DURECT Corp (DRRX) 2024 Q4 法說會逐字稿

Greetings, and welcome to the DURECT Corporation fourth-quarter and full-year 2024 earnings conference call. (Operator Instructions) As a reminder, this conference is being recorded.

您好，歡迎參加 DURECT 公司 2024 年第四季和全年財報電話會議。（操作員指示）提醒一下，本次會議正在錄音。

It's now my pleasure to introduce Tim Papp, Chief Financial Officer.

現在我很高興介紹財務長 Tim Papp。

Good afternoon, and welcome to DURECT Corporation's fourth quarter 2024 earnings conference call. This is Tim Papp, Chief Financial Officer of DURECT.

下午好，歡迎參加 DURECT Corporation 2024 年第四季財報電話會議。我是 DURECT 財務長 Tim Papp。

Before we begin, I would like to remind you of our safe harbor statement. During the course of this call, we may make forward-looking statements regarding DURECT's products and development, expected product benefits, our development plans, future clinical trials or projected financial results. These forward-looking statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements. Further information regarding these and other risks can be found in our SEC filings, including our 10-K and 10-Qs under the heading Risk Factors.

在我們開始之前，我想提醒您注意我們的安全港聲明。在本次電話會議期間，我們可能會對 DURECT 的產品和開發、預期產品效益、我們的開發計劃、未來臨床試驗或預期的財務結果做出前瞻性陳述。這些前瞻性陳述涉及風險和不確定性，可能導致實際結果與此類前瞻性陳述的結果有重大差異。有關這些風險和其他風險的更多資訊可以在我們的 SEC 文件中找到，包括標題為「風險因素」下的 10-K 和 10-Q。

To begin, I would like to review our fourth-quarter and full-year 2024 financial results. The following financial information relates solely to our continuing operations and therefore, does not include the operations of our ALZET product line, which we sold in the fourth quarter of 2024.

首先，我想回顧一下我們 2024 年第四季和全年的財務表現。以下財務資訊僅與我們的持續經營有關，因此不包括我們在 2024 年第四季出售的 ALZET 產品線的經營。

Total revenues in 2024 were $2 million compared with $2.6 million in 2023 and $0.5 million for the fourth quarter of '24 compared to $0.9 million for the prior year. 2024 revenues were lower due to lower earn-out revenue from Indivior, lower revenue recognized from feasibility agreements with other companies and lower sales of excipients.

2024 年總營收為 200 萬美元，而 2023 年為 260 萬美元，2024 年第四季為 50 萬美元，而前一年為 90 萬美元。 2024 年收入較低是由於來自 Indivior 的盈利收入較低、與其他公司達成的可行性協議確認的收入較低以及輔料銷售額較低。

R&D expense was $10.4 million in 2024 as compared to $29.4 million for the prior year and $1.9 million for the fourth quarter compared with $5.6 million for the prior year 2023. The decreases were primarily due to lower clinical trial-related expenses following completion of the AHFIRM trial. We also experienced lower contract manufacturing expenses and other external expenses as well as lower employee-related costs.

2024 年研發費用為 1,040 萬美元，而前一年為 2,940 萬美元，第四季研發費用為 190 萬美元，而前一年為 2023 年為 560 萬美元。減少的主要原因是 AHFIRM 試驗完成後臨床試驗相關費用降低。我們的合約製造費用和其他外部費用以及員工相關成本也有所降低。

SG&A expenses were $10 million in 2024 as compared to $12.7 million for the prior year and $2 million for the fourth quarter of '24 compared with $2.2 million for the prior year. These decreases were primarily due to lower employee expenses as well as lower consulting, patent and audit-related expenses.

2024 年銷售、一般及行政費用為 1,000 萬美元，而前一年為 1,270 萬美元；2024 年第四季銷售、一般及行政費用為 200 萬美元，而前一年為 220 萬美元。這些減少主要是由於員工費用降低以及諮詢、專利和審計相關費用降低。

As of the end of 2024, we had cash and investments of $12 million as compared to $29.8 million at December 31, 2023. We believe our cash on hand is sufficient to fund operations through the third quarter of 2025.

截至 2024 年底，我們的現金和投資為 1,200 萬美元，而 2023 年 12 月 31 日為 2,980 萬美元。我們相信，我們手頭上的現金足以支持到 2025 年第三季的營運。

As I previously mentioned, we completed the sale of the ALZET product line during the fourth quarter of 2024. We used a portion of the proceeds to repay the remainder of our term loan and are now debt-free.

正如我之前提到的，我們在 2024 年第四季完成了 ALZET 產品線的銷售。我們用部分收益償還了定期貸款的剩餘部分，現在已無債務。

This transaction both strengthened our balance sheet and was consistent with our corporate strategy of streamlining our operations to focus on developing larsucosterol for alcohol-associated hepatitis. We are continuing to explore all options for funding the clinical development of larsucosterol, including strategic partnerships and financing through the capital markets.

這項交易不僅增強了我們的資產負債表，也符合我們精簡營運、專注於開髮用於治療酒精性肝炎的拉魯司特羅的公司策略。我們正在繼續探索資助 larsucosterol 臨床開發的所有選擇，包括策略合作夥伴關係和透過資本市場融資。

Now I would like to turn the call over to Jim for a business update.

現在我想將電話轉給吉姆，讓他介紹一下業務最新情況。

Thank you, Tim, and hello, everyone. Thank you for joining us today for our fourth quarter 2024 update. I'd like to use our call today to provide some context for the rare opportunity we have here at DURECT. Our lead asset, larsucosterol, for the treatment of alcohol-associated hepatitis, has shown life-saving potential for a disease with no approved therapy.

謝謝你，蒂姆，大家好。感謝您今天加入我們，了解 2024 年第四季的更新。我想利用今天的電話會議來介紹我們在 DURECT 所擁有的難得機會。我們的主要資產 larsucosterol 用於治療酒精性肝炎，對於這種尚未批准的治療方法的疾病，已顯示出挽救生命的潛力。

About 30% of the 164,000 US patients hospitalized due to AH will die within 90 days of hospitalization. This means AH is responsible for greater than 40,000 deaths each year in the US, more than 100 people each day. This is roughly equivalent to the number of deaths from breast cancer or car accidents, but the awareness of this disease remains limited. We believe we have a potential solution that can save a large portion of these patients.

美國因AH住院的164,000名患者中約有30％會在住院後90天內死亡。這意味著 AH 每年在美國造成超過 40,000 人死亡，每天超過 100 人死亡。這大致相當於因乳癌或車禍死亡的人數，但人們對這種疾病的認識仍然有限。我們相信我們有一個潛在的解決方案，可以挽救很大一部分患者。

In our Phase IIb trial, we saw nearly 60% reductions in mortality with both doses of larsucosterol compared with placebo in the 232 US patients. This represents approximately 75% of the total patients enrolled in this study. These strong results have garnered significant attention in the medical and scientific community, highlighted by the FDA granting larsucosterol breakthrough therapy designation, the New England Journal of Medicine's publication of our Phase IIb results in NEJM evidence and the late-breaker presentation of our top line data at EASL last year.

在我們的 IIb 期試驗中，我們發現，在 232 名美國患者中，與安慰劑相比，兩種劑量的 larsucosterol 使死亡率降低了近 60%。這約佔本研究中患者總數的 75%。這些強勁的結果引起了醫學界和科學界的廣泛關注，其中最引人注目的是 FDA 授予 larsucosterol 突破性療法認定、新英格蘭醫學雜誌在 NEJM 證據中發表了我們的 IIb 期結果以及去年在 EASL 上最新展示了我們的頂線數據。

We are committed to developing larsucosterol to provide hope for our AH patients, for their families and loved ones and for the medical professionals who have no effective treatments to offer these patients.

我們致力於開發 larsucosterol，為我們的 AH 患者、他們的家人和親人以及無法為這些患者提供有效治療的醫療專業人員帶來希望。

Our sole focus as a company is to secure the funding to complete our Phase III trial, whether through financing or business development. With such funding, we are ready to initiate our Phase III trial and once underway, we expect to be able to report top line data in approximately two years. We firmly believe that larsucosterol represents the best hope for a breakthrough in the treatment of AH and look forward to the opportunity to demonstrate this in our Phase III trial.

作為一家公司，我們唯一的重點是確保資金完成我們的第三階段試驗，無論是透過融資還是業務發展。有了這些資金，我們準備啟動第三階段試驗，一旦開始，我們預計能夠在大約兩年內報告頂線數據。我們堅信，larsucosterol 代表著 AH 治療領域取得突破的最大希望，並期待有機會在我們的 III 期試驗中證明這一點。

We would now like to take any questions that you may have.

我們現在想回答您可能提出的任何問題。

(Operator Instructions) Francois Brisebois, Oppenheimer & Company.

（操作員指示）Francois Brisebois，Oppenheimer & Company。

Just a couple of quick ones here. I was just wondering if you have an idea, or you can share how much you think this trial will cost you? And then I have a follow-up.

這裡僅簡單介紹幾個。我只是想知道您是否有想法，或者您可以分享一下您認為這次試驗將花費多少錢？然後我有一個後續問題。

Sure. Yeah. I think we -- right now, we're estimating it would be about $20 million. There are some things that we are considering that might make it a little bit under that, but that's approximately what it would cost.

當然。是的。我認為我們——現在，我們估計它大約是 2000 萬美元。我們正在考慮一些因素，可能會使實際成本略低於這個數字，但大致就是這樣。

And two years to data, is that what you said?

還有兩年的數據，這是您說的嗎？

Right, right. Yeah.

對，對。是的。

Okay. Great. And then is there any -- just a quick chance for you to kind of elaborate a little bit more maybe on the variations in time from hospitalization to first dose that were highlighted in kind of the recent -- in the article and New England Journal evidence here. So just anything there that kind of totally makes sense where the issue might have been ex-US here? And that's it for me.

好的。偉大的。然後，您能否稍微詳細闡述最近的文章和《新英格蘭雜誌》證據中強調的從住院到第一次服藥的時間變化。那麼，這裡發生的任何事都完全合理，而問題可能出在美國之外？對我來說就是這樣。

Yeah. It does totally make sense. It makes intuitive sense because this is an acute assault based on chronic conditioning of the liver. So I kind of think about it almost like a heart attack for the liver. So it's hepatitis, right? It's acute inflammation of the liver. And so time to intervention is very important. And we certainly learned that in this trial. We're fortunate enough on the call to have both Norman and WeiQi, and I think I'll ask both of them in their turn to kind of speak to that and also how we're looking to address that in the Phase III. So maybe Norman, you can start and then WeiQi can follow on.

是的。這確實很有道理。這是符合直覺的，因為這是基於肝臟慢性調節的急性攻擊。所以我認為這幾乎就像肝臟的心臟病發作一樣。那麼這是肝炎，對嗎？這是肝臟的急性發炎。因此介入的時間非常重要。我們在這次試驗中確實了解到了這一點。我們很幸運能邀請到 Norman 和 WeiQi 參加這次電話會議，我想我會請他們兩人談談這個問題，以及我們打算如何在第三階段解決這個問題。所以也許諾曼可以先開始，然後圍棋可以跟進。

Frank, so the previous -- there's been no effective therapy. And so time was never a factor and steroids -- time to dosing didn't make any difference. But if you have an effective therapy in acute evolving disease, it really makes sense that it would be effective. And you saw the graphs in the New England Journal article, they're quite impressive. There clearly appears to be an effect of early dosing or dosing within the first, in this case, nine days.

弗蘭克，之前沒有有效的治療方法。因此，時間從來都不是因素，類固醇的服用時間也沒有任何差異。但是如果你對急性發展性疾病有有效的治療方法，那麼它確實有效。你們看到了《新英格蘭醫學雜誌》文章中的圖表，它們非常令人印象深刻。早期服藥或在前九天內服藥顯然有效果。

Yes. WeiQi, would you want to add anything to that?

是的。魏奇，您還有什麼要補充的嗎？

I think Jim and Norman have both answered very well about this time to treat importance of that. And then I think it's certainly critical for us to control the time to treat in this particular patient population.

我認為吉姆和諾曼都對這次的重要性做出了很好的回答。我認為，對我們來說，控制針對這個特定患者群體的治療時間至關重要。

But I just want to add on top of Jim and Norman is that time to treat indeed contribute a large part to the differences between US and ex-US patient population, what the difference we saw in the results, but it's just one of those. But although it's a very important factor, but it's one of the multiple factors. So that's what I would like to add.

但我只想補充一點，除了吉姆和諾曼的觀點之外，治療時間確實是造成美國和美國以外患者群體之間差異的主要原因，我們在結果中看到的差異只是其中之一。但儘管這是一個非常重要的因素，但它只是多個因素之一。這就是我想補充的內容。

Yes, I think that's an important point. And in the US, typically, patients are treated within four days or so. And in the poorest performing region in the Franco, Belgium region, it was two weeks. So there's a substantial difference if you've got an acute circumstance to wait TWO weeks before you do much.

是的，我認為這是一個重要的觀點。在美國，患者通常會在四天左右內得到治療。而在法國表現最差的比利時地區，這一時間是兩週。因此，如果您遇到緊急情況，需要等待兩週才能做很多事情，這有很大的不同。

And so we're really excited about the -- what this might mean for our Phase III because we intend to dose everyone within nine days or so in the Phase III trial, which will eliminate the longer-term duration. In fact, most of the patients will probably be treated very quickly based on what we've learned. And we anticipate that we should even possibly have a stronger signal because that certainly was the case when we looked at these data.

因此，我們對此感到非常興奮——這對我們的第三階段來說可能意味著什麼，因為我們打算在第三階段試驗的大約九天之內給每個人注射藥物，這將消除長期用藥的需要。事實上，根據我們了解的情況，大多數患者可能很快就會得到治療。我們預計我們甚至可能會得到更強的訊號，因為當我們查看這些數據時確實如此。

Carl Byrnes, Northland Capital Markets.

卡爾‧伯恩斯 (Carl Byrnes)，北國資本市場 (Northland Capital Markets)。

I'm wondering if you can share any updates on potential strategic partnerships or business development discussions that you might be having that would support the Phase III study, whether it's a co-development or regional licensing or other nondilutive opportunities?

我想知道您是否可以分享有關潛在策略合作夥伴關係或業務發展討論的最新情況，這些討論可能會支持第三階段研究，無論是共同開發還是區域許可或其他非稀釋性機會？

Yes. Certainly, we've been in that process, and we continue in that process. But I think I'll let maybe Tim, since you're leading the effort, why don't you maybe have a comment here.

是的。當然，我們已經處於這一進程中，並將繼續這一進程。但我想我會讓提姆，因為你在領導這項工作，為什麼不在這裡發表評論呢？

Yes, Carl, we certainly have ongoing efforts on to explore the full range of possibilities to take this product forward. As you can appreciate, I'm sure we can't comment on specifics or give a sense of what the timing would be. But we have been very active over the past couple of quarters, certainly in having discussions, and we're optimistic that we'll be able to find a solution despite the challenges of the capital markets these days.

是的，卡爾，我們確實在不斷努力探索推動該產品發展的各種可能性。如您所知，我確信我們無法對具體細節發表評論或透露具體時間。但我們在過去幾季一直非常活躍，當然也在進行討論，儘管最近資本市場面臨挑戰，但我們樂觀地認為我們能夠找到解決方案。

Ed Arce, H.C. Wainwright.

艾德·阿爾斯、H.C.溫賴特。

This is Thomas Yip asking a couple of questions for Ed. So first question, Jim, given the statistical significant 90-day mortality reduction observed in US patients in the Phase IIb AHFIRM study, is there a possibility to seek funding for a smaller but more rigorous Phase IIb study to generate new data to confirm larsucosterol and under a tighter setting in the US market?

我是 Thomas Yip，想問 Ed 幾個問題。第一個問題，Jim，鑑於 IIb 期 AHFIRM 研究中美國患者的 90 天死亡率顯著降低，是否有可能尋求資金資助一項規模較小但更嚴格的 IIb 期研究，以產生新的數據來驗證 larsucosterol 的效果，並且在美國市場更嚴格的環境下進行？

It's an interesting question. We actually -- what we're looking at right now with our Phase III is a very tight study. What we're looking at here is we're taking advantage of the fact that this trial is going to be conducted entirely in the US where the healthcare system is more uniform than what one sees the disease is diagnosed and patients are presented in a more timely manner as they are in the US versus ex-US. So that's the first thing is going to be US.

這是一個有趣的問題。實際上，我們現在正在進行的第三階段的一項非常嚴格的研究。我們在這裡考慮的是，我們要利用這樣一個事實，即這項試驗將完全在美國進行，美國的醫療保健系統比人們看到的疾病診斷更加統一，並且患者在美國而不是美國以外的地方得到更及時的治療。所以第一件事就是美國。

The next piece we're going to do is we're going to centralize -- or excuse me, we're going to randomize by site versus central randomization. And that will hopefully eliminate any regional biases that we certainly saw with the ex-US group. And we didn't see nearly as much of that in the US when we have now randomization.

我們下一步要做的是集中化——或者不好意思，我們將按站點隨機化，而不是中央隨機化。希望此舉能消除我們在美國以外地區看到的任何地區偏見。當我們在美國實行隨機化時，我們幾乎沒有看到這麼多的情況。

So if you have a site in New York, let's say, you're going to receive a kit of four, two will be placebo, two will be active. And when you burn through that, then you get another kit of four. And so we'll keep the randomization balanced across the various sites.

因此，如果您在紐約有一個站點，假設您將收到一套包含四件試劑盒的試劑盒，其中兩件為安慰劑，兩件為活性劑。當你用完它時，你就會得到另一套四件套。因此，我們將保持各個站點之間的隨機平衡。

And then lastly, we're going to control that time to dose that we spoke about earlier, and that's going to be very important. So everyone who's in the trial will be dosed within nine or ten days or earlier, probably much earlier based -- since it's based in the US. But to conduct another Phase IIb trial, you'd have to have about 200 patients to show a reasonable signal.

最後，我們要控制之前談到的服藥時間，這非常重要。因此，參加試驗的每個人都將在九天或十天或更早的時間內接受劑量治療，可能要早得多——因為試驗是在美國進行的。但要進行另一項 IIb 期試驗，你必須有大約 200 名患者才能顯示出合理的訊號。

And by the time you've done that, you've done the Phase III. And so I think at this point, it's faster and more cost effective for us simply to do a Phase III trial rather than an underpowered Phase IIb might still leave you guessing.

當你完成這一步時，你就完成了第三階段。因此我認為，就目前而言，對我們來說，進行 III 期試驗比進行力度不足的 IIb 期試驗更快、更經濟，這可能仍會讓你猜測。

I don't know, I mean, Norman, do you have any thoughts on that?

我不知道，我的意思是，諾曼，你對此有什麼想法嗎？

Well, what I would say is the other trial First of all, it was a 300-patient trial, but there were two doses. So we really had two active arms, and they gave nearly identical results. So in my mind, that was the equivalent of two Phase II trials. Also with FDA's enthusiasm for the product and where they're saying if you have a good result in another trial, we would consider that sufficient. I don't know why we wouldn't just move to the Phase III trial. It is, as Jim says, a very compact and streamlined trial.

嗯，我想說的是另一項試驗首先，這是一項有 300 名患者參與的試驗，但有兩劑。所以我們實際上有兩個活躍的團隊，並且他們給出了幾乎相同的結果。所以在我看來，這相當於兩次第二階段試驗。此外，FDA 對該產品的熱情以及他們所說的如果在另一項試驗中取得良好結果，我們會認為這已經足夠了。我不知道為什麼我們不直接進入第三階段試驗。正如吉姆所說，這是一次非常緊湊和精簡的試驗。

Got it. Yes, understood the rationale there. And then what about opportunities? Would there be opportunity for nondilutive funding in ex-US countries just where you could generate new data perhaps in a country, you mentioned trial conducts in countries with rigorous control in place. Would that be possible?

知道了。是的，我理解其中的原理。那麼機會又如何呢？在美國以外的國家是否有機會進行非稀釋性融資，您可以在這些國家產生新數據，您提到在實施嚴格控制的國家進行試驗。這可能嗎？

We do some work outside the US? Certainly, we could. There are obviously numerous other indications one could pursue as well. But what we're doing right now is just focusing entirely the entirety of our effort on AH. But the possibility of doing a regional study with an ex-US partner is certainly something that we would consider. So that might indeed be -- there are certain markets that like to have that for sure. They like to see it in their population.

我們在美國以外做一些工作嗎？當然可以。顯然，還有許多其他跡象可以供人們追蹤。但我們現在所做的就是將全部精力集中在 AH 上。但我們肯定會考慮與前美國合作夥伴進行區域研究的可能性。所以這確實可能是——某些市場肯定喜歡這樣。他們樂於看到自己的人口出現這種情況。

Ladies and gentlemen, there are no further questions at this time. I would like to turn the call back to Jim Brown for closing remarks.

女士們、先生們，現在沒有其他問題了。我想請吉姆·布朗作最後發言。

Thank you. And we thank you all for your time today and look forward to catching up if you have any further questions, just please reach out. Thank you all and take care.

謝謝。我們感謝大家今天抽出時間，並期待與您交流。如果您還有其他問題，請與我們聯絡。謝謝大家，保重。

This concludes today's conference. You may disconnect your lines at this time. Enjoy the rest of your day.

今天的會議到此結束。現在您可以斷開線路。享受剩餘的一天。