Natera Inc (NTRA) 2023 Q4 法說會逐字稿

Ladies and gentlemen, thank you for standing by. My name is Desiree, and I will be your conference operator today. At this time, I would like to welcome everyone to the Natera, Inc. Fourth Quarter 2023 Earnings Call. (Operator Instructions)

女士們先生們，謝謝你們的支持。我叫 Desiree，今天我將擔任你們的會議操作員。此時，我謹歡迎大家參加 Natera, Inc. 2023 年第四季財報電話會議。 （操作員說明）

I would now like to turn the conference over to Michael Brophy, Chief Financial Officer. Please go ahead.

我現在想將會議交給財務長邁克爾·布羅菲 (Michael Brophy)。請繼續。

Thanks, operator. Good afternoon. Thank you for joining our conference call to discuss the results of our fourth quarter of 2023. On the line, I'm joined by Steve Chapman, our CEO; Solomon Moshkevich, President, Clinical Diagnostics; and Al Aleshin, General Manager of Oncology and Chief Medical Officer. John Fesko, President and Chief Business Officer, is also on the line and will be available for Q&A.

謝謝，接線生。午安.感謝您參加我們的電話會議，討論 2023 年第四季的業績。我們的執行長 Steve Chapman 也加入了我的電話會議。 Solomon Moshkevich，臨床診斷總裁； Al Aleshin，腫瘤科總經理兼首席醫療官。總裁兼首席商務官約翰費斯科 (John Fesko) 也在線上接受問答。

Today's conference call is being broadcast live via webcast. We will be referring to a slide presentation that has been posted to investors.natera.com. A replay of the call will also be posted to our IR site as soon as it's available.

今天的電話會議透過網路直播進行直播。我們將參考已發佈到 Investors.natera.com 的幻燈片簡報。電話會議的重播也將在發布後立即發佈到我們的 IR 網站。

Starting on Slide 2. During the course of this conference call, we will make forward-looking statements regarding future events and our anticipated future performance such as our operational and financial outlook and projections, our assumptions for that outlook, market size, partnerships, clinical studies and expected results, opportunities and strategies and expectations for various current and future products, including product capabilities, expected release dates, reimbursement coverage and related effects on our financial and operating results. We caution you that such statements reflect our best judgment based on factors currently known to us and that actual events or results could differ materially.

從投影片2 開始。在本次電話會議期間，我們將就未來事件和我們預期的未來業績做出前瞻性陳述，例如我們的營運和財務前景和預測、我們對該前景的假設、市場規模、合作夥伴關係、臨床對目前和未來各種產品的研究和預期結果、機會、策略和期望，包括產品功能、預期發布日期、報銷範圍以及對我們財務和經營績效的相關影響。我們提醒您，此類陳述反映了我們根據目前已知因素做出的最佳判斷，實際事件或結果可能存在重大差異。

Please refer to the documents we file from time to time with the SEC, including our most recent Form 10-K or 10-Q and the Form 8-K filed with today's press release. Those documents identify important risks and other factors that may cause our actual results to differ materially from those contained or suggested by the forward-looking statements. Forward-looking statements made during the call are being made as of today, February 28, 2024. If this call is replayed or reviewed after today, the information presented during the call may not contain current or accurate information. Natera disclaims any obligation to update or revise any forward-looking statements.

請參閱我們不時向 SEC 提交的文件，包括我們最新的 10-K 或 10-Q 表格以及與今天的新聞稿一起提交的 8-K 表格。這些文件確定了可能導致我們的實際結果與前瞻性陳述中包含或暗示的結果有重大差異的重要風險和其他因素。電話會議期間所做的前瞻性陳述截至今天，即 2024 年 2 月 28 日。如果在今天之後重播或審查該電話會議，則電話會議期間提供的資訊可能不包含當前或準確的資訊。 Natera 不承擔更新或修改任何前瞻性聲明的義務。

We will provide guidance on today's call but will not provide any further guidance or updates on our performance during the quarter unless we do so in a public forum. We will quote a number of numeric or growth changes as we discuss our financial performance. And unless otherwise noted, each such reference represents a year-on-year comparison.

我們將在今天的電話會議上提供指導，但不會就本季度的業績提供任何進一步的指導或更新，除非我們在公共論壇上這樣做。在討論我們的財務表現時，我們將引用一些數字或成長變化。除非另有說明，否則每個此類參考均代表同比比較。

And now I'd like to turn the call over to Steve. Steve?

現在我想把電話轉給史蒂夫。史蒂夫？

Great. Thanks, Mike. Natera is focused on transforming the diagnosis and management of disease worldwide. Our growth is driven by combining our innovative technology with significant peer-reviewed clinical evidence that supports the utility of our products.

偉大的。謝謝，麥克。 Natera 致力於改變全球疾病的診斷和管理。我們的成長是透過將我們的創新技術與支持我們產品實用性的重要同行評審臨床證據相結合來推動的。

We've had a lot of great news since our presentation at the JPMorgan conference, and we're excited to get into the highlights.

自從我們在摩根大通會議上發表演講以來，我們已經收到了很多好消息，我們很高興能夠了解其中的亮點。

We finished Q4 with $311 million of revenue, which was $11 million ahead of the pre-announcement we made in January and represents 43% growth over Q4 of 2022. Full year revenues were $1.08 billion, an increase of more than 30% compared to 2022.

我們第四季的營收為 3.11 億美元，比 1 月的預先公告提前了 1,100 萬美元，比 2022 年第四季成長了 43%。全年營收為 10.8 億美元，比 2022 年成長了 30% 以上。

On volumes, we processed 2,496,000 tests in 2023, which is roughly 6,000 units ahead of the pre-announcement. We processed 341,000 oncology tests in 2023, representing year-over-year growth of 73.5%. And we also saw strong growth metrics in women's health and organ health.

就數量而言，我們在 2023 年處理了 2,496,000 次測試，比預公告提前了約 6,000 次。 2023 年，我們處理了 341,000 次腫瘤學檢測，較去年同期成長 73.5%。我們也看到女性健康和器官健康的強勁成長指標。

Gross margins in Q4 came in at 51.4% compared to our Q1 margin of 39.9%. We finished the full year at 45.5%, above the top end of the Q3 guide.

第四季的毛利率為 51.4%，而第一季的毛利率為 39.9%。我們全年的成長率為 45.5%，高於第三季指引值的上限。

As Mike will cover later in the call, we had some revenue true-ups and lab savings in Q4 that don't repeat every quarter. We estimate organic revenues in Q4 were roughly $306 million and gross margins were roughly 49%, which still represents a significant improvement versus previous quarters.

正如麥克稍後將在電話會議中談到的那樣，我們在第四季度實現了一些收入調整和實驗室節省，但這些不會每季都會重複。我們估計第四季的有機收入約為 3.06 億美元，毛利率約為 49%，與前幾季相比仍然有顯著改善。

And as we discussed at the JPMorgan conference, we also made great progress on cash burn throughout the course of the year, ultimately reducing our cash burn by roughly $193 million in 2023 compared to 2022.

正如我們在摩根大通會議上討論的那樣，我們在全年現金消耗方面也取得了巨大進展，最終與 2022 年相比，2023 年現金消耗減少了約 1.93 億美元。

The guidance for 2024 reflects the continued momentum in the business that generated these very strong results in 2023. We are guiding revenues of $1.320 billion to $1.350 billion, gross margins of 50% to 53% and cash burn for the full year of $50 million to $75 million. On cash, we estimate we will be cash flow breakeven by Q3 or sooner. What's most impressive is we will be achieving this cash flow breakeven quarter while still making very significant investments into our core business.

2024 年的指引反映了業務的持續發展勢頭，並在2023 年創造了非常強勁的業績。我們預計全年收入為13.2 億美元至13.5 億美元，毛利率為50% 至53%，現金消耗為5,000萬美元至2023 年。7,500 萬美元。就現金而言，我們估計到第三季或更早我們將實現現金流收支平衡。最令人印象深刻的是，我們將在本季度實現現金流盈虧平衡，同時仍對我們的核心業務進行大量投資。

You'll see later in the guidance that our investment in research and development and commercial operations remains robust in 2024. This includes major investments in core product enhancements and line extensions, plus potentially guideline-enabling clinical trials that we believe could benefit patients in the years to come. We can do this because our core fundamentals are so strong. We're in large, expanding markets; our volume is growing rapidly; and our margin is expanding, with ASP increasing and COGS going down.

您稍後將在指南中看到，到2024 年，我們對研發和商業營運的投資仍然強勁。這包括對核心產品增強和產品線擴展的重大投資，以及潛在的支援指南的臨床試驗，我們相信這些試驗可以使患者受益未來幾年。我們之所以能做到這一點，是因為我們的核心基礎非常強大。我們處於不斷擴大的大型市場；我們的數量正在快速成長；隨著平均售價的增加和銷貨成本的下降，我們的利潤率正在擴大。

I'll now hit a few other highlights before we go into more details on each.

在我們詳細介紹每個要點之前，我現在將介紹一些其他要點。

First, we think our recent acquisition of Invitae's women's health assets is well timed given the clinical value of expanded carrier screening and the strong trends we are seeing there, and we're feeling positive about our progress on the acquisition thus far.

首先，我們認為，鑑於擴大攜帶者篩檢的臨床價值以及我們在那裡看到的強勁趨勢，我們最近收購 Invitae 的女性健康資產恰逢其時，而且我們對迄今為止的收購進展感到積極。

In organ health, we're building momentum as we complete enrollment and read out major innovative clinical trials. We'll be talking today about some big first-of-their-kind prospective studies in donor-derived cell-free DNA and how they may positively impact patient care.

在器官健康方面，隨著我們完成註冊並宣讀重大創新臨床試驗，我們正在儲蓄動力。今天我們將討論一些關於供體來源的無細胞 DNA 的大型首創前瞻性研究，以及它們如何對患者護理產生積極影響。

Finally, in oncology, earlier this week, we were pleased to announce that the MolDX has expanded coverage for Signatera to neoadjuvant monitoring in breast cancer and separately, for MRD and recurrence monitoring in ovarian cancer. We've had a drumbeat of exciting clinical developments across a range of indications, including CRC, muscle invasive bladder cancer and breast cancer. I'm excited for Alex to also talk about the modern study in bladder cancer, which just enrolled its first patient a few weeks ago. Finally, we've had a string of good results on the IP front that I think puts us in an excellent position in 2024 and beyond.

最後，在腫瘤學方面，本週早些時候，我們很高興地宣布，MolDX 已將 Signatera 的覆蓋範圍擴大到乳腺癌的新輔助監測，並分別擴大到卵巢癌的 MRD 和復發監測。我們在一系列適應症方面取得了令人興奮的臨床進展，包括大腸癌、肌肉層浸潤性膀胱癌和乳癌。我很高興亞歷克斯也能談論膀胱癌的現代研究，該研究幾週前剛招募了第一位患者。最後，我們在智慧財產權方面取得了一系列良好成果，我認為這使我們在 2024 年及以後處於有利地位。

Okay. Great. Let's get into details of the results on the next slide. Revenues exceeded our expectations at $311 million driven by continued strong volume growth and the excellent ASP traction across the business, particularly in women's health and oncology. We previously had a goal to get oncology ASPs above $1,000 by the end of 2024, and we actually hit that level in Q4 of 2023. That's great news because we now think we can get a full year's benefit of higher ASPs in 2024, and we think there's still room to drive Signatera clinical ASPs another $50 to $75 higher just by continuing to execute on currently covered indications. Of course, this week's announcement on new Medicare coverage will help us as well.

好的。偉大的。讓我們在下一張投影片上詳細了解結果。由於銷售量持續強勁成長以及整個業務領域（尤其是女性健康和腫瘤學領域）出色的 ASP 牽引力，收入超出了我們的預期，達到 3.11 億美元。我們先前的目標是到2024 年底將腫瘤學ASP 提高到1,000 美元以上，我們實際上在2023 年第四季達到了這一水平。這是個好消息，因為我們現在認為我們可以在2024 年獲得更高ASP 的全年效益，我們認為只要繼續執行目前涵蓋的適應症，仍有空間推動 Signatera 臨床 ASP 再上漲 50 至 75 美元。當然，本周宣布的新醫療保險範圍也將對我們有所幫助。

The commentary in women's health ASPs is broadly similar. We saw encouraging sequential quarterly progress throughout the course of 2023, and preliminary analysis of Q1 trends suggest that we are on track for continued improvement so far in 2024.

婦女健康 ASP 中的評論大致相似。我們在 2023 年期間看到了令人鼓舞的連續季度進展，對第一季趨勢的初步分析表明，我們預計在 2024 年迄今為止持續改善。

Volume was a strong driver of Q4 performance as well, and you can see the annual volume trend on the next slide. As mentioned earlier, we came in 6,000 units ahead of our pre-announcement in January. I have a separate slide on oncology coming up, so I'll focus on women's health and organ health here where we saw strong growth in the full year 2023.

成交量也是第四季業績的強大推動力，您可以在下一張投影片上看到年度成交量趨勢。如前所述，我們在 1 月預先宣布之前就已經購買了 6,000 台。我將有一張關於腫瘤學的單獨幻燈片，因此我將重點關注女性健康和器官健康，我們在 2023 年全年看到了強勁的增長。

As the year ended, we saw an acceleration of women's health, including hitting a record units per receiving day in December. This strong momentum carried into January as well, and that was prior to the acquisition of Invitae's women's health assets where we're just now starting to see volume come in.

到年底，我們看到女性健康狀況加速改善，其中 12 月的每個收訊日數量創下新紀錄。這種強勁勢頭也延續到了 1 月份，那是在收購 Invitae 的女性健康資產之前，我們才剛開始看到銷售量的增加。

In organ health, as the year progressed, we saw a return to growth in the donor-derived cell-free DNA business after the initial pullback in early 2023 due to the coverage changes. We think we're well positioned going forward in donor-derived cell-free DNA to compete given the significant body of peer-reviewed evidence that we generated and the unique features of our tests.

在器官健康領域，隨著時間的推移，我們看到供體來源的無細胞 DNA 業務在 2023 年初因覆蓋範圍變化而出現最初回落後恢復增長。鑑於我們產生的大量經過同行評審的證據以及我們測試的獨特功能，我們認為我們在供體來源的無細胞 DNA 領域處於有利的競爭地位。

Also, we continue to see strong interest in Renasight after the RenaCARE publication. This momentum is great, and we're off to a fast start across women's health, organ health and oncology.

此外，在 RenaCARE 發布後，我們繼續看到人們對 Renasight 的濃厚興趣。這種勢頭是巨大的，我們在女性健康、器官健康和腫瘤學方面正在快速起步。

On the next slide, we're showing the ramp of our oncology business, which continues to outperform. In Q4, we did 98,000 units, another strong sequential quarter, increasing by 9,000 clinical units over Q3 of 2023. For the full year of 2023, the growth rate was 73.5% over 2022. We're continuing to see strong growth across the core indications, including colorectal cancer and breast cancer, muscle invasive bladder cancer and immunotherapy monitoring even as we add new indications. Roughly 40% of oncologists used Signatera in Q4, which shows the strong clinical utility of the test, and we have strong momentum going into 2024.

在下一張幻燈片中，我們將展示我們的腫瘤業務的成長，該業務繼續表現出色。第四季度，我們生產了98,000 個單位，這是另一個強勁的季度，比2023 年第三季度增加了9,000 個臨床單位。2023 年全年，增長率比2022 年增長73.5%。我們繼續看到核心業務的強勁成長適應症，包括大腸癌和乳癌、肌肉浸潤性膀胱癌和免疫療法監測，即使我們添加了新的適應症。第四季度，大約 40% 的腫瘤學家使用了 Signatera，這表明該測試具有強大的臨床實用性，我們在進入 2024 年時勢頭強勁。

Just as critical as revenue and volume growth is the gross margin traction we are seeing. I think this slide is a good snapshot of the business maturing. Over the course of the year, our ASP and COGS initiatives delivered above our expectations, particularly in Signatera ASP and COGS, both of which improved over the course of 2023.

與收入和銷量成長同樣重要的是我們看到的毛利率牽引力。我認為這張投影片很好地反映了業務的成熟。在這一年中，我們的 ASP 和 COGS 計劃超出了我們的預期，特別是 Signatera ASP 和 COGS，這兩項計劃在 2023 年都有所改善。

As I mentioned at the top of the call, we think the underlying repeatable gross margin in the quarter was roughly 49%. Our 2024 guide implies meaningful continued gross margin improvements based on ASPs and COGS drivers that are within our control. In addition, we've also got a number of potential upside drivers to both revenue and gross margins that we'll discuss later in the call that aren't included in our guide.

正如我在電話會議開頭提到的，我們認為本季的基本可重複毛利率約為 49%。我們的 2024 年指南意味著基於我們控制範圍內的平均售價和銷貨成本驅動因素，毛利率將持續有意義的改善。此外，我們還有許多潛在的收入和毛利率上行驅動因素，我們將在稍後的電話會議中討論這些因素，但這些因素未包含在我們的指南中。

So the net result of strong revenue growth and expanding margins on stable operating expenses is a dramatic reduction in cash burn we achieved in 2023. This is essentially in line with the data we released in January.

因此，強勁的收入成長和穩定的營運費用帶來的利潤率不斷擴大的最終結果是我們在 2023 年實現了現金消耗的大幅減少。這與我們 1 月發布的數據基本一致。

As discussed previously, we accelerated a chunk of 2024 scheduled CapEx in December to take advantage of some large year-end discounts, which has helped us set up for an efficient year in 2024. Two years ago, we set a long-term target to get a cash flow breakeven quarter this year. And based on these results, plus the early data we are seeing so far in Q1, we are confident that we can reach that milestone by Q3 of this year, if not sooner.

正如前面所討論的，我們在12 月加速了2024 年計劃資本支出的一大部分，以利用一些較大的年終折扣，這幫助我們在2024 年建立了高效的一年。兩年前，我們設定了一個長期目標今年季度現金流實現損益兩平。根據這些結果，加上我們在第一季迄今為止看到的早期數據，我們有信心在今年第三季甚至更早達到這一里程碑。

Of course, cash flows are dependent in part on payer response times to submitted claims and so are inherently difficult to forecast with precision on a quarterly basis. But the point is we're continuing to build momentum and our confidence in achieving this goal is stronger than ever.

當然，現金流量部分取決於付款人對提交的索賠的回應時間，因此本質上很難按季度進行精確預測。但關鍵是我們正在繼續積累動力，並且我們實現這一目標的信心比以往任何時候都更強。

Finally, I think anyone that follows this space has taken note of our results on the IP front. Since we created the category of tumor-informed MRD in 2017, we've had 2 companies attempt to follow us into the space, requiring us to enforce our IP against them. The good news is that they've now both been enjoined for violating our IP. The permit injunction against ARCHER and Invitae was ordered after the conclusion of a jury trial. And then subsequently, a preliminary injunction was entered against NeoGenomics.

最後，我認為關注這個領域的任何人都已經注意到我們在智慧財產權方面的成果。自從我們在 2017 年創建腫瘤相關 MRD 類別以來，已經有兩家公司試圖跟隨我們進入該領域，要求我們對他們執行我們的智慧財產權。好消息是，他們現在都因侵犯我們的智慧財產權而被禁止。針對 ARCHER 和 Invitae 的許可禁令是在陪審團審判結束後下令的。隨後，針對 NeoGenomics 發出了初步禁令。

One notable point about these results is the different sets of patent and different judges are an issue in each of these cases, which I think demonstrates the strength of the IP estate that protects our core technology.

這些結果值得注意的一點是，不同的專利組和不同的法官在每個案件中都是一個問題，我認為這表明了保護我們核心技術的智慧財產權財產的力量。

The CareDX IP litigation offers another case in point which generated a sizable jury verdict for damages based only on past infringement of our patents. The process is still ongoing to determine whether future royalties will be awarded.

CareDX 智慧財產權訴訟提供了另一個適當的案例，陪審團僅根據過去對我們專利的侵權行為就損害賠償做出了相當大的裁決。該過程仍在進行中，以確定是否會授予未來的特許權使用費。

And on the Ravgen trial, we were found to not willfully infringe, and the damages awarded were obviously much lower than what Ravgen was requesting, but we still respectfully disagree with the outcomes of the trial and we plan to appeal certain of the rulings.

在 Ravgen 審判中，我們被認定沒有故意侵權，並且判給的損害賠償明顯比 Ravgen 要求的要低得多，但我們仍然不同意審判結果，併計劃對某些裁決提出上訴。

Okay. Now let me hand it over to Solomon to discuss updates in women's health and organ health. Solomon?

好的。現在讓我把它交給所羅門來討論女性健康和器官健康的最新情況。所羅門？

Thanks, Steve. Let's start with the Invitae deal.

謝謝，史蒂夫。讓我們從 Invitae 交易開始。

First, recall we secured a judgment on past damages in our ARCHER IP litigation of roughly $20 million. We anticipated that it could be difficult to collect that amount from Invitae given their financial issues, so we applied that judgment amount as part of the consideration in this deal.

首先，回想一下，我們在 ARCHER IP 訴訟中獲得了對過去損害賠償金約 2000 萬美元的判決。我們預計，鑑於 Invitae 的財務問題，可能很難從他們那裡收回這筆金額，因此我們將該判斷金額作為本次交易對價的一部分。

We also paid Invitae $10 million upfront. And if we have excellent retention of Invitae's accounts, there's a potential milestone payment that we can make of up to $22.5 million (sic) [$42.5 million]. We would be very happy to make that payment because it would mean that the deal is working extremely well for us.

我們也向 Invitae 預付了 1000 萬美元。如果我們能很好地保留 Invitae 的帳戶，我們就可以支付高達 2250 萬美元（原文如此）[4250 萬美元]的潛在里程碑付款。我們很樂意支付這筆款項，因為這意味著這筆交易對我們來說非常順利。

As a reminder, we did not take on any of Invitae's products, its lab operations nor its physical assets. We did hire roughly 30 of their women's health sales reps, and our goal is to provide a seamless transition of those Invitae accounts to Natera's Panorama and Horizon products.

提醒一下，我們沒有收購 Invitae 的任何產品、實驗室營運或實體資產。我們確實僱用了大約 30 名女性健康銷售代表，我們的目標是讓這些 Invitae 帳戶無縫過渡到 Natera 的 Panorama 和 Horizo​​n 產品。

Our team is working hard to retain as much volume as we can and we're doing well. We expect to retain at least $20 million to $25 million in high-quality recurring revenue per year. But we think there's a potential to increase that up to $50 million to $60 million, depending on how things go, especially if we see clinical practice guidelines for expanded carrier screening, or 22q, which we think could come as soon as this spring and will provide upside to these numbers. So we think the deal rationale was strong, and we look forward to providing more updates as the year progresses.

我們的團隊正在努力保持盡可能多的銷售量，而且我們做得很好。我們預計每年至少保留 2,000 萬至 2,500 萬美元的高品質經常性收入。但我們認為有可能將其增加至5,000 萬至6,000 萬美元，具體取決於情況進展，特別是如果我們看到擴大攜帶者篩檢或22q 的臨床實踐指南，我們認為該指南最早可能在今年春天發布，並且將在為這些數字提供上行空間。因此，我們認為這筆交易的理由很充分，我們期待隨著時間的推移提供更多更新。

One of the keys to our offering in women's health is our highly differentiated screening test for the 22q micro deletion. As 22q goes into societal guidelines and becomes commonplace, as we believe it will, the differentiation that Natera has in its 22q test is going to become increasingly valuable.

我們為女性健康提供服務的關鍵之一是針對 22q 微缺失的高度差異化篩檢測試。正如我們所相信的那樣，隨著 22q 進入社會準則並變得普遍，Natera 在 22q 測試中的差異化將變得越來越有價值。

When we run our test, we're using our core SNP-based technology that allows us to target this very small region of the genome, which is around 2.5 to 3 megabases. This allows us to get over 25x more observations in this particular region of interest than companies doing massively parallel shotgun sequencing, which creates a significant technical advantage that has translated into excellent clinical performance as demonstrated in the SMART trial.

當我們進行測試時，我們使用基於 SNP 的核心技術，該技術使我們能夠針對基因組中這個非常小的區域（大約 2.5 到 3 兆鹼基）。與進行大規模並行鳥槍測序的公司相比，這使我們能夠在這個特定的興趣區域獲得超過25 倍的觀察結果，這創造了顯著的技術優勢，並轉化為出色的臨床表現，如SMART試驗所證明的那樣。

We think the SMART trial represents the gold standard in clinical validation that would be very hard to repeat. As a reminder, SMART was a 7-year multicenter prospective trial that enrolled more than 20,000 patients and collected genetic outcomes from prenatal specimens and newborn blood spots. In this trial, Panorama demonstrated an overall clinical sensitivity of 83% and specificity of 99.95%, which translates to PPV of 52.6% overall and a PPV of 100% in cases with ultrasound anomalies.

我們認為 SMART 試驗代表了臨床驗證的黃金標準，很難重複。需要提醒的是，SMART 是一項為期 7 年的多中心前瞻性試驗，招募了 20,000 多名患者，並從產前標本和新生兒血斑中收集了遺傳結果。在這項試驗中，Panorama 表現出 83% 的整體臨床敏感性和 99.95% 的特異性，這意味著整體 PPV 為 52.6%，在超音波異常情況下 PPV 為 100%。

As 22q had gotten more attention in the wake of a strong guideline from ACMG and anticipated guidelines from ACOG, we have noticed competitors starting to present data sets with PPV metrics that look high but with screen positive rates that are low or completely unreported. In one report from a lab doing shutdown sequencing, the screen positive rate was approximately 1 in 6,500, which is 3 or 4x lower than the expected population incidence, suggesting that they might be missing a significant number of affected pregnancies.

由於在 ACMG 的強有力指導和 ACOG 的預期指導之後，22q 受到了更多關注，我們注意到競爭對手開始提供 PPV 指標看起來很高但螢幕陽性率很低或完全未報告的數據集。在進行關閉定序的實驗室的報告中，篩檢陽性率約為 6,500 人中的 1 人，比預期的人群發病率低 3 或 4 倍，這表明他們可能會錯過大量受影響的懷孕。

In addition, other labs are making comparative claims based on patient cohorts that had very high rates of ultrasound findings where we saw PPV of 100% in the SMART trial, as I mentioned previously.

此外，其他實驗室正在根據超音波發現率非常高的患者群組做出比較聲明，正如我之前提到的，我們在 SMART 試驗中看到 PPV 為 100%。

In our view, a test is not appropriate for population screening if you don't know the clinical sensitivity and specificity. These are typical marketing tactics that we've seen before and we do think physicians will see through it.

我們認為，如果不了解臨床敏感性和特異性，則不適合進行人群篩檢。這些是我們以前見過的典型行銷策略，我們確實認為醫生會看穿它。

Moving now into carrier screening. We've seen really strong adoption in the past year, and we believe we're the #1 ordered next-gen sequencing-based carrier screening test in the United States. Our mix of broader panels increased after the exit of Sema4 from the market in late 2022. And we are finding that quite a few of the new transitioning Invitae accounts also have a strong mix of broad panels.

現在進入攜帶者篩檢階段。在過去的一年裡，我們看到了非常廣泛的採用，我們相信我們是美國排名第一的基於訂購的下一代定序的攜帶者篩檢測試。在 2022 年底 Sema4 退出市場後，我們的更廣泛的面板組合有所增加。我們發現，相當多新的過渡 Invitae 帳戶也擁有強大的廣泛面板組合。

So in addition to our existing portfolio, we are really pleased to be launching a new 613 gene panel and a totally flexible custom panel option to serve these customers. Horizon provides high detection across all genes, including the challenging ones where other labs may struggle.

因此，除了我們現有的產品組合之外，我們非常高興推出新的 613 基因面板和完全靈活的客製化面板選項來為這些客戶提供服務。 Horizo​​n 可以對所有基因進行高檢測，包括其他實驗室可能難以做到的具有挑戰性的基因。

With these new panels, together with our investments in variant curation, our genetic counselor team and lab automation, we think Horizon is well positioned to remain a leader in the field. Broad panel carrier screening is also a hot topic for ACOG where we expect to see an expanded guideline in 2024.

憑藉這些新的小組，再加上我們對變異管理、遺傳諮詢團隊和實驗室自動化的投資，我們認為 Horizo​​n 處於有利位置，可以保持該領域的領導地位。廣泛的面板載體篩選也是 ACOG 的熱門話題，我們預計將在 2024 年看到擴展的指南。

Turning now to organ health where we are excited about the prospects for 2024 and beyond. We think the strength of our clinical data, our commercial execution and our intellectual property estate enables us to compete for the leadership position in this space. Our clinical data generation in organ health has been prodigious in the last 5 years where we now have 39 papers published or accepted in top journals.

現在轉向器官健康，我們對 2024 年及以後的前景感到興奮。我們認為，我們的臨床數據、商業執行力和智慧財產權的實力使我們能夠競爭該領域的領導地位。在過去 5 年裡，我們在器官健康方面的臨床數據生成量驚人，目前有 39 篇論文在頂尖期刊上發表或接受。

In the heart indication, we recently had our third paper accepted for publication, the Trifecta heart study, which demonstrated strong correlation between Prospera and endomyocardial biopsy assessed with a molecular microscope. Reporting an area under the ROC curve of 0.9, you can see in these 3 high-quality data sets on the page the consistent performance across the Trifecta, DTRT and DEDUCE trials, including in adults and pediatrics. This performance laid the foundation for us to start the randomized, controlled ACIS trial, which aims to show the non-inferiority of using surveillance with Prospera compared to surveillance biopsies that most centers do on a monthly basis, in the first year after a heart transplant. Sites are preparing for their first enrollment this summer.

在心臟適應症方面，我們最近接受發表了第三篇論文，即 Trifecta 心臟研究，該研究證明了 Prospera 與分子顯微鏡評估的心內膜心肌活檢之間存在很強的相關性。報告 ROC 曲線下面積為 0.9，您可以在頁面上的這 3 個高品質資料集中看到 Trifecta、DTRT 和 DEDUCE 試驗（包括成人和兒科）的一致表現。這一表現為我們啟動隨機對照 ACIS 試驗奠定了基礎，該試驗旨在證明在心臟移植後的第一年，使用 Prospera 進行監測與大多數中心每月進行的監測活檢相比具有非劣效性。各站點正在為今年夏天的首次註冊做準備。

Now in the kidney transplant space, we have finished enrollment of 3 major trials: ProActive, PEDAL and MOTR.

現在在腎臟移植領域，我們已經完成了 3 個主要試驗的入組：ProActive、PEDAL 和 MOTR。

Our first paper from the ProActive study has now been accepted, showing that Prospera can detect active rejection up to 4 months ahead of biopsy. No other cell-free DNA lab has lead time data like this. And we think this data might support payer coverage in the surveillance setting. We look forward to this publication, and we're already working on additional readouts from this study.

我們的第一篇 ProActive 研究論文現已被接受，表明 Prospera 可以在活檢前 4 個月檢測到主動排斥反應。沒有其他無細胞 DNA 實驗室擁有這樣的交貨時間數據。我們認為這些數據可能支持監控環境中的付款人覆蓋範圍。我們期待著這份出版物，我們已經在研究這項研究的更多讀數。

Moving on to the PEDAL trial. With over 500 patients enrolled from 28 different sites, this is an important prospective utility study aiming to show how Prospera can be used serially after a rejection event to predict therapeutic response and outcomes. We believe this study can bring significant value to the field for this important indication.

繼續進行 PEDAL 試驗。這是一項重要的前瞻性實用研究，招募了來自 28 個不同地點的 500 多名患者，旨在展示如何在排斥事件後連續使用 Prospera 來預測治療反應和結果。我們相信這項研究可以為這一重要適應症領域帶來重大價值。

Finally, the MOTR study is generating novel clinical validity data showing the performance of Prospera in cases of multi-organ transplantation, including kidney-heart, kidney-pancreas and kidney-liver. We expect these key trials to extend our data leadership in a meaningful way. So we're excited about 2024.

最後，MOTR 研究正在產生新的臨床有效性數據，顯示 Prospera 在多重器官移植（包括腎臟-心臟、腎臟-胰臟和腎臟-肝臟）病例中的表現。我們期望這些關鍵試驗能夠以有意義的方式擴展我們的數據領先地位。所以我們對 2024 年感到興奮。

Moving now to oncology. Signatera continues to benefit from a significant first-mover advantage across multiple areas.

現在轉向腫瘤學。 Signatera 繼續受益於多個領域顯著的先發優勢。

The first is our significant leadership in technology and innovation, as exemplified by our strong IP portfolio and 2 recent favorable injunction decisions. We continue to invest in new innovation projects with multiple MRD-related products that we plan to launch in 2024 and 2025.

首先是我們在技術和創新方面的顯著領先地位，我們強大的智慧財產權組合和最近的 2 項有利的禁令決定就是例證。我們繼續投資新的創新項目，計劃於 2024 年和 2025 年推出多種 MRD 相關產品。

We also continue to invest in expanding our market-leading clinical portfolio. Now with 70 peer-reviewed oncology publications to date and multiple prospective randomized trials ongoing, many of which were designed several years ago, we believe this pipeline will continue generating data over the coming years that can become practice changing.

我們也繼續投資擴大我們市場領先的臨床產品組合。目前，已有70 篇經過同行評審的腫瘤學出版物和多項正在進行的前瞻性隨機試驗（其中許多試驗是幾年前設計的），我們相信該管道將在未來幾年繼續產生數據，從而改變實踐。

In market access and reimbursement, today, the Signatera test is covered by Medicare and a growing number of private payers in colorectal cancer, bladder cancer, breast cancer and pan-cancer immunotherapy monitoring. We have now added ovarian cancer to that list, which Alex will cover in greater detail in a moment. This broad coverage allows oncologists to use Signatera across the majority of their patients.

在市場准入和報銷方面，如今，Signatera 檢測已被醫療保險和越來越多的結直腸癌、膀胱癌、乳腺癌和泛癌免疫治療監測的私人付款人覆蓋。我們現在已將卵巢癌添加到該列表中，亞歷克斯稍後將更詳細地介紹這一點。這種廣泛的覆蓋範圍使腫瘤學家能夠在大多數患者中使用 Signatera。

Finally, I want to highlight the operational capabilities that we've developed over nearly half a decade of experience. I believe many in the field discount the complexity of delivering tumor-informed and personalized MRD results back to physicians and patients in a timely manner and at scale. There is a real experience curve here, which is not easy to replicate. We continue to expand and refine these capabilities through improvements to the turnaround time, expansion of our mobile phlebotomy services, integration into electronic medical records, and the launch of industry-leading digital solutions for patients and physicians.

最後，我想強調一下我們在近五年的經驗中發展出來的營運能力。我相信該領域的許多人都低估了及時、大規模地向醫生和患者提供腫瘤資訊和個人化 MRD 結果的複雜性。這裡有一條真實的經驗曲線，不容易複製。我們透過縮短週轉時間、擴展我們的行動靜脈切開術服務、整合到電子病歷以及為患者和醫生推出行業領先的數位解決方案來繼續擴展和完善這些功能。

Now I want to hand the call over to Alex to cover recent clinical updates. Alex?

現在我想將電話轉交給 Alex，以介紹最近的臨床更新。亞歷克斯？

Great. Thanks, Solomon. Turning now to key indications. In colorectal cancer, there are multiple events worth noting.

偉大的。謝謝，所羅門。現在轉向關鍵指標。在大腸直腸癌中，有多個事件值得注意。

We reported the first data from our BESPOKE-CRC registry study, which enrolled patients across more than 100 centers in the United States. The study's initial results were presented at ASCO GI this year and showed exceptional assay performance consistent with prior readouts. Additionally, for the first time, it was shown that Signatera testing markedly reduced patient anxiety in over 73% of respondents. Additionally, 96% of participants reported that they wanted to continue using Signatera going forward.

我們報告了 BESPOKE-CRC 註冊研究的第一份數據，該研究招募了美國 100 多個中心的患者。該研究的初步結果已在今年的 ASCO GI 上公佈，並顯示出與先前的讀數一致的卓越檢測性能。此外，首次顯示 Signatera 測試顯著降低了超過 73% 受訪者的患者焦慮感。此外，96% 的參與者表示他們希望繼續使用 Signatera。

The next study I wanted to highlight is the INTERCEPT trial that was done by MD Anderson Cancer Center with over 1,100 patients tested using commercial Signatera. The observational component of this study was able to characterize the impact of Signatera testing on a routine clinical practice and showed a median DFS of approximately 5.6 months between Signatera positivity and clinical relapse.

我想強調的下一項研究是 MD 安德森癌症中心進行的 INTERCEPT 試驗，使用商業 Signatera 對 1,100 多名患者進行了測試。本研究的觀察部分能夠描述 Signatera 檢測對常規臨床實踐的影響，並顯示 Signatera 陽性和臨床復發之間的中位 DFS 約為 5.6 個月。

Interestingly, the investigators also presented preliminary results from the Phase II TAS-102 sub-study, which enrolled 13 patients to receive TAS-102 based on a positive Signatera result. Despite the small sample size, the study is notable since TAS-102 is the same drug being used in the randomized, prospective ALTAIR study. The exciting finding was that 54% of patients had CK clearance at 3 months, suggesting high single-agent activity of TAS-102 in this patient population compared to an untreated Signatera positive population where our data suggests a spontaneous clearance freight should be around 3% to 4%. Additionally, this study reported a median disease-free survival of 9.4 months, which compares favorably to the 5.6 months I presented a moment ago from the broader observational cohort. Though we know the study was not randomized, we believe this all provides a positive signal for the ALTAIR study.

有趣的是，研究人員也發表了 II 期 TAS-102 子研究的初步結果，該研究根據 Signatera 陽性結果招募了 13 名患者接受 TAS-102 治療。儘管樣本量較小，但該研究仍值得注意，因為 TAS-102 與隨機前瞻性 ALTAIR 研究中使用的藥物相同。令人興奮的發現是，54% 的患者在3 個月時有CK 清除，這表明與未經治療的Signatera 陽性人群相比，TAS-102 在該患者群體中的單藥活性較高，我們的數據顯示自發清除率應約為3%至 4%。此外，這項研究報告的中位無疾病存活期為 9.4 個月，這比我剛才在更廣泛的觀察隊列中提出的 5.6 個月要好。儘管我們知道研究不是隨機的，但我們相信這一切都為 ALTAIR 研究提供了積極的信號。

We expect the top line readout from the ALTAIR trial in Q3 of this year, with full results being presented and perhaps concomitantly published in Q4. If the study is positive, we expect it to be practice changing in the U.S., in Japan and likely many other countries.

我們預計 ALTAIR 試驗的頂線數據將在今年第三季公佈，完整的結果將在第四季度公佈並可能同時發布。如果這項研究是正面的，我們預計它將改變美國、日本以及其他許多國家的做法。

Next, let us review our progress towards key catalysts in bladder cancer. Just to remind everyone, we currently have Medicare reimbursement both in the neoadjuvant, adjuvant and recurrence monitoring settings. While we do not talk about bladder cancer often, with around 35,000 new patients being diagnosed every year, we believe this indication could become highly penetrated and well reimbursed pending the readout of the 2 studies highlighted on this slide.

接下來，讓我們回顧一下我們在膀胱癌關鍵催化劑方面的進展。只是提醒大家，我們目前在新輔助、輔助和復發監測環境中都有醫療保險報銷。雖然我們不常談論膀胱癌，但每年約有35,000 名新患者被診斷出來，但我們相信，在這張幻燈片上強調的兩項研究公佈之前，這一適應症可能會變得高度滲透並得到非常好的報銷。

We have previously discussed the randomized, placebo-controlled global IMvigor011 study that is being done in collaboration with Genentech. The study continues to enroll well. And if the readout is positive, it would form the basis for our first Signatera FDA submission likely in the second half of 2025. We believe the advanced status of our work with the FDA gives us an advantage.

我們之前討論過與 Genentech 合作進行的隨機、安慰劑對照的全球 IMvigor011 研究。研究的入組情況持續良好。如果讀數是正面的，這將成為我們可能在 2025 年下半年向 FDA 提交的第一份 Signatera 申請的基礎。我們相信，我們與 FDA 合作的先進狀態為我們帶來了優勢。

We also want to find that the prospective, non-randomized DFS data from the Signatera negative arm of this study will be presented in oral format at the European Association of Urology Conference later this year, and it may create an interim commercial tailwind if it shows convincing data that Signatera negative patients have good outcomes, especially if an improvement is noted beyond the great results we already saw in the IMvigor010 data set published in 2021.

我們還希望發現，這項研究的Signatera 陰性組的前瞻性、非隨機DFS 數據將以口頭形式在今年稍後的歐洲泌尿外科協會會議上提出，如果它表明，它可能會創造一個臨時的商業順風車令人信服的數據表明，Signatera 陰性患者俱有良好的結果，特別是如果注意到的改善超出了我們在 2021 年發布的 IMvigor010 數據集中已經看到的出色結果。

We are also pleased to announce the MODERN study being done in collaboration with the NCI-funded Alliance Group. The lead PI of the study is Dr. Matthew Galsky, a leading expert in this space. And the study design is a testament to his and Alliance's leadership and forward-thinking, with the study incorporating both an escalation and a deescalation cohort, similar to design of the CIRCULATE trial in colorectal cancer. The deescalation cohort has multiple similarities to the VEGA study and, if it meets its primary end point, could have significant implications for patient management, making it possible to reduce unnecessary and expensive treatment in the MRD-negative patient population.

我們也很高興地宣布 MODERN 研究正在與 NCI 資助的聯盟集團合作進行。該研究的首席 PI 是該領域的領先專家 Matthew Galsky 博士。該研究設計證明了他和 Alliance 的領導力和前瞻性思維，該研究結合了升級和降級隊列，類似於結直腸癌 CIRCULATE 試驗的設計。降級隊列與 VEGA 研究有許多相似之處，如果它達到其主要終點，可能會對患者管理產生重大影響，從而有可能減少 MRD 陰性患者群體中不必要且昂貴的治療。

Moving on to the next slide. We were excited this week to announce expansion of Medicare's coverage of Signatera to include ovarian cancer as well as the neoadjuvant setting in breast cancer.

轉到下一張投影片。本週我們很高興地宣布擴大 Medicare 對 Signatera 的承保範圍，將卵巢癌以及乳癌的新輔助治療納入其中。

Ovarian cancer affects close to 20,000 women per year in the United States, has a median age of diagnosis of 63 years and is the fifth leading cause of cancer death in women. Current tools, including imaging and biomarkers such as CA-125 are inadequate to guide adjuvant and surveillance decisions in Stage 2 to 4 disease. Based on Natera's prospective, multicenter study evaluating 69 patients across over 160 time points, we reported longitudinal sensitivity and specificity of 100% to detect recurrence with an average lead time of around 10 months.

在美國，卵巢癌每年影響近 2 萬名女性，中位診斷年齡為 63 歲，是女性癌症死亡的第五大原因。目前的工具，包括影像和 CA-125 等生物標記物，不足以指導 2 至 4 期疾病的輔助和監測決策。根據 Natera 的前瞻性多中心研究，對 160 多個時​​間點的 69 名患者進行了評估，我們報告了檢測復發的縱向敏感性和特異性為 100%，平均提前時間約為 10 個月。

In breast cancer, as a reminder, Signatera has already been reimbursed in the postoperative setting for Stage IIb and higher patients regardless of disease subtype. What's interesting is that up to 50% of all resectable Stage 2 to 4 breast cancer patients currently receive neoadjuvant therapy, which is any treatment prior to surgery, both to improve surgical outcomes and to assess the tumor sensitivity to systemic therapy. However, as the NCCN guidelines themselves note, current tools available for assessing neoadjuvant treatment response are not perfect.

提醒一下，在乳癌方面，Signatera 已經在 IIb 期及以上患者的術後環境中獲得報銷，無論疾病亞型如何。有趣的是，目前在所有可切除的2 至4 期乳癌患者中，高達50% 接受新輔助治療，即手術前的任何治療，既可以改善手術結果，也可以評估腫瘤對全身治療的敏感性。然而，正如 NCCN 指南本身所指出的那樣，目前可用於評估新輔助治療反應的工具並不完美。

Signatera has been extensively validated in this setting, particularly through our collaboration with ISPY-2 consortium, which is a leading group we have now been working with for over half a decade, to study how bespoke ctDNA dynamics in the neoadjuvant setting can further improve on existing methods. In a study of over 280 patients and over 1,000 time points, we have shown that early Signatera clearance was highly predictive of therapy response. And persistent ctDNA detection was associated with poor surgical response as well as a very poor distant relapse-free survival. We believe this expanded coverage can help inform care for tens of thousands of patients every single year.

Signatera 在此環境中得到了廣泛的驗證，特別是透過我們與ISPY-2 聯盟的合作，該聯盟是我們現在已經合作超過五年的領導小組，以研究新輔助環境中的定制ctDNA 動力學如何進一步改善現有的方法。在一項針對 280 多名患者和 1,000 多個時​​間點的研究中，我們表明早期 Signatera 清除率可以高度預測治療反應。持續的 ctDNA 檢測與較差的手術反應以及非常差的遠端無復發生存率有關。我們相信，擴大的覆蓋範圍可以幫助每年為數以萬計的患者提供護理。

These coverage determinations are a great way to start the year, especially as biomarker legislation kicks in across multiple states. We look forward to additional indications for MolDX in 2024 based on our published clinical data.

這些覆蓋範圍的確定是新年伊始的一個很好的方式，尤其是在多個州開始實施生物標記立法之際。根據我們已發表的臨床數據，我們期待 2024 年 MolDX 獲得更多適應症。

Now let me hand the call over to Mike to cover the financials. Mike?

現在讓我把電話轉給麥克，負責處理財務事宜。麥克風？

Great. Thanks, Alex. The first slide here is just a summary of our Q4 results compared to Q4 last year. Steve hit some of the highlights already. Revenues were up 43% and gross margins expanded by almost 10 full percentage points.

偉大的。謝謝，亞歷克斯。這裡的第一張投影片只是我們第四季業績與去年第四季相比的總結。史蒂夫已經談到了一些亮點。營收成長了 43%，毛利率成長了近 10 個百分點。

On revenues, we estimate that we had roughly $5 million in true-ups beyond what we typically get in a quarter that contributed to the $311 million in total revenues. So I would estimate organic revenue number to be roughly $306 million.

在收入方面，我們估計我們有大約 500 萬美元的調整，超出了我們通常在一個季度獲得的總收入 3.11 億美元的收入。因此，我估計有機收入約為 3.06 億美元。

Steve also mentioned some lab-related savings that helped gross margins in the quarter. The way the holiday landed this year, with the entire last week of December bracketed by Christmas and New Year's, meant that we have fewer cases coming in from customers that last week of the quarter and so didn't experience a typical COGS-related expenditures we would normally expect in a week. It takes about a week for us to report out most of our tests, so this resulted in slightly lower COGS expenses but did not significantly impact revenue, which is only accrued on reported units.

史蒂夫也提到了一些與實驗室相關的節省，這些節省有助於提高本季的毛利率。今年假期的到來方式，即 12 月最後一周被聖誕節和新年包圍，這意味著我們收到的客戶案例數量比本季度最後一周要少，因此沒有經歷典型的銷貨成本相關支出我們通常預計在一周內。我們大約需要一周的時間來報告大部分測試，因此這導致銷貨成本略有下降，但並沒有顯著影響收入，收入僅根據報告的單位計提。

Netting all of that benefit out from our Q4 gross margin of 51.4% gives you our estimate of roughly 49% repeatable gross margins which, of course, still represents a huge sequential step-up from Q3 of '23.

從我們第 4 季 51.4% 的毛利率中扣除所有這些收益，我們估計可重複毛利率約為 49%，當然，這仍然比 23 年第 3 季有巨大的連續提升。

We were able to drive these results on operating expenses that were stable compared to 2022. As Steve described, we've invested heavily to build the critical infrastructure needed to rapidly scale the business, and we believe we're in a position to drive significant future innovation with relatively modest increases in operating expenses from our current levels. This combination of expanding revenues and improving margins on stable expenses fits precisely with the multiyear strategy we've laid out in the past. The net result of that is that we cut our Q4 loss per share by more than half compared to Q4 2022 and now have clear line of sight to a cash flow breakeven quarter, as Steve described.

與2022 年相比，我們能夠透過穩定的營運支出來推動這些結果。正如Steve 所描述的，我們投入了大量資金來建立快速擴展業務所需的關鍵基礎設施，並且我們相信我們有能力推動顯著的成長未來的創新，營運費用相對目前水準的成長相對較小。這種擴大收入和提高穩定費用利潤率的結合恰好符合我們過去製定的多年策略。最終的結果是，與 2022 年第四季相比，我們第四季的每股虧損減少了一半以上，現在我們對現金流盈虧平衡季度有了清晰的認識，正如史蒂夫所描述的那樣。

Okay. That's a good segue to the guidance on the next slide. We're excited to be initiating the revenue guide at $1.32 billion to $1.35 billion, gross margins at 50% to 53%, with relatively stable operating expenses leading to another dramatic reduction in our cash burn. While there are a lot of variables that will cause cash flow to fluctuate from quarter-to-quarter, we now believe we can get to a cash flow breakeven quarter by Q3, if not sooner.

好的。這是下一張投影片中指導的一個很好的延續。我們很高興將收入指南設定為 13.2 億至 13.5 億美元，毛利率為 50% 至 53%，相對穩定的營運費用導致我們的現金消耗再次大幅減少。儘管有許多變數會導致現金流量出現季度波動，但我們現在相信，即使不是更早，我們也可以在第三季度實現現金流量盈虧平衡。

This guide presumes a steady continuation of the strong underlying trends in volumes, ASPs and COGS we've seen over the past year but does not rely on upside drivers from potential guideline changes, any spike in volumes from further Signatera data or any meaningful benefit from the biomarker legislation in the calendar year and with just a modest contribution from the recent MolDX coverage decisions. That approach leads to a fairly cautious guide on further margin expansion. I would expect to start the year in the high 40s, consistent with our organic estimate for Q4, with the goal of getting gross margins to the top end of the range and possibly beyond that by Q4 of 2024.

本指南假設我們在過去一年中看到的銷售、平均售價和銷貨成本方面的強勁基本趨勢將穩步延續，但不依賴潛在的指南變化、進一步的Signatera 數據帶來的任何銷量激增或任何有意義的收益帶來的上行驅動因素。日曆年的生物標記立法，最近的 MolDX 覆蓋決策僅做出了微薄的貢獻。這種方法導致對進一步擴大利潤率的指導相當謹慎。我預計年初的毛利率將達到 40 多美元，這與我們對第四季度的有機估計一致，目標是到 2024 年第四季度使毛利率達到該範圍的上限，並可能超過這一水平。

We have also assumed a relatively modest volume contribution from Invitae accounts we are picking up now, consistent with Steve's base case described earlier, but hope to be raising that forecast as we get more clarity on account retention in the coming months.

我們還假設我們現在獲得的 Invitae 帳戶的交易量貢獻相對較小，這與 Steve 之前描述的基本情況一致，但希望隨著我們在未來幾個月對帳戶保留情況更加清晰，提高這一預測。

In our R&D organization, the team has a steady drumbeat of product launches, clinical trial work and COGS initiatives slated to launch this year. Once those initiatives are complete, we anticipate having bandwidth to keep driving innovation in future years without large increases in spending. The SG&A guide includes the pickup of the Invitae sales reps and several other product launch initiatives we have slated for this year.

在我們的研發組織中，團隊穩步推進產品發布、臨床試驗工作和計劃於今年推出的 COGS 計劃。一旦這些舉措完成，我們預計未來幾年將擁有足夠的頻寬來繼續推動創新，而無需大幅增加支出。 SG&A 指南包括邀請 Invitae 銷售代表以及我們今年計劃的其他幾項產品發布計劃。

So at the midpoint of the guide, we are forecasting revenue growth well above 20%, about 650 basis points expansion in the gross margin against annual 2023 full year actual margins and operating expense growth of about 4%.

因此，在指南的中點，我們預測營收成長遠高於 20%，毛利率較 2023 年全年實際利潤率成長約 650 個基點，營運費用成長約 4%。

Those of you that have followed us for a few years know that we prefer to start the year with a guide that feels challenging but achievable to us. And I think there are several sources of upside that could allow us to outperform once again this year.

那些關注我們幾年的人都知道，我們更喜歡以一份對我們來說具有挑戰性但可以實現的指南來開始新的一年。我認為有幾個上升空間可以讓我們今年再次跑贏大盤。

And that's another good segue to the next slide, which just summarizes those catalysts. We are making great progress on ASPs, volume growth and COGS in our core business, as I just described. And I'm looking forward to sharing our progress on earnings calls this year as we continue to just execute on the initiatives within our control. If we can do that, I think we are in a position to outperform once again in 2024.

這是下一張投影片的另一個很好的延續，下一張投影片總結了這些催化劑。正如我剛才所描述的，我們的核心業務在平均售價、銷售成長和銷貨成本方面取得了巨大進展。我期待在今年的財報電話會議上分享我們的進展，因為我們將繼續執行我們控制範圍內的舉措。如果我們能做到這一點，我認為我們有能力在 2024 年再次超越大盤。

Beyond that, we have some potentially significant catalysts on tap. Of course, we have the potential guideline expansion and carrier screening in 22q that Steve described earlier in the call. The timing of those updates are always uncertain and subject to change. But tentatively, you could see some society guideline updates as early as this spring.

除此之外，我們還有一些潛在的重要催化劑。當然，我們在 22 季有潛在的指南擴展和營運商篩選，正如 Steve 之前在電話會議中所描述的那樣。這些更新的時間始終不確定並且可能會變更。但初步而言，您最早可能會在今年春天看到一些社會指南的更新。

In oncology, we are working to expand MolDx coverage to several additional tumor types, and the advent of biomarker legislation in a number of heavily populated states creates an opportunity to drive commercial coverage higher for Signatera in those states.

在腫瘤學領域，我們正在努力將 MolDx 的覆蓋範圍擴大到其他幾種腫瘤類型，而生物標記立法在一些人口稠密的州的出現，為提高 Signatera 在這些州的商業覆蓋率創造了機會。

We are excited about the ALTAIR-CRC escalation in treatment on molecular relapse study readout in colorectal cancer that Solomon touched on in his remarks, which we expect to get in the summer or early fall, as he described.

我們對 ALTAIR-CRC 治療大腸直腸癌分子復發研究結果的升級感到興奮，所羅門在他的演講中提到了這一點，正如他所描述的，我們預計將在夏季或初秋得到結果。

And finally, we are really excited about a number of significant product launches in women's health and oncology we have planned for this year. Consistent with our typical practice, we will dive into each of those product launches in the first earnings call post the launch.

最後，我們對今年計劃在女性健康和腫瘤學領域推出的一系列重要產品感到非常興奮。按照我們的典型做法，我們將在產品發布後的第一次財報電話會議中深入探討每一款產品的發布。

So in summary, I don't think we've ever been in a stronger position to start the year, and we are very pleased to be sharing these updates with you.

總而言之，我認為我們在今年伊始就處於前所未有的有利地位，我們很高興與您分享這些最新消息。

So let me now hand the call over to the operator for questions. Operator?

現在讓我將電話轉交給接線員詢問問題。操作員？

(Operator Instructions) Your first question comes from the line of Subbu Nambi with Guggenheim.

（操作員說明）您的第一個問題來自 Subbu Nambi 與古根漢的線路。

You guided to $1.32 billion to $1.35 billion in 2024 revenue. This is well above Street expectations. That said, as you noted on your last slide, there are still a lot of sources of upside. To unpack this a little bit, can you talk more about the key assumptions for things that are not in the guidance? Specifically, how are you thinking about the potential for, Invitae aside, potential ASP increases for Signatera biomarker bill, 22q, potentially Renasight? What I'm trying to get at is essentially the magnitude of upside for each of these in 2024. I can easily see a path to $50 million to $75 million in upside to your guide. When I look at these components, does that seem reasonable?

您預計 2024 年營收為 13.2 億至 13.5 億美元。這遠高於華爾街的預期。也就是說，正如您在上一張投影片中指出的那樣，仍然有很多上升空間。為了稍微解釋一下這個問題，您能否多談談指南中未包含的內容的關鍵假設？具體來說，除了 Invitae 之外，您如何看待 Signatera 生物標記法案、22q 和 Renasight 潛在的 ASP 成長潛力？我想要了解的本質上是 2024 年這些因素的上漲幅度。根據您的指南，我可以輕鬆看到 5,000 萬至 7,500 萬美元的上漲空間。當我查看這些組件時，這看起來合理嗎？

Yes. Thanks for the question. This is Steve. So maybe I'll just make a couple of comments on these different things, and then Mike, you can sort of talk about the magnitude. I mean certainly, there's a lot of opportunities for upside. You've listed a couple of them. I think with Invitae, we're working hard to move as many of those accounts over as we can. And we think that is going well, as we said in the prepared remarks. We'll have a little more visibility as time goes on.

是的。謝謝你的提問。這是史蒂夫。所以也許我只會對這些不同的事情發表一些評論，然後邁克，你可以談談其嚴重程度。我的意思是，當然有很多上升的機會。您已經列出了其中幾個。我認為，透過 Invitae，我們正在努力將盡可能多的帳戶轉移出去。正如我們在準備好的發言中所說，我們認為進展順利。隨著時間的推移，我們將會有更多的知名度。

From a guideline standpoint, all we can really do on guidelines is produce the peer-reviewed evidence. And we feel incredibly good about the evidence that's been produced, particularly on 22q and on broad panel carrier screening. Now I think it's really up to the societies and the physicians to decide what they want to do. But certainly, that would provide a lot of upside as we're the market leader in noninvasive prenatal testing. We have a high attachment rate of micro deletion testing. And as we said here, we believe we're the market leader as well in next-gen sequencing-based broad panel test. When you look at Signatera and ASP, certainly, there's a lot of opportunities for upside, the same with biomarker bill.

從指南的角度來看，我們在指南上真正能做的就是提供經過同儕審查的證據。我們對已經產生的證據感到非常滿意，特別是在 22q 和廣泛的載體篩檢方面。現在我認為真正應該由社會和醫生來決定他們想要做什麼。但當然，這將帶來很大的好處，因為我們是無創產前檢測的市場領導者。我們的微缺失測試附著率很高。正如我們在此所說，我們相信我們也是基於下一代定序的廣泛面板測試的市場領導者。當你看看 Signatera 和 ASP 時，當然，有很多上漲的機會，生物標記物帳單也是如此。

So Mike, do you want to comment further?

麥克，你想進一步發表評論嗎？

I mean I think those are really kind of the key drivers as you kind of think about kind of catalysts and beyond. I mean I would just reiterate what we said in the prepared remarks, which are, the underlying trends in the core business that we've been seeing these last couple of quarters have been quite strong. And if we can just continue to see those continue to hit our marks as best as we can, I think we're in a good position for '24.

我的意思是，我認為這些確實是關鍵驅動因素，因為你會考慮催化劑及其他因素。我的意思是，我只想重申我們在準備好的發言中所說的話，即我們在過去幾季看到的核心業務的基本趨勢非常強勁。如果我們能夠繼續看到這些繼續盡可能地達到我們的目標，我認為我們在 24 世紀處於有利位置。

Our next question comes from the line of Puneet Souda with Leerink Partners.

我們的下一個問題來自 Puneet Souda 和 Leerink Partners 的電話。

First of all, congrats on the quarter beyond the preannounced numbers and really great momentum you're seeing in the business. Maybe just wanted to follow up on the guide. Steve or Mike, maybe can you elaborate a bit more, just putting together the pieces here. I mean if I look at where you have guided to versus the consensus and our expectations, I mean, you're obviously increasing the ASP on the MRD side. You have recent indication expansion that you're seeing here. Obviously, there's momentum on Panorama, ASP on Panorama from last year, carrier screening. I mean, the list is fairly long. And then we have Invitae's volumes adding on top of it. So maybe just walk me through sort of why this prudent guide still just given sort of the momentum you have. And also maybe if you can talk a little bit about the 22q micro deletion timing. I know you mentioned that briefly, but what else needs to happen there? And I have a follow-up.

首先，恭喜本季超出預先公佈的數字以及您在業務中看到的巨大勢頭。也許只是想跟進指南。史蒂夫或麥克，也許你可以詳細說明一下，只是將這些部分放在一起。我的意思是，如果我看看你們的指導意見與共識和我們的期望相比，我的意思是，你們顯然提高了 MRD 方面的 ASP。您在此處看到了最近的指示擴充。顯然，Panorama 的勢頭強勁，從去年開始Panorama 的 ASP、營運商篩選。我的意思是，這個清單相當長。然後我們還添加了 Invitae 的捲。所以也許請帶我解釋為什麼這個謹慎的指南仍然為你帶來了動力。也許您可以談談 22q 微刪除時間。我知道你簡短地提到了這一點，但是還需要做什麼呢？我有一個後續行動。

Yes, Mike, do you want to take that?

是的，麥克，你想接受嗎？

Yes, sure. Yes, so to me, I think that's a good summary of a lot of the drivers we have going forward on '24, as Steve covered in the prior question. And I would just go back, in each of these drivers, you're going to take like some judgment around setting the guide for the year. We want to set something that, so clearly, as you referenced, requires really good execution. It's going to require good volume execution. It's going to require continued momentum in ASPs and COGS. We think we can deliver that. And it's just a matter of kind of setting the level of what's challenging but achievable for the beginning-of-the-year guide. So really no change in philosophy from what you've seen from us in prior years.

是的，當然。是的，所以對我來說，我認為這是對我們 24 年即將到來的許多驅動程式的一個很好的總結，正如史蒂夫在上一個問題中所提到的那樣。我想回顧一下，在每一個驅動因素中，你都會對設定今年的指南做出一些判斷。正如您所提到的，我們想要設定一些需要非常好的執行力的東西。這將需要良好的批量執行。這需要平均售價和銷貨成本保持持續成長的勢頭。我們認為我們可以做到這一點。這只是為年初指南設定具有挑戰性但可實現的水平的問題。因此，與您在前幾年看到的我們的理念相比，實際上沒有任何變化。

On the 22q front, I think really it's the same commentary that we provided previously. The SMART trial, as we covered in our prepared remarks, we really feel like it is the landmark trial in the space. Those results were excellent. They've now had time to kind of get those data out and get it published. They've been presented at multiple conferences. I think we've got 4 or 5 publications that have now come out of that study. And so we think that merits further guideline consideration. Of course, the guideline committees run their own show and we don't have perfect visibility into the timing of those things. And hence, you never include benefit from guideline inclusions in a guide to start the year, but we remain very optimistic about our prospects.

在 22q 方面，我認為這確實與我們之前提供的評論相同。正如我們在準備好的發言中所述，SMART 試驗確實是該領域具有里程碑意義的試驗。這些結果非常好。他們現在有時間取出這些數據並將其發布。它們已在多個會議上發表過。我想我們現在已經從這項研究中發表了 4 到 5 篇出版品。因此，我們認為值得進一步考慮指導方針。當然，指導委員會有自己的表演，我們對這些事情的時間表並沒有完全的了解。因此，您永遠不會在年初的指南中納入指南內容的好處，但我們對我們的前景仍然非常樂觀。

Got it. And then if I could cover, on the MRD side, you had ovarian cancer and as well as neoadjuvant breast cancer expansion. When do you think that starts to come in into the volumes? Just wanted to confirm they should also benefit from the ADLT rate that you have currently.

知道了。然後，如果我可以介紹一下，在 MRD 方面，您患有卵巢癌和新輔助乳癌擴張。您認為這是什麼時候開始出現在書中的？只是想確認他們也應該從您目前的 ADLT 費率中受益。

And also maybe Alex can talk about it. Within the framework of the clinical trials that you have with ALTAIR and a new trial that you announced today, can you maybe just sort of stack them? Because this does look like a series of sort of data sets that enhance your position in the marketplace. But also maybe just how does all of this play into the NCCN guideline update when we do hear that? And if you have any updates on that front, that would be great as well.

也許亞歷克斯也可以談談它。在 ALTAIR 臨床試驗和今天宣布的一項新試驗的框架內，您可以將它們疊加起來嗎？因為這看起來確實像是一系列可以增強您在市場中地位的資料集。但當我們確實聽到這些消息時，也許所有這些都如何影響 NCCN 指南更新？如果您有這方面的任何更新，那就太好了。

Yes. So first, I'll just say on ovarian and neoadjuvant breast, we're really excited about those indications. We've got some great data and more data coming out. I think generally, once we get coverage in place, that's really when the medical liaison team and commercial team can start going out and educating physicians really about the benefit, so that will take a little bit of time to come in. But certainly, there's volume there today that we'll benefit from.

是的。首先，我只想說關於卵巢和新輔助乳房，我們對這些適應症感到非常興奮。我們已經獲得了一些很棒的數據，而且還有更多數據正在出現。我認為一般來說，一旦我們得到了覆蓋，醫療聯絡團隊和商業團隊就可以開始出去，向醫生進行真正的好處教育，所以這需要一點時間才能介入。但當然，有今天我們將從中受益。

Alex, do you want to talk about ALTAIR and the potential there for upside opportunity and guidelines?

Alex，您想談談 ALTAIR 以及其潛在的上升機會和指導方針嗎？

Yes. Absolutely, Steve. Puneet, thanks for the question. I think as we presented in our prepared remarks, we're expecting a readout, a top line readout, kind of in Q3 for the ALTAIR study. And we do believe that this study, if positive, may be one of the largest events in how early-stage cancer is managed in quite a while.

是的。當然，史蒂夫。普尼特，謝謝你的提問。我認為正如我們在準備好的發言中所提出的那樣，我們期待 ALTAIR 研究的第三季的結果，頂線讀數。我們確實相信，這項研究如果是積極的，可能是相當長一段時間內治療早期癌症的最大事件之一。

Just to put this in perspective, the last study that truly changed how early-stage colon cancer is managed was the MOSAIC study published in 2004. So I think there's a lot of pent-up interest in approving new treatment modalities for these patients. We believe that any positive, statistically significant result will be significantly impactful for how patients are treated. And we're frequently asked like what are some of the numbers that would be even more significant. And I would kind of guide folks to look at the MOSAIC study, which showed a hazard ratio of 0.77 and an absolute risk reduction of 5%. So we strongly feel that if we wanted both of these metrics, the study would be even more significant.

客觀地說，最後一項真正改變早期結腸癌治療方式的研究是 2004 年發表的 MOSAIC 研究。因此，我認為人們對批准這些患者的新治療方式有很多被壓抑的興趣。我們相信，任何積極的、具有統計意義的結果都將對患者的治療方式產生重大影響。我們常被問到哪些數字會比較重要。我會引導人們查看 MOSAIC 研究，該研究顯示風險比為 0.77，絕對風險降低了 5%。因此，我們強烈認為，如果我們想要這兩個指標，那麼這項研究將會更加重要。

And then in terms of the other readouts, the IMvigor011 study, we're expecting top line readout for that in Q1 of 2025. And again, if that study is positive, we also believe that would significantly not just change the guidelines but really fundamentally alter how early stage bladder cancer is managed.

然後就其他讀數而言，IMvigor011 研究，我們預計 2025 年第一季會出現頂線讀數。同樣，如果該研究是積極的，我們也相信這不僅會顯著改變指南，而且會從根本上改變改變早期膀胱癌的治療方式。

So I think these are the two most kind of immediate binary events to look forward to. And we have many other studies currently ongoing that we'll be reading out the next year or 2.

所以我認為這是兩個最值得期待的直接二元事件。我們目前正在進行許多其他研究，我們將在明年或兩年內宣讀這些研究。

Next question comes from the line of David Westenberg with Piper Sandler.

下一個問題來自大衛·韋斯特伯格和派珀·桑德勒的對話。

Congrats on an extremely strong quarter. So I'm going to dig in to get to the guidance. I'm really happy with the guidance, but I do want to tell you the upside, looking to the upside as well. So just in terms of the Invitae acquisition, I mean, I would assume your ASPs are higher than theirs in a lot of the reproductive health areas. And you're calling for 25% or $25 million, I think, in a $100 million business. So I mean, that would imply a little bit even less than maybe, say, 25%. So can you just like walk me through your 50% share, kind of why you would anticipate just maybe that low of picking up of that share? And if it's share you don't really want, I would assume other companies in the space would also not want it, and we maybe see a melt-up in pricing. Is a melt-up in pricing in those kind of accounts contemplated in the guide?

祝賀一個非常強勁的季度。因此，我將深入研究以獲取指導。我對指導感到非常滿意，但我確實想告訴你它的好處，也期待它的好處。因此，就 Invitae 收購而言，我的意思是，我假設你們的 ASP 在許多生殖健康領域都高於他們。我想，你要求在 1 億美元的業務中獲得 25% 或 2500 萬美元的股份。所以我的意思是，這意味著甚至可能低於 25%。那麼，您能否向我介紹您的 50% 份額，這就是為什麼您預計該份額的漲幅可能會這麼低？如果這是你不真正想要的份額，我認為該領域的其他公司也不會想要它，而且我們可能會看到定價的融化。指南中是否考慮了此類帳戶的定價熔化？

And then finally, on that one, a lot of those OB sales force sell BRCA, too. I know BRCA's not that big of a business for you, but is BRCA cross-selling also something to contemplate in that. Sorry, that was a long question. One follow-up, it will be shorter.

最後，在這一點上，許多 OB 銷售人員也銷售 BRCA。我知道 BRCA 對您來說並不是什麼大生意，但 BRCA 交叉銷售也值得考慮。抱歉，這是一個很長的問題。後續一篇，會更短。

Yes. No, no, that makes sense, and it's a good question. So we said we're thinking somewhere in the sort of $20 million to $30 million range is a conservative number, but we also said that we think that can get up to $50 million to $60 million. So we really have to see how things come in as we look into this sort of post-acquisition window.

是的。不，不，這是有道理的，這是一個很好的問題。所以我們說我們認為 2000 萬到 3000 萬美元的範圍是一個保守的數字，但我們也說我們認為這個數字可以達到 5000 萬到 6000 萬美元。因此，當我們研究這種收購後窗口時，我們確實必須看看事情是如何發生的。

A couple of things to note that I think are important. I think the first thing is that the volume that we started with at the end of January after the acquisition was, I think, a decent amount less than maybe where Invitae was the last time they reported out their volume in Q3. And that makes sense because they had announced some initiatives to reduce some of their low-margin business. So for example, some of their low cash pay business. So I think the starting point for us is different maybe than what you're what your expectations were.

有幾件事我認為很重要。我認為第一件事是，我們在收購後 1 月底開始的交易量比 Invitae 上次在第三季報告交易量時的交易量要少很多。這是有道理的，因為他們已經宣布了一些舉措來減少一些低利潤業務。例如，他們的一些低現金支付業務。所以我認為我們的起點可能與您的期望不同。

Now with that said, we're working hard now to transition over as many of the accounts, which is generally the high-margin accounts, because those were the ones that were remaining over to Natera. And we think we're doing really well. Generally, when you look at these things, you go back and you look at Sema4, I know this is a little bit different than that situation, but Natera has generally done very, very well in these settings, retaining the vast majority of the business, certainly, 50% plus of the business, and I think that's what we'll see here.

話雖如此，我們現在正在努力轉移盡可能多的帳戶，這些帳戶通常是高利潤帳戶，因為那些是剩下給 Natera 的帳戶。我們認為我們做得非常好。一般來說，當你看這些東西時，你回去看Sema4，我知道這和那種情況有點不同，但是Natera在這些設置上總體上做得非常非常好，保留了絕大多數業務，當然，超過50% 的業務，我想這就是我們將在這裡看到的。

And I guess the last question on BRCA that I forgot the answer, we do think there's an opportunity there on hereditary cancer testing. We have a very good product that we think is competitive. We've actually done quite well there through the OB channel, and we think there's some opportunities there as well on the oncology side. So certainly, with the disruption happening, there will be some upside opportunity there.

我想關於 BRCA 的最後一個問題我忘記了答案，我們確實認為遺傳性癌症檢測有機會。我們有一個非常好的產品，我們認為它具有競爭力。事實上，我們透過產科管道做得很好，我們認為在腫瘤學方面也有一些機會。因此，隨著顛覆的發生，肯定會有一些上行機會。

I appreciate it. I forgot I asked that part. So just in terms of expectation, now you have neoadjuvant breast, adjuvant breast, bladder, CRC, IO. Can you talk about your expectation for lung? And just given that you have all these tissue types, and I'm asking you to predict a bureaucratic agency, but have you had any conversations with MolDX or expectations on MolDX and just saying, "You know what, this science works in every tumor type. So when does that get coverage?"

我很感激。我忘了我問過那部分。所以就預期而言，現在你有新輔助乳房、輔助乳房、膀胱、CRC、IO。能談談您對肺的期望嗎？考慮到您擁有所有這些組織類型，我要求您預測一個官僚機構，但是您是否與 MolDX 進行過任何對話或對 MolDX 的期望，然後只是說，“您知道嗎，這門科學適用於每種腫瘤類型。那麼什麼時候會得到報道呢？”

Yes, that's a good question. So I think this question of pan-cancer is something that I think a lot of people have asked over time. And certainly, as you start to look at the long tail of cancers getting covered, I think at some point in the future, there may be an opportunity for just kind of across-the-board pan-cancer coverage. But we haven't set up to be dependent on that. What we're doing is we're doing very thoughtful, detailed clinical validations on all the different tumor types, and we're generating the data that's needed to obtain coverage.

是的，這是一個好問題。所以我認為，隨著時間的推移，很多人都在問這個泛癌問題。當然，當你開始關注癌症被覆蓋的長尾時，我認為在未來的某個時候，可能有機會進行全面的泛癌症覆蓋。但我們還沒準備好依賴於此。我們正在做的是對所有不同的腫瘤類型進行非常周到、詳細的臨床驗證，我們正在產生獲得覆蓋範圍所需的數據。

And we think that's, I think, one of the reasons why we're in a leadership position today is because we've done that hard work. We generated these studies. We spent now 5 or 6 years working on some of these trials. And other companies, they may come in and not put that work in, and then they end up not getting coverage. So we think we have a great opportunity.

我們認為，我認為，這就是我們今天處於領導地位的原因之一，因為我們已經做了艱苦的工作。我們進行了這些研究。我們現在花了五、六年的時間進行其中一些試驗。而其他公司，他們可能進來後並沒有投入這項工作，然後他們最終沒有得到覆蓋。所以我們認為我們有一個很好的機會。

Obviously, there's more tumor types that are in submission. We're excited about ovarian and neoadjuvant breast. But you mentioned lung. I guess you didn't mention gastroesophageal, we think it's a big opportunity for us that fits nicely with the colorectal indication. So lots of upside, and we're continuing to focus here and generate data.

顯然，還有更多的腫瘤類型正在提交。我們對卵巢和新輔助乳房治療感到興奮。但你提到了肺。我猜你沒有提到胃食道，我們認為這對我們來說是一個很大的機會，非常適合大腸適應症。有很多好處，我們將繼續關注這裡並產生數據。

Next question comes from the line of Tejas Savant with Morgan Stanley.

下一個問題來自 Tejas Savant 與摩根士丹利的關係。

Steve, Mike, I'll spare you the question why you've decided to be prudent with the guide and take a slightly different tack here. What I want to know is what would carrier screening and ACOG guideline inclusion for 22q mean in terms of gross margin upside. I know it's not baked in, but were those two guidelines to fall in place in the spring, what does that look like? And Steve, on the exit of some of these lower-margin Invitae accounts over the course of the year, is that something that we should be thinking about in terms of just the phasing of the gross margins through '24?

史蒂夫、麥克，我不會問你們為什麼你們決定謹慎對待本指南並在這裡採取稍微不同的策略。我想知道的是，就毛利率上升而言，22 季的營運商篩選和 ACOG 指南納入意味著什麼。我知道它還沒有被確定下來，但是如果這兩個指導方針在春天落實到位，那會是什麼樣子呢？史蒂夫，在今年退出一些利潤較低的 Invitae 帳戶時，我們是否應該考慮在 24 年前逐步調整毛利率？

Yes, it's a good question. So let me just comment on Invitae first. And so what I mentioned there is that Invitae themselves had actually taken steps, I believe, in Q3 time frame of last year to exit some of their lower-margin accounts or maybe move away from some of that business. And so that's why the starting point of where we took over in January was maybe a little bit different than what you might have seen from Invitae in Q3. From the Natera side, when we bring this business on, it's obviously through the Natera insurance contracts with the Natera products, and so we think the margin should be in line with what is currently now kind of an accelerating and expanding Natera gross margin. Hopefully, that makes sense.

是的，這是一個好問題。那我先來評論一下Invitae。所以我提到的是，我相信，Invitae 本身實際上已經在去年第三季度的時間範圍內採取了措施，退出了一些利潤率較低的帳戶，或者可能放棄了部分業務。這就是為什麼我們一月份接手的起點可能與您在第三季度從 Invitae 看到的有點不同。從 Natera 方面來看，當我們開展這項業務時，顯然是透過 Natera 產品的 Natera 保險合同，因此我們認為利潤率應該與目前 Natera 毛利率的加速和擴張保持一致。希望這是有道理的。

From the upside opportunity, obviously, there's an enormous amount of upside in the guidance. We didn't include anything for 22q coverage. We didn't include anything from broad panel carrier screening. So obviously, there's upside as these things come in. If you just think about the clinical impact and the data that we generated, we really think that that's the most important piece. 22q is a very severe disorder. It's the leading cause of congenital heart defects; causes hypocalcemia, which can lead to seizures and brain damage at birth, if it's not treated. So this is a very serious disorder. We test for it with, I think, a very well-validated test that was prospectively done over a 7-year period. We think we've checked all the boxes for society guidelines.

從上行機會來看，顯然，指導中有巨大的上行空間。我們沒有包含任何 22 季度覆蓋範圍的內容。我們沒有納入廣泛的載體篩檢中的任何內容。顯然，這些東西的出現是有好處的。如果你只考慮臨床影響和我們產生的數據，我們真的認為這是最重要的部分。 22q 是一種非常嚴重的疾病。它是先天性心臟病的主要原因；導致低血鈣，如果不及時治療，可能會導致出生時癲癇發作和腦損傷。所以這是一種非常嚴重的疾病。我認為，我們使用了經過充分驗證的測試來進行測試，該測試預期在 7 年的時間內完成。我們認為我們已經檢查了社會準則的所有方框。

If you look at the very high attachment rate that we have, I think 75% plus of our NIPTs get a 22q. Obviously, there's upside opportunity, but we think it's really important that patients get access to this test and then it's covered by their insurance company.

如果你看看我們非常高的附著率，我認為 75% 以上的 NIPT 都獲得了 22 季的結果。顯然，存在上升的機會，但我們認為患者獲得這項測試並由保險公司承保非常重要。

The same thing for expanded panel carrier screening, as we said today, we believe we're the market leader in next-gen sequencing-based expanded panel testing. But there's still opportunity there as guidelines come in place both to extend the volume. Today, there are still customers and OB offices around the country that are ordering smaller panels. As the guidelines come in, we think that they will transition to broader panels, which will put Natera in a good position. And there's also a lot of business today that we're just not reimbursed on where the payers maybe have a negative coverage policy or there's an opportunity to get paid and get coverage for testing that the physicians want and that we think are important for patients.

對於擴展面板載體篩選也是如此，正如我們今天所說，我們相信我們是基於下一代定序的擴展面板測試的市場領導者。但隨著指南的出台，仍然存在機會來擴大數量。如今，全國各地仍有客戶和 OB 辦事處訂購較小的面板。隨著指南的出台，我們認為它們將過渡到更廣泛的小組，這將使 Natera 處於有利地位。今天還有很多業務，我們只是沒有得到報銷，因為付款人可能有負面承保政策，或者有機會獲得報酬並獲得醫生想要的、我們認為對患者重要的測試的承保。

Got it. That's helpful. And then switching gears to oncology, Steve. Just curious as to what's your thought process in terms of time lines to reimbursement in the breast recurrence monitoring indication? I mean that's clearly the big price.

知道了。這很有幫助。然後轉向腫瘤學，史蒂夫。只是好奇您在乳房復發監測適應症的報銷時間表方面的思考過程是什麼？我的意思是這顯然是一個很大的代價。

Second, can you comment on the FoundationOne tracker progress? I mean given the broader launch in Medicare coverage here, where do you expect that to be in terms of perhaps in attach rate by year-end '24?

其次，您能評論一下FoundationOne追蹤器的進度嗎？我的意思是，考慮到這裡醫療保險覆蓋範圍更廣泛，您預計到 24 年底附加費率可能會達到什麼水平？

And then finally, the data on early detection, I believe the first readout there is relatively imminent. But just curious as to how you sort of perhaps updated your thought process there in terms of the go/no-go decision, in terms of the performance specs you'd like to see from that data, that would be helpful.

最後，關於早期檢測的數據，我相信第一次讀出相對迫在眉睫。但只是好奇你如何在進行/不進行決策方面更新你的思考過程，就你希望從這些數據中看到的效能規格而言，這會很有幫助。

Yes. Thanks. So maybe I'll comment quickly on early cancer detection and then hand it over to Solomon to talk about breast cancer recurrence monitoring and some of the exciting data potentially coming around treatment on molecular recurrence.

是的。謝謝。因此，也許我會快速評論早期癌症檢測，然後將其交給所羅門談論乳癌復發監測以及分子復發治療可能出現的一些令人興奮的數據。

So on early cancer detection, we are planning probably in Q2 to read out a case-controlled study that's going to include both colorectal and advanced adenoma patients. And we're excited about that readout. The vast majority of those samples were prospectively collected and matched with colonoscopy, not all of them, but the vast majority were. So then after that, we're going to take a look at how that data looks. Obviously, we're excited about it.

因此，在早期癌症檢測方面，我們計劃可能在第二季度宣讀一項病例對照研究，該研究將包括大腸直腸癌和晚期腺瘤患者。我們對這一結果感到興奮。這些樣本中的絕大多數是前瞻性收集的，並與結腸鏡檢查相匹配，不是全部，但絕大多數都是。之後，我們將看看這些數據的外觀。顯然，我們對此感到興奮。

After that, in October time frame, maybe sometime September, October, we're going to be reading out roughly a 1,000-patient prospective study that will be 100% colonoscopy match. That's already recruiting patients today. And then depending on the readout there, we'll make a decision about what we do going forward as far as the FDA enabling trial. But the way that we've set this up is that the 1,000-patient study that's going to read out in Q3, that's actually the exact same protocol that would be used for the FDA-enabling trial. So if we do want to go ahead with the FDA, we discontinue enrolling into that study. So it's not like there's going to be a delay in that trial.

之後，在 10 月的時間範圍內，也許是 9 月、10 月的某個時候，我們將宣讀大約 1,000 名患者的前瞻性研究，該研究將 100% 大腸鏡檢查匹配。今天已經在招募病患了。然後根據那裡的讀數，我們將決定我們下一步要做什麼，直到 FDA 批准試驗。但我們制定的方式是，將在第三季公佈的 1,000 名患者研究，實際上與 FDA 授權試驗中使用的方案完全相同。因此，如果我們確實想繼續與 FDA 合作，我們將停止參與研究。所以審判不會被推遲。

Now as we said before, the decision for us is going to depend on what the performance of the test looks like. And everything that we're doing this year is included in our budget. It's not any additional cost. We said we're moving rapidly to cash flow breakeven. We're going to hit that in Q3 or sooner. So all of the expenses on early cancer detection will be included in that. We'll still be getting the cash flow breakeven with the same schedule. If we do decide to move forward and do an FDA-enabling trial, that would be based on us seeing market-leading performance. And that needs to be, I think, better than anything else out there from a blood standpoint for both colorectal and advanced adenoma.

正如我們之前所說，我們的決定將取決於測試的性能。我們今年所做的一切都包含在我們的預算中。這不是任何額外費用。我們說過我們正在迅速實現現金流損益兩平。我們將在第三季或更早實現這一目標。所以早期癌症檢測的所有費用都將包含在其中。我們仍將以相同的時間表實現現金流收支平衡。如果我們確實決定繼續進行 FDA 授權的試驗，那將基於我們看到市場領先的表現。我認為，從血液的角度來看，對於結直腸腺瘤和晚期腺瘤來說，這比其他任何東西都要好。

So Solomon, do you want to talk about breast cancer?

所羅門，你想談談乳癌嗎？

Sure. I think the question was specifically about coverage in breast cancer recurrence monitoring. And we do have that already. Signatera was covered for recurrence monitoring in all subtypes of breast cancer. That decision came out early last year. That's been a very high-demand area for Signatera. So as a reminder, almost 300,000 new breast cancer diagnoses per year in the U.S., we estimate over 100,000 of those are eligible under the Medicare coverage, which is Stage IIb and above. And that's for both adjuvant decision-making and recurrence monitoring. And then for many of those patients, especially in the hormone receptor positive disease, recurrence monitoring is something people do not just for a few years after surgery but 5 to 10 years after surgery. So that's a very important area for us to be helping our patients and we've been doing that.

當然。我認為這個問題具體是關於乳癌復發監測的覆蓋範圍。我們已經做到了。 Signatera 涵蓋所有乳癌亞型的復發監測。該決定是去年初做出的。這對 Signatera 來說是一個需求量非常大的領域。提醒一下，美國每年有近 30 萬例新診斷乳癌，我們估計其中超過 10 萬例符合醫療保險覆蓋範圍，即 IIb 期及以上階段。這適用於輔助決策和復發監測。對於許多這樣的患者，尤其是荷爾蒙受體陽性疾病的患者，人們不僅在術後幾年內進行復發監測，而且在術後 5 至 10 年內進行監測。因此，這對我們來說是幫助患者的一個非常重要的領域，我們一直在這樣做。

Our next question comes from the line of Doug Schenkel with Wolfe Research.

我們的下一個問題來自沃爾夫研究中心的道格‧申克爾 (Doug Schenkel)。

First, let me just start with, I guess, a clarification on ALTAIR. In terms of defining success in getting NCCN guideline inclusion and driving broader commercial reimbursement, if you get 5 to 9 months of disease-free survival, is that enough? Is that a win? I picked this range because I think that's the range of DFS demonstrated in the 2 INTERCEPT sub-studies. So as we think about the readout this summer, is that kind of the goalpost that we should be setting?

首先，我想先對 ALTAIR 進行澄清。就成功納入 NCCN 指南和推動更廣泛的商業報銷而言，如果獲得 5 到 9 個月的無病生存期，就足夠了嗎？這是一場勝利嗎？我選擇這個範圍是因為我認為這是 2 個截距子研究中演示的 DFS 範圍。因此，當我們考慮今年夏天的讀數時，我們應該設定這樣的目標嗎？

Alex, why don't you take that?

亞歷克斯，你為什麼不接受這個？

Yes, absolutely. So I would think instead of the hazard ratio for DFS. And if the MOSAIC study is any comparator, the hazard ratio there was 0.77. And then the second thing that's usually pretty important is the absolute risk reduction, so what percentage of patients do you prevent from recurring with a new therapy. And for that study, I think that rate went down from 26.1% to something like 21.1% with the addition of oxaliplatin. So I would use those two as benchmarks. I think the median DFS improvement in absolute terms, that may be a little bit difficult, and I would not extrapolate those numbers from INTERCEPT to ALTAIR. Instead, I would focus on the hazard ratio as well as the absolute risk reduction.

是的，一點沒錯。所以我認為 DFS 不是風險比。如果 MOSAIC 研究是任何比較器，則風險比為 0.77。然後，通常非常重要的第二件事是絕對風險降低，那麼新療法可以防止多少百分比的患者復發。對於這項研究，我認為添加奧沙利鉑後，比率從 26.1% 下降到 21.1% 左右。所以我會用這兩個作為基準。我認為中位數 DFS 改進的絕對值可能有點困難，而且我不會將這些數字從 INTERCEPT 推斷到 ALTAIR。相反，我會關注風險比以及絕對風險降低。

Okay. That is super helpful. The next topic I wanted to touch on is MRD competition. So you guys have had a tremendous amount of success awarding competition, defending your intellectual property estate. That said, there's been a ton of focus out there on how this landscape is going to evolve even with those wins by Natera. There's a potential bevy of companies intending to launch new products over the next couple of years.

好的。這非常有幫助。我想談的下一個主題是 MRD 競爭。所以你們在獎勵競爭、捍衛智慧財產權方面取得了巨大的成功。也就是說，即使 Natera 取得了這些勝利，人們仍然非常關注這一格局將如何演變。可能會有很多公司打算在未來幾年內推出新產品。

So two questions. One, can you talk about what you expect in terms of stickiness associated with existing accounts and really a material first-mover advantage that you have? And what can be gleaned from your experience in NIPT, which is a competitive market where you have what I think is a very, fair to say, sticky position.

那麼兩個問題。第一，您能談談您對現有帳戶的黏性以及您所擁有的實質先發優勢的期望嗎？從您在 NIPT 的經驗中可以得到什麼，這是一個競爭激烈的市場，我認為您擁有一個非常、公平地說、黏性的位置。

And then the second question is, if you were another company and you were trying to move forward with studies in MRD today, how much time and how much money would you need to invest to catch up with Natera, a company that's still doing more studies, including one that you announced for the first time today?

第二個問題是，如果你是另一家公司，而你今天正試圖推進 MRD 的研究，你需要投入多少時間和多少錢才能趕上 Natera，一家仍在做更多研究的公司，包括您今天首次宣布的一個？

Yes, that's a great question. I'll make a couple of comments and then maybe, Solomon, you can talk a little bit more about all the things that we've done as we look toward the future.

是的，這是一個很好的問題。我會發表一些評論，然後，所羅門，你可以多談談我們在展望未來時所做的所有事情。

First, I'll say there is competition. We think the tumor-informed MRD companies are the real competitors here. And particularly, I think NeoGenomics is a strong competitor. Of course, they've been enjoined right now, but they have a very strong footprint. And although I think, when you look at the performance of the NeoGenomics product, from an analytical standpoint, they've made some very significant claims. But if you dig into the details, they've really increased the amount of plasma input to make it seem like the test analytically performs potentially better than it does. And I think that hurts us when you look at comparative claims that they're making based on different levels of plasma input.

首先，我要說的是，存在競爭。我們認為了解腫瘤的 MRD 公司才是真正的競爭對手。特別是，我認為 NeoGenomics 是一個強大的競爭對手。當然，他們現在已經被禁止了，但他們的足跡非常強大。儘管我認為，當你從分析的角度來看 NeoGenomics 產品的表現時，他們已經提出了一些非常重要的主張。但如果你深入研究細節，他們確實增加了血漿輸入量，使測試的分析性能看起來可能比實際情況更好。我認為，當你看到他們根據不同水平的血漿輸入做出的比較聲明時，這傷害了我們。

Now when you look at the clinical validation, what we see on the RaDaR product is that the performance doesn't really hold up. And we see this where analytical validation maybe looks good, but then you look at the clinical validation and it doesn't quite look as good. So you just have to be careful with that with any competitors that are making claims about the performance of their tests.

現在，當您查看臨床驗證時，我們會發現 RaDaR 產品的效能並不真正可靠。我們看到分析驗證可能看起來不錯，但是當你看到臨床驗證時，它看起來不太好。因此，您必須小心對待任何聲稱其測試性能的競爭對手。

Solomon, do you want to talk about some of the stuff that we've done, I think the investments that we've made into clinical data and clinical trials?

所羅門，你想談談我們所做的一些事情嗎？我想我們對臨床數據和臨床試驗的投資？

Sure. I spoke about this in the prepared remarks as well. I would say that one of the most fundamental pieces here is that once a Signatera patient, always a Signatera patient. So once you've got a personalized assay designed for a particular patient, it's extremely unlikely that they would go design a new personalized assay with some other lab. And there's ripple effects to that, right, so that means a physician's office that's testing a bunch of Signatera patients quarterly or every 6 months. And that creates its own level of switching costs for that practice to bring on another lab.

當然。我在準備好的發言中也談到了這一點。我想說，這裡最基本的內容之一是，一旦成為 Signatera 患者，就永遠是 Signatera 患者。因此，一旦您為特定患者設計了個人化檢測，他們就極不可能與其他實驗室一起設計新的個人化檢測。這會產生連鎖反應，對吧，這意味著醫生辦公室每季或每 6 個月對一批 Signatera 患者進行測試。這為建立另一個實驗室的做法創造了一定程度的轉換成本。

Now that being said, we are not resting on our heels from that perspective. It's always been a part of Natera's core recipe to be on the cutting edge with test performance and to continue pushing the boundaries with clinical validity and utility. And I think that's where you see us continuing to invest following that strategy. So as we pointed out on the call, we're planning to put out multiple new features and enhancements in MRD-related products over the next 12 to 24 months, and we've got a ton of investment in clinical trials. So I don't think I can give you a specific number that you asked for, how many hundreds of millions of dollars would you need to be able to catch up, but it's definitely in the hundreds of millions of dollars.

話雖如此，從這個角度來看，我們並沒有就此止步。處於測試表現的前沿並繼續突破臨床有效性和實用性的界限一直是 Natera 核心秘訣的一部分。我認為這就是我們繼續遵循該策略進行投資的地方。因此，正如我們在電話會議上指出的那樣，我們計劃在未來 12 到 24 個月內推出 MRD 相關產品的多項新功能和增強功能，並且我們在臨床試驗方面進行了大量投資。所以我想我不能給你一個具體的數字，你需要多少億美元才能趕上，但肯定是數億美元。

And Doug, maybe I'll just add to that a little bit. I mean if you look at the different areas Solomon broke out, you look at data, I mean we now have a significant number of peer-reviewed studies that have been published. But not only that, we have multiple randomized trials that are ongoing that have been underway, some now for kind of 5 years or something in that time frame. And I think the key thing is, with these randomized trials, the data really is only applicable to the test that was used in the trial. So I think we're seeing some groups now coming and doing clinical validations where they're looking just at the performance of their test. As you go forward, that's really not going to be good enough. You have to have a randomized study that shows how patient outcomes were impacted based on using your test in the randomized study. And that's where we're going to be and that's where we think things are going as we move forward and moving away from analytical validations and from clinical validation.

道格，也許我會補充一點。我的意思是，如果你看看所羅門爆發的不同領域，看看數據，我的意思是我們現在已經發表了大量經過同行評審的研究。不僅如此，我們還有多項正在進行的隨機試驗，有些已經持續了 5 年或在那個時間範圍內。我認為關鍵是，透過這些隨機試驗，數據實際上僅適用於試驗中使用的測試。因此，我認為我們現在看到一些小組正在進行臨床驗證，他們只是專注於測試的表現。當你繼續前進時，這確實還不夠好。您必須進行一項隨機研究，以顯示根據在隨機研究中使用您的測試對患者結果的影響。這就是我們將要達到的目標，這就是我們認為隨著我們向前邁進並遠離分析驗證和臨床驗證而事情正在發展的方向。

Next question comes from the line of Matt Sykes with Goldman Sachs.

下一個問題來自高盛的馬特·賽克斯 (Matt Sykes)。

Congrats on the quarter and the year last year. Maybe just given the importance of the gross profit line, could you maybe just talk about your expectations for ASP trends for women's health kind of ex potential guideline inclusion? Like, what do you kind of envision in terms of ASPs for this year? And then I have one quick follow-up.

恭喜去年這個季度和一年。也許只是考慮到毛利線的重要性，您能否談談您對女性健康領域 ASP 趨勢（包括潛在指南）的期望？例如，您對今年的平均售價有何預期？然後我會進行快速跟進。

Mike, do you want to take that?

麥克，你想要那個嗎？

Yes, sure. Yes, thanks, Matt, for the question. Yes, I mean I think we expect to see stable trends in the women's health ASPs that we saw toward the end of last year. So as folks that follow us for some time will recall, we saw really strong kind of sequential movements upward in the ASPs, particularly for carrier screening but also for the NIPT product through the course of the year, and that was a big driver, along with, obviously, Signatera ASPs of the margin expansion you saw in the calendar year '23 results.

是的，當然。是的，謝謝馬特提出的問題。是的，我的意思是，我認為我們預計會看到去年年底女性健康平均售價的穩定趨勢。因此，關注我們一段時間的人會記得，我們​​看到ASP 出現了非常強勁的連續上升趨勢，特別是在攜帶者篩檢方面，而且在這一年中，NIPT 產品也是如此，這是一個很大的推動因素，顯然，Signatera ASP 的利潤率擴張是您在 23 年的業績中看到的。

And now in '24, what the guide implies is that you should get the full year benefit of the ASPs that we saw in Q4. So obviously, that does leave room for there to be continued improvement, and we're working every day to continue to do what we can operationally to make sure that we get the reimbursement for the coverage services that we think we deserve. So there's room for that to continue to improve above the expectations we've set this year. I think that's a good kind of starting point for the guidance.

現在，在 24 年，該指南暗示您應該獲得我們在第四季度看到的 ASP 的全年收益。顯然，這確實為持續改進留下了空間，我們每天都在努力繼續盡我們所能，以確保我們獲得我們認為應得的承保服務報銷。因此，這方面還有持續改善的空間，高於我們今年設定的預期。我認為這是指導的一個很好的起點。

Got it. And then just Mike again, just on COGS reduction, you guys have done a good job, it's obviously been a key gross margin driver. As you kind of look across your businesses, where do you see the most upside for reduction in COGS, whether it's in women's health, Signatera, organ health, et cetera? Like, where do you think the biggest levers are for COGS reduction this year that could actually drive those gross margins to the top end of the guide like you talked about?

知道了。然後，麥克再次強調，在降低銷售成本方面，你們做得很好，這顯然是毛利率的關鍵驅動因素。當您審視您的業務時，您認為減少銷售成本的最大好處在哪裡，是否在女性健康、Signatera、器官健康等領域？例如，您認為今年降低銷貨成本的最大槓桿在哪裡，實際上可以像您所說的那樣將這些毛利率推至指南的頂端？

Yes. I mean I think the first project that comes to mind there, obviously, is the in-house project for Signatera exome in Austin. So as a reminder, we launched our exome capability in San Carlos last year. We've driven a significant portion of the volumes to the in-house exome. And then launching in Austin unlocks another wave of cost efficiencies just because you've got more space, you can deploy more automation, so on and so forth, in that Austin lab, so we're very excited about that. We'd like to have that launched in the summer or early fall.

是的。我的意思是，我想到的第一個項目顯然是奧斯汀 Signatera 外顯子組的內部項目。提醒一下，我們去年在聖卡洛斯啟動了外顯子組能力。我們已將很大一部分量轉移到內部外顯子組。然後在奧斯汀的啟動釋放了另一波成本效率，因為你在奧斯汀實驗室有更多的空間，可以部署更多的自動化等等，所以我們對此感到非常興奮。我們希望在夏季或初秋推出。

In addition to that, though, I mean I think we've got across each of the major products, I mean, Panorama, carrier screening and Signatera, we've got workflow launches and improvements coming this year that can drive COGS lower across the business. And those COGS projects because, Matt, as you mentioned, like we have a long track record of putting those COGS projects on the board, scheduling them, investing in them and then hitting our marks in terms of actually yielding the savings, those COGS projects are in the guide. So there's not a lot of hedge in the guide for those. But again, we're excited to deploy those, and we think they can help us mature.

除此之外，我認為我們已經掌握了所有主要產品，我的意思是，Panorama、運營商篩選和 Signatera，我們今年將推出工作流程並進行改進，這可以降低整個行業的 COGS。商業。那些銷貨成本項目是因為，馬特，正如你提到的，我們在將這些銷貨成本項目放在董事會上、安排它們、投資它們，然後在實際產生節省方面達到了我們的目標，這些銷貨成本項目有著悠久的記錄。都在指南裡。因此，指南中沒有太多針對這些的限制。但我們再次很高興部署這些，我們認為它們可以幫助我們成熟。

Ladies and gentlemen, this concludes today's conference call. You may now disconnect.

女士們、先生們，今天的電話會議到此結束。您現在可以斷開連線。