NovoCure (NVCR) 2026 年第三季財報電話會議：營收達 1.93 億美元，上調財測指引

重點摘要

• NovoCure 創下單季淨營收歷史新高，達 1.93 億美元，年增 16%，主要受惠於 活躍患者數成長 19%，以及美國與德國更高的給付核准率帶來的單次 400 萬美元 挹注。
• 毛利率提升至 77%，高於去年同期的 73%。調整後 EBITDA 達到 正 1,600 萬美元，相較於 2025 年第三季的負 300 萬美元顯著改善。
• 該公司將 2026 年淨營收財測上調至 7.36 億至 7.43 億美元，代表 12% 至 13% 的成長，並將調整後 EBITDA 財測調升至 2,400 萬至 3,400 萬美元。
• Optune Gio 在本季度末的 GBM 活躍患者數達 4,729 人，創下歷史新高，年增 11%。
• Optune Lua 全球營收達 800 萬美元，活躍患者數達到 255 人。其中日本市場貢獻了 110 名活躍患者 及 400 萬美元 營收。
• 在 daraxonrasib 推出後，Optune Pax 在美國的推廣動能放緩，第三季結束時 活躍患者數為 276 人，淨營收為 370 萬美元。

主要財務數據

營收亦包含 200 萬美元的外匯逆風。管理層將毛利率改善部分歸因於患者數量增加所帶來的供應鏈效率提升。

業務與營運表現

Optune Gio 與膠質母細胞瘤

Optune Gio 仍是 NovoCure 的主要成長動力。GBM 活躍患者數年增 11% 至 4,729 人，成熟市場與新興市場均有貢獻。

第三期 KEYNOTE-D58 研究正在評估 Optune Gio 聯合 pembrolizumab 及低劑量化療治療膠質母細胞瘤。管理層表示受試者招募進度正常，預計將於 2026 年底前完成。

Optune Mya

美國 FDA 正審查 NovoCure 針對非小細胞肺癌腦轉移的 Optune Mya 預市許可 (PMA) 申請。該申請基於第三期 METIS 試驗，結果顯示接受腫瘤治療電場 (TTFields) 治療組的中樞神經系統疾病進展時間較對照組增加了一倍。

管理層繼續預期 FDA 將於 2026 年底前做出決定，並表示上市可能於 2027 年初進行。公司預計會在上市後兩年內確立醫療保險給付。

Optune Lua

Optune Lua 全球達到 255 名活躍患者，並創造了 800 萬美元 的單季營收。日本市場佔了 110 名患者 與 400 萬美元 營收。

管理層特別強調了該產品在日本的適應症標籤與二線免疫檢查點抑制劑的使用相契合。日本協商出的每月價格與 Optune Gio 的全球價格大致相當。

Optune Pax

Optune Pax 在第三季結束時有 276 名活躍患者，淨營收為 370 萬美元。管理層表示，在 daraxonrasib 推出後，由於胰臟癌診所面臨更多與保險申訴及皮膚過敏處置相關的需求，美國市場的增長動能有所放緩。

NovoCure 計劃開展兩項涉及 KRAS 抑制劑的小型安全性與可行性研究。PANOVA-5 將評估 Optune Pax 聯合 gemcitabine、nab-paclitaxel 及 Verastem 的 VS-7375 在局部晚期胰臟癌中的療效。PANOVA-6 將評估 Optune Pax 聯合 daraxonrasib 在轉移性疾病中的療效。兩者均預計於 2027 年上半年啟動，各招募約 25 名患者。

管理層業績指引

管理層預計在可預見的未來，研發支出將大致維持在目前水平或低於目前水平。到了 2027 年，研發費用預計將持平或略有下降，其中 KEYNOTE-D58 與 LUNAR-2 仍是主要的支出項目。

公司打算主要依賴現有的銷售團隊，同時對 Optune Pax 及 Optune Mya 進行有限的增量行銷投資。一般及行政費用預計將保持在目前水平附近，僅受通膨相關的微幅增加影響。

管理層重申了實現雙位數營收成長的長期目標。此外還概述了三階段的獲利路徑：首先達到調整後 EBITDA 損益兩平，其次是現金流量損益兩平，最後是淨利潤損益兩平。季度進展可能會有所波動，特別是在 NovoCure 為新產品上市做準備之際。

風險與關注焦點

• 在 daraxonrasib 推出後，因競爭分散了醫師的關注度，Optune Pax 在美國的上市推廣速度有所放緩。
• 商業醫療保險機構對 Optune Pax 更廣泛的給付涵蓋，部分取決於其是否會納入更新後的 NCCN 胰臟癌指南。Elevance 已建立了針對該產品的給付政策。
• 第三季營收包含一次性的核准率效益，限制了與第四季進行直接的季增率比較。
• 外匯波動使第三季營收減少了 200 萬美元。
• 由於營收的波動性以及與產品上市相關的支出，調整後 EBITDA 可能會出現季度間的波動。

分析師問答集錦

管理層表示，尚未看到大量患者放棄 Optune Pax 改用 daraxonrasib，也沒有強有力的證據顯示除了無法耐受標準化療的患者之外有廣泛的一線 daraxonrasib 使用情況。公司目前認為，繁忙診所的接觸機會有限是限制 Optune Pax 處方開出的主要原因。

在談到日本市場時，管理層預計 Optune Pax 將在 2027 年第一季獲得健保給付，進而推動其商業化上市。公司認為肺癌與胰臟癌在日本都是巨大的市場機會，並預計日本最終將成為僅次於美國的第二大市場。

關於第四季營收，管理層解釋，在扣除約 440 萬美元 的一次性效益後，若第四季能延續第三季的表現，全年的營收將接近 7.4 億美元，大約落在更新後財測的中點。

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完整財報電話會議逐字稿

管理層陳述

Operator

Good day, and welcome to the NovoCure Q3 2026 Earnings Call. [Operator Instructions]

Please note, this call may be recorded. I would now like to turn the call over to Adam Daney. Please go ahead.

Adam Daney

Good morning, and thank you for joining us to review NovoCure's third quarter 2026 performance. I'm joined on the phone today by our Executive Chairman, Bill Doyle; CEO, Frank Leonard, Chief Innovation and Medical Officer, Uri Weinberg; and CFO, Christoph Brackmann.

For your reference, slides accompanying this earnings release can be found on our website, www.novocure.com on the Investor Relations page under Quarterly Results. Before we start, I would like to remind you that our discussions during this conference call will include forward-looking statements, and actual results could differ materially from those projected in these statements.

These statements involve a number of risks and uncertainties, some of which are beyond our control and are described from time to time in our SEC filings. We do not intend to update publicly any forward-looking statement, except as required by law. Where appropriate, we will refer to non-GAAP financial measures to evaluate our business and specifically adjusted EBITDA, a measure of earnings before interest, taxes, depreciation, amortization and share-based compensation.

We believe adjusted EBITDA is an important metric as it removes the impact of earnings attributable to our capital structure, tax rate and material noncash items and best reflects the financial value generated by our business.

We do not provide forward-looking guidance for adjusted EBITDA on a GAAP basis due to the inability to predict share-based compensation expenses contained in the reconciled GAAP measure, net income without reasonable efforts.

Reconciliations of non-GAAP to GAAP financial measures are included in our press release, earnings slides and in our Form 10-Q filed with the SEC today. These materials can be accessed from the Investor Relations page of our website. Following our prepared remarks, we will open the line for questions. I will now turn the call over to our Executive Chairman, Bill Doyle.

William Doyle

Thank you, Adam. This morning, NovoCure reported results for the third quarter of 2026. This quarter was marked by solid execution with continued momentum in our Optune Gio business and our promising launch of Optune Lua in Japan. We reached a record number of active patients on therapy, generated record high quarterly net revenue, and made strong progress on our path to profitability.

We experienced headwinds in our Optune Pax launch this quarter, but remain committed to establishing TTFields therapy in the evolving PDAC standard of care. As we enter the final months of the year, we are on track to achieve our 2026 goals, and we believe we are well positioned to drive this positive momentum into 2027.

I will begin this morning with a review of our Optune Gio and Optune Mya programs. Frank will provide an update on Optune Pax and Optune Lua, and Christoph will conclude our prepared remarks with a review of our third quarter financial results and updated guidance. We will then open the line for questions.

Q3 was another strong quarter for our Optune Gio business. We finished the period with 4,729 GBM patients on therapy, an 11% increase year-over-year and our highest GBM active patient count to date. A notable feature of this growth cycle is the mix of contributions from both new and established markets. We continue to believe many more patients can benefit from Optune Gio, and we are determined to find the avenues to reach them.

Each of our active markets has opportunities to increase adoption in GBM, and our country-level teams are focused on improving outreach and targeting to connect with physicians and patients at the optimal points in their treatment journeys. Optune Gio is a standard of care for newly diagnosed GBM, established on the foundation of the best-in-class clinical data for overall survival. And we are working to extend survival further.

Our Phase III KEYNOTE-D58 clinical trial is evaluating adding the immunotherapy pembrolizumab to Optune Gio and low-dose chemotherapy in diagnosed glioblastoma. We've been pleased with the strong interest in D58 since launch as physicians are eager to see whether concomitant use of TTFields and immunotherapy can improve survival in GBM further. D58 remains on track to complete enrollment by year-end, and we look forward to sharing more information from this trial in the periods ahead.

Turning to Optune Mya, our PMA application for the treatment of brain metastases from non-small cell lung cancer is under review with the FDA. As a reminder, this application is based on the data from the Phase III METIS trial, which showed a doubling in time to intracranial progression in patients on the TTF arm compared to control.

We continue to expect a final decision on our PMA application by year-end with a potential launch in early 2027. As with our other launches, we expect to establish reimbursement within two years of launch.

NovoCure continues to grow and evolve. We have reignited growth in our core GBM business and launched Optune Lua and Pax in multiple countries, with Mya expected to follow. We've established the infrastructure to service larger patient populations and have initiated structural changes to accelerate our transition to profitability. I'll now pass the call to Frank to discuss the ongoing launches of Optune Pax and Lua.

Frank Leonard

Thank you, Bill. We believe that we have multiple drivers of long-term growth, including increasing adoption of Optune Gio, successfully launching new indications like Optune Pax and Mya and pursuing opportunistic launches such as the Optune Lua launch in Japan. We are 2.5 quarters into our launch of Optune Pax, and we finished the third quarter with 276 active patients on therapy and generated $3.7 million in net revenue.

We have seen momentum slow in the U.S. due to the introduction of daraxonrasib. Our ability to access practices to detail Optune Pax is significantly limited at this time. We acknowledge the challenges in the Optune Pax launch, and we will continue to evolve our tactics to ensure we maintain our share of voice in our approved indication, which is different than the approved indication for daraxonrasib.

We will also continue to monitor the details of the daraxonrasib launch and invest appropriately in relation to the market realities. We look forward to the upcoming annual update of the NCCN guidelines for the treatment of pancreatic cancer, and we'll update our marketing materials accordingly.

Most importantly, we will work closely with our physician collaborators to establish the best next set of clinical trials to establish TTFields more firmly as the standard of care for PDAC.

We are specifically eager to generate data focused on concomitant use of TTFields and KRAS inhibitors. The initial step in this effort will be through two small safety and feasibility trials. The PANOVA-5 trial will explore the concomitant use of Optune Pax, gemcitabine, nab-paclitaxel and Verastem's KRAS G12D inhibitor, VS-7375 in our approved locally advanced setting. We are excited to collaborate with Verastem in this effort and expect to initiate this study in the first half of 2027.

The PANOVA -6 trial will explore concomitant use of Optune Pax and daraxonrasib in the metastatic setting, which we also expect to initiate in the first half of 2027.

Moving to Optune Lua. We continue to see momentum in our launch in Japan. We finished the quarter with 255 Optune Lua active patients and $8 million net revenue globally, with 110 active patients and $4 million in net revenue contributed by Japan. Second-line use of immune checkpoint inhibitors is standard of care in Japan, which overlaps well with our label and the strongest outcomes from the LUNAR trial data.

In addition to the promising commercial landscape, the negotiated monthly price for Optune Lua in Japan is approximately in line with our global price for Optune Gio. Optune Pax was also approved by Japanese regulators earlier this year with reimbursement likely in the first half of 2027. Together with our growing Optune Gio business, we expect Japan will eventually be our second largest market behind the U.S.

As Bill said earlier, we focused in recent years on diversifying and expanding our growth drivers. We are beginning to see those drivers contribute, specifically in our continued Optune Gio growth and Optune Lua launch in Japan. We expect Optune Pax to return to growth in the coming quarters. And with these drivers in place as well as enhanced controls on operating expenses, we believe we are well positioned to make material strides forward in our path to profitability next year. I'll now pass the call over to Christoph to review our third quarter financials.

Christoph Brackmann

Thank you, Frank. This was a very strong commercial quarter. We generated $193 million in net revenue, an increase of 16% year-over-year. This includes contributions of $8 million and $4 million from Optune Lua and Optune Pax, respectively. The increase in net revenue was primarily driven by a 19% year-over-year increase in active patients as well as a onetime benefit of $4 million from increased approval rates in the U.S. and Germany. We also experienced a $2 million headwind from foreign exchange rates in the quarter.

Based on our strong commercial performance this quarter, we are raising our revenue guidance. We now expect 2026 net revenue between $736 million and $743 million, representing 12% to 13% growth. This includes net revenues from Optune Lua and Optune Pax collectively between $30 million and $34 million.

Gross margin for the quarter was 77% compared to 73% in Q3 of last year. An important aspect in our pursuit of profitability is optimizing our supply chain efficiency as we treat larger patient populations, and we continue to see progress on these initiatives. We expect to maintain our gross margin in the mid- to high 70s through the final quarter of 2026.

Turning to our operating expenses. Research and development costs this quarter were $58 million, an increase of 8% year-over-year. The increase was primarily driven by expenses related to our KEYNOTE-D58 trial as we finalize enrollment.

R&D expenses can fluctuate quarter-to-quarter, largely around clinical activity for services delivered in the period. We are confident that we can keep R&D costs roughly at or below current levels for the foreseeable future.

Sales and marketing expenses in the quarter were $53 million, a decrease of 9% from the same period last year. The change was primarily driven by lower share-based compensation and lower general marketing expenses in the quarter. As we look ahead to Q4 and 2027, we intend to largely leverage our existing sales forces.

We do expect to make limited incremental marketing investment intended to support the launches of Optune Pax and Optune Mya.

General & Administrative Expenses for the quarter were $44 million, a decrease of 5% year-over-year. The primary driver of the decrease was lower share-based compensation expenses. We have made the G&A investments required to support larger patient populations, and our aim is to maintain the current level of G&A with minimal increases due to inflation.

Net loss in the quarter was $10 million compared to a $37 million loss for Q3 of last year and loss per share was $0.09. Our EBITDA loss in the quarter was $2 million compared to a loss of $32 million in Q3 of 2025.

Adjusted EBITDA, which removes the impact from share-based compensation was positive $16 million this quarter compared to a negative $3 million of last year. We are updating our full year adjusted EBITDA guidance today to a range of $24 million to $34 million.

Our cash and investment balance as of September 30 was $463 million. Our focus on profitability has been a key performance metric for the entire organization in 2026, and we are pleased with the progress made this quarter. The third quarter marked a new record high net revenue generated and our strongest EBITDA and adjusted EBITDA quarter in over four years.

The investments necessary to launch new indications and support larger patient populations have largely been made. As we continue to gain traction across our commercial portfolio, we believe there is significant P&L leverage to be realized. Achieving adjusted EBITDA positivity this year is an important first step in the profitability journey, and we look forward to updating you on our progress and future objectives in the coming months.

With that, we will now open the line for your questions.

Operator

[Operator Instructions]

Our first question comes from Vijay Kumar with Evercore ISI.

分析師問答

Vijay Kumar

Frank, maybe my first one on Pax trends. And I know in the past, you've said this is not like a drug launch. Don't expect script volume similar to drugs. And I understand that, but sequential step down here on patients and script volumes, right? If you could just elaborate on what happened in the quarter? How are we thinking about Pax launch, I think that will be helpful.

Frank Leonard

Yes. Thank you, Vijay, for the question. It's clear, we had a record quarter overall in terms of our commercial execution, as Christoph just detailed, really strong progress across Gio around the world as well as our Japan launch. But it is clear to us that we faced significant challenges in the U.S. Pax launch this quarter. To give a little bit of color, I think we all need to think about just the sheer volume of patients now coming into practices and asking for daraxonrasib.

And that has an immediate effect on the practice in a few different ways. I mean, one is that immediately, the insurance appeals start. And I think as some on the line are tracking, the journey for daraxonrasib through the insurance process is just starting. And on the other side, as the patients progress on therapy, they do see a lot of skin irritation.

So what we face in terms of getting into practices right now is really just a share of voice issue as we see it right now that the practices are just a bit overwhelmed. They're overwhelmed with appeals, they're overwhelmed with skin irritation. But we do see that continued interest when we engage with clinicians in explaining Optune Pax.

So to look ahead, we are committed to this market. We still see strong recognition of the clinical value of Optune Pax as a first-line treatment in locally advanced pancreatic cancer. And we are eager to see this early disruption kind of the practice disruption settle down in the coming quarters and give us a chance to really get back in there and earn the patients that could really benefit from Tumor Treating Fields.

Vijay Kumar

Understood. Maybe Christoph, one for you. Adjusted EBITDA performance here in the quarter was really a standout. Sustainability of this level of sequential improvements in adjusted EBITDA. I mean what's the path forward when you think about adjusted EBITDA trends?

Christoph Brackmann

Yes. Thank you, Vijay. Yes, you said it. I mean, we had a very strong quarter of financial performance, both across all lines really on the P&L, right? I mean, starting with revenue growth, very strong revenue growth based on active patient growth, but also with some onetime benefit. We had strong gross margin, relatively lower cost to previous quarters. And all of that culminated in a record high EBITDA and adjusted EBITDA. So the first comment is, as we said in the past, we are really committed to this path of profitability, and we always said for us, it's three steps.

Step 1 is to get adjusted EBITDA breakeven.

Step 2 is then cash flow breakeven, step 3 is net income breakeven.

And we are very happy that we passed the first step, and we are committed to adjusted EBITDA breakeven if you look at it on a full year basis.

Now I would caution, we will have some fluctuations quarter-to-quarter. You can also take from our guidance for adjusted EBITDA that we're not just straight line projecting a quarter-over-quarter increase, but we gave ourselves some room. One is on -- we have a range on revenue for our guidance, but then two is also now with Q4 coming up. It's typically a difficult quarter to estimate because we are getting ready for launches for next year.

So in short, we are committed to adjusted EBITDA breakeven. We are committed to really focus on the next call is cash flow breakeven, but I wouldn't want to commit to a straight line on a quarter-to-quarter basis.

Operator

Our next question comes from Larry Biegelsen with Wells Fargo.

Larry Biegelsen

So one on 2027, one on Pax. So Frank, I think at our healthcare conference, you talked about striving for double-digit growth in 2027. Is that still the case? And can you talk about the headwinds and tailwinds behind the outlook?

Frank Leonard

Thanks, Larry. Yes. So as we've talked about the future of NovoCure, what we have aspired to be is a company that produces double-digit top line growth and returns to profitability, as Christoph just outlined. We were really pleased in this quarter to have delivered double-digit growth, both when you look at all products together, but even in the Gio franchise, where existing markets like the U.S. were growing strong, and we found new markets to continue building like Spain.

I think that our commercial organization is really firing on all cylinders right now. And where there's opportunity, they're taking it. And I think I'm quite proud of those results. So yes, that's our vision is we remain committed to delivering that top line double-digit growth into the future.

Larry Biegelsen

That's helpful. And Japan was obviously very strong again this quarter. What are your expectations for Lua and Pax? Just remind us of the time line for reimbursement there. We saw, obviously, you got approval and remind us why this is an exciting opportunity.

Frank Leonard

Thank you, Larry. And I realize I missed the very end of your question. I didn't answer the very end of your first question here. In terms of possible tailwinds or real tailwinds for the company overall, our business in Japan is definitely one of those tailwinds. We have launched Optune Lua successfully, continued to build our active patient volume through the year this year.

We are already looking ahead to next year where we have our national symposium with all of the relevant physicians who treat non-small cell lung cancer in Japan coming into Tokyo to do a symposium just focused on Optune Lua in January. So we see that strong continued interest for Lua to continue growing in Japan.

Optune Pax was just approved for regulatory approval in the quarter, and we expect to have reimbursement early in 2027, first quarter of 2027, which would then allow us to begin the launch in Optune Pax. And as a reminder, for both of these products, we were able to reset our price levels with the MHLW in Japan. Both Lua is already priced at a higher level than our Gio product in Japan. And we're hopeful that we'll be able to achieve a similar outcome for the Pax product as it comes to market.

So the last thing I'll say is just to remind everyone in Japan, historically, our business in Japan has appeared relatively small, relative to the rest of the company because the incidence of GBM is very low in Japan. That's not the case for lung cancer. And in fact, in pancreatic cancer, it's actually a higher incidence than in the U.S. So these are real sizable markets with strong physician interest, and we are very excited for our Pax launch in Japan.

Operator

Our next question comes from Jason Bednar with Piper Sandler.

Jason Bednar

I'll ask the obligatory question here on Optune Pax as well. Just curious, Frank, I mean, I guess, what are you able to control with the process here? And when we think about the accounts you had that were initial users of Pax are they still using? Or did activity -- prescribing activity more or less dry up after the approval? And sorry, I'm going to add another one. Is this an issue you think of practices simply being overwhelmed and they don't have time? Or are you seeing just a lot of practices putting both locally advanced and metastatic PDAC patients on therapy?

Frank Leonard

Okay. Thank you, Jason. Yes, I'll jump in on the second part of this. That's obviously our focus right now is trying to understand what has caused the slowdown in prescribing patterns. We're looking at it both quantitatively in terms of buying data and qualitatively in terms of speaking with physicians. And first and foremost, what I want to highlight is that we're not seeing patients leaving Optune Pax in substantial numbers to start daraxonrasib.

And when we look at qualitative and quantitative data as well, we don't see strong signals that daraxonrasib is being used widespread in first line, except in the patients where they can't tolerate standard chemotherapy. So that leads us back to the hypothesis that we see the practices as just being simply overwhelmed right now and that is what's limiting our ability to get in.

As we spoke briefly about earlier in the call, again, this is a device-based launch. practices need training, they need support. They need help educating the patient. So we do see this as a bit of -- right now, we see it as an issue with the noise of getting into the practice. What can we control? I think first and foremost, we are as an organization, we remain committed to this indication, and our teams know we're committed to the indication, and we are continuing to get as much as we can to get to our physicians.

On that front, I would highlight one of the really promising signals that I picked up recently is I just came back from the ESMO conference in Madrid, we had incredible engagements with physicians across all of our indications. But when I look back at the numbers from the booth of unsolicited inquiries, the #1 product that led to inquiries in our booth was Optune Pax.

So that's where we feel that the recognition of the clinical value is still there. It is up to us to execute with our teams in the field, getting that message out and highlighting the different indications, different stage of treatment that our product is approved for. And then lastly, as we announced yesterday and spoke about today, we are going to continue building the evidence to support and consolidate our status as a valuable and standard of care treatment for PDAC.

Jason Bednar

Right. Very helpful and very clear. One follow-up quick and then a separate question. I'm not sure if I caught where you're at with respect to commercial payers on Optune Pax. Sorry if I missed that, but refresh me there. And then on R&D, obviously, a little bit of a step-up in the quarter, but you're coming to the close of KEYNOTE-D58. How should we think about R&D trending as we move beyond '26 once that KEYNOTE D58 trial ends? I know you got a couple of earlier-stage trials, but those should be far cheaper than KEYNOTE-D58.

Frank Leonard

Yes. Jason, I'll start and then I'll turn it over to Christoph. In terms of our payer engagement in the U.S., the next major milestone for us is to secure inclusion in the NCCN guidelines. The NCCN guidelines for pancreatic cancer are typically published once a year, either at the end of the year or early in the new year.

We have submitted. We understand that we've been reviewed, and we're eagerly waiting for those results to be published. That will trigger additional engagement with payers where we've already had and reported on our one success with Elevance, where we now have a coverage policy in place. Christoph, I'll turn it over to you to talk about any other emerging trends with payers as well as the R&D question.

Christoph Brackmann

Yes. I think on the payer side, I mean, as you noted, I think the real next milestone is NCCN guideline. And apart from that, we are having the discussions with the payer on the commercial side on the inclusion in policies. Obviously, this is a function of, one, the number of patients on therapy that helps us to mess and build pressure with payers and then two, the guideline inclusion is an important factor for that as well.

On the R&D question, Jason, so from a big picture perspective, 2026, we had larger Phase III trials roll off, as you know. And then we had particularly D58 now being close to full enrollment is really at the, let's say, highest level of activity and from that also from a spend intensity perspective at the highest level.

That essentially replaced the studies that we had that were rolling off. For 2027, we expect D58, but also LUNAR-2 still be a significant portion of our spend. So as we said, we expect our R&D expenses flat to slightly declining. And then going beyond that time frame, as large Phase III trials roll off, namely D58 and LUNAR-2, we would expect our R&D expense to go down if we don't replace it with other larger trials.

Operator

Our next question comes from Jessica Fye with JPMorgan.

Tanmay Patwardhan

This is Tanmay on for Jess. I have a question around the updated total revenue guidance. And when I was calculating, I saw that your revised annual revenue guidance now implies $185 million to $192 million in 4Q revenue, which is below the $193 million revenue recorded in 3Q. So can you talk about what assumptions are driving this sequential step down?

Christoph Brackmann

Yes, I can take this. So maybe I share a bit more thoughts on our revenue guidance in general. First, Q3 was really a very successful quarter in terms of net revenue, adding about $9 million of revenues to what we had as a record quarter in Q2, right? So thinking about Q4 revenue guidance, if we do in Q4, what we did in Q3, less the $4.4 million onetime revenue in Q3 that we pointed out, that essentially gets you to $740 million, which is around the midpoint of our guidance. And that was the thinking here. And then we accounted for some potential risk on collection side and some opportunities that we have.

Operator

Our next question comes from Kevin DeGeeter with Ladenburg Thalmann.

Kevin DeGeeter

I just had one on the Verastem collaboration or a clinical trial you announced yesterday. And from the NovoCure perspective, what's the more important learning from that study? Is it really kind of appreciating the patient sort of antitumor clinical benefit of a combination with the KRAS inhibitor? Or does it really learn more about how the skin toxicities kind of play together? I just kind of want to understand, I guess this is an NovoCure-funded study kind of from your perspective, what are we trying to learn?

Frank Leonard

Excellent. Thank you for the question. I'll start off, and then I'll turn it over to my colleague, Dr. Weinberg, to speak to some of the specifics of the trial. First, I just want to note that we are very pleased to have this collaboration in place with Verastem. We think that this asset has the potential to be best-in-class, and we are excited to work with them. I think I would also highlight that I think this trial being done in locally advanced pancreatic cancer, first line, which is our FDA-approved indication, is strong validation of Tumor Treating Fields as an effective therapy in that indication already. And that really drove our ability to get a top-tier partner to work with us on a study here. So my thanks to our partner, our collaborators at Verastem. And I'll turn it over to Dr. Weinberg to talk a little bit about what we hope to see and how it dovetails off some of the things we've already seen in preclinical research.

Uri Weinberg

Thank you. So the PANOVA-5 study is going to focus on our approved indication in pancreatic cancer, namely locally advanced unresectable patients. And it will incorporate the Verastem's G12D VS-7375 inhibitor, KRAS inhibitor concomitantly with gemcitabine, nab-paclitaxel and of course, Optune Pax.

This study will include around 25 patients. And we have also announced that we are opening the PANOVA-6 study that will use daraxonrasib in its approved indication of metastatic pancreatic adenocarcinoma concomitantly with Optune Pax enrolling a similar number of patients. So we are being very attentive to the developments in the field and dynamic in our approach to that, considering everything that we have done in pancreatic cancer so far.

And these two smaller single-arm studies intend to give the first experience showing feasibility and tolerability and toxicity of the concomitant use of Optune Pax with KRAS inhibition in the disease. And as you mentioned, the first and foremost goal of these two studies is to give physicians with the right level of confidence and experience to see the feasibility of this.

We will learn about toxicity, but we're not particularly concerned about this considering the local nature of our therapy and the nature of the skin toxicity that we observed so far in pancreatic adenocarcinoma. And I would just remind everybody that preclinically, we have seen a very important activity of TTFields affecting downstream transcription factors to KRAS, which suggests that the concomitant use of our device with KRAS inhibitors of any kind might be very interesting and even could be synergistic, hopefully.

Operator

I'm showing no other questions. I'd like to turn the call over to Bill Doyle for closing remarks.

William Doyle

Thank you very much. I'd like to conclude today with a big thank you to the NovoCure team. This was an exceptionally strong quarter. And as Frank noted, it was strong across the board. Our emerging markets performed very well. But importantly, our established markets really showed growth across the board.

We've said for years that there are many more patients who can benefit from Tumor Treating Fields than have been currently prescribed. And our teams have begun to figure out the ways to get to those patients and their clinicians at the moment that decisions are made so that they can benefit from the therapy, and we saw it in the numbers.

We're focused on Pax, as you described. There's a tremendous amount of change in the pancreatic market. We're all aware of this. As Frank described in detail, it's creating quite a bit of work within the practices. And that work involves learning how to use the new therapy, learning how to guide patients through the reimbursement process. But we also know that the KRAS therapies are not cures, and we're going to see a wave of recurrence later this year as well if the data that we've seen in the clinical trials bears out, which we expect it to.

That's where we're really going to see, I think, the opportunity to, one, get back into the practices, but really find the sweet spot for Tumor Treating Fields in this emerging landscape, along with the activities that Uri described, really studying the concomitant use of the therapies together. And then finally, we are a company that's committed to profitability. And I think we have shown tangible progress on that path over the last few quarters. And we're very pleased to be able to increase our guidance, both in terms of revenue, but importantly, in terms of adjusted EBITDA today. So thank you very much for your interest in NovoCure, and we look forward to our next report.

Operator

Thank you for your participation. This does conclude the program. You may now disconnect. Good day.