X4 Pharmaceuticals Inc (XFOR) 2023 Q4 法說會逐字稿

Greetings, and welcome to the X4 Pharmaceuticals fourth-quarter and full-year 2023 financial and operating results conference call. (Operator Instructions) As a reminder, this conference is being recorded.

您好，歡迎參加 X4 Pharmaceuticals 第四季和 2023 年全年財務和營運業績電話會議。（操作員指示）謹此提醒，本次會議正在錄製中。

It is now my pleasure to introduce your host, Dan Ferry from LifeSci Advisors. Please begin.

現在我很高興向您介紹主持人，來自 LifeSci Advisors 的 Dan Ferry。請開始。

Thank you, operator, and good morning, everyone.

謝謝接線員，大家早安。

Presenting on today's call will be X4's Chief Executive Officer, Dr. Paula Ragan; and Chief Financial Officer, Adam Mostafa. Following prepared remarks by each, we will open the call to your questions, and we'll be joined by Chief Commercial Officer, Mark Baldry; Chief Medical Officer, Dr. Christophe Arbet-Engels; Chief Operating Officer; Mary DiBiase; and Chief Scientific Officer, Art Taveras.

X4 執行長 Paula Ragan 博士將出席今天的電話會議；財務長 Adam Mostafa。在每個人準備好發言後，我們將開始電話詢問您的問題，商務長 Mark Ba​​ldry 也將加入我們。首席醫療官 Christophe Arbet-Engels 博士；營運長;瑪麗·迪比亞斯；兼 Art Taveras 首席科學官。

As a reminder, on today's call, the company will be making forward-looking statements regarding regulatory and product development plans, as well as research activities. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted. Description of these risks can be found in X4's most recent filings with the SEC, including this year's Form 10-K, which is expected to be filed after market close today.

提醒一下，在今天的電話會議上，該公司將就監管和產品開發計劃以及研究活動發表前瞻性聲明。這些陳述存在風險和不確定性，可能導致實際結果與預測不同。這些風險的描述可以在 X4 最近向 SEC 提交的文件中找到，包括今年的 10-K 表格，預計將於今天收盤後提交。

I'd now like to turn the call over to X4's President and CEO, Dr. Paula Ragan. Paula?

我現在想將電話轉給 X4 的總裁兼執行長 Paula Ragan 博士。寶拉？

Thanks, Dan. Good morning, everyone, and thank you for joining us on the call today. As we look ahead to 2024, we thought we'd take the time to reflect on all that we've accomplished over the past year, milestones that have set the stage for what we expect will be an incredibly exciting and truly transformative year for X4, a year where we aim to become a fully integrated research, development, and commercialization company with the goal of delivering new options for rare disease patients.

謝謝，丹。大家早安，感謝您今天加入我們的電話會議。當我們展望 2024 年時，我們認為我們應該花時間反思過去一年所取得的所有成就，這些里程碑為我們預計 X4 將是令人難以置信的激動人心且真正變革的一年奠定了基礎，這一年我們的目標是成為一家完全一體化的研究、開發和商業化公司，目標是為罕見疾病患者提供新的選擇。

Throughout 2023, we hit several major milestones; most importantly, submission and acceptance under FDA's priority review process of our NDA seeking approval of mavorixafor, our oral targeted CXCR4 antagonist for the treatment of WHIM syndrome. As you may recall, WHIM is a rare combined primary immunodeficiency caused by genetic variations to the CXCR4 receptor. The CXCR4 pathway helps regulate the migration of white blood cells, including neutrophils and lymphocytes, into the bloodstream.

2023 年，我們實現了幾個重大里程碑；最重要的是，根據 FDA 優先審查程序提交並接受了我們尋求批准 mavorixafor 的 NDA，mavorixafor 是我們用於治療 WHIM 綜合徵的口服靶向 CXCR4 拮抗劑。您可能還記得，WHIM 是一種罕見的聯合原發性免疫缺陷疾病，由 CXCR4 受體的遺傳變異引起。CXCR4 路徑有助於調節白血球（包括嗜中性球和淋巴球）遷移到血液中。

WHIM is named for its four most common manifestations: warts, which are typically caused by unresolved HPV infections; hypogammaglobulinemia or low levels of antibodies; infections, both viral and bacterial; and myelokathexis or retention of white blood cells in the bone marrow. Diagnosis of WHIM has historically proven challenging because only a minority of patients actually experience all four manifestations in the acronym, although not all symptoms are required for diagnosis.

WHIM 因其四種最常見的表現而得名： 疣，通常由未解決的 HPV 感染引起；低丙種球蛋白血症或抗體水平低；病毒和細菌感染；以及骨髓中白血球滯留或骨髓滯留。歷史上 WHIM 的診斷被證明具有挑戰性，因為只有少數患者實際上經歷了縮寫詞中的所有四種表現，儘管診斷並不需要所有症狀。

The most challenging burden faced by people with WHIM syndrome results from their low blood levels of neutrophils, or neutropenia, and low blood levels of lymphocytes, or lymphopenia, which research supports are experienced by essentially all WHIM patients. As a consequence of neutropenia and lymphopenia, an estimated 92% of WHIM patients experience frequent recurrent infections that significantly impact their health and quality of life.

WHIM 症候群患者面臨的最具挑戰性的負擔是由於血液中中性粒細胞水平低（或稱中性粒細胞減少症）和血液中淋巴細胞水平低（或稱為淋巴細胞減少症），研究支持基本上所有WHIM 患者都會經歷這種情況。由於中性粒細胞減少症和淋巴細胞減少症，估計 92% 的 WHIM 患者會經歷頻繁的複發性感染，這嚴重影響了他們的健康和生活品質。

Over time, WHIM patients with recurrent infections may experience debilitating and life-threatening complications, including increased cancer risk, irreversible end organ damage, and/or sepsis. I mention this not only to emphasize the incredible burden of disease for these patients and their caregivers, but also to highlight that mavorixafor has been granted breakthrough therapy designation by the FDA, indicating their recognition of mavorixafor as a product candidate with the potential to provide substantial improvement over the standard of care in the treatment, diagnosis, or prevention of a serious condition.

隨著時間的推移，反覆感染的 WHIM 患者可能會出現衰弱和危及生命的併發症，包括癌症風險增加、不可逆的終末器官損傷和/或敗血症。我提到這一點不僅是為了強調這些患者及其照護者所承受的令人難以置信的疾病負擔，也是為了強調mavorixafor 已被FDA 授予突破性治療指定，表明他們認可mavorixafor 作為候選產品，有潛力提供實質的幫助。改善治療、診斷或預防嚴重疾病的護理標準。

So we were very pleased to have reported on the additional positive safety and efficacy results from our completed global pivotal Phase 3 trial in WHIM in May of last year and further analyses of the trial at several important medical meetings and congresses, both last year and earlier this year. Publication of the full 4WHIM trial results is currently pending at a highly respected international medical journal.

因此，我們非常高興地報告了去年5 月在WHIM 中完成的全球關鍵3 期試驗的額外積極的安全性和有效性結果，以及去年和早些時候在幾次重要的醫學會議和代表大會上對該試驗的進一步分析。今年。完整的 4WHIM 試驗結果目前正在等待在一家備受推崇的國際醫學雜誌上發表。

As you know, the Phase 3 trial successfully met its primary endpoint and several key secondary endpoints, with participants on mavorixafor achieving statistically significant elevations in both their neutrophil and lymphocyte counts versus placebo and, importantly, statistically significant reductions in the rate of annualized infections and clinically meaningful reductions in the severity and duration of infections versus placebo. Based on these results, we submitted our first NDA to the FDA in late August of last year, receiving notice of acceptance for priority review, setting a target PDUFA date of April 30, which is fast approaching.

如您所知，3 期試驗成功地達到了其主要終點和幾個關鍵的次要終點，與安慰劑相比，mavorixafor 參與者的中性粒細胞和淋巴細胞計數均實現了統計上顯著的升高，重要的是，年化感染率和死亡率均顯著降低。與安慰劑相比，感染的嚴重程度和持續時間有臨床意義的降低。基於這些結果，我們在去年 8 月下旬向 FDA 提交了第一份 NDA，收到了優先審查接受通知，將 PDUFA 的目標日期定為 4 月 30 日，這一日期即將到來。

As you can well appreciate, we've been incredibly busy preparing for this potential approval since we spoke with you last year. We've been having discussions with our payers, multiple meetings with FDA, and finalizing our supply and distribution arrangements to be ready in the event that we receive FDA approval.

正如您所理解的，自從去年與您交談以來，我們一直忙於為這項潛在的批准做準備。我們一直在與付款人進行討論，與 FDA 進行多次會議，並最終確定我們的供應和分銷安排，以便在獲得 FDA 批准時做好準備。

Our commercial and medical affairs organizations have grown meaningfully, although prudently, as we've continued to build our brand marketing and sales infrastructure to increase our presence at medical meetings and engage with our targeted hematologists and immunologists that we expect to have WHIM patients under their care. We look forward to leveraging our rare disease commercial capabilities to start building the WHIM market over time, with 2024 as the year to lay the foundation for future success and, looking beyond 2024, as we are successful in educating physicians, helping them identify WHIM patients and build demand for our product candidate.

我們的商業和醫療事務組織雖然謹慎，但卻取得了有意義的發展，因為我們繼續建立我們的品牌行銷和銷售基礎設施，以增加我們在醫學會議上的影響力，並與我們的目標血液學家和免疫學家接觸，我們希望將WHIM 患者納入他們的研究範圍。關心。我們期待利用我們的罕見疾病商業能力，隨著時間的推移開始建立 WHIM 市場，2024 年將為未來的成功奠定基礎，展望 2024 年之後，我們將成功地教育醫生，幫助他們識別 WHIM 患者並建立對我們候選產品的需求。

WHIM syndrome is a very rare form of combined immunodeficiency first described over 60 years ago in the medical literature. Given its rarity and lack of available therapies, disease awareness amongst our targeted physician audience has historically been quite low, with no approved treatments for WHIM and only supportive care for symptomatic management, not addressing the underlying cause of the disease.

WHIM 症候群是一種非常罕見的聯合免疫缺陷形式，60 多年前首次在醫學文獻中被描述。鑑於其稀有性和缺乏可用的治療方法，我們的目標醫生受眾對疾病的認識歷來相當低，沒有批准針對 WHIM 的治療方法，僅對症狀進行支持性治療，而沒有解決疾病的根本原因。

With our successful Phase 3 WHIM trial recently being presented at major medical conferences, we are very encouraged that the physician community is now gaining more awareness. Additionally, we've experienced strong engagement with our What If It's WHIM? disease awareness campaign, which is also demonstrating an even broader interest in WHIM syndrome.

隨著我們最近在主要醫學會議上成功展示了 3 期 WHIM 試驗，我們感到非常鼓舞的是，醫生界現在獲得了更多的認識。此外，我們也體驗到了「如果這是突發奇想怎麼辦？」的強烈參與度。疾病意識運動，這也顯示人們對 WHIM 症候群有更廣泛的興趣。

At the ASH Meeting in December, the organizers made a point of highlighting the need for new research and development in classical hematological diseases. At the meeting, our Chief Medical Officer, Dr. Christophe Arbet-Engels, gave a talk on the lack of innovation and the need for new treatments at the meeting. His presentation was enthusiastically welcomed by a standing room only audience.

在 12 月的 ASH 會議上，組織者強調了經典血液疾病新研究和開發的必要性。在會議上，我們的首席醫療官Christophe Arbet-Engels博士在會議上就缺乏創新和需要新療法進行了演講。他的演講受到了全場觀眾的熱烈歡迎。

We're also pleased to report that at the recent AAAI Immunology Meeting in late February, not only was our abstract on the lymphocyte subset data from our 4WHIM trial accepted as an oral presentation by Dr. Teresa Tarrant, an esteemed immunologist from Duke University, whom you've heard from our several past investor events, but Dr. Tarrant was also invited by the conference organizers to give a non-X4-sponsored talk on mavorixafor and WHIM syndrome specifically. Both of her presentations were extremely well attended, as was our What If It's WHIM booth, all of which served to increase our visibility and enable what we believe can result in a major leap forward for patients through physician awareness and education.

我們也很高興地報告，在 2 月底舉行的 AAAI 免疫學會議上，我們的 4WHIM 試驗淋巴細胞亞群數據摘要不僅被杜克大學受人尊敬的免疫學家 Teresa Tarrant 博士接受為口頭報告，您在我們過去的幾次投資者活動中都聽說過他，但Tarrant 博士也受會議組織者邀請，專門就mavorixafor 和WHIM 綜合徵進行了一次非X4 贊助的演講。她的兩次演講和我們的 What If It's WHIM 展位都受到了熱烈歡迎，所有這些都有助於提高我們的知名度，並讓我們相信透過醫生意識和教育可以為患者帶來重大飛躍。

The X4 team working on our congress exhibition booths have recounted many stories of physicians thanking them for drawing their attention to this disorder. And they've reported that multiple physicians who approached us, never before having heard of WHIM syndrome, left believing they might in fact have a WHIM patient under their care.

在我們的大會展位上工作的 X4 團隊講述了許多醫生的故事，感謝他們引起人們對這種疾病的關注。他們報告說，多名來找我們的醫生以前從未聽說過 WHIM 綜合徵，但離開時相信他們實際上可能有一位 WHIM 患者正在接受治療。

As you can imagine, we get the question often about the size of the market for WHIM in the US. With rare diseases that have no treatments, it's always difficult to assess. These interactions with physicians serve to reinforce our belief that there may, in fact, be more WHIM patients out there beyond the thousand or so that we've estimated are diagnosed at present based on claimed data and analyses.

正如您可以想像的那樣，我們經常收到關於美國 WHIM 市場規模的問題。對於無法治療的罕見疾病，評估總是很困難。這些與醫生的互動增強了我們的信念，即事實上，可能有更多的 WHIM 患者，超過我們目前根據聲稱的數據和分析估計的診斷人數。

And while we eagerly await word from the FDA on our first NDA, we're continuing to advance our plans to seek approval for mavorixafor and WHIM outside of the US as well. We've had productive interactions with regulators in Europe and now believe we may be able to submit for EMA approval in late 2024, early 2025. We've had discussions with potential partners on how best to leverage our US approval, if received, across other geographies as well; more to come on that later this year.

雖然我們熱切等待 FDA 關於我們的第一份 NDA 的消息，但我們仍在繼續推進我們的計劃，以尋求美國境外 mavorixafor 和 WHIM 的批准。我們與歐洲監管機構進行了富有成效的互動，現在相信我們可能能夠在 2024 年底、2025 年初提交 EMA 批准。我們已經與潛在合作夥伴討論瞭如何在其他地區最好地利用我們在美國的批准（如果獲得批准）；今年晚些時候還會有更多內容。

Now turning to our chronic neutropenia program, we were able to make significant progress in advancing mavorixafor in CN during 2023 as well. Although our Phase 2 clinical trial was a little slower to enroll than we'd initially expected, we were able to learn and increase enrollment and achieve our target of at least 15 patients by early November, and we continue to expect to announce additional Phase 2 results in the 15-plus trial participants in the coming months.

現在轉向我們的慢性中性粒細胞減少症項目，我們在 2023 年在 CN 推進 mavorixafor 方面也取得了重大進展。儘管我們的2 期臨床試驗的入組速度比我們最初預期的要慢一些，但我們能夠學習並增加入組人數，並在11 月初實現至少15 名患者的目標，並且我們繼續期望宣布更多的2 期臨床試驗未來幾個月將有超過 15 名試驗參與者。

We expect that our data to be presented will include a meaningful number of patients who are receiving mavorixafor alone, without concomitant GCSF treatment, enabling the assessment of mavorixafor as a potential monotherapy in those diagnosed with CN. We also expect that data to be presented will include information on additional participants being treated with a combination of mavorixafor and GCSF.

我們預計我們將提供的數據將包括大量單獨接受 mavorixafor 治療而不同時接受 GCSF 治療的患者，從而能夠評估 mavorixafor 作為診斷為 CN 的潛在單一療法。我們還希望提供的數據將包括接受 mavorixafor 和 GCSF 聯合治療的其他參與者的資訊。

Importantly, all of the preliminary data presented to date and other learnings from the Phase 2 trial, along with our interactions with the FDA, have enabled us to finalize the protocol for a global, pivotal, Phase 3 clinical trial of mavorixafor in CN and advance the initiation of this important next trial in the first half of 2024. As we've previously discussed, we plan to enroll approximately 150 participants in the trial, which will be a 52-week, double-blinded, placebo-controlled trial with one-to-one randomization.

重要的是，迄今為止提供的所有初步數據和 2 期試驗的其他知識，以及我們與 FDA 的互動，使我們能夠最終確定 mavorixafor 在中國進行的全球關鍵 3 期臨床試驗的方案，並推進這項重要的下一次試驗將於2024 年上半年啟動。正如我們之前討論的，我們計劃招募大約 150 名參與者參加該試驗，這將是一項為期 52 週、雙盲、安慰劑對照、一對一隨機化的試驗。

We will be assessing the safety and efficacy of mavorixafor, plus or minus concomitant GCSF treatment, in those with congenital, autoimmune, or idiopathic neutropenia. The patients included into the study will also have to present with neutropenia and symptomatic infections despite current standard of care, including GCSF.

我們將評估 mavorixafor 合併或合併 GCSF 治療對於先天性、自體免疫或特發性嗜中性白血球減少症患者的安全性和有效性。儘管目前的護理標準包括 GCSF，但納入研究的患者也必須出現嗜中性白血球減少症和症狀感染。

There is a significant unmet medical need across this established Phase 3 patient population, a US market we estimate to represent approximately 15,000 people. The primary endpoint will be a two-component endpoint, comprised of both the annualized infection rate and ANC responder analysis across the study population. Secondary endpoints will include the severity and duration of infections, antibiotic use, quality of life measurements, among others, and of course, safety.

在已建立的 3 期患者群體中，存在大量未滿足的醫療需求，我們估計美國市場約有 15,000 人。主要終點將是一個由兩個組成部分組成的終點，包括研究族群的年化感染率和 ANC 反應者分析。次要終點包括感染的嚴重程度和持續時間、抗生素的使用、生活品質測量等，當然還有安全性。

We are in the process of initiating our global study sites and are looking forward to enrolling patients across a number of these sites beginning in the next few months. We are, as of now, planning to host a CN event before the end of June to update on both the Phase 2 trial data and CN Phase 3 trial progress. So stay tuned for more information on that.

我們正在啟動我們的全球研究中心，並期待在未來幾個月開始在其中一些研究中心招募患者。目前，我們計劃在 6 月底前舉辦 CN 活動，以更新 CN 2 期試驗數據和 CN 3 期試驗進度。因此，請繼續關注有關這方面的更多資訊。

I'll now turn it over to our CFO, Adam Mostafa, to review the fourth-quarter and full-year 2023 financials. Adam?

現在我將把它交給我們的財務長 Adam Mostafa，讓他審查 2023 年第四季和全年的財務狀況。亞當？

Thanks, Paula, and thanks to all of you for being on the call with us today.

謝謝保拉，也謝謝大家今天接受我們的電話。

Having raised more than $87 million during 2023, comprised of a mix of equity and debt capital through an at-the-market pipe and through our expanded loan facility with Hercules, we ended 2023 with $115.2 million in cash and cash equivalents, short-term marketable securities, and restricted cash. We expect that these funds will support our operations into 2025.

2023 年，我們籌集了超過 8,700 萬美元，其中包括透過市場管道以及透過我們與 Hercules 擴大的貸款融資混合的股本和債務資本，截至 2023 年末，我們的現金和現金等價物、短期資金為 1.152 億美元。有價證券和受限制的現金。我們預計這些資金將支持我們到 2025 年的營運。

We would like to note that we may have multiple non-dilutive sources of funding available to us throughout 2024. Given mavorixafor's rare pediatric disease designation, we are optimistic that we'll receive a priority review voucher, which can be used for a subsequent application or sold to another drug sponsor should mavorixafor be approved. If all goes well, we also may have additional access to milestone-based debt tranches through our Hercules facility this year and anticipate revenues from US sales of mavorixafor over the course of this year and beyond.

我們想指出，2024 年我們可能有多種非稀釋性資金來源可供使用。鑑於 mavorixafor 被指定為罕見兒科疾病，我們樂觀地認為我們將收到優先審查憑證，該憑證可用於後續申請或在 mavorixafor 獲得批准時出售給其他藥物申辦者。如果一切順利，我們今年還可能透過 Hercules 融資獲得額外的基於里程碑的債務部分，並預計今年及以後 Mavorixafor 在美國的銷售收入。

A quick recap of our 2023 financials -- R&D expenses were $15.3 million and $72 million for the fourth quarter and full year ended December 31, 2023, respectively, compared to $19 million and $61.1 million for the comparable periods in 2022. Our R&D expenses included $1.1 million and $4.4 million of certain non-cash expenses for the fourth quarter and full year ended December 31, respectively.

快速回顧一下我們2023 年的財務狀況——截至2023 年12 月31 日的第四季度和全年的研發費用分別為1,530 萬美元和7,200 萬美元，而2022 年同期的研發費用為1,900 萬美元和6,110 萬美元。截至 12 月 31 日的第四季和全年，我們的研發費用分別包括 110 萬美元和 440 萬美元的某些非現金費用。

SG&A expenses were $9.9 million and $35.5 million for the fourth quarter and full year of 2023, respectively, compared to $6.6 million and $27 million for the comparable periods in 2022. Our SG&A expenses included $1.4 million and $4.3 million of certain non-cash expenses for the fourth quarter and full year ended December 31, respectively.

2023 年第四季及全年的銷售管理及行政費用分別為 990 萬美元及 3,550 萬美元，而 2022 年同期為 660 萬美元及 2,700 萬美元。截至 12 月 31 日的第四季和全年，我們的 SG&A 費用分別包括 140 萬美元和 430 萬美元的某些非現金費用。

Finally, we reported a net loss of $19.1 million and $101.2 million for the fourth quarter and full year ended December 31, compared to $29.1 million and $93.9 million for the comparable periods in 2022.

最後，我們報告截至 12 月 31 日的第四季和全年淨虧損為 1,910 萬美元和 1.012 億美元，而 2022 年同期淨虧損為 2,910 萬美元和 9,390 萬美元。

Net losses included $2.5 million and $8.7 million of stock-based compensation expenses for the fourth quarter and full year 2023, respectively, compared to $1.1 million and $5.2 million for the comparable periods in 2022.

淨虧損包括 2023 年第四季和全年的股票補償費用分別為 250 萬美元和 870 萬美元，而 2022 年同期為 110 萬美元和 520 萬美元。

With that, I'll pass it back to Paula.

這樣，我會把它傳回給寶拉。

Thanks so much, Adam.

非常感謝，亞當。

To conclude, as we said in the press release earlier this morning, the excitement at X4 is now palpable. We have a countdown clock on the wall as our expected PDUFA date, and we could not be more energized to know that we are so close to potentially achieving our vision of delivering meaningful benefits to those with rare diseases of the immune system by gaining approval for what would be the first and only targeted therapy for the treatment of people with WHIM syndrome. And we look forward to continuing to report out on our other milestones throughout the rest of the year.

總而言之，正如我們在今天早上早些時候的新聞稿中所說，X4 的興奮點現在顯而易見。我們的牆上掛著一個倒數時鐘，作為我們預期的 PDUFA 日期，我們非常興奮地知道，我們已經非常接近實現我們的願景，即通過獲得批准為免疫系統罕見疾病患者提供有意義的益處。什麼是第一個也是唯一一個治療WHIM 症候群患者的標靶療法。我們期待在今年剩餘時間內繼續報告我們的其他里程碑。

We'll now open up the call for your questions. Operator?

我們現在將開始電話詢問您的問題。操作員？

(Operator Instructions) Kristen Kluska, Cantor Fitzgerald.

（操作員說明）Kristen Kluska、Cantor Fitzgerald。

Hi, everyone. Thanks for taking the questions, and kudos. I've seen your team at a lot of these medical conferences, so great work getting the community aware of what's going on there.

大家好。感謝您提出問題，並表示敬意。我在許多這類醫學會議上見過你們的團隊，你們在讓社區了解那裡發生的事情方面做得非常出色。

I wanted to ask about commercialization and thoughts around CN. So the KOLs that we speak to note that even meeting some GCSF would be a huge win, but understand that in a commercial setting, patients are going to present differently, some on monotherapy mav, some on combination, and some on combinations that may be less GCSF. So to account for this, what is your expectation on what the monitoring and neutrophil measured protocols would look like in a commercial setting?

我想問一下關於CN的商業化和想法。因此，我們採訪的KOL 指出，即使會見一些GCSF 也將是一個巨大的勝利，但要明白，在商業環境中，患者的表現會有所不同，有些人接受單一療法，有些人接受聯合治療，有些人則接受合併治療減少 GCSF。因此，考慮到這一點，您對商業環境中的監測和嗜中性球測量方案的期望是什麼？

Thanks, Kristen. I think what we're hearing each explore is around neutrophil counts in chronic neutropenia and then how we are considering how best to develop the product to address the range of patients. So assuming that I got that right, we're certainly very excited about our pending data update on the Phase 2 study coming up in the first half of this year. Of course, in our first three patients, we saw a nice durable elevation in patients with combination GCSF.

謝謝，克里斯汀。我認為我們聽到的每次探索都是圍繞慢性中性粒細胞減少症的中性粒細胞計數，然後我們如何考慮如何最好地開發產品來解決一系列患者的問題。因此，假設我的觀點是正確的，我們當然對今年上半年即將發布的第二階段研究的待定數據更新感到非常興奮。當然，在我們的前三名患者中，我們看到聯合 GCSF 患者的血壓持續升高。

Importantly, we'll be having data on a group of monotherapy patients, so I think that'll really help us appreciate the impact of mavorixafor on neutrophil counts in this broader patient population. And of course, we'll continue to study the drug in combination with G. There's more work to do to support physicians and patients on the best hybrid combination or introduction of mav and then if and when GCSF might be needed. So hopefully I got your question.

重要的是，我們將獲得一組單一療法患者的數據，因此我認為這將真正幫助我們了解 mavorixafor 對更廣泛患者群體中中性粒細胞計數的影響。當然，我們將繼續研究該藥物與 G 的組合。還有更多工作要做，以支持醫生和患者選擇最佳混合組合或引入 mav，以及是否需要以及何時需要 GCSF。希望我能聽到你的問題。

Yes, thank you. And maybe if I could squeeze in a second one. For WHIM syndrome, you noted that, sometimes, physicians are thinking, hey, actually, maybe I do have a patient that fits the criteria for WHIM syndrome. Curious if you're seeing any trends about what specifically it is about the indication that it's kind of putting this light bulb in their head or if you've heard any specific feedback there to help with your education efforts?

是的，謝謝。也許我可以擠進第二個。對於 WHIM 綜合徵，您注意到，有時，醫生會想，嘿，實際上，也許我確實有一個符合 WHIM 綜合徵標準的患者。是否好奇您是否看到了任何趨勢，表明它在某種程度上將這個燈泡放在他們的腦海中，或者您是否聽到了任何具體的反饋來幫助您的教育工作？

Yeah. I mean, I think what the field has been sharing with us is just the general excitement because the data are so strong with an oral once daily. But I do think some of the interesting light bulbs are around -- there is no ICD-10 code. It's a very poorly educated disease, so I'll turn it over to our Chief Commercial Officer to add a bit more color.

是的。我的意思是，我認為該領域與我們分享的只是普遍的興奮，因為每天一次口頭的數據是如此強大。但我確實認為一些有趣的燈泡就在附近——沒有 ICD-10 代碼。這是一種非常缺乏教育的疾病，所以我會把它交給我們的首席商務官來添加更多的色彩。

Yeah, thanks. And what's been interesting is through our disease awareness campaign, we've really seen that light bulb go on as we highlight the fact that these patients can present very differently. No one WHIM patient is alike. And so this kind of dispels the whole assumption that you have to have all four symptoms to be a WHIM patient. And physicians are beginning to realize they may have more WHIM patients in their practice than they originally thought.

是的，謝謝。有趣的是，透過我們的疾病意識活動，當我們強調這些患者的表現可能非常不同時，我們確實看到了燈泡的亮起。沒有一位 WHIM 患者是相似的。因此，這消除了「必須具備所有四種症狀才能成為 WHIM 患者」的假設。醫生們開始意識到，他們的實踐中可能有比他們最初想像的更多的 WHIM 患者。

Thanks very much.

非常感謝。

Ted Tenthoff, Piper Sandler.

特德·滕索夫，派珀·桑德勒。

Great. Thank you very much. Really getting excited for the launch here. I have just a couple questions. Firstly, on the FDA side, appreciating that there's not a panel, are there any final issues to resolve in terms of manufacturing visits? Have you initiated labeling discussions? When do you think that happens, all those kinds of things?

偉大的。非常感謝。在這裡發布真的很興奮。我只有幾個問題。首先，在FDA方面，由於沒有專門小組，在生產訪問方面還有什麼最終問題需要解決嗎？您是否已發起標籤討論？您認為什麼時候會發生所有這些事情？

And then when it comes to the actual selling effort, how many reps do you anticipate to satisfy the US and what do you think the kind of cost would be -- annual cost for that sales force? Thanks so much.

然後，當涉及實際的銷售工作時，您預計有多少銷售代表能夠滿足美國的要求，以及您認為該銷售人員的成本是多少——每年的成本？非常感謝。

Sure. Our Chief Medical Officer will take your regulatory question, and Mark can comment on the commercial.

當然。我們的首席醫療官將回答您的監管問題，馬克可以對廣告發表評論。

So our interactions with the FDA has been the typical interactions. We are on track for PDUFA dates on April 30, and we're working through the regular process with the FDA.

因此，我們與 FDA 的互動是典型的互動。我們預計 PDUFA 日期為 4 月 30 日，我們正在與 FDA 合作完成常規流程。

Yeah. And assuming we get approved at the end of April, we'll be ready to deploy a fully trained, experienced rare disease field team. We can share more details around the time of approval in terms of the size of the sales force. But we'll be also engaging with payers to communicate the burden of WHIM and the value proposition of mavorixafor and offering a comprehensive suite of patient support services, so patients can get access to mavorixafor as quickly as possible after approval.

是的。假設我們在四月底獲得批准，我們將準備部署一支訓練有素、經驗豐富的罕見疾病現場團隊。我們可以在批准時分享有關銷售人員規模的更多詳細資訊。但我們也將與付款人合作，傳達 WHIM 的負擔和 mavorixafor 的價值主張，並提供一整套患者支援服務，以便患者在獲得批准後能夠盡快獲得 mavorixafor。

Okay, great. Thank you. Good luck.

好的，太好了。謝謝。祝你好運。

Sean Lee, with H.C. Wainwright.

李 (Sean Lee) 與 H.C.溫賴特。

Hey, good morning. This is Sean on for RK. I just have a quick question in terms of the awareness campaign. So because it's such a rare disease, once it's launched, would you be doing a marketing campaign targeting patients as well just to have the outreach there, too, so that they can start reaching out for mavorixafor?

嗨，早安。我是 RK 的肖恩。我只是有一個關於宣傳活動的簡單問題。因此，因為這是一種罕見的疾病，一旦推出，您是否也會針對患者進行行銷活動，以便在那裡進行推廣，以便他們能夠開始接觸 mavorixafor？

Sure, great question. Of course, we encourage everyone to check the What If It's WHIM website that's available to the public. So certainly, we are developing the tools that would be directed towards physicians and, of course, support the patient groups appropriately. I'll turn it over to Mark for a bit more detail.

當然，很好的問題。當然，我們鼓勵大家查看向公眾開放的 What If It's WHIM 網站。當然，我們正在開發針對醫生的工具，當然也會適當地支持患者群體。我會把它交給馬克了解更多細節。

Yeah, it's a great question. And as Paula said, we're really building the foundations for a launch that enables the product to get to patients as quickly as possible.

是的，這是一個很好的問題。正如保拉所說，我們確實正在為產品的發布奠定基礎，使產品能夠盡快到達患者手中。

For clarity, we don't expect a bolus of patients at launch. Our goal is to get patients back in to see their doctors and as we build demand for our products. So we'll be doing marketing campaigns targeted at physicians where we expect to have WHIM patients in their practice, as well as marketing campaigns to potential patients and also educating payers on the burden of WHIM syndrome and the value proposition of mavorixafor.

為清楚起見，我們預計啟動時不會有大量患者。我們的目標是讓患者重新去看醫生，同時增加對我們產品的需求。因此，我們將針對希望在實踐中遇到 WHIM 患者的醫生開展行銷活動，並向潛在患者開展行銷活動，並教育付款人了解 WHIM 綜合徵的負擔和 mavorixafor 的價值主張。

Great. Thank you for that.

偉大的。謝謝你。

(Operator Instructions) Stephen Willey, Stifel.

（操作員說明）Stephen Willey，Stifel。

Yeah, good morning. Thanks for taking the questions. Maybe just a couple Phase 3 CN questions. So I think you are stratifying on CN subtype in the Phase 3, but I guess I'm just wondering how you expect those subtypes to be represented within the Phase 3, given patient eligibility criteria, and if you're enrolling in a way to get kind of a minimal representation of each of these, whether it's congenital, autoimmune, or idiopathic.

是的，早安。感謝您提出問題。也許只是幾個第三階段 CN 問題。因此，我認為您在第3 階段對CN 亞型進行分層，但我想我只是想知道，考慮到患者資格標準，以及您是否以某種方式入組，您希望這些亞型在第3 階段中如何體現獲得每種疾病的最小代表，無論是先天性的、自體免疫性的或特發性的。

So yes, this is Christophe here. The included criteria will have congenital, idiopathic, and/or autoimmune patients. Into the study, we will have the patients on monotherapy and on GCSF as well. We're not planning on stratifying specifically for some of those subtypes, but we'll do additional analysis obviously when we have -- given the sample size, we'll have a substantial number of those subtypes that we'll be able to consequently analyze.

是的，這是克里斯托夫。納入的標準包括先天性、特發性和/或自體免疫性患者。在這項研究中，我們將讓患者接受單一療法和 GCSF 治療。我們不打算專門針對其中一些子類型進行分層，但顯然，當我們有足夠的樣本量時，我們將進行額外的分析，因此我們將能夠獲得大量的子類型分析。

Yeah. And just to add to Christophe's comment, the idiopathic, autoimmune are essentially the same bucket. They're different words for the same group of patients, and that's quite a large majority, and then there's the congenital. So we'll be able to stratify by those bigger buckets. The congenitals are so variable. It's really -- we're not able to stratify based on the heterogeneity of congenital. So we're stratifying across the big buckets that Christophe mentioned and also GCSF and monotherapy.

是的。補充克里斯托夫的評論，特發性和自體免疫性本質上是同一類。對於同一組患者來說，它們是不同的詞，而且佔絕大多數，然後是先天性。因此，我們將能夠透過那些更大的桶子進行分層。先天性如此多變。事實上，我們無法根據先天性的異質性進行分層。因此，我們將 Christophe 提及的大桶以及 GCSF 和單一療法進行分層。

Okay. And then is there a lower limit of neutrophils that a patient must have to be Phase 3 eligible? And then, I guess, just given the inherent variability of neutrophil counts, how many measurements do you require during the screening process prior to randomization?

好的。那麼，患者必須達到第 3 階段資格的中性粒細胞數量是否有下限？然後，我想，鑑於中性粒細胞計數固有的變異性，在隨機化之前的篩選過程中需要進行多少次測量？

So yes, we do have the -- so the measurements first, let me start with this. We have several measurements that we're going to be looking at. For the screening, we're looking at one measurement on the screening, and then we will establish the baseline on several hours of measurements.

所以，是的，我們確實有——所以首先是測量，讓我從這個開始。我們將要考慮幾個測量結果。對於篩選，我們將查看篩選中的一項測量結果，然後我們將在幾個小時的測量結果中建立基準。

And the first part of the questions was if there is a lower limit of ANC, we don't have a lower limit of ANC. There will be some patients that can be fairly low, especially in the congenital population, and we have a range in our inclusion criteria that include those severe all the way to the mild and moderate neutropenic patients.

問題的第一部分是 ANC 是否有下限，我們沒有 ANC 下限。有些患者的中性粒細胞減少症可能相當低，特別是在先天性人群中，我們的納入標準有一系列，包括那些嚴重的一直到輕度和中度中性粒細胞減少症患者。

And Steve, just as a reminder of benchmark, our WHIM Phase 3, their baseline were about 180 cells per microliter, so quite severely neutropenic. So we would expect to be able to accommodate patients certainly well into those ranges and, hopefully, to see an effect similar to what we've seen in WHIM.

Steve，作為基準的提醒，我們的 WHIM 第 3 階段，他們的基線約為每微升 180 個細胞，因此中性粒細胞減少症相當嚴重。因此，我們希望能夠將患者很好地適應這些範圍，並希望看到與我們在 WHIM 中看到的效果類似的效果。

Okay, very helpful. Thanks for taking the questions.

好的，非常有幫助。感謝您提出問題。

Kalpit Patel, B. Riley.

卡爾皮特·帕特爾，B.萊利。

Hi. Good morning. This is [Jay] on for Kalpit. Thanks for taking the questions. My first question is for the upcoming Phase 2 update, where we see data from patients who are on higher dose or GCSF. Believe the data staying to date were for patients less than 1 microgram per kilogram by the approved dose of a GCSF is much higher?

你好。早安.這是 [Jay] 為卡爾皮特主持的節目。感謝您提出問題。我的第一個問題是關於即將到來的第二階段更新，我們將看到來自接受較高劑量或 GCSF 的患者的數據。相信迄今為止的數據是針對每公斤體重低於 1 微克的患者，GCSF 的批准劑量要高得多嗎？

And my second question is for the Phase 3 that you are planning to start. What, in your view, is a good delta for reduction in infection rate versus the control arm? Thank you.

我的第二個問題是關於您計劃啟動的第三階段。您認為，與對照組相比，降低感染率的最佳增量是多少？謝謝。

So we'll tag team here. I mean, so in terms of the GCSF dosing, you're incredibly sharp in assessing that the average dose of GCSF of the patients is much lower than the labeled dose, and that is practice. Unfortunately, this drug is so challenging to take and to manage that physicians and patients stay on the very low end, sometimes as low as 20% of base -- of the labeled dose.

所以我們將在這裡標記團隊。我的意思是，就 GCSF 劑量而言，您的評估非常敏銳，患者的 GCSF 平均劑量遠低於標籤劑量，這就是實踐。不幸的是，這種藥物的服用和管理非常具有挑戰性，以至於醫生和患者只能使用標籤劑量的極低劑量，有時甚至低至基礎劑量的 20%。

And again, we don't give guidance on what doses patients are on. They come in at their own stable doses. So we would expect if that's the standard of care that that's the range that we'll continue to see in the trial. So I hope that addresses your first question.

再說一遍，我們不會就患者服用的劑量提供指導。它們以自己穩定的劑量進入。因此，我們預計，如果這是護理標準，那麼我們將在試驗中繼續看到這一範圍。所以我希望這能解決你的第一個問題。

And then I think your second question was around what type of infection benefit target are we aiming for in the Phase 3.

然後我認為你的第二個問題是我們在第三階段的目標是什麼類型的感染福利目標。

So in our Phase 3, I want to remind you about our WHIM data, on average, have seen an improvement of 60% of infections, and we've taken a rather conservative approach and we're estimating with power of that study for 40% difference in annualized infection rates.

因此，在我們的第 3 階段，我想提醒您注意我們的 WHIM 數據，平均而言，感染率改善了 60%，我們採取了相當保守的方法，我們正在利用該研究的力量估計 40年感染率差異百分比。

Okay, thank you. That's very helpful.

好的謝謝。這非常有幫助。

Thank you. At this time, I would like to turn the floor back over to Paula Ragan for closing comments.

謝謝。現在，我想把發言權交還給保拉·拉根 (Paula Ragan)，以供結束發言。

Thank you so much for joining us today. We appreciate all the attention and insightful questions and wish you an enjoyable rest of your day.

非常感謝您今天加入我們。我們感謝所有的關注和富有洞察力的問題，並祝您度過愉快的一天。

Thank you. This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation and have a great day.

謝謝。今天的電話會議到此結束。此時您可以斷開線路。感謝您的參與，祝您有美好的一天。