer patients. Slide 45, to talk a little bit about HER-Seq, which is our HER2 mutation screening protocol. So on Slide 46, we have a trial known as HER-Seq, which is a trial in which we have an NGS assay that we developed in-house. And we're doing this as a cfDNA trial, where we're looking at the plasma ctDNA and screening patients. And if they have HER2 mutations, we're then using that for enrollment in the SUMMIT trial. So this is showing a little more detail on Slide 47. HER-Seq was set up in December of 2018 for both metastatic and cervical patients. The patients consented. We take a blood sample. We send it to a central lab. We then run this proprietary mutation sequencing test on it. If a HER2 mutation pops up, we then refer them to the SUMMIT study. If it does not, we then retest them 3 to 6 months later to see whether a mutation has popped up at that point. On Slide 48, the HER-Seq trial is open at 21 sites. We have been -- we expanded it throughout 2020 to a number of the other sites as well. The goals were to screen 2,500 patients with breast and 1,200 patients with cervical, which we felt would be enough to be able to enroll what we needed in the SUMMIT trial. So on Slide 49, we also have a number of ongoing ISTs, and these go into some of the tumors we're testing in other situations but also in tumors that we're not doing anything from a registrational perspective in either. So this includes areas like HER2-amplified and HER2-mutated colon cancer, as you can see on the left on Slide 49. Also glioblastoma, we are part of the INSIGhT trial, which is in EGFR-mutated glioblastoma. We do have a number of trials ongoing in breast as well like plasmaMATCH and some of the other studies being done at MD Anderson or SOLTI and then also just in a variety of other HER2-mutated tumors as well. We anticipate that some of these trials could read out sometime in 2021. So as they read out, we look forward to reporting those to investors. So in terms of the milestones for Puma on Slide 50. We're looking to report the Phase II data from the cohort of patients treated with bile duct cancer, and that's actually going to be at ASCO GI this week. Then we also will have the Phase II data from the cohort of patients and SUMMIT with non-small cell lung cancer, which is the EGFR exon 18 mutations in the first half of 2021. We're hoping to conduct our pre-NDA meeting with the FDA to discuss the accelerated approval for neratinib in the HER2-mutated HR-positive breast, and cervical, also sometime in the first half of 2021. We have the Phase II data from the TBCRC 022 trial, which we mentioned was the Kadcyla plus neratinib in patients with HER2-positive breast cancer with brain mets previously treated with Kadcyla, and that should probably be in the second half of 2021. And then also, sometime during the year, conduct a meeting with the FDA to discuss the potential accelerated approval pathway for neratinib in EGFR exon 18 mutated lung cancer who have been previously treated with an EGFR tyrosine kinase inhibitor. On Slide 51, to talk a little bit about the IP for the drug. Our composition of matter patent is issued. That expires in 2025. We have filed for Hatch-Waxman extension. We are waiting to hear back from that. If we do get that extension, that would take the composition out to 2030. We also have use patents in the treatment of cancer going out to 2025. There's 2 polymorphs that have the IP around them that go out to 2028. The third line metastatic, which is in combination with capecitabine, we have a use patent that covers that combination that goes out to 2031. And then we also have a patent on the use and extended adjuvant, which is our first indication that goes out to 2030. On Slide 52. We also have IP in a related area, which is in the EGFR T790M mutations. This includes issued claims in Europe, Asia and Australia, which expire right now, in 2026, and there might be the possibility of extending that for up to 5 years. We also have issued claims in the United States as well that expire in 2026 as well. These patent claims in Europe were initially challenged at an opposition hearing that -- and they were -- and we won and they were upheld in February 2014. There was also an appeal to that, and that opposition occurred in December of 2020. And again, the patent claims are upheld after that appeal as well. The specific claims are for a pharmaceutical composition that comprises an irreversible EGFR inhibitor for use in treating cancer that has a T790M mutation and then also claims for pharmaceutical composition for use in the treatment of cancer, including lung cancer and non-small cell lung cancer. While we are not clinically developing neratinib in this specific indication, we do recognize that there are a number of drugs both on the market or in development that are indeed in this indication. And this opens up an opportunity, we believe, for a potential licensing opportunity for us, where we can bring in additional value to the shareholders. On Slide 53, from a management perspective, I act as the CEO and President of the company, Dr. Richard Bryce is our Chief Medical and Scientific Officer, and he has prior experience at Onyx and Roche, where he ran breast cancer trials. Jeff Ludwig is our Chief Commercial Officer, and Jeff has a very extensive background in the commercialization of oncology drugs, both at Astellas and Amgen. Maximo Nougues is our Chief Financial Officer. As you can see, he's got a very extensive background in health care finance. And then Doug Hunt is our Senior Vice President of Regulatory Affairs. And Doug has very extensive experience, both at small and large companies, from a regulatory affairs perspective. The Board of the company is showed on Slide 54. This includes myself, Ann Miller, Mike Miller, Jay Moyes, Hugh O'Dowd; Adrian Senderowicz, Brian Stuglik and Troy Wilson. Importantly, we have a number of people on our Board with a commercial background, specifically in oncology. Being a commercial company, we feel that's very important to have, and we're very pleased to have them as well as the other Board members on the Board at this time. So on Slide 55. From a financial perspective, our stock currently trades on the NASDAQ under the ticker PBYI. Our cash, cash equivalents and marketable securities at the end of September 30 was about $109 million. In the third quarter of 2020, we were actually slightly cash flow positive to the tune of a cash earned of about $1.8 million. We have a debt outstanding with Oxford Finance, and this is straight debt. This is not a convertible debt. Originally, it was a $155 million loan. We paid some of that down. And so now it's a $100 million loan. And that refinance was done in June of 2019. And our shares issued and outstanding is roughly 39.8 million. So to close with the company highlights. NERLYNX is the first HER2-positive -- HER2-directed drug that's approved by the FDA for the extended adjuvant treatment of early-stage HER2-positive breast cancer in patients who've had prior trastuzumab, which is Herceptin. It's also the first HER2-directed tyrosine kinase inhibitor approved in both the early stage and metastatic HER2-positive breast cancer indications. We've got a number of potential other indications, which I discussed in the presentation, like HER2-positive metastatic breast cancer with brain mets, HER2-mutated breast cancer, HER2-mutated cervical cancer, EGFR exon 18 mutated non-small cell lung cancer and other HER2-mutated solid tumors. We've got full U.S. commercial rights to the drug as we believe that's where the value for the shareholders lies. And we've got a very large initial market opportunity with additional label expansion potential. So I would very much like to thank JPMorgan for allowing us to present at this conference and also thank all of the investors for listening to the webcast. Thank you.