Heron Therapeutics Inc (HRTX) 2022 Q4 法說會逐字稿

Good day, ladies and gentlemen. Thank you for standing by. Welcome to the Heron Therapeutics Fourth Quarter 2022 Earnings Conference.

女士們先生們，美好的一天。謝謝你的支持。歡迎來到 Heron Therapeutics 2022年第四季度收益會議。

As a reminder, this conference is being recorded. And now I would like to turn the call over to David Szekeres, Executive Vice President, Chief Operating Officer. Please proceed.

提醒一下，這次會議正在錄製中。現在我想把電話轉給執行副總裁兼首席運營官 David Szekeres。請繼續。

Thank you, Lisa. Good afternoon, everyone, and thank you for joining us.

謝謝你，麗莎。大家下午好，感謝您加入我們。

With me today from Heron are Barry Quart, Chief Executive Officer and Chairman; John Poyhonen, President and Chief Commercial Officer; and Kimberly Manhard, Executive Vice President of Drug Development.

今天和我一起來自 Heron 的有首席執行官兼董事長 Barry Quart；總裁兼首席商務官 John Poyhonen；和藥物開發執行副總裁 Kimberly Manhard。

For those of you participating via conference call, the slides are made available via webcast and can also be accessed by going to the Investor Relations page of our website following conclusion of today's call.

對於那些通過電話會議參加的人，可以通過網絡廣播獲得幻燈片，也可以在今天的電話會議結束後訪問我們網站的投資者關係頁面來訪問這些幻燈片。

Before we begin, I would like to remind you that this call will contain forward-looking statements concerning Heron's future expectations, plans, prospects, corporate strategy and performance, which constitute forward-looking statements for the purposes of the safe harbor provision under the Private Securities Litigation Reform Act of 1995.

在我們開始之前，我想提醒您，本次電話會議將包含有關 Heron 的未來預期、計劃、前景、公司戰略和業績的前瞻性陳述，這些陳述構成了針對 Private 下安全港條款的前瞻性陳述。 1995 年證券訴訟改革法案。

Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in our filings with the SEC. In addition, any forward-looking statements represent our views only as of the date of this webcast and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update such statements.

由於各種重要因素，包括我們在提交給美國證券交易委員會的文件中討論的因素，實際結果可能與這些前瞻性陳述所表明的結果存在重大差異。此外，任何前瞻性陳述僅代表我們截至本次網絡廣播之日的觀點，不應被視為代表我們截至任何後續日期的觀點。我們特別聲明不承擔任何更新此類聲明的義務。

Now I'll turn the call over to Barry.

現在我會把電話轉給巴里。

Thank you, David. Welcome, everyone. Thank you for joining us this afternoon. For those who are wondering why this call is later in the month than usual, we are currently not an accelerated filer, and we wanted to give our newly reconstituted Board of Directors the opportunity to get to know the company before closing the quarter. We had an excellent fourth quarter and are obviously delighted with the strong increase in sales of ZYNRELEF last quarter, along with the growth of our CINV business.

謝謝你，大衛。歡迎大家。感謝您今天下午加入我們。對於那些想知道為什麼這次電話會議比平時晚的人，我們目前不是加速申報人，我們希望讓我們新重組的董事會有機會在本季度結束前了解公司。我們在第四季度表現出色，顯然對上季度 ZYNRELEF 銷售額的強勁增長以及我們 CINV 業務的增長感到高興。

This month's launch of APONVIE, our fourth commercial product rounds out our portfolio. First quarter has started off more slowly for ZYNRELEF, due to the normal seasonal decline in surgeries in the first quarter of each year. Even with the expected decline in surgeries, we continue to see growth of ZYNRELEF, albeit at a slower pace than fourth quarter. The Board has been working hard with the management team to develop a strategy to accelerate growth of ZYNRELEF and our other products.

本月推出的 APONVIE 是我們的第四款商業產品，進一步完善了我們的產品組合。由於每年第一季度手術量的正常季節性下降，ZYNRELEF 第一季度的開局速度較慢。即使手術量預計會下降，我們仍繼續看到 ZYNRELEF 的增長，儘管增速低於第四季度。董事會一直與管理團隊一起努力製定戰略，以加速 ZYNRELEF 和我們其他產品的增長。

The real-world experience with ZYNRELEF continues to show strong efficacy, consistent with our clinical trials, but feedback from customers is that there are 2 opportunities to improve growth, expanding the label and improving withdrawal of the drug product from the vial. Correcting the limited label is already in progress with our December submission of sNDA #2, requesting a label covering soft tissue and orthopedic procedures. This requested indications, if approved, would cover essentially all our 14 million target procedures. We currently provide a vented vial spike in the ZYNRELEF kit, designed to withdraw the product as simply as possible.

ZYNRELEF 的真實世界經驗繼續顯示出強大的療效，這與我們的臨床試驗一致，但客戶的反饋是有 2 個機會可以促進增長、擴大標籤和改善藥物產品從小瓶中的取出。我們在 12 月提交的 sNDA #2 中已經開始更正有限的標籤，要求標籤涵蓋軟組織和骨科手術。這一請求的適應症如果獲得批准，將基本上涵蓋我們所有的 1400 萬個目標程序。我們目前在 ZYNRELEF 套件中提供一個通氣瓶尖頭，旨在盡可能簡單地取出產品。

The high turnover of nurses, post-COVID, has added an unexpected complexity. Because ZYNRELEF is viscous, it can still take several minutes to withdraw all the product, and even if the nurse doesn't follow instructions, it can take even longer. This can be annoying and diminish use of the product. With the broader label expected later this year, we want to make sure the product is as easy to use as possible.

COVID 後護士的高流動性增加了意想不到的複雜性。由於 ZYNRELEF 是粘性的，抽出所有產品仍需要幾分鐘時間，即使護士不按照說明進行操作，也可能需要更長時間。這可能很煩人並且會減少產品的使用。預計今年晚些時候會有更廣泛的標籤，我們希望確保產品盡可能易於使用。

Optimization will be in 2 steps. Step 1 is to complete the development and gain approval of a greatly improved custom device designed to speed the withdrawal of the product. With step 2 being the continued development of a prefilled syringe.

優化將分兩步進行。第 1 步是完成開發並獲得批准，這是一種經過大幅改進的定制設備，旨在加快產品的撤回速度。第二步是預充式註射器的持續開發。

Because customers have indicated that they would use more ZYNRELEF if it was easier to remove from the vial and the prefilled syringe will take a few years, we have developed an innovative vial access needle or VAN, which not only reduces the withdrawal time from minutes to around 30 seconds. It also covers the vial to eliminate the need for a non-sterile nurse to be involved withdrawing the drug product. This seamless single person withdrawal tested very well by both customers and noncustomers. We are pushing hard to get this device approved by the middle of next year.

由於客戶表示，如果更容易從小瓶中取出，他們會使用更多的 ZYNRELEF，而預裝注射器將需要幾年時間，因此我們開發了一種創新的小瓶接入針或 VAN，它不僅將取出時間從幾分鐘縮短到大約 30 秒。它還包括藥瓶，以消除非無菌護士參與取出藥品的需要。這種無縫的單人提款在客戶和非客戶中都得到了很好的測試。我們正在努力爭取在明年年中之前獲得該設備的批准。

As noted, the prefilled syringe is the optimal presentation for ZYNRELEF, and we have been working on it for several years. We are very familiar with this technology as SUSTOL is provided in a prefilled syringe. However, ZYNRELEF has proved to be much more complicated and has significant -- which has significantly lengthened the time to development.

如前所述，預裝注射器是 ZYNRELEF 的最佳表現形式，我們已經為此努力了數年。我們非常熟悉這項技術，因為 SUSTOL 在預裝注射器中提供。然而，事實證明，ZYNRELEF 要復雜得多，而且具有重要意義——這顯著延長了開發時間。

The great news is that we have recently overcome several of the most difficult obstacles and are now ready to push this development project forward. An added benefit is that prefilled syringes of ZYNRELEF should also help reduce the cost of goods.

好消息是，我們最近克服了幾個最困難的障礙，現在準備好推進這個開發項目。另一個好處是 ZYNRELEF 的預裝注射器也應該有助於降低商品成本。

I will now turn the call over to John.

我現在將電話轉給約翰。

Thank you, Barry. We made solid progress across our acute care and oncology care franchises during the fourth quarter. During my presentation, I'll start with a number of updates on key performance metrics related to ZYNRELEF, then I'll provide an update on our APONVIE launch and finish with an update on another strong commercial quarter with our oncology care business.

謝謝你，巴里。第四季度，我們在急症護理和腫瘤護理特許經營方面取得了穩步進展。在我的演講中，我將首先介紹一些與 ZYNRELEF 相關的關鍵績效指標的更新，然後我將提供我們 APONVIE 發布的更新，並以我們腫瘤護理業務的另一個強勁商業季度的更新作為結束。

I'll start by summarizing ZYNRELEF's quarterly performance of our lead performance indicators. The fourth quarter has historically been the strongest quarter of our currently indicated surgical procedures. We were able to take advantage of the seasonality as ZYNRELEF net sales grew to $3.9 million for the quarter, representing a 44% increase over the prior quarter and a 362% increase over the same quarter in the prior year.

首先，我將總結 ZYNRELEF 在我們的主要績效指標中的季度表現。從歷史上看，第四季度是我們目前指定的外科手術中最強勁的季度。我們能夠利用季節性因素，因為 ZYNRELEF 本季度的淨銷售額增長到 390 萬美元，比上一季度增長 44%，比去年同期增長 362%。

Fourth quarter demand units grew to 20,765 units, representing a 38% increase over the prior quarter and a 301% increase over the same quarter in the prior year. Total ZYNRELEF unique ordering accounts grew to 793 through the end of the fourth quarter compared to 704 through the end of the third quarter.

第四季度需求單位增長至 20,765 單位，比上一季度增長 38%，比去年同期增長 301%。截至第四季度末，ZYNRELEF 唯一訂購賬戶總數從第三季度末的 704 個增至 793 個。

Total formulary approvals for ZYNRELEF grew to 522 through the end of February 2023 compared to 416 approvals through the end of October 2022. Importantly, we're also seeing growth with integrated delivery networks, or IDNs, with an updated total of 74 IDNs that have added ZYNRELEF to formulary. Gaining IDN support is a critical component to drive therapeutic interchanges with our key accounts substituting ZYNRELEF for Exparel for indicated procedures in the future. Overall, we made solid progress in Q4 and are implementing key initiatives to accelerate ZYNRELEF sales in our existing user accounts in 2023.

到 2023 年 2 月底，ZYNRELEF 的總處方批准數量從 2022 年 10 月底的 416 個增加到 522 個。重要的是，我們還看到集成交付網絡或 IDN 的增長，更新後的 IDN 總數為 74 個將 ZYNRELEF 添加到處方集中。獲得 IDN 支持是推動治療交流的關鍵組成部分，我們的主要客戶在未來用 ZYNRELEF 代替 Exparel 進行指定程序。總體而言，我們在第四季度取得了穩步進展，並正在實施關鍵舉措，以在 2023 年加速現有用戶賬戶中的 ZYNRELEF 銷售。

As mentioned on the prior slide, there has been consistent quarterly seasonality in elective procedures. The fourth quarter has always been the highest volume quarter based on patients having met their annual deductibles during the year, along with holiday time off to recover and revamp. The line graph on this slide demonstrates the quarterly seasonality when looking at Exparel historical sales from 2018 through 2022, which have been adjusted by removing 2020 results to eliminate the direct impact of COVID.

如前一張幻燈片所述，選擇性程序一直存在季度季節性。根據患者在這一年中達到年度免賠額的情況，以及休假恢復和改造的情況，第四季度一直是銷量最高的季度。這張幻燈片上的折線圖展示了查看 Exparel 從 2018 年到 2022 年的歷史銷售額時的季度季節性，這些數據已經通過刪除 2020 年的結果進行了調整，以消除 COVID 的直接影響。

Historically, the fourth quarter has shown significant growth versus the third quarter, only to be followed with a significant reduction in the first quarter results. As previously mentioned, ZYNRELEF demand units grew by 38% in the fourth quarter over the third quarter. This translates into an average of 1,597 units per week during the quarter. With 2 weeks remaining in the first quarter of 2023, the ZYNRELEF weekly average is about 1,760 units per week, representing a 10% increase over the Q4 weekly average.

從歷史上看，第四季度與第三季度相比出現了顯著增長，但緊隨其後的是第一季度業績的大幅下滑。如前所述，第四季度 ZYNRELEF 需求單位比第三季度增長了 38%。這相當於本季度平均每週 1,597 個單位。 2023 年第一季度還剩 2 週，ZYNRELEF 週均值約為 1,760 台，較 Q4 週均值增長 10%。

Next, I wanted to provide an update on a key top-down strategy of targeting integrated delivery networks, or IDNs, to create new system-wide opportunities for Therapeutic Interchange from Exparel to ZYNRELEF for indicated procedures. Thus far, 74 IDNs have added ZYNRELEF to their formularies compared to 66 in our last uptake report. These 74 IDNs account for over 1.1 million annuals ZYNRELEF indicated procedures.

接下來，我想提供有關針對集成交付網絡或 IDN 的關鍵自上而下戰略的更新，以為指定程序從 Exparel 到 ZYNRELEF 的治療交換創造新的全系統機會。到目前為止，有 74 個 IDN 將 ZYNRELEF 添加到他們的處方集，而在我們上一份採用報告中有 66 個。這 74 個 IDN 佔每年超過 110 萬個 ZYNRELEF 指示程序。

Finally, our IDN formulary expansion now covers $149 million annual Exparel sales, and we've expanded to 17 IDNs at various stages of evaluating switching from Exparel to ZYNRELEF. Previously, we introduced a new metric to help evaluate the impact we're making with IDNs. As a reminder, the metric to measure performance is branded market share, which is simply ZYNRELEF units divided by the total number of Exparel units plus ZYNRELEF units.

最後，我們的 IDN 處方集擴展現在涵蓋了 1.49 億美元的 Exparel 年銷售額，並且我們已經擴展到 17 個處於評估從 Exparel 到 ZYNRELEF 轉換的不同階段的 IDN。之前，我們引入了一個新指標來幫助評估我們對 IDN 產生的影響。提醒一下，衡量績效的指標是品牌市場份額，即 ZYNRELEF 單位除以 Exparel 單位總數加上 ZYNRELEF 單位。

In order to benchmark the IDN progress against the entire market basket, we've included a total market branded share in addition to the IDN subcategories. The IDN subcategory branded results have not been updated to include the full 74 IDNs, with formulary approval and the 17 IDNs evaluating Therapeutic Interchange since many of these decisions came right in the fourth quarter or in this quarter. We'll update these numbers to reflect all our IDN wins in our next quarterly earnings report.

為了對照整個市場籃子來衡量 IDN 的進展，除了 IDN 子類別之外，我們還包括了總市場品牌份額。 IDN 子類別品牌結果尚未更新，以包括完整的 74 個 IDN、處方批准和 17 個 IDN 評估 Therapeutic Interchange，因為其中許多決定是在第四季度或本季度做出的。我們將更新這些數字，以反映我們在下一個季度收益報告中贏得的所有 IDN。

Overall, in the 66 IDNs with formulary approval, we're demonstrating solid branded market share growth at 9.1%, which is about twice the level of the total market. Advancing IDNs to evaluation of a Therapeutic Interchange is an important step in accelerating ZYNRELEF growth. As the table shows the 15 IDN evaluating TI have combined for a 12.5% branded share in Q4, which is significantly higher than the average for the 66 IDNs, which have ZYNRELEF on formulary.

總體而言，在獲得處方批准的 66 個 IDN 中，我們展示了穩健的品牌市場份額增長 9.1%，大約是整個市場水平的兩倍。將 IDN 推進治療交換評估是加速 ZYNRELEF 增長的重要一步。如表所示，15 個 IDN 評估 TI 在第 4 季度合併為 12.5% 的品牌份額，這明顯高於 66 個 IDN 的平均值，後者在處方集上有 ZYNRELEF。

Finally, we've also provided ZYNRELEF's branded market share for the top 5 IDN accounts out of the 15 IDNs evaluating Therapeutic Interchange from Exparel to ZYNRELEF. And this table, demonstrates our branded market share can grow very quickly to an approach to a high approaching 50% for the fourth quarter. Based on our current indicated procedures, 50% is approaching the upper limit of what we expect to receive until an additional label expansion, which is expected in October of this year.

最後，我們還提供了 ZYNRELEF 在評估從 Exparel 到 ZYNRELEF 的 Therapeutic Interchange 的 15 個 IDN 中排名前 5 的 IDN 賬戶的品牌市場份額。這張表表明，我們的品牌市場份額可以快速增長，第四季度接近 50%。根據我們目前指定的程序，50% 接近我們預計在今年 10 月進行額外標籤擴展之前收到的上限。

We share different versions of this slide in the past. Today's version upstates the pricing based on WAC price increases effective January 1, 2023. Switching to ZYNRELEF provides a cost savings of 23% to 34% based on wholesale acquisition cost. Even with Pacira finally offering 340B pricing in the fourth quarter of 2022, ZYNRELEF's 340B pricing still provides 340B accounts with a 23% to 32% savings compared to Exparel. Many 340B customers that we've spoken with have indicated the Pacira's response with the ZYNRELEF pricing strategy just doesn't allow them to effectively compete based on our clinical and value proposition.

我們過去分享過這張幻燈片的不同版本。今天的版本更新了基於 2023 年 1 月 1 日生效的 WAC 價格上漲的定價。根據批發採購成本，改用 ZYNRELEF 可節省 23% 至 34% 的成本。即使 Pacira 最終在 2022 年第四季度提供 340B 定價，與 Exparel 相比，ZYNRELEF 的 340B 定價仍為 340B 賬戶提供 23% 至 32% 的優惠。與我們交談過的許多 340B 客戶表示，Pacira 對 ZYNRELEF 定價策略的回應不允許他們根據我們的臨床和價值主張進行有效競爭。

Finally, from a reimbursement standpoint, using ZYNRELEF remains much more profitable with Medicare patients. In challenging financial times only ZYNRELEF provides separately reimbursed outside the surgical bundle payment and the hospital outpatient setting of care, which represents about 60% of the market opportunity. Based on these economic values, it's not surprising that large IDNs continue to evaluate ZYNRELEF for Therapeutic Interchange and the indicated procedures and are anxious to limit Exparel's usage. With FDA approval of our expanded indications anticipated later this year, we would expect many more IDNs to move towards switching.

最後，從報銷的角度來看，使用 ZYNRELEF 對於 Medicare 患者來說仍然更有利可圖。在充滿挑戰的金融時代，只有 ZYNRELEF 提供手術捆綁支付和醫院門診護理之外的單獨報銷，這代表了約 60% 的市場機會。基於這些經濟價值，大型 IDN 繼續評估 ZYNRELEF 治療交換和指定程序並急於限制 Exparel 的使用也就不足為奇了。隨著 FDA 批准我們預計在今年晚些時候擴大的適應症，我們預計會有更多的 IDN 轉向轉換。

Our top priority is to build consistent usage in existing ordering accounts. Our sales force is working to increase pull-through and build average order size. This could be accomplished by increasing the number of surgeons using ZYNRELEF at each count and the number of surgical procedures were achieved. During the fourth quarter, we began deploying new flexible resources to ensure that we have additional personnel for in-servicing surgeons and their staff. We have piloted 2 types of flexible resources. The hospital implementation team utilizes operating room educators to start new accounts with focus in services across all indicated surgical lines to establish a strong base for the future.

我們的首要任務是在現有訂購賬戶中建立一致的使用。我們的銷售人員正在努力提高拉動率並建立平均訂單量。這可以通過增加每次計數時使用 ZYNRELEF 的外科醫生的數量來實現，並實現外科手術的數量。在第四季度，我們開始部署新的靈活資源，以確保我們為在職外科醫生及其員工提供更多人員。我們試點了兩種靈活資源。醫院實施團隊利用手術室教育工作者開辦新客戶，重點關注所有指定手術線的服務，為未來打下堅實的基礎。

In addition, we have utilized medical device representatives in certain territories to build our Orthopedic business with TKA, THA and foot and ankle surgeries. It's important to note these reps are only paid for incremental growth they're generating. We're also focused on increasing communications on a number of outstanding real-world evidence studies using ZYNRELEF. For example, Dr. Kevin Warner, of Covenant Healthcare presented a poster at orthopaedics today with preliminary results comparing the use of ZYNRELEF versus a generic joint cocktail. Their results indicated that ZYNRELEF as part of a multimodal protocol in TKA, significantly reduced pain and morphine usage for 24 hours compared to the joint cocktail.

此外，我們利用某些地區的醫療器械代表來建立我們的骨科業務，包括 TKA、THA 以及足踝手術。重要的是要注意，這些代表只為他們產生的增量增長付費。我們還專注於使用 ZYNRELEF 加強對許多傑出的現實世界證據研究的交流。例如，Covenant Healthcare 的 Kevin Warner 博士今天在整形外科展示了一張海報，其中初步結果比較了 ZYNRELEF 與普通關節雞尾酒的使用。他們的結果表明，與聯合雞尾酒相比，ZYNRELEF 作為 TKA 多模式方案的一部分，在 24 小時內顯著減少了疼痛和嗎啡的使用。

Importantly, their patient length of stay was over 24 hours shorter with ZYNRELEF. We believe this type of real-world data will change practice, and we're working with other health care providers to share their data. Our efforts with IDNs have produced meaningful results in growing ZYNRELEF branded market share, and we'll continue to look for opportunities to expand our pipeline and pursue therapeutic interchanges with new customers. And finally, as Barry already indicated in his comments, we know that ZYNRELEF works exceptionally well with patients. But some customers would like to see the product easier to withdraw from the bile and we are committed to enhancing that process going forward.

重要的是，使用 ZYNRELEF，他們的患者住院時間縮短了 24 小時以上。我們相信這種類型的真實世界數據將改變實踐，並且我們正在與其他醫療保健提供者合作以共享他們的數據。我們在 IDN 方面的努力在增加 ZYNRELEF 品牌市場份額方面取得了有意義的成果，我們將繼續尋找機會擴大我們的管道並尋求與新客戶的治療交流。最後，正如 Barry 在他的評論中已經指出的那樣，我們知道 ZYNRELEF 對患者的效果非常好。但一些客戶希望看到產品更容易從膽汁中取出，我們致力於加強這一過程。

Now I'd like to shift the presentation to APONVIE, our new product for the prevention of post-operative nausea and vomiting or PONV. We truly believe that APONVIE and the PONV market is a big opportunity for Heron. We'll start with the name. APONVIE conveys aprepitant or PONV. The market research on the brand name was extremely positive from health care providers and importantly, differentiates this lower dosage offering of aprepitant emulsion from CINVANTI are highly effective and successful product for CINV.

現在我想將演示轉移到 APONVIE，這是我們用於預防術後噁心和嘔吐或 PONV 的新產品。我們堅信 APONVIE 和 PONV 市場對 Heron 來說是一個巨大的機遇。我們將從名稱開始。 APONVIE 傳送阿瑞匹坦或 PONV。醫療保健提供者對品牌名稱的市場研究非常積極，重要的是，將這種較低劑量的阿瑞匹坦乳劑產品與 CINVANTI 區分開來，是 CINV 的高效和成功產品。

We'll be targeting 36 million annual procedures in patients in moderate-to-high risk of PONV. In this segment, an estimated 12 million moderate-to-high-risk patients are not receiving any prophylaxis at all. One of our goals will be to use the 2020 consensus guidelines to change this practice, growing the market, addressing one of the most concerning side effects for patients undergoing surgery.

我們的目標是每年對 PONV 中高風險患者進行 3600 萬次手術。在這一部分中，估計有 1200 萬中度至高風險患者根本沒有接受任何預防措施。我們的目標之一是使用 2020 年共識指南來改變這種做法，發展市場，解決接受手術的患者最關心的副作用之一。

Market research identified a significant unmet need in the current market, including a more convenient product with faster onset, which APONVIE meets with a rapid IV push and 97% receptor occupancy within 5 minutes. A more effective product is desired and aprepitant is the most effective product for PONV prevention, alone, or in combination. And finally, longer-lasting treatment with APONVIE providing PONV prevention for up to 48 hours.

市場研究確定了當前市場中一個重大未滿足的需求，包括更方便、起效更快的產品，APONVIE 滿足了快速 IV 推動和 5 分鐘內 97% 的受體佔用。需要一種更有效的產品，而阿瑞匹坦是預防 PONV 最有效的產品，無論是單獨使用還是聯合使用。最後，使用 APONVIE 進行更持久的治療，可提供長達 48 小時的 PONV 預防。

This last unmet need is especially important with the growth in outpatient surgeries and patients being discharged after surgery. In short, APONVIE is clearly differentiated in this market and positioned for success. APONVIE is also the perfect strategic fit for Heron based on the synergies with our commercial organization. It starts with tremendous overlaps of accounts we are already targeting for ZYNRELEF. We have existing trusted relationships with anesthesia and pharmacy, which is critical for formulary access and usage. In addition, about 65% of our CINVANTI business comes from the hospital market. The existing positive experiences and major hospitals and IDNs should help us jump start upon the access and usage.

隨著門診手術和手術後出院患者的增長，這一最後未滿足的需求尤為重要。簡而言之，APONVIE 在這個市場上具有明顯的差異化優勢，並為成功做好了準備。基於與我們商業組織的協同作用，APONVIE 也非常適合 Heron。它始於我們已經針對 ZYNRELEF 定位的大量帳戶重疊。我們與麻醉和藥房建立了現有的信任關係，這對於獲取和使用處方集至關重要。此外，我們約 65% 的 CINVANTI 業務來自醫院市場。現有的積極經驗以及主要醫院和 IDN 應該可以幫助我們快速開始訪問和使用。

Next, I wanted to share some early plans and highlights on the APONVIE launch. Our most critical success factor will be accelerating formulary access to APONVIE. It all starts with a strong value proposition. We'll be offering 340B pricing, GPO contracts and full line wholesaler prime vendor discounts. Importantly, APONVIE will be the only product for PONV prevention that will have separate reimbursement outside the surgical bundled payment for PONV prevention for 3 years based on the pass-through for Medicare patients.

接下來，我想分享一些關於 APONVIE 發布的早期計劃和亮點。我們最關鍵的成功因素將是加速對 APONVIE 的處方訪問。這一切都始於強大的價值主張。我們將提供 340B 定價、GPO 合同和全線批發商主要供應商折扣。重要的是，APONVIE 將是唯一一種 PONV 預防產品，根據 Medicare 患者的傳遞，在 3 年的 PONV 預防手術捆綁支付之外單獨報銷。

Utilizing effective targeting will be key in building early access, and we'll start with oral aprepitant, CINVANTI and ZYNRELEF user account. Finally, we believe that we can leverage the 2020 consensus PONV guidelines with a focus on high-to-moderate risk PONV patients. We've had prior success promoting the NCCN guidelines where we were able to grow the NK market by 35% during the first year of the CINVANTI launch.

利用有效的目標定位將是建立早期訪問的關鍵，我們將從口服阿瑞匹坦、CINVANTI 和 ZYNRELEF 用戶帳戶開始。最後，我們相信我們可以利用 2020 年共識 PONV 指南，重點關注高至中度風險的 PONV 患者。我們之前在推廣 NCCN 指南方面取得了成功，在 CINVANTI 推出的第一年，我們能夠將 NK 市場增長 35%。

I also want to share some very early commercial progress on APONVIE. On March 6, 2023, we completed initial stocking of the distribution channel and full line and specialty distributors, and several have already placed reorders for APONVIE. As announced last week, CMS has approved pass-through status for APONVIE for 3 years, beginning April 1, 2023, under C-code C9145.

我還想分享一些關於 APONVIE 的非常早期的商業進展。 2023 年 3 月 6 日，我們完成了分銷渠道和全線和專業分銷商的初始備貨，並且有幾家已經為 APONVIE 下了再訂單。正如上周宣布的那樣，CMS 已根據 C 代碼 C9145 批准了 APONVIE 的直通狀態，為期 3 年，從 2023 年 4 月 1 日開始。

We're excited about the early customer feedback. On March 7 at the investor conference, we reported the first formulary approval and first end-user sale for APONVIE. Now I can report that we've achieved our first IDN formulary approval with a 9 hospital system, and the medical executive committee approved the formulary addition today with -- starting in April. Obviously, this is very early days, but we look forward to reporting additional details as we progress through the year.

我們對早期的客戶反饋感到興奮。在 3 月 7 日的投資者會議上，我們報告了 APONVIE 的首次處方批准和首次終端用戶銷售。現在我可以報告，我們已經通過 9 家醫院系統獲得了第一個 IDN 處方集批准，並且醫療執行委員會今天批准了處方集的添加——從 4 月開始。顯然，現在還為時尚早，但我們期待在今年取得進展時報告更多詳細信息。

Now I'd like to shift gears and review the fourth quarter results for our oncology care franchise. During the fourth quarter, our oncology care team did a tremendous job of growing our CINV business by -- net sales by 32% over the same quarter in the prior year. We're very proud of restoring growth to our CINV franchise, following generic arbitrages with both products and believe this will remain a valuable and highly profitable franchise for years to come. For the full year, our CINV franchise net sales were $97.5 million, an increase of 17% over the prior year.

現在我想換檔並回顧我們腫瘤護理特許經營權的第四季度業績。在第四季度，我們的腫瘤護理團隊在 CINV 業務增長方面做得非常出色——淨銷售額比去年同期增長了 32%。在對這兩種產品進行通用套利之後，我們為恢復 CINV 特許經營權的增長而感到自豪，並相信這在未來幾年仍將是一個有價值且高利潤的特許經營權。全年，我們的 CINV 特許經營淨銷售額為 9750 萬美元，比上年增長 17%。

The outlook for our CINV products remains positive based on continuing reimbursement tailwinds over the past year. As shown on the table, both CINVANTI and SUSTOL are in a very favorable reimbursement position versus the competition. In addition, the elimination of separate reimbursement for generic fosaprepitant in the hospital outpatient segment, effective January 1, 2022, continues to make the CINVANTI value proposition much more attractive. The new CMS guidelines implemented, effective January 1, 2023, that reimbursed or 340B accounts at a rate of ASP plus 6% compared to the prior rate of ASP minus 22% creates a windfall for those customers.

基於過去一年持續的報銷順風，我們 CINV 產品的前景仍然樂觀。如表中所示，與競爭對手相比，CINVANTI 和 SUSTOL 都處於非常有利的報銷位置。此外，自 2022 年 1 月 1 日起，取消醫院門診部門對仿製藥福沙匹坦的單獨報銷，繼續使 CINVANTI 的價值主張更具吸引力。新的 CMS 指南於 2023 年 1 月 1 日生效，以 ASP 加 6% 的比率報銷或 340B 帳戶，而之前的 ASP 比率為負 22%，這為這些客戶創造了一筆意外之財。

We believe with a significant portion of our CINVANTI demand sales already in 340B accounts. This new opportunity will help us increase unit sales to an even greater extent this year.

我們相信我們的 CINVANTI 需求銷售的很大一部分已經在 340B 賬戶中。這個新機會將幫助我們在今年更大程度上增加單位銷售額。

Finally, the large-scale CINVANTI manufacturing is now in line with product in the distribution channel resulting in gross margin increasing from about 50%, moving towards 75%. For the full year 2023, we expect CINV franchise net sales in the range of $99 million to $103 million.

最後，大規模的 CINVANTI 製造現在與分銷渠道中的產品保持一致，導致毛利率從 50% 左右增加到 75%。對於 2023 年全年，我們預計 CINV 的特許經營淨銷售額在 9900 萬至 1.03 億美元之間。

That completes my prepared remarks, and I'll now turn the call back over to Barry.

我準備好的發言到此結束，現在我將把電話轉回給巴里。

Thank you, John. We will conclude the formal presentation with our financial overview slide. Heron had cash, cash equivalents and short-term investments of $84.9 million as of December 31, 2022. Net cash used for operating activities for the 3 months ended December 31, 2022, was $37.5 million, including a payment of approximately $10 million for polymer. Without the polymer payment, our underlying burn was about $27 million and the full impact of reducing headcount by approximately 34% last year, will continue to be realized through this year and next.

謝謝你，約翰。我們將以我們的財務概覽幻燈片結束正式演示。截至 2022 年 12 月 31 日，Heron 擁有現金、現金等價物和短期投資 8,490 萬美元。截至 2022 年 12 月 31 日止三個月，用於經營活動的現金淨額為 3,750 萬美元，其中包括約 1,000 萬美元的聚合物付款.如果不支付聚合物費用，我們的潛在損失約為 2700 萬美元，去年裁員約 34% 的全部影響將在今年和明年繼續實現。

R&D expense declined to $11.1 million in fourth quarter 2022 compared to $28.9 million in fourth quarter of '21 and $20.5 million last quarter. We are also working with all our manufacturers to reduce external spending over the next few years as sales continue to ramp. We would expect cash burn in the teens in the second and third quarter. Having spent the last several days with our newly reconstituted board, I can safely say that they are completely dedicated to extending our cash runway and improving our valuation.

研發費用在 2022 年第四季度下降至 1110 萬美元，而 2021 年第四季度為 2890 萬美元，上一季度為 2050 萬美元。我們還與我們所有的製造商合作，隨著銷售的持續增長，在未來幾年內減少外部支出。我們預計第二和第三季度青少年會出現現金消耗。在過去幾天與我們新重組的董事會一起度過後，我可以肯定地說，他們完全致力於擴大我們的現金跑道和提高我們的估值。

After delving into the data and spending time with our sales force, the new Board members continue to be excited about our products. Slides 21 through 24 contain important safety information for ZYNRELEF and APONVIE. The slides are available on our website.

在深入研究數據並與我們的銷售人員共度時光後，新的董事會成員繼續對我們的產品感到興奮。幻燈片 21 至 24 包含 ZYNRELEF 和 APONVIE 的重要安全信息。這些幻燈片可在我們的網站上找到。

With that, we are ready for your questions. Operator?

這樣，我們就可以回答您的問題了。操作員？

(Operator Instructions)

（操作員說明）

We'll take our first question from Josh Schimmer with Evercore.

我們將從 Evercore 的 Josh Schimmer 那裡回答我們的第一個問題。

First, a quick one on the accounts receivable line. It looks like that bumped up quarter-over-quarter. What is that attributable to?

首先，快速了解應收賬款行。看起來這比上一季度有所上升。那歸因於什麼？

It's attributable to just some minor timing in payments, which, as you know, 100% of that gets paid and also an increase in sales over the course of the year.

這歸因於付款的一些小時間，如您所知，其中 100% 得到支付，而且銷售額在一年中有所增加。

Okay. I guess, I'm trying to reconcile the comments about the headwinds from the label and the suboptimal device, delivery device. In light of the obviously challenging launch thus far, which seemed a little bit juxtaposed to John's supremely optimistic adoption metrics in the IDNs. And so trying to figure out, is there any meaningful near-term growth prospects this year? Why continue to push on commercialization until you've checked the box on the broader label and the simpler device product profile?

好的。我想，我正在嘗試調和關於來自標籤和次優設備、交付設備的逆風的評論。鑑於迄今為止明顯具有挑戰性的啟動，這似乎與 John 在 IDN 中極其樂觀的採用指標有點並列。所以想弄清楚，今年是否有任何有意義的近期增長前景？在勾選更廣泛的標籤和更簡單的設備產品配置文件之前，為什麼要繼續推動商業化？

Well, I'll let John answer. But I think to start off, we continue to see growth of the product. We're making significant inroads. What we've identified, obviously, is an area that -- 2 areas that will have impact on accelerating growth over what we're seeing today. But we want to obviously continue to get the message out, grow the product.

好吧，我會讓約翰回答。但我認為首先，我們會繼續看到產品的增長。我們正在取得重大進展。顯然，我們已經確定的是一個領域 - 2 個領域將對我們今天看到的加速增長產生影響。但我們顯然希望繼續傳播信息，發展產品。

As John talked about, there's an opportunity for dissemination of real-world data that's now being generated as the product has become available. And as we've talked about over the last year. One of the time-consuming aspects of the launch were virtually every large site conducting their own trials before they would start using the product just because of prior experience with other products in this category.

正如 John 所說，隨著產品的推出，現在正在生成的真實世界數據有機會傳播。正如我們在去年談到的那樣。發布的一個耗時方面是幾乎每個大型站點在開始使用該產品之前都進行了自己的試用，這僅僅是因為之前使用過該類別中其他產品的經驗。

And so there's now an abundance of data going to be coming out that will continue to support adoption of the product between now and later this year when we get the expanded label and hopefully, shortly after adding to the product by making it easier to use the product. So this is obviously a continuum, but we continue to see adoption. And obviously, we want to continue to push that as hard as we can. John, do you want to add to that?

因此，從現在到今年晚些時候，我們將獲得大量數據，這些數據將繼續支持該產品的採用，屆時我們將獲得擴展標籤，並希望在添加到產品後不久，通過使其更易於使用產品。所以這顯然是一個連續體，但我們繼續看到採用。顯然，我們希望繼續盡我們所能推動它。約翰，你想補充嗎？

Yes, certainly. So I think if we look at the IDNs, as Barry mentioned, the fact that they are all doing internal evaluations, and that takes some time. That's an important aspect, and shown in some of the growth that we've seen. But the results that they are generating was generally -- actually have been terrific. And that's why we continue to add new IDNs. We've added some very large ones just at the end of last year. And those accounts are very interested and excited about switching out their Exparel business for ZYNRELEF because of the clinical profile as well as what we have from a value proposition.

是的，當然了。所以我認為，如果我們看一下 IDN，就像 Barry 提到的那樣，他們都在進行內部評估，這需要一些時間。這是一個重要方面，並在我們看到的一些增長中得到體現。但他們產生的結果通常——實際上非常好。這就是我們繼續添加新 IDN 的原因。就在去年年底，我們增加了一些非常大的。由於臨床概況以及我們從價值主張中獲得的東西，這些客戶對將他們的 Exparel 業務換成 ZYNRELEF 非常感興趣和興奮。

Now as Barry has pointed out, there are some hurdles from a preparation standpoint. One of the ways that we're looking to solve that is by utilization of medical device representatives. They're in the operating room, especially for orthopedics, every single day. So they can help and make sure that the product is on the tray when the surgeon needs it. So it's a short-term solution that can really help us be very effective.

現在正如巴里所指出的，從準備的角度來看存在一些障礙。我們尋求解決該問題的方法之一是利用醫療設備代表。他們每天都在手術室裡，尤其是骨科手術室。因此，當外科醫生需要時，他們可以提供幫助並確保產品在托盤上。所以這是一個短期解決方案，可以真正幫助我們非常有效。

The other thing that we think is important is we expect a label expansion in October, which isn't that far away. And as accounts and IDNs have been getting great results really, they'll look at adding additional service lines once we get that label expansion. So I think we can continue to grow. I think, second quarter, just based on seasonality has always been stronger than first quarter, and we would certainly expect that as we go forward.

我們認為重要的另一件事是我們預計 10 月份標籤擴張，這並不遙遠。由於帳戶和 IDN 確實取得了很好的成果，一旦我們獲得標籤擴展，他們就會考慮添加額外的服務線。所以我認為我們可以繼續發展。我認為，僅基於季節性因素，第二季度就一直比第一季度強，我們肯定會在前進的過程中期待這一點。

And then, John, you provided some encouraging uptake metrics early on for APONVIE. On the other hand, you provided encouraging uptake metrics for ZYNRELEF, and that's been, I think, most investors would agree, to date, a fairly significant disappointment. So why should we have confidence in your APONVIE commentary in light of the fact that the commentary really didn't portend a launch that investors have been looking for?

然後，John，您在早期為 APONVIE 提供了一些令人鼓舞的採用指標。另一方面，你為 ZYNRELEF 提供了令人鼓舞的吸收指標，我認為，迄今為止，大多數投資者都會同意，這是一個相當大的失望。那麼，鑑於您的 APONVIE 評論實際上並未預示投資者一直在尋找的發布這一事實，我們為什麼要對您的評論充滿信心？

Yes. It's a very fair question. And I would tell you that I think APONVIE is entirely different. First of all, we have a broad indication for PONV prevention. So we're not limited in the surgical procedures that we can be used. The other thing from an ease of use, Josh, we don't have the same training hurdles. It's really just a 30 seconds IV push. It's something that hospitals are used to using every single day. So the representatives don't have to remain in the accounts and make sure that the training is -- takes place, withdrawn the product from the vial.

是的。這是一個非常公平的問題。我會告訴你，我認為 APONVIE 完全不同。首先，我們有廣泛的 PONV 預防指徵。所以我們不局限於我們可以使用的外科手術。另一件事是易用性，Josh，我們沒有相同的培訓障礙。這實際上只是 30 秒的靜脈注射。這是醫院每天都習慣使用的東西。因此，代表不必留在賬戶中並確保培訓是--發生，從小瓶中取出產品。

So I think while certainly there are some very encouraging initial results that we're seeing, we believe this is a very different product and ease of use, and we'll have a very rapid uptake as we get going and get formulary access.

所以我認為，雖然我們確實看到了一些非常令人鼓舞的初步結果，但我們相信這是一種非常不同的產品和易用性，並且隨著我們的開始和獲得處方訪問，我們將得到非常迅速的吸收。

We'll take our next question from Brandon Folkes with Cantor Fitzgerald.

我們將接受 Brandon Folkes 和 Cantor Fitzgerald 的下一個問題。

Congratulations on progress. Maybe firstly for me, can you just elaborate on some of the options you have for shoring up your cash runway? I know you did talk about that and sort of working with the Board on that. So maybe just if you could elaborate there? And then along the same line, how should we think about R&D going forward in light of the ZYNRELEF label expansion sNDA now being filed, but then also the sort of prefilled syringe and VAN you talked about today?

祝賀進步。也許首先對我來說，你能詳細說明一下你有哪些選擇來支撐你的現金跑道嗎？我知道你確實談過這個問題，並且在某種程度上與董事會就此進行了合作。所以也許只是如果你能在那裡詳細說明？然後沿著同一條線，我們應該如何根據正在提交的 ZYNRELEF 標籤擴展 sNDA 以及您今天談到的那種預填充注射器和 VAN 來考慮研發的進展？

Yes. Thanks, Brandon. So the -- in terms of the second question, first. Looking at R&D expense going forward, we continue to do our best to moderate R&D over the course of this year, even with our activities in terms of trying to move the prefilled syringe forward. That's a relatively modest investment compared to running large-scale clinical trials. We will do it as economically as possible.

是的。謝謝，布蘭登。所以 - 首先是第二個問題。展望未來的研發費用，我們在今年繼續盡最大努力適度研發，即使我們的活動試圖推動預灌封注射器向前發展。與進行大規模臨床試驗相比，這是一筆相對適中的投資。我們將盡可能經濟地做到這一點。

So -- and we've already taken significant measures to reduce our R&D expense as I think, indicative of the numbers that we put up for fourth quarter, and we'll continue to look at ways to reduce burn, both in R&D as well as elsewhere I can't go into specifics at this point. The Board is still in the kind of data accumulation stage working together very closely with management and we'll certainly provide updates when available.

所以 - 我們已經採取了重大措施來減少我們的研發費用，正如我認為的那樣，這表明我們為第四季度提供的數字，我們將繼續尋找減少研發費用的方法與其他地方一樣，我現在無法詳細說明。董事會仍處於與管理層密切合作的數據積累階段，我們一定會在可用時提供更新。

Great. And maybe just one follow-up. In terms of the 10% growth, volume growth. Any pushes and pulls around revenue that we should think about in the first quarter there, just sort of why revenue may or may not track that closely?

偉大的。也許只有一次跟進。就 10% 的增長而言，數量增長。我們應該在第一季度考慮的任何推動和拉動收入，只是為什麼收入可能會或可能不會密切跟踪？

Yes, great question. And there's no doubt that in the first quarter on an annual basis, you have what we show in terms of seasonality of the use of ZYNRELEF and also ordering patterns and the mix of the 2 vial sizes may be different. So I don't know if there's any specifics that John or David can add in terms of Brandon's question.

是的，很好的問題。毫無疑問，在每年第一季度，我們展示了 ZYNRELEF 使用的季節性以及訂購模式，兩種小瓶尺寸的組合可能不同。所以我不知道 John 或 David 是否可以針對 Brandon 的問題添加任何細節。

Brandon, were you asking about ZYNRELEF, specifically?

布蘭登，你問的是 ZYNRELEF 嗎？

Correct. Yes.

正確的。是的。

Yes. So if you look at it, I think Barry is right. So what we have seen is additional general surgery procedures coming on board, which is very encouraging. Our initial launch was really focused much more on orthopedics. So with that, there's a higher mix of the 200-milligram SKU, which would have a lower cost value.

是的。所以如果你看一下，我認為巴里是對的。因此，我們看到的是更多的普通外科手術即將上線，這非常令人鼓舞。我們最初的發布確實更側重於骨科。因此，200 毫克 SKU 的組合更高，成本價值更低。

And then I think you can see that by some of the numbers historically, overtime, from a demand standpoint. Also as we gain business in 340B accounts, there will be a bit of reduction in what the net selling price will be. So there will be some sensitivity that we'll continue to look at.

然後我認為你可以從需求的角度通過一些歷史上的加班數字看到這一點。此外，隨著我們在 340B 賬戶中獲得業務，淨售價將會有所降低。因此，我們將繼續關註一些敏感性。

I think the final piece is we took our first price increase in -- effective January 1. So there was a very minor buy-in that occurred at the end of last quarter, probably in the neighborhood of a week or 2. So those would be the factors that would impact the actual results for Q1.

我認為最後一點是我們第一次提價——從 1 月 1 日開始生效。所以在上個季度末有一個非常小的買入，可能在一周或兩週左右。所以那些會是影響第一季度實際結果的因素。

(Operator Instructions)

（操作員說明）

We'll take our next question from Serge Belanger with Needham & Company.

我們將接受 Needham & Company 的 Serge Belanger 的下一個問題。

A couple of questions for us. First one, Barry, can you just talk about the overall fiscal volume trends? I know your competitor has been -- as previously mentioned that, the lack of full recovery has been a headwind. So just curious what you've seen so far this year? I know first quarter is usually slow, but usually by the time we get to March, for us to normalize. So curious what you see in terms of those strengths?

我們有幾個問題。第一個，巴里，你能談談整體財政量趨勢嗎？我知道你的競爭對手一直——如前所述，缺乏完全恢復一直是一個不利因素。所以很好奇你今年到目前為止看到了什麼？我知道第一季度通常很慢，但通常到 3 月時，我們就會恢復正常。很好奇您在這些優勢方面看到了什麼？

Yes. And I think John can comment on -- give a little more color. No question, January is very slow. And we've seen a good movement in February and strong March, which leads to overall growth over the quarter. John, do you want to give any more color?

是的。我認為 John 可以發表評論-- 多加一點色彩。毫無疑問，一月非常緩慢。我們已經看到 2 月份的良好走勢和 3 月份的強勁走勢，這導致了本季度的整體增長。約翰，你想再給點顏色嗎？

Yes. I think that if you look at the slide that we showed, based on the seasonality of the product that continues to hold true. Overall, our indicated procedures, last year, they were down 4.1 -- 4.6% compared to 2021 volume. So far in the first quarter of this year, they're running very comparable to what they were in 2022, Serge. So -- but it's still early. The claims data tends to run a bit behind when the actual unit volume is available. So it's something that we can look at and report on that during our next earnings call.

是的。我認為，如果您看一下我們展示的幻燈片，就會發現基於產品的季節性仍然適用。總體而言，我們指出的程序去年與 2021 年的數量相比下降了 4.1-4.6%。 Serge，今年第一季度到目前為止，它們的運行情況與 2022 年非常相似。所以 - 但現在還早。當實際單位數量可用時，索賠數據往往會落後一點。因此，我們可以在下一次財報電話會議上查看並報告這一點。

Okay. And then secondly, you highlighted your plans to improve the presentation of the ZYNRELEF product. Just curious what the regulatory, I guess, implications are here? What is required from an FDA standpoint to get these improvements approved for the product presentation?

好的。其次，您強調了改進 ZYNRELEF 產品展示的計劃。只是好奇，我猜這裡的監管意味著什麼？從 FDA 的角度來看，需要什麼才能使這些改進獲得批准用於產品展示？

It would be just like a development of any other device similar to the Luer Lock applicator that we provide in the kit. You have to go through a normal manufacturing activities in terms of demonstration of the sterility, how you're using radiation to sterilize the device and packaging of that device. You put all of that material together, all of that's being done by an external manufacturer that contract manufacturer has many, many of these type of devices that they make, they're expert at this activity.

這就像我們在套件中提供的類似於 Luer Lock 塗抹器的任何其他設備的開發。你必須通過正常的製造活動來證明無菌性，你如何使用輻射對設備和設備的包裝進行消毒。你把所有這些材料放在一起，所有這些都是由外部製造商完成的，合同製造商有很多，他們製造的很多這類設備，他們是這項活動的專家。

And so they provide all that information for the filing. And then it's really a question of 2 parallel paths that can be taken filing 510(K) as a device as well as filing pre-approval supplement in order to package the product in the kit. The 510(K) goes faster, generally. And so we're currently evaluating opportunities to see if we can accelerate this process using that approach.

因此，他們提供了所有用於備案的信息。然後這實際上是一個 2 條並行路徑的問題，可以採取將 510(K) 作為設備提交以及提交預批准補充，以便將產品打包到套件中。通常，510(K) 速度更快。因此，我們目前正在評估機會，看看我們是否可以使用該方法加速這一過程。

There's some technical issues associated with that, that we need to work through with the FDA. But in either pathway, it's really development of the device and showing that you can write instructions on how to use it appropriately. Not a lot of big hurdles. This is a -- although, the device is quite novel in how we've designed it, the general concept of a vial access needle is extremely common. And the amount of education or instruction in order to use it will be really minimal.

有一些與之相關的技術問題，我們需要與 FDA 合作解決。但在任何一種途徑中，它都是設備的真正開發，並表明您可以編寫有關如何正確使用它的說明。沒有太多的大障礙。這是一個——儘管該設備在我們的設計方式上非常新穎，但小瓶接入針的一般概念非常普遍。並且為了使用它而進行的教育或指導量將非常少。

We'll take our next question from Kelly Shi with Jefferies.

我們將與 Jefferies 一起接受 Kelly Shi 的下一個問題。

This is Claire on for Kelly. So my first question is on ZYNRELEF. So I wonder if you can give us more color on your strategy on getting more uptake from those accounts that already have consistent ordering? And what do you think will be the inflection point in terms of the sales trajectory for ZYNRELEF? And also, can you share a little bit more about the progress on the EU launch?

這是凱利的克萊爾。所以我的第一個問題是關於 ZYNRELEF。所以我想知道你是否可以給我們更多關於你的策略的顏色，以從那些已經有一致訂購的賬戶中獲得更多的吸收？您認為 ZYNRELEF 銷售軌蹟的拐點是什麼？另外，您能否分享更多關於歐盟啟動的進展情況？

Yes. John, do you want to take the first part?

是的。約翰，你想參加第一部分嗎？

Of course. So our focus, right now, is in our existing accounts, making sure that our representatives are able to really maximize the number of surgeons using a product. So oftentimes in these initial evaluations that are coming about, they'll start with maybe 2 or 3 orthopedic surgeons, and there may be 5 to 8 in practice. So our goal is to really leverage the positive results at the initial trial period had and expand to those other surgeons.

當然。所以我們現在的重點是我們現有的賬戶，確保我們的代表能夠真正最大限度地增加使用產品的外科醫生的數量。因此，在即將進行的這些初步評估中，他們通常會從 2 或 3 名整形外科醫生開始，而實際上可能有 5 到 8 名。因此，我們的目標是真正利用最初試用期的積極結果，並將其擴展到其他外科醫生。

The other thing that we're looking to do is expand within the procedures that we're doing, so if we're starting with total -- someone maybe could go on mute, there's an awful lot of background noise there. So the other thing that we're doing is looking to expand the surgical procedures. So if someone is starting in TKA, we're obviously looking to do hips. We're also then looking to expand within an account to other surgical lines. So if it's going well in orthopedics, what can we do in general surgery and bariatrics. What can we do in C-section, where are additional places that we can grow the business. And we are beginning to see good traction on taking that approach.

我們要做的另一件事是在我們正在做的程序中擴展，所以如果我們從總計開始——有人可能會繼續保持靜音，那裡有很多背景噪音。所以我們正在做的另一件事是尋求擴大外科手術。因此，如果有人開始進行 TKA，我們顯然希望進行臀部手術。然後，我們還希望在一個帳戶內擴展到其他手術線。因此，如果它在骨科方面進展順利，我們在普通外科和減肥方面能做些什麼。我們可以在剖腹產中做什麼，我們可以在哪些地方發展業務。我們開始看到採用這種方法的良好牽引力。

Some of the flexible resources that we're adding like the medical device reps are helping a lot, too, because they have such a strong relationship with orthopedic surgeons, there may be some that we don't have strong relationships and are harder to convert. And we've already seen growth coming from accounts by using that. So there's a variety of really strategies that we're using there. But I think most of it is just making sure that we're leaving no stone unturned within accounts that already have existing business.

我們添加的一些靈活資源，如醫療設備代表，也有很大幫助，因為他們與整形外科醫生有著如此牢固的關係，可能有些我們沒有牢固的關係並且更難轉換.我們已經看到通過使用它來自賬戶的增長。因此，我們在那裡使用了多種真正的策略。但我認為其中大部分只是確保我們在已經擁有現有業務的賬戶中不遺餘力。

Yes. And on the EU question, really no update. We have continually seen a challenging process to find an EU partner, and we have no intention of launching the product ourself that's an expensive endeavor, and we certainly would not want to use our cash for that at this time.

是的。關於歐盟問題，真的沒有更新。我們一直看到尋找歐盟合作夥伴的過程充滿挑戰，我們無意自己推出產品，因為這是一項昂貴的嘗試，而且我們現在當然不想為此動用現金。

Got it. That's very helpful. And on the APONVIE launch, you have talked about the early signals you have seen from the launch 2 weeks ago. And could you maybe give us more color on the APONVIE ramp-up? And like what are the additional sales force you might need to support the APONVIE ramp-up? And how should we expect the cost increase associated with that?

知道了。這很有幫助。在 APONVIE 發佈時，您談到了您在 2 週前發佈時看到的早期信號。您能否為我們提供更多有關 APONVIE 升級的信息？您可能需要哪些額外的銷售人員來支持 APONVIE 的升級？我們應該如何預期與此相關的成本增加？

Yes, John, do you want to take that?

是的，約翰，你想接受嗎？

Of course. So with respect to the sales ramp-up, it will really be determined on how quickly we can get formulary approval. So that's a key priority that we have right now. As with any of our products, we don't give guidance during a launch phase. So we're really not providing any additional insights at this time. What we hope to do is continue to provide updates on the progress as we get further in, but we're only 2 weeks out.

當然。因此，就銷售增長而言，這實際上取決於我們能多快獲得處方批准。所以這是我們現在的一個關鍵優先事項。與我們的任何產品一樣，我們不會在發布階段提供指導。所以我們現在真的不提供任何額外的見解。我們希望做的是隨著我們進一步深入，繼續提供最新進展，但我們只有 2 週時間了。

With respect to the additional cost, we're using our existing ZYNRELEF sales force. They call on the exact same audience. Our team is already calling on anesthesiologists, on pharmacy, on surgeons. And fortunately, there's a tremendous overlap of the target accounts that we're going after, especially the oral aprepitant accounts with the ZYNRELEF accounts that we have. So it's a very small percentage of the overall budget that's used incrementally to launch APONVIE compared to what we're doing as a commercial spend.

關於額外成本，我們正在使用現有的 ZYNRELEF 銷售人員。他們呼籲完全相同的聽眾。我們的團隊已經在召集麻醉師、藥房和外科醫生。幸運的是，我們正在追踪的目標賬戶有很大的重疊，尤其是口服阿瑞匹坦賬戶與我們擁有的 ZYNRELEF 賬戶。因此，與我們作為商業支出所做的相比，用於啟動 APONVIE 的總預算只佔很小的比例。

That does conclude the question-and-answer session. I would like to turn the call back over to Dr. Quart for any additional or closing remarks.

問答環節到此結束。我想將電話轉回給 Quart 博士，以獲得任何補充或結束語。

Thank you. And thanks, everyone, for joining us today on the call. We look forward to keeping you updated in the future.

謝謝。感謝大家今天加入我們的電話會議。我們期待著讓您在未來更新。

Ladies and gentlemen, that concludes today's conference call. Thank you for your participation, and you may now disconnect. Goodbye.

女士們，先生們，今天的電話會議到此結束。感謝您的參與，您現在可以斷開連接。再見。