Grail Inc (GRAL) 2025 Q4 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the GRAIL fourth-quarter 2025 earnings call. (Operator Instructions) Please be advised that this conference call is being recorded. GRAIL Investor Relations, please begin.

各位女士、先生，大家好，歡迎參加 GRAIL 2025 年第四季財報電話會議。（操作員說明）請注意，本次電話會議正在錄音。GRAIL投資者關係部，請開始。

Thank you, operator, and thank you all for joining us today. On the call are Bob Ragusa, our Chief Executive Officer; Aaron Frieden, our Chief Financial Officer; Josh Ofman, President; Sir Harpal Kumar, Chief Scientific Officer and President, International; and Andy Partridge, Chief Commercial Officer. Before we get underway, I'll remind you that we'll be making forward-looking statements based on current expectations.

謝謝接線員，也謝謝各位今天收看我們的節目。參加電話會議的有：執行長 Bob Ragusa；財務長 Aaron Frieden；總裁 Josh Ofman；首席科學官兼國際總裁 Harpal Kumar 爵士；以及首席商務官 Andy Partridge。在正式開始之前，我要提醒各位，我們將根據目前的預期做出一些前瞻性陳述。

It's our intent that all statements, other than statements of historical fact, including statements regarding our anticipated financial results and commercial activity will be covered by the safe harbor provisions for forward-looking statements under federal securities laws. Forward-looking statements are subject to risks and uncertainties and -- actual events or results may differ materially from those projected or discussed.

我們希望除歷史事實陳述外，所有陳述，包括有關我們預期財務業績和商業活動的陳述，都能受到聯邦證券法中關於前瞻性陳述的安全港條款的保護。前瞻性陳述存在風險和不確定性，實際事件或結果可能與預測或討論的內容有重大差異。

All forward-looking statements are based upon currently available information, and GRAIL assumes no obligation to update these statements. To better understand the risks and uncertainties that could cause actual results to differ, we refer you to the documents that GRAIL files with the SEC, including GRAIL's most recent quarterly report and upcoming annual report. This call will also include a discussion of GAAP results and certain non-GAAP financial measures, including adjusted gross profit and adjusted EBITDA, which excludes certain specified items.

所有前瞻性陳述均基於目前可獲得的信息，GRAIL 不承擔更新這些陳述的義務。為了更了解可能導致實際結果出現差異的風險和不確定性，我們建議您參閱 GRAIL 向美國證券交易委員會提交的文件，包括 GRAIL 最新的季度報告和即將發布的年度報告。本次電話會議也將討論 GAAP 結果和某些非 GAAP 財務指標，包括調整後的毛利和調整後的 EBITDA（不包括某些特定項目）。

Our non-GAAP financial measures are intended to supplement your understanding of GRAIL's financials. Reconciliations of the non-GAAP measures to most directly comparable GAAP financial measures are available in the press release issued today which is posted to our website.

我們的非GAAP財務指標旨在幫助您更了解GRAIL的財務狀況。今天發布的新聞稿已發佈在我們的網站上，其中包含了非GAAP指標與最直接可比較的GAAP財務指標的調節表。

And with that, we turn to Bob.

接下來，我們把目光轉向鮑伯。

Good afternoon, everyone, and thank you for joining us to review results for the fourth quarter and full year 2025 and discuss recent business updates. 2025 was a year of significant commercial growth for GRAIL, and we have shared a number of exciting developments so far in 2026. We issued a press release this afternoon with top line results from our NHS Galleri trial. We observed a substantial reduction in Stage 1 cancer diagnosis, increased Stage 1 in new detection of deadly cancers and a fourfold higher cancer detection rate outcomes that matter for patient care.

各位下午好，感謝各位參加本次會議，共同回顧2025年第四季及全年業績，並探討近期業務進展。 2025年是GRAIL實現顯著商業成長的一年，我們在2026年也分享了一系列令人振奮的進展。今天下午我們發布了一份新聞稿，公佈了我們在英國國家醫療服務體系 (NHS) 進行的 Galleri 試驗的主要結果。我們觀察到 1 期癌症診斷大幅減少，致命癌症新發 1 期病例增加，癌症檢出率提高了四倍，這對患者護理至關重要。

While there was a trend towards reduction in combined Stage 3 and 4, the trial did not meet the primary endpoint of statistically significant reduction. These data show the benefit of multi-cancer screening with Galleri and provide the strongest evidence for the recommended annual screening interval, or Paul will talk through the top line NHS calorie trial results shortly. In our earnings press release, we also noted full results from all 35,000 participants in PATHFINDER 2 and were consistent with data presented from the first 25,000 participants presented at ESMO last year. We anticipate presenting full data from both NHS Galleri and PATHFINDER 2 in mid-2026.

雖然第 3 期和第 4 期合併病例有減少的趨勢，但該試驗並未達到統計學上顯著減少的主要終點。這些數據表明使用 Galleri 進行多癌症篩檢的好處，並為建議的年度篩檢間隔提供了最有力的證據，或者 Paul 將很快討論 NHS 卡路里試驗的主要結果。在我們的收益新聞稿中，我們也提到了 PATHFINDER 2 所有 35,000 名參與者的完整結果，並且與去年在 ESMO 上公佈的前 25,000 名參與者的數據一致。我們預計將於 2026 年年中公佈 NHS Galleri 和 PATHFINDER 2 的完整數據。

Based on strong results from the NHS Galleri trial and the PATHFINDER 2 study, we also announced today that we are moving forward with a planned expansion of our field sales and medical team. We believe this expanded engagement will enable us to continue to drive commercial momentum.

基於 NHS Galleri 試驗和 PATHFINDER 2 研究的強勁結果，我們今天也宣布，我們將按計劃擴大我們的現場銷售和醫療團隊。我們相信，此次擴大合作將使我們能夠繼續推動商業發展。

To recap quickly, on the strong commercial performance for Galleri in 2025, which we shared in January. The US Galleri test volume grew 36% to more than 185,000 Galleri tests and US Galleri revenue grew by 26%. Our prescriber base is now approximately 17,000 providers, up 30% from prior year.

簡單回顧一下，我們在 1 月分享了 Galleri 在 2025 年強勁的商業表現。美國 Galleri 測試量增加了 36%，達到 185,000 多次 Galleri 測試，美國 Galleri 收入成長了 26%。我們的處方醫生數量目前約為 17,000 人，比前一年增長了 30%。

Galleri's growth in 2025 was driven by both breadth and depth of prescribing. We have been in the market with the Galleri test now for more than four years. And from the launch of Galleri through December 31, we have sold almost 0.5 million Galleri tests. We remain on track for continued commercial growth in 2026 with new and expanding partnerships, including digital health opportunities and further integration into health systems.

Galleri 在 2025 年的成長得益於處方範圍的廣度和深度。我們推出 Galleri 測試產品已經超過四年了。從 Galleri 上市到 12 月 31 日，我們已經售出了近 50 萬份 Galleri 測試。我們仍有望在 2026 年實現持續的商業成長，透過建立和擴大合作夥伴關係，包括數位健康機會以及進一步融入醫療系統。

We are focused on expanding awareness of multi-cancer early detection and Galleri's important performance and capability differentiation. We anticipate growing patient, provider and employer conviction in Galleri as other performance, safety and clinical utility data sets are read out.

我們致力於提高人們對多癌種早期檢測的認識，並強調 Galleri 在性能和能力方面的重要差異化優勢。我們預計，隨著其他效能、安全性和臨床實用性資料集的公佈，患者、醫療服務提供者和雇主對 Galleri 的信心將會增強。

A few weeks ago, we announced that we completed our PMA submission with the FDA. The PMA marks a critical step forward making Galleri available to more people and advancing early detection to provide a significant public health benefit. The submission represents years of focus, disciplined work to achieve design, development and validation of all large diverse screening populations. Josh will share more about our PMA later in this call.

幾週前，我們宣布已完成向FDA提交的PMA申請。PMA 標誌著 Galleri 向前邁出了關鍵一步，使更多人能夠使用 Galleri，並推進早期檢測，從而帶來顯著的公共衛生效益。這項成果代表了多年來的專注和嚴謹工作，旨在實現所有大型多樣化篩檢族群的設計、開發和驗證。稍後，Josh 將在本次通話中詳細介紹我們的 PMA。

Additionally, earlier this month, the Nancy Gardner sold Medicare multi-cancer early detection screening coverage Act became federal law. This establishes a Medicare coverage pathway for FDA-approved multi-cancer early detection tests. As a leading MSAD developer, it is our privilege to stand with legislators, patient advocates, clinicians and researchers who have championed the cause. I'll now hand it over to Harpal to discuss top line results from the NHS Galleri study.

此外，本月初，南希·加德納出售的《醫療保險多癌症早期檢測篩檢覆蓋法案》成為聯邦法律。這為獲得 FDA 批准的多癌種早期檢測建立了醫療保險覆蓋途徑。作為領先的 MSAD 開發商，我們很榮幸能與倡導這項事業的立法者、患者權益倡導者、臨床醫生和研究人員站在一起。現在我將把發言權交給哈帕爾，讓他來討論 NHS Galleri 研究的主要結果。

Thank you, Bob. We're very pleased to share top line results from the NHS Galleri trial. I want to begin with a huge thank you to the more than 142,000 participants who took part in this study as well as to NHS England, the Cancer Prevention Trials Unit at Queen Mary University of London, cancer alliances, investigators and the clinical teams whose dedication made this landmark trial possible.

謝謝你，鮑伯。我們非常高興地與大家分享 NHS Galleri 試驗的初步結果。首先，我要衷心感謝參與這項研究的 142,000 多名參與者，以及英國國家醫療服務體系 (NHS England)、倫敦瑪麗女王大學癌症預防試驗中心、癌症聯盟、研究人員和臨床團隊，正是他們的奉獻精神才使得這項具有里程碑意義的試驗成為可能。

Detailed results from the NHS Galleri trial will be submitted for presentation at the upcoming ASCO meeting in Chicago in late May. The design of the NHS Galleri trial was informed by a large body of evidence showing that across multiple cancer types, reductions in late-stage disease are strongly associated with reductions in cancer mortality. While we did not observe a statistically significant reduction in combined Stage 3 and 4 cancers through the trial, which was the primary endpoint of the study, there was a favorable trend after the prevalent screening round, and we saw compelling evidence of Galleri's benefit.

NHS Galleri 試驗的詳細結果將提交給 5 月下旬在芝加哥舉行的 ASCO 會議進行展示。NHS Galleri 試驗的設計參考了大量證據，這些證據表明，在多種癌症類型中，晚期疾病的減少與癌症死亡率的降低密切相關。雖然在試驗中，我們沒有觀察到 3 期和 4 期癌症合併病例的統計學顯著減少（這是研究的主要終點），但在普遍篩檢輪次之後出現了有利的趨勢，我們看到了 Galleri 療效的有力證據。

Comparing the two arms of the study, Stage 4 diagnoses in the prespecified group of 12 deadly cancers decreased with each year of sequential Galleri screening with a greater than 20% reduction in the second and third rounds. Similar reductions were observed across all cancers. The reduction in Stage 4 cancer diagnosis is a critically important outcome, which we believe can lead to more effective intervention for patients particularly given the substantial and growing arsenal of effective treatments for many Stage 1 cancers.

對照研究的兩組，在預先設定的 12 種致命癌症中，4 期診斷率隨著 Galleri 篩檢的逐年遞減，第二輪和第三輪的減少幅度超過 20%。所有癌症類型均觀察到類似的減少。減少第 4 期癌症的診斷是一個至關重要的結果，我們相信這可以為患者帶來更有效的干預，尤其是在針對許多 1 期癌症的有效治療方法種類繁多且不斷增加的情況下。

In fact, there is a dramatic improvement in survival for many types of cancer at Stage 3 as compared with Stage 4. These results are the first time a multi-cancer early detection test has demonstrated population scale stage shift and reduction in metastatic disease in a randomized trial. Screening with Galleri increased the overall cancer detection rate fourfold compared to standard of care, and identified substantially more Stage 1 and 2 cancers in types that are typically detected at late stage.

事實上，與第四期癌症相比，第三期癌症的許多類型患者的存活率都有顯著提高。這是多癌種早期檢測測試首次在隨機試驗中證明能夠實現人群規模的疾病分期轉變和轉移性疾病減少。與標準治療相比，使用 Galleri 進行篩檢可使癌症整體檢出率提高四倍，並能發現更多通常在晚期才被發現的 1 期和 2 期癌症。

Screening with the Galleri test also resulted in a substantial reduction in the number of cancers detected clinically through emergency presentation, which are associated with significantly higher mortality and health care costs. And these benefits came with a strong safety profile. No serious safety concerns were reported in any of the approximately 70,000 participants who received the Galleri test across three rounds of testing.

使用 Galleri 檢測進行篩檢也大幅減少了透過急診就診臨床發現的癌症數量，而這些癌症與更高的死亡率和醫療成本有關。而這些優勢還伴隨著很高的安全性。在三輪測試中，接受 Galleri 測試的約 70,000 名參與者中，沒有報告任何嚴重的安全問題。

This is the first randomized multi-cancer early detection data set and is unprecedented in scale. Additional analysis are underway to better understand these rich data. As with any study, it's important to evaluate the results in the context of the design and execution. One observation is that we saw higher-than-anticipated incidents of Stage 1 cancers in this trial as compared with prior study experience.

這是首個隨機多癌種早期檢測資料集，規模前所未有。目前正在進行進一步分析，以更好地理解這些豐富的數據。與任何研究一樣，評估結果時必須結合研究的設計和執行。一項觀察結果是，與先前的研究經驗相比，本次試驗中 1 期癌症的發生率高於預期。

The number and distribution of cancer stages across screening rounds suggests the potential for a stronger effect with longer follow-up as data matures. And so we're planning to extend data collection by 6 to 12 months, and we'll reevaluate the impact with more mature data.

各輪篩檢中癌症分期的數量和分佈表明，隨著數據日趨成熟，更長的追蹤時間可能會產生更強的效果。因此，我們計劃將數據收集延長 6 到 12 個月，並使用更成熟的數據重新評估其影響。

In both the US and the NHS data, the time to diagnostic resolution appears to improve over time as physicians gain experience with the Galleri test and diagnostic workup. Our learnings from this trial enrich our understanding of cancer biology, multi-cancer screening and the importance of implementation, particularly in ensuring rapid and thorough diagnostic investigation after a positive test result.

無論是美國還是英國國家醫療服務體系 (NHS) 的數據都顯示，隨著醫生在 Galleri 測試和診斷工作方面累積經驗，診斷解決時間似乎會隨著時間的推移而改善。我們從這項試驗中獲得的經驗豐富了我們對癌症生物學、多癌篩檢以及實施重要性的理解，尤其是在檢測結果呈陽性後確保快速徹底的診斷調查。

Our mission is to detect cancer early when it can be cured. And we're delighted that these results show the potential for more patients to receive treatment with curative intent and have more time with their family and friends. We believe this is the best chance to bend the cancer mortality curve at population scale. As a reminder, the data we're sharing today is limited to our top line analysis. We plan to submit the detailed results for presentation at ASCO later in the year.

我們的使命是儘早發現癌症，以便在癌症可以治癒時進行治療。我們很高興這些結果表明，更多患者有可能接受以治癒為目的的治療，並有更多的時間陪伴家人和朋友。我們認為這是在人口層面扭轉癌症死亡率曲線的最佳機會。再次提醒，我們今天分享的數據僅限於我們的初步分析。我們計劃將詳細結果提交給美國臨床腫瘤學會（ASCO），並在今年稍後進行展示。

I'll now pass it to Josh Ofman, to review more about our recently completed PMA application.

現在我將把這個任務交給 Josh Ofman，讓他進一步審查我們最近完成的 PMA 申請。

Thank you, Harpal. At the end of January, we completed the submission of the final module of our PMA application to the FDA for Galleri. We're extremely proud of this pivotal milestone in advancing early cancer detected and addressing unmet needs in cancer screening. From the beginning, GRAIL has been completely committed to rigorous, scientific and clinical evaluation to ensure that multi-cancer early detection testing is supported by strong data.

謝謝你，哈帕爾。1 月底，我們完成了向 FDA 提交 Galleri PMA 申請的最後一個模組。我們為這一在推進早期癌症檢測和解決癌症篩檢方面未滿足的需求方面取得的關鍵里程碑感到無比自豪。從一開始，GRAIL 就完全致力於嚴格的科學和臨床評估，以確保多癌種早期檢測測試有強有力的數據支持。

The PMA submission is focused on test performance and safety results from two large registrational studies, including the first 25,000 participants in the US-based PATHFINDER 2 study with one-year follow-up and data from the prevalent screening round were the first year of the NHS Galleri trial, the largest and only randomized controlled intended-use trial of any NSAID test.

PMA 申請重點關注兩項大型註冊研究的測試性能和安全性結果，包括美國 PATHFINDER 2 研究的前 25,000 名參與者的一年隨訪數據，以及 NHS Galleri 試驗第一年的普遍篩檢數據，這是迄今為止規模最大、也是唯一一項針對 NSAID 測試的隨機對照預期用途試驗。

The PMA submission is also supported by a bridging analysis, to compare performance of the version of Galleri used in our registrational trials to the updated version that has been submitted to the FDA for premarket approval. The results from the first 25,000 participants enrolled in PATHFINDER 2 were presented in October at the ESMO Congress. And we've now completed the analysis of the full 35,000 participants and the results are consistent.

PMA 申請還得到了橋接分析的支持，以比較我們在註冊試驗中使用的 Galleri 版本與已提交給 FDA 以獲得上市前批准的更新版本的性能。PATHFINDER 2 前 25,000 名參與者的結果已於 10 月在 ESMO 大會上公佈。我們現在已經完成了對全部 35,000 名參與者的分析，結果一致。

The performance data from the prevalent screening round of the NHS Galleri study, including metrics focused on test performance, clinical validation and the clinical benefit of detection at Stages 1 through 3, including a reduction in Stage 4 were also included to further enhance the data set and provide additional data on more cancers to the FDA. As a reminder, the FDA designated the test as a breakthrough device in 2018. The PMA was submitted at the end of January, and we are anticipating about a 12-month review period.

NHS Galleri 研究的現行篩檢輪次中的性能數據，包括專注於測試性能、臨床驗證以及 1 至 3 期檢測的臨床益處（包括 4 期減少）的指標，也被納入其中，以進一步增強數據集，並向 FDA 提供有關更多癌症的額外數據。提醒一下，FDA 於 2018 年將該檢測方法認定為突破性醫療器材。PMA申請已於1月底提交，我們預計審查期約為12個月。

To discuss our fourth quarter financial results, I'll pass it off to Aaron.

關於第四季財務表現的討論，我將交給亞倫。

Thanks, Josh, and good afternoon, everyone. I'm pleased to present our results for the fourth quarter and the full year of 2025. Fourth quarter results were strong with revenue of $43.6 million, up $5.3 million or 14% as compared to Q4 2024. Total revenue for the quarter is comprised of $42.3 million of screening revenue and $1.3 million of development services revenue. Development services revenue includes services we provide to biopharmaceutical and clinical customers, including support of clinical studies, pilot testing, research therapy development.

謝謝你，喬希，大家下午好。我很高興向大家介紹我們2025年第四季和全年的業績。第四季業績強勁，營收達 4,360 萬美元，比 2024 年第四季成長 530 萬美元，成長 14%。本季總收入包括 4,230 萬美元的篩選收入和 130 萬美元的開發服務收入。開發服務收入包括我們為生物製藥和臨床客戶提供的服務，包括支援臨床研究、試點測試、研究療法開發。

Full year total revenue was $147.2 million, up 17% from full year revenue in 2024. Full year 2025 revenue was comprised of $138.6 million of screening revenue, up 28% over full year 2024. US Galleri revenue in 2025 was $136.8 million, up 26% over 2024 and in line with our guidance of 20% to 30% growth. Revenue also included $8.6 million of development services revenue, a decrease of 49% from 2024.

全年總收入為 1.472 億美元，比 2024 年全年營收成長 17%。2025 年全年收入包括 1.386 億美元的篩選收入，比 2024 年全年成長 28%。美國 Galleri 公司 2025 年的營收為 1.368 億美元，比 2024 年成長 26%，符合我們 20% 至 30% 的成長預期。收入還包括 860 萬美元的開發服務收入，比 2024 年減少了 49%。

We are seeing continued demand for the Galleri test, and we sold more than 57,000 tests in the fourth quarter and more than 185,000 tests for the year. Screening revenue of $42.3 million in the fourth quarter was up 34% as compared with the fourth quarter of 2024, primarily based on an increase in sales volume.

我們看到市場對 Galleri 檢測的需求持續成長，第四季度我們售出了超過 57,000 個檢測，全年售出了超過 185,000 個檢測。第四季篩檢收入為 4,230 萬美元，比 2024 年第四季成長 34%，主要原因是銷售量增加。

In 2025, we began leaning into the price elasticity we see in the market and are finding success in expanding access with our discounting programs. Development service revenue in the fourth quarter of 2025 was $1.3 million.

2025年，我們開始利用市場中的價格彈性，並透過折扣計劃成功地擴大了市場覆蓋範圍。2025 年第四季開發服務收入為 130 萬美元。

Net loss for the fourth quarter of 2025 was $99.2 million, an increase of 2% as compared to Q4 2024. Net loss for the full year was $408.4 million, an improvement of 80% as compared to the full year 2024. Net loss in 2024 included goodwill and intangible asset impairment of $1.4 billion. In addition, net loss for 2025 and 2024, included amortization of Illumina acquisition-related intangible assets of $138.3 million.

2025 年第四季淨虧損為 9,920 萬美元，較 2024 年第四季成長 2%。全年淨虧損為 4.084 億美元，與 2024 年全年相比改善了 80%。2024 年淨虧損包括 14 億美元的商譽和無形資產減損。此外，2025 年和 2024 年的淨虧損包括與收購 Illumina 相關的無形資產攤銷 1.383 億美元。

Non-GAAP adjusted gross profit for the fourth quarter of 2020 was $23.1 million, an increase of $5.2 million or 29% as compared with Q4 2024. Full year non-GAAP adjusted gross profit was $73.6 million, an increase of $15.8 million or 27% as compared with the full year of 2024. Primary drivers of the increased margin were revenue mix and efficiencies of scale related to increased Galleri volume.

2020 年第四季非 GAAP 調整後毛利為 2,310 萬美元，比 2024 年第四季增加了 520 萬美元，增幅達 29%。全年非GAAP調整後毛利為7,360萬美元，比2024年全年增加了1,580萬美元，增幅達27%。利潤率成長的主要驅動因素是收入結構和 Galleri 銷售成長帶來的規模效益。

Adjusted EBITDA for the fourth quarter of 2025 was a negative $71.8 million representing an improvement of $12.2 million or 15% as compared to Q4 2024. Adjusted EBITDA for the full year 2025 was a negative $320.6 million, an improvement of $163 million or 34% as compared to the full year 2024.

2025 年第四季調整後 EBITDA 為負 7,180 萬美元，與 2024 年第四季相比改善了 1,220 萬美元，增幅達 15%。2025 年全年調整後 EBITDA 為負 3.206 億美元，與 2024 年全年相比改善了 1.63 億美元，增幅達 34%。

We ended the quarter with a cash position of $904.4 million, this balance included $436 million in proceeds from both our private placement of equity in October as well as our ATM equity issuance program in November and December. As a reminder, we have shared in the past our long-term gross margin target of 50% to 60% at scale. We are making good progress on attaining these margin targets. And as we saw in the third quarter, volume efficiencies make a big difference.

本季末，我們的現金餘額為 9.044 億美元，其中包括 10 月份私募股權融資以及 11 月和 12 月 ATM 股權發行計劃的 4.36 億美元收益。再次提醒大家，我們之前曾分享過，我們的長期毛利率目標是在規模化生產後達到 50% 至 60%。我們在實現這些利潤率目標方面取得了良好進展。正如我們在第三季看到的那樣，提高產量效率會產生很大的影響。

In connection with our supply agreement with Illumina, we are obligated to pay them a royalty on revenues. Those royalty payments are suspended until December of 2026. When resumed, we expect to pay alumina a royalty in the high single digits, subject to certain terms and perpetuity on net sales generated by our products on revenues and oncology. We expect that these payments will make an impact on our gross margins beginning in 2027.

根據我們與 Illumina 的供貨協議，我們有義務向其支付收入分成。這些版稅支付將暫停至 2026 年 12 月。恢復生產後，我們預計將向氧化鋁支付接近兩位數的特許權使用費，具體條款和期限將根據我們產品在收入和腫瘤學領域產生的淨銷售額而定。我們預計這些款項將從 2027 年開始對我們的毛利率產生影響。

Given strong performance in the self-pay market and the momentum we are seeing with positive data readouts, we are reiterating the guidance we shared in January today of Galleri sales growth of 22% to 32% and cash burn for the full year of 2026 to be no more than $300 million. Our cash runway extends into 2030, and we are well positioned to navigate growth over the next several years as we pursue critical milestones toward broad access.

鑑於自費市場的強勁表現以及我們從積極的數據讀數中看到的勢頭，我們重申今天在 1 月份分享的指導意見，即 Galleri 的銷售額增長 22% 至 32%，2026 年全年的現金消耗不超過 3 億美元。我們的現金儲備可以維持到 2030 年，我們已經做好充分準備，在未來幾年內實現成長，同時朝著廣泛普及的目標邁進。

Bob, back to you for concluding remarks.

鮑勃，現在輪到你做總結發言了。

Thanks, Aaron. To close, our teams at GRAIL continue to do great work advancing towards our vision of population scale multi-cancer early detection. We are approaching our tenth anniversary as a company this March, and we are energized by recent milestones and achievements, including the consistently strong performance we are seeing for Galleri across our studies. We presented positive registrational clinical study results for the first 25,000 participants in the PATHFINDER 2 study in October and to today share top line results for the NHS Galleri trial and the full 35,000 participant PATHFINDER 2 study. We're looking forward to data presentations for both studies later in the year.

謝謝你，亞倫。最後，GRAIL 的團隊繼續努力，朝著我們實現大規模多癌種早期檢測的願景邁進。今年三月，我們將迎來公司成立十週年，近期取得的里程碑式成就和成就令我們倍感振奮，其中包括 Galleri 在我們各項研究中持續強勁的表現。我們在 10 月公佈了 PATHFINDER 2 研究前 25,000 名參與者的積極註冊臨床研究結果，今天我們將分享 NHS Galleri 試驗和完整的 35,000 名參與者的 PATHFINDER 2 研究的主要結果。我們期待在今年稍後看到這兩項研究的數據展示。

The business continues to grow and we are excited about expanding or partnerships with digital health companies and health systems to continue to expand access to Galleri. We have now completed our PMA submission with the FDA and new federal law provides a pathway for Medicare to cover FDA-approved multi-cancer early detection test. We're in a strong financial position with more than $900 million in cash as of December 31. I'd like to thank each of our employees for their incredible commitment and dedication to our mission to detect cancer early when it could be cured.

業務持續成長，我們很高興能夠與數位健康公司和醫療系統擴大合作，以繼續擴大 Galleri 的覆蓋範圍。我們現在已經完成了向 FDA 提交的 PMA 申請，新的聯邦法律為 Medicare 提供了一條途徑，使其能夠涵蓋 FDA 批准的多癌種早期檢測測試。截至12月31日，我們擁有超過9億美元的現金，財務狀況穩健。我要感謝我們每一位員工，感謝他們為我們儘早發現癌症並進行治癒這項使命所做出的巨大貢獻和奉獻。

We'll now turn the call over to question and answer. Operator, please go ahead.

現在我們將把通話轉至問答環節。操作員，請開始。

(Operator Instructions) Subbu Nambi, Guggenheim

（操作員指示）Subbu Nambi，古根漢

Can you confirm that you don't expect the FDA approval decision to be impacted by the miss of the state shift endpoint? We know the FDA PMA package only included the prevalent screening round of net but reasonably reviewers at the FDA will see this outcome, right?

您能否確認，您認為 FDA 的核准決定不會受到未達到狀態轉換終點的影響？我們知道 FDA PMA 套件僅包括目前普遍採用的網狀物篩選輪次，但 FDA 的審查員理應會看到這樣的結果，對吧？

Yes. Thanks for the question, Subbu. So as you know, the FDA will look at the effectiveness and safety of our submission. And so with the data that we have, both from PATHFINDER 2 as well as the current -- the prevalent around of the NHS Galleri we'll be looking at that data. So there's not an obvious correlation or obvious impact between the final results of the NHS calorie study and the FDA on the test.

是的。謝謝你的提問，Subbu。如您所知，FDA 將審查我們提交資料的有效性和安全性。因此，我們將利用 PATHFINDER 2 以及 NHS Galleri 周圍目前普遍存在的數據來研究這些數據。因此，NHS 卡路里研究的最終結果與 FDA 對此測試的結果之間沒有明顯的關聯或明顯的影響。

Perfect. And 1 follow-up. Is there any read-through from missing the NHS Galleri state shift endpoint to the Medicare REACH study which has a primary endpoint of incidence rates of Stage 4 cancers, right? And does that have any impact as Medicare as you look to getting some college?

完美的。還有 1 個後續問題。錯過 NHS Galleri 狀態轉換終點是否會影響 Medicare REACH 研究（研究的主要終點是 4 期癌症的發生率）？那麼，當你打算上大學時，醫療保險（Medicare）會對你產生什麼影響嗎？

Yes. Thanks again. Josh, do you want to take that?

是的。再次感謝。喬希，你想拿嗎？

Sure. Yes. No, you're absolutely correct. So the primary endpoint of the REACH study is a Stage 4 reduction. -- which is what was observed quite strongly in the NHS Galleri trial.

當然。是的。不，你說得完全正確。因此，REACH 研究的主要終點是 4 期疾病的減少——這與 NHS Galleri 試驗中觀察到的結果非常吻合。

So I think the only read through is that we believe that it's critically important and clinically important to reduce the incidence of metastatic disease in Stage 4 cancer, and it's a really important clinical end point, and we're looking forward to assessing that in the REACH trial.

因此，我認為唯一可以理解的是，我們認為降低 4 期癌症轉移性疾病的發生率至關重要，具有重要的臨床意義，這是一個非常重要的臨床終點，我們期待在 REACH 試驗中對此進行評估。

Josh, what if we don't reach the statistical significance there. Would that have any impact? Or you are saying because it's 50,000, the study is not powered enough?

喬希，如果我們達不到統計顯著性怎麼辦？那會產生什麼影響嗎？還是你的意思是，因為樣本數只有 5 萬，所以這項研究的統計效力不足？

Yes. No, we believe this study is properly powered. It will have a control group, and we believe it is properly powered for that type of study, given the effect size that we know in the cancer detection rate that we're seeing. So we're very optimistic about observing that effect, but we need to study, obviously, to read out. That's going to take some time.

是的。不，我們認為這項研究的樣本數足夠。它將設定對照組，並考慮到我們所看到的癌症檢出率的效果大小，我們相信它對於這類研究來說是足夠有統計效力的。因此，我們對觀察到這種效應非常樂觀，但顯然我們需要進行研究才能得出結果。這需要一些時間。

Kyle Mikson, Canaccord Genuity.

Kyle Mikson，Canaccord Genuity。

Hopefully, can hear me. I guess the first 1 would be how does the results here kind of impact your strategy to expand Galleri to other countries in terms of data generation and rollout plans, how would that differ now? And then maybe you could just touch on what are next steps in the UK? Have you had any discussions with them so far is that later on?

希望你能聽到我說話。我想第一個問題是，就資料產生和推廣​​計劃而言，這裡的結果會如何影響您將 Galleri 擴展到其他國家的策略，現在會有什麼不同？然後，您或許可以簡單談談英國的下一步計畫是什麼？你目前和他們有過任何討論嗎？是之後的事嗎？

Thanks, Kyle. So we do think as we outlined in the releases that the strong reduction that we saw in Stage 1 cancer, the fourfold improvement in cancer detection rate compared to standard of care the absolute number of Stage 1 and 2 cancers increasing and the reduction in emergency presentation, we think all of those will be important as we go to other countries and the discussions with them.

謝謝你，凱爾。因此，正如我們在新聞稿中概述的那樣，我們認為，我們看到的 1 期癌症病例大幅減少，癌症檢出率比標準治療提高了四倍，1 期和 2 期癌症的絕對數量增加，以及急診就診人數減少，所有這些在我們與其他國家進行討論時都將非常重要。

Obviously, other countries will -- each one will evaluate those elements independently, but we do think that's going to be a strong data set to go out there. So I think that's going to be very useful. Maybe I'll pass it over to Harpal to comment on the UK and the impact there.

顯然，其他國家也會——每個國家都會獨立評估這些因素，但我們認為這將是一套強而有力的數據集。所以我認為這會非常有用。或許我會把這個話題交給哈帕爾，讓他來評論英國以及對英國的影響。

Yes. Thanks, Bob. I mean, just adding to what said first. I mean we think this is a really strong dataset that demonstrates compelling clinical benefit. We know that there is now a growing arsenal of very effective treatments for many types of stage -- many types of cancer at Stage 3.

是的。謝謝你，鮑伯。我的意思是，只是在前面說的基礎補充一下。我的意思是，我們認為這是一個非常強大的數據集，證明了其令人信服的臨床益處。我們知道，目前針對多種類型的癌症（包括許多類型的 3 期癌症）已有了越來越多的非常有效的治療方法。

And so the potential benefits that we're talking about here from the NHS Galleri study are going to be applicable worldwide. And so I don't think it has any -- certainly no negative bearing on our international approach. Indeed, I would hope it has a positive bearing on our international approach. So we feel we're really very pleased with the overall set of results.

因此，我們在這裡討論的 NHS Galleri 研究帶來的潛在益處將適用於全世界。因此，我認為這肯定不會對我們的國際方針產生任何負面影響。我希望這能對我們的國際戰略產生正面影響。因此，我們對整體結果非常滿意。

With respect to the UK specifically and the NHS, yes, look, we've just got these data. We haven't started having those conversations yet. My anticipation would be that they would want to see the full results before engaging in meaningful conversations, and we expect to have those at ASCO.

就英國和英國國家醫療服務體系（NHS）而言，是的，你看，我們剛剛掌握了這些數據。我們還沒開始進行這些對話。我預計他們會希望在進行有意義的對話之前看到完整的結果，而我們預計會在 ASCO 上看到這些結果。

And then I hate to nitpick, but if you're expanding the sales force if the results didn't meet the endpoint, I guess like what's the thought process there, you're pretty bullish on the future here. I'm just curious what's driving that.

然後，我不想吹毛求疵，但如果業績沒有達到預期目標，你卻要擴大銷售隊伍，我想問你的想法是什麼？你對未來相當樂觀。我只是好奇是什麼原因導致這種情況。

Yes. So again, if you think about the things that we saw in terms of reduction in Stage 1 and 2, the -- I assume the increase Stage 1 cancers and the reduction in Stage 4 cancer. Those are things that we've looked at within the US that are very, very reliant to clinicians. Maybe to give a little more color, I pass it over to Andy, our Chief Commercial Officer.

是的。所以，再想想我們看到的 1 期和 2 期癌症病例減少的情況——我假設是 1 期癌症病例增加和 4 期癌症病例減少。這些都是我們在美國研究過的問題，這些問題非常非常依賴臨床醫師。為了增添一些色彩，我把麥克風交給我們的商務長安迪。

Yes. Thanks, Bob. Based on the market research studies that we've done and also consistent customer feedback that we've received from early adopting customers, the NHS Galleri results that we've released today, we believe, based on everything we've heard and done will be both compelling and meaningful to our customers in terms of the magnitude of both the Stage 4 reduction that we've disclosed and also the increased cancer detection rates are fourfold. And we believe that's going to increase both the depth and breadth of prescribing. Hence, we're expanding the provider sales force territories in the US.

是的。謝謝你，鮑伯。根據我們進行的市場調查以及我們從早期採用者客戶那裡收到的持續客戶反饋，我們相信，今天發布的 NHS Galleri 結果，基於我們所聽到和所做的一切，對於我們的客戶來說，無論是我們披露的 4 期癌症減少幅度，還是癌症檢出率提高四倍，都將具有說服力和意義。我們相信這將增加處方的深度和廣度。因此，我們正在擴大在美國的供應商銷售團隊的業務範圍。

Your next question will come from Schenkel with Wolfe Research.

您的下一個問題將來自 Wolfe Research 的 Schenkel。

I'll try to get them all out there upfront. And then listen. So first, really a follow-up to the very first question, and I think it's the most important question tonight given the stock reaction in the aftermarket. So I want us to be air tight on this. is the probability of FDA approval unchanged as a result of the NHS Galleri readout.

我會盡量提前把它們全部公佈出來。然後仔細聆聽。首先，我想就第一個問題做個後續，考慮到售後市場的股票反應，我認為這是今晚最重要的問題。所以我想確保我們在這件事上萬無一失。 NHS Galleri 的結果是否會影響 FDA 批准的可能性？

Because if the answer is the probability is unchanged. It would mean the value associated with FDA approval and by extension CMS reimbursement is also unchanged. So that's the first question. Yes or no, it has the probability not changed.

因為如果答案是，機率就不會改變。這意味著與 FDA 批准相關的價值，以及由此延伸的 CMS 報銷，也不會改變。這是第一個問題。是或否，機率都不會改變。

The second question is on NHS coverage in the UK. I know -- again, you just got a question on this, but I'm curious if there are any examples you can point to where a diagnostic has been reimbursed after missing a primary end point. And then my third question is, has your analysis of NHS Gallar results led you to any explanation regarding why you came up short of the primary endpoint? Are there potential design issues or population SKUs, anything like that?

第二個問題是關於英國國民醫療服務體系（NHS）的覆蓋範圍。我知道——你剛剛又被問到這個問題了，但我很好奇你是否能舉出一些例子，說明在未能達到主要終點的情況下，診斷費用是如何獲得報銷的。我的第三個問題是，您對 NHS Gallar 結果的分析是否讓您對未能達到主要終點的原因做出了任何解釋？是否有潛在的設計問題或產品庫存單位（SKU）問題之類的？

Yes. Thanks, Doug. Maybe Josh, I'll hand over to a question to you.

是的。謝謝你，道格。喬什，或許我該把問題交給你了。

Thanks for the question, Doug. Everything we've learned from the FDA, their history with us, our conversations has been their focus is going to be on clinical performance and safety. And the data set that we are -- that we have submitted includes the full PATHFINDER I study of the first 25,000 participants and the first year which is the performance period of the NHS Galleri trial. In their advisory board meetings and their public comments, they have been quite clear that their focus is on clinical validation and not clinical utility.

謝謝你的提問，道格。我們從FDA、他們與我們的歷史以及我們的對話中了解到，他們的重點將放在臨床表現和安全性上。我們提交的數據集包括 PATHFINDER I 研究的前 25,000 名參與者的完整數據，以及 NHS Galleri 試驗的第一年（即績效期）。在他們的顧問委員會會議和公開評論中，他們已經非常明確地表示，他們的重點是臨床驗證而不是臨床實用性。

And what we've tried to demonstrate in the NHS trial is a population level effect well beyond clinical validation and clinical performance. And we were able to demonstrate a really important finding of a substantial reduction in Stage 1 cancers and a fourfold improvement in the cancer detection rate. But those are things that are not part of our submission right now to the FDA. And based on their own comments, they're going to be focused on clinical validation.

我們在 NHS 試驗中試圖證明的是，其效果遠遠超出臨床驗證和臨床表現，達到了人口層面的顯著水準。我們取得了一項非常重要的成果，第一期癌症病例大幅減少，癌症檢出率提高了四倍。但這些內容目前不屬於我們提交給FDA的申請資料範圍。根據他們自己的表態，他們將專注於臨床驗證。

And maybe, Harpal, you want to.

或許，哈帕爾，你也想這麼做。

Yes, so I think you -- Doug, I think your second question was around endpoints on diagnostic studies. I think it's just worth pointing out that it's extremely rare for any diagnostic to go through a randomized controlled trial, it's very common for drugs to go through randomized controlled trials, but you actually very rarely see a diagnostic test evaluated as rigorous way as we have done through the NHS Galleri trial. I just think it's really important to make that point. Not only have we rigorously assessed it through an RCT, but it's a nor large trial, 142,000 people.

是的，所以我覺得你——道格，我覺得你的第二個問題是關於診斷研究的終點。我認為值得指出的是，任何診斷方法都極少經過隨機對照試驗，藥物經過隨機對照試驗很常見，但實際上，你很少會看到診斷測試像我們透過 NHS Galleri 試驗所做的那樣受到如此嚴格的評估。我覺得強調這一點非常重要。我們不僅透過隨機對照試驗對其進行了嚴格評估，而且這是一項規模也不大的試驗，涉及 142,000 人。

So we have a data set, the likes of which I am not aware any other diagnostic has been through other than sort of really significant interventional diagnostic type products. So I think that's the first thing to say. The second thing to say is this is an enormously rich data set, and it has a large number of components to it, and we've shared those with you today. It's absolutely right to say we didn't hit the primary endpoint, but what we did see was a very compelling clinical benefit here.

所以我們擁有一個資料集，據我所知，除了某些非常重要的介入性診斷產品之外，沒有其他診斷方法經歷過類似的資料集。所以我覺得這是首先要說的。第二點要說的是，這是一個極其豐富的資料集，它包含大量組成部分，我們今天已經與大家分享了這些部分。沒錯，我們沒有達到主要終點，但我們確實看到了非常令人信服的臨床效益。

And I think that story stands in terms of generating excitement out there in the clinical community around what's possible with a test like this, being able to reduce Stage 1 cancers gives clinicians the opportunity to use curative treatments that they otherwise wouldn't have the opportunity to use. So I think that's really very compelling.

我認為這個故事的意義在於，它激發了臨床界對這類檢測可能性的興奮之情，能夠減少 1 期癌症，使臨床醫生有機會使用他們原本沒有機會使用的治癒性療法。所以我認為這真的很有說服力。

And then your third question, I think, was about what are we learning looking at the data? And just a couple of comments on that. First of all, it's -- we've not had this data for very long. We're looking into it. There's a lot of data to work through.

那麼，我想你的第三個問題是關於我們從數據中學到了什麼？關於這一點，我還有幾點要補充。首先，我們掌握這些數據的時間並不長。我們正在調查此事。需要處理的數據很多。

One of the things we've seen is that -- if I break apart the primary endpoint, it's a combined Stage 3 and 4 reduction. And so when you break that apart, we did see a Stage 4 reduction, but as we've commented on, we saw an increase in Stage 3 cancers.

我們發現的其中一點是——如果我把主要終點分解開來，那就是 3 階段和 4 階段的綜合減少。因此，當我們把這些因素分開來看時，我們確實看到了 4 期癌症病例的減少，但正如我們之前提到的，我們看到 3 期癌症病例增加。

And one of the things that looks to be the case when we look at the data is that we expect to see a stronger effect if we were to continue to follow up this cohort for a longer period of time. And that's why we're saying we want to extend the follow-up for a further 6 to 12 months, and that's why we'll be doing that. So that's one of the things that we've seen when we're looking at the data, but there's a lot more to learn.

從數據來看，似乎存在這樣的情況：如果我們繼續對這組人群進行更長的隨訪，我們預計會看到更顯著的效果。所以，我們才說要延長後續研究 6 到 12 個月，而我們也確實會這樣做。這是我們在查看數據時發現的事情之一，但還有很多東西需要學習。

(Operator Instructions) Catherine Schulte, Baird.

（操作說明）凱瑟琳·舒爾特，貝爾德。

I guess, first, just on that last point of extending the trial follow-up by 6 to 12 months. Is that something that you NHS have already agreed on? And I guess what is the goal of what you will see in that 6 to 12 months? Is it to push more on the Stage 3 reduction? Or is there something else that NHS is hoping to see?

我想，首先，就最後一點，即把試驗追蹤期延長 6 到 12 個月。這是英國國家醫療服務體系（NHS）已經達成共識的事嗎？那麼，你希望在未來6到12個月內看到什麼目標呢？是為了進一步推進第三階段減排嗎？或者，英國國家醫療服務體系（NHS）還有其他希望看到的嗎？

Andrew?

安德魯？

Yes. Thanks, Catherine. We haven't discussed it in any detail with the NHS yet, but I think it's -- I really can't see any obstacles in being able to do that. What it requires is not going back to participants or clinicians.

是的。謝謝你，凱瑟琳。我們還沒有和英國國家醫療服務體系 (NHS) 詳細討論過這個問題，但我認為——我真的看不出有任何障礙可以做到這一點。關鍵在於不要再去找參與者或臨床醫師。

It would be a continuation of passive data collection which is already being recorded. And so it's just about the passage of time and agreeing with the NHS team that we can get access to that data. I think that will I don't foresee any significant obstacles in that regard.

這將是目前已在進行的被動式資料收集的延續。所以現在的問題只是時間問題，以及與 NHS 團隊達成一致，以便我們能夠獲得這些數據。我認為，在這方面我預見不到任何重大障礙。

And in answer to your second question, yes, what we want to see is particularly the control data maturing more than we've been able to. And perhaps if I just elaborate a little bit on that, what you tend to see in a screening trial in any screening trial is that you're finding cancers that would have been detected later, and so if you think about what that means in practice, you're pulling forward to your intervention arm cancers from the future.

至於你的第二個問題，是的，我們希望看到的是控制資料能夠比我們目前所能獲得的更成熟。如果我再詳細解釋一下，在任何篩檢試驗中，你往往會發現一些原本會在晚些時候才被發現的癌症，所以如果你想想這在實踐中意味著什麼，你就相當於把原本應該在以後出現的癌症提前到了你的干預組。

For a control arm of the study, those cancers may not yet have manifested. So when you're comparing 2 arms of the study, what you'd like to have is long enough follow-up that you can compare the 2 arms really well together. And what we've concluded looking at the data is, we probably need a longer follow-up time to be able to do that adequately.

對於該研​​究的對照組而言，這些癌症可能尚未顯現。因此，在比較研究的兩組時，你需要足夠長的追蹤時間，以便能夠很好地比較這兩組。我們透過分析數據得出的結論是，我們可能需要更長的追蹤時間才能充分做到這一點。

And then for the NHS, I know they put out their national cancer plan earlier this month and still reiterated their commitment to and interest in multi-cancer early detection they've got OLS closed and application process for what sounds kind of kind of like a DAC related study using ultacancer tests and primary caratatriage patients with nonspecific abdominal symptoms. Is that something that you guys are involved in? And maybe just talk to the broader relationship with NHS.

至於英國國家醫療服務體系 (NHS)，我知道他們在本月初發布了國家癌症計劃，並重申了他們對多癌症早期檢測的承諾和興趣。他們已經關閉了 OLS，並且正在啟動一項聽起來有點像 DAC 相關研究的申請流程，該研究使用 ultacancer 檢測和對有非特異性腹部症狀的原發性癌症分流患者進行篩檢。你們也參與其中嗎？或許可以談談與英國國家醫療服務體系（NHS）更廣泛的合作關係。

Yes, happy to do so. So we've been having ongoing conversations with the NHS really over the last five or six years. Those conversations continue very actively and certainly we'll continue here on in. Of course, we were very pleased to see in the NHS cancer plan a couple of weeks ago, a number of references to multi-cancer early detection.

是的，我很樂意這樣做。所以，在過去的五、六年裡，我們一直在與英國國家醫療服務體系（NHS）進行持續的對話。這些對話仍在積極進行中，我們當然也會繼續在這裡討論。當然，我們非常高興地看到幾週前英國國家醫療服務體系 (NHS) 的癌症計劃中多次提到了多癌症早期檢測。

And indeed, the excitement within the NHS and the Department of Health in England for the possibilities that this new technology offers for really transforming the landscape for cancer patients. So the multiple references in the cancer plan, I don't think it's an exaggeration to say comes from the conversations and relationships we've been having with the NHS over the last five or six years.

事實上，英國國家醫療服務體系 (NHS) 和英國衛生部都對這項新技術為真正改變癌症患者的現狀所帶來的可能性感到興奮。因此，癌症計畫中的多次提及，我認為毫不誇張地說，都源於我們在過去五、六年與英國國家醫療服務體系 (NHS) 進行的對話和建立的關係。

With respect to the second part of your question, yes, there is a process underway to further evaluate the role of multi-cancer detection in a symptomatic context. And this is a follow-up from our SIMPLIFY study that we reported a couple of years ago, necessarily, the Department of Health has to go through a competitive application process, it doesn't -- it can't just offer that opportunity to GRAIL.

關於您問題的第二部分，是的，目前正在進行一項流程，以進一步評估在有症狀的情況下進行多癌症檢測的作用。這是我們幾年前報道的 SIMPLIFY 研究的後續，衛生部必須經過競爭性申請流程，它不能——它不能直接把這個機會提供給 GRAIL。

So that application process is underway. And as you might expect, we applying to be part of that process and are hopeful that, that will move forward. Certainly, we believe our data from the SIMPLIFY study is very strong and very encouraging in that context.

申請流程已經開始。正如您所料，我們正在申請參與這個過程，並希望這個過程能順利進行。當然，我們認為，從 SIMPLIFY 研究中獲得的數據非常有力，也非常令人鼓舞。

Dan Brennan, TD Cowen.

丹·布倫南，TD Cowen。

Maybe just one on Medicare. So assuming you're successful with FDA, I'm just wondering, I know Medicare, you have the favorable pathway obviously an FDA approval, assuming you get that, that would be terrific. But we're under the impression that Medicare does consider clinical utilities. So how do you think they would look the NHS trial, and how would that potentially impact the Medicare decision.

或許只有一位參加聯邦醫療保險（Medicare）。所以，假設你成功獲得了 FDA 的批准，我只是想知道，我知道 Medicare，你顯然有一條有利的途徑，那就是獲得 FDA 的批准，假設你得到了批准，那將是極好的。但我們認為，聯邦醫療保險確實會考慮臨床效用。那麼你認為他們會如何看待 NHS 的試驗，以及這可能會對 Medicare 的決定產生怎樣的影響？

Josh, do you want to take that?

喬希，你想拿嗎？

Great. Yes. Obviously, Medicare is going to -- upon FDA approval now has the statutory authority to provide coverage for multi-cancer early detection tests and we'll initiate a national coverage analysis and really looked very carefully at the data. And we believe we're going to have a very robust package of data to submit to CMS, including all of our registrational trials everything about NHS Galleri, including the substantial Stage 4 reduction, the fourfold increase in the population cancer detection rate, the increase in detection of Stage 1 and 2 cancers and also very strong clinical performance overall.

偉大的。是的。顯然，一旦獲得 FDA 批准，Medicare 現在就擁有法定權力為多種癌症早期檢測提供保險，我們將啟動一項全國性的保險覆蓋分析，並非常仔細地研究了相關數據。我們相信，我們將向 CMS 提交一套非常強大的數據，包括我們所有的註冊試驗，以及關於 NHS Galleri 的一切，包括 4 期癌症病例的大幅減少、人群癌症檢出率的四倍增長、1 期和 2 期癌症檢出率的提高，以及整體上非常強勁的臨床表現。

And so we think that, that, combined with our real-world evidence, our clinical surveillance program and the REACH study in Medicare patients at the time of NCD will be a very robust package for them to evaluate. Again, Medicare has never evaluated in multicancer early detected test before. There's no known bar that has been set, and so we feel like we're going to be able to provide them an incredibly robust package of evidence to consider coverage for Gallagher.

因此我們認為，結合我們的真實世界證據、我們的臨床監測計劃以及在NCD發生時Medicare患者中進行的REACH研究，這將是一個非常強大的方案供他們評估。此外，Medicare 先前從未對多癌種早期檢測進行過評估。目前還沒有設定任何標準，因此我們覺得我們能夠向他們提供非常有力的證據，以便他們考慮為加拉格爾提供保險。

And then maybe just on I appreciate the Stage 4 is down, which is terrific, but the 3 given some of the anomalies you discussed was up, like collectively across the agent Stage 3 and Stage 4, can you say if there was a decrease and kind of what the level of that decrease was?

然後，也許只是關於第四階段下降這一點，這很棒，但是考慮到您討論的一些異常情況，第三階段卻上升了，比如代理第三階段和第四階段整體上，您能說一下是否存在下降，以及下降的程度如何嗎？

Yes. I can't really comment any further at the moment. There was not a statistically significant reduction. But what we did see was a trend towards a reduction over time, and that was a favorable trend. I think that's as much as I can say at the moment, but we are planning to present the full results at ASCO later in the year.

是的。目前我無法發表更多評論。統計學上未發現顯著的減少。但我們確實看到隨著時間的推移，這種趨勢有所下降，這是一個有利的趨勢。目前我只能透露這麼多，但我們計劃在今年稍後的ASCO會議上公佈全部結果。

And then if I could sneak in 1 final one. So the trial was set up for 3 years. Obviously, it was going to be a surrogate for mortality because mortality would just take too long. So I think that was pretty well established. Was there a decision when you set it up for 3 years as opposed to maybe setting it up with a longer follow-up period kind of how that decision was made?

如果我能偷偷加最後一個就好了。因此，審判期定為3年。顯然，這只能作為死亡率的替代指標，因為死亡本身的計算過程太漫長了。所以我覺得這一點已經相當明確了。當初決定將期限設定為 3 年，而不是設定更長的後續追蹤期，當時是如何做出這個決定的？

Obviously, it sounds like now you're hoping, obviously, the longer follow-up will still prove out the study, but I'm just wondering when you went into it, how was that decision made?

顯然，聽起來你現在希望，顯然，更長的追蹤期仍然能夠證明這項研究的正確性，但我只是想知道，當初你是如何做出這個決定的？

Yes. I mean, look, as with any study, it's designed and sized and powered with the best information you have at the time. And at the time, we felt that 3 rounds of screening followed by a year of follow-up would be sufficient. I think with the benefit of hindsight, we probably should have allowed for a longer follow-up period. The interestingly been a number of publications over the last couple of years about screening studies in general, not just about NHS Galleri, which make this exact point, that the trial should be followed up for longer than 12 months post the last appointment.

是的。我的意思是，你看，任何研究都是根據當時掌握的最佳資訊來設計、規模和進行的。當時，我們認為進行 3 輪篩檢，然後進行一年的追蹤就足夠了。事後看來，我們或許應該允許更長的追蹤期。有趣的是，在過去幾年裡，有許多關於篩檢研究的出版物（不僅僅是關於 NHS Galleri 的）都提出了這一點，即試驗的追蹤時間應該在最後一次預約後超過 12 個月。

As I say, this trial was designed 6 years ago, and that was the best information we had at the time. But as I've already touched on, on this call, we have the ability to continue to flow up, so that's what we're going to be doing.

正如我所說，這項試驗是6年前設計的，而當時我們掌握的資訊也僅限於此。但正如我剛才在這次電話會議上提到的，我們有能力繼續向上發展，所以這就是我們要做的事情。

And it's probably just worth noting that most screening trials have going on for decades, at least one decade, if not two. And so this was a very -- in the context of screening trials, this was actually a very short trial with a very ambitious end point, and that's part of the story here. But it is the first time that an MSA test has shown the ability to shift the stage at diagnosis for the population in a randomized clinical trial. And I don't think we should let that kind of go by.

值得注意的是，大多數篩檢試驗已經進行了幾十年，至少一個十年，甚至二十年。因此，就篩選試驗而言，這實際上是一項非常短暫的試驗，其終點目標非常遠大，這也是故事的一部分。但這是 MSA 檢測首次在隨機臨床試驗中顯示出能夠改變人群診斷階段的能力。我認為我們不該就此罷休。

Kyle Mikson, Canaccord Genuity.

Kyle Mikson，Canaccord Genuity。

So just given you you see these results now, at this point, can you go to the FDA kind of narrow or adjust looks say your label maybe to cancers that you performed the best in or maybe like an older patient, like an older subset perhaps? And just generally, like how does this impact your thoughts on the -- like a potential advisory committee based on there was a comeback in 2030 already.

既然您現在看到了這些結果，那麼在這一點上，您能否向 FDA 提出一些調整或修改申請，例如將您的標籤範圍縮小到您療效最佳的癌症類型，或者像老年患者群體那樣，比如老年患者亞群？總的來說，這會如何影響你對——例如一個潛在的諮詢委員會——的看法，因為在 2030 年就已經出現了復甦。

Yes, sure. Again, we don't think that this finding is going to impact the approvability of Galleri with the FDA. The FDA is clearly going to be focused on clinical performance, safety and the profile of data that was delivered to them, and in that context, we will work through labeling with the agency. Should they seek clarification on the intended use, a narrowing of the indication to the things that you suggest, we'll be negotiating that with them in due time.

當然可以。我們再次認為，這項發現不會影響 Galleri 獲得 FDA 批准。FDA 顯然會專注於臨床表現、安全性和提交給他們的數據概況，在此背景下，我們將與該機構合作完成標籤工作。如果他們希望澄清預期用途，或希望將適應症範圍縮小到您建議的範圍內，我們將在適當的時候與他們協商。

But we feel like we have a very strong and compelling evidence package for our current intended use, which is adults at elevated risk for cancer such as adults over the age of 50 and with additional risk factors, if they're younger than the age of 50. So we feel like we have a robust package and we'll see where the labeling ends up.

但我們認為，對於我們目前的預期用途，即癌症風險較高的成年人（例如 50 歲以上的成年人以及 50 歲以下但有其他風險因素的成年人），我們已經掌握了非常有力且令人信服的證據。所以，我們覺得我們已經有了一套完善的方案，接下來就來看看標籤最終會是什麼樣子吧。

Yes. Maybe just to add to that. The -- it's also -- we really brought up is across the three rounds of the large participants in NHS calories well as the 35,000 and PATHFINDER 2. There was no serious adverse events across the entire trials. So those are really large numbers. So from a safety perspective, it was really good showing.

是的。或許只是想補充一點。此外，我們還提到了 NHS 卡路里的三輪大型參與者，以及 35,000 和 PATHFINDER 2。整個試驗過程中未發生嚴重不良事件。這些數字真的很大。所以從安全角度來看，表現非常好。

And we think the benefit risk profile is quite compelling as a result of that.

因此，我們認為其收益風險比相當有吸引力。

And just to add something that Josh said. In relation to your point about the 12 cancers, the reason we specify this group of 12 cancers is because it represents two-thirds of all cancer mortality. So if you can make a difference in that group, you really are making a dramatic impact at population scale.

我還要補充一下喬希說的話。關於您提到的 12 種癌症，我們之所以特別指出這 12 種癌症，是因為它們佔所有癌症死亡人數的三分之二。所以，如果你能改變這個群體，你其實就是在人口層面上產生巨大的影響。

But I would draw your attention to something that's in our press release, which is when we talk about this Stage 4 reduction, and the fact that it's more than 20% in the second and third rounds of screening, yes, true for the 12 cancers, but it's also true for all cancers. And so I don't think there's any reason at this stage to think that we should be narrowing our claims only to the 12 cancer types.

但我想提請大家注意我們新聞稿中的一點，當我們談到 4 期癌症病例減少時，我們提到在第二輪和第三輪篩檢中，病例減少超過 20%，是的，這適用於這 12 種癌症，也適用於所有癌症。因此，我認為現階段沒有任何理由認為我們應該將我們的訴求範圍縮小到僅針對這 12 種癌症類型。

It's a great point, Harpal. Thank you for making that. And just to your last question about the AdCom it's certainly possible that there can be an AdCom. The FDA has already held an AdCom. And so we are not sure whether that's going to happen, we will wait and see.

哈帕爾，你說得很有道理。謝謝你製作了這個。至於你最後一個關於招生委員會的問題，招生委員會當然是有可能成立的。FDA已經召開過一次諮詢委員會會議。所以我們不確定這是否會發生，我們會拭目以待。

But we've made the case to the FDA that based on their prior AdCom that they've already held and the fact that we've addressed all of those issues in our submission, which was just completed recently that there's likely no need for one, but we'll see what the FDA decides.

但我們已經向 FDA 說明，根據他們之前召開的諮詢委員會會議以及我們最近完成的提交資料中已經解決了所有這些問題，可能沒有必要再召開一次諮詢委員會會議，但我們會看看 FDA 的決定。

Just a quick follow-up. Obviously, the NHS Galleri results are pretty relevant to the FDA submission. But I don't believe there's much read-through to USPSTF inclusion. So in a worst-case scenario, you don't get at the April, which you get not the US would expect that.

再補充一點。顯然，NHS Galleri 的研究結果與 FDA 的申請密切相關。但我認為，美國預防服務工作小組（USPSTF）的納入並沒有太大的影響。所以，在最糟糕的情況下，你4月份收不到貨，而美國也不會期望收到貨。

You could get a USPSTF conclusion, get into -- or get Medicare coverage according to the legislation and so forth. Are your thoughts on guideline inclusion unchanged? Or is that -- you still don't think that's necessary milestone for you guys that FDA is most likely going to happen?

您可以獲得美國預防服務工作組 (USPSTF) 的結論，加入—或根據相關法律獲得醫療保險等等。您對納入指南的看法是否沒有改變？或者說——你們仍然認為FDA很可能取得的進展對你們來說並不是一個必要的里程碑？

Well, I'm not sure I'm fully following your question, but let me try to take a stab at it. We think the first most important milestone is to get an FDA approval. And we think that, that is going to be an incredible moment for patients and provide amazing amounts of conviction in the clinical community and the payer community. Many of the payers have told us that, that would be the gating step for them. They would like to see an FDA approval before they would provide coverage or consider Galleri for coverage.

嗯，我不太確定我是否完全理解了你的問題，但我試著回答一下。我們認為最重要的首要里程碑是獲得FDA的批准。我們認為，這對患者來說將是一個令人興奮的時刻，並能大大增強臨床界和支付方的信心。許多付款方告訴我們，這將是他們考慮的門檻。他們希望看到 FDA 的批准，才會提供保險或考慮將 Galleri 納入保險範圍。

And then obviously, there will be a CMS NCA, a National Coverage Analysis decision, as we've discussed already. So we think those are the most critical things. And a USPSTF valuation would then come after that. And obviously, that was that is important if you don't have a coverage pathway within CMS. And that's why the USPSTF pathway was put into place because the CMS had no statutory authority to provide coverage for preventive services.

然後，很顯然，還會有一項 CMS NCA（國家醫療保險覆蓋範圍分析）決定，正如我們之前討論過的。所以我們認為這些是最關鍵的事情。最後，美國預防服務工作小組（USPSTF）才會進行估價。顯然，如果你沒有 CMS 的核保途徑，這一點就非常重要。正因如此，美國預防服務工作組 (USPSTF) 制定了相關途徑，因為美國醫療保險和醫療補助服務中心 (CMS) 沒有法定權力提供預防性服務的保險。

But the CS does have statutory authority now. So we see the USPSTF as being supplemental to that. But in terms of guidelines, we think the FDA approval is going to be one of the most critical parts and then the very strong and robust evidence base we have about all the clinical benefits that Harpal has described.

但CS現在確實擁有法定權力。因此，我們認為美國預防服務工作小組（USPSTF）是對該工作小組的補充。但就指導方針而言，我們認為 FDA 的批准將是最關鍵的部分之一，其次是我們擁有的關於 Harpal 所描述的所有臨床益處的非常強大和可靠的證據基礎。

Yes. Just to clarify, I was just saying like if the USPSTF Committee, if they're going to take this data into account, but it's -- we're talking to years in the future probably. So maybe it's not relevant. But anyway, thanks for the time. Appreciate it.

是的。澄清一下，我剛才說的是，如果美國預防服務工作小組（USPSTF）委員會會考慮這些數據，但這可能是幾年後的事了。所以也許這並不重要。總之，謝謝你抽出時間。謝謝。

Thank you. There are no further questions at this time. I will now turn the call back to GRAIL for closing remarks.

謝謝。目前沒有其他問題了。現在我將把電話轉回給 GRAIL，請他作總結發言。

We look forward to presenting full data from our two registrational studies in mid-2026, a longitudinal randomized controlled NHS trial, including clinical utility and performance and the full 35,000 participant PATHFINDER 2 study. So we look forward to providing future updates. And thanks, everyone, for joining the call.

我們期待在 2026 年年中公佈兩項註冊研究的完整數據，一項是縱向隨機對照 NHS 試驗，包括臨床實用性和性能，另一項是完整的 35,000 名參與者的 PATHFINDER 2 研究。因此，我們期待為大家帶來後續的更新資訊。感謝各位參加本次通話。

Ladies and gentlemen, this concludes the call. You may now disconnect.

女士們、先生們，通話到此結束。您現在可以斷開連線了。