Heron Therapeutics Inc (HRTX) 2023 Q4 法說會逐字稿

Thank you for standing by, and welcome to the Heron therapeutics fourth quarter 2023 conference call. I would now like to welcome [Melissa Duran], Executive Director, legal to begin the call. Melissa, over to you.

感謝您的耐心等待，歡迎參加 Heron Therapeutics 2023 年第四季電話會議。現在我歡迎執行董事 [Melissa Duran] 開始電話會議。梅麗莎，交給你了。

Thank you, operator, and good afternoon, everyone. Thank you for joining us on the Heron Therapeutics conference call this afternoon to discuss the company's financial results for the fourth quarter ended December 31, 2023.

謝謝接線員，大家下午好。感謝您今天下午參加 Heron Therapeutics 電話會議，討論該公司截至 2023 年 12 月 31 日的第四季度財務業績。

With me today from hereon are Craig Collard, Chief Executive Officer; Ira Duarte, Executive Vice President, Chief Financial Officer; Bill Forbes, Executive Vice President, Chief Development Officer, and Kevin Werner, Senior Vice President, Medical Affairs Strategy Engagement.

從今天起，與我同在的有執行長克雷格‧科拉德 (Craig Collard)； Ira Duarte，執行副總裁兼財務長； Bill Forbes，執行副總裁兼首席開發官，Kevin Werner，醫療事務策略參與資深副總裁。

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

對於那些透過電話會議參加的人，可以透過網路廣播提供幻燈片，也可以在今天的電話會議結束後透過我們網站的投資者關係頁面存取幻燈片。

Before we begin, let me quickly remind you that during the course of this conference call, the company will make forward-looking statements, we caution you that any statement that is not a statement of historical fact is a forward-looking statement.

在我們開始之前，讓我快速提醒您，在本次電話會議期間，本公司將做出前瞻性陳述，我們提醒您，任何不是歷史事實陳述的陳述都是前瞻性陳述。

This includes remarks about the company's projections, expectations plans, beliefs and future performance, all of which constitute forward-looking statements for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995.

其中包括有關公司預測、預期計劃、信念和未來業績的評論，所有這些都構成 1995 年《私人證券訴訟改革法案》中安全港條款所規定的前瞻性陳述。

These statements are based on judgment and analysis as of the date of this conference call and are subject to numerous important risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statement.

這些陳述是基於截至本次電話會議之日的判斷和分析，並受到許多重要風險和不確定性的影響，可能導致實際結果與前瞻性陳述中所述的結果有重大差異。

The risks and uncertainties associated with the forward-looking statements made in this conference call and webcast are described in the Safe Harbor statement in today's press release, and Heron's public periodic filings with the SEC. Except as required by law, Heron assumes no obligation to update forward-looking statements to reflect future events or actual outcomes and does not intend to do so.

今天新聞稿中的安全港聲明以及 Heron 向 SEC 提交的公開定期文件中描述了與本次電話會議和網路廣播中的前瞻性陳述相關的風險和不確定性。除法律要求外，Heron 不承擔更新前瞻性聲明以反映未來事件或實際結果的義務，也不打算這樣做。

And with that, I would now like to turn over the call to Craig Collard, Chief Executive Officer of Heron.

現在，我想將電話轉給 Heron 執行長 Craig Collard。

Good afternoon, and welcome to the Heron Therapeutics fourth quarter 2023 earnings call. Today, we are pleased to update you on our latest achievements in 2023, financial performance, threshold on our development projects, fastlane training and some insight into where we are headed strategically with our products.

下午好，歡迎參加 Heron Therapeutics 2023 年第四季財報電話會議。今天，我們很高興向您介紹我們 2023 年的最新成就、財務業績、開發專案的門檻、快車道培訓以及對我們產品策略發展方向的一些見解。

Since joining Heron Therapeutics as CEO back in April 2023, we have taken significant steps to get this business back on track, starting with headcount and expense reduction, combined with getting the right management team in place. We've implemented a comprehensive streamlining of our financial processes, enhancing efficiency and accountability across the organization.

自 2023 年 4 月加入 Heron Therapeutics 擔任執行長以來，我們採取了重大措施，讓這項業務重回正軌，首先是減少員工人數和開支，同時組建合適的管理團隊。我們對財務流程進行了全面精簡，提高了整個組織的效率和問責制。

As you can see from this slide, we have had a number of significant achievements in 2023 and have us well-positioned as we move into 2024 and beyond. We've been able to reduce operational expenses for $182 million in 2022 to $135 million in 2023. And we should be in a range of $108 million to $116 million in operating expenses in 2024.

正如您從這張幻燈片中看到的，我們在 2023 年取得了許多重大成就，並且在進入 2024 年及以後的過程中處於有利地位。我們已將 2022 年的營運支出從 2022 年的 1.82 億美元減少到 2023 年的 1.35 億美元。到 2024 年，我們的營運支出應該在 1.08 億至 1.16 億美元之間。

As part of this process, we have also looked to improve our gross margin. Historically, the company has had gross margins in the 50% range. However, through better inventory management and with some renegotiations with our manufacturers, we've been able to reduce COGS and improve gross margins over 70%.

作為此過程的一部分，我們還尋求提高毛利率。從歷史上看，該公司的毛利率一直在 50% 左右。然而，透過更好的庫存管理以及與製造商的一些重新談判，我們已經能夠降低銷貨成本並將毛利率提高超過 70%。

We anticipate future gross margins to continue to improve up into the mid 70s range. We completed a capital raise early in 2023, which will allow us to have enough cash to get to profitability by late 2024. We closed the year in 2023 with over $80 million in cash and cash equivalents, which again, has enough cash for us to reach profitability in Q4 of '24.

我們預計未來毛利率將繼續提高至 70 年代中期。我們在 2023 年初完成了融資，這將使我們擁有足夠的現金，以便在 2024 年底之前實現盈利。我們在 2023 年結束時擁有超過 8000 萬美元的現金和現金等價物，這再次有足夠的現金讓我們在 24 年第四季度實現盈利。

Moving down the list, we were able to restart the Vial Access Needle or VAN project along with the Prefilled Syringe. Both of these projects are progressing nicely with the expected VAN approval by the end of this year and a Prefilled Syringe approval expected in 2026.

向下移動列表，我們能夠重新啟動 Vial Access Needle 或 VAN 專案以及預裝注射器。這兩個項目都進展順利，預計 VAN 將於今年年底獲得批准，預灌封注射器預計將於 2026 年獲得批准。

Both of these projects will provide significant improvement to our products ZYNRELEF, which is indicated for post offers surgical pain. Our oncology franchise continues to outperform, and I'm happy to report total net revenues of $107.9 million, which exceeded full year 2023 guidance.

這兩個項目都將為我們的產品 ZYNRELEF 提供顯著改進，該產品適用於術後疼痛。我們的腫瘤專營業務繼續表現出色，我很高興地報告總淨收入為 1.079 億美元，超過了 2023 年全年指引。

We are also very pleased with ZYNRELEF performance in Q4 of 2023. For the first time in our history, we were able to do over $5 million in net revenue for the quarter, even while significant changes happening in the business.

我們對 ZYNRELEF 在 2023 年第四季的表現也非常滿意。即使業務發生重大變化，我們本季的淨收入仍能實現超過 500 萬美元，這在我們歷史上還是第一次。

And last, in January 2024, we're able to file prostate agreement combined getting on label expansion for ZYNRELEF, these two events should have a significant impact to ZYNRELEF revenues as we move through 2024 and beyond.

最後，在 2024 年 1 月，我們能夠提交前列腺協議，合併 ZYNRELEF 的標籤擴展，隨著我們進入 2024 年及以後，這兩個事件應該會對 ZYNRELEF 收入產生重大影響。

Now moving to product performance. The oncology franchise continues to outperform our expectations with CINVANTI net revenues coming in at $94.9 million for the year and SUSTOL coming in at $13 million. We have been very pleased in the oncology franchise, and we believe the pie will continue to show the same consistency as in past years.

現在轉向產品性能。腫瘤專營業務持續超出我們的預期，CINVANTI 今年的淨收入為 9,490 萬美元，SUSTOL 的淨收入為 1,300 萬美元。我們對腫瘤學特許經營權感到非常滿意，我們相信這塊蛋糕將繼續表現出與過去幾年相同的一致性。

The acute franchise is where we anticipate the majority of our product growth to come from as we move forward. We were very pleasingly hit a record of $5.6 million in net revenue for the quarter, which is the first time this product has ever been over $5 million per quarter.

隨著我們的前進，我們預計大部分產品成長將來自於敏銳的特許經營權。我們非常高興地創下了本季淨收入 560 萬美元的記錄，這是該產品首次每季超過 500 萬美元。

Sole acute care net revenues for the year were $19.1 million, which included APONVIE net revenues of $1.4 billion. We believe ZYNRELEF, APONVIE are both well-positioned as we move into 2024. With CrossLink partnership, expanded label environment, increasing morale, improves sales business and targeting. We believe this is going to be a great year for both products.

本年度單一急診護理淨收入為 1,910 萬美元，其中 APONVIE 淨收入為 14 億美元。我們相信，在進入 2024 年時，ZYNRELEF 和 APONVIE 都處於有利位置。透過 CrossLink 合作夥伴關係，擴大了標籤環境，提高了士氣，改善了銷售業務和目標定位。我們相信這對這兩種產品來說都將是偉大的一年。

Moving to CrossLink partnership, this agreement was signed on January 7, and really kicked off in early February. We began the training process of in-person training of approximately executive team, which went extremely well. We will continue that process through March and early April that will lead to having over 150 salesforces trained and ready-to-go. Post this initial group being trained, we will continue to roll out other areas of the country.

轉向 CrossLink 合作夥伴關係，該協議於 1 月 7 日簽署，並於 2 月初真正啟動。我們開始對大約管理團隊進行現場培訓，進展非常順利。我們將在 3 月和 4 月初繼續這一過程，這將使 150 多名銷售人員接受培訓並做好準備。在第一批人員接受培訓後，我們將繼續在該國其他地區推廣。

As you look at the slide, it would give you a better understanding of what our footprint, post all the implementation approximately will look like and consider that this will add an additional 650 reps across the country that will be fully trained. We anticipate having the entire group fully trained and up and running by the end of '24.

當您查看投影片時，它會讓您更了解我們的足跡，發布所有實施方案的大致情況，並考慮到這將在全國範圍內增加 650 名接受全面培訓的代表。我們預計整個團隊將在 24 年底前接受全面培訓並投入運作。

We also believe that we will see an impact of '24 from this med representatives coming into place. But I do want to temper enthusiasm, obviously, this will take time before we really start to hit on all cylinders. I really believe the inflection for ZYNRELEF will take place as we move into 2025 after the launch of VAN and having all the new reps fully trained, but we certainly have positive momentum, and we believe across the ZYNRELEF will have an impact in 2024.

我們也相信，我們將看到這位醫學代表對 24 年的影響正在顯現。但我確實想緩和熱情，顯然，在我們真正開始全力以赴之前，這需要時間。我真的相信，在VAN 推出後，隨著我們進入2025 年，所有新代表都接受了全面培訓，ZYNRELEF 將會發生變化，但我們肯定有積極的勢頭，我們相信整個ZYNRELEF 將在2024 年產生影響。

We have been looking at doing more ASC level, as we have tried to focus more of our efforts around orthopedic space. After signing the partnership with CrossLink, it has become increasingly apparent that CrossLink has a significant footprint in this space and our product mix works in parallel with the strategy of the ASC, which get these patients out of surgery and into rehabs as quickest possible.

我們一直在考慮做更多的 ASC 級別的工作，因為我們試圖將更多的努力集中在骨科領域。與 CrossLink 簽署合作夥伴關係後，越來越明顯的是，CrossLink 在這一領域佔有重要地位，我們的產品組合與 ASC 的策略並行，使這些患者盡快擺脫手術並進入康復中心。

Our very often one-two punch for the APONVIE and ZYNRELEF will be extremely beneficial to our potential partners at the ASC level.

我們經常對 APONVIE 和 ZYNRELEF 進行一打二打，這對我們在 ASC 級別的潛在合作夥伴非常有利。

I'm now going to pass it all through our newest hire, Kevin Werner, who is our new Senior VP of Medical Affairs. Strategy Engagements. Kevin builds a vital need for us of having handling experience with our products at the finishing level and is going to have a significant influence in our ASC strategy as we move forward. Go ahead, Kevin.

現在我將把這一切轉達給我們新聘的凱文‧維爾納（Kevin Werner），他是我們新任的醫療事務資深副總裁。戰略參與。Kevin 為我們建立了一個至關重要的需求，即在精加工層面上擁有我們產品的操作經驗，隨著我們的前進，他將對我們的 ASC 策略產生重大影響。繼續吧，凱文。

Thank you, Craig. [Very pleased to] Heron Therapeutics team and supporting the commercial portfolio of acute care and oncology care products. I had over 15 years of clinical benefit with a focus on peri-operative care pharmacists. In addition, over a decade of experience in drug development, discovery and clinical trials as Director of pharmaceutical science to the Ocular Therapeutix.

謝謝你，克雷格。[非常高興]Heron Therapeutics 團隊支持急性護理和腫瘤護理產品的商業組合。我有超過 15 年的臨床效益經驗，專注於圍手術期護理藥劑師。此外，作為 Oural Therapeutix 藥物科學總監，他在藥物開發、發現和臨床試驗方面擁有十多年的經驗。

As Senior Vice President of Medical Affairs, Strategy and Engagement for Heron, it will be my job to support the accurate determination of medical information to our team and providers to screening patients have access to the best possible care forming strategic alliances and collaborating with medical community through a shared heritage products become part of the standard of care and medical literature dictate.

作為 Heron 醫療事務、戰略和參與部高級副總裁，我的工作是支持我們的團隊和提供者準確確定醫療信息，篩選患者以獲得盡可能最好的護理，形成戰略聯盟並與醫療界合作通過共同的遺產，產品成為護理標準和醫學文獻規定的一部分。

I look forward to working with our team at Heron at expanding indications, access, adoption and medical literature with our current commercial portfolio and future products. I will focus on our acute care portfolio today, as I have the pleasure of having extensive real-world experience with ZYNRELEF and APONVIE, witnessing the positive impact on our patients and health systems.

我期待與 Heron 的團隊合作，透過我們目前的商業產品組合和未來的產品來擴大適應症、取得、採用和醫學文獻。今天我將重點放在我們的急診護理產品組合，因為我很高興能夠在 ZYNRELEF 和 APONVIE 方面獲得豐富的實際經驗，見證其對我們的患者和衛生系統的積極影響。

Enhanced recovery after surgery protocols are evidence-based protocols that are essentials to the patient outcomes and sustaining the financial viability of our health system. The primary clinical focuses of enhanced recovery after surgery are reducing postoperative pain, while minimizing [opioid consumption] and the control of postoperative nausea and vomiting.

加速復健外科方案是基於證據的方案，對於患者的治療結果和維持我們衛生系統的財務生存能力至關重要。加速復健外科的臨床主要重點是減少術後疼痛，同時盡量減少[阿片類藥物的消耗]以及控制術後噁心和嘔吐。

Postoperative pain and postoperative nausea and vomiting are two of the most common concerns of both patients and clinicians. ZYNRELEF and APONVIE offer what we consider best-in-class long acting solutions to these problems.

術後疼痛和術後噁心嘔吐是患者和臨床醫師最常見的兩個問題。ZYNRELEF 和 APONVIE 為這些問題提供了我們認為一流的長效解決方案。

Implementation of ZYNRELEF and APONVIE as the foundation of our enhanced recovery after surgery protocols, we believe it may improve overall patients satisfaction, clinical outcomes and overall quality of life.

ZYNRELEF 和 APONVIE 的實施作為我們加速術後復健方案的基礎，我們相信它可以提高患者的整體滿意度、臨床結果和整體生活品質。

At an institutional level while supporting enhanced recovery after surgery, both ZYNRELEF and APONVIE can have a positive financial impact on our institutions. Both products are currently separately payable in the hospital outpatient and ambulatory surgical centers by CMS.

在機構層面，在支持術後加速復原的同時，ZYNRELEF 和 APONVIE 都可以對我們的機構產生正面的財務影響。目前，這兩種產品均由 CMS 在醫院門診和門診手術中心單獨支付。

In addition many commercial payers are providing coverage for ZYNRELEF outside the surgical bundle. Improving the efficacy of our enhanced recovery after surgery protocols, combined with separate reimbursement outside of the surgical bundle, it's critical to the financial viability of our health system and clinical outcomes of our patients.

此外，許多商業付款人還在手術組合之外為 ZYNRELEF 提供承保。提高術後加速復健方案的效果，再加上手術包以外的單獨報銷，這對於我們衛生系統的財務可行性和患者的臨床結果至關重要。

Let's touch on APONVIE, aprepitant injectable emulsion and the current unmet need and lack of awareness, postoperative nausea and vomiting often overlooked or under-recognized, secondaries the timing and different phases of care in which patients can experience it.

讓我們談談 APONVIE、阿瑞匹坦注射乳劑以及當前未滿足的需求和缺乏認識，術後噁心和嘔吐經常被忽視或認識不足，其次是患者可以經歷的護理的時間和不同階段。

Postoperative nausea and vomiting ranked the number one most undesirable [post-op] complications by patients, but also prevents clinical risk factors as well that need to increase length of stay, readmissions and surgical complications. Postoperative nausea and vomiting rates can reach as high as 80% in high-risk patients.

術後噁心和嘔吐是患者最不希望出現的[術後]併發症之一，但也可以預防需要增加住院時間、再入院和手術併發症的臨床危險因子。高風險患者術後噁心嘔吐發生率高達80%。

The current guidelines recommend the use three or four agents in patients with risk factors making them moderate to high risk.

目前的指引建議對具有中度至高風險風險因素的患者使用三種或四種藥物。

In the United States before over 65 billion diagnostic and surgical procedures, of which 50% of those patients are at moderate to high risk for postoperative nausea and vomiting. In fact, it is that on the market, an oral formulation and as a pro-drug infusion passive product. The oral formulation and delayed onset of action of about one to five hours. Passive drug requires compounding and a 20 to 30 minute infusion, followed by systemic conversion prodrug to the active form.

在美國，已有超過 650 億例診斷和外科手術，其中 50% 的患者處於術後噁心和嘔吐的中度至高度風險。事實上，它是市面上的一種口服製劑和作為前藥輸注的被動產品。口服製劑起效約延遲一到五小時。被動藥物需要混合並輸注 20 至 30 分鐘，然後全身將前藥轉化為活性形式。

Because of this, they had not been widely adopted in perioperative space despite a drug and being ranked the number one, most effective anti-medic for large-scale impact from an analysis of nearly 100,000 patients, along with the efficacy impact and also has an excellent safety profile without sharing typical side effects that are commonly used antiemetic therapy such as QT prolongation, sedation, anticholinergic effects or extrapyramidal side effects.

因此，儘管有一種藥物，並且在對近100,000 名患者進行的分析中被列為排名第一、最有效的抗藥物藥物，具有大規模影響力，並且具有療效影響，但它們尚未在圍手術期廣泛採用。具有出色的安全性，且沒有常用止吐療法的典型副作用，例如 QT 延長、鎮靜、抗膽鹼能作用或錐體外系副作用。

The safety profile is critical, and we are combining multiple agents for our moderate to high-risk patients. APONVIE’s 30-second IVP and rapid target receptor occupancy will allow for greater implementation of aprepitant in the acute perioperative pain by those providers mainly anesthesia most likely to prescribe.

安全性至關重要，我們正在為中高風險患者聯合使用多種藥物。APONVIE 的 30 秒 IVP 和快速目標受體佔用將使那些主要是最有可能開處方的麻醉提供者在急性圍手術期疼痛中更好地使用阿瑞匹坦。

Finally, safety and efficacy profile in the long acting solution with a 48 hour duration, one of our most productive postoperative complication, postoperative nausea and vomiting. We're looking forward to the updated guidelines on prevention of postoperative nausea and vomiting expected in 2024, which will enhance the education and awareness around its impact upon the scenario.

最後，持續 48 小時的長效解決方案的安全性和有效性概況，這是我們最有效的術後併發症之一，術後噁心和嘔吐。我們期待預計在 2024 年發布關於預防術後噁心和嘔吐的更新指南，這將加強有關其對情況影響的教育和認識。

For ZYNRELEF, our focus will be on broadening provider awareness and associated patient impact. The clinical trials and the ability to speak for themselves being the first and only FDA-approved extended-release anesthetic proven to reduce pain and opioid consumption.

對於 ZYNRELEF，我們的重點將是擴大提供者的意識和相關的患者影響。臨床試驗和不言而喻的能力是第一個也是唯一一個經 FDA 批准的緩釋麻醉劑，被證明可以減少疼痛和鴉片類藥物的消耗。

Today, I want to highlight some of the significant drivers to growth that have been implemented or will be this year. First of all, the significant label expansion presumably, approved by the FDA on January 23, 2024.

今天，我想強調今年已經實施或即將實施的一些重要的成長驅動因素。首先，FDA 可能在 2024 年 1 月 23 日批准了標籤的重大擴展。

With ZYNRELEF have now indicated in adults for installations produce postsurgical analgesia for up to 72 hours after soft tissue and orthopedic procedures, including foot and ankle and other procedures, which direct exposure to articular cartilage is voided. It has essentially doubled the number of significant indicated prodcedure.

ZYNRELEF 現在已在成人中表明，在軟組織和骨科手術（包括足部和踝關節及其他手術）後，裝置可產生長達 72 小時的術後鎮痛，避免直接暴露於關節軟骨。它基本上使重要指示手術的數量增加了一倍。

As a clinician when I think of indicated procedures and appropriate facilities, I consider any procedure which provided would typically prescribed in opioid postoperative. It shouldn't be considerations daily as a combination product for postoperative analgesia to minimize or eliminate the need for opioids, minimizing the acute pain risk of developing chronic pain and support clinical recovery.

作為一名臨床醫生，當我想到指定的手術和適當的設施時，我認為所提供的任何手術通常都會在阿片類藥物術後處方。它不應該被每天考慮作為術後鎮痛的組合產品，以最大限度地減少或消除對阿片類藥物的需求，最大限度地減少急性疼痛發展為慢性疼痛的風險並支持臨床康復。

For label expansion will also have a great impact on formularies substitution. Both formularies have been hesitant to adoption due to the limited number of indications that fascinating need for having multiple agents on formulary and subsequent budget impact.

對於標籤的擴大也會對處方藥替代產生很大的影響。由於有限的跡象表明需要多個代理人來影響處方集和隨後的預算影響，這兩個處方集一直對採用猶豫不決。

With the new brand name of that, generally other agents that have claimed long acting but have not proven superior to standard of care and that it can be removed from forming very conveniently can be impacted in the long acting foundational element, along with cheaper generic anesthetic for the acute pains.

有了新的品牌名稱，通常其他聲稱長效但尚未證明優於護理標準並且可以非常方便地從成型中去除的藥物可能會受到長效基礎成分以及更便宜的通用麻醉劑的影響對於急性疼痛。

Additionally, third-party data continues to service with the bulk that align with our clinical trial showing significant impact on postoperative pain, opioid consumption, length of stay and functional outcomes. You're good at it and it continues to be at the top of our new speed, passing US health system, an estimated $1.5 trillion in 2020 and many patient lives.

此外，第三方數據繼續提供與我們的臨床試驗一致的大量數據，顯示出對術後疼痛、鴉片類藥物消耗、住院時間和功能結果的顯著影響。你很擅長，它繼續處於我們新速度的頂端，超過了美國衛生系統，預計 2020 年將達到 1.5 兆美元，並挽救許多患者的生命。

Our major accrediting bodies and government agencies are taking notice and stepping in. The Joint Commission now includes metrics for Opioid Stewardship to be accredited and NOPAIN Act, which will begin in 2025, will provide payment for non-opioids in the outpatient surgical setting that has proven to reduce or eliminate the need for opioids.

我們的主要認證機構和政府機構正在註意到並介入。聯合委員會現在包括了待認證的阿片類藥物管理的指標，以及將於2025 年開始實施的NOPAIN 法案，將為門診手術中的非阿片類藥物提供付款，這已被證明可以減少或消除對阿片類藥物的需求。

Along with the opioid settlements, currently being distributed to states in the amount of $53 million that will be utilized to support awareness, prevention, treatment of the opioid epidemic. All these factors will have major impacts on awareness and adoption of ZYNRELEF.

與阿片類藥物和解協議一起，目前正在向各州分發 5,300 萬美元，用於支持阿片類藥物流行病的認識、預防和治療。所有這些因素都會對 ZYNRELEF 的認知和採用產生重大影響。

One of the most important factors that believe will be the CrossLink partnership that Craig outlined previously, having the additional boots on the ground, if you will, will be critical to the successful implementation of ZYNRELEF as the foundation of multimodal analgesia across the nation to change how we view postoperative pain and the need for opioids across the surgical paradigm.

最重要的因素之一是克雷格之前概述的 CrossLink 合作夥伴關係，如果願意的話，在實地提供額外的支持對於 ZYNRELEF 的成功實施至關重要，作為全國多模式鎮痛的基礎，以實現變革我們如何看待手術範例中的術後疼痛和阿片類藥物的需求。

I would like to now turn the call over to Dr. Bill Forbes.

我現在想把電話轉給比爾福布斯博士。

Thank you, Kevin. We are certainly excited to have him join our team. The development opportunities for ZYNRELEF has envisioned three-step. The first will be label expansion, which has been realized the next step involves device modification in the form of the Vial Access Needle or VAN. And the final step concludes with the Prefilled Syringe or PFS.

謝謝你，凱文。我們當然很高興他加入我們的團隊。ZYNRELEF的發展機會設想為三步驟。第一個是標籤擴展，已經實現，下一步涉及以小瓶訪問針或 VAN 形式進行設備修改。最後一步以預充式註射器或 PFS 結束。

In regards to the VAN, it is designed to improve efficiency and preparation and it will achieve this in two ways. Firstly, the VAN will substitute the current market presentation of the device, which includes vented vial spike or VVS. The VAN will provide a more rapid and easy withdraw of the drug product into the syringe that is used for installation into the patient by the physician.

就VAN而言，它旨在提高效率和準備工作，它將透過兩種方式實現這一目標。首先，VAN 將取代目前市場上出現的設備，其中包括通風瓶尖峰或 VVS。VAN 可以更快速、更輕鬆地將藥品提取到注射器中，由醫生將注射器安裝到患者體內。

The VAN has been specifically designed for this purpose and in testing the VAN has outperformed other vented vial spikes available on the market today.

VAN 是專門為此目的而設計的，在測試中，VAN 的性能優於當今市場上的其他通風小瓶尖峰。

Secondly, the VAN will allow for an even more secure presentation of the product into the sterile field present in the surgical room by (inaudible) ZYNRELEF vial into the sterile shroud of the VAN. This will result in a more efficient process for operating room staff to prepare the product for physician use. We anticipate the VAN approval in Q4 of this year.

其次，VAN 將允許透過（聽不清楚）ZYNRELEF 小瓶將產品更安全地放入 VAN 的無菌護罩中，將產品放入手術室中的無菌區域。這將為手術室工作人員提供更有效率的流程來準備醫生使用的產品。我們預計 VAN 將於今年第四季獲得批准。

Of course, the ultimate solution to ease of use of ZYNRELEF is the PFS, and we expect the PFS to get approved in Q4 of 2026. In this product presentation, entire tray is sterilized and ready for immediate use. The challenges to this program involve a new container closure system and the sterilization process itself. Once this is available, all barriers to preparation will be removed.

當然，ZYNRELEF易用性的最終解決方案是PFS，我們預計PFS將於2026年第四季獲得批准。在本產品示範中，整個托盤都已消毒並可立即使用。該計劃面臨的挑戰涉及新的容器封閉系統和滅菌過程本身。一旦實現，所有準備障礙都將被消除。

With that I will now turn this over to Ira Duarte. Ira?

現在我將把這個問題交給艾拉‧杜阿爾特 (Ira Duarte)。艾拉？

Thanks, Bill. Craig has covered our product performance in his comments, and I will just add a few additional points about our Q4 2023 and year-to-date results. Gross profit for the fourth quarter was $24.3 million and $61.9 million for the 12 months ended December 31, 2023, representing 71% and 49% of net revenue, respectively.

謝謝，比爾。克雷格在他的評論中介紹了我們的產品表現，我將補充一些關於我們 2023 年第四季和年初至今業績的額外觀點。截至2023年12月31日的12個月，第四季毛利為2,430萬美元及6,1​​90萬美元，分別佔淨收入的71%及49%。

The annual margins were negatively impacted by write-offs of ZYNRELEF inventory during the year. We do not anticipate any ZYNRELEF in the future. SG&A expenses for the three and 12 months ended December 31, 2023, with $23.6 million and $116.7 million respectively, compared to $26.7 million and $119.9 million in the same period of 2022.

年度利潤率受到 ZYNRELEF 庫存沖銷的負面影響。我們預計未來不會出現任何 ZYNRELEF。截至 2023 年 12 月 31 日的三個月和 12 個月的銷售、一般管理費用分別為 2,360 萬美元和 1.167 億美元，而 2022 年同期為 2,670 萬美元和 1.199 億美元。

Research and development expenses were $10.9 million and $55.9 million for the three and 12 months ended December 31, 2023, compared to the $11.1 million and $107.5 million in the comparable period of 2022. The decrease in spend was primarily related to decreases in cost related to ZYNRELEF as production scaled up validation activities, raw material cost came through completed in 2022.

截至2023年12月31日止的三個月和十二個月，研發費用分別為1,090萬美元和5,590萬美元，而2022年同期分別為1,110萬美元和1.075億美元。支出減少主要與 ZYNRELEF 相關成本下降有關，因為生產規模擴大了驗證活動，原材料成本於 2022 年完成。

In addition, overall personnel and related costs decreased due to reductions in force implemented in June 2022 and June 2023. We believe we can continue to reduce costs moving forward in this area as we continued to increase efficiencies.

此外，由於 2022 年 6 月和 2023 年 6 月實施的兵力裁減，人員和相關成本總體下降。我們相信，隨著我們繼續提高效率，我們可以繼續降低該領域的成本。

The net loss was $10.7 million for Q4 2023 and [$19.9 million] for the comparable period in 2022. Looking to total year to date of 2023 net loss of $110.6 million compared with $182 million in the comparable period of 2022.

2023 年第四季的淨虧損為 1,070 萬美元，2022 年同期的淨虧損為 [1,990 萬美元]。預計 2023 年迄今淨虧損總額為 1.106 億美元，而 2022 年同期淨虧損為 1.82 億美元。

I'd now like to give a little bit more clarity on our overall operational spend and cash burn for 2023, we began implementing our OpEx reduction plan in early June, which includes several cost-saving strategies, including a reduction in force as well as overall company-wide expense reduction. We now have much more visibility into our operational spend and see a clear path to profitability.

我現在想更清楚地說明我們 2023 年的整體營運支出和現金消耗，我們於 6 月初開始實施營運支出削減計劃，其中包括多項成本節約策略，包括減少兵力以及全公司範圍內的整體費用減少。現在，我們對營運支出有了更多的了解，並看到了清晰的獲利之路。

If you look at the slide on that provides, you will see our overall operational spend for 2023 of about $172 million with reduced to $155 million after excluding reorganization charges of [$18 million], reducing these expenses for non-cash stock compensation and not related to severance, and depreciation and amortization of $27 million. Our cash OpEx spend was $128 million for the year. This compares to $177 million of cash OpEx spend for 2022.

如果您查看該投影片，您將看到我們2023 年的總體營運支出約為1.72 億美元，扣除[1800 萬美元] 的重組費用後減少至1.55 億美元，減少了非現金股票補償和不相關的費用遣散費、折舊和攤提 2700 萬美元。今年我們的現金營運支出為 1.28 億美元。相較之下，2022 年的現金營運支出為 1.77 億美元。

Please keep in mind that we started implementing our company-wide reduction midyear 2023. As mentioned in our previous earnings call, we believe our operational run rate, excluding stock compensation and depreciation and amortization on forward will be between $108 million to [$160 million], and cash burn will decrease every order that we have stabilized our spend and when revenues are increasing every quarter.

請記住，我們在 2023 年中開始在全公司範圍內實施裁員。正如我們在先前的財報電話會議中提到的，我們相信我們的營運運行率（不包括股票補償以及遠期折舊和攤銷）將在1.08 億美元至[1.6 億美元]之間，並且現金消耗將減少我們穩定支出的每個訂單以及何時每季的收入都在成長。

Moving now onto our guidance for 2024. We are reaffirming our previously given guidance for revenue of $138 million to $158 million for 2024 and improved gross margins between 68% to 70%. Our operating spend, excluding stock compensation and depreciation and amortization, is anticipated to be between $108 million to $116 million. And EBITDA, excluding stock comp will be between a loss of $22 million to income of $3 million.

現在轉向我們的 2024 年指導。我們重申先前給出的 2024 年收入指引為 1.38 億至 1.58 億美元，毛利率提高至 68% 至 70%。我們的營運支出（不包括股票補償以及折舊和攤提）預計在 1.08 億至 1.16 億美元之間。扣除股票補償後的 EBITDA 將在虧損 2,200 萬美元到收入 300 萬美元之間。

I would like to reiterate that we anticipate getting to positive EBITDA in Q4 2024. And based on this strong balance sheet and our current operation plan, we do not anticipate having to raise a little capital.

我想重申，我們預計 2024 年第四季將實現正 EBITDA。基於強大的資產負債表和我們目前的營運計劃，我們預計不需要籌集一點資金。

And now like to open the call for any questions.

現在想打開電話詢問任何問題。

The floor is now open for your questions. (Operator Instructions)

現在請大家提問。（操作員說明）

Serge Belanger, Needham & Company.

謝爾蓋貝蘭格 (Serge Belanger)，李約瑟公司。

Got it. So two questions related to ZYNRELEF. The first one, it's been six or seven weeks since the label expansion. Just curious if you've seen any impact in demand or usage since that?

知道了。有兩個與 ZYNRELEF 相關的問題。第一個，距離廠牌擴充已經六、七週了。只是想知道自那時起您是否看到需求或使用受到任何影響？

And then maybe secondly, if you can just talk about what the NOPIAN Act means for ZYNRELEF? I guess specifically, what kind of coverage do you have now and how do you think that changes once we flip the calendar to January '25, when the NOPIAN Act takes effect? Thanks.

其次，您能否談談《NOPIAN 法案》對 ZYNRELEF 意味著什麼？我想具體來說，您現在擁有什麼樣的承保範圍？一旦我們將日曆翻到 25 年 1 月，《NOPIAN 法案》生效，您認為這種情況會發生什麼變化？謝謝。

Sure. Yeah, I would say again, anecdotally, when we got the label expansion, obviously, there's a lot of excitement when we go into service centers where we already have some business. It's certainly easier to go deeper into those accounts. And we're seeing some of that.

當然。是的，我想再說一遍，有趣的是，當我們擴大標籤時，顯然，當我們進入已經有一些業務的服務中心時，人們感到非常興奮。更深入地了解這些帳戶當然更容易。我們正在看到其中的一些。

Actually the day one of a label expansion, I guess, first on label spine surgery. I was actually in the surgery in Asheville, North Carolina. So we're certainly getting some of that. I think that thought combined with a certainly, CrossLink, we had the meeting at AAOS, out of San Francisco.

實際上，我想，標籤擴展的第一天，首先是標籤脊椎手術。我實際上是在北卡羅來納州阿什維爾做手術的。所以我們肯定會得到一些。我認為這個想法與 CrossLink 結合，我們在舊金山的 AAOS 舉行了會議。

We were with CrossLink and had some physicians coming by the booth everything and just the excitement around that. But I don't think you're going to see necessarily a dramatic impact as of yet, but we're certainly seeing some impact.

我們與 CrossLink 合作，有一些醫生來到展位，了解一切，並對此感到興奮。但我認為目前還不一定會看到巨大的影響，但我們肯定會看到一些影響。

But I think again, over time, as I said in my comments, I think with CrossLink, with the label expansion, the launch of VAN later in the year, I think this really begins to take off late into the year into '25 when we really start to see an inflection. But we're certainly seeing some positive momentum.

但我再次想到，隨著時間的推移，正如我在評論中所說，我認為透過CrossLink，隨著標籤的擴展，今年晚些時候VAN 的推出，我認為這真的開始在25 年晚些時候開始起飛。我們確實開始看到變化。但我們確實看到了一些正面的勢頭。

Regarding the NOPAIN, I'm going to turn it to Kevin Werner and who can give a little bit more insight into that.

關於 NOPAIN，我將把它交給 Kevin Werner，他可以對此提供更多的見解。

Yeah, Serge, thanks for that question. So the NOPAIN Act is going to be significant for multiple facets. So what the NOPAIN Act does provide reimbursement in the hospital outpatient procedure department and the ambulatory surgical centers for products that have been proven to reduce the need for opioids.

是的，Serge，謝謝你提出這個問題。因此，NOPAIN 法案將在多個方面發揮重要作用。因此，NOPAIN 法案確實為醫院門診手術部門和門診手術中心的產品提供了報銷，這些產品已被證明可以減少對鴉片類藥物的需求。

So in ZYNRELEF instance, we're already covered in both the HOPD and ASC through 2025 for Q1. So the NOPAIN Act is going to go through 2027. So essentially establish that reimbursement for our facilities through 2027, and CMS has discussed a longer time frame from that beyond possibly extending all the way to 2030.

因此，在 ZYNRELEF 實例中，我們已經涵蓋了截至 2025 年第一季的 HOPD 和 ASC。因此，NOPAIN 法案將持續到 2027 年。因此，基本上要在 2027 年之前對我們的設施進行報銷，CMS 已經討論了一個更長的時間框架，超出了可能一直延長到 2030 年的範圍。

So we look forward to working with our legislatures on that and continuing to get reimbursement for our patients to assure that it is covered, but that'll help assure the adoption and the pull through for many institutions.

因此，我們期待與我們的立法機構就此合作，並繼續為我們的患者獲得報銷，以確保其得到承保，但這將有助於確保許多機構的採用和順利實施。

Thank you.

謝謝。

Carl Byrnes, Northland Capital Markets.

卡爾‧伯恩斯，北國資本市場。

Thanks for the question. And congratulations on the results and the progress. Understanding the 2025 is really set up to be the ramp year for ZYNRELEF and APONVIE. How do you see it -- I know you touched on this a bit already. How do you see the cross-selling collaboration and label expansion transitioning into ZYNRELEF in '24? I think the prior language was acute care products and 50% year over year growth still comfortable with that number? Or do you think that that's likely to prove conservative? Thanks.

謝謝你的提問。並對結果和進展表示祝賀。了解 2025 年確實將成為 ZYNRELEF 和 APONVIE 的成長年。你怎麼看——我知道你已經談到了這一點。您如何看待 24 年向 ZYNRELEF 過渡的交叉銷售合作和品牌擴張？我認為之前的說法是急診護理產品，50% 的同比增長仍然對這個數字感到滿意嗎？或者你認為這可能被證明是保守的？謝謝。

Yeah, again, one of the reasons we did give that range was we weren't sure exactly when and how this may take off, but to your point, expand label. And the thing I'd say about the CrossLink partnership -- I mean, every now and then you do one of these where things seem to work perfectly from a standpoint of the personnel and just how things come together, and we really do feel that way that the CrossLink folks have been fantastic.

是的，再說一遍，我們確實給出這個範圍的原因之一是我們不確定它何時以及如何起飛，但就你的觀點而言，擴大標籤。關於 CrossLink 合作夥伴關係，我想說的是，我的意思是，時不時地，你會做其中的一件事，從人員的角度來看，事情似乎完美地運作，而且我們確實覺得CrossLink 的工作人員太棒了。

We certainly are bringing a different relationships that we may have currently with your some of the surgent and so forth. So that's been everything we had hoped for at this point. I think one of the surprises that we had and we did the initial training and I was there along with our team, we did that in person and it gives us very receptive. We have the executive team at CrossLink.

我們確實正在帶來一種不同的關係，就像我們目前與你們的一些急流等人之間的關係一樣。這就是我們此時所希望的一切。我認為我們遇到的驚喜之一是我們進行了初步培訓，我和我們的團隊一起在那裡，我們親自進行了培訓，這讓我們非常容易接受。我們擁有 CrossLink 的執行團隊。

And so from there, we did another training last week in person with some of the sales folks there. And so we're going to continue to do those. And so, we should -- as I mentioned, we should have in the next 30 days or so about 150 reps that will be sort of fully out there and running. And so again, we will certainly see some impact.

因此，從那時起，我們上週親自與那裡的一些銷售人員進行了另一次培訓。所以我們將繼續這樣做。因此，正如我所提到的，我們應該在接下來的 30 天左右的時間安排大約 150 次代表完全投入運行。同樣，我們肯定會看到一些影響。

I'm just trying to temper this a bit because until we really get fully up and running and do this for a little while in terms of these or other areas of the country, I don't think it's going to really take off and inflect until next year. But look, we're having positive things happen so far and we're pleased. So far, this has gone as planned.

我只是想稍微緩和一下這一點，因為直到我們真正完全啟動並運行並在該國的這些或其他地區這樣做一段時間之前，我認為它不會真正起飛和改變直到明年。但是看，到目前為止我們已經發生了一些積極的事情，我們很高興。到目前為止，這一切都按計劃進行。

Great, thanks. And then just a follow-up. There also seems to be -- if you can touch on this a significant opportunity in the ASC segment, particularly to cross sell both ZYNRELEF and APONVIE with your sales force and with the CrossLink collaboration. Can you elaborate a little bit about what your thoughts are in terms of how big that opportunity might be?

萬分感謝。然後只是後續行動。如果您能觸及 ASC 領域的一個重要機會，似乎還有一個重要機會，特別是與您的銷售人員和 CrossLink 合作交叉銷售 ZYNRELEF 和 APONVIE。您能否詳細說明一下您對這個機會可能有多大的想法？

Well, certainly the market is moving that way. And again, we've tried tom -- I hate to say overly simplified things, but we've really tried to go where we think we'd be most successful now in sort of niche this product a bit. And so that has led us to the orthopedic space and we'll certainly expand from there. But that really is in parallel where that space is going with ASC.

嗯，市場肯定正在朝這個方向發展。湯姆，我們再次嘗試過——我不想說過於簡化的事情，但我們確實嘗試過我們認為現在在該產品的利基市場中最成功的地方。因此，我們進入了骨科領域，我們肯定會從那裡擴展。但這確實與 ASC 的空間並行。

So as we look at our business, we think there's a real opportunity as that space expands for us to really have a true partner there. Because again, if you think about the goal of an ASC is to get these patients out quickly to get them to rehab. The last thing you want is any patients that would have any kind of nausea associated with the surgery going back into the hospital.

因此，當我們審視我們的業務時，我們認為隨著空間的擴大，我們確實有一個真正的機會在那裡擁有真正的合作夥伴。因為，如果您考慮 ASC 的目標，就是讓這些患者快速出院並接受復健治療。您最不想看到的就是任何因手術而出現噁心的患者返回醫院。

And so, this is where APONVIE come in and play and so for those high-risk patients. So with our kind of peri-operative one-two punch, we really do feel that these two products are really positioned perfectly with exactly what the ASC is trying to do. And so again, with crosslink already having some presence there, we think that's going to be extremely helpful in opening some doors for us there and really trying to move down that path.

因此，這就是 APONVIE 發揮作用的地方，對於那些高風險患者也是如此。因此，透過我們的圍手術期一打二拳，我們確實覺得這兩種產品的定位非常完美，完全符合 ASC 想要做的事情。再說一遍，由於交聯已經在那裡有了一些存在，我們認為這對於為我們打開一些大門並真正嘗試沿著這條道路前進非常有幫助。

Great. Thanks, and congratulations again.

偉大的。謝謝，並再次恭喜。

Thanks, Carl.

謝謝，卡爾。

(Operator Instructions) Kelly Shi, Jefferies.

（操作員說明）Kelly Shi，Jefferies。

This is Clara on for Kelly. Congrats on the great progress. And just one quick question on the cost reductions. Just wondering, do you have any plan to further -- it that your cost reduction plan in 2024 like should we expect R&D and SG&A to continue go down in 2024 and 2025, unlike at what point, do you think you are operating costs will be at a more stable level? Thank you.

這是克拉拉為凱利代言的。祝賀取得的巨大進步。還有一個關於成本削減的簡單問題。只是想知道，您是否有進一步的計劃- 您在2024 年的成本削減計劃，例如我們是否應該期望研發和銷售、一般管理費用在2024 年和2025 年繼續下降，而不是在什麼時候，您認為您的營運成本會是處於更穩定的水平？謝謝。

So thanks Clara. I appreciate the question. Now the range we've given from $108 million to $116 million. I mean, again, we'd love to be at the lower end of that. We're just -- again, as we've made some of these changes, we are trying to now kind of sort through what that may look like this year.

謝謝克拉拉。我很欣賞這個問題。現在我們給出的範圍是 1.08 億美元到 1.16 億美元。我的意思是，我們希望處於較低水平。我們只是——再次，當我們做出了一些改變時，我們現在正在嘗試對今年可能會發生的情況進行排序。

And we've given ourselves a little bit of wiggle room, but I don't think you're going to see significant cost reductions from here. I think we're sort of at a level now where you can kind of expect going forward. But again, we feel pretty comfortable within this range.

我們給自己留了一點迴旋餘地，但我認為您不會看到成本大幅降低。我認為我們現在處於可以期待未來發展的水平。但同樣，我們在這個範圍內感到非常舒適。

Got it. Okay.

知道了。好的。

There are no further questions at this time. I would now like to turn the call over to Craig Collard for closing remarks.

目前沒有其他問題。我現在想將電話轉給克雷格·科拉德（Craig Collard）發表結束語。

I just want to thank everyone for joining the call today, and we really look forward to speaking to everyone next quarter. Thank you.

我只想感謝大家今天加入電話會議，我們非常期待下個季度與大家交談。謝謝。

This concludes today's call. You may now disconnect.

今天的電話會議到此結束。您現在可以斷開連線。