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spk09: Thank you for standing by, and welcome to the Clovis Oncology Quarter 1 Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press Star 1 on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press Star 0. I would now like to hand the conference over to your speaker today, Ms. Anna Sussman. Please go ahead.
spk10: Thank you, Polly. Good morning, everyone. Welcome to the Clovis Oncology First Quarter 2021 Conference Call. Thank you for joining us. You've likely seen this morning's news release. If not, it's available on our website at ClovisOncology.com. As a reminder, this conference call is being recorded and webcast. Remarks may be accessed live on our website during the call and will be available in our archive for the next several weeks. Today's agenda includes the following. Patrick Mahaffey, our president and CEO, will review the highlights of today's corporate update and Rubreca commercial progress. Then Dr. Thomas Harding, our chief scientific officer, will review the FAP2286 program and targeted radionuclide therapy development program. Dr. Lindsay Rolf, our chief medical officer, will discuss the anticipated clinical milestones for both Rubreca and lucitinib during 2021. And then Daniel, our Chief Financial Officer, will cover the quarter's financial results in greater detail. Pat will make a few closing remarks, and then we'll open the call for Q&A, during which time Pat, Dan, Tom, and Lindsay will be available to answer questions. Before we begin, please note that during today's conference call, we may make forward-looking statements within the meaning of the federal securities laws, including statements concerning our financial outlook and expected business plans. All of these statements are subject to risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. Our actual results could differ materially due to a number of factors, including the extent and duration of the effects of the COVID-19 pandemic and the timing and extent of recovery from the COVID-19 pandemic. Please refer to our recent filing to the SEC for a full review of the risks and uncertainties associated with our business. Forward-looking statements speak only as the date on which they are made, and Clovis undertakes no obligation to update or revise any forward-looking statements. Additionally, please note that we'll be discussing cash burn, a non-GAAP financial measure, during today's conference call. Recorded disclosures related to this are in today's news release, which can be found on our website. Now I'd like to turn the call over to Patrick Mahaffey.
spk04: Thanks, Anna. Good morning. Welcome, everybody. Appreciate you taking the time today. While the continuing headwinds from COVID-19 impacted rubrica sales in the U.S. and in Europe this quarter, we believe the effect of the pandemic on patient diagnoses is Patient visits and access to oncology practices, which began in late March last year, will lessen over the course of 2021. Sales in Q1 2021 were $38.1 million, which were lower than both Q1 2020, our last pre-pandemic quarter and our best U.S. sales quarter ever, and also lower than Q4 2020. It is extremely important to note that the sequential decline that we experienced in Q1 2021 in the U.S. is consistent with the minimal growth or decline for other approved PARP inhibitors indicated for ovarian cancer in the U.S., which is a result or appears to be a result of the ongoing impact of COVID-19. We are hoping that Q2 2021 represents the beginning of a return to a more normal post-pandemic environment. While it is encouraging that office visits at the end of 2020 had returned to pre-pandemic levels, Office visits are only a leading indicator. The number of ovarian cancer diagnoses and debulking surgeries declined 15% or more during the fall and winter. The reduced number of ovarian cancer debulking surgeries and reduced administration of platinum-based chemotherapy had a continuing impact on the maintenance use of PARP inhibitors broadly, and as a consequence, rubraca specifically. We do anticipate that as patient visits begin to rise, As diagnoses increase and the urgent need to more actively manage this often fatal disease grows, the maintenance treatment of ovarian cancer patients will increase, including the use of Rebecca for women with advanced disease. In terms of advancing our pipeline, I'm extremely pleased to announce that we achieved an important milestone in our commitment to target radionuclide therapies with the FDA clearance of our INDs for FAP2286 for treatment and imaging, which enables us to open for enrollment the Lumiere Phase I-II trial this quarter. In addition, we anticipate announcing top-line Athena data for the rubracomonotherapy versus placebo arms in the first-line ovarian cancer maintenance treatment setting in the second half of this year. Interim efficacy data from the non-clear cell ovarian cancer Phase II court of the leolucitinib and Odevo combination will be presented in a poster at ASCO in June. And while evidence of clinical activity has been observed, We do not believe that the efficacy data support further development in non-clear cell ovarian cancer. Enrollment continues in the other three expansion cohorts in gynecological cancers, and we plan to provide an update on the endometrial cohort later this year at a medical meeting. Let me turn now to a rubrica commercial update. Our global net revenue for the first quarter of 2021 was $38.1 million, down 11% over the comparable prior year period. Dan will describe these results in greater detail. As we've discussed previously, an additional effect of COVID-19 is the substantial acceleration of what was already a trend toward reduced in-person access to academic and community-based clinics by sales reps. We believe this reduced access to oncology practices will continue, even once the pandemic is ultimately under control, as practices increasingly prefer digital programming and communication that can be accessed on their own time. We believe the commercial strategy we introduced last fall will enable us to meet these preferences as the effects of COVID-19 lessen over time. This strategy embraces a hybrid approach that elevates easily accessible digital programming, virtual communication, and peer-to-peer interactions. In-person promotion is reduced, and those remaining in-person activities are much more targeted. We remain energized about our strategy and believe that we are an early adopter of a trend that will be increasingly common for oncology marketers. In fact, several companies across the industry have announced similar changes in recent months. We adopted this hybrid strategy to better reach physicians the way they want to be reached, utilizing resources customized to their practices with the goal of accelerating growth as the ongoing impact of the virus resolves over time. Despite our lower sales in Q1 compared to Q4, we believe we maintained our U.S. market share given that our competitors also appeared to experience COVID-related impact on U.S. sales. While this is not yet proof of the potential for our hybrid commercial model, we maintained our share in a difficult environment with the hybrid model and with the 30% reduction in SG&A compared to Q1 2020. Not all of this reduction was specific to selling costs, but we clearly believe we have found a more cost-effective commercial model to address our position customers in the U.S. Obviously, as we come out of COVID-19, we hope our model will also accelerate growth. With regard to the U.S. prostate indication, while still a modest contributor to U.S. revenues, sales over BRCA in the prostate indication were consistent with our sales in Q4 2020. Turning to Europe, we're very pleased with our progress to date, despite the COVID-19 lockdowns that remain in place in most countries. Sales over BRCA were up significantly compared to the first quarter of 2020. As in the U.S., we believe that a more normal oncology practice will reemerge as Europe reopens. We have a smaller commercial organization in Europe and have been utilizing virtual communication in each of our primary territories as regulations allow. While national regulations vary among European countries and as compared to the U.S., we are tailoring a hybrid digital strategy for each country to better reach our clinician prescribers. As we explained previously, December 19, 2020, was the earliest date that an ANDA could have been filed for rubrica. Since that time, generic entities have been permitted to file an ANDA for Rubratka with a paragraph 4 certification, asserting that one or more patents listed in the Orange Book for Rubratka are either not infringed, invalid, or not enforceable. We have not received any paragraph 4 certification notice letters, and to our knowledge, no ANDA filings for Rucaparib have been made to date. Because Rucaparib Camsulate is considered a cytotoxic drug, The published FDA guidance requires any party seeking approval for a generic form of rucaparib to file a bio-IND and recommend showing bioequivalence in, I'm quoting here, female patients with a deleterious BRCA mutation associated with advanced cancer who have been treated with two or more chemotherapies and are receiving a regimen of rucaparib camphlate. The guidance sets forth additional criteria, including the demonstration of bioequivalence to a 90% confidence interval. Demonstrating bioequivalence with Rubraca would only be an initial step in the ANDA approval process. In a potential ANDA litigation, a generic challenger would also need to successfully challenge or design around Orange Book-listed patents, some of which do not expire until 2035. Now, let me turn the call over to Dr. Thomas Harding, our Chief Scientific Officer, to briefly discuss the FAP-2286 and targeted nucleotide therapeutic programs topics of growing interest as we are now moving into clinical development with FAP2286. Tom? Thanks, Pat.
spk03: Hello. It's a pleasure to speak with you today. As Pat mentioned, our enthusiasm continues to grow for our targeted radionuclide therapeutic program, including our lead asset, FAP2286, which we expect to enter into clinical development in this quarter with our Phase I-II Lumiere study. Targeted radionuclide therapy uses cancer-targeting molecules to deliver radiation-missing isotopes specifically to tumors. These targeting molecules can be peptides, antibodies, or small molecules. When injected into a patient's bloodstream, the targeting molecule attaches to cancer cells, delivering high doses of radiation to the tumor while sparing normal tissue. Our lead compound, FAP2286, licensed as part of our ongoing collaboration with 3B Pharmaceuticals, is an investigational peptide-targeted radionuclide therapy, which targets fibroblast activation protein, or FAP. FAP is highly expressed on cancer-associated fibroblasts, or CAS, which represent one of the most abundant cell components in tumors and are found in the majority of cancer types. potentially making it a suitable target across a wider range of solid tumors, including breast, lung, colorectal, and pancreatic carcinomas. Cancer-associated fibroblasts play a critical role in tumor initiation, progression, metastasis, and therapeutic resistance. For example, recent studies have demonstrated that FAP-expressing casts exert a potent immunosuppressive activity that can promote tumor progression and confer resistance to immune-based therapies, such as PD-1 and PD-L1 blockade. In certain tumor types, such as sarcoma and mesothelioma, FAP may also be expressed on the tumor cells themselves in addition to the cancer-associated fibroblasts. FAP2286 consists of two function elements. First, a targeting peptide that binds to FAP-expressing caths and tumor cells. And second, a site that can be used to attach radioactive isotopes. Depending on the specific radioactive isotope attached, FAP2286 can be used for patient imaging and selection or therapeutic applications. In our Phase I-II Lumiere study, FAP2286 will be attached to the isotope gallium-68 to allow positron emission tomography or PET imaging and selection of patients for inclusion in the study. To the therapeutic agent, FAP2286 will be attached to the isotope lutetium-177 an emitter of beta particle ionizing radiation that causes DNA damage and cell death. Non-clinical studies, including animal models presented at ESMO last year, show that FAP2286 can potently and selectively bind to FAP. In addition, antitumor efficacy of FAP2286 linked to lutetium is observed in FAP expression tumor models. We look forward to sharing additional preclinical and clinical data at future meetings. We submitted two IND applications for FAP2286 for use as an imaging and therapeutic agent at the end of 2020 to support our Lumiere study, with expansion cohorts planned in multiple tumor types as part of a global development program. We are pleased to announce that the IND is cleared following acceptance by the FDA of CMC data from the first of our clinical sites, each of which will effectively serve as real-time manufacturers of the imaging agent given the extremely short half-life of Gallium-68. With FDA clearance of our INDs, the Lumiere study is expected to open for enrollment by the end of this quarter. The phase one portion of Lumiere study will evaluate the safety of the FAP-targeting investigational therapeutic agent and identify the recommended phase two dose and schedule of lutetium-177 labeled FAP-2286. Once the recommended phase two dose is determined, phase two expansion cohorts are planned in multiple different tumor types. FAP2286 labeled with Gallium-68 will be utilized as an investigational imaging agent to identify patients with FAP-positive tumors appropriate for treatment with a therapeutic agent. In addition, studies of FAP2286 linked to an alpha particle-emitting radionuclide and combination studies with other oncology compounds are also being planned. Given the role of FAP-expressing CAFs in mediating immunosuppression, combination with PD-1 and PD-O1 blockade will be a priority. In addition to our own program, a separate investigator-sponsored imaging study with FAP2286 is underway at UCSF to evaluate FAP expression in multiple tumor types and is currently enrolled in patients. Results from this study, along with preclinical data we are generating, are expected to help inform selection of tumor types for our Phase II expansion cohorts. In addition, we and 3B Pharmaceuticals are collaborating on a discovery program directed at three additional targets for targeted radionuclide therapeutic development, to which we have global rights. With our achievements to date, we believe we have the opportunity to be a leader in the emerging field of targeted radiotherapy for the treatment of solid tumors and to be the first to clinically develop a peptide-targeted radionuclide therapy targeting FAP. We are also enthusiastic about the target and the subject of our discovery collaboration and look forward to providing additional data where appropriate. One last thing, some exciting new data for the entire targeted radionuclide therapy field will be reported in a plenary session at ASCO in June. In March, Novartis announced that the Phase III vision trial of PSMA617 in approximately 1,000 metastatic castrate-resistant prostate cancer patients had achieved both primary endpoints, including overall survival. We look forward to seeing the details from the study and believe it will offer a new treatment option for men with advanced prostate cancer and further validate targeted radiotherapy as an important new therapeutic class. Now, I'll turn the call over to Lindsay Rolfe to discuss the pipeline for Rubraka and Lusitnib. Lindsay?
spk08: Thanks. Good morning. I'm glad to be here with you today to discuss the key clinical milestones expected for Rubraka and for Lusitnib in 2021. For Rubraka, we expect to announce top-line clinical data from the Athena trial monotherapy arm in the second half of 2021. although exact timing is contingent upon the occurrence of the pre-call specified PFS events. As a reminder, Athena is a phase three 1,000 patient study in frontline newly diagnosed advanced ovarian cancer maintenance. With Athena, we believe we are uniquely positioned to evaluate with BRCA in terms of two independent outcomes, monotherapy versus placebo in the first line of maintenance settings. in the HRB population, inclusive of BRCA, and in the all-comers or intent-to-treat population, as well as evaluating any potential advantage of the combination of Rebraca and Opdivo over Rebraca alone. We believe this study offers an opportunity to truly differentiate Rebraca in the first-line maintenance setting. As I mentioned earlier, the Athena readouts are dependent on the timing of data maturity driven by PFA events. Once top-line results are available, we would plan to file an FMDA shortly thereafter. Continuing with near-term milestones for BRCA, the Lodestar study, our phase 2 pan-tumor study to evaluate with BRCA in homologous recombination repair genes, including BRCA across tumor types, continues to enroll patients. The study evaluates with BRCA in patients with recurrent solid tumors associated with a deleterious homologous recombination repair gene mutation. Based on our interactions with FDA, this study may be registration enabling for a targeted gene and tumor agnostic label. Pending later, we could potentially file for approval in the US for this indication in the first half of 2022. And the newest phase three clinical trial for rubraca is the CASPA study. being sponsored by the Alliance for Clinical Trials in Oncology, which is part of the National Cancer Institute. CASPER is a Phase III study comparing Xtandi and Rubraka to Xtandi and Decebo as a novel therapy in first-line MZRPC in an all-commerce population. The approximately 1,000-patient study will begin enrollment shortly following an amendment to remove the run-in pharmacokinetic sub-studies, which is no longer necessary following the successful completion of the Clovis-sponsored Phase I RAMP study, evaluating the same combination. Now I'll discuss lucitinib. Lucitinib is our investigational angiogenesis inhibitor, which inhibits vascular endothelial growth factor receptors 1 through 3, platelet-derived growth factor receptors alpha and beta, and fibroblast growth factor receptors 1 through 3. The Clovis-sponsored LEA-1 study is a phase 1B2 study evaluating leucitinib in combination with Opdivo in gynecologic cancers, which is currently enrolling patients into phase 2 expansion cohorts. Interim data from the non-clear cell ovarian cancer expansion cohort have been accepted as a poster presentation at ASTHOM. While evidence of clinical activity has been observed, we believe the efficacy data do not support further developments in non-clear cell ovarian cancer. The industry cohort, non-clear cell endometrial, cervical, and clear cell ovarian slash endometrial cancers continue to enroll patients, and we plan to submit an abstract describing the endometrial data to a medical meeting later this year. Lastly, I'm pleased to report that on the development front, the effect of COVID-19 on our clinical trial enrollment remains minimal. And with that, I'll turn the call over to Dan to discuss first quarter financial results.
spk11: Thanks, Lindsay, and hello, everyone. We reported net product revenues for REBRAC of $38.1 million for Q1 2021. which included U.S. net product revenues of $31.7 million and ex-U.S. net product revenues of $6.4 million. This includes comparable net revenues from our prostate indication in the U.S. in Q1 2021 as seen in Q4 2020. First quarter 2021 net revenues represent an 11% decrease compared to Q1 2020, in which we reported net revenues of $42.6 million, including net product revenues in the U.S. of $39.3 million and ex-U.S. of $3.3 million. As Pat mentioned, we believe we maintain U.S. market share during the quarter, despite the decrease in revenues, as each of the marketers of PARP inhibitors with ovarian cancer indications face some COVID-related impact in the U.S. in Q1 2021 compared to Q4 2020. Gross-to-net adjustments totaled 25.6% globally in Q1 2021 compared to 25.6% in Q4 2020, the same as last quarter. This metric fluctuates quarter to quarter and is difficult to estimate on future revenues, but a range in the mid to high 20% seems likely, depending on the revenue and distribution mix for the U.S. and Europe. As European revenues increase in proportion to the U.S., global GTN will increase correspondingly. Research and development expenses totaled $52.8 million for Q1 2021, down 23% compared to $68.2 million for the comparable period in 2020, primarily due to lower spending on Rebecca clinical trials. We expect research and development expenses to be lower in the full year 2021 compared to the full year 2020. Selling general and administrative expenses totaled $29.9 million for Q1 2021, down 30%, compared to $42.6 million for the comparable period in 2020, with savings due to the COVID-19 situation globally and overall cost reduction efforts. Further, we expect SG&A expenses to decrease in 2021 compared to 2020. We reported a net loss for Q1 of $66.3 million, or $0.64 per share, compared to a net loss for the first quarter of 2020 of $99.3 million, or $1.39 per share. Net loss for Q1 included share-based compensation expense of $4 million compared to $13 million for the comparable period in 2020. Turning now to a discussion of cash, as of March 31st, we had $190.9 million in cash and equivalents, And as of March 31st, we had drawn approximately $113.6 million under the Sixth Street Partners LLC Athena clinical trial financing and had up to $61.4 million available to draw under the agreement to fund expenses of the Athena trial. Based on the company's anticipated revenues, spending, available financing sources, and existing cash and cash equivalents, we believe we have sufficient cash and cash equivalents to fund our operations into early 2023. including any cash repayment unless refinanced earlier of the remaining $64.4 million aggregate principal amount of the 2.5% convertible notes at the maturity in September 2021. Net cash used in operating activities was $61.9 million for Q1 2021, down from $82.5 million recorded in Q1 2020. Cash burn in Q1 2021 was $48.1 million, down 28% from $66.9 million in Q1 2020. We have reduced our R&D and SG&A expenses considerably compared to prior years. Most recently, we reduced R&D and SG&A expense by $28.1 million and reduced net cash used in operating activities by 25% compared to Q1 2020. We expect this trend of lower cash burn to continue through 2021. Now I'll turn it back to Pat.
spk04: Thanks, Dan. In summary, we're very enthusiastic about FAP2286 and our targeted radionuclide therapeutic development program overall and look forward to providing updates as Lumiere opens for enrollment and our programs continue to advance. We believe that targeted radionuclide therapy will become an extremely important component of anti-cancer therapy and believe that our early commitment to this field has been validated by the recent Phase III vision trial for PSMA617 in metastatic castration-resistant prostate cancer, which, as Tom noted, will be reported at ASCO in June. If anything, we believe FAP may be an even more important target, given its presence in multiple solid tumors, and we are pleased to be the first company to enter clinical development with an FAP-targeted peptide-targeted radionuclide therapeutic. While the last 12 months of COVID headwinds have been challenging, we believe that we are well positioned as the effect of the pandemic lessens over time for several reasons. Athena data later this year, which we anticipate may ultimately support Rubraka's use in what will likely be its most important indication, the first-line maintenance ovarian cancer setting, which includes the largest patient population of women with advanced ovarian cancer following successful treatment with platinum-based chemotherapy. We believe that the hybrid approach incorporated into our U.S. commercial strategy last fall best enables us to reach clinicians in the way they want to be reached and positions us well as the impact of COVID-19 on oncology practices lessens over time. We remain focused on discipline cost control, as Dan discussed, and our cash burn will be lower in 2021 than 2020. Finally, based on current revenue and expense forecasts, we believe we have sufficient resources to fund our operations into early 2023. With that, we'll be happy to answer any questions you may have.
spk09: As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Your first question comes from the line of Corey Cosimo with JP Morgan.
spk01: Hey, this is Gavin. I'm for Corey. Thanks for taking our question. Just quickly on the FAP program, clearly there's some interest there. Curious what your expectations are for patient accrual there. Do you expect physicians to, you know, be receptive of enrolling patients in the study? And just any color you can provide on your expectations. Thank you.
spk04: You know, it's a standard phase one. But, Lindsay, maybe I'll let you answer that question with a little more detail.
spk08: Sure. Thanks, Pat. Thanks, Gavin. So, as Pat said, it's a standard phase one trial with cohort by cohort enrollment. So, timeline-wise, we'd expect it to proceed in that fashion. In terms of investigation enthusiasm, At each of the investigational sites, we're working with a nuclear medicine physician and one or more oncologists. And that maximizes the engagement and the appropriate expertise. So we're not expecting oncologists just to manage this whole new therapeutic modality. They're doing it hand in hand within every case of very enthusiastic nuclear medicine partners.
spk10: Great. Next question, please, Paul.
spk04: Uh-oh. Anna?
spk08: Your next question comes from Ed White with HC Wainwright.
spk02: Good morning. Thanks for taking my questions. Just to, as a follow-up on the FAPs, To be more clear, could we see some Phase I data this year?
spk04: Ed, what we've said is that, you know, the Phase I will be continuing this year. It's more likely to be presented formally at a medical meeting next year. That being said, we've committed to providing updates on the program on these quarterly calls, including if and when and as we see them, initial evidence of clinical benefit. So these calls will be a forum for an update on progress, but the formal presentation of scientific data will be probably sometime in the first half of next year.
spk02: Okay. Thanks, Pat. And I just want to get a little bit of clarity on... the expenses, I know that you had said that costs will be down or expected to be down in 2021 versus 2020. But looking at the first quarter and thinking on going forward on a sequential basis quarterly, are we looking at a new base now or could we expect to see additional cuts going forward on a quarter to quarter basis?
spk11: Dan? Um, yeah, thanks for the question. Um, you know, as we've talked about in the past, we've had a declining slope of R and D spent primarily around the Rebecca trials, which are, um, you know, for the most part, awfully enrolled and going down, you know, the other side of the slope. So there will be continued reductions, you know, really driven by that. Um, and on the SG and a side where, um, you know, we clearly expect to have lower SG and a for the year. Um, and The rate of how that will proceed for the rest of this year, we haven't specifically disclosed, but part of that will get back to activities that we may or may not contemplate in the second half of the year related to the sales marketing group. But clearly we're at a much lower level of spend than we were compared to last year.
spk02: Okay, thanks, Dan. And my last question, if I may, Pat, you had mentioned that you maintained share in the U. S. Park market. Can you give us a little bit more color on what's going on in the U. S. Park market? We had talked in the past about penetration being, you know, 40 to 45% in the second line maintenance area and just want to get your thoughts on where it is now. And what, if anything, can be done to get the penetration of the market to grow the overall market? I know you've worked on it in the past. Or is it just getting through the pandemic?
spk04: Yeah, so in terms of sort of Q4 versus Q1, you know, you heard our numbers today. Zajula was down 5% from Q4. to Q1, and actually that included a 5% price hike on January 1st, so they were effectively down 10%. Olaparib sales were effectively flat, and they noted that the primary growth driver for them in the U.S. was in the prostate indication. At SGO, there was a presentation on kind of what's happening in real-world experience, and utilization of PARP inhibitors in the maintenance setting, it remained at around 50%, Ed. So while many physicians have adopted maintenance treatment in the second-line setting and to some extent in the first-line setting, either they're limiting it to a subset of populations who they think would benefit most, maybe it's BRCA, maybe it's HRD, maybe it's related to the patient's experience on platinum, we still see a number of physicians who are a percentage of the physician population that limit their use of PARP inhibitors to a very small number of patients. And that's why we're at this 50% number that we as a community have not cracked for whatever it's been now, three years. In addition, a driver of the market's performance in Q1 is was just the continuing effect of COVID-19 and the cumulative effect of COVID-19 on ovarian cancer debulking surgeries, on primary diagnoses, and on a more limited use because of that of platinum-based chemotherapies, which are a precedent therapy for use of PARP maintenance. Office visits are back to normal. I think that this is going to correct itself. Tragically, many patients are going to be diagnosed with more advanced disease, which is going to create an urgency around care. And so it's why I referenced in my prepared remarks that we think as COVID lessens, that things will improve over the course of this year. But we did see that cumulative effect on the part market in Q1.
spk02: Okay. Thanks, Pat, for taking my questions. You bet, Ed. Thank you.
spk09: And your next question comes from the line of Paul Choi with Goldman Sachs.
spk07: Hi. Thanks. Good morning and thank you for taking our questions. Two pipeline questions for Lindsey, if I may. Just with regard to your commentary on Lodestar, could you please elaborate just on what, you know, FDA feedback has been that gives you confidence that the trial could be registration-enabling? Is this something that you had in minutes, post, you know, recent FDA update or meetings? And then, second, on the LEO-1 update, and the decision to not proceed in non-clear cell ovarian. Can you comment whether the MTD dose was reached for that particular cohort, and that's the particular reason, or was it just underwhelming efficacy? Thank you very much.
spk08: Thank you for all the questions. For load staff, as you know, there's plenty of precedent now for approvals in pan tumor. genetically defined indications. But, of course, we have discussed our development plan in person with FDA and designed the LODESDA study, taking that feedback into account. So that gives us confidence that we're on the right track there. For LIA1 in the non-clear cell ovarian cohort, We, this was underwhelming efficacy. The dosing was just as we'd expected. You'll recall that we had the possibility built in for patients to escalate the dose if they got through the first cycle without significant adverse effects. And, you know, we saw the proportion of patients just as we anticipated. The adverse event profile was also just as we'd anticipated. So right dose unsuitable tumor type probably I think is the answer. And of course the other three independent cohorts in unconnected tumor types are continuing as planned. Thanks for the question.
spk11: Thank you.
spk09: And your next question comes from the line of Andrew Behrens with SVB.
spk06: Hi, thanks. I was wondering if you guys could give some more color on the LODESTAR program. How much do you think the tumor agnostic indication would expand the addressable market, and what's the status of the other PARP inhibitors in this indication? And then I have a question about your cash runway after that.
spk04: The largest population of BRCA-mutated patients is in ovarian cancer, in breast cancer, and in prostate cancer. So I think it will have an effect if approved. And obviously, we think the opportunity to bring targeted therapies to other indications where they may be effective is what we're here to do. I would actually focus everybody's attention, however, on two trials that are going to be markedly larger in opportunity for us. That's Athena, which we'll read out prior to any data from Lodestar, and Triton 3, which will at the latest fully enroll in the first quarter, early second quarter of next year, and we'll definitely have data next year. And those are far bigger indications for us than Lodestar. We're enthusiastic about Lodestar. Obviously, directing a trial consistent with... fda um interactions and and pleased to be doing it but the two big drivers for us over the next year 18 months are uh athena and triton 3. and you got another question yeah just i want on that what what is the status of the other park inhibitors um in our tumor agnostic indication before i ask the cash runway question They're not as forthcoming on those programs as we are or as Tesoro used to be. So it's hard to know exactly what their status are. Others are running either monotherapy trials. I believe Pfizer is running a combo trial with an IO agent as well. So as ever in the PARP class, there is likely to be competition.
spk06: Okay. Thanks. And then Just on the cash runway, I'd just like to get some more clarity because I don't see how it stretches to 2023. Did you guys say that it includes repaying the 2021 note? Based on our numbers, I just don't see even if you back, you know, rein in expenses further and back out Athena, you could stretch $190 million to 2023. Yeah, this is Dan.
spk11: So those are a few components that obviously, so from a revenue point of view, we have a range of outcomes that we plan for. And, you know, we're effectively in those ranges. And as you saw, although we're having some struggles in the US at the moment, the European sales continue to do well. And, and, you know, we're feeling pretty good about that. And we do hope for improvement, you know, as the year goes on with the COVID situation. And on the expense lines, as you can see, we've pretty dramatically reduced expenses, and we've continued to do that over the last year or so. And, you know, so that is a large contributor to that as well. It does include repaying the 2021, so $64 million. But we also, keep in mind, have the $61 million left coming in on the Athena financing. So it's really $190 million plus the $61 is the way to look at it, you know, over that timeframe. So it's more like $250 million. And we do have, you know, expense levers that we have, you know, that, you know, help us to get there. So, you know, we've, you know, obviously looked at it pretty carefully. It's an important disclosure. So we're, you know, that's where we are.
spk06: Okay. Thank you very much for the call. I appreciate it. Thanks, Andy.
spk09: And your next question comes from the line of Joe Catanzaro with Piper Sandler.
spk12: Hey, guys. Thanks for taking my questions. Maybe one first on Leo and Lindsay. I think you kind of alluded to this, but does the signal you've seen in non-clear cell ovarian provide any read-through to the other cohorts? And then relatedly, I know we've seen data for lumbatinib plus PEMBRO in ovarian cancer, but don't specifically recall if they've broken out clear cell versus non-clear cell. Just wondering if you have any insight into that.
spk08: Thanks, Joe, for the question. I think the four cohorts really are independent. The only commonality is that they're tumors that all affect women. And molecularly, really, non-clear cell ovarian is not similar to the other types of tumors that we're studying. I blanked on the second question. What was it again? Sorry.
spk12: It's whether levatinib plus PEMBRO has broken out their ovarian cancer data based on non-clear cell versus clear cell.
spk08: So I'm pretty sure that they didn't include clear cell cancer patients in their cohort, and it was mainly a high-grade serious population.
spk12: Okay. Got it. And then if I could just ask a follow-up, I'm wondering if you could elaborate a little bit on what you saw in 4Q of last year around root bracket dynamics that contributed to a relatively strong quarter then that you didn't see this quarter. Yeah, I'll take that.
spk04: We've tried to figure that out, and I think the primary thing we saw is that in Q4, new patient starts combined with continuing therapy from patients enrolled as early as the end of the prior year and in Q1, allowed us to kind of continue with a good sales performance. And, in fact, we didn't see a number of patients fall out of therapy, and our average duration of use actually continued to go up some. In Q1, some of those patients fell off and were not adequately – I'll say replaced, with newly diagnosed patients eligible for second-line maintenance for the reasons I described, the falloff in the reduction in debulking surgeries, platinum-based chemo, and overall diagnoses. We believe that dynamic will change over the remainder of this year, particularly as inpatient visits, office visits, have gone back to normal. And obviously, this is a tragically difficult disease to treat when it's not treated because of concerns about COVID or other things, it doesn't stop growing, and it doesn't stop occurring. And so patients are going to be diagnosed, they're going to be requiring therapies, and they're going to get back into the maintenance use of PARP inhibitors, including bubraca. So as diagnoses increase, new patient starts will increase, and that will be the driver of sales over the remainder of this year, for the class, not just for us. Okay, thanks for taking my question.
spk12: You bet.
spk09: And your final question comes from the line of Tazeen Ahmad with Bank of America.
spk05: Hi, good morning. Thanks for taking my question. Pat, I just wanted to get some color on your thoughts about what kind of off-target talks might you expect to see with 2286? And then as it relates to the Athena study, assuming that you do have the positive data come in, what would be the next step to filing for the SNDA, and when would you expect to actually have that new label ad? Thank you.
spk04: Yep. So with regard to FAP2286, we have a limited amount of data, as you may recall, from the 10 or 11 patients that were imaged and treated on compassionate use in Germany. And we did not see off-target accumulation in any tumor type. Sorry, in any tissue type. And we're pleased that we didn't. We also didn't see anything in animal models that caused us any concern. Obviously, with any new drug, it can be hard to predict what a side effect might be and if there would be off-target accumulation. The two areas I think we would be most focused on would be the potential for myelosuppression, true of any DNA-damaging agent. And the second is because of the way each of PSMA617, Lutathera, and our agent, all peptides, are eliminated, we will see some accumulation in the kidney. And the question is whether that has any acute or chronic It has not for Lutathera or PSMA617, at least to our knowledge. We'll get an update on the entirety of PSMA617 in a month or so. But there's nothing in our data that caused us to be thinking, oh, man, you know, we're really worried about something. When we did see the original scans from the 10 or 11 patients in Germany, because of the known off-target accumulation in the salivary glands of PSMA617, all of us looked at the salivary glands. And of course, we didn't see any accumulation there that's very specific to PSMA617. So we're optimistic. Obviously, it's a phase one study that will start at a low dose. And so if a signal emerges, we'll see it. Lindsay, anything you would add to that?
spk08: No, that was .
spk04: Great. And then what was, oh, the timing. So the timing of the Athena data, as Lindsay noted, will be driven by when we achieve a specified number of PFS events. I would suggest that when we see those data and announce those data, we'd be about three months from filing an SNDA, and then the FDA would have up to six months to review it. So think of Think of an approval on or around, well, a potential approval on or around nine months from when we announced top line data.
spk05: Okay. So hopefully, you know, we'll be well into COVID recovery by then.
spk04: I believe strongly, I think all of us do, that we will be and hope so fervently for all sorts of reasons.
spk05: Okay. Thank you, Pat.
spk04: Thanks, Susie. Anna? Anna?
spk10: Okay. Thanks, everyone. Thank you for your interest in Clovis today. If you have any follow-up questions, please call me at 303-625-5022 or Brianna at 303-625-5023. This call can be accessed via a replay of our webcast at ClovisOncology.com beginning in about an hour and will be available for 30 days. Again, we appreciate your interest and time and thank you and have a good day.
spk09: And thank you. This concludes today's conference call. You may now disconnect.
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