TSRO Q2 CC Transcript

Q2 2017 TESARO Inc Earnings Call Waltham Aug 10, 2017 -- Edited Transcript of TESARO Inc earnings conference call or presentation =============================================================================== Corporate Participants ================================================================================ * Jennifer Davis Tesaro, Inc. - Senior Director of Corporate Development & IR * Leon O. Moulder Tesaro, Inc. - Co-Founder, CEO and Director * Mary Lynne Hedley Tesaro, Inc. - Co-Founder, President, COO and Director * Timothy R. Pearson Tesaro, Inc. - CFO and EVP ================================================================================ Conference Call Participants ================================================================================ * Asthika Goonewardene * Boris Peaker Cowen and Company, LLC, Research Division - MD and Senior Research Analyst * Charles Anthony Butler Guggenheim Securities, LLC, Research Division - MD and Senior Equity Analyst * Christopher Joseph Raymond Raymond James & Associates, Inc., Research Division - MD and Senior Biotech Analyst * David Matthew Nierengarten Wedbush Securities Inc., Research Division - MD * Eliana Rachel Merle Crédit Suisse AG, Research Division - Research Analyst * James William Birchenough Wells Fargo Securities, LLC, Research Division - MD and Senior Biotechnology Analyst * Jing He G. Research, LLC - Research Analyst * Peter Richard Lawson SunTrust Robinson Humphrey, Inc., Research Division - Director * Richard Groves Goss Leerink Partners LLC, Research Division - Associate * Robyn Karnauskas Citigroup Inc, Research Division - Director and Senior Analyst * Tazeen Ahmad BofA Merrill Lynch, Research Division - VP ================================================================================ Presentation -------------------------------------------------------------------------------- Operator [1] -------------------------------------------------------------------------------- Good afternoon, and welcome to the TESARO Second Quarter 2017 Conference Call. (Operator Instructions) As a reminder, this call is being recorded and webcast. I will now turn the call over to Jennifer Davis, Vice President of Investor Relations and Corporate Communications at TESARO. Please go head. -------------------------------------------------------------------------------- Jennifer Davis, Tesaro, Inc. - Senior Director of Corporate Development & IR [2] -------------------------------------------------------------------------------- Thank you, operator. Good afternoon, and thank you for joining us today to discuss our recent business progress and TESARO's second quarter 2017 operating results. With me here today are our CEO, Lonnie Moulder; our President and COO, Dr. Mary Lynne Hedley; and our CFO, Tim Pearson. Earlier this afternoon, we issued a news release detailing our Q2 results. Please note that this news release and the slide presentation that we'll refer to during this conference call are both available in the Investors section of our website, www.tesarobio.com. Before we begin, I'd like to remind you that discussions during this conference call will include forward-looking statements. These statements are subject to a number of risks and uncertainties that could cause our actual results to differ materially from those described in these forward-looking statements. We undertake no obligation to update or revise any forward-looking statement for any reason. The factors that could cause actual results to differ are discussed in the press release issued today and in our SEC filings, including our annual report on Form 10-K for the year ended December 31, 2016, and our quarterly report on Form 10-Q for the quarter ended March 31, 2017. During today's call, we may refer to certain non-GAAP financial measures that involve adjustments to GAAP figures. These non-GAAP financial measures are not a substitute for GAAP financial measures and are unlikely to be comparable to non-GAAP information provided by other companies. We believe non-GAAP measures may be useful to investors as a supplement to, but not as a substitute for, the applicable GAAP number. I'd now like to turn the call over to Lonnie Moulder, CEO of TESARO. Lonnie? -------------------------------------------------------------------------------- Leon O. Moulder, Tesaro, Inc. - Co-Founder, CEO and Director [3] -------------------------------------------------------------------------------- Thank you, Jen, and thank you, everyone, for joining us this afternoon. TESARO experienced an eventful second quarter with 2 product launches, ZEJULA in the U.S. for women with recurrent ovarian cancer and VARUBY oral in Europe for the prevention of CINV. These were the first 2 of 4 planned product launches during 2017, marking our transition into a global multiproduct company with broad capabilities to develop and commercialize innovative products that meaningfully improve the lives of people living with cancer. The initial ZEJULA launch is going very well by all measures. ZEJULA is now the market-leading PARP inhibitor in the U.S. There is also a significant interest in our European expanded access program or EAP for niraparib, and we anticipate the European launch of ZEJULA by year-end. Finally, our partnership with Takeda will enable us to accelerate the development of ZEJULA for patients in Japan and certain other countries. We continue to advance our development portfolio highlighted by: significant progress in expanding our niraparib clinical development program; definition of our registration strategy with FDA for TSR-042, our anti-PD-1 antibody, in MSI-high cancers; initiation of a combination study of TSR-042 with TSR-022, our anti-TIM-3 antibody; and advancing TSR-033, our anti-LAG-3 antibody, into a Phase I study. Mary Lynne will speak in greater detail about these programs and our plans later on in the call. Following FDA approval of ZEJULA, maintenance treatment with PARP inhibitors has become the new standard of care for patients with recurrent ovarian cancer. And ZEJULA is the first and only once-daily PARP inhibitor that is available at first recurrence regardless of biomarker status. Our landmark Phase III NOVA study was conducted with the highest level of rigor with a progression-free survival primary endpoint using blinded independent central review of a radiographic progression and importantly, clinical progression, along with frequent scan intervals. The results of the primary analysis of this trial are unsurpassed across all populations of recurrent ovarian cancer patients evaluated. In the second quarter, more than 1,500 patients began treatment with ZEJULA. Based upon physician surveys, we understand that about half of those patients carry germline BRCA mutations. Nearly all patients have started ZEJULA treatment at the recommended 300-milligram dose. And as expected, we began to see sub-refills at the 200-0milligram dose level in June. Our refill rate continues to increase as expected and represents nearly half of the ZEJULA units shipped in the last month of the quarter. Since approval, there have been over 1,000 unique ZEJULA prescribers. And more than twice as many prescribers have written a prescription for ZEJULA than for either one of the other approved PARP inhibitors within the first quarter of launch. Reimbursement coverage for ZEJULA has been excellent, and more than 95% of lives are covered for ZEJULA across Medicare, Medicaid and private insurance. Approximately 60% of patients treated with ZEJULA have commercial insurance coverage and about 1/3 are covered by Medicare. We are proud of our robust patient assistance programs, which support broad access for patients who could not otherwise benefit from ZEJULA. To date, utilization of our patient assistance programs has been in line with the current industry average for oral oncology products of 20% to 30% of total unit volume. I would like to thank our field and home office commercial and medical organizations for the outstanding work they have done and continue to do in support of ovarian cancer patients with this important product launch. Since the beginning of the ZEJULA launch, the TESARO field team of approximately 170 associates has held the market-leading share of voice in ovarian cancer among the 4 leading companies marketing the 3 approved PARP inhibitors and the approved IV VEGF inhibitor. As a result of this team's dedication, ZEJULA became the most prescribed PARP inhibitor and had an approximate 60% share of patients in June. As we move into the second quarter of product availability, we expect to gain additional visibility into patient demographics, duration of therapy and dosing. And we look forward to keeping you apprised of our progress. Turning to VARUBI. During the second quarter, approximately 9,000 units of VARUBI were shipped from specialty distributors and specialty pharmacies in the U.S. And VARUBI was the most prescribed oral NK-1 receptor antagonist in the U.S. for the quarter. We intend to carry the momentum generated from our experience with VARUBY oral into the latter half of the year with our planned launch of VARUBI IV in the fourth quarter, following our October 25 PDUFA date. A successful launch of our IV formulation will allow us to reach the largest part of the U.S. market and over time, extend the use of NK-1 receptor antagonists to the majority of patients receiving chemotherapy regimens such as cisplatin, carboplatin and anthracycline/cyclophosphamide combinations as recommended by the NCCN and, as of last week, the updated ASCO guidelines. With that, I'll turn the call over to our CFO, Tim Pearson, for a review of our second quarter financial results. Tim? -------------------------------------------------------------------------------- Timothy R. Pearson, Tesaro, Inc. - CFO and EVP [4] -------------------------------------------------------------------------------- Thanks, Lonnie. For the second quarter of 2017, TESARO reported net product revenue of $28.8 million compared to $1.2 million for the second quarter of 2016. This growth was primarily driven by the strong launch of ZEJULA in the U.S. ZEJULA revenue totaled $25.9 million for the second quarter. Revenue from ZEJULA sales is recorded net of estimated discounts, returns, chargebacks, rebates, co-pay assistance and other allowances. These gross-to-net adjustments represented approximately 10% of gross ZEJULA product sales for the second quarter. ZEJULA is available to prescribers and patients through both specialty pharmacies and specialty distributors. And since launch, the majority of patients have received ZEJULA via our specialty pharmacy channel. Importantly, ZEJULA data reported by IMS Health only includes prescriptions filled by specialty distributors and does not include any prescriptions filled through our specialty pharmacy channel. VARUBI revenue totaled $2.9 million for the second quarter compared to $1.2 million for the second quarter of 2016. VARUBI shipments from specialty distributors and specialty pharmacies in the U.S. represented unit volume growth of approximately 40% sequentially for the second quarter compared to the first quarter of this year. We look forward to bringing our IV formulation to U.S. customers in the fourth quarter pending FDA approval, which will enable us to reach the largest market segment. License, collaboration and other revenue was approximately $600,000 for the second quarter of 2017, compared to $34.6 million in Q2 2016, which included an upfront payment related to the execution of our agreement with Janssen for the development of niraparib in prostate cancer. In Q3 2017, we expect to recognize the majority of the $100 million upfront payment received as part of our Takeda license agreement as license revenue. Research and development expenses increased to $71.4 million for the second quarter compared to $50.1 million in Q2 of 2016. The increase was driven primarily by increased headcount, expansion of the TSR-042 and TSR-022 programs and advancement of our earlier-stage immuno-oncology portfolio. Selling, general and administrative expenses increased to $93 million for the second quarter compared to $36.2 million in Q2 of 2016, primarily due to activities in support of the launches of VARUBI and ZEJULA in the U.S. and Europe, increased headcount and higher professional service fees. Acquired in-process research and development expenses totaled $7 million for the second quarter of 2017 and included milestone payments related to our immuno-oncology portfolio. For Q2 of 2017, TESARO reported a net loss of $152.1 million compared to a net loss of $59.2 million for the second quarter of 2016. As of June 30, 2017, TESARO had approximately $508 million in cash and cash equivalents, reflecting cash utilization during the second quarter of approximately $129 million, excluding $35 million of onetime regulatory milestone payments related to the approval of ZEJULA in the U.S. and the first commercial sale of VARUBY oral in Europe. This June 30 cash and cash equivalents balance does not include the $100 million upfront payment received during the third quarter as part of the Takeda license agreement. Looking ahead, we expect that our cash and cash equivalents balance will decrease by approximately $110 million to $120 million on average per quarter during the second half of 2017. And that's excluding the $100 million upfront payment from Takeda in Q3 and a $15 million milestone payable upon approval of ZEJULA in Europe anticipated in Q4. With that, I'll hand the call over to Mary Lynne for an update on our development programs. -------------------------------------------------------------------------------- Mary Lynne Hedley, Tesaro, Inc. - Co-Founder, President, COO and Director [5] -------------------------------------------------------------------------------- Thank you, Tim. A continuation of our regulatory strategy following the successful NOVA trial includes the submission and ongoing review of the MAA for ZEJULA as a potential new treatment for women in Europe with recurrent ovarian cancer following a response to platinum. Interest in our expanded access program, or EAP, has been very high. And to date, more than 200 patients have enrolled across 9 European countries. We continue to expect approval and launch in Europe towards the end of this year. Our strategy to benefit women across the full spectrum of ovarian cancer began with the successful completion of NOVA, the regulatory approval of ZEJULA in the recurrent ovarian cancer setting and the subsequent ongoing U.S. launch. We believe the treatment benefits of niraparib monotherapy can be further expanded to the frontline ovarian cancer setting, and we intend to establish our foothold there with PRIMA. A successful PRIMA outcome may mean a greater number of patients can benefit for an even longer time from niraparib maintenance treatment, more time for more women. Expansion of that strategy will include the initiation in Q1 next year of our combination study which accommodates the use bevacizumab, an agent currently approved in Europe for frontline ovarian cancer, and also assesses combination treatment with an anti-PD-1 antibody. Details related to the trial design will be provided before the end of this year. Again, the goal here is clear, a combination approach to provide more time for more women. Beyond the frontline setting, we continue to pursue recurrent ovarian cancer with 2 approaches. For those women who are platinum-responsive upon recurrence, the AVANOVA trial is assessing the activity of niraparib in combination with bevacizumab. For those women who are platinum-resistant upon recurrence, we continue to advance the TOPACIO study in which patients are treated with niraparib and pembrolizumab. A substantial body of market research confirmed a continuing unmet need, in particular, in this population. As a reminder, PRIMA is a trial designed to assess the activity of niraparib versus placebo control in patients with newly diagnosed Stage III/IV ovarian cancer following a response to platinum. Patients are randomized 2:1, niraparib to placebo, and stratification factors include the homologous recombination deficiency or HRD status of the tumor. Primary endpoint analysis will include a hierarchical step-down approach for progression-free survival first in patients with HRD-positive tumors. And if the results are statistically significant, we will assess PFS in the entire population. Enrollment in this trial is proceeding quite well, and we currently anticipate data readout in 2019. AVANOVA, which is being conducted by our ENGOT collaborators, is evaluating the combination of niraparib plus bevacizumab in patients with recurrent ovarian cancer. Initial promising data reported last year at ASCO, led to the expansion in the ongoing Phase II portion of the study in which patients are randomized to niraparib versus niraparib plus bevacizumab. We expect to report updated data from the AVANOVA study during ESMO in September. Finally, as a reminder, the TOPACIO study evaluates niraparib in combination with the anti-PD-1 antibody, pembrolizumab, in patients who have recurrent platinum-resistant ovarian cancer or triple negative breast cancer. Patients with these tumors have demonstrated low response rates and a relatively short duration of response to anti-PD-1 antibody and PARP inhibitor monotherapies, and we hope to improve upon the clinical activity with this combination approach. Early data from the dose escalation portion of the study were shared at our ASCO investor event in June. Of 13 evaluable patients, 8 with platinum-resistant ovarian cancer and 5 with triple negative breast cancer, 3 partial and 1 complete response were observed in the patients with ovarian cancer. One patient with triple negative breast cancer experienced long-term stable disease. Stage I of the expansion study includes 2 cohorts, one each for patients with TNBC and platinum-resistant ovarian cancer, and is fully enrolled with approximately 24 patients in each cohort. In addition, all patients required for Stage II of the expansion have been dosed or identified for dosing. We will report additional data from this trial during the ESMO Congress in September. But at this point, we expect that before ESMO, about a dozen patients from the expansion cohort will have had 2 post-treatment scans and be evaluable for response. Lung cancer is a particular interest as a potential opportunity for niraparib treatment to benefit patients. A large number of these patients have reduced expression of genes involved in DNA repair pathways, a high rate of homologous recombination deficiency and platinum responsiveness, all hallmarks of sensitivity to PARP inhibition. There is also ample evidence in lung cancer of a reactive tumor-infiltrating T cell population that can be further activated with an anti-PD-1 antibody therapy. In preparation for our Phase III niraparib lung study, we have initiated the following 3 clinical studies. First, patients with lung cancer will receive monotherapy niraparib treatment in a Phase II study, which should enroll the first patient within the next month. Second, lung cancer patients naïve to anti-PD-1 therapy are currently being enrolled in a lung cancer-specific cohort of the TSR-042 expansion study, GARNET, at the dose selected for registration. Third, a combination study of TSR-042 and niraparib has been initiated to assess the appropriate combination dose of niraparib and TSR-042. More details on these studies will be provided at an appropriate time, such that we can continue to maximize any potential competitive advantage in this space. Moving finally to our immuno-oncology programs. Our current pipeline includes antibodies directed to PD-1, TIM-3 and LAG-3. Beginning with TSR-042, our anti-PD-1 antibody. We have now agreed with FDA a registration strategy for approval of TSR-042 in patients with metastatic microsatellite instability high or MSI-high cancers. Patients with MSI-high tumors are currently enrolling in the expansion phase of the ongoing GARNET study and receive a fixed dose of TSR-042 4 times, once every 3 weeks followed by administration every 6 weeks until disease progression. The primary efficacy assessments in this trial are overall response rate and duration of response. We will share additional data at ESMO in September from Part II of our Phase I study that includes the fixed dose safety cohort. TSR-022 is our anti-TIM-3 antibody. TIM-3 expression on CD4-positive and CD8-positive tumor-infiltrating T cells has been associated with the generation of an immunosuppressive tumor microenvironment and resistant to anti-PD-1 therapy. Pre-existing TIM-3 expression might contribute to the relatively low response rates for anti-PD-1 therapy observed in multiple tumor types, including unselected non-small cell lung cancer. The dose escalation stage of our Phase I AMBER study of TSR-022 is now complete, and the combination phase in which TSR-022 plus TSR-042 are administered at fixed doses of each antibody has been initiated. With this anti-TIM-3 and anti-PD-1 combination study, we will assess multiple hypotheses in appropriate tumor types. We look forward to sharing initial data from this combination next year. Finally, we continue to advance TSR-033, our anti-LAG-3 antibody. A Phase I clinical trial of TSR-033 was recently initiated, with flat dosing and a Q2-week dosing schedule, which should condense the development time line so that we are positioned to initiate combination TSR-042 and TSR-033 studies early next year. And with that, I'll turn the call back over to Lonnie. Lonnie? -------------------------------------------------------------------------------- Leon O. Moulder, Tesaro, Inc. - Co-Founder, CEO and Director [6] -------------------------------------------------------------------------------- Thanks, Mary Lynne. In summary, we are extremely pleased with the ZEJULA launch and our progress so far this year. We are well-positioned to successfully launch 2 more products in 2017, including VARUBI IV in the U.S. and ZEJULA in Europe. We anticipate multiple data readouts, including TOPACIO and AVANOVA and data for TSR-042 at ESMO. Our IO portfolio will continue to advance as we enroll the registration program for TSR-042 in MSI-high cancers, the combination study of TSR-042 and TSR-022 and the Phase I trial for TSR-033. In addition, we are rapidly advancing our early-stage IO candidates and look forward to updating you on our progress. Operator, at this point, could you open up the call for questions. ================================================================================ Questions and Answers -------------------------------------------------------------------------------- Operator [1] -------------------------------------------------------------------------------- (Operator Instructions) The first question is from Robyn Karnauskas of Citi. -------------------------------------------------------------------------------- Robyn Karnauskas, Citigroup Inc, Research Division - Director and Senior Analyst [2] -------------------------------------------------------------------------------- So a couple. So first, I guess the question on everyone's mind is help us understand how you view your data positioned versus the ARIEL-3 data on how do we think about that in the marketplace over time? And the second question is, as you're thinking or moving forward with your PD-1 and your TIM-3 and your LAG-3, what are your thoughts about how to develop these drugs given the recent differences in results in those checkpoint space? -------------------------------------------------------------------------------- Leon O. Moulder, Tesaro, Inc. - Co-Founder, CEO and Director [3] -------------------------------------------------------------------------------- I'll just comment, Robyn, thanks for the question, and then turn it over to Mary Lynne. As it relates to the competitive nature of data being generated by other companies with PARP inhibitors, I think we're really just focused on the fact that we have the first broad indication for maintenance treatment in recurrent ovarian cancer and have established really a new paradigm in a short period of time. We have a drug that has data that's unsurpassed. There are no data points in the primary analyses of any other data sets that exceed the benefit provided in our -- from our primary endpoint analyses across all populations. And in addition, not only the broad payer coverage, the fact that this is a once-a-day therapy, but we have instituted with our field organization and our specialty pharmacy partners a way to really manage the initiation and the dosing of these patients so that they stay on therapy and get to the right dose. And that's what we're seeing and I think the results speak for just how well the ZEJULA data are playing out in the hands of clinicians and how well the team is executing. -------------------------------------------------------------------------------- Mary Lynne Hedley, Tesaro, Inc. - Co-Founder, President, COO and Director [4] -------------------------------------------------------------------------------- So yes, Robyn. Just related to the PD-1, TIM-3 and LAG-3 question, our intent is to explore parallel testing of select hypotheses in very specific tumor types that's pretty much based on the work we've been doing over the last 2 years to immunophenotype multiple tumor types across human cancers using fresh tumor isolated out of patients. All of this information has been very useful to us in terms of specifically identifying where we would take a PD-1/TIM-3 versus a PD-1/LAG-3 combination. And we look forward to sharing more of that as we enter our combination study. -------------------------------------------------------------------------------- Robyn Karnauskas, Citigroup Inc, Research Division - Director and Senior Analyst [5] -------------------------------------------------------------------------------- And just a follow-up, though. I mean, the #1 question I get from people is if you look at the BICR data, so the independent review data, and you look at the TESARO data, the data sets look similar. And so how -- and people are very worried that after a certain amount of time, when Clovis' drug goes generic, that it could negatively influence the market for PARPs. So is there anything you could say that helps people get more comfortable with just the -- that this market can evolve with 2 drugs that may have similar data even if you're looking from the secondary endpoint to a primary endpoint or understand that? -------------------------------------------------------------------------------- Mary Lynne Hedley, Tesaro, Inc. - Co-Founder, President, COO and Director [6] -------------------------------------------------------------------------------- So I guess I'll take that. I think if we're going to focus on the data from ARIEL-3, Clovis themselves have indicated that they did not or were not able to surpass the NOVA data with any of the specific endpoints that were looked at. From our perspective, the data from the NOVA trial are very strong and demonstrate across all of the population a very significant benefit. And even in the worst patient population, the HRD-negative patient population, there's a 3.1 month benefit from a median PFS perspective in patients, which is equivalent to essentially bevacizumab, which is probably the greatest competitor right now because it's what physicians are most used to using in bev across the entire patient population. And even more importantly than that and far surpassing what has been observed in recent publications associated with that molecule, is the fact that 24 months after initiating chemotherapy, again, even in the worst patient population identified with the HRD biomarker, so HRD-negative patients, 20% of those patients are still progression-free. So that's the worst. The best patient population, as identified in the NOVA study on being the BRCA mutations, 50% of those patients 2 years after initiating chemotherapy are still progression-free. So we think the data speak quite loudly and have been very enthusiastically embraced by physicians as evident by the powerful launch. -------------------------------------------------------------------------------- Operator [7] -------------------------------------------------------------------------------- The next question is from Tony Butler of Guggenheim Securities. -------------------------------------------------------------------------------- Charles Anthony Butler, Guggenheim Securities, LLC, Research Division - MD and Senior Equity Analyst [8] -------------------------------------------------------------------------------- So just sticking with the competition, if I may. Could you provide a view of maybe why and if you think that LYNPARZA could also obtain a broad label? I know they've gone to the FDA and asked for this, and that's number one. And then maybe, Mary Lynne, number 2. The interest in GARNET I study is looking at doses of 022 -- 042 that at 500 Q3 and then 1,000 Q6. So I'm just wondering if you could elaborate why you're looking at a Q6 dose because it could be very interesting given the competition really is looking at shorter intervals. Having a longer interval may actually be of some benefit if that's the way you're thinking about it. -------------------------------------------------------------------------------- Mary Lynne Hedley, Tesaro, Inc. - Co-Founder, President, COO and Director [9] -------------------------------------------------------------------------------- Sure. I guess starting with the first question, will LYNPARZA get a broad label. I guess you would have to refer to the FDA in terms of an answer to that question. Obviously, the SOLO-2 data only explored activity of LYNPARZA in the gBRCA mutant selected patient population. And as expected, those data were positive. Related to GARNET, we are studying a Q6 schedule after ensuring over 4 doses that we have activity and safety in our patients in the initial dosing with Q3. Because when we went out and talked to physicians and patients about their experience with PD-1 therapies, they are very enthusiastic about PD-1 therapies. But once you get a patient to a response and you ask them to come back in every 2, 3 or 4 weeks, that's a -- that becomes a significant burden for patients who are benefiting for very long periods of time on these therapies. So they all told us, "We'd prefer a longer dosing interval if you could do that." So we worked through all of the different schedules that we could come up and identified Q6 as one that we felt was appropriate and -- appropriately balanced patient-centric view and also a safety perspective, so keeping our patients safe. And it enabled us to maintain receptor occupancy above a minimal threshold as identified by 2 separate receptor occupancy studies. So that was the reason for the Q6. -------------------------------------------------------------------------------- Operator [10] -------------------------------------------------------------------------------- The next question is from Alethia Young of Crédit Suisse. -------------------------------------------------------------------------------- Eliana Rachel Merle, Crédit Suisse AG, Research Division - Research Analyst [11] -------------------------------------------------------------------------------- This is Ellie on for Alethia. Can you give us a little bit more color on your thinking around which PD-1 you plan on bringing forward to Phase III combinations with niraparib? It sounds like you're going to test your in-house PD-1 in niraparib in a long cohort. But as you move towards a registration program, do you feel you need to run a trial in combination with an approved PD-1 to help derisk the program? -------------------------------------------------------------------------------- Mary Lynne Hedley, Tesaro, Inc. - Co-Founder, President, COO and Director [12] -------------------------------------------------------------------------------- So from our perspective, based on the data that we have seen to date, which -- in which we've treated, at this point, well over 60 patients with TSR-042, we're very confident that we have a PD-1 antibody that is at least as good as the 2 that are currently being marketed today. And as I've said previously, it makes the most sense from our perspective, and I imagine from our shareholders, to utilize our PD-1 antibody TSR-042 whenever we are able to do so. And so that will be the strategy we utilize moving forward. And we'll provide more details on the Phase III study as we complete the Phase II study and move forward with the finalization of those designs. -------------------------------------------------------------------------------- Operator [13] -------------------------------------------------------------------------------- The next question is from Tazeen Ahmad of Bank of America. -------------------------------------------------------------------------------- Tazeen Ahmad, BofA Merrill Lynch, Research Division - VP [14] -------------------------------------------------------------------------------- Just a couple of small ones. In terms of what your current size sales force is, Lonnie, can you give us an idea of are you where you want to be based on the first couple of months of launch? Do you think you need to make any tweaks? And then in terms of your R&D organization, do you plan on hiring more people? You are running multiple studies. Do you think that the stuff that you have is sufficient for that? Or do you foresee needing to add some more people? -------------------------------------------------------------------------------- Leon O. Moulder, Tesaro, Inc. - Co-Founder, CEO and Director [15] -------------------------------------------------------------------------------- Yes. As far as the field organization, Tazeen, we're right where we need to be with the current portfolio, that is ZEJULA and VARUBI in the U.S. The overall field organization is approximately 170 people. About 100 of those are what you would classically categorize as salespeople, a group primarily focused on community cancer centers and community clinics, another small group focused on the larger academic centers. And then in support of their efforts and patients, we have our oncology nurse educators that provide education around our products who work closely with oncology nurses and practitioners in all of the treatment settings. We have a group of MSLs, obviously, that are credentialed, trained people to really cover scientific questions. We have a large account management team working with providers and payers and integrated systems and then -- and the distribution and PBM customers. And then in addition, we have a really novel team that we call provider solutions, a group of very experienced oncology background people that assist all of our different field teams to ensure, through the electronic medical records, through formularies, that our products have the appropriate position. So we're well-positioned there. We are in a hiring phase. As you can see, we're expanding our clinical programs, advancing our IO portfolio. So there are R&D positions open, and anyone can look at our recruiting link on our website and take a look at those positions. -------------------------------------------------------------------------------- Mary Lynne Hedley, Tesaro, Inc. - Co-Founder, President, COO and Director [16] -------------------------------------------------------------------------------- TESARO, a great place to work. -------------------------------------------------------------------------------- Tazeen Ahmad, BofA Merrill Lynch, Research Division - VP [17] -------------------------------------------------------------------------------- Okay. And then maybe can we get a little bit of color on, I guess, any more feedback that you've gotten from physicians about the side effect profile and how TESARO -- your sales force or your MSLs prep doctors to look for signs of, let's say, thrombocytopenia in your patients. -------------------------------------------------------------------------------- Leon O. Moulder, Tesaro, Inc. - Co-Founder, CEO and Director [18] -------------------------------------------------------------------------------- Yes, so with any anticancer drug, it's important to keep patients safe upfront. As you know, all PARP inhibitors are associated with myelosuppression. All PARP inhibitors require monthly CBCs, labs, so that blood counts can be monitored. With ZEJULA, we ask that, of course, there be a baseline CBC, just like the others and then, once a week for the first month, do a lab and look at the blood counts. And we have our oncology nurse educators go into clinics, once a prescription has been written for a patient, to reinforce that and to explain the dosing schedule. And our specialty pharmacy is in contact with the patients on a weekly basis, along with in contact with the clinic on a weekly basis, to ensure that the patients are being assessed appropriately based on however their blood counts come out. And as you know from the NOVA trial, as we proceed through the cycles, once a patient achieves the dose that's right for them, which is after cycle 2 in most cases, the incidence of grade 3/4 thrombocytopenia is only 1% -- approximately 1%. And going forward, patients, although starting at 300 milligrams, approximately 40% to 50% will settle into 200 milligrams, with the remaining being split evenly between 300 and 100. And since we started with a large number of patients as early as late April and May, we're able to track those patients. And what we're finding is the actual utilization of the product is matching very nicely with the NOVA study. Patients are staying on therapy. They're getting refills. And as you can tell, the doctors are having experience in writing more and more new prescriptions now that we have, at least through the second quarter only, over 15,000 patients -- I mean, 1,500 patients on the drug. So they know how to use this drug now, but we'll continue our educational support as we move throughout the year. -------------------------------------------------------------------------------- Tazeen Ahmad, BofA Merrill Lynch, Research Division - VP [19] -------------------------------------------------------------------------------- And then maybe the last question. In terms of your breadth of scriptwriting, are you seeing doctors who tried the drug writing additional scripts for more patients? Or is it still the phase where you're seeing doctors kind of sampling with a couple of patients and you're continuing to grow sales primarily by adding new doctors? -------------------------------------------------------------------------------- Leon O. Moulder, Tesaro, Inc. - Co-Founder, CEO and Director [20] -------------------------------------------------------------------------------- That's a great question. There's really 3 groupings here. There's a group of early adopters that have written a lot of prescriptions and continue to write a lot of prescriptions. There are a group of doctors that have a lesser number of patients. If you just think about this the way we've characterized the market, there are approximately 10,000 patients annually that would be eligible under our label. And you break that down, that's about 180 patients per week, right, in the country that come off of their platinum in response that are eligible for maintenance. And we -- if you hear the prescribers, there's a group of doctors that don't have as many patients but we're getting a large share of their scripts. And then there's another group where they're just initially -- it's an initial trial period where they put a few patients on and they're watching to see how those patients do. So for each of those 3 groups, we, of course, have different approaches where the doctors that are writing a lot of scripts, large volume of patients, those doctors, of course, we're reinforcing and they're self-reinforcing because they're seeing how the drug is working. The doctors that have less patients, but we have a high share for them, it's a similar approach. The doctors that are just now in a trial phase, we need to really support them and give them the opportunity to think about using the drug as opposed to watchful waiting, using the drug based on the data compared to bevacizumab. -------------------------------------------------------------------------------- Tazeen Ahmad, BofA Merrill Lynch, Research Division - VP [21] -------------------------------------------------------------------------------- And then are you able to give us roughly what the breakdown is between those groups that you just described? -------------------------------------------------------------------------------- Leon O. Moulder, Tesaro, Inc. - Co-Founder, CEO and Director [22] -------------------------------------------------------------------------------- It's a bit early to do that. -------------------------------------------------------------------------------- Tazeen Ahmad, BofA Merrill Lynch, Research Division - VP [23] -------------------------------------------------------------------------------- Okay. And then maybe one last question. Can you tell me what your gross to net is? -------------------------------------------------------------------------------- Timothy R. Pearson, Tesaro, Inc. - CFO and EVP [24] -------------------------------------------------------------------------------- Our ZEJULA was roughly 90% for the quarter. -------------------------------------------------------------------------------- Operator [25] -------------------------------------------------------------------------------- The next question is from Jim Birchenough of Wells Fargo. -------------------------------------------------------------------------------- James William Birchenough, Wells Fargo Securities, LLC, Research Division - MD and Senior Biotechnology Analyst [26] -------------------------------------------------------------------------------- Couple of questions. Just wondering if you'd be willing to break out the new patient starts across April, May and June just so we get a sense of the build. And if you're willing to do that, if you could do July as well? And then one of the questions we get on the PD-1 niraparib combination is just combinability. Some people seem to think there's an overlap in terms of adverse events. And so could you speak to the combinability of your PARP and PD-1 versus the other PARPs? And then finally, for Mary Lynne, on the PD-1/TIM-3 combo versus PD-1/LAG-3 combo, give us a sense, based on your fresh tumor sample data, what gives you better opportunity? Where do you think you're going to get a bigger bang for your buck? -------------------------------------------------------------------------------- Leon O. Moulder, Tesaro, Inc. - Co-Founder, CEO and Director [27] -------------------------------------------------------------------------------- Jim, I'll start out. And we utilized a slide today and I know many of you don't have access to the slides as you're listening to the call, but those are available on the website, and what you'll see is based on the data source we have, the tracking of the launch of the various PARP inhibitors, including what we have posted in April, May and June from a utilization standpoint. And clearly, April, we only shipped product during the last week. And so those were new prescriptions. And if you look at the May chart, or the May bar on the chart, the May prescriptions were virtually all new prescriptions also, right? June is when we started seeing refills come in, of course. And across the June and July time period, about 50% of the prescriptions are refills. So it's about an even split between new prescriptions and refills. Obviously, we -- as we go forward, the refills will become greater than new -- the new prescriptions. And as I mentioned earlier, the actual weekly eligible new patients is somewhere in the 180 range. And if you look at this chart, you can kind of -- you can probably kind of map out how that's going to play out over time. Mary Lynne? -------------------------------------------------------------------------------- Mary Lynne Hedley, Tesaro, Inc. - Co-Founder, President, COO and Director [28] -------------------------------------------------------------------------------- Sure. So Jim, in terms of the PD-1 niraparib tolerability of the combination, we haven't seen any issues combining niraparib with pembro at this point and don't anticipate seeing any because the toxicities associated with niraparib are primarily limited to myelosuppression in which we might have to do dose reductions. We don't have any concerning liver toxicities which lead to potential challenges like possibly another PARP inhibitor. In terms of the PD-1/TIM-3 PD-1/LAG-3 combination, yes. In fact, the data that we have generated from multiple human fresh tumors does guide us towards certain tumor types with the TIM-3 combination and other tumor types with the LAG-3 combination. And when we start dosing in the cohort expansion, that's when you will see us start to focus on those specific tumor types. And until that, I would rather not describe the specific tumors. -------------------------------------------------------------------------------- Operator [29] -------------------------------------------------------------------------------- The next question is from David Nierengarten of Wedbush Securities. -------------------------------------------------------------------------------- David Matthew Nierengarten, Wedbush Securities Inc., Research Division - MD [30] -------------------------------------------------------------------------------- I had one kind of relating to competition, not exactly on the other peer group. But I noticed you said that you had 50% share -- or 50% of the patients were gBRCA-positive. Is -- has that changed in the first few months? Did you start out with a higher percentage of gBRCA or lower? And do you anticipate entering into the non-gBRCA or having a greater share of the non-gBRCA population over time? -------------------------------------------------------------------------------- Leon O. Moulder, Tesaro, Inc. - Co-Founder, CEO and Director [31] -------------------------------------------------------------------------------- Yes, David. So on the statement around BRCA, the surveys we deployed were really in the June time frame. It's too early to actually try and track that. And again, it's small in the number of patients in these patient chart surveys or the qualitative physician research. But the question was BRCA. And we note from the patient chart surveys, what we're getting is gBRCA and somatic BRCA. So it's both. It's not just gBRCA when we say 50% are BRCA, right. And over time, clearly, if you look at the population as it exists that's eligible for ZEJULA based on our label indication, there are more patients that are a BRCA wild-type than BRCA mutated. As you know from the NOVA study, it was about 1/3 gBRCA and 2/3 of patients who were not gBRCA mutated. But within that group, there were also somatic BRCA patients. So we would anticipate over time, we'll have more patients that do not have a BRCA mutation. But the early use is about 50-50. -------------------------------------------------------------------------------- David Matthew Nierengarten, Wedbush Securities Inc., Research Division - MD [32] -------------------------------------------------------------------------------- Okay. And as a follow-up, part of the reason for that question was in BRCA patients, it seems the BRCA-positive patients, gBRCA or somatic, it seemed like the data from across the PARPs were more similar than different perhaps arguably, and we can argue about that. But is there then just other competitive advantages that you're using in your detailing? Or is it just too early to say? -------------------------------------------------------------------------------- Leon O. Moulder, Tesaro, Inc. - Co-Founder, CEO and Director [33] -------------------------------------------------------------------------------- I think something that really stands out, and it seems really straightforward is a once-a-day drug is just preferred. So if you think about it, we have the indication for maintenance treatment. There's no adjudication or prescription complications or delays because a BRCA mutation has to be documented; that helps a lot. And then, of course, having the data set we have and having really a head start with a drug that has data that is not surpassed. And as you all -- all of you know, in markets, being first is a great place to be. Being first with the only once-a-day drug really helps. And the fact that any follow-up drug doesn't have data that's any better, I think bodes well for where we are right now and where we're headed. -------------------------------------------------------------------------------- Operator [34] -------------------------------------------------------------------------------- The next question is from Peter Lawson of SunTrust. -------------------------------------------------------------------------------- Peter Richard Lawson, SunTrust Robinson Humphrey, Inc., Research Division - Director [35] -------------------------------------------------------------------------------- Just thinking about data that's coming up at ESMO, what should we expect in for, say, the triple negative and AVANOVA? -------------------------------------------------------------------------------- Mary Lynne Hedley, Tesaro, Inc. - Co-Founder, President, COO and Director [36] -------------------------------------------------------------------------------- I'm sorry, Peter, what was the question? -------------------------------------------------------------------------------- Peter Richard Lawson, SunTrust Robinson Humphrey, Inc., Research Division - Director [37] -------------------------------------------------------------------------------- Just around the data at ESMO. What should we be thinking the number of patients for triple negative and AVANOVA number of patients? And can you give us the standard of care, the bar to really beef for that trial? And then I guess a follow-up would be around (inaudible) data if that's still expected in the second half? -------------------------------------------------------------------------------- Mary Lynne Hedley, Tesaro, Inc. - Co-Founder, President, COO and Director [38] -------------------------------------------------------------------------------- So the AVANOVA and TOPACIO trials will be presented, at least the update will be presented at ESMO as you point out. And for the AVANOVA trial, because it's a randomized trial ongoing, you'll really see an update of the Part I of that study. And that was about 12, 15 patients. In terms of TOPACIO, you'll see additional data from Part I of that study, which was the dose escalation part and then a longer follow-up, plus about a dozen or so of the patients from the second part of the study in each of the cohorts because we don't have a long enough follow-up to provide more than that. -------------------------------------------------------------------------------- Operator [39] -------------------------------------------------------------------------------- The next question is from Seamus Fernandez of Leerink Partners. -------------------------------------------------------------------------------- Richard Groves Goss, Leerink Partners LLC, Research Division - Associate [40] -------------------------------------------------------------------------------- This is Rich Goss calling in for Seamus. Just wondering if you'd give us any more color on the expanded access program in Europe such as which countries account for the bulk of patients, what lines of therapy it's being used in and what percentage of the patients are BRCA versus non-BRCA? -------------------------------------------------------------------------------- Leon O. Moulder, Tesaro, Inc. - Co-Founder, CEO and Director [41] -------------------------------------------------------------------------------- The EAP is in place in line with the label we seek in Europe, which is the label we've received in the U.S. So there's no requirement of determining whether the patient has a BRCA mutation or not. So I don't have any information on that. We'll gather that type of information over time because this is really a protocol and the information about these patients is collected. But as far as where the EAP is most active, U.K. and Germany are leading right now. The 2 combined may be almost half of that, and then the remaining 100 patients or so are spread over 7 other countries. -------------------------------------------------------------------------------- Operator [42] -------------------------------------------------------------------------------- The next question is from Boris Peaker of Cowen. -------------------------------------------------------------------------------- Boris Peaker, Cowen and Company, LLC, Research Division - MD and Senior Research Analyst [43] -------------------------------------------------------------------------------- Just 2 commercial questions on ZEJULA. First, maybe just to follow-up on the conversation on the BRCA mutants. I'm just curious, since BRCA testing is not required for ZEJULA or platinum treatment, what fraction of patients are just not getting BRCA testing or are getting which [refresh] you may be aware of? -------------------------------------------------------------------------------- Leon O. Moulder, Tesaro, Inc. - Co-Founder, CEO and Director [44] -------------------------------------------------------------------------------- If I'm understanding your question, Boris, the number of patients that aren't at all BRCA tested in the ovarian cancer space is shrinking. It's probably, I don’t know, 20 -- I don't know, not even 1/4 now. There's been good uptake in understanding the germline BRCA status for patients with ovarian cancer and breast cancer. It's important that they have that information for planning purposes, for genetic counseling and thinking about their families. So that's our understanding of the testing rate. -------------------------------------------------------------------------------- Mary Lynne Hedley, Tesaro, Inc. - Co-Founder, President, COO and Director [45] -------------------------------------------------------------------------------- I would just emphasize that most of the testing that's being done is done in the -- at the time of diagnosis. As per the NCCN guidelines, that's when patients should be tested, so that, as Lonnie pointed out, the information that is appropriate to their family members can be shared. -------------------------------------------------------------------------------- Boris Peaker, Cowen and Company, LLC, Research Division - MD and Senior Research Analyst [46] -------------------------------------------------------------------------------- Got you. And my second question. I'm just curious if you have a sense of for the ZEJULA scripts to date, what fraction are coming from community docs versus major academic centers? -------------------------------------------------------------------------------- Leon O. Moulder, Tesaro, Inc. - Co-Founder, CEO and Director [47] -------------------------------------------------------------------------------- Yes. We split it out looking at sort of a hospital-based and a community-based, and it's about 50-50 from the specialty pharmacies. And then that's a significant channel for us. But we also have a specialty distributor channel, and they deliver product to hospital pharmacies and to in-office dispensing pharmacies in clinics. And that is probably -- probably leans a bit more towards the community clinic dispensing than hospital dispensing. But overall, it's about 50-50 hospital and community. -------------------------------------------------------------------------------- Operator [48] -------------------------------------------------------------------------------- The next question is from Jing He of Gabelli. -------------------------------------------------------------------------------- Jing He, G. Research, LLC - Research Analyst [49] -------------------------------------------------------------------------------- So I'm just wondering after seeing an increase in commercial and R&D deals in the PARP space, both LYNPARZA and Rubraca are partnering with marketed PD-1s. So do you think -- or you would think that advancing 042 plus ZEJULA potentially limits ZEJULA's use in first line or in other indications? -------------------------------------------------------------------------------- Mary Lynne Hedley, Tesaro, Inc. - Co-Founder, President, COO and Director [50] -------------------------------------------------------------------------------- So the question is whether or not partnering with ZEJULA with 042 will limit its use in the frontline setting? -------------------------------------------------------------------------------- Jing He, G. Research, LLC - Research Analyst [51] -------------------------------------------------------------------------------- Right. So the rationale is -- well, would you be -- still be open to seek partners other than your current trial with KEYTRUDA? -------------------------------------------------------------------------------- Mary Lynne Hedley, Tesaro, Inc. - Co-Founder, President, COO and Director [52] -------------------------------------------------------------------------------- So sure, I mean, if it made sense and we were in a position where the trial's not executable, if you can't do it with an approved PD-1, then that may make sense. But as I had indicated earlier, our goal is to maximize the opportunities for our patients with 042 and niraparib combinations. So where possible, that is going to be our preferred approach. -------------------------------------------------------------------------------- Leon O. Moulder, Tesaro, Inc. - Co-Founder, CEO and Director [53] -------------------------------------------------------------------------------- And a follow-up on that, with the rest of our immuno-oncology portfolio using TSR-042 with our anti-TIM-3 antibody, ultimately with our anti-LAG-3 antibody. If there's value that we think we could create for patients and for the company and the shareholders to do collaborations, well then, of course, we'll assess that. But we're in a unique position where we have a significant portfolio and have combinable agents that we're quite excited about and we believe over time are going to create a lot of value. -------------------------------------------------------------------------------- Jing He, G. Research, LLC - Research Analyst [54] -------------------------------------------------------------------------------- Yes, and I'm also curious that -- so what gives you confidence that the combo could be approved, let's say, if the data is positive, could be approved without a separate approval on 042 monotherapy? Have you communicated with the agencies? -------------------------------------------------------------------------------- Leon O. Moulder, Tesaro, Inc. - Co-Founder, CEO and Director [55] -------------------------------------------------------------------------------- Well, just remember, 042 is in a registration program now. So 042, based on our current plan, will be approved. We're assuming it will be an approved anti-PD-1 antibody, and this is an accelerated strategy that we've agreed with the agency. And it's enrolling patients right now. -------------------------------------------------------------------------------- Jing He, G. Research, LLC - Research Analyst [56] -------------------------------------------------------------------------------- Sure. And also, just a quick one on your financials. I'm just wondering when would you plan to tie your SG&A and R&D expenses to your top line? -------------------------------------------------------------------------------- Leon O. Moulder, Tesaro, Inc. - Co-Founder, CEO and Director [57] -------------------------------------------------------------------------------- Tie our SG&A and expenses to top line. I think right now, we're executing on a really broad development program across multiple pipeline drugs. We're in the midst of launching really important products, and our focus is on execution of that. Of course, over time, as the revenue ramps up as anticipated, that will occur. But that's not in the foreseeable future. -------------------------------------------------------------------------------- Jing He, G. Research, LLC - Research Analyst [58] -------------------------------------------------------------------------------- Sure. And lastly, I'm just wondering have you observed any off-label use in other tumor types as your competitor did? -------------------------------------------------------------------------------- Leon O. Moulder, Tesaro, Inc. - Co-Founder, CEO and Director [59] -------------------------------------------------------------------------------- That's a good question. The specialty pharmacy actually track the ICD-10 codes. So about 80% of the prescriptions are -- were ovarian cancer, 10% are fallopian and 2 have been primary peritoneal, which are also part of the label. So that's 90%. It's about 10% of the use are in other tumors according to the ICD-10 codes. -------------------------------------------------------------------------------- Operator [60] -------------------------------------------------------------------------------- The next question is from Asthika Goonewardene of Bloomberg Intelligence. -------------------------------------------------------------------------------- Asthika Goonewardene, [61] -------------------------------------------------------------------------------- A couple on reimbursement, if I may. What percentage of scripts are rejected and what's the rationale for the rejection? And then are the BRCA mutant patients more preferentially reimbursed versus the non-BRCA mutant? And then I have a follow-up, please. -------------------------------------------------------------------------------- Leon O. Moulder, Tesaro, Inc. - Co-Founder, CEO and Director [62] -------------------------------------------------------------------------------- Yes. So the second part of your question, there's no requirement to even look at the BRCA mutation. The only BRCA mutation data we get is after-the-fact survey data. So the pharmacies are covering the PBMs and the payers are covering the drug to label, which means there's no test. So there aren't any rejections at all relative to a patient's BRCA status. The number of rejections is minimal. I mean it's a handful of the -- clearly, there's been a lot of prescriptions written and filled. In the first few weeks, as a new drug, there were denials. A denial means you now need to go through an administrative process. But that's minimized at this point in time as expected with an oncology drug. -------------------------------------------------------------------------------- Asthika Goonewardene, [63] -------------------------------------------------------------------------------- Excellent. And then a recent Scientific Journal of Immunology published a piece that was -- when looking at macrophage action on PD-1 antibodies, there's a lot of the PD-1 antibodies that was ingested by the macrophage and this is attributed to attaching to the Fc region. And since we've seen others competitors come up and say that they have an Fc modified region that helps prevent this macrophage ingestion, I was wondering to support your Q6W dosing, you had any sort of modification to your PD-1 antibody that helped minimize this macrophage ingestion effect? -------------------------------------------------------------------------------- Mary Lynne Hedley, Tesaro, Inc. - Co-Founder, President, COO and Director [64] -------------------------------------------------------------------------------- We don't have any specific modifications. And even with the Q6 dosing regimen, we are able to stay above the threshold for receptor occupancy that's desired based on 2 assays that are currently used. And those would be the 2 that are used by the companies selling the currently approved PD-1 antibodies. -------------------------------------------------------------------------------- Operator [65] -------------------------------------------------------------------------------- And the last question is from Chris Raymond of Raymond James. -------------------------------------------------------------------------------- Christopher Joseph Raymond, Raymond James & Associates, Inc., Research Division - MD and Senior Biotech Analyst [66] -------------------------------------------------------------------------------- So Lonnie, I think I heard you guys say 50% to 60% of patients dose reduced, if I heard that right. So first of all, is that -- did I hear that right? -------------------------------------------------------------------------------- Leon O. Moulder, Tesaro, Inc. - Co-Founder, CEO and Director [67] -------------------------------------------------------------------------------- In the NOVA study, about 50% to 60% of the patients end up at either -- well, let's -- let me back up. In the NOVA study, between 40% and 50% of the patients end up, by cycle 3 or 4, on 200 milligrams, right, and then the remaining split evenly between 300 milligrams and 100 milligrams and that in the NOVA study, the median dose was around 200, most common dose. Commercially, if you think about it, where are we in the launch, we can look at the patients that came onboard in May, right, and what happened with them was a delay and then a restart at a dose reduction level. And right now, overall, it's really only about 20% of the patients are down to 200 milligrams. But we have May data and then we have June data where less of the patients would have gotten to that point. And then the July data, most everyone, of course, is on 300 milligrams, right. But according to the large number of patients that came onboard last week of April and May and tracking them, and they're actually matching up nicely with what we saw in the NOVA trial. And that's all I can speak to is that first 5 weeks of patients. -------------------------------------------------------------------------------- Christopher Joseph Raymond, Raymond James & Associates, Inc., Research Division - MD and Senior Biotech Analyst [68] -------------------------------------------------------------------------------- Yes. And I guess here's the question and here's why I'm asking it. I guess once you get into the field, you find things out that you didn't know necessarily in the trial, and oftentimes, you see emerging patterns of physician behavior or sort of attitude. Now I guess is it too early for you to have seen any emerging trend of mitigation of strategies for docs to keep patients on that higher dose? That's kind of what I'm getting at, is are you seeing anybody hanging in there, I guess, to -- with the higher dose with mitigation of side effects? Or are they just -- are you seeing folks just pull that trigger for dose reduction? I guess I'm just wondering if you're seeing opportunity for maybe a better dose reduction number than you saw in NOVA. -------------------------------------------------------------------------------- Leon O. Moulder, Tesaro, Inc. - Co-Founder, CEO and Director [69] -------------------------------------------------------------------------------- No, no. The NOVA dose reduction number is the correct dose reduction number. Because remember, this is a exposure response relationship and you need to get the right exposure to the patient and that's determined, in some ways, by this clinical marker of platelets. And we now have over 1,000 prescribers and 1,500 -- well, just through June, 1,500 patients that have experienced this. So they kind of get it. I mean, it's part of a promotion and education and it matches up with NOVA. And I don't believe it's going to be much different based on what I've seen today. -------------------------------------------------------------------------------- Christopher Joseph Raymond, Raymond James & Associates, Inc., Research Division - MD and Senior Biotech Analyst [70] -------------------------------------------------------------------------------- And then also you guys, for VARUBI at least, were very descriptive of the stocking dynamic. And I'm sorry if you addressed this early on the call, but I don't -- is -- can you maybe give some picture of that, this revenue number is, I would assume, ex-stocking or not please? -------------------------------------------------------------------------------- Leon O. Moulder, Tesaro, Inc. - Co-Founder, CEO and Director [71] -------------------------------------------------------------------------------- Yes, there's no stocking involved in this number. The only time we pointed to that was back in December. In anticipation of potential price increase, at least one very large network had made a large purchase which then negatively impacted January and then that washed out in February. But now, the actual revenue you're seeing nicely matches the true demand. -------------------------------------------------------------------------------- Christopher Joseph Raymond, Raymond James & Associates, Inc., Research Division - MD and Senior Biotech Analyst [72] -------------------------------------------------------------------------------- Okay. And so should we expect going forward a stable inventory picture? Or would you provide commentary on that going forward? -------------------------------------------------------------------------------- Leon O. Moulder, Tesaro, Inc. - Co-Founder, CEO and Director [73] -------------------------------------------------------------------------------- Yes, it's always going to be just a few weeks of inventory. -------------------------------------------------------------------------------- Operator [74] -------------------------------------------------------------------------------- I will now turn the call back over to Lonnie Moulder. You may begin. -------------------------------------------------------------------------------- Leon O. Moulder, Tesaro, Inc. - Co-Founder, CEO and Director [75] -------------------------------------------------------------------------------- All right, everyone. Thank you for your interest and have a good evening, and we look forward to updating you soon. -------------------------------------------------------------------------------- Operator [76] -------------------------------------------------------------------------------- Thank you. Ladies and gentlemen, this concludes today's conference. You may now disconnect. Good day.