INTELLIA THERAPEUTICS, INC. (NTLA) 2026 Q2 法說會逐字稿

Hello, welcome to Intellia Therapeutics' second quarter conference call. My name is Chloe, and I will be your conference operator today. Please be advised that today's call is being recorded.

您好，歡迎參加 Intellia Therapeutics 第二季財報電話會議。我叫 Chloe，今天將擔任會議接線員。請注意，今天的電話會議將被錄音。

I would now like to turn the call over to Jason Fredette, Vice President of Investor Relations and Corporate Communications at Intellia. Please proceed.

現在我想把電話交給 Intellia 投資人關係與企業傳播副總裁 Jason Fredette。請開始。

Thank you, operator, hello, everyone. Earlier this morning, we issued a press release outlining recent business updates in our second quarter financial results. This document can be found on the Investors and Media section of Intellia's website intelliatx.com.

謝謝，接線員，各位大家好。今天稍早，我們發布新聞稿，概述我們第二季財務結果中的近期業務更新。該文件可在 Intellia 網站 intelliatx.com 的「投資人與媒體」專區找到。

At this time, I would like to take a minute to remind listeners that during this call, Intellia management may make certain forward-looking statements. We ask that you refer to our SEC filings available at sec.gov for a discussion of potential risks and uncertainties. All information presented on this call is current as of today, and Intellia undertakes no duty to update this information unless required by law. Joining me on the call are John Leonard, our Chief Executive Officer, and Ed Dulac, our Chief Financial Officer.

此時，我想花一分鐘提醒各位聽眾，在本次電話會議中，Intellia 管理層可能會作出若干前瞻性陳述。我們請您參閱 sec.gov 上可取得的我們向美國證券交易委員會（SEC）提交的文件，以了解潛在風險與不確定性之討論。本次電話會議所呈現的所有資訊均以今日為準，除非法律要求，Intellia 不承擔更新該等資訊之義務。與我一同參與本次電話會議的還有我們的執行長 John Leonard，以及財務長 Ed Dulac。

With that, I'll now turn the call over to John to begin our business discussion.

接下來，我將把電話交給 John，開始我們的業務討論。

Thank you, Jason, good morning, everyone. We're excited to be speaking with you to recap the tremendous progress we made in our Phase 3 development programs of lonvo-z in hereditary angioedema, or HAE, nex-z in transthyretin amyloidosis, or ATTR.

謝謝你，Jason，各位早安。我們很高興與各位交流，回顧我們在 lonvo-z（用於遺傳性血管性水腫，或 HAE）以及 nex-z（用於轉甲狀腺素蛋白類澱粉沉積症，或 ATTR）的第三期開發計畫中所取得的重大進展。

The full results of our Phase 3 HALO trial in HAE position us very well for potential approval and launch of the world's first in vivo gene-editing product in the first half of next year. We also have gained important new genomic insights that further our understanding of nex-z's profile and could help position us even more favorably within a large and dynamic ATTR market.

我們在 HAE 的第三期 HALO 試驗完整結果，使我們在明年上半年有望取得核准並推出全球首個體內（in vivo）基因編輯產品方面處於非常有利的位置。我們也獲得了重要的新基因體洞見，進一步加深對 nex-z 特徵的理解，並可能協助我們在龐大且充滿活力的 ATTR 市場中取得更有利的定位。

Let's begin with lonvo-z. Simply put, the second quarter was a momentous period for this program. In April, we reported positive top-line results from HALO and got our rolling BLA submission underway with the FDA. This was followed by our late-breaking oral presentation at EAACI and a concurrent publication in The New England Journal of Medicine, Intellia's sixth manuscript in this prestigious journal.

我們先從 lonvo-z 談起。簡而言之，第二季對這個計畫而言是具有里程碑意義的時期。4 月，我們公布 HALO 的正向主要結果，並開始向 FDA 進行滾動式 BLA 申請提交。隨後，我們在 EAACI 進行了最新突破口頭報告，並同步於《新英格蘭醫學期刊》發表論文，這是 Intellia 在這本權威期刊上的第六篇稿件。

HALO was an unequivocal success as we achieved statistical significance for the primary and all key secondary endpoints. More specifically, during the six-month primary observation period, we reported an 87% reduction in mean monthly attacks for lonvo-z versus placebo. 62% of patients were entirely attack-free and therapy-free in the lonvo-z arm. A 23 point improvement was observed for the lonvo-z arm in the total angioedema quality of life score from baseline.

HALO 取得了明確的成功，我們在主要終點與所有關鍵次要終點均達到統計顯著性。更具體而言，在為期六個月的主要觀察期內，我們報告 lonvo-z 相較安慰劑使平均每月發作次數降低 87%。在 lonvo-z 組中，62% 的病患完全無發作且不需治療。lonvo-z 組的總血管性水腫生活品質量表分數相較基線改善 23 分。

For context, a change of just six points is considered to be clinically meaningful. The New England Journal manuscript also contained compelling figures and analyses underscoring the unique value proposition that could be afforded by this one-time therapy if it's approved.

作為背景說明，僅 6 分的變化即被視為具有臨床意義。《新英格蘭醫學期刊》的論文亦包含具說服力的圖表與分析，凸顯若此一次性療法獲核准，可能帶來的獨特價值主張。

For instance, patient-level data demonstrated that all patients in the lonvo-z arm experienced attack rate reductions from baseline for weeks 5 to 28. In other words, every single patient received a clinical benefit, including those who are not yet fully attack-free during that six-month period. A subgroup analysis demonstrated meaningful attack rate reductions in the lonvo-z arm regardless of age, sex, race, weight, geography, baseline attack rate, or prior therapy.

例如，病患層級資料顯示，在第 5 週至第 28 週期間，lonvo-z 組所有病患的發作率相較基線均有所下降。換言之，每一位病患都獲得臨床效益，包括在該六個月期間尚未完全無發作的病患。次族群分析顯示，不論年齡、性別、種族、體重、地理區域、基線發作率或既往治療，lonvo-z 組均呈現具意義的發作率降低。

The publication also included a figure depicting the mean number of HAE attacks over time. It traced patients from when they were on prior therapies before screening through the entire efficacy evaluation period and into crossover, and it showed that mean attack rates for the lonvo-z arm dropped well below the pre-screening attack rates by week four. Attacks continued to decline in the months that followed and approached zero in the crossover period after week 28.

該發表亦包含一張圖，描繪 HAE 發作平均次數隨時間的變化。該圖追蹤病患從篩檢前使用既往治療的期間，經過整個療效評估期並進入交叉治療，並顯示 lonvo-z 組的平均發作率在第 4 週即降至遠低於篩檢前的發作率。在接下來的數月中，發作持續下降，並在第 28 週後的交叉期趨近於零。

In the placebo arm, not surprisingly, mean attack rates didn't drop below pre-screening levels until patients crossed over to lonvo-z. At that point, they dropped steeply and approached zero within a few months. Also, notably, all patients who received lonvo-z at baseline or in crossover remained free from long-term prophylaxis therapy as of the data cutoff.

在安慰劑組中，不出所料，平均發作率直到病患交叉接受 lonvo-z 後才降至低於篩檢前水準。在那之後，發作率大幅下降，並在數個月內趨近於零。此外，值得注意的是，截至資料截止日，所有在基線或交叉期接受 lonvo-z 的病患仍不需長期預防性治療。

And finally, favorable safety and tolerability data were observed. The most common treatment emergent adverse events were infusion-related reactions, headache, and fatigue. All treatment emergent adverse events were Grade 1 or Grade 2, and there were no serious adverse events observed in the lonvo-z arm as of the data cutoff. These results are unsurpassed by chronic long-term prophylaxis therapies or LTPs. We believe it is clear, moreover, that they truly stand alone in the HAE space, given that this is a one-time treatment.

最後，我們觀察到良好的安全性與耐受性資料。最常見的治療期間出現不良事件為輸注相關反應、頭痛與疲勞。所有治療期間出現不良事件皆為第 1 級或第 2 級，且截至資料截止日，lonvo-z 組未觀察到嚴重不良事件。這些結果優於慢性長期預防性治療（LTP）。此外，我們認為很清楚的是，鑑於這是一種一次性治療，這些結果在 HAE 領域確實獨樹一幟。

Most patients were attack-free and therapy-free for the entire six-month efficacy observation period following a single lonvo-z dose. Based on our preclinical work and observations from our Phase 1/2 trial, our expectation is that this percentage will increase further over time as patients who have lived with HAE their entire lives adjust to their new normal. What's next for us? Well, we expect to be in a position to announce the FDA's acceptance of a BLA filing for lonvo-z by the end of this year.

多數病患在單次 lonvo-z 給藥後，於整個六個月療效觀察期內皆無發作且不需治療。根據我們的臨床前研究以及第一/二期試驗的觀察，我們預期隨時間推移，這一比例將進一步提高，因為終其一生與 HAE 共存的病患會逐步適應新的常態。接下來我們要做什麼？我們預期在今年年底前，有望宣布 FDA 受理 lonvo-z 的 BLA 申請。

In the meantime, our pre-commercial readiness efforts are advancing well as we prepare for a potential US launch in the first half of next year. Most of these efforts are well underway, including work streams across medical engagement, payer outreach, treatment center readiness, distribution planning, and access strategy.

同時，隨著我們為明年上半年可能在美國上市做準備，我們的上市前準備工作也在順利推進。其中多數工作已在進行中，包括醫學端互動、支付方（payer）溝通、治療中心就緒度、配送規劃以及可近性策略等多條工作線。

We've completed hiring for our field medical, reimbursement, and strategic accounts teams, and they're now engaging with treatment centers around the country to ensure they are well-prepared to address patient needs shortly after approval. We're also building awareness of the many burdens associated with HAE.

我們已完成現場醫學、給付/報銷以及策略客戶團隊的招募，他們目前正與全國各地的治療中心互動，確保在核准後不久即可充分準備以滿足病患需求。我們也正在提升對 HAE 相關多重負擔的認知。

During the second quarter, we launched HAEreframed.com, a disease awareness initiative designed to elevate understanding of the challenges patients face, including those related to lifelong chronic therapy. Together, these efforts reflect meaningful progress in building the infrastructure, awareness, and access pathways needed to support our planned launch.

在第二季，我們推出 HAEreframed.com，這是一項疾病認知倡議，旨在提升對病患所面臨挑戰的理解，包括與終身慢性治療相關的挑戰。綜合而言，這些努力反映出我們在建立支援既定上市計畫所需的基礎設施、認知度與可近性途徑方面取得了實質進展。

So let's turn to the progress we've made with nex-z, our potential one-time treatment for patients with ATTR cardiomyopathy and polyneuropathy. We were pleased to resolve the clinical holds on our Phase 3 trials quite rapidly earlier this year.

接著談談我們在 nex-z 上取得的進展；nex-z 是我們針對 ATTR 心肌病變與多發性神經病變病患的潛在一次性治療。我們很高興今年稍早能相當迅速地解除第三期試驗的臨床暫停（clinical hold）。

I'm excited to report today that we were able to resume enrollment and dosing in both trials in Q2. Investigator engagement enthusiasm remain high, and our screening rate is rapidly increasing globally once again. ATTR is a large, growing, and highly underdiagnosed market with significant unmet need.

我很高興今天報告，我們已在第二季恢復兩項試驗的收案與給藥。研究者的參與熱情仍然高昂，我們的篩檢速度也再次在全球快速提升。ATTR 是一個規模龐大、持續成長且嚴重未被診斷的市場，存在顯著未被滿足的醫療需求。

Today, patients are predominantly served by stabilizers, silencers, or a combination of the two. About a month ago, disappointing top-line results were shared from CARDIO-TTRansform, the pivotal trial of eplontersen, a TTR silencer for patients with ATTR cardiomyopathy. Since then, there's been some debate about whether a silencer can work on top of a stabilizer.

目前，病患主要接受穩定劑（stabilizers）、沉默劑（silencers）或兩者合併治療。約一個月前，針對 ATTR 心肌病變病患的 TTR 沉默劑 eplontersen 之關鍵性試驗 CARDIO-TTRansform 公布了令人失望的主要結果。自那之後，市場上對於沉默劑是否能在穩定劑基礎上發揮作用出現了一些討論。

We and others believe the negative outcome is specific to eplontersen in this particular trial, and it does not speak to combination outcomes in general. We remain firm believers that combination therapy will work, but only with the right agent. This belief is based empirically on clinical evidence. First, we would point to the fact that another chronically dose silencer, patisiran, has already shown a directional benefit on top of stabilizers in a well-controlled trial.

我們與其他人認為，這項負面結果是此特定試驗中 eplontersen 所特有，並不代表一般而言的聯合治療結果。我們仍堅信聯合治療會奏效，但前提是必須搭配正確的藥物。此一信念是以臨床證據的實證基礎為依據。首先，我們會指出，另一種慢性給藥的沉默劑 patisiran 已在一項嚴謹對照試驗中，於穩定劑治療基礎上顯示出方向性的額外效益。

But even more importantly, we would point to what was observed in the monotherapy data for each of the chronically dosed stabilizers and silencers. If you go back and look at the readouts for approved stabilizers like tafamidis and acoramidis and approved silencers like eplontersen and patisiran, you'll see that patients continue to progress while they're on those therapies.

但更重要的是，我們會指出在各種慢性給藥的穩定劑與沉默劑之單藥治療數據中所觀察到的現象。如果你回頭看已核准的穩定劑（如 tafamidis 與 acoramidis）以及已核准的沉默劑（如 eplontersen 與 patisiran）的讀出結果，你會看到病患即使在接受這些治療期間仍持續惡化。

Why is that? Well, we and others are convinced it's because they inadequately reduce or control TTR protein. Focusing in on the approved silencers, you'll see that mean TTR reductions for each of them are about 80%. However, the details behind that number matter.

為什麼會這樣？我們與其他人深信，原因在於它們對 TTR 蛋白的降低或控制不足。聚焦於已核准的沉默劑，你會看到它們各自的平均 TTR 降幅約為 80%。然而，這個數字背後的細節很重要。

For instance, it takes many months for those silencers to achieve their 80% data of reduction. There's significant variability in TTR from patient to patient, with some achieving a 90% knockdown and many others receiving reductions of only 50% or 60%. And even within an individual patient, the knockdown fluctuates due to issues with PK and issues with dose interruptions and adherence, whether due to patient behavior or toxicity.

例如，這些沉默劑需要好幾個月才能達到 80% 的降幅數據。不同病患之間的 TTR 變異很大，有些可達到 90% 的抑制，但也有許多人僅降低 50% 或 60%。即使在同一位病患體內，抑制程度也會因藥物動力學（PK）問題、劑量中斷與用藥依從性等因素而波動，無論是由病患行為或毒性所致。

Simply put, it appears today's silencers and stabilizers are leaving efficacy on the table. In a progressive disease with high mortality like ATTR-CM, every day and every microgram per milliliter of TTR counts. nex-z has demonstrated its ability to deliver an unsurpassed knockdown of TTR protein for patients in both relative and absolute terms. Our Phase 1 data demonstrated a mean TTR reduction of 90%. While that percentage is impressive, we believe the absolute TTR reduction is even more clinically relevant.

簡言之，現今的沉默劑與穩定劑似乎仍有未被充分發揮的療效空間。在像 ATTR-CM 這種進行性且高死亡率的疾病中，每一天、以及每毫微克/毫升的 TTR 都至關重要。nex-z 已證明其能在相對與絕對層面，為病患帶來無可匹敵的 TTR 蛋白抑制效果。我們的第 1 期數據顯示平均 TTR 降幅為 90%。雖然這個百分比令人印象深刻，但我們認為絕對 TTR 降幅在臨床上更具相關性。

When nex-z is provided as monotherapy, mean serum TTR was less than 20 micrograms per milliliter, about one-third of the absolute level seen with the leading chronic silencer. That knockdown was achieved rapidly within one month of the infusion, and it was extremely consistent across all patients. Best of all, patients began receiving therapeutic doses of nex-z in 2021, and as of our latest data cutoff, intra-patient TTR control was constant and was maintained across all patients following their one-time nex-z treatment.

當 nex-z 作為單藥治療時，平均血清 TTR 低於 20 微克/毫升，約為領先的慢性沉默劑所見絕對水準的三分之一。該抑制效果在輸注後一個月內迅速達成，且在所有病患之間極為一致。最重要的是，病患自 2021 年起即開始接受 nex-z 的治療劑量；截至我們最新的數據截止日，病患體內的 TTR 控制維持恆定，且在所有病患接受一次性 nex-z 治療後皆得以維持。

We look forward to presenting updated long-term durability data at future congresses. We believe nex-z's distinct TTR knockdown is why disease stabilization or reversal is observed in most patients in our Phase 1, while our would-be competitors have observed disease progression.

我們期待在未來的學術會議上發表更新的長期持久性數據。我們相信，nex-z 獨特的 TTR 抑制能力，是我們在第 1 期中多數病患觀察到疾病穩定或逆轉、而潛在競爭對手卻觀察到疾病進展的原因。

Additionally, the response has been consistent across patients of all New York Heart Association classes, those with either variant or wild-type disease, and it also includes patients who have progressed on past silencers. And so we continue to have significant confidence in our ability to show a benefit on top of tafamidis and MAGNITUDE.

此外，反應在所有紐約心臟協會（NYHA）分級的病患中皆一致，無論是變異型或野生型疾病皆然，也包括曾在先前沉默劑治療下仍出現進展的病患。因此，我們對於在 tafamidis 與 MAGNITUDE 基礎上展現額外效益的能力，仍保持高度信心。

Additionally, unlike CARDIO-TTRansform, which was a time-bound study, MAGNITUDE's primary endpoint is strictly event-based. We've enrolled well over 650 patients in MAGNITUDE. We've been accruing events for quite some time.

另外，不同於屬於時間界定型研究的 CARDIO-TTRansform，MAGNITUDE 的主要終點嚴格採事件驅動。我們在 MAGNITUDE 中已納入遠超過 650 名病患。我們累積事件已經有相當長一段時間。

And those events continued unabated through the clinical hold. While it's still premature for us to guide as to data timing, what I can say today is that the blinded event rate in the trial remains within the range we'd projected internally. We're looking forward to reviewing the detailed CARDIO-TTRansform data later this month at ESC.

而這些事件在臨床暫停期間仍持續累積、未曾中斷。雖然目前我們仍言之過早，無法就數據時程提供指引，但我今天可以說的是：試驗中盲態事件率仍落在我們內部預估的範圍內。我們期待在本月稍晚於 ESC 會議上檢視 CARDIO-TTRansform 的詳細數據。

And of course, we have the opportunity to consider changes that further optimize MAGNITUDE's design based on what we learn. Now let's move on to one other encouraging update we're able to share today related to nex-z. As we reported late last year, Grade 4 liver transaminase elevations had been observed in less than 1% of patients enrolled in MAGNITUDE. These were transient, and in most cases, they resolved without any intervention.

當然，我們也有機會根據所學，考慮進一步優化 MAGNITUDE 試驗設計的變更。現在讓我們談談今天能分享的另一項與 nex-z 相關、令人鼓舞的更新。如同我們在去年年底所報告，MAGNITUDE 中不到 1% 的受試者觀察到第 4 級肝轉氨酶升高。這些升高是暫時性的，且多數情況下無需任何介入即可恢復。

Based in part on the fact that the observations consistently occurred two to five weeks after dosing, we hypothesized they were caused by an adaptive immune response. As a result, we implemented mitigation measures to enhance monitoring for transaminase elevations and intervene if they are observed. These measures are very straightforward and could easily be implemented in a real-world commercial setting if required. We also went further.

部分基於這些觀察一貫發生在給藥後 2 至 5 週，我們推測其由適應性免疫反應所致。因此，我們導入了緩解措施，以加強對轉氨酶升高的監測，並在觀察到時進行介入。這些措施非常直接，若有需要，也可在真實世界的商業化環境中輕易落實。我們也更進一步。

Working with Regeneron and other external experts, we sequenced and analyzed data from over 600 patient samples across all nex-z clinical trials to date. Our goal was to understand if there were subpopulations that might be most susceptible to higher-grade transaminase elevations. This work focused on HLAs, which are proteins on the surface of cells that play a key role in regulating the immune system and helping to distinguish native and foreign peptides. This blinded analysis revealed one statistically significant finding.

我們與 Regeneron 及其他外部專家合作，對迄今所有 nex-z 臨床試驗中超過 600 份病患樣本的資料進行定序與分析。我們的目標是了解是否存在某些亞族群，可能更容易出現較高等級的轉氨酶升高。此項工作聚焦於 HLA（人類白血球抗原），其為細胞表面蛋白，在調控免疫系統以及協助辨識自體與外來胜肽方面扮演關鍵角色。這項盲態分析揭示了一項具統計顯著性的發現。

Patients carrying one specific HLA allele that's known as C0501 had a significantly higher rate of Grade 3 or greater transaminase elevations than the broader population. In fact, each of the five highest elevations observed following dosing occurred in patients carrying this allele. Now, some important context on what this does and doesn't mean.

攜帶一種特定 HLA 等位基因（稱為 C0501）的病患，其第 3 級或以上轉氨酶升高的發生率，顯著高於整體族群。事實上，給藥後觀察到的最高五個升高值，皆出現在攜帶此等位基因的病患身上。現在，針對這項結果所代表與不代表的意義，提供一些重要背景。

Only 12% of the 600-plus samples we analyzed carry this allele, and the strong majority of C0501-positive patients did not experience severe transaminase elevations. So we continue to see the potential for a favorable benefit/risk profile even in this subgroup, particularly with the mitigation strategy that is now in place.

在我們分析的 600 多份樣本中，僅有 12% 攜帶此等位基因，而且絕大多數 C0501 陽性的病患並未出現嚴重的轉氨酶升高。因此，即便在此亞族群中，我們仍持續看到具利多於弊的效益/風險概況之潛力，尤其是在目前已到位的緩解策略之下。

What the finding gives us is valuable. A mechanistic explanation for a general signal we'd already flagged and a way to identify patients who are more likely to be affected before it happens. In doing so, it further increases our confidence in nex-z's ability to deliver on its long-recognized potential. So here are our next steps. We're engaging with FDA to review the findings. In the meantime, we already have updated our protocols, investigators brochures, and informed consents to incorporate HLA typing for all patients in the Phase 3 trials.

這項發現帶給我們的價值很大。它為我們先前已標記的一般性訊號提供了機轉層面的解釋，也提供了一種在事件發生前辨識較可能受影響病患的方法。如此一來，進一步提升我們對 nex-z 能夠實現其長期被認可之潛力的信心。接下來是我們的下一步。我們正與 FDA 接洽以審視這些發現。同時，我們已更新第 3 期試驗的方案、研究者手冊與知情同意書，將所有病患的 HLA 分型納入其中。

These documents are in the process of being rolled out to regulatory authorities, IRBs, and sites globally. Following the reviews, investigators and patients will be informed about the HLA results during screening or prior to crossover so they can make more informed treatment decisions.

這些文件正逐步推送至全球各地的主管機關、IRB（機構審查委員會）與試驗中心。在完成審查後，研究者與病患將於篩檢期間或交叉治療前獲知 HLA 結果，以便做出更充分知情的治療決策。

And so to close, I'm exceedingly proud of all the team continues to accomplish here at Intellia. We're marching towards the world's first potential launch of an in vivo gene editing therapy with lonvo-z. We're on track to complete enrollment in MAGNITUDE-2 later this year, and we're demonstrating precision medicine at its finest with our HLA work on nex-z. These achievements layer on top of all the other pioneering work we've undertaken as we seek to harness the power of gene editing to deliver optimal treatment outcomes for patients with just one dose.

最後作個總結，我對 Intellia 團隊持續在此所達成的一切感到無比自豪。我們正朝向全球首個潛在上市的體內基因編輯療法 lonvo-z 穩步前進。我們也按計畫在今年稍晚完成 MAGNITUDE-2 的收案，並透過 nex-z 的 HLA 研究展現精準醫療的極致。在我們致力於運用基因編輯的力量、以單次給藥為病患帶來最佳治療結果之際，這些成果也疊加在我們已展開的其他開創性工作之上。

So with that, let's now turn the call over to Ed to share some financial color.

那麼，接下來我們把電話交給 Ed，請他分享一些財務方面的補充說明。

Thank you, John, and hello, everyone. In addition to the tremendous clinical pre-commercial and scientific progress we made in the second quarter, we also kept the company on sound financial footing. In April, we completed an equity financing that yielded approximately $195 million in net proceeds for the company.

謝謝你，John，各位大家好。除了我們在第二季取得的重大臨床（商業化前）與科學進展之外，我們也讓公司維持在穩健的財務狀態。4 月，我們完成了一次股權融資，為公司帶來約 1.95 億美元的淨募資款。

Cash, cash equivalents, and marketable securities were $628.4 million as of June 30, 2026, compared to $605.1 million on December 31, 2025. We believe this cash balance will be sufficient to get us at least into 2028.

截至 2026 年 6 月 30 日，現金、約當現金及有價證券為 6.284 億美元，相較於 2025 年 12 月 31 日的 6.051 億美元。我們相信這個現金餘額足以支應我們至少到 2028 年。

Importantly, while we expect to obtain approval and launch lonvo-z in the US in the first half of 2027, our cash runway guidance is conservative in that it excludes all product revenues. Collaboration revenue was $7.7 million for the second quarter of 2026, compared to $14.2 million for the prior year quarter. This change is primarily due to a reduction in revenue from Regeneron.

重要的是，雖然我們預期在 2027 年上半年於美國取得 lonvo-z 的核准並上市，但我們對現金可支應期間（cash runway）的指引相對保守，因為其中不包含任何產品營收。2026 年第二季的合作收入為 770 萬美元，較去年同期的 1,420 萬美元下降。這項變動主要是因為來自 Regeneron 的收入減少。

R&D expenses were $82.6 million for the second quarter of 2026, compared to $97 million during the prior year quarter. The decrease was primarily driven by lower external costs related to lonvo-z and nex-z and reduced stock-based compensation, partially offset by higher employee-related expenses due to increased headcount. Stock-based compensation expense included in R&D was $9.4 million for the second quarter of 2026.

2026 年第二季研發（R&D）費用為 8,260 萬美元，較去年同期的 9,700 萬美元下降。下降主要由於與 lonvo-z 與 nex-z 相關的外部成本較低，以及以股份為基礎的薪酬減少；但部分被因人員編制增加而帶來的較高員工相關費用所抵銷。計入研發費用的以股份為基礎的薪酬，在 2026 年第二季為 940 萬美元。

G&A expenses were $37.8 million during the second quarter of 2026, compared to $27.2 million for the prior year quarter. This increase was primarily driven by costs associated with the ongoing build-out of our commercial infrastructure, higher legal expenses, and stock-based compensation. Stock-based compensation expense included in G&A was $8.6 million for the second quarter of 2026.

2026 年第二季一般及行政（G&A）費用為 3,780 萬美元，較去年同期的 2,720 萬美元增加。增加主要由於我們持續建置商業化基礎設施所產生的成本、較高的法律費用，以及以股份為基礎的薪酬。計入一般及行政費用的以股份為基礎的薪酬，在 2026 年第二季為 860 萬美元。

And finally, net loss for the second quarter of this year was $106.6 million, which compared with the $101.3 million for the prior year quarter.

最後，今年第二季的淨損失為 1.066 億美元，對比去年同期為 1.013 億美元。

With that, we are ready to begin our question and answer session. Operator, would you please open the line for questions?

那麼，我們已準備好開始問答環節。接線員，麻煩您開放提問。

(Operator Instructions) Maury Raycroft, Jefferies.

（接線員指示）Jefferies 的 Maury Raycroft。

Congrats on the progress and thanks for taking my question. I'll ask one on the allele finding, which is interesting for that C0501 allele. Can you talk about the implications for the 12% of patients where there could be some added risk? And is there another parameter that you could use to help fine-tune patient selection?

恭喜進展，也謝謝讓我提問。我想問一個關於等位基因發現的問題，這個 C0501 等位基因很有意思。你們能談談對於約 12% 病患可能存在額外風險的意涵嗎？另外，是否還有其他參數可以用來協助更精準地微調病患篩選？

And Lastly, is there more you can share on the biologic relationship or what exactly is triggering the immune response?

最後，你們是否能再多分享一些關於生物學上的關聯，或究竟是什麼在觸發免疫反應？

Thanks, Maury, for your question. We think that the finding confirms our initial thinking about an adaptive immune response. As many will know, HLAs are deeply implicated in cell-mediated immunity, and this would be an important part of understanding what we saw with our early observations with timing of the immune response. So it gives us significant confidence that the mitigation measures that we put in place are appropriate and are on target for what seems to be going on.

謝謝你的問題，Maury。我們認為這項發現確認了我們最初對適應性免疫反應的判斷。如同許多人所知，HLA 與細胞媒介免疫密切相關，而這將是理解我們早期觀察到免疫反應發生時點的重要一環。因此，這讓我們對已採取的緩解措施更有信心，因為這些措施看起來與實際發生的機制相符、也切中要點。

With respect to the patients that carry 0501, as I said in my comments during the earlier portion of the call here, we're making that information available to all investigators and patients. There's a relationship that's significant, but many of the patients that carry 0501 do not have ALT elevations.

至於攜帶 0501 的病患，正如我在先前通話前段的評論中所說，我們會把這項資訊提供給所有研究者與病患。兩者之間存在顯著關聯，但許多攜帶 0501 的病患並沒有 ALT 升高。

The first order of business is to make sure that if patients have that, they're aware of it, and they can discuss the elevated risk with their physicians and make a determination of what's appropriate for them. Our expectation, just based on conferring with our steering committee members and people, the experts that we've been working on this during the course of our findings, is that many of the patients may choose to self-exclude, and that's appropriate for them.

首要之務是確保若病患具有該等位基因，他們能知情，並可與其醫師討論風險升高的情況，進而判斷什麼做法最適合他們。根據我們與指導委員會成員以及在本次發現過程中合作的專家們討論的結果，我們的預期是，許多病患可能會選擇自行排除（不參與），而這對他們而言是合適的。

For those who believe that the state of their disease and the other opportunities available to them warrant continuing to receive the therapy and advancing the trial, we're making the drug available for them. As we continue to learn during the course of our trial, we discuss with the FDA these findings and any further implications.

對於那些認為自身疾病狀態以及其他可用選項仍值得繼續接受治療並推進試驗的病患，我們會讓他們可以取得藥物。隨著我們在試驗過程中持續學習，我們也會與 FDA 討論這些發現及任何進一步的影響。

But in the meanwhile, we think that this will give enhanced confidence to the physicians and patients who are entering that they can derive the best possible outcome, all things considered.

但同時，我們認為這將提升醫師與病患在入組時的信心，使他們在綜合考量下能獲得最佳可能的結果。

Joseph Thome, TD Cowen.

TD Cowen 的 Joseph Thome。

Hey, this is Jacob on for Joe. Thanks for taking our question. Just sticking with the HLA allele, wanted to confirm that this was something specific to nex-z and not lonvo-z. And then also you said, I believe that it was 12% of the 600 samples that carried the allele, but only a fraction of that 12% actually had elevations. Is that correct?

嗨，我是代 Joe 提問的 Jacob。謝謝讓我們提問。延續 HLA 等位基因的問題，我想確認這是 nex-z 特有的現象，而不是 lonvo-z。另外，你們提到我記得是 600 份樣本中有 12% 攜帶該等位基因，但其中只有一部分的 12% 實際出現升高。這樣理解正確嗎？

Yes. In my comments, I said that across the study, there's about 12% of patients who carry the C0501, and that broadly reflects what's seen in a North American, Western European population. There will be some variance across different ethnic groups, with numbers sometimes lower than that, but that's what we've observed in the study.

是的。在我的評論中我提到，整個研究中約有 12% 的病患攜帶 C0501，這大致反映北美與西歐族群中所見的比例。不同族群之間會有一些差異，有時比例會低於此，但這是我們在研究中觀察到的結果。

With respect to specificity, almost certainly this would be specific to nex-z and not have any implications for lonvo-z. There's a couple reasons for that. When you think about what an HLA molecule is, it binds to a very specific short peptide, and we wouldn't expect those peptides to be implicated in any way with the lonvo-z treatment effect. So that's further supported by the fact that, as shown in the New England Journal publication that was recently released, there's no signal in patients with lonvo-z.

至於特異性，幾乎可以確定這會是 nex-z 特有，且不太可能對 lonvo-z 有任何影響。原因有幾點。當你思考 HLA 分子是什麼時，它會結合一段非常特定的短胜肽，而我們不預期這些胜肽會以任何方式與 lonvo-z 的治療效果相關。此外，近期發表於《新英格蘭醫學期刊》的論文也支持這點：在使用 lonvo-z 的病患中沒有出現任何訊號。

At this point, we think that this is just a finding that's going to be limited to nex-z.

目前我們認為，這項發現將僅限於 nex-z。

I'll just add one thing, John. I think there's a comment about just the vast majority of those patients that had 0501 did not experience severe transaminase elevations. So 12% of the samples do represent those that are carrying the allele, but only a small subset have had these higher grade elevations.

John，我再補充一點。我想強調的是，絕大多數攜帶 0501 的病患並未出現嚴重的轉胺酶升高。因此，樣本中 12% 代表的是攜帶該等位基因的人，但只有其中一小部分出現了這些較高等級的升高。

Luca Issi, RBC Capital Markets.

RBC Capital Markets 的 Luca Issi。

Congrats, obviously, on all the progress. Obviously, we have yet to see the full CARDIO-TTRansform trial. I'm looking forward to that data at European Society of Cardiology. But I think, John, you already mentioned potential to maybe optimizing your trial to maximize the probability of success. Can you just talk about what are the options that you're contemplating at this point? Can you enroll more patients? Can you extend the minimum follow-up longer than 18 months? I don't know. Can you limit the use of SGLT2? Like just walk us through a big picture how you're thinking about potentially tweaking your trial. Thanks so much.

恭喜，顯然你們取得了很多進展。我們顯然還沒看到完整的 CARDIO-TTRansform 試驗結果。我很期待在歐洲心臟病學會（European Society of Cardiology）看到那些數據。不過我想，John，你已經提到可能會優化試驗設計以最大化成功機率。你能談談目前正在考慮哪些選項嗎？你們能納入更多病患嗎？你們能把最短追蹤期延長到超過 18 個月嗎？我不確定。你們能限制 SGLT2 的使用嗎？請從宏觀角度帶我們了解你們如何思考可能調整試驗的方向。非常感謝。

Thanks for the question, Luca. The first order of business is really understanding the data that comes from the CARDIO-TTRansform study. As I said in the prepared comments, we believe, based on everything we know thus far, that the findings are likely specific to eplontersen and not generally applicable to how we think about treatment of patients with TTR disease or patients receiving combination therapy.

謝謝你的提問，Luca。首要之務其實是理解來自 CARDIO-TTRansform 研究的數據。如我在事先準備的評論中所說，基於我們目前所知的一切，我們相信這些發現很可能是 eplontersen 特有的，而非普遍適用於我們如何看待 TTR 疾病患者的治療或接受合併療法的患者。

What we think is going to be the most important information is the degree to which TTR is reduced, the variability or lack thereof, as we see in our own patients, the speed with which treatment effect is achieved, and then obviously the durability as patients go through the many months of observation where variability may be attributable to pharmacokinetics or interruptions for toxicity, for example.

我們認為最重要的資訊將是 TTR 降低的幅度、變異程度或缺乏變異（如我們在自身患者中所見）、達到治療效果的速度，然後當然還有在患者經歷多個月觀察期間的持久性；在此期間，變異可能可歸因於藥物動力學或例如因毒性而中斷治療。

All of those elements will erode the overall treatment effect and it's important, I think, to really understand that before we jump to conclusions about combination therapy and how best to use it. But with an understanding in hand, and we will of course work with experts who are deep in the data. We'll consider if there's anything that we need to change.

所有這些要素都會削弱整體治療效果，因此我認為在我們對合併療法及其最佳使用方式下結論之前，確實理解這些非常重要。但在掌握了這些理解之後，我們當然會與深入研究數據的專家合作。我們會評估是否有任何需要改變之處。

We remain open-minded. We adapt as necessary; we certainly try to learn at a prodigious rate as information becomes available. The factors that you mentioned are possible to change. But we don't start with a thesis in mind until we have a really good understanding of the data. And like you all on this call, and many others, we're very anxious to see what that information is before we make any changes.

我們仍保持開放的心態。我們會視需要調整；隨著資訊出現，我們確實努力以極快的速度學習。你提到的因素是有可能改變的。但在我們對數據有非常充分的理解之前，我們不會先入為主地帶著一個論點。而且和在這通電話上的各位以及許多人一樣，在做出任何改變之前，我們也非常急切想看到那些資訊。

Salveen Richter, Goldman Sachs.

Salveen Richter，高盛。

Can you remind us of the background stabilizer used in the study and if you expect that to change given recent CARDIO-TTRansform results? Also, on the HLA filing finding, do you see enrollment changes just given screening for HLA? Thank you.

你能提醒我們研究中使用的背景穩定劑是什麼嗎？鑑於近期 CARDIO-TTRansform 的結果，你是否預期這會有所改變？另外，關於 HLA 申報的發現，你是否認為僅因為進行 HLA 篩檢就會影響入組情況？謝謝。

Thanks for the question, Salveen. Background stabilizer use is running around 80%, which is what we projected when we set out and what we've been confirming on various data releases along the way. And so that does not appear to be changing one way or the other. I think it reflects how stabilizers are broadly used around the world and obviously in sites where we're doing the investigation.

謝謝你的提問，Salveen。背景穩定劑的使用率約在 80% 左右，這與我們啟動時的預估一致，也是在過程中各次數據釋出時持續得到確認的。因此看起來並沒有朝任何方向改變。我認為這反映了穩定劑在全球的廣泛使用情況，當然也包括我們進行研究的各個中心。

With respect to HLA, as we talk to investigators and people who we're working with in this trial, most of them view this as confidence building in terms of how to think about patients and who to enter and potentially who to exclude should the patient or the doctor think that that's the most appropriate course of action for any particular patient.

至於 HLA，當我們與本試驗的研究者以及合作夥伴交流時，他們多數認為這有助於建立信心，讓大家更清楚如何看待患者、應納入哪些患者，以及在患者或醫師認為對特定患者最合適時，可能應排除哪些患者。

But across the board, as we've gone through the data with people who are practicing cardiologists and experts in the field, to a person, all of them have viewed this as a very favorable finding that enhances overall confidence. And our job now is to make that information available to those doctors and physicians in the trial and patients in the trial as quickly as possible, and that's well underway.

但整體而言，當我們與臨床心臟科醫師及領域專家一起檢視數據時，所有人無一例外都認為這是一項非常正面的發現，能提升整體信心。而我們現在的工作，是盡快把這些資訊提供給試驗中的醫師與研究者，以及試驗中的患者；這項工作正在積極推進中。

Silvan Tuerkcan, Citizens.

Silvan Tuerkcan，Citizens。

Maybe can you talk a little bit about the patient gateway that you're building with HAEreframed and is that more to get data points to you for potential later marketing or is that to push a message out around some of these endpoints where one-time treatment could be helpful, and if so, what are those? And maybe related to that, what can we see at the Bradykinin Symposium data that's coming up here? Thank you so much.

或許你能談談你們透過 HAEreframed 正在建立的患者入口（patient gateway）？這更多是為了蒐集資料點以利未來可能的行銷，還是為了對外傳遞一些訊息，說明一次性治療在某些終點上可能有幫助？如果是，具體是哪些？另外相關地，我們在即將到來的 Bradykinin Symposium 上可以看到哪些數據？非常感謝。

Let me speak first to the symposium that you referenced. You'll remember that across the entire HAE program, virtually every single patient at some point gets to something that resembles no attacks and no therapy. It takes some patients longer to get there than others, but virtually everybody ceases to use Long-Term Prophylaxis, and almost all the patients no longer require on-demand therapy.

我先談你提到的研討會。你會記得，在整個 HAE 計畫中，幾乎每一位患者在某個時間點都會達到一種近似「無發作、無治療」的狀態。有些患者需要更長時間才能達到，但幾乎所有人都會停止使用長期預防（Long-Term Prophylaxis），而且幾乎所有患者也不再需要按需治療。

They may carry it with them, but the overall utilization for these patients really plummets, which we think is exciting for the patients, for the doctors, and certainly for the payers who are supporting these patients. At the symposium, we'll go through what we think is very important information for how the drug behaves from a molecular level and how you can trace that with respect to the high-molecular-weight kininogen.

他們可能仍會隨身攜帶，但這些患者的整體使用量確實大幅下降；我們認為這對患者、醫師，當然也對支持這些患者的支付方而言都令人振奮。在研討會上，我們會說明我們認為非常重要的資訊：藥物在分子層級的作用方式，以及你如何就高分子量激肽原（high-molecular-weight kininogen）來追蹤這些變化。

That has specific reference to one particular patient who had a significant benefit from the drug but did not reach an attack-free status. And the long and short of it is, the patient probably has a second process, unrelated HAE, and we'll speak to that. So I think that's really exciting information that speaks to one particular patient who stood out from the vast majority of patients who have all done very well.

這特別涉及一位特定患者：他從藥物中獲得了顯著益處，但並未達到無發作狀態。簡而言之，該患者可能存在第二個與 HAE 無關的病理過程，我們會就此說明。因此我認為這是非常令人興奮的資訊，聚焦於一位在絕大多數表現都非常好的患者之中、相對突出的個案。

With respect to the website, we're trying to make sure that people have a good understanding of what the burden of HAE really is. We typically talk about disease attacks and the efficacy and safety of drugs that they receive.

至於網站，我們希望確保大家能充分理解 HAE 的真實負擔。我們通常談的是疾病發作，以及患者所接受藥物的療效與安全性。

But what's left out of the discussion many times is what patients have to go through just to get that and stay on their therapy, and still how HAE continues to affect their lives, because for all practical purposes, they continue to suffer from the disease. So by having a better understanding of what patients need to do to get the drug on a recurring basis, sometimes requiring prior authorizations even twice in a year.

但很多時候討論中被忽略的是：患者為了取得治療並持續用藥，必須經歷哪些流程；以及即便如此，HAE 仍如何持續影響他們的生活，因為就實際情況而言，他們仍在承受疾病的折磨。因此，透過更深入理解患者為了反覆取得藥物所需做的事情（有時甚至一年需要事前授權兩次），

We want to make sure that payers, patients, and doctors have a really good understanding of what that burden is. And the when they see the profile of lonvo-z, the contrast will be very apparent.

我們希望確保支付方、患者與醫師都能非常清楚地理解這種負擔。而當他們看到 lonvo-z 的特徵概況時，對比將會非常明顯。

Leah Cann, Brookline Capital Markets.

Leah Cann，Brookline Capital Markets。

My question has been answered.

我的問題已經被回答了。

Jonathan Miller, Evercore ISI.

Jonathan Miller，Evercore ISI。

Yuanyuan for John. Thanks for taking my question. I would like to double-click on the allele analysis. Two questions. First, how many patients with Grade 3 liver signals do not carry the allele? And are there any patients with lower grade signals that actually carry the allele?

我是 Yuanyuan，代 John 提問。謝謝讓我提問。我想更深入追問等位基因分析。兩個問題。第一，有多少出現 3 級肝臟訊號的患者並不攜帶該等位基因？以及是否有任何較低等級訊號的患者其實攜帶該等位基因？

And the second question is, are you considering additional prophy for patients carrying the C0501 allele? What are the additional risks to consider for those carriers? And any particular bad antigens on the cell surface that has caught your attention that may be relevant for the liver injuries? Thanks.

第二個問題是，你們是否正在考慮為攜帶 C0501 等位基因的患者採取額外的預防措施（prophy）？對於這些攜帶者，還需要考量哪些額外風險？以及在細胞表面是否有任何特別不利的抗原引起你們注意，可能與肝損傷相關？謝謝。

Yes. Thank you for the question. With respect to the full data set and the analysis, we'll release that information at the appropriate time, go through the molecular findings, the statistics that support that, et cetera. And that's not something that we're in a position to do today. You asked, are we doing something different for patients who choose to participate in a study if they're 0501 positive?

是的。謝謝你的提問。關於完整數據集與分析，我們會在適當的時間釋出相關資訊，並說明分子層面的發現、支持該結論的統計等。這不是我們今天能做到的。你問到：對於選擇參與研究且 0501 陽性的患者，我們是否會採取不同做法？

And at this point, the answer to that is no. We believe the mitigation measures that are put in place are entirely appropriate for a cell-mediated immune adaptive response, which now we have some increased confidence that that's exactly what's occurring in these patients with these high LFT elevations.

目前答案是否定的。我們認為已採取的風險緩解措施，對於細胞媒介的免疫適應性反應而言完全適當；而現在我們更有信心，這正是這些出現高 LFT 升高患者所發生的情況。

But what we have found is that we can identify patients before the event occurs and give them the opportunity not to participate, recognizing that the likelihood of their having one of these increases is higher, substantially higher than the broader patient population.

但我們發現的是，我們可以在事件發生之前識別出患者，並給他們選擇不參與的機會；因為我們知道，他們出現這類升高的可能性更高，且顯著高於更廣泛的患者族群。

To flip it around, I think a helpful way to think about this is for the approximately 90% of people who don't carry 0501, the likelihood of a high LFT elevation is extremely low. And that is confidence-building for anyone who may wonder about what the likelihood might be for them, given the general data that's been released previously. And as was stated earlier, even for the 0501s, most patients will not have the elevations, but we do know that when they do occur, these tend to be the ones that are most severe.

反過來看，我認為一個有助於理解的方式是：對於約 90% 不帶有 0501 的人而言，發生高幅度 LFT（肝功能檢驗）升高的機率極低。而這對於任何可能在想、基於先前已公布的一般資料自己會有多大機率的人來說，是能建立信心的。並且如先前所述，即使是 0501 攜帶者，多數病人也不會出現升高；但我們確實知道，一旦發生，往往就是最嚴重的那些。

Terence Flynn, Morgan Stanley.

Terence Flynn，摩根士丹利。

This is Chris on for Terence. Thank you for taking our question. Maybe just double-click on the HLA genotyping finding. Just kind of looking ahead, do you expect that to be potentially on the label if approved? And then in the commercial setting, do you expect every patient to get genotyped? Thank you.

我是 Chris，代 Terence 發言。謝謝你們回答我們的問題。想再深入追問一下 HLA 基因分型的發現。往前看，如果獲批，你們預期這可能會寫進標籤（仿單）嗎？另外在商業化情境下，你們預期每位病人都會做基因分型嗎？謝謝。

I think it's too early to say. Oftentimes, as you well know, labels reflect many of the aspects of how clinical trials are done and the data that they accumulate. But that's a bridge that we'll pass when we get to that point. I think in the meanwhile, what we're excited about and what our investigators are excited about is that this will give really good information with respect to how to focus in the best possible way, the benefit-risk on those patients who can most benefit from it.

我認為現在還太早下定論。如你所知，仿單往往會反映臨床試驗的許多執行方式以及所累積的資料。但那是等我們走到那一步再處理的事。同時，我們以及研究者都很振奮的是，這將提供非常好的資訊，讓我們能以最佳方式聚焦於那些最能受益的病人，並評估其效益—風險。

We will collect information during the screening process in the study. We don't think that it will slow down screening at all. This is a relatively straightforward process, and many of our investigators believe that this will actually pick up the pace of screening, which is already rapidly accelerating.

我們會在研究的篩選流程中收集資訊。我們不認為這會讓篩選速度變慢。這是一個相對直接的流程，而且許多研究者相信，這實際上會加快篩選進度，而目前篩選本來就正在快速加速。

So we are very excited about this finding and the very positive things it can do for us.

因此我們對這項發現，以及它能為我們帶來的非常正面的影響，感到非常興奮。

Myles Minter, William Blair.

Myles Minter，William Blair。

I've been getting a few inbounds since you published in the New England Journal on lonvo-z in HAE in the supplement. You show the ALT ASTs over time. I think in the ASTs at week 30 to 32 in patients that got lonvo-z first up at randomization, it looks pretty benign to me, but there are three patients that have got an excursion outside of the reference range. Is that just variability or is there something else going on there at the later stages? Thanks very much.

自從你們在《新英格蘭醫學期刊》補充資料中發表 lonvo-z 用於 HAE 的內容後，我收到一些詢問。你們展示了 ALT、AST 隨時間的變化。我看在第 30 到 32 週、於隨機分派時先接受 lonvo-z 的病人之 AST 變化，對我來說看起來相當溫和，但有三位病人的數值曾超出參考範圍。那只是變異性，還是後期有其他狀況在發生？非常感謝。

Yes. Thanks for the question, Myles. The data's laid out in the New England Journal for anybody who wants to see it. Across the entire program, there's never been an LFT elevation greater than Grade 2. Of those, there are other confounding reasons to consider them. In one case, as you're referring to, this is somebody late, many months after receiving the drug, and this is almost certainly related to another thing that was occurring for the patient, and that's what his investigator thought.

是的。謝謝你的問題，Myles。資料已在《新英格蘭醫學期刊》中列出，任何想看的人都可以查閱。在整個計畫中，從未出現超過第 2 級（Grade 2）的 LFT 升高。而在那些案例中，也有其他混雜因素需要納入考量。其中一例如你所指，是在用藥後很晚、數個月之後才出現的個案，幾乎可以確定與病人當時發生的其他狀況有關，這也是其研究者的看法。

The elevation was benign. Nothing was done with respect to it, and it was low grade. For other patients that we've reported in the various stages of active clinical observation, patients either were confounded by the ongoing use of alcohol with one patient with a Grade 2 that resolved rapidly.

該升高是良性的。對此沒有做任何處置，而且屬於低等級。至於我們在不同階段的主動臨床觀察中所報告的其他病人，有些個案受到混雜因素影響，例如其中一位第 2 級個案與持續飲酒有關，且很快就恢復。

And in a second case, again, reported in the Phase 3 study here, a patient had LFT elevations during the screening phase and had a Grade 2 elevation with a concomitant viral infection. Across the board, we see no signal. There's variability, as we all know about patients, how they live their lives. We're very excited about the efficacy and the safety profile of the drug as we move towards what we hope will be BLA approval.

第二個案例同樣是在此第 3 期研究中報告：一位病人在篩選期就有 LFT 升高，且在合併病毒感染的情況下出現第 2 級升高。整體而言，我們沒有看到任何訊號。如大家所知，病人之間存在變異性，也與他們的生活方式有關。隨著我們朝向（我們希望的）BLA 核准邁進，我們對該藥物的療效與安全性特徵感到非常振奮。

Yanan Zhu, Wells Fargo.

Yanan Zhu，富國銀行。

This is Jeff on for Yanan. Thanks for taking our questions. For the lonvo-z BLA, can you mention if the final BLA has been submitted to the FDA, and if not, which remaining modules need to be completed? And based on your conversations with clinical sites for lonvo-z, are you expecting a bolus of patients at launch if approved? Thanks.

我是 Jeff，代 Yanan 提問。謝謝你們回答我們的問題。關於 lonvo-z 的 BLA，你們能否說明最終版 BLA 是否已提交 FDA？如果尚未，還有哪些模組需要完成？另外，根據你們與 lonvo-z 臨床試驗中心的對話，若獲批，你們是否預期上市初期會有一波病人湧入？謝謝。

We are far into the BLA filing. And I would anticipate that the next time you'll hear from us, we'll be announcing what we hope will be the acceptance of the BLA. And with that, we'll all gain a lot more information with respect to PDUFA dates, priority review, and things like that. So we've been excited with the team's preparation, the very rapid and efficient way that they've been able to work with the FDA, and we're very excited about the progress that we've made.

我們的 BLA 申報已進行到相當後期。我預期你們下次聽到我們的消息時，我們會宣布我們所希望的——BLA 已被受理（acceptance）。屆時，我們也將獲得更多關於 PDUFA 日期、優先審查等事項的資訊。因此，我們對團隊的準備感到振奮，他們能以非常快速且高效率的方式與 FDA 合作，我們也對目前取得的進展感到非常興奮。

(Operator Instructions) Andy Chen, Wolfe Research.

（接線員指示）Andy Chen，Wolfe Research。

This is Jason taking it for Andy. Wanted to ask really quickly about the HLA genotyping, if this is specific for ATTR-CM, or do we see this in other indications, like maybe ATTRv-PN? Do we see any sort of genotyping for maybe some of your other trials coming up? Thank you.

我是 Jason，代 Andy 提問。想很快問一下 HLA 基因分型：這是否僅針對 ATTR-CM，或我們在其他適應症（例如 ATTRv-PN）也會看到？另外，你們接下來的一些其他試驗，是否也會看到某種基因分型？謝謝。

Thank you. We're not currently doing genotyping on a standard basis for any program that we begin. We don't think that that would be necessary, and it would be hard to know what to look for, as we believe that what we're finding here is a very specific finding. Could you repeat your first question? Maybe Ed, if you heard it. I didn't hear one.

謝謝。我們目前並未在任何新啟動的計畫中以標準作業方式進行基因分型。我們不認為那是必要的，而且也很難知道該找什麼，因為我們相信這次的發現非常特定。你可以重複一下你的第一個問題嗎？也許 Ed，如果你有聽到。我沒有聽到第一個問題。

Your line is open now, Andy.

Andy，你的線路現在已開通。

Thank you. I just wanted to ask if this genotyping was unique for ATTR-CM, and maybe if it's usable in polyneuropathy. Thank you.

謝謝。我只是想問，這個基因分型是否是 ATTR-CM 特有的，以及是否也可用於多發性神經病變（polyneuropathy）。謝謝。

No, the genotyping is done across the entire program, irrespective of the indication. And we're treating it as a relevant finding for both polyneuropathy and for cardiomyopathy and are applying the same rules and providing the same information for both studies.

不是，基因分型是在整個計畫中進行的，不論適應症為何。我們將其視為對多發性神經病變與心肌病變都相關的發現，並對兩項研究採用相同規則並提供相同資訊。

This concludes our question and answer session. I would like to turn the conference back over to Jason Fredette for any closing remarks.

問答環節到此結束。我想把會議交回給 Jason Fredette，請他做結語。

Thanks, operator, and thanks everyone for joining us. We hope you have a great end to the summer. And we'll look forward to seeing many of you at the upcoming conferences in September. That concludes the call.

謝謝接線員，也謝謝各位加入。祝各位夏末愉快。我們期待在 9 月即將到來的各場會議上見到各位。本次電話會議到此結束。

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.

本次會議現已結束。感謝各位參加今天的簡報。您現在可以掛線。