Halozyme Therapeutics Inc (HALO) 2022 Q4 法說會逐字稿

Good afternoon. My name is Regina, and I will be your conference operator today. At this time, I would like to welcome everyone to the Halozyme Fourth Quarter and Full Year 2022 Financial and Operating Results Conference Call. (Operator Instructions) Please note that this event is being recorded.

下午好。我叫 Regina，今天我將擔任你們的會議接線員。此時，我想歡迎大家參加 Halozyme 第四季度和 2022 年全年財務和經營業績電話會議。 （操作員說明）請注意，正在記錄此事件。

I will now turn the call over to Tram Bui, Halozyme's Vice President of Investor Relations and Corporate Communications. Please go ahead.

我現在將電話轉給 Halozyme 的投資者關係和企業傳播副總裁 Tram Bui。請繼續。

Thank you, operator. Good afternoon, and welcome to our fourth quarter and full year 2022 financial and operating results conference call. In addition to the press release issued today after the market close, you can find a supplementary slide presentation that will be referenced during today's call in the Investor Relations section of our website.

謝謝你，運營商。下午好，歡迎來到我們的第四季度和 2022 年全年財務和經營業績電話會議。除了今天收市後發布的新聞稿外，您還可以在我們網站的“投資者關係”部分找到今天電話會議期間將引用的補充幻燈片演示。

Leading the call will be Dr. Helen Torley, Halozyme's President and Chief Executive Officer, who will provide an update on our business; and Nicole LaBrosse, our Chief Financial Officer, will review our financial results for the fourth quarter and full year 2022 as well as guidance for 2023.

主持此次電話會議的將是 Halozyme 總裁兼首席執行官 Helen Torley 博士，她將介紹我們業務的最新情況；我們的首席財務官 Nicole LaBrosse 將審查我們 2022 年第四季度和全年的財務業績以及 2023 年的指導意見。

On today's call, we will be making forward-looking statements. I refer you to our SEC filings for a full list of risks and uncertainties. During the call, both GAAP and non-GAAP financial measures will be discussed. Certain non-GAAP or adjusted financial measures are reconciled with the comparable GAAP financial measures in our earnings press release and slide presentation.

在今天的電話會議上，我們將發表前瞻性聲明。我建議您參閱我們向美國證券交易委員會提交的文件，以獲取完整的風險和不確定性列表。在電話會議期間，將討論 GAAP 和非 GAAP 財務措施。某些非 GAAP 或調整後的財務指標與我們的收益新聞稿和幻燈片演示中的可比 GAAP 財務指標相一致。

I will now turn the call over to Helen Torley.

我現在將把電話轉給海倫托利。

Thank you, Tram, and good afternoon, everyone. I'm very pleased with our fourth quarter and full year 2022 results, which continues to reflect strong financial and operational performance across the entire company, creating positive momentum and positioning Halozyme for an exciting 2023. In 2022, we extended our leadership as a subcutaneous drug delivery platform company through the continued expansion and progress of our ENHANZE portfolio and through the acquisition of Antares Pharma and the small volume auto-injector platforms. The acquisition also resulted in a diversification of our revenues with the addition of the auto-injector and specialty to testosterone products businesses.

謝謝 Tram，大家下午好。我對我們第四季度和 2022 年全年的業績感到非常滿意，這繼續反映出整個公司強勁的財務和運營業績，創造了積極的勢頭並為 Halozyme 定位了令人興奮的 2023 年。2022 年，我們擴大了我們作為皮下注射劑的領導地位通過我們的 ENHANZE 產品組合的持續擴展和進步以及通過收購 Antares Pharma 和小容量自動注射器平台，成為藥物輸送平台公司。此次收購還導致我們的收入多樣化，增加了自動注射器和專業的睾丸激素產品業務。

Moving to Slide 3. We achieved record revenue of $660 million in 2022, an increase of 49% year-over-year. This strong performance was primarily driven by the continued growth of our ENHANZE portfolio includes revenues from our acquired auto-injector and specialty product businesses. Fourth quarter 2022 revenue was $181 million, an increase of 78% over the same period in the prior year, resulting from continued growth of ENHANZE royalty revenues, incremental product sales and royalties from our small volume auto-injectors and sales of Biotec our commercial cooption replacement therapy products.

轉到幻燈片 3。我們在 2022 年實現了創紀錄的 6.6 億美元收入，同比增長 49%。這種強勁的業績主要是由我們的 ENHANZE 產品組合的持續增長推動的，包括我們收購的自動注射器和專業產品業務的收入。 2022 年第四季度收入為 1.81 億美元，比去年同期增長 78%，這是由於 ENHANZE 特許權使用費收入的持續增長、我們小容量自動注射器的產品銷售和特許權使用費增量以及我們商業合作夥伴 Biotec 的銷售替代療法產品。

As we look ahead, we entered the new year with compelling growth opportunities. Our enhanced capabilities support our goal to expand the number of current and new partners utilizing ENHANZE, are high-volume auto-injector plus ENHANZE and our small volume auto-injectors. As a result, Halozyme is well positioned for continued growth. This growth is reflected in our guidance for 2023. We project record revenues of $815 million to $845 million, growth of 23% to 28% over 2022, and we project EBITDA of $415 million to $440 million, greater than 30% year-over-year growth.

展望未來，我們以令人矚目的增長機會進入了新的一年。我們增強的能力支持我們的目標，即擴大使用 ENHANZE 的現有和新合作夥伴的數量，包括大容量自動注射器加上 ENHANZE 和我們的小容量自動注射器。因此，Halozyme 處於持續增長的有利位置。這一增長反映在我們對 2023 年的指導中。我們預計創紀錄的收入為 8.15 億美元至 8.45 億美元，比 2022 年增長 23% 至 28%，我們預計 EBITDA 為 4.15 億美元至 4.4 億美元，同比增長超過 30%年增長。

In 2023, we have multiple drivers of new opportunity contributing to near and long-term growth. These include 2 potential new commercial launches for ENHANZE for subcutaneous efgartigimod and subcutaneous atezolizumab. Current partners advancing new targets into the clinic and advancing their development programs. And it is our goal to sign a new ENHANZE agreements and ENHANZE plus high-volume auto-injector agreement and a small volume auto-injector agreement.

到 2023 年，我們將有多種新機遇驅動因素推動近期和長期增長。其中包括 ENHANZE 的 2 個潛在的新商業上市，用於皮下 efgartigimod 和皮下 atezolizumab。目前的合作夥伴將新目標推向臨床並推進他們的開發計劃。我們的目標是簽署新的 ENHANZE 協議和 ENHANZE plus 大容量自動注射器協議和小容量自動注射器協議。

Moving now to Slide 4. I'll provide an overview of the royalty revenue projections. For 2023, we project total royalty revenue, including ENHANZE and our auto-injector devices of $445 million to $455 million, growth of 23% to 26% from royalty revenue of $360 million in 2022. This guidance continued projected growth from our strong fourth quarter performance, in which total royalty revenue was a record $106 million, which represented 69% growth over the fourth quarter of 2021.

現在轉到幻燈片 4。我將概述特許權使用費收入預測。到 2023 年，我們預計包括 ENHANZE 和我們的自動注射器設備在內的特許權使用費總收入為 4.45 億美元至 4.55 億美元，比 2022 年 3.6 億美元的特許權使用費收入增長 23% 至 26%。該指南繼續預測我們強勁的第四季度的增長業績，其中特許權使用費總收入達到創紀錄的 1.06 億美元，比 2021 年第四季度增長 69%。

Our Wave 2 product, DARZALEX subcutaneous and Phesgo continue to drive the strong royalty revenue growth. The robust and rapid reduction of DARZALEX subcutaneous in the U.S. and Europe demonstrate that adoption faces no real barriers in either geography. As growth growing rapidly in Europe demonstrates the acceptance of our fifth product launch utilizing ENHANZE. The strong adoption of our ENHANZE subcutaneous products by physicians and patients worldwide supports our excitement for the upcoming Wave 3, 4, and 5 product launches.

我們的第 2 波產品 DARZARLEX 皮下注射和 Phesgo 繼續推動強勁的特許權使用費收入增長。在美國和歐洲，DARZARLEX 皮下注射的強勁和快速減少表明，在這兩個地區採用都沒有真正的障礙。隨著歐洲的快速增長表明我們對使用 ENHANZE 的第五個產品發布的接受。我們的 ENHANZE 皮下產品被世界各地的醫生和患者廣泛採用，支持我們對即將推出的第 3 波、第 4 波和第 5 波產品的興奮。

I'll now move to Slide 5, which focuses on DARZALEX, which is continuing on its remarkable growth trajectory. DARZALEX FASPRO, the subcutaneous version of DARZALEX in the United States continued to grow share of total sales, achieving 86% share of total sales of DARZALEX by the end of the fourth quarter of 2022. Importantly, total DARZALEX sales in 2022 also continued to demonstrate strong growth. Janssen's parent Johnson & Johnson reported full year 2022 worldwide sales of DARZALEX, including both the IV and subcutaneous forms of $8 billion, an increase of almost 40% year-over-year on an operational basis. For the fourth quarter, worldwide sales of DARZALEX were more than $2 billion, an increase of almost 34% year-over-year on an operational basis.

我現在轉到幻燈片 5，重點介紹 DARZARLEX，它正在繼續其顯著的增長軌跡。 DARZARLEX FASPRO，DARZARLEX 在美國的皮下注射版本在總銷售額中的份額持續增長，到 2022 年第四季度末達到 DARZARLEX 總銷售額的 86% 的份額。重要的是，2022 年 DARZARLEX 的總銷售額也繼續展示強勁的增長。楊森（Janssen）的母公司強生（Johnson & Johnson）報告稱，DARZARLEX 的 2022 年全年全球銷售額（包括靜脈注射和皮下給藥形式）為 80 億美元，在運營基礎上同比增長近 40%。第四季度，DARZARLEX 的全球銷售額超過 20 億美元，在運營基礎上同比增長近 34%。

Johnson & Johnson highlighted on their year-end results call that the increase in DARZELEX sales was driven by share gains in all regions, continued strong market growth and continued uptake of FASPRO. With the opportunity for more use in frontline therapy, analyst projections for DARZALEX total revenue are estimated to achieve more than $16 billion in annual sales by 2028. We predict DARZALEX FASPRO will continue to grow for years to come as a result of this strong growth in DARZALEX where the vast majority of use is and will continue to be DARZALEX subcutaneous.

強生公司在其年終業績電話會議上強調，DARZELEX 銷售額的增長是由所有地區的份額增長、持續強勁的市場增長和 FASPRO 的持續採用所推動的。由於有機會更多地用於一線治療，分析師預測 DARZARLEX 的總收入預計到 2028 年將實現超過 160 億美元的年銷售額。我們預計 DARZARLEX FASPRO 將在未來幾年繼續增長，因為這種強勁增長在DARZARLEX 的絕大多數使用是並將繼續是 DARZARLEX 皮下注射。

Our second Wave 2 commercial product is Roche's PHESGO, which is a combination of Perjeta and Herceptin for subcutaneous injection for patients with early and metastatic HER2-positive breast cancer. In 2022, PHESGO continued to saw a good update with Roche reporting CHF 714 million in sales for the full year 2022, well underway to becoming a $1 billion brand. With 33% conversion in the early loan countries, PHESGO offers a 5 to 8 minutes subcutaneous administration time compared to ours with standard intravenous administration. On their recent fourth quarter call, they stated that they expect continued growth and significant conversion to Celso to continue.

我們的第二個 Wave 2 商業產品是羅氏的 PHESGO，它是 Perjeta 和赫賽汀的組合，用於早期和轉移性 HER2 陽性乳腺癌患者的皮下注射。 2022 年，PHESGO 繼續取得良好的進展，羅氏報告稱 2022 年全年銷售額為 7.14 億瑞士法郎，正在朝著成為價值 10 億美元的品牌邁進。 PHESGO 在早期貸款國家的轉化率為 33%，與我們的標準靜脈內給藥相比，皮下給藥時間為 5 至 8 分鐘。在他們最近的第四季度電話會議上，他們表示他們預計持續增長和向 Celso 的重大轉變將繼續。

On Slide 6 is an overview of our waves of potential launches. Focusing on Wave 3, these products represent a mix set of royalty revenue opportunities with potential launches projected between 2023 and 2025. The Wave 3 products are subcutaneous escatizumod, atezolizumab, nivolumab and oprolizumab. Our long-term growth trajectory is further supported by our Wave 4 product with potential launches in the 2025 to 2027 time frame. Wave 4 is comprised of 10 partner products, 2 of which are in or about to start Phase III and the remaining 8 are in ongoing Phase I clinical testing or have completed Phase I testing.

幻燈片 6 概述了我們可能推出的浪潮。專注於第 3 波，這些產品代表了一組混合的特許權使用費收入機會，預計將在 2023 年至 2025 年之間推出。第 3 波產品是皮下注射 escatizumod、atezolizumab、nivolumab 和 oprolizumab。我們的 Wave 4 產品進一步支持了我們的長期增長軌跡，該產品可能會在 2025 年至 2027 年的時間框架內推出。第 4 波由 10 種合作夥伴產品組成，其中 2 種處於或即將開始 III 期，其餘 8 種正在進行 I 期臨床試驗或已完成 I 期試驗。

I'll move now to Slide 7 and say a few words about why I am so excited about the potential that is represented by our Wave 3 launches. Firstly, all of the waste products are approved in at least one indication as an intravenous administration. This is an important derisker in terms of development risk. Secondly, over the potential to long soon between this year and 2022. Thirdly, further derisking the opportunity 2 of these products, subcutaneous efgartigimod from argenx and Roche subcutaneous atezolizumab have completed positive Phase III studies and are currently under regulatory review with the potential for approval decision and launch in 2023. And the fourth key point is that the opportunity represented here in terms of analyst projections for total product sales is $30 billion in 2028, significantly higher than the opportunity for our Wave 2 products that are driving our strong royalty revenue growth to date.

我現在將轉到幻燈片 7，並談談為什麼我對我們的 Wave 3 發布所代表的潛力如此興奮。首先，所有廢品都被批准用於至少一種靜脈內給藥適應症。就開發風險而言，這是一個重要的去風險因素。其次，關於今年到 2022 年之間的長期潛力。第三，進一步降低這些產品的風險，argenx 的皮下注射 efgartigimod 和羅氏皮下注射的 atezolizumab 已完成積極的 III 期研究，目前正在接受監管審查，有可能獲得批准決定並在 2023 年推出。第四個關鍵點是，根據分析師對 2028 年產品總銷售額的預測，此處代表的機會為 300 億美元，大大高於推動我們強勁的特許權使用費收入增長的 Wave 2 產品的機會迄今為止。

Let me now provide some more detail on each product. A summary of the ongoing indication-seeking studies for the waste products is provided on Slide 8. Beginning with organic. In November of 2022, again announced FDA acceptance of the biologics license application for subcutaneous expected utilizing ENHANZE for the treatment of adults with generalized myasthenia battle. And also the submission of a marketing authorization application to the European Medical Agency. In January of 2023, argenx provided an update that the PDUFA date has been extended to June 20, 2023, to allow the FDA sufficient time for a review of the data that has been submitted.

現在讓我提供有關每種產品的更多詳細信息。幻燈片 8 提供了正在進行的廢物產品適應症尋求研究的摘要。從有機開始。 2022 年 11 月，再次宣布 FDA 接受皮下注射生物製劑許可申請，預計利用 ENHANZE 治療成人全身性肌無力症。以及向歐洲醫療機構提交上市許可申請。 2023 年 1 月，argenx 提供了 PDUFA 日期已延長至 2023 年 6 月 20 日的更新，以便 FDA 有足夠的時間審查已提交的數據。

We are excited that subcutaneous efgartigimod has the potential to be the first of our Wave 3 partner launches with U.S. approval and commercial launch projected in the second half of 2022. As argenx pipeline products efgartigimod is being developed for the treatment of multiple autoimmune disease indications with subcutaneous development of 6 indications, of which 4 indications are only for subcu delivery. Multiple data readouts were projected in 2023, including data in chronic inflammatory demyelinating polyneuropathy in the second quarter of 2023. And for idiopathic thrombocytopenic copra and pemphigus in the second half of the year.

我們很高興皮下注射 efgartigimod 有可能成為我們第 3 波合作夥伴推出的第一個產品，並預計在 2022 年下半年獲得美國批准和商業上市。作為 argenx 管道產品，efgartigimod 正在開髮用於治療多種自身免疫性疾病適應症皮下開發適應症6個，其中4個適應症僅為皮下給藥。預計 2023 年將有多個數據讀出，包括 2023 年第二季度慢性炎症性脫髓鞘性多發性神經病的數據。以及下半年的特發性血小板減少性椰子肉和天皰瘡的數據。

Analysts predict potential total efgartigimod annual revenue of approximately $5 billion in 2028. The launch of the intravenous version is certainly off to a strong start in the early launch countries. In its preliminary results for the fourth quarter, argenx noted strong physician and patient demand for Vicar and reported total quarterly net product revenues of $175 million and full year 2022 revenue of $402 million.

分析師預測，到 2028 年，efgartigimod 的潛在總年收入約為 50 億美元。靜脈注射版本的推出在早期推出的國家無疑是一個強勁的開端。在第四季度的初步業績中，argenx 注意到醫生和患者對 Vicar 的強勁需求，並報告季度淨產品總收入為 1.75 億美元，2022 年全年收入為 4.02 億美元。

Moving now to Roche. Roche is one of our longest-standing and experienced partners with ENHANZE, and we're delighted to collaborate with them on 2 of our way 3 opportunities, subcutaneous atelizumab and subcutaneous ocrelizumab. Beginning with atezolizumab. In November of 2022, Roche and the submission of a biologics license application to the FDA and a marketing authorization application to the EMA for subcutaneous atezolizumab with ENHANZE. Subcutaneous atezolizumab has the potential to be more convenient for patients and physicians with an approximate 7-minute subcutaneous administration time compared to 30 to 60 minutes for IV treatment.

現在搬到羅氏。羅氏 (Roche) 是我們與 ENHANZE 合作時間最長、經驗最豐富的合作夥伴之一，我們很高興與他們就我們的 3 個機會中的 2 個進行合作，即皮下注射 atelizumab 和皮下注射 ocrelizumab。從 atezolizumab 開始。 2022 年 11 月，羅氏向 FDA 提交了生物製劑許可申請，並向 EMA 提交了 ENHANZE 皮下注射 atezolizumab 的上市許可申請。皮下注射 atezolizumab 有可能使患者和醫生更加方便，皮下給藥時間約為 7 分鐘，而靜脈注射治療需要 30 至 60 分鐘。

With the PDUFA date of September 15, 2023, Roche expects atezolizumab to the only subcutaneous anti-PDL1 on the market for a full year. We're excited to see the continued growth of Tecentriq. In its recent earnings call, Roche reported IV Tecentriq revenues increased 14% year-over-year to CHF 3.7 billion for full year 2022. Transitioning naturals OCREVUS for multiple sclerosis. OCREVUS achieved sales of more than CHF 6 billion in 2022, representing an increase of 17% year-over-year for Roche. Currently, there are 2 IV regimens approved for use. We consider during both the treatment and the observation schedule, the range of time for patients receiving IV OCREVUS is 3.5 hours at the fastest to 6 hours at the longest.

隨著 PDUFA 日期為 2023 年 9 月 15 日，羅氏預計 atezolizumab 將成為市場上唯一的皮下抗 PDL1 藥物一整年。我們很高興看到 Tecentriq 的持續增長。在最近的財報電話會議上，羅氏報告稱 IV Tecentriq 的收入在 2022 年全年同比增長 14% 至 37 億瑞士法郎。用於治療多發性硬化症的過渡性天然藥物 OCREVUS。 OCREVUS 在 2022 年實現銷售額超過 60 億瑞士法郎，對羅氏來說同比增長 17%。目前，有 2 種 IV 方案被批准使用。我們考慮在治療和觀察時間表中，患者接受 IV OCREVUS 的時間範圍最快為 3.5 小時，最長為 6 小時。

The Phase III trial for subcutaneous atezolizumab is ongoing or subcutaneous, the target total administration and observation time for the first and second dose is 1 hour. With the goal that for each subsequent dose, the data supports regulators approving a 10-minute administration and observation time. As you read out from this study is expected in mid-2023.

皮下注射 atezolizumab 的 III 期試驗正在進行或皮下注射，第一和第二劑的目標總給藥和觀察時間為 1 小時。目標是對於每個後續劑量，數據支持監管機構批准 10 分鐘的給藥和觀察時間。正如您從這項研究中讀出的那樣，預計在 2023 年年中。

Moving to our fourth week 3 products in nivolumab, BMS continues to progress with its Phase III study of subcutaneous nivolumab, utilizing ENHANZE in patients with renal cell carcinoma. And BMS also recently initiated the second Phase III study of nivolumab subcutaneous with ENHANZE in patients with melanoma. On its recent fourth quarter call, BMS noted Opdivo IV sales of $8.2 billion for full year 2022, an increase of 10% year-over-year or 14% excluding FX.

轉向我們在 nivolumab 的第 3 週產品，BMS 繼續推進其皮下 nivolumab 的 III 期研究，在腎細胞癌患者中使用 ENHANZE。 BMS 最近還啟動了 nivolumab 與 ENHANZE 皮下注射治療黑色素瘤患者的第二項 III 期研究。在最近的第四季度電話會議上，BMS 指出 Opdivo IV 到 2022 年全年的銷售額為 82 億美元，同比增長 10%，不包括外彙在內增長 14%。

In summary, Wave 3 represents substantial more derisked near-term new royalty revenue opportunity for Halozyme. With that opportunity driven by the timing of approval of the subcutaneous versions of the drugs within the projected 2023 to 2025 time window and also the speed and peak of conversion to subcutaneous.

總而言之，第 3 波代表了 Halozyme 的實質性的、風險更低的近期新特許權使用費收入機會。在預計的 2023 年至 2025 年時間窗口內批准皮下版本藥物的時間以及皮下轉化的速度和峰值推動了這一機會。

Let me now just make a brief comment on the ENHANZE pipeline progress in 2022. I'm very pleased to report that we continue to advance and expand our ENHANZE pipeline, supporting 12 new partner study starts, meeting our 2022 goal to support initiation of at least 10 new studies. The starts included supporting partners advancing 2 new products with ENHANZE into the clinic and supporting initiation of 3 new Phase III programs, the final step in development prior to regulatory submission.

現在讓我對 ENHANZE 管道在 2022 年的進展做一個簡短的評論。我很高興地報告我們繼續推進和擴大我們的 ENHANZE 管道，支持 12 個新的合作夥伴研究開始，實現我們的 2022 年目標以支持在至少 10 項新研究。啟動包括支持合作夥伴將 ENHANZE 的 2 個新產品推進臨床，並支持啟動 3 個新的 III 期項目，這是提交監管之前的最後開發步驟。

In addition, we support the initiation of an additional 7 new studies designed to further explore and potentially expand the profile of ongoing partner subcutaneous programs. In 2022, this pipeline progress contributed strongly to recognition of the approximately $109 million in total collaboration revenue with notable milestones recognized for Phase III study initiations for amivantamab subcu and nivolumab (inaudible) subcu. In 2022 and beyond, our goal is to continue to expand the number of products in development and to advance products through development to regulatory approval and launch, adding multiple new royalty revenue streams.

此外，我們支持啟動另外 7 項新研究，旨在進一步探索並可能擴大正在進行的合作夥伴皮下計劃的概況。 2022 年，這一管道進展為確認約 1.09 億美元的合作總收入做出了巨大貢獻，並為 amivantamab subcu 和 nivolumab（聽不清）subcu 的 III 期研究啟動確認了顯著的里程碑。在 2022 年及以後，我們的目標是繼續擴大開發中產品的數量，並通過開發推進產品到監管批准和發布，增加多個新的特許權使用費收入來源。

I'll now move to our Wave 4 product candidate pipeline, which is shown on Slide 9. We have 10 product candidates in our Wave 4 pipeline, which if they proceed in development and to approval and launch represent potential revenue drivers between 2025 and 2027. The 2 most advanced products against is amivantamab and BMS' 6-dose combination of nivolumab plus relatlimab with ENHANZE, which are in or soon to start Phase III development. Both of these products are already approved as IV treatment, an important subcutaneous development (inaudible).

我現在轉到我們的第 4 波候選產品管道，如幻燈片 9 所示。我們的第 4 波管道中有 10 個候選產品，如果它們繼續開發並獲得批准和發布，則代表 2025 年至 2027 年之間的潛在收入驅動因素. 2個最先進的產品是amivantamab和BMS的nivolumab加relatlimab與ENHANZE的6劑量組合，處於或即將開始III期開發。這兩種產品都已被批准作為 IV 治療，這是一種重要的皮下開發（聽不清）。

In 2022, Janssen initiated a Phase III study of [lapatimab] plus amivantamab with ENHANZE in patients with EGFR mutated advanced (inaudible) small cell lung cancer. In 2022 first of March, we've also initiated the Phase III study called Relative 127, which has the goal of demonstrating that drug exposure levels of nivolumab plus relatlimab fixed-dose combination of ENHANZE is not inferior to intravenous administration of the same combination. And this is being studied in patients with previously untreated metastatic or unresectable melanoma. We're expecting the first patient to be dosed in this study in early 2023.

2022 年，楊森在 EGFR 突變的晚期（聽不清）小細胞肺癌患者中啟動了 [lapatimab] 加 amivantamab 和 ENHANZE 的 III 期研究。 2022 年 3 月 1 日，我們還啟動了稱為 Relative 127 的 III 期研究，其目的是證明 enhanze 的 nivolumab 加 relatlimab 固定劑量組合的藥物暴露水平不低於相同組合的靜脈內給藥。並且正在對先前未經治療的轉移性或無法切除的黑色素瘤患者進行研究。我們預計第一位患者將於 2023 年初在這項研究中接受給藥。

Let me now transition to an update on our auto-injector and Specialty Product businesses beginning on Slide 10. Our acquisition of Antares last year or the strengthened our leadership in direct delivery, creating the opportunity to develop a high-volume auto-injector by combining ENHANZE with our auto-injector know how. In the fourth quarter, we continued our discussions on the opportunity for our high and small volume auto-injectors with current and new potential partners.

現在讓我從幻燈片 10 開始介紹我們的自動注射器和特殊產品業務的最新情況。我們去年收購了 Antares 或加強了我們在直接交付方面的領導地位，創造了通過結合開發大容量自動注射器的機會借助我們的自動注射器專業知識來增強效果。在第四季度，我們繼續與現有和新的潛在合作夥伴討論大容量和小容量自動注射器的機會。

Our high volume auto-injector for rapid delivery of up to 10 ml enabled in trends offers a truly differentiated opportunity for patient-friendly, high-volume subcutaneous treatment delivery that can be utilized across the spectrum of disease areas for both small molecule drugs and biologics. In 2022, the team made significant progress on the development of the working prototype. The prototype is ready for clinical testing, and we expect to initiate and complete human feasibility studies by midyear 2023. Our goal in 2022 is to gain an agreement with a current or a new partner to elaborate on the custom development of a high-volume auto-injector.

我們的大容量自動注射器可快速輸送高達 10 ml 的趨勢，為患者友好的大容量皮下治療輸送提供了真正差異化的機會，可用於小分子藥物和生物製劑的各種疾病領域. 2022 年，團隊在工作原型的開發上取得了重大進展。該原型已準備好進行臨床測試，我們預計將在 2023 年年中啟動並完成人體可行性研究。我們在 2022 年的目標是與現有或新合作夥伴達成協議，詳細說明大批量汽車的定制開發-注射器。

I'll turn now to our commercial business, which includes XYOSTED and TLANDO, shown on Slide 11. Beginning with XYOSTED, this is our weekly virtually painless subcutaneous testosterone replacement treatment, which is patients delivered by auto-injector. Our goal in 2023 is to grow XYOSTED to over $100 million in revenue as a stepping stone to accelerate growth in 2024 and beyond. In 2022, in the 7 months since the acquisition, we focused on increasing XYOSTED demand, identifying opportunities to reduce gross to net deductions and identifying and developing plans to address points of prescription leakage that we have identified.

現在我將談談我們的商業業務，其中包括 XYOSTED 和 TLANDO，如幻燈片 11 所示。從 XYOSTED 開始，這是我們每週幾乎無痛的皮下睾酮替代治療，由自動注射器為患者提供。我們在 2023 年的目標是將 XYOSTED 的收入增長到超過 1 億美元，以此作為在 2024 年及以後加速增長的墊腳石。 2022 年，在收購後的 7 個月裡，我們專注於增加 XYOSTED 的需求，尋找機會將總扣除額減少到淨扣除額，並確定和製定計劃來解決我們已經確定的處方洩漏點。

While we have continued to achieve new weekly high prescription levels each month in 2022, Q4 XYOSTED revenue came in slightly lower than our expectations, driven by a mix of lower demand and lower net price than projected. As we start 2023, year-to-date, I'm pleased to see that XYOSTED demand is off to an excellent start, with the growth over Q4 exit on track with our plan to deliver $100 million in revenues in 2023. Our growth strategy focuses on converting patients from the most common treatment approach, which is intravascular injections. In testosterone injection can be associated with pain and can require physician or health care practitioner administration. XYOSTED with its weekly virtually painless subcutaneous injection delivered by a patient-administered auto-injector offers a new approach that may address these challenges.

雖然我們在 2022 年每個月繼續達到新的每周高處方水平，但由於需求下降和淨價格低於預期，第四季度 XYOSTED 收入略低於我們的預期。在 2023 年年初至今，我很高興看到 XYOSTED 的需求開局良好，第四季度的增長步入正軌，我們計劃在 2023 年實現 1 億美元的收入。我們的增長戰略側重於將患者從最常見的治療方法——血管內註射——轉變過來。睾酮注射可能與疼痛有關，可能需要醫生或醫療保健從業者進行管理。 XYOSTED 每週通過患者自動注射器進行幾乎無痛的皮下注射，提供了一種可以應對這些挑戰的新方法。

We also remain focused on gaining access for TLANDO, our oral testosterone treatment. We have not yet reached agreements with pharmacy benefit managers on an appropriate rebate rate. Until access is established, we are projecting low revenue for TLANDO in 2023. Closing on Antares, our total revenue since the acquisition was $113 million, which came in slightly below our projected range of $115 million to $125 million, which we have provided at the time of the acquisition.

我們還繼續專注於獲得我們的口服睾丸激素治療 TLANDO 的使用權。我們尚未與藥房福利經理就適當的回扣率達成協議。在接入建立之前，我們預計 TLANDO 2023 年的收入較低。在 Antares 結束後，我們自收購以來的總收入為 1.13 億美元，略低於我們在收購的時間。

Before I hand the call over to Nicole, let me reiterate our commitment to our strategic growth and capital allocation priorities shown on Slide 12. Our goal continues to be to maximize revenue growth and durability. We're continuing to return capital to our shareholders with our share buyback plan. We've now completed $350 million of the $750 million 3-year program that was approved by the Board of Directors in December of 2021. Our goal in 2023 is to repurchase up to an additional $15 million pending market conditions and other factors as part of this plan. And we're also continuing to evaluate M&A opportunities, seeking additional platforms or companies with DRIP assets, platforms or technologies where we see the opportunity for significant revenue growth and revenue durability.

在我將電話轉交給妮可之前，讓我重申我們對幻燈片 12 中顯示的戰略增長和資本分配優先事項的承諾。我們的目標仍然是最大限度地提高收入增長和持久性。我們將繼續通過股票回購計劃向股東返還資本。我們現在已經完成了董事會於 2021 年 12 月批准的 7.5 億美元的 3 年計劃中的 3.5 億美元。我們在 2023 年的目標是回購最多 1500 萬美元的額外待定市場條件和其他因素，作為這個計劃。我們還在繼續評估併購機會，尋找更多的平台或擁有 DRIP 資產、平台或技術的公司，我們認為這些平台或公司有機會實現顯著的收入增長和收入持久性。

I will now turn the call over to Nicole, who will discuss our financial results for 2022 and the outlook for 2023. Nicole?

我現在將電話轉給妮可，她將討論我們 2022 年的財務業績和 2023 年的展望。妮可？

Thank you, Helen. 2022 was a year marked by strong financial performance. Halozyme recorded record revenue as a result of growing enhanced royalties in the addition of the Antares business. We completed the acquisition of Antares that met our expectations in being accretive to revenue and non-GAAP EPS. We also strengthened our balance sheet through a strategic refinancing walking into a lower interest rate that, combined with our cash generation, puts us in a strong capital position with a net debt-to-EBITDA ratio of 3.2% at year-end.

謝謝你，海倫。 2022 年是財務表現強勁的一年。由於 Antares 業務的增加，特許權使用費不斷增加，Halozyme 創下了創紀錄的收入。我們完成了對 Antares 的收購，這符合我們在增加收入和非 GAAP 每股收益方面的預期。我們還通過進入較低利率的戰略再融資加強了我們的資產負債表，結合我們的現金生成，使我們在年末的淨債務與 EBITDA 比率為 3.2% 時處於強大的資本狀況。

And as Helen mentioned, we remain committed to deploying capital through our share repurchase program to complement our EPS growth. With our 2022 repurchases, our share buyback programs have resulted in the repurchase of 30.6 million shares since 2019, which contributed $0.32 to non-GAAP earnings per share for the full year 2022.

正如海倫所提到的，我們仍然致力於通過我們的股票回購計劃來部署資本，以補充我們的每股收益增長。自 2022 年回購以來，我們的股票回購計劃已導致自 2019 年以來回購 3060 萬股股票，這為 2022 年全年的非 GAAP 每股收益貢獻了 0.32 美元。

I'll now turn to Slide 13 for our fourth quarter 2022 financial highlights. Here, I'll focus on total revenue for the fourth quarter, which was $181.5 million, a 78% increase compared to $102 million for the fourth quarter of 2021. The increase was driven by an increase in royalty revenue, primarily attributable to subcutaneous DARZALEX and the addition of product sales as a result of Empire's acquisition. Revenue for the quarter included $106 million in royalties an increase of 69% compared to $62.6 million in the prior year period. Lastly, for the quarter, GAAP diluted earnings per share was $0.42 and non-GAAP diluted earnings per share was $0.48.

我現在將轉到幻燈片 13，了解我們 2022 年第四季度的財務亮點。在這裡，我將重點關注第四季度的總收入，為 1.815 億美元，與 2021 年第四季度的 1.02 億美元相比增長 78%。這一增長是由特許權使用費收入的增加推動的，這主要歸因於皮下 DARZAREX以及由於 Empire 的收購而增加的產品銷售。本季度的收入包括 1.06 億美元的特許權使用費，與去年同期的 6260 萬美元相比增長了 69%。最後，本季度 GAAP 攤薄每股收益為 0.42 美元，非 GAAP 攤薄每股收益為 0.48 美元。

I'll now turn to Slide 14 for a review of the full year 2022 results. I'll briefly touch on some highlights here with more details available in our press release and 10-K filed with the SEC today. Total revenues grew 49% to $660.1 million in 2022, off of an already substantial revenue base in 2021 of $443.3 million. The main contributor to this increase was higher revenue from royalties of $360.5 million, up 77% from 2021. Product sales of $191 million were up sharply from $104.2 million in 2021 due to the product contribution from the Antares acquisition.

我現在將轉到幻燈片 14，回顧 2022 年全年的結果。我將在這裡簡要介紹一些要點，更多詳細信息請參閱我們的新聞稿和今天向美國證券交易委員會提交的 10-K 文件。 2022 年總收入增長 49% 至 6.601 億美元，而 2021 年本已可觀的收入基礎為 4.433 億美元。這一增長的主要原因是特許權使用費收入增加，達到 3.605 億美元，比 2021 年增長 77%。由於 Antares 收購的產品貢獻，產品銷售額從 2021 年的 1.042 億美元大幅增長至 1.91 億美元。

Collaborative revenues of $18.6 million saw a decrease from prior year of 20% from $135.3 million, resulting from fewer partner milestone driving events. Now for the year is amortization expense of $43.1 million as a result of the Antares acquisition, in which we acquired intangible assets that are amortized over a useful life related to the auto-injector technology platform and proprietary products. Research and development expenses were $66.6 million compared to $35.7 million in 2021. Selling, general and administrative expenses were $143.5 million compared to $50.3 million in 2021.

協作收入為 1,860 萬美元，較上年的 1.353 億美元下降 20%，這是由於合作夥伴里程碑推動事件的減少。由於收購 Antares，今年的攤銷費用為 4310 萬美元，在收購中，我們收購了在與自動注射器技術平台和專有產品相關的使用壽命內攤銷的無形資產。研發費用為 6660 萬美元，而 2021 年為 3570 萬美元。銷售、一般和管理費用為 1.435 億美元，而 2021 年為 5030 萬美元。

These increases were primarily due to the acquisition and an increase in compensation expense related to the ongoing combined larger workforce. GAAP EPS was $1.44 compared to $2.74 in 2021. As a reminder, 2021 GAAP EPS included a onetime tax benefit from the reversal of our tax valuation allowance, representing approximately $1.05 per share. Non-GAAP EPS for the year was $2.21, an increase from $2 in the prior year and an impressive achievement as 2022 reflects our first year recognizing income tax expense, impacting 2022 non-GAAP EPS by approximately $0.50 per share. Cash equivalents and marketable securities were $362.8 million on December 31, 2022, compared to $74.9 million on December 31, 2021.

這些增長主要是由於收購和與持續合併的更大勞動力相關的補償費用增加。 GAAP 每股收益為 1.44 美元，而 2021 年為 2.74 美元。提醒一下，2021 年 GAAP 每股收益包括因我們的稅收估值津貼逆轉而產生的一次性稅收優惠，相當於每股約 1.05 美元。本年度非 GAAP 每股收益為 2.21 美元，高於上年的 2 美元，這是一項令人印象深刻的成就，因為 2022 年反映了我們確認所得稅費用的第一年，對 2022 年非 GAAP 每股收益的影響約為 0.50 美元。現金等價物和有價證券在 2022 年 12 月 31 日為 3.628 億美元，而 2021 年 12 月 31 日為 7,490 萬美元。

Now let me turn to our 2023 guidance on Slide 15, which we are reiterating and was first provided on January 1 of this year. For the full year 2023, we expect total revenues of $815 million to $845 million, representing growth of between 23% to 28% over 2022 total revenue. We expect revenue from royalties to increase between 23% to 26% over revenue from royalties in 2022, to a range of $445 million to $455 million. We expect EBITDA of $415 million to $440 million, representing growth of more than 30% over 2022 EBITDA and excludes the impact of amortization costs related to the Antares acquisition. We expect non-GAAP diluted earnings per share of $2.50 to $2.65. Our earnings per share guidance does not consider the impact of potential future share repurchases.

現在讓我轉向我們在幻燈片 15 上的 2023 年指南，我們正在重申該指南並於今年 1 月 1 日首次提供。對於 2023 年全年，我們預計總收入為 8.15 億美元至 8.45 億美元，比 2022 年總收入增長 23% 至 28%。我們預計 2022 年特許權使用費收入將比特許權使用費收入增長 23% 至 26%，達到 4.45 億美元至 4.55 億美元。我們預計 EBITDA 為 4.15 億美元至 4.4 億美元，比 2022 年 EBITDA 增長超過 30%，並且不包括與 Antares 收購相關的攤銷成本的影響。我們預計非 GAAP 每股攤薄收益為 2.50 美元至 2.65 美元。我們的每股收益指引未考慮未來潛在股票回購的影響。

With that, I'll now turn the call back over to Helen.

有了這個，我現在將把電話轉回給海倫。

Thank you, Nicole. 2022 was a transformational year for Halozyme. We made great strides as a combined company with our One Team culture that enhanced our leadership in drug delivery and supported our continued growth. 2023 will be another year with significant growth opportunities. Highlights include the potential start of our Wave 3 product launches with 2 potential approvals in 2023 for subcutaneous efgartigimod and subcutaneous atezolizumab, continued progress in the development of our high-volume auto-injector with ENHANZE, the goal of signing new collaboration agreements across our platform and continued revenue growth resulting from our commercial products.

謝謝你，妮可。 2022 年是 Halozyme 轉型的一年。我們作為一家合併後的公司取得了長足的進步，我們的 One Team 文化增強了我們在藥物輸送方面的領導地位，並支持我們的持續增長。 2023 年將是又一個充滿重大增長機會的一年。亮點包括我們的第 3 波產品發布可能開始，2023 年皮下 efgartigimod 和皮下 atezolizumab 可能獲得 2 項批准，我們與 ENHANZE 的大容量自動注射器開發繼續取得進展，目標是在我們的平台上簽署新的合作協議我們的商業產品帶來的持續收入增長。

I will end by thanking our Halozyme and our partners and collaborators for the strong progress made in 2022. I'm excited regarding our 2023 plan that is resulting in our strong revenue and EBITDA growth guidance. And with that, we would be now delighted to take your questions. Thank you, everyone, for joining us today. Operator, would you please open the call for question.

最後，我將感謝我們的 Halozyme 以及我們的合作夥伴和合作者在 2022 年取得的巨大進步。我對我們的 2023 年計劃感到興奮，該計劃將帶來強勁的收入和 EBITDA 增長指導。因此，我們現在很樂意回答您的問題。謝謝大家今天加入我們。接線員，請打開問題電話。

(Operator Instructions) Our first question will come from the line of Mohit Bansal with Wells Fargo.

（操作員說明）我們的第一個問題將來自富國銀行的 Mohit Bansal 系列。

Congrats on all the progress. Maybe one question we get a lot is, do we have some clarity on how Inflation Reduction Act will create ENHANZE products at this point, especially the products which have longer patent protection due to the co-formulation patterns?

祝賀所有的進步。也許我們得到很多的一個問題是，我們是否清楚地了解通貨膨脹法案將如何在這一點上創造 ENHANZE 產品，尤其是由於聯合配方模式而具有更長專利保護的產品？

Thanks, Mohit. At this time, we are still awaiting CMS to provide their regulations and the details as to exactly how it's going to be implemented. And so there still is not a clarity. We obviously are watching that closely, and we'll provide an update as it becomes clearer. And obviously, the question really is as to whether it's a subcutaneous, which has a different BLA filing and a difference that launch date would restart a different clock. And so no answer we can give them that yet, Mohit, but that's definitely of interest to us and our partners.

謝謝，莫希特。目前，我們仍在等待 CMS 提供其法規和具體實施方式的詳細信息。所以仍然不清楚。我們顯然正在密切關注這一點，我們會在它變得更加清晰時提供更新。顯然，真正的問題是它是否是皮下的，它有不同的 BLA 備案和不同的發射日期將重新啟動不同的時鐘。所以我們還不能給他們答案，Mohit，但這絕對是我們和我們的合作夥伴感興趣的。

Your next question will come from the line of Mike DiFiore with Evercore ISI.

您的下一個問題將來自 Evercore ISI 的 Mike DiFiore。

Congrats on the quarter. 2 for me. Number 1, I noticed that Merck is conducting a Phase III non-small cell lung cancer trial of pembrolizumab plus hyaluronidase. Any thoughts on how this may be different from ENHANZE? And the second question is concerning subcutaneous ViivGard. Obviously, ViivGard expected to be a big project in 2023. And it seem to be pretty bullish on the size of the subcu opportunity. So having said that, why didn't the ViivGard/PDUFA delay not lead to a change in your guidance?

祝賀這個季度。 2 對我來說。第一，我注意到默克公司正在進行 pembrolizumab 加透明質酸酶的 III 期非小細胞肺癌試驗。關於這與 ENHANZE 有何不同的想法？第二個問題是關於皮下注射 ViivGard。顯然，ViivGard 預計將在 2023 年成為一個大項目。而且它似乎非常看好 subcu 機會的規模。所以話雖如此，為什麼 ViivGard/PDUFA 的延遲沒有導致您的指南發生變化？

Yes. Thanks for those questions. Let me begin with the question on Merck. We noted that the data on that study start. Mike, we don't have any details as to exactly what out Merck is using and how they are proceeding. So we really can't comment on that would be a question, obviously, better address to them. What we can see is with regard to ENHANZE, we obviously have established (inaudible) proven well-tested leader in supporting subcutaneous delivery of drugs. And we do find that our (inaudible) record of success with 5 approvals, more than 600,000 patients who have received treatment with ENHANZE drug really puts us in a great position and a great negotiation position for continue to expand the number of deals we have. So that's all I will say on that one.

是的。謝謝你的問題。讓我從默克公司的問題開始。我們注意到該研究的數據開始。邁克，我們沒有關於默克到底使用什麼以及他們如何進行的任何細節。所以我們真的不能評論這將是一個問題，顯然，更好地解決他們。我們可以看到，關於 ENHANZE，我們顯然已經建立了（聽不清）在支持皮下給藥方面經過充分測試的領導者。我們確實發現，我們的（聽不清）成功記錄有 5 個批准，超過 600,000 名患者接受了 ENHANZE 藥物治療，這確實使我們處於有利地位和談判地位，可以繼續擴大我們的交易數量。所以這就是我要說的。

On ViivGrad, as people may be aware, the FDA did feel that due to some additional data that was submitted during the review process that they needed more time to review. They extended the PDUFA date by 3 months. And so now that PDUFA date is June of 2023. We do have milestones associated with approval of products. And so obviously, this pushing out 3 months doesn't any change to our guidance as we still expect this to fall within 2023 based on all the information we have today.

在 ViivGrad 上，正如人們可能知道的那樣，FDA 確實認為由於在審查過程中提交了一些額外的數據，他們需要更多時間來審查。他們將 PDUFA 日期延長了 3 個月。所以現在 PDUFA 日期是 2023 年 6 月。我們確實有與產品批准相關的里程碑。很明顯，推遲 3 個月不會改變我們的指導方針，因為根據我們今天掌握的所有信息，我們仍然預計這將在 2023 年內完成。

Your next question comes from the line of Jason Butler with JMP Securities.

你的下一個問題來自 Jason Butler 與 JMP Securities 的對話。

2 for me. First of all, you pointed previously to the potential for an ENHANZE to injector partnership or collaboration this year. Is that still your expectation that, that could occur? And then secondly, the clinical work that you're doing, the feasibility testing, can you maybe give us some parameters about how you're assessing success or progress would that work in 2023?

2 對我來說。首先，您之前指出了今年 ENHANZE 與註射器合作或協作的潛力。您仍然期望那會發生嗎？其次，你正在做的臨床工作，可行性測試，你能不能給我們一些關於你如何評估成功或進展的參數，這些參數將在 2023 年發揮作用？

Yes. Thanks for that, Jason. Yes, we are indeed still planning and actively discussing with both current and potential new partners, the beginning development program of ENHANZE with a high volume auto-injector. So very happy with the progress of those discussions. The clinical studies, of which we -- in my prepared remarks mentioned, we expect to have data for that midyear is a feasibility study. We created a prototype. We tested it in some other models by the end of last year, which was our goal. But now we want to take it into patients, human volunteers and basically just show the feasibility and reliability of it. So as an example, the primary endpoint will focus on the number of devices that fired appropriately and delivered the drug in the required amount of time. That's pretty standard for these types of tests, and it's a nice way just to confirm the prototype is effective in doing what it was designed to do.

是的。謝謝你，傑森。是的，我們確實仍在計劃並與現有和潛在的新合作夥伴積極討論 ENHANZE 的大容量自動注射器的初始開發計劃。對這些討論的進展非常滿意。我們在準備好的發言中提到的臨床研究是一項可行性研究，我們希望獲得該年中的數據。我們創建了一個原型。我們在去年年底之前在其他一些模型中對其進行了測試，這是我們的目標。但現在我們想把它帶到病人、人類誌願者身上，基本上只是展示它的可行性和可靠性。因此，作為一個例子，主要終點將關注適當發射並在所需時間內輸送藥物的設備數量。這對於這些類型的測試來說是非常標準的，而且這是確認原型在執行其設計目的時有效的好方法。

Your next question will come from the line of Jessica Fye with JPMorgan.

您的下一個問題將來自 JPMorgan 的 Jessica Fye。

First, can you elaborate a little bit on the studies, the profile enhancing studies mentioned on the last slide of the deck regarding patient preference and on-body device? Just curious to learn a little more there.

首先，您能否詳細介紹一下研究，最後一張幻燈片上提到的關於患者偏好和身體設備的概況增強研究？只是想在那裡多學一點。

And then second, following up on an earlier question about Merck's subcu pembro that sounds like it's using hyaluronidase as well. Can you walk through why you would not be worried about partners trying to pursue a similar approach, creating their own enhances products with hyaluronidase and/or whether you expect Merck to infringe any IP?

其次，跟進一個關於默克公司 subcu pembro 的早期問題，聽起來它也在使用透明質酸酶。你能解釋一下為什麼你不擔心合作夥伴會嘗試採用類似的方法，用透明質酸酶創造他們自己的增強產品和/或你是否期望默克公司侵犯任何知識產權？

(inaudible) those questions, yes. I'll begin with the profile enhancing studies and for everybody that's on Slide 18 of the deck that we showed. And I think Jess, you particularly wanted to hear about the patient preference study and the on-body device. These are studies that partners are doing for already commercialized or late-stage development drugs. And it's all -- these types of studies are done to enhance the profile or provide additional information to inform patients and/or physicians with regard to how the drug can be used. These are trials that are actually listed on clinicaltrials.gov, but we didn't have permission from our partners to actually list them here. But you can find more about them and pretty routine and I think exciting that partners are continuing to explore and expand the profile of drugs that are in development.

（聽不清）那些問題，是的。我將從個人資料增強研究和我們展示的幻燈片 18 上的每個人開始。我想 Jess，你特別想听聽有關患者偏好研究和體上設備的信息。這些是合作夥伴正在為已經商業化或處於後期開發階段的藥物進行的研究。僅此而已——進行這些類型的研究是為了增強概況或提供額外信息，以告知患者和/或醫生有關如何使用藥物的信息。這些試驗實際上列在 clinicaltrials.gov 上，但我們沒有得到合作夥伴的許可，無法在此處實際列出它們。但是你可以找到更多關於它們的信息和非常常規的信息，我認為合作夥伴正在繼續探索和擴大正在開發的藥物的概況令人興奮。

With regard to more accounts, I think the reason we are not worried about our current partners wanting to move and develop their own higher (inaudible) and start incorporating that really focuses on a number of factors. The first one is that we bring a very strong safety track record. The issue when you combine 2 biologics together is they worry about immunogenicity. And with 600,000 patients treated, they know that, that has been a very well-characterized safety profile. First question comes up in all of our new deal negotiations is that worry.

關於更多客戶，我認為我們不擔心我們當前的合作夥伴想要移動和開發他們自己的更高（聽不清）並開始合併的原因確實集中在許多因素上。第一個是我們帶來了非常強大的安全記錄。當您將 2 種生物製劑組合在一起時，問題是它們擔心免疫原性。他們知道，有 600,000 名患者接受治療，這是一個非常典型的安全性特徵。在我們所有的新協議談判中出現的第一個問題就是這種擔憂。

I think that's the first one, Jess. We also have established a very strong relationship with all of our partners demonstrating our expertise in development and regulatory and reliability of supply. And if you like the phrase of the aim broken, why fix it, I think that is another reason that would not consider doing that. We obviously are very conscious about being reliable and a low-cost supplier to our partners. So then thinking about that would make no sense. And then the third one, I think, is a little bit more strategic for the partners. And they are, as we look at our partners, many of them are more focused on developing new molecular entities to deliver new large revenue streams rather than take the time and resources to focus on in modest reduction to what it's costing, for example, in a royalty rate. And so for all of those factors, we think it's highly unlikely that our partners would want to develop their own RUPH20 and with no indication they are.

我認為這是第一個，Jess。我們還與所有合作夥伴建立了非常牢固的關係，展示了我們在開發和監管以及供應可靠性方面的專業知識。如果您喜歡“目標已損壞，為什麼要修復”這句話，我認為這是不考慮這樣做的另一個原因。顯然，我們很清楚要成為我們合作夥伴的可靠和低成本供應商。那麼再考慮這個就沒有意義了。然後第三個，我認為，對合作夥伴來說更具戰略意義。他們是，當我們審視我們的合作夥伴時，他們中的許多人更專注於開發新的分子實體以提供新的大量收入流，而不是花時間和資源專注於適度降低成本，例如，特許權使用費率。因此，對於所有這些因素，我們認為我們的合作夥伴不太可能想要開發他們自己的 RUPH20，而且沒有跡象表明他們會這樣做。

Our next question will come from the line of Corinne Jenkins with Goldman Sachs.

我們的下一個問題將來自 Corinne Jenkins 與高盛的合作。

So I think maybe just for clarification for me. I think we've previously talked a lot about the 5 ml, but now you're talking about a 10 ml as well. Can you just talk about where you stand in the development of that 10 ml version? And what are some of the gating steps before that can enter the clinic?

所以我想也許只是為了澄清一下。我想我們之前已經談了很多關於 5 毫升的，但現在你也在談論 10 毫升。您能談談您在開發 10 毫升版本時的立場嗎？在進入診所之前有哪些門控步驟？

Yes. Thanks for that, Corinne. And our prototype has actually been designed with flexibility that depending on what a partner actually wants, it can deliver anything from 5 ml to 10 ml. And so it's the same basic prototype that we have in development. It's just the fill cartage, will be able to be varied depending on what volume that partner actually wants. So this clinical testing that we plan to do this year will evaluate some several options of volume up to 10 ml.

是的。謝謝你，科琳。我們的原型設計實際上具有靈活性，根據合作夥伴的實際需求，它可以提供 5 毫升到 10 毫升的任何東西。因此，它與我們開發中的基本原型相同。這只是填充運輸，可以根據合作夥伴實際需要的數量而變化。因此，我們計劃今年進行的這項臨床測試將評估一些容量高達 10 毫升的幾種選擇。

And then as you think about kind of your current portfolio of partnered products, what portion of them fall under 10 ml versus 5 ml versus less than that? Is that something you can provide clarity on?

然後，當您考慮您當前的合作產品組合時，其中哪些部分低於 10 毫升，哪些低於 5 毫升，哪些低於 10 毫升？您可以澄清一下嗎？

Yes. We've mentioned when we did the acquisition, that we have a small number of our partner programs today that are in those volume ranges. We tended to work on larger volumes, 15 ml they've been quite common for our going. But there are certainly a handful of current partners who are in that 5 ml to 10 ml range. They haven't provided that information publicly, so we're not in a position to do that. But as we said when we did the acquisition, this is also a part of the strategy and moving to ENHANZE was the high-volume auto-injector is to get new deals and new collaboration partners. And I can say from us evaluating the landscape, we see a number of opportunities out there that maybe new deals for us in the future that allow us to be delivering that 5ml to 10 ml a month as well. So think of it as some opportunity for the current partners, but really this was to open up a whole market of opportunity for ENHANZE Halozyme.

是的。我們在進行收購時提到過，我們今天有少量合作夥伴計劃處於這些數量範圍內。我們傾向於使用更大的體積，15 毫升對我們來說已經很常見了。但肯定有少數當前的合作夥伴在 5 毫升到 10 毫升的範圍內。他們沒有公開提供這些信息，所以我們無法做到這一點。但正如我們在進行收購時所說的那樣，這也是戰略的一部分，轉向 ENHANZE 是大容量自動注射器是為了獲得新交易和新合作夥伴。我可以說，從我們對前景的評估來看，我們看到了很多機會，這些機會可能會在未來為我們提供新的交易，讓我們每月也能提供 5 毫升到 10 毫升的產品。因此，將其視為當前合作夥伴的一些機會，但實際上這是為 ENHANZE Halozyme 開闢了一個充滿機會的市場。

Maybe just one last one for me. We've got a couple of product launches coming this year. How should we think about the path to co-formulation patents for those products? Is that something we can get some visibility on in the near term?

也許對我來說只是最後一個。今年我們將推出幾款產品。我們應該如何思考這些產品的聯合配方專利路徑？這是我們可以在短期內獲得一些可見性的東西嗎？

Yes, I can say that all of our currently marketed products have received or have pending patents for co-formulation patents. I can also say Corinne that all of our development partners are very actively engaged in a number of the ones who've got advanced to late-stage development have already filed applications for co-formulation patents. So specific by partner is not something we can talk about because that's partner confidential information. And I think the visibility will come as patents are issued, those become public domain. And at that point in time, you'll be able to find them and we'll be able to talk about them.

是的，我可以說我們目前銷售的所有產品都已獲得或正在申請聯合配方專利。我還可以說 Corinne，我們所有的開發合作夥伴都非常積極地參與了一些已經進入後期開發的合作夥伴已經提交了聯合配方專利的申請。合作夥伴如此具體我們不能談論，因為那是合作夥伴的機密信息。而且我認為隨著專利的發布，這些成為公共領域，知名度將會到來。屆時，您將能夠找到它們，我們將能夠討論它們。

But our partners have been unanimous in their support of protecting their inventions and filing co-form patents, which obviously, we are very pleased about and support because, in general, those have benefits to us in terms of the duration of time we get royalties, and they can also push out the time for the stack on. So we're very lined in our very active focus on new co-form submissions.

但是我們的合作夥伴一致支持保護他們的發明和申請聯合專利，顯然，我們對此感到非常高興和支持，因為總的來說，就我們獲得專利使用費的持續時間而言，這些對我們有好處，他們還可以推遲堆棧的時間。因此，我們非常積極地關注新的聯合表單提交。

Your next question will come from the line of Vikram Purohit with Morgan Stanley.

您的下一個問題將來自 Vikram Purohit 與摩根士丹利的合作。

So we had one question on subcutaneous ocrelizumab. So assuming the Phase III data here is positive, how do you foresee uptake for a subcu option ramping in this market, particularly given some recent competitive developments here in the multiple sclerosis space?

所以我們有一個關於皮下注射 ocrelizumab 的問題。因此，假設此處的 III 期數據是積極的，您如何預見該市場對 subcu 選項的採用，特別是考慮到多發性硬化症領域最近的一些競爭發展？

Yes. And so we are expecting, based on latest comments from Roche, the data midyear, which with the goal of taking therapy from the treatment and observation time for a minimum of 3.5 hours to 6 hours then to the initial doses with subcu being an hour for injection and observation. And ultimately, the goal is 10 minutes if the data supports that. So you can see what a transformation that will be for patients who are receiving MS therapy, lifelong and having to go to an infusion suite. And so I do think that based on that profile and be able to get to a simple 10-minute injection, this will be very competitive with the other products that are available on the market. Roche has not commented on specific uptake, but they have commented that they see an exciting market for the subcu option and delivery.

是的。因此，根據羅氏公司的最新評論，我們預計年中的數據，其目標是從治療和觀察時間開始至少 3.5 小時至 6 小時，然後再到初始劑量，subcu 為 1 小時注射和觀察。最終，如果數據支持的話，目標是 10 分鐘。因此，您可以看到對於終生接受 MS 治療並且不得不去輸液室的患者來說，這將是一個多麼大的轉變。因此，我確實認為，基於該配置文件並能夠進行簡單的 10 分鐘注射，這將與市場上的其他產品相比具有很強的競爭力。羅氏沒有對具體的吸收發表評論，但他們評論說，他們看到了 subcu 選項和交付的令人興奮的市場。

(Operator Instructions) Your next question will come from the line of David Risinger with SVB Securities.

（操作員說明）您的下一個問題將來自 SVB 證券公司的 David Risinger。

This is Dan Tarjan on for Dave. 2 questions for us, please. So one, can you provide some more color on your portfolio of Phase I candidates and including the historical of a Phase I candidate have actually advance into Phase III and also the typical time line for a Phase III go/no-go decision after candidates enters Phase I? Second question, any modeling color you can provide on the first quarter of 2023 and the following quarters?

我是 Dave 的 Dan Tarjan。請問我們 2 個問題。那麼，您能否在第一階段候選人的投資組合中提供更多顏色，包括第一階段候選人實際上已經進入第三階段的歷史，以及候選人進入後第三階段通過/不通過決定的典型時間線第一階段？第二個問題，2023年第一季度及之後的幾個季度，你們有什麼造型顏色可以提供嗎？

So with regard to the Phase I candidate that those really today would be what we are calling our Wave 4 products.

因此，關於第一階段候選產品，今天真正的產品就是我們所說的第 4 波產品。

And let's turn to that page. So that will be listed on Page 9. And as you can imagine that it really does all the on the individual partners plans and programs as to exactly what that time line is. The 2 products that are at the top of the list in that case, anivacumab and nivolumab moved pretty rapidly from their end of Phase I into the Phase III decision. In other cases, we have studies that are ongoing, such as argenx-117 and repivy. So those are still active studies, and so you wouldn't move forward.

讓我們翻到那個頁面。所以這將列在第 9 頁上。正如您可以想像的那樣，它確實在各個合作夥伴的計劃和計劃中完成了關於該時間表的所有內容。在這種情況下，排在首位的 2 種產品，anivacumab 和 nivolumab 非常迅速地從 I 期末期進入 III 期決策。在其他情況下，我們有正在進行的研究，例如 argenx-117 和 repivy。所以那些仍然是活躍的研究，所以你不會前進。

There is one study there, atezolizumab. I think we've talked about that before, where we heard comments from Horizon to say they were evaluating going forward in options with and without Page 20. And so we're still waiting for a final decision on the plan there. But I would say just based on those examples, the majority of the studies here listed are still ongoing in the Phase I with atezolizumab being one that's completed. And so once those studies are finished and a decision is made and often there's a conversation with the FDA about the design of the Phase III study. It usually is measured in months time, I think 6 months plus or minus, is a reasonable time frame for a transition, we might see between a Phase I and a Phase III for a partner who is wanting to move quickly to move forward into Phase III development.

那裡有一項研究，atezolizumab。我想我們之前已經討論過這個問題，我們聽到 Horizon 的評論說他們正在評估有和沒有第 20 頁的選項。因此我們仍在等待那裡的計劃的最終決定。但我想說，僅僅基於這些例子，這裡列出的大部分研究仍在第一階段進行，其中 atezolizumab 是一個已經完成的研究。因此，一旦這些研究完成並做出決定，通常會與 FDA 就 III 期研究的設計進行對話。它通常以月為單位來衡量，我認為 6 個月或更短是過渡的合理時間框架，對於希望快速進入階段的合作夥伴，我們可能會在第一階段和第三階段之間看到三、發展。

If I -- sorry, can you just repeat the second question? You cut a little bit for us.

如果我——抱歉，你能重複第二個問題嗎？你為我們剪了一點。

So the second question was any modeling perspective for the first quarter of 2023 and the following quarters.

因此，第二個問題是 2023 年第一季度及隨後幾個季度的任何建模觀點。

Yes, I'll ask Nicole to address that.

是的，我會請 Nicole 解決這個問題。

Yes. Happy to share. So while we don't provide guidance on a quarterly basis, what I can say as we look forward to Q1, from a revenue perspective, we are able to share that total collaboration revenue. We are forecasting to be relatively flat in 2023 versus 2022. And we do have line of sight to milestones beginning in the second quarter of the year and really being more weighted into the second half of the year. So that can give you a little bit of line of sight to expectations.

是的。樂於分享。因此，雖然我們不按季度提供指導，但在我們期待第一季度時，我可以說，從收入的角度來看，我們能夠分享合作總收入。我們預測 2023 年與 2022 年相比會相對持平。我們確實看到了從今年第二季度開始的里程碑，並且實際上在下半年更加重視。這樣可以讓您對預期有一點了解。

And then when I talk about maybe looking at royalty. So just to reiterate, our royalty guidance for the full year is $445 million to $455 million. Well, what we do see in Q1 is sequential growth to be flattening in the first quarter and then grow sequentially thereafter throughout the year. And that's really a driver of seasonality with our (inaudible). We have FX leases at the start of the year. And I'm also looking into Q1, we're expecting minimal true-up in the first quarter.

然後當我談到可能會考慮版稅時。因此，重申一下，我們全年的特許權使用費指導價為 4.45 億美元至 4.55 億美元。好吧，我們在第一季度看到的是第一季度的環比增長趨於平緩，然後全年環比增長。這確實是我們（聽不清）的季節性驅動因素。我們在年初有外匯租賃。而且我也在研究第一季度，我們預計第一季度的調整最少。

And so I will just add that we wanted to provide that bit of color. We're very excited about the continued growth that we're going to see in the subsequent quarters, both in terms of our royalties but also milestones that are a little -- that will begin in Q2 as Nicole said.

所以我只想補充一點，我們想提供那種顏色。我們對接下來幾個季度將看到的持續增長感到非常興奮，無論是在我們的特許權使用費方面，還是在里程碑方面——正如妮可所說，這將在第二季度開始。

We have no further questions at this time. Ladies and gentlemen, that will conclude today's meeting. Thank you all for joining. You may now disconnect.

目前我們沒有其他問題。女士們，先生們，今天的會議到此結束。謝謝大家的加入。您現在可以斷開連接。