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spk01: Ladies and gentlemen, thank you for standing by and welcome to the Clovis Oncology Q2 2021 Operating Results Webcast Conference Call. At this time, all participant signs are in the 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 zero. I would now like to hand the conference over to your speaker, Anna Sussman, Vice President of Investor Relations. Thank you. Please go ahead.
spk04: Thank you, Phyllis. Good morning, everyone. Welcome to the Clovis Oncology Second Quarter 2021 Conference Call. Thanks for joining us. You've likely seen this morning's press release, and if not, it's available on our website at clovisoncology.com. As a reminder, this conference call is being recorded in webcast. Remarks may be accessed live on our website during the call and will be available in our archives for the next several weeks. Today's agenda includes the following. Patrick Mahaffey, our president and CEO, will discuss the highlights of today's corporate update, and then Dr. Thomas Harding, our chief scientific officer, will present an update on our FAP-2286 and targeted radionuclide therapy development programs. Dr. Lindsay Rolfe, our chief medical officer, Braca and FAP 2286. Then Daniel, our chief financial officer, will cover the quarter's results in greater detail. Patrick will make a few brief remarks, sorry, a brief review of corporate strategy and 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 for 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 these statements are subject to risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statement. 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, extent, and recent filings with the SEC for a full review of the risks and uncertainties associated with our business. Forward-looking statements speak only as of 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. Required disclosures related to this are in today's news release, which can be found on our website. Now, I'll turn the call over to Patrick Mahaffey.
spk02: Thanks, Anna. Morning, everybody. Thanks for joining. Appreciate you taking the time. Look, while these are clearly complicated times, I'm encouraged that based on the data available to us, we have maintained our U.S. market share for Rubraka, and we have achieved meaningful growth in sales in Europe in the second-line maintenance ovarian cancer setting. Sales in Q2 2021 were $36.8 million, lower than both Q2 2020 and Q1 2021. This decline is primarily a result of the ongoing effects of the pandemic on oncology treatment and practice, and in particular, in ovarian cancer. While we fully expect this to reverse when the pandemic finally abates, and as reported by other oncology-focused companies, it has clearly had an impact on new patient diagnoses and new patient starts. We anticipate that when 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 Rubraka for women with advanced disease. We are encouraged, however, that we've successfully maintained enrollment in our clinical studies, and accordingly, we've made significant progress in our clinical trial program for Rubraka. Importantly, we are ever closer to not one but three Phase III readouts for Rubraka in the next 6 to 18 months. We anticipate basary readouts from our Athena monotherapy, Triton3, and Athena combination studies of Rubraka, all of which will occur in 2022. As a reminder, Athena is evaluating Rubraka in the first-line ovarian cancer maintenance treatment setting, first as monotherapy versus placebo, and later in a separate analysis in combination with Odevo versus Rubraka monotherapy. Triton3 is evaluating Rubraka versus physician's choice of chemotherapy or second-line androgen deprivation therapy, in patients with metastatic castration-resistant prostate cancer with BRCA and APM mutations. These offer the potential to address larger patient populations in earlier lines of therapy for both ovarian and prostate cancer, which we anticipate will drive growth in the BRCA sales in both the U.S. and Europe. Lindsay will shortly provide an update on these clinical programs. We have great enthusiasm for the early stage pipeline opportunity that targeted radiotherapeutic development offers, and we continue to advance our targeted radionuclide therapy pipeline as we seek to establish ourselves as a leader in this emerging field of oncology development. FAP2286 is the first peptide targeted radionuclide therapeutic targeting FAP to enter clinical development, and the next 18 months will be potentially transformational for this program. Tom and Lindsay will speak in more detail into developments about this program. And lastly, I'm pleased to announce that during the quarter, we raised $72.5 million in net proceeds through our at-the-market or ATM equity offering program. As of June 30th, we have $230.2 million in cash and cash equivalents and $48.1 million in available funding under the Athena financing. And Dan will speak to this in greater detail shortly. Before I turn the call over to Tom, I'd like to take a moment to welcome Dr. Romit Simantov as the newest addition to our Board of Directors. Romit is currently Chief Medical Officer at Danita Cell and has served in senior leadership roles at Pfizer, OSI, Curagen, and Bayer. We believe her experience and expertise in oncology clinical development and research will be invaluable to us as we advance our development pipeline. We're very pleased to welcome her to the Clovis Board. Now I'll turn the call over to Dr. Thomas Harding, our Chief Scientific Officer, to discuss the FAP2286 and targeted radionuclide therapeutic development programs.
spk11: Tom? Thanks, Pat. Hello. It's a pleasure to speak with you today. As we've discussed, we are seeking to establish ourselves as a leader in the targeted radiotherapy class. Shirsty is a developer of FAP2286, our lead targeted radiotherapeutic compound, licensed as part of our ongoing collaboration with 3B Pharmaceuticals. FAP2286 is the first peptide-targeted radiotherapy candidate, or PTRT, targeting fibroblast activation protein, also known as FAP, in clinical development. And as Pat mentioned, the next 18 months will be transformative for this program. FAP is highly expressed on cancer-associated fibroblasts, or casts, which represent one of the most abundant cell components in tumors and are found in the majority of cancer types. making it potentially a suitable target across a wider range of tumors, including breast, lung, colorectal, and pancreatic carcinomas. CAFs play a critical role in tumor initiation, progression, metastasis, and therapeutic resistance. For example, recent studies have demonstrated that FAP-expressing CAFs exert a potent immunosuppressive activity that can promote tumor progression and confer resistance to immune-based therapies such as PD-1 or PD-L1 blockade. In certain tumor types, such as sarcoma and mesothelioma, FAP may also be expressed on the tumor cells in addition to the CAFs. FAP2286 consists of two functional elements. First, a targeting peptide that binds to FAP-expressing CAFs 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 use. In our Phase 1-2 Lumiere study, FAP2286 is attached to the isotope Gallium-68 to allow positron emission tomography or PET imaging and selection of patients for inclusion in the study. For the therapeutic agent, FAP2286 is attached to the isotope Lutetium-177, an emitter of beta particle ionizing radiation that causes DNA damage and cell death. The phase one portion of the Lumiere study, which is now enrolling patients, 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-20286. FAP-20286 labeled with gallium-68 will be used as an investigational imaging agent to identify patients with FAP-positive tumors appropriate for treatment in Lumiere. Once the Phase 2 dose is determined, Phase 2 expansion cohorts are planned in multiple tumor types. 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 in those currently enrolling patients. Results from this study, along with the preclinical data we are generating, are expected to help inform selection of tumor types for our Phase 2 expansion cohorts. As evidence of our commitment to this emerging field, we have created educational materials to enhance our investors' understanding of targeted radiotherapy. The first of these materials are a microsite and introductory video that provide more information about targeted radiotherapy, SAP 2286, and Clovis' targeted radionuclide development program. To learn more, please visit targetedradiotherapy.com. Lastly, we are collaborating with 3D Pharmaceuticals on a discovery program directed at three additional targets for targeted radionuclide therapeutic development, to which we have global rights. We may potentially file an IND for a second candidate for this program in the second half of 2022. And with that, I'll now turn the call over to Lindsey Rolf for a clinical update.
spk05: Thanks, Tom. Good morning, everyone. I'm glad to be here with you today to discuss the key clinical milestones expected for Rubraka and SAP 2286 in 2022. For Rubraka, we are expecting top-line clinical data from the Athena monotherapy arm in the first quarter of 2022, based on event-based projections. Data from the combination arm of Rubraka plus Opdivo versus Rubraka monotherapy are expected in the second half of 2022, based on our post-portified assumptions. As a reminder, Athena is a Phase III 1,000-patient study in frontline newly diagnosed advanced ovarian cancer maintenance. With Athena, we believe we are uniquely positioned to evaluate Rubraka in terms of two independent outcomes. monotherapy versus placebo in the first-line maintenance setting, as well as the potential advantage of the combination of Rubraka plus Opzevo over Rubraka alone in the same first-line maintenance setting. We believe this study offers an opportunity to truly differentiate Rubraka in the front-line maintenance setting. Once top-line monotherapy results are available, we plan to file an SMDA shortly thereafter. Continuing with the milestones for Rebraca, top-line data from the TRITON3 trial are expected in the second quarter of 2022. TRITON3 is a phase three study evaluating Rebraca versus physician's choice of chemotherapy or second-line antigen deprivation therapy in patients with MCRPC with BRCA or ATM mutations. This trial is expected to serve as the confirmatory study for Lubraca's current approval in the prostate indication, as well as a potential second-line label expansion. And we plan to file an SMDA shortly after results are available. These three anticipated data readouts, athene monotherapy, athene combination, and TRIMED-3, provide the potential to reach larger patient populations in earlier lines of therapy for both ovarian and prostate cancer, for which Rebraca is currently approved in later line indication. The timing for each data readout is contingent upon the occurrence of the protocol-specified progression-free survival events. These studies have been a long and dedicated effort on the part of our Rebraca team, and I'm very grateful to the many colleagues and investigators whose dedicated efforts are shepherding these phase three trials to maturity. Lastly, through BRCA, the load-staff study is our phase two planned tumor study. The study evaluates through BRCA in patients with recurrent solid tumors associated with a bilaterous homologous recombination repair, or HRR, gene mutation that includes BRCA or certain other genes. Based on initial results from the ongoing study, we see encouraging evidence of activity in the subgroup of patients with the bililip tumor mutation or double-hit in BRCA or other HRR-targeted genes. Importantly, for BRCA-mutated breast, pancreatic, and certain other tumors, the majority of tumors do have biallelic loss. Based on these early data, we are evaluating the potential development timeline and commercial opportunity, as well as determining a diagnostic strategy to provide an update on our next quarterly call. Tom has provided a brief overview of the ongoing Phase 1 Lumiere study of FAP2286, and I'll take a moment to highlight the efforts underway to identify the tumotypes for our planned Phase 2 expansion cohorts, which we expect to initiate in 2022, as well as other anticipated milestones. The identification of the expansion cohorts is a considerable focus for us, as the high levels of FAP expression observed in multiple tumor sites make it challenging to limit those expansion cohorts to the five tumor sites currently planned. We look forward to updating you on our choices for phase II development in the coming quarters. In addition to initiating linear phase II expansion cohorts during 2022, we anticipate several key milestones for the program, including The first presentation of phase one from Lumiere at a medical meeting. The launch of our combination study program to explore SAP 20286 in combination with other oncology compounds. Given the role of SAP expressing tasks in mediating immunosuppression, exploring the combination with PD1, PDL1 blockade is a priority. And lastly, a potential IMD filing of SAP 2286 linked to an SAP targeted alpha emitter, PTRT. And with that, I'll turn the call over to Dan to discuss second quarter financial results.
spk09: Thanks, Lindsay, and hello, everyone. We reported net product revenues for Rebecca of $36.8 million for Q2 2021, which included U.S. net product revenues of $27.7 million and ex-U.S. net product revenues of $9.1 million. Second quarter 2021 net revenues represent an 8% decrease compared to Q2 2020, in which we reported net revenues of $39.9 million, including net product revenues in the U.S. of $36.7 million and ex-U.S. of $3.2 million. Based on the data available to us, we continue to maintain U.S. market share during the quarter, despite a decrease in sequential revenues. By contrast, our ex-U.S. business increased sequentially from Q1 to Q2, and we are encouraged by our progress there. Globus reported net product revenue for Abraca of $74.9 million for the six months ended June 30, 2021, which included U.S. net product revenue of $59.4 million and ex-U.S. product revenue of $15.5 million. compared to net product revenue for the same period in 2020 of $82.5 million, which included U.S. net product revenue of $76 million and ex-U.S. net product revenue of $6.5 million. First net adjustments totaled 28.6% globally in Q2 2021 compared to 25.6% in Q1 2021, increasing ex-U.S. revenues and public health service discounts in the U.S. were the main drivers. This metric fluctuates quarter to quarter, and it's difficult to estimate our future revenues, but the high 20% level seems likely, depending on the revenue and distribution mix with the U.S. and Europe. As previously discussed, as European revenues increase in proportion to the U.S., global GPN will increase correspondingly. Research and development expenses totaled $45.8 million for Q2 2021, down 35% compared to $69.9 million for the comparable period in 2020. primarily due to lower spending under bracket clinical trials. We expect research and development expenses to be lower in the full year 2021 compared to the full year 2020. Selling general administrative expenses totaled $32.9 million for Q2 2021, down 21% compared to $41.9 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 Q2 of 66.4 million, or 61 cents per share, compared to a net loss for the second quarter of 2020 of 92.2 million, or $1.15 per share. Turning now to the discussion of cash, as of June 30, we had 230.2 million in cash and cash equivalents, During the quarter, we raised $72.5 million in net proceeds to our at-the-market equity offering program. Also, as of June 30, we had approximately $126.9 million under the Sixth Street Partners LLC Athena clinical trial financing and had up to $48.1 million available to draw under the agreement to fund the expenses of the Athena trial. We expect this $48.1 million to be mostly drawn down between Q3 2021 and Q4 2022. Net cash used in operating activities was $46.8 million for Q2 2021, down 22% from the $59.9 million recorded in Q2 2020. Cash burned in Q2 2021 was $33.4 million, down 33% from $50.1 million in Q2 2020. We have reduced both our R&D and SG&A expenses considerably compared to prior years. Most recently, we reduced R&D and SG&A expense by 33.1 million, or 30%, and reduced net cash use and operating activities by 22% compared to Q2 2020. As you can see, we have aggressively reduced expenses and cash burn over the last year, and we'll continue a strong focus on this moving forward. I'd like to take a moment to discuss the absence of long-term cash guidance in today's news release. Our long-term revenue projection ranges have been continually analyzed and adjusted during the pandemic. It has become increasingly difficult to anticipate or predict the ongoing and severe effect of COVID, especially with the return and uncertainty caused by the Delta variant and its associated impacts. The upstream patient visits, cancer diagnoses, and debulking surgeries that affect uptake of Rebraca in the second line ovarian cancer maintenance setting have not recovered to pre-pandemic levels. This makes revenue range assumptions less predictable. At this time, as will be disclosed in our Form 10Q for the period ending June 30, based on current revenue estimates, we have sufficient cash and available liquidity under our Athena financing agreement to fund our current operating plan for at least the next 12 months. However, we cannot predict revenues with sufficient accuracy to provide cash guidance beyond that. We need additional clarity into the abatement of the pandemic before this can be done. As noted earlier, we maintain our focus on cost controls and balance sheet management to mitigate the cash impact of Rebecca's unpredictable revenue situation in this challenging environment. We believe that there is adequate flexibility within our operating plan to adjust variations in our expected revenue, Rebecca revenues, and the availability and timing of potential sources of financing. I'll turn the call back to Pat.
spk02: Thanks, Dan. Obviously, I echo Dan's statement about this being a challenging time. But also note that programs we implemented over the last several years are setting the stage for what I believe will be a strong and exciting 2022 and beyond. Let me review our key strategies and our focus on creating value for shareholders over the next few years. First, we seek to drive Rubraka revenue growth. We continue to pursue organic growth of Rubraka in the U.S. and Europe in our current indications as the effect of the COVID-19 pandemic resolves over time. However, we believe the more significant opportunity to drive revenue growth for Rubraka will come from the three Phase III studies of the readout over the next 6 to 18 months. Each readout, if successful, offers the opportunity to expand Rubraka's labels in the U.S. and Europe to a larger and career-line patient population. Second, we seek to become a leader in targeted radionuclide therapies. The Lumiere Phase I-II clinical study of FAP2286, the first peptide-targeted radionuclide therapy targeting FAP in clinical development, is now open for enrollment. We intend to aggressively move FAP2286 in the Phase II cohorts of Lumiere, initiate additional monotherapy and combination studies, and begin clinical candidates of an additional radiotherapeutic candidate in 2022 as part of that commitment to lead in this emerging field of oncology development. And third, we seek to achieve long-term financial stability by transitioning our R&D focus from large Phase III Rubraka studies to our earlier stage targeted radionuclide development programs, maximizing Rubraka's revenue potential through label expansion, as well as a return to growth in our current indication when this damn pandemic finally ends. We will maintain our ongoing cost containment efforts, which have resulted in significantly lower total SG&A and R&D spending. These strategies form the foundation of our focus to create value for shareholders A corporate presentation describing these goals will be available on the investor section of our website after today's call. I'm very proud of our team at Clovis, whose hard work, dedication, and commitment to improving the lives of cancer patients moves us all toward our goals. We expect the next six to 18 months to be eventful with the potential to transform Clovis and provide additional value creation. And with that, we will be happy to answer any questions you may have.
spk01: Thank you. 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 Kasimov with JP Morgan.
spk10: Your line is open. Hi, this is Gavin on for Corey. Thanks for taking our questions. Just a quick one on 2286 development program. For Lumiere, can you just talk about the rate of patient accrual and when we should expect ? Lindsay?
spk05: So it's, as you'd expect, for a first-in-land study. It's a dose escalation study. with each cohort being enrolled sequentially with a safety follow-up period after the last patient in each cohort has been enrolled to ensure that it's safe enough to move through to the next dosing cohort. We'll expect the safety data coming right from the beginning, but as I say, it's a first-in-man study, so it will take us a few cohorts to get to the dosing levels where we may potentially see activity. So safety first, then activity coming through later.
spk11: Okay, great. Thank you.
spk01: Your next question comes from the line of Tazine Amaz with Bank of America.
spk06: Hi, good morning. Can you hear me?
spk01: Yes.
spk06: Okay, great. Hi, Pat. How are you? Good, Tazine. Good. Can you give us some color about the dynamics? You know, you've talked about having made changes to your marketing strategy. efforts, you know, very, very early on in COVID. And as we've unfortunately continued to live through the effects of it, just wondering the changes that you made, how do you think that they have played out? I mean, do you think that, you know, if things never go back to completely normal, you know, but improve from here, that the changes you've made will position your team to still market effectively? And then I have a follow-up.
spk02: i do um obviously access you'll hear this from everybody improved somewhat but it's still somewhat limited and so uh in an era where where access is is very limited and uh the the sales reps are are limited to zoom calls that they can get them other means of electronic communication it became evident that augmenting those activities with a significant digital presence was not only good practice because of COVID, but directionally is where our physician population wants to gain information on their own time at home in their office. And I think, and others have suggested they will pursue a similar approach. We pursue it as well to the extent we can in Europe. And I think that it actually was timely. As we noted at the time, it did result in a cost savings annually of around $10 million. We're grateful for that. The metrics we have, the program is being rolled out in a targeted way. And the metrics we have in the targeted population demonstrate improvements in market share in most cases, And we're learning ever more about the number of hits, whether it's in-person or digital, that are necessary to drive a script and adoption. So we're learning a lot. We continue to be affected, as everybody is, by COVID. But I don't doubt this is a better 21st century version of oncology promotion and marketing.
spk06: Okay. And... you know, assuming that the Athena results are positive, would your efforts to expand into earlier lines of therapy require to make any changes to these efforts, or would it be just, you know, add-on? Would you need additional resources?
spk02: I mean, there'll be some marketing spend to reflect the new data and the launch, almost relaunch of Rubraka into this indication, but I don't anticipate any meaningful, if any, change in the organizational structure or in our approach to using this hybrid model. So I think the dollar effects will be largely, I was going to say invisible, at a minimum limited in terms of our SG&A spend.
spk06: Okay, great. Thanks, Tom. Thank you.
spk01: Your next question comes from the line of Paul Choi with Goldman Sachs.
spk07: Hi, everyone. Good morning. A few from us. Maybe starting with prostate, could you maybe just sort of comment on field or physician office dynamics? And if you are seeing perhaps greater access or utilization in one setting, such as urology versus the medical oncologist, then I have a follow-up question.
spk02: We have a limited effort directed at urologists thus far, just because we're all aware that until the Triton3 data get into the label, that we do have a label disadvantage. So I don't have an easy answer. I would say, though, that the access issues are regional and tend to be quite a bit more significant in the Northeast than, for instance, in parts of the South. But we wonder if that will change again in relationship to COVID and the Delta variant driving so many cases now in the South. And so I would say, Paul, that it is variable. It's getting a little bit better. The number of in-person calls made in Q2 versus Q1 were a meaningful step forward, but still not where we want to be. And again, I'll say again, I think that COVID not only causes effects, but accelerates ongoing trends. And I think the ongoing trend of more limited access, particularly in academic institutions, will continue even as COVID finally goes away.
spk07: Okay. Maybe just to follow up on that, Pat, given that this is largely a mostly, you know, COVID vaccinated population, in your mind, will the inflection largely be driven by the Triton 3 label change pending that update in your view over time? Or is it still over the near to intermediate term largely pandemic driven?
spk02: Paul, I don't know that I understood that question, and I apologize. Do you mind asking that again?
spk07: Oh, yeah, sure. I guess just, you know, what primary factor do you see as the driving future inflection or uptake in this setting? Is it more resolution of COVID or future label changes to your earlier comment?
spk02: We need Triton 3. Okay, got it. We need Triton 3. We need to move into an early line. an earlier line of therapy that has us on an equivalent ground with Olaparib.
spk07: Okay, great. Thanks for that. Then just a quick one on 2286, which is just with regard to the supply chain, can you maybe just comment, you know, just given the, I guess, relative scarcity of lutetium, just where you are with regard to supplying, sourcing that, and, you know, your manufacturing process on that, and just, you know, how you think about sourcing that for your clinical development. Thank you very much.
spk02: Yep. We haven't named our supplier, but it's one of the larger. And we don't have a long-term supply agreement like a commercial supply agreement. We anticipate that will develop over the next couple of years. But we do have a clinical supply agreement with them, and we don't have any doubts that they will be able to meet our trial needs and potentially serve as our commercial supplier as we get closer to a potential, hopefully accelerated approval in the coming several years. I will also note that you're right. that supply of both lutetium and actinium, for that matter, have been historically limited. But not only are current manufacturers of lutetium expanding their capacity, new suppliers are emerging because it is evidently an opportunity as the field demonstrates progress and success. And there's nothing I know that suggests we have any risk of a supply issue with lutetium supply.
spk07: Okay, thank you, Pat. I'll hop back in queue. Thank you. Thanks, Paul.
spk01: Your next question comes from the line of Andrew Behrens with SBB Learing.
spk03: Hi, thanks. Pat, I just wanted to understand the comments about the LODESTAR trial and the strategy you guys are planning. It sounded from the prepared comments that you found a commutation biomarker. It could lead to a tumor agnostic label, and I wasn't really sure what you said about breast, ovarian, and prostate. I thought those tumors had been excluded from the trial. So can you clarify that? And then also, is it correct that the submitted tumor types need to be exclusive of the tumor types that the class has already approved or your drug? And then I may have missed it, but what did you say is the status of the dead instrument that's due to expire this year?
spk02: um lindsay will answer lindsay and tom will answer the um the uh the questions on lodestar uh just briefly um we we the the status of the the debt that is due in september is that fully within our our cash planning is paying off the roughly 64 million dollars in cash uh to the owners of the september 21s in september so that That remains as planned. That has been a part of our cash use planning for the last, well, for several years. Lodestar. Lindsay, do you want to start? Or Tom, do you want to talk about bilelic mutations? Or no, go ahead, Lindsay.
spk05: OK. So thanks for the questions, Andy. You're right. When it comes to ovarian and prostate cancer, patients with BRCA-mutated tumors aren't included in Lodestar. But they are included if they have mutations in the three other genes that we're looking at, RAC1, CD, and PALB2. And the comment about the subgroup with the bi-linear mutation, that applies equally well to BRCA1, 2, and the other three genes. Tom, do you want to elaborate a little bit about the double-hit phenomenon?
spk11: Yeah, sure. Hello, Andy. What we've observed in our preclinical and our clinical studies to date is that it's not sufficient just to have one BRCA mutant or deleterious mutation in the five genes we're examining. What we observe is that to have efficacy, you need hits in both copies that's present in the cancer cell. And for ovarian breast pancreatic, that happens at a very high rate. However, if you look at other tumor types, such as lung, colorectal, the frequency of this double hit that gives you the efficacy of rubaraca is less. And so we see this kind of difference in the frequency of this double hit or bi-allelic loss depending on the tumor type. And because of that, we're looking at this with Foundation Medicine to actually try and work out bi-allelic loss as a potential companion diagnostic down the road.
spk03: Okay, and just to clarify, if a patient has a BRCA mutation but has another mutation of the class that you're looking at, are they included or is BRCA excluded from the candidate pool?
spk02: The rules are always a little uncertain. But by focusing on bilelic mutations, which is a specific subset, We optimistically believe that this would include, this could be a true pan tumor indication, even including in tumor types where for a different biomarker, a member of the class is already approved. But that is to be worked out with FDA. Okay. All right. Thanks a lot. Appreciate all the color.
spk01: Again, to ask a question, please press star, then the number one on your telephone keypad. To withdraw your question, press the pound key. Your next question comes from the line of Joe Catanzaro with Piper Sandler.
spk08: Hey, guys. Thanks so much for taking my question. Maybe two from me. The first, is the delay in the monotherapy versus placebo arm of the Athena trial due to slower-than-expected event accrual? It sounds like that's the case. And you've always guided towards the combination coming one year later. Is there any risk that the combination top line readout gets delayed into 2023? And how does the potential shift in top line readouts impact the timing of PPG debt repayment and when that starts? Thanks.
spk02: Dan will answer the PPG question in a moment. But Lindsey, perhaps you could answer the clinical result timing questions.
spk05: Sure. So thanks for the question, Joe. Our estimation for readout for monotherapy, as you suggested, is guided by the current event rate. And so it has been pushed out a little bit because the events are coming more slowly than we anticipated when we designed the trial. For the combination therapy part, we expect that to read out later. And right now, we're still using our protocol-defined assumptions to predict when that reads out. to maturity for the combination on, we'll be able to make a more precise estimate of when the readout will occur. But at this stage, it's possible that it could go into 2023. It's also possible that it could go earlier than the end of 2022. When we get nearer the time, we'll be able to estimate that much more precisely. And for us, of that TPG part?
spk09: Dan Bauschardt Hi, Joe. This is Dan. It doesn't have any impact on the TPG agreement. The timing of that is already set. So, you know, as I indicated in my comments, we'll draw down the remainder of it, mostly between Q3 and Q4 of next year, and that's when the payments start under any scenario.
spk08: Male Speaker Okay, thanks. That's helpful. And I might just ask a follow-up. I don't think I heard Lucitinib mention anywhere Are there still expectations to present data from the Nevo, Camo, and Demetrio cohort later this year? And does the full approval of Lamatinib and Pembro in this setting impact how you think about the longer opportunity? Thanks.
spk02: Yeah, we may present later this year data from an additional cohort. Obviously, any... commercial thoughts about lucidinib and further clinical thoughts about lucidinib are currently under review. And we'll await data from cohorts that are still enrolling to inform that decision.
spk08: OK, got it. Thanks for taking my question.
spk01: Keep it. At this time, there are no further questions. I would like to turn the call back over to Anna Sessman, VP of investor relations.
spk04: Thank you, Phyllis. We thank you all for your interest in Clovis Oncology today. If you have any follow-up questions, please contact me at 303-625-5022 or Brianna at 303-625-5023. The call can be accessed via a replay at our website beginning in about an hour and will be available for 30 days. We appreciate your interest and time and thank you and have a good day.
spk01: Ladies and gentlemen, that does conclude today's conference. We thank you for participating. You may now disconnect.
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