Dogwood Therapeutics Inc (DWTX) 2024 Q3 法說會逐字稿

Good morning and welcome to the Dogwood Therapeutics Incorporated third quarter, 2024 earnings call.

早安，歡迎參加 Dogwood Therapeutics Incorporated 2024 年第三季財報電話會議。

At this time, all participants have been placed on a listen-only mode. Please be advised that today's call is being recorded at the company's request.

目前，所有參與者都處於只聽模式。請注意，今天的通話是應公司要求錄音的。

At this time. I'd like to turn the call over to Angela Walsh, Chief Financial Officer for Dogwood Therapeutics. Please proceed, Miss Walsh.

此時。我想將電話轉給 Dogwood Therapeutics 的財務長 Angela Walsh。請繼續，沃爾什小姐。

Good morning everyone and thank you for joining us on today's conference call. We are pleased to be with you today to discuss dog with therapeutics third quarter financial results and to provide a corporate update. Please note that our financial results press release is now available on our website.

大家早安，感謝你們參加今天的電話會議。我們很高興今天能與您一起討論狗療法第三季度的財務表現並提供公司最新消息。請注意，我們的財務業績新聞稿現已在我們的網站上發布。

Before we begin. I'd like to remind everyone that statements made during this conference call will include forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1,995 which involve risks and uncertainties that can cause actual results to differ materially from the information expressed or implied by these forward-looking statements.

在我們開始之前。我想提醒大家，本次電話會議中所作的陳述將包括 1995 年《私人證券訴訟改革法案》所定義的前瞻性陳述，這些陳述涉及風險和不確定性，可能導致實際結果與這些前瞻性陳述所表達或暗示的資訊有重大差異。

For more information regarding such risks and uncertainties. Please see the risk factors outlined in the company's filings with the sec.

有關此類風險和不確定性的詳細資訊。請參閱本公司向美國證券交易委員會提交的文件中概述的風險因素。

Any forward-looking statements are made only as of today and we disclaim any obligation to update these forward-looking statements other than as required by law for today's agenda. I will provide a brief financial update and then turn the call over to our CEO Greg Duncan and Chief Medical Officer Dr Mike Gen to provide our corporate summary and highlights related to our recently announced business combination which formed dog with therapeutics.

任何前瞻性陳述僅截至今日為止，我們不承擔更新這些前瞻性陳述的任何義務，除非法律要求今天的議程。我將提供簡短的財務更新，然後將電話轉交給我們的首席執行官 Greg Duncan 和首席醫療官 Mike Gen 博士，以提供我們的公司摘要和與我們最近宣布的業務合併相關的亮點，該合併形成了狗與治療學。

Our financial results for the third quarter, 2024 were published this morning in our press release and are available on our website.

我們 2024 年第三季的財務業績已於今天上午在我們的新聞稿中公佈，並可在我們的網站上查閱。

Therefore, I will just provide a brief summary of our financial status on today's call as of September 30th 2024 dog with therapeutics cash totaled $2 million. On October 7th 2024 we announced a business combination with Pharmagest Holding Incorporated, the parent company of Wex Pharmaceuticals Incorporated to form dog with therapeutics. A key component of the combination was a concurrent $19.5 million strategic financing by an affiliate of CKLS. CK Life Sciences International Holdings Incorporated, a Hong Kong Exchange listed company and an indirect parent company of Pharmas and Wex Pharmaceuticals. We have received $16.5 million in loan proceeds in connection with this financing with an additional $3 million expected to be received in February 2025 resulting in approximately $23 million in working capital including combined cash of the entities at the time of the combination.

因此，在今天的電話會議上，我將簡要概述我們的財務狀況，截至 2024 年 9 月 30 日，治療現金總額為 200 萬美元。2024 年 10 月 7 日，我們宣布與 Wex Pharmaceuticals Incorporated 的母公司 Pharmagest Holding Incorporated 進行業務合併，成立狗用治療公司。此次合併的關鍵要素是 CKLS 的一家附屬公司同時提供的 1,950 萬美元策略融資。長江生命科技國際集團有限公司是一家香港交易所上市公司，也是Pharmas和Wex Pharmaceuticals的間接母公司。我們已收到與此融資相關的 1,650 萬美元貸款收益，預計 2025 年 2 月還將收到 300 萬美元，從而形成約 2,300 萬美元的營運資金，包括合併時實體的綜合現金。

Based on our projections, this should fund research and operations through 2025 and through several key milestones including the announcement of top line results from the long COVID phase two. A study expected in the middle of this month and the release of results from the how neuron phase two B interim analysis assessment expected in the second half of 2025.

根據我們的預測，這筆資金應該能夠支持到 2025 年的研究和運營，並支持幾個關鍵里程碑，包括宣布長期 COVID 第二階段的頂線結果。預計本月中旬將進行一項研究，並預計在 2025 年下半年發布 How Neuron 第二階段 B 中期分析評估的結果。

We expect to file the form eight K A with the combined entity financial statements in mid December of this year and look forward to keeping you updated on our progress.

我們預計今年 12 月中旬提交合併實體財務報表的 8KA 表格，並期待隨時向您通報我們的進展。

Now it is my pleasure to turn the call over to our CEO Greg Duncan to provide a corporate summary, Greg.

現在我很高興將電話轉給我們的執行長格雷格鄧肯 (Greg Duncan)，讓他提供公司概要，格雷格。

Thank you very much, Angela and good morning all. As Angela referenced last month, we announced the formation of dogwood therapeutics by the integration of verys therapeutics and wex pharmaceuticals given the proximity of this transformative transaction. We think today's earnings update represents an opportune time to share our thoughts on the key value creation opportunities that now reside within the expanded Doug with therapeutics pipeline, Mike. And I provide you with highlights on our three late stage program with a particular focus on the newest addition to this pipeline hal neuron, our NAV 1.7 modulator that will be the focus of the forthcoming chemotherapy induced neuropathic pain phase two program. We expect to commence in quarter one of next year, Mike and I will be making forward-looking statements through the course of our discussion today. We'll have a Q&A at the end of our overview. And if you have additional queries post today's call, you can reach out to us directly at IR at DWTX dotcom.

非常感謝，安吉拉，大家早安。正如安吉拉上個月提到的，鑑於這次變革性交易的臨近，我們宣布透過整合 verys therapy 和 wex pharmaceuticals 成立 dogwood therapy。我們認為，今天的收益更新代表著一個恰當的時機，可以分享我們對目前存在於擴大的 Doug 和治療管道 Mike 中的關鍵價值創造機會的看法。我向您重點介紹我們的三個後期項目，特別關注該管道 hal 神經元的最新成員，即我們的 NAV 1.7 調節器，它將成為即將開展的化療引起的神經性疼痛第二階段項目的重點。我們預計將於明年第一季開始，麥克和我將在今天的討論過程中做出前瞻性陳述。我們將在概述結束時進行問答。如果您在今天的電話會議後還有其他疑問，您可以直接透過 IR at DWTX dotcom 與我們聯繫。

Before diving into the specific programs, I thought I might just summarize or refresh the highlights of the transaction to form Dogwood Therapeutics.

在深入研究具體項目之前，我想我可以先總結或回顧一下組建 Dogwood Therapeutics 的交易的亮點。

Your main to this formation was an expansion of our pipeline to include hal neuron currently projected to have interim data in the phase two B program for chemotherapy induced neuropathic pain in the second half of next year, as Angela referenced the strategic financing by an affiliate of Life Sciences, a hong Kong exchange listed company and existing cash provides us with working capital of approximately $23 million to fund operations to quarter four of next year. Importantly, this enables us to deliver interim results from the phase two B program focused on how neuron in this time period. Additionally, IMC two, a combination of ALSIC and SOIC is the focus of a phase two, a study run by the Bateman Horn Center and we have data expected in the middle of this month as part of the transaction. Our stockholders as of record of October 17th were granted a contingent value right or CV R as you may know it tied to potential future milestone payments associated with future partnering transactions for I MC, one or I MC two, particularly related to development or regulatory milestones.

此次組成的主要目的是擴大我們的產品線，包括目前預計在明年下半年獲得化療引起的神經性疼痛的第二階段 B 計劃中期數據的 Hal Neuron，正如 Angela 提到的，由香港交易所上市公司 Life Sciences 的一家附屬公司提供的戰略融資和現有現金為我們提供了約 2300 萬美元的營運資金，以資助到明年第四季度的運營。重要的是，這使我們能夠提供第二階段 B 計劃的中期結果，該計劃重點關注這一時期的神經元。此外，IMC two（ALSIC 和 SOIC 的組合）是第二階段的重點，這是由貝特曼霍恩中心進行的一項研究，作為交易的一部分，我們預計將在本月中旬獲得數據。截至 10 月 17 日的記錄，我們的股東被授予了或有價值權或 CV R，您可能知道它與 I MC 一或 I MC 二的未來合作交易相關的潛在未來里程碑付款相關，特別是與開發或監管里程碑相關的付款。

And this team, the combined team of Rio therapeutics and WEX pharmaceuticals that is now the dog with therapeutics. Management team has extensive experience in developing and commercializing several blockbuster drugs, including the pain medicines, CeleBREX, Lyrica, and SA as you can see on slide number four, in addition to Angela Mike and myself, we'll be presenting today. We have Ralph Crossword, who's our senior Vice President of Operations and M Joe, our VP of manufacturing. You can see the companies, the team has worked at have extensive training and experience. And you can see on the right hand side of slide number four, a number of drugs that we've been involved in including pain therapeutics. And so we we are really excited about the potential of hell neuron and the life cycle opportunities in this new addition to our portfolio.

這個團隊是 Rio therapy 和 WEX pharmaceuticals 的聯合團隊，也就是現在的 dog with therapy。管理團隊在開發和商業化幾種重磅藥物方面擁有豐富的經驗，包括止痛藥、CeleBREX、Lyrica 和 SA，正如您在第四張幻燈片上看到的，除了 Angela Mike 和我之外，我們今天也將進行演講。我們有 Ralph Crossword，他是我們的營運資深副總裁，還有 M Joe，他是我們的製造副總裁。您可以看到，團隊工作過的公司都有豐富的培訓和經驗。您可以在第四張投影片的右側看到我們參與研發的多種藥物，包括疼痛治療藥物。因此，我們對地獄神經元的潛力以及我們投資組合中這一新成員的生命週期機會感到非常興奮。

Speaking of our portfolio, as you can see a rate on slide 5, we now have the expanded Doug with therapeutics pipeline which targets several areas of unmet medical need and has in our opinion, very significant value creation potential. There are really two pillars to the pipeline. First is the nav 1.7 platform. The focus of which is how neuron and specifically our phase two B program and chemo induced neuropathic pain.

說到我們的投資組合，正如您在幻燈片 5 上看到的，我們現在擁有擴展的 Doug 治療產品線，該產品線針對幾個未滿足的醫療需求領域，並且在我們看來，具有非常顯著的價值創造潛力。該管道實際上有兩大支柱。首先是nav 1.7平台。重點是神經元，特別是我們的第二階段 B 計劃和化療如何引起神經性疼痛。

I will mention we're excited about data, some data that Mike will share with you in the next few moments and how no one's potential to treat broader cancer related pain. We also believe this mechanism has potential in acute pain and recently filed intellectual property protection for unique contact lens formulation, delivery formulation of the NAV 1.7 therapeutic. So, really a potential for this platform to deliver in many different areas among that need. The second pillar of the portfolio is our combination anti viral program featuring I MC one, the combination of Baam, CYCL and BCCL and the Long COVID or past program, which features I MC two, which is a combination of bowel cyclo and Celecox I MC. One is poised to progress into phase three development. And as I mentioned earlier, and we'll speak more about this later in the course of today's presentation, we expect a long COVID phase two A results in the middle of this month. So with that background, let me turn it over to doctor general to talk a little bit about the mechanism of the NAV 1.7 platform. And some of the data that has us really excited about how neurons potential Mike.

我要說的是，我們對數據感到興奮，麥克將在接下來的幾分鐘內與您分享一些數據，以及如何治療更廣泛的癌症相關疼痛的潛力。我們也相信這種機制在治療急性疼痛方面具有潛力，並且最近為獨特的隱形眼鏡配方、NAV 1.7 治療的遞送配方申請了智慧財產權保護。因此，該平台確實有潛力滿足許多不同領域的需求。產品組合的第二個支柱是我們的組合抗病毒計劃，其特色是 I MC one，即 Baam、CYCL 和 BCCL 的組合，以及 Long COVID 或過去計劃，其特色是 I MC two，即腸道環路和 Celecox I MC 的組合。其中一個項目即將進入第三階段開發。正如我之前提到的，我們稍後會在今天的演講中詳細討論這個問題，我們預計本月中旬將公佈長期 COVID 第二階段 A 的結果。因此，在這樣的背景下，讓我把主題交給將軍來談談 NAV 1.7 平台的機制。有些數據讓我們對神經元的潛力感到非常興奮。

Thanks Greg. So going to first present the newest addition to our development, stable hail neuron. Ha neuron is a voltage gated sodium channel modulator. Sodium channel are integral to how neurons propagate electrical signals through the through them to the spinal cord and ultimately to the brain. And the particular NAV 1.7 channel, which hell neuron is specifically targeted for is very involved with peripheral pain. So there's nine known sodium channels, some of which are more involved with cardiac conduction and other parts of the body. But the NAV 1.71 0.8 and 1.9 are those that are most associated with pain and inflammation. So, hell neuron being a 1.7 modulator has the ability to really change how pain is transmitted in the body. And we think it has potential for both chronic and acute pain as we've talked about.

謝謝格雷格。因此，首先要介紹的是我們開發的最新成果——穩定的冰雹神經元。Ha神經元是一種電壓門控鈉通道調節器。鈉通道對於神經元如何將電訊號通過它們傳播到脊髓並最終到達大腦至關重要。而特定的 NAV 1.7 通道（地獄神經元專門針對該通道）與周圍疼痛密切相關。已知的鈉通道有九種，其中一些與心臟傳導和身體其他部位有關。但 NAV 1.71 0.8 和 1.9 與疼痛和發炎最相關。因此，地獄神經元作為 1.7 調節器，能夠真正改變疼痛在身體中的傳遞方式。正如我們所討論的，我們認為它對治療慢性疼痛和急性疼痛都有潛力。

So let's go to the next slide and we'll talk about the opportunities for what we think the applications for hell neuron would be. The prior work that was done by the predecessor company focused on two different areas. There was a phase two study looking at cancer related pain that is they took people who were having, you know, had cancer, had pain from that cancer and then treated them with injections of hell neuron to try and reduce the pain that they were experiencing subsequent to their cancer, their surgery or the chemotherapy, whatever the cause of that pain was.

那麼讓我們進入下一張投影片，我們將討論我們認為地獄神經元的應用機會。前任公司所做的前期工作主要集中在兩個不同的領域。有一項第二階段研究針對的是癌症相關的疼痛，即他們招募了患有癌症並因此感到疼痛的人，然後透過注射地獄神經元來治療他們，試圖減輕他們在癌症、手術或化療之後所經歷的疼痛，無論疼痛的原因是什麼。

And that study generated statistically significant reductions in pain in a, in a study that had enrolled 165 patients. That was encouraging to us and we were specifically encouraged by the duration of the improvement we saw in some of those patients, which we'll talk about in a minute. The other study that was done prior to our combination was a phase two, a signal seeking study in chemotherapy induced neuropathic pain. So that is the indication our next study will be focused on and what was done there. It was 125 patients were recruited and they were randomized to one of three different doses and two different dosing strategies either once a day or twice a day to determine what the optimal dose and dosing frequency would be to carry forward in a future study. And that future study is the one we're planning right now. So given that that background, we were very excited about the potential for hell neuron in treating pain, secondary to chronic conditions like cancer related pain, that slide.

該研究在一項招募了 165 名患者的研究中，統計結果顯示患者的疼痛顯著減輕。這對我們來說是令人鼓舞的，尤其讓我們感到鼓舞的是，我們看到一些患者的病情改善持續時間很長，我們稍後會談到這一點。在我們合併之前進行的另一項研究是第二階段，一項針對化療引起的神經性疼痛的訊號尋求研究。因此，這表明我們的下一項研究將重點放在該研究，並且已經進行了相關研究。研究人員招募了 125 名患者，並將他們隨機分配到三種不同劑量和兩種不同的給藥策略中，即每天一次或每天兩次，以確定未來研究中的最佳劑量和給藥頻率。我們現在正在計劃未來的研究。因此，考慮到這一背景，我們對地獄神經元在治療癌症相關疼痛等慢性疾病引起的疼痛方面的潛力感到非常興奮。

So this is data from that cancer related pain. I mentioned where we had statistically significant results in terms of pain reduction due to hell neuron. This is a responder analysis where we looked at patients who had at least a 30% reduction in pain from their baseline before they were treated with he neuron. And what we saw was that there was a statistically significant increase in the rate of response in the patients treated with hail neuron versus those treated with placebo. Even though this was a relatively small study with less than 160 some odd patients. It was still statistically significant in terms of this responder analysis after three weeks of treatment.

這是與癌症相關的疼痛的數據。我提到了我們在地獄神經元減輕疼痛方面取得了具有統計意義的結果。這是一項反應分析，我們觀察了在接受神經元治療之前疼痛程度較基線至少減輕 30% 的患者。我們發現，與接受安慰劑治療的患者相比，接受冰雹神經元治療的患者的反應率有顯著提高。儘管這是一項相對較小的研究，患者人數不到 160 人。經過三週的治療後，根據反應分析，它仍然具有統計意義。

What was even more interesting in this, however, was the duration of response we saw from this treatment which we'll talk about in a minute. Looks like this shows now the duration of response and the curve on the top where you can see these blue lines, this was the patients who were initial responders. That is at week three of the study, they had at least a 30% reduction in pain from their baseline. If they were a responder, they were continued to be followed on a weekly basis to see how long that pain improvement lasted. And if they if they continue to be followed, you can see that there were a number of patients who went out quite a long way, some went over a year in terms of pain reduction. The bottom curve are those responders to placebo. You do get patients who reach improve on placebo. But you can see here, the main improvement in those who were initial responders was on the order of 10 days that before they lost their effect, the main change in the hell neuron group was over 50 days and in some cases, it was beyond a year before the patient finally got tired of giving us data. But you can see there's a very big difference between the duration of the improvement we see with treatment versus placebo. And that, that really intrigued us and made us think that something special is going here because they were only treated for four days initially. And then we have this long response as a result.

然而，更有趣的是，我們從這種治療中看到的反應持續時間，我們稍後會討論。看起來這現在顯示了反應持續時間和頂部的曲線，您可以看到這些藍線，這是最初有反應的患者。也就是說，在研究的第三週，他們的疼痛感比基線時減少了至少 30%。如果他們有反應，我們會繼續每週追蹤他們，以觀察疼痛改善持續了多長時間。如果繼續跟踪，你會發現很多患者的疼痛減輕情況已經好轉了不少，有些甚至持續了一年多。底部曲線代表對安慰劑有反應的人。你確實會發現服用安慰劑後病情好轉的患者。但您可以看到，最初有反應的患者的主要改善是在 10 天內，然後才失去效果，而地獄神經元組的主要變化是在 50 多天后，在某些情況下，患者最終厭倦了向我們提供數據，這已經超過一年了。但你可以看到，治療組和安慰劑組的改善持續時間有很大差異。這確實引起了我們的好奇，讓我們覺得這裡一定發生了一些特別的事情，因為他們最初只接受了四天的治療。然後我們就得到了這個長篇回應。

Let's go to the next slide, please.

請看下一張投影片。

So I think Greg we're going to hand that back to you to talk about the potential.

所以我認為格雷格，我們會把這個任務交還給你，來討論潛力。

Sure, Mike referenced the second study, the chemo induced neuropathic pain phase two, a study, the signal seeking study which assessed three doses and two different dosage regimens of hell neuron to treat specifically cinp.

當然，麥克提到了第二項研究，即化療引起的神經性疼痛第二階段研究，一項信號尋求研究，該研究評估了三種劑量和兩種不同的地獄神經元劑量方案，以專門治療 cinp。

The results of this study are a rate on the left hand side of slide number 10, very specifically higher hell neuron doses deliver greater pain reduction as compared to lower doses, which we think is very consistent with the utility of this particular mechanism.

這項研究的結果在第 10 張投影片的左側，具體來說，與較低劑量相比，較高劑量的地獄神經元可以減輕更多的疼痛，我們認為這與這種特殊機制的效用非常一致。

We also noted that he neuron when dosed once a day. QD provided comparable pain reduction to the B ID dose twice a day but exhibited a better tolerability profile.

我們也注意到，每天服用一次時，神經元就會改變。QD 提供的疼痛減輕效果與每天兩次的 B ID 劑量相當，但表現出更好的耐受性。

How neuron pain relief was evident four weeks, post treatment in this particular study and the hell neuron high doses in particular, delivered clinically meaningful pain reduction for 35 to 40% of patients in this relatively small study.

在這項特定的研究中，神經元疼痛緩解在治療後四周明顯，特別是高劑量的地獄神經元，在這項相對較小的研究中為 35% 至 40% 的患者帶來了具有臨床意義的疼痛減輕。

AC A MP we believe represents a very significant market opportunity. Presently, there are no FDA approved treatments for chemo induced neuro neuropathic pain.

我們相信 AC A MP 代表著非常重要的市場機會。目前，尚無 FDA 批准治療化療引起的神經性疼痛的方法。

We know from our secondary market research data that more than half of the sales for the global pain market are actually prescribed for opioids.

我們從二級市場研究數據得知，全球疼痛市場超過一半的銷售量其實都是鴉片類藥物。

I don't think I have to tell anybody on the phone here that that's a bad fact for any particular disease, given the abuse potential and the side effects that are associated with opioids. I think we'd all probably agree as well. If we have something that can work to replace or reduce the utilization of opioids, we have something that's commercially speaking a winner.

考慮到阿片類藥物的濫用潛力和副作用，我認為我不必在電話中告訴任何人，這對任何特定疾病來說都是一個壞事實。我想我們可能也會同意。如果我們有某些東西可以替代或減少鴉片類藥物的使用，那麼從商業角度來說，我們就有了一個成功的東西。

Over time, most patients get some form of neuropathic pain. If you look at the background data for chemo induced neuropathic pain, one month after treatment, there's about 70% of patients who have some form of neuropathic pain. Three months that drops down to 60% but even at six months, you have 30% of patients in neuropathic pain. This is six months after the discontinuation of the chemotherapy. This is a bad fact. And in fact, if you look at just the big five markets in the Eu Japan and the US, there are 1.7 million induced neuropathic pain patients in just those territories. When you add in developing markets and other potential markets across Europe, you have well north of $2.5 million patients that are actually suffering from chemo AUC. So the size of the opportunity, the heavy utilization of opioids and the fact that this is impacting one in three patients who have chemotherapy six months after they stop their chemotherapy represents in our opinion, a very significant commercial opportunity.

隨著時間的推移，大多數患者都會出現某種形式的神經性疼痛。如果您查看化療引起的神經性疼痛的背景數據，治療一個月後，大約有 70% 的患者會出現某種形式的神經性疼痛。三個月後，這一比例下降到 60%，但即使六個月後，仍有 30% 的患者出現神經性疼痛。這是停止化療六個月後。這是一個糟糕的事實。事實上，如果只看歐盟、日本和美國這五大市場，光是這些地區就有 170 萬名神經性疼痛患者。如果加上歐洲的發展中市場和其他潛在市場，那麼實際遭受化療 AUC 折磨的患者將遠遠超過 250 萬美元。因此，我們認為，這個機會的規模、阿片類藥物的大量使用以及這影響到三分之一在停止化療六個月後接受化療的患者的事實，代表著非常重要的商業機會。

So to summarize the hell Neuron program, which we think represents a very novel non opioid pain development opportunity. This is a novel 1.7 voltage gated sodium channel inhibitor, highly differentiated from other therapeutics and specifically non opioid in its particular mechanism.

因此，總結一下地獄神經元計劃，我們認為它代表了一種非常新穎的非鴉片類疼痛開發機會。這是一種新型的 1.7 電壓門控鈉通道抑制劑，其特殊機制與其他治療藥物有很大區別，特別是非鴉片類藥物。

This is a validated mechanism supported by both pre clinical and clinical data.

這是一個經過臨床前和臨床數據支持的驗證機制。

We've seen Mike and I just share with you reduction in both general cancer related pain and chemo induced neuropathic pain in human clinical trials. This is a large market opportunity and this is a team that understands the pain stays well both from a development and a commercialization potential.

我們已經看到了麥克，我剛剛與大家分享了在人體臨床試驗中一般癌症相關疼痛和化療引起的神經性疼痛的減輕情況。這是一個巨大的市場機遇，這個團隊非常了解開發和商業化潛力的痛點。

So we are really excited to add Helmo run to the deal with therapeutics pipeline. And we're very excited about the interim analysis. We plan for the second half next year.

因此，我們非常高興將 Helmo run 添加到治療方案中。我們對中期分析感到非常興奮。我們計劃明年下半年。

Now we turn our attention to the legacy various therapeutics products. The combination antiviral therapies, which we believe are targeting two very significant areas of IMC. One is poised to progress into phase three development as a treatment for fibromyalgia, a condition for which there has been nothing approved for the past few years. In fact, well, over a decade, we have agreement with FDA based on our phase two B study for a four part phase three program, that program will consist of a pharmacokinetic and food effect study with a new formulation would progress into phase three development for fibromyalgia.

現在我們將注意力轉向傳統的各種治療產品。我們認為聯合抗病毒療法針對的是 IMC 的兩個非常重要的領域。其中一項療法即將進入第三階段研發，用於治療纖維肌痛，而過去幾年中，針對纖維肌痛的療法尚未獲得批准。事實上，十多年來，我們已與 FDA 達成協議，基於我們的第二階段 B 研究，開展由四部分組成的第三階段計劃，該計劃將包括藥代動力學和食物效應研究，新配方將進入纖維肌痛的第三階段開發。

Two direct studies of 12 weeks duration, one head to head study of I MC one versus placebo and then a multifactorial trial of I MC one versus placebo versus the individual components that comprise I MC. One is a combination there, patients who have an interest can progress from study. One or study two into our long term safety extension which allows us to collect the safety data required to submit an NDA to the Food and Drug Administration.

兩項為期 12 週的直接研究，一項是 I MC 一與安慰劑的頭對頭研究，然後是 I MC 一與安慰劑以及組成 I MC 的各個成分的多因素試驗。一種是組合，有興趣的患者可以透過學習取得進步。將一項或兩項研究納入我們的長期安全擴展，這使我們能夠收集向食品藥物管理局提交 NDA 所需的安全資料。

We're presently exploring phase three partnership opportunities both to conduct the study as well as to develop an extended release dosage formulation to extend the IP of I MC one beyond its current intellectual property protection, we'll report out on that sometime in the first half of next year. And then we have I MC two, the combination of Valico and SOIC coin the focus of a phase two long COVID study.

我們目前正在探索第三階段的合作機會，以進行研究並開發緩釋劑型，以將 I MC 的 IP 擴展到其當前的智慧財產權保護之外，我們將在明年上半年的某個時候報告此事。然後我們有了 I MC two，Valico 和 SOIC 硬幣的組合是第二階段長期 COVID 研究的重點。

We had a proof of concept study complete in 2023 Michael share the data with you that have us excited about this particular mechanism that study allowed us to file new IP with patent protection if granted to 2044. Importantly, this study gave us the data to go to FDA and work out what the development requirements are for I MC two to treat non COVID symptoms. And in particular, we've now agreed with FDA that for the first time to our belief is the first time FDA is approved, fatigue is the primary endpoint for a development candidate. There's a three arm phase two investigator initiated study ongoing right now, topline data which we expect in the middle and with that background on the two programs, I'm going to ask Mike to dive into the data from the proof of concept study. We communicated out in 2023 as a refresher as we get excited about the release of the current study in the next week or so.

我們在 2023 年完成了一項概念驗證研究，Michael 與您分享了數據，這些數據讓我們對這一特殊機制感到興奮，該研究允許我們在 2044 年獲得專利保護的情況下提交新的智慧財產權。重要的是，這項研究為我們提供了向 FDA 提交的數據，並確定 I MC 2 治療非 COVID 症狀的開發要求。特別是，我們現在已經與 FDA 達成一致，我們認為這是 FDA 第一次批准，疲勞是開發候選藥物的主要終點。目前正在進行一項由三組研究人員發起的第二階段研究，我們預計會在中間階段獲得頂線數據，並且根據這兩個項目的背景，我將請麥克深入研究概念驗證研究的數據。我們在 2023 年進行了交流，作為複習，因為我們對下週左右發布當前研究感到興奮。

Right.

正確的。

Sure, great. So we, we did have a proof of concept study previously run by the Bateman Horn Center. This was an investigator initiated study where they were the first question was, was there any feasibility to show with applying this an viral approach to a long COVID patient population? The Bateman Horn Center has a long COVID clinic where they had a number of patients. They were, they were monitoring and taking care of and when they initiated this study, they recruited from that long COVID population and they enrolled 22 patients to be treated with the combination of the al Cyclos COXY to treat their lung COVID symptoms. This step conducted open label. So these 22 patients were aware they were getting the antiviral treatment and they were, the results were compared to 17 match controls drawn from the same population and they were matched for their gender for their age for how long they've had long COVID, whether they've been vaccinated and so on. So they were well matched group. And then the comparison was reduction in symptoms of long COVID in the treated population versus the mass control population. It's interesting to note that the duration of long COVID symptoms in this population was over two years in both groups. So this is a group of patients that had long standing lung COVID had been difficult to treat with other therapies and then treated with this antiviral combination to see if we could really improve their symptoms. And as you can see on the slide with the study endpoints, there was fairly dramatic improvement in a number of symptoms in this patient population. The primary endpoint was fatigue improvement. We see that this long COVID population looks quite a bit like chronic fatigue populations. And the ba and Harm Center is a specialty center in treating fatigue and pain conditions. They were very interested in fatigue in this population. And the NH promise fatigue score was used as primary. And again, you can see even though this is 22 patients compared to 17, it was highly statistically significant in favor of the antiviral treatment. Fatigue was also measured on a 0 to 10 numeric rating scale. The standard scale we've improved on that as well. We saw some movement in pain. We asked a patient global impression of change question two different ways to ask the patient since they enrolled in the study, how they were doing. And in both cases, the patients reported significant improvement in the quality of life.

當然，太好了。因此，我們確實進行了由貝特曼霍恩中心先前進行的概念驗證研究。這是一項由研究人員發起的研究，他們提出的第一個問題是，將這種病毒治療方法應用於長期 COVID 患者群體是否有可行性？貝特曼霍恩中心有一個長期的 COVID 診所，那裡有很多病人。他們當時正在監測和照顧，當他們啟動這項研究時，他們從長期 COVID 人群中招募了 22 名患者，使用 Cyclos COXY 聯合治療來治療他們的肺部 COVID 症狀。此步驟進行開放標籤。因此，這 22 名患者知道他們正在接受抗病毒治療，並將結果與來自同一人群的 17 名匹配對照進行了比較，並根據他們的性別、年齡、患 COVID 的時間長短、是否接種過疫苗等進行了匹配。所以他們是一個非常匹配的群體。然後比較接受治療的人群與接受大規模控制的人群中長期 COVID 症狀的減少情況。有趣的是，這兩組族群的長期 COVID 症狀持續時間均超過兩年。因此，這是一組長期患有肺癌且難以用其他療法治療的患者，然後使用這種抗病毒組合進行治療，看看我們是否真的可以改善他們的症狀。正如您在研究終點幻燈片上看到的那樣，該患者群體的許多症狀都有了相當顯著的改善。主要終點是疲勞改善。我們發現，長期感染 COVID 的人看起來很像慢性疲勞族群。而 ba and Harm Center 是專門治療疲勞和疼痛症狀的中心。他們對這一人群的疲勞狀況非常感興趣。並以NH承諾疲勞評分作為主要評分。再次，您可以看到，儘管這是 22 名患者，而之前只有 17 名，但從統計學上看，抗病毒治療非常有利。疲勞程度也透過 0 到 10 的數字評定量表來衡量。我們也對標準規模進行了改進。我們看到了一些痛苦的動作。我們用兩種不同的方式詢問了患者對變化的整體印象，以了解患者自參加研究以來的狀況。在這兩種情況下，患者都報告生活品質有顯著改善。

We also had a an assessment of orthostatic intolerance. This is the feeling that patients get when their autonomic nervous system doesn't respond quite properly. So when you go from sitting to standing or lying down to sitting, you might feel faint, you might feel like you're going to black out. That's orthostatic intolerance. It's common in the long COVID population. And we saw a significant movement on the orthostatic scales in this study as well. That was something the Bateman Horn Center was specifically interested in. It was new to Dogwood, but we were quite pleased with the results that we saw on this orthostatic scale and we even saw some movement in in mood disorders probably because patients were feeling that their symptoms overall were improving.

我們也對直立不耐受進行了評估。這是患者的自主神經系統反應不正常時所產生的感覺。因此，當您從坐姿變為站姿或從躺姿變為坐姿時，您可能會感到頭暈，甚至感覺自己快要昏過去了。這就是直立不耐受。這在長期 COVID 人群中很常見。我們在這項研究中也看到了直立量表上的顯著變化。這是貝特曼號角中心特別感興趣的事。這對 Dogwood 來說是新事物，但我們對在這個直立量表上看到的結果非常滿意，我們甚至看到情緒障礙有所改善，可能是因為患者感覺他們的症狀總體上有所改善。

Now, as I said, this was an open label study. The treatment was very well tolerated. We know that val cyclo VR has very little interaction with mammalian cells. So it's very well tolerated. Celecoxib is the best tolerated of the nonsteroidal anti inflammatories. So real, it was not a surprise that it was well tolerated with seeing that before with the other antivirals. But nonetheless, it really suggest that this could be a first line treatment If it continues to do well, being open label, we wanted to confirm this in a more classic double blind placebo controlled study. So we did approach Ba and Horn Center about doing a follow up study, which would be the placebo controlled double blind study and so on. So that study has been run at the BX.

現在，正如我所說，這是一項開放標籤研究。該治療的耐受性非常好。我們知道 val cyclo VR 與哺乳動物細胞的相互作用非常小。因此它的耐受性非常好。塞來昔布是非類固醇抗發炎藥中耐受性最好的。因此，由於之前看到其他抗病毒藥物具有良好的耐受性，所以這並不奇怪。但儘管如此，它確實表明這可能是一種一線治療方法，如果它繼續表現良好，作為開放標籤，我們希望在更經典的雙盲安慰劑對照研究中證實這一點。因此，我們確實與巴和霍恩中心接洽，希望進行一項後續研究，即安慰劑對照雙盲研究等等。因此該研究已在 BX 進行。

They've enrolled 45 patients that they randomized three arms 1 to 1 to 1 a high doses, the antiviral combination, low dose antiviral combination and a placebo arm that result is still blinded. We will be getting the results shortly. But we're looking forward to seeing if we can reply the results we saw in the proof of concept study. Primary end point again is fatigue reduction. We'll be looking for improvement in sleep orthostatic symptoms, anxiety, depression, and overall health when we get the results from this study. And as we've already mentioned, the top line results are expected in the next few weeks. So with that, that's a, that's our antiviral platform and where we stand on that, I'll turn it back to Greg to wrap up.

他們招募了 45 名患者，並將其隨機分為三組，即高劑量抗病毒組合組、低劑量抗病毒組合組和安慰劑組，結果仍然是盲法的。我們很快就會得到結果。但我們期待看到我們是否能夠回應我們在概念驗證研究中看到的結果。主要終點仍然是減少疲勞。當我們獲得這項研究的結果時，我們將尋求睡眠直立症狀、焦慮、憂鬱和整體健康狀況的改善。正如我們已經提到的，預計最終結果將在未來幾週內公佈。這就是我們的抗病毒平台以及我們的立場，我將把它交還給 Greg 來總結。

Sure. Just one word about long COVID and the opportunity. They are pretty clear that this is a major global event. Estimates from CDC suggest that long COVID'S impacted around 400 million individuals across the globe and has an annual economic impact of approximately $1 trillion. That's equivalent to about 1% of the global economy.

當然。關於長期 COVID 和機遇，我只想說一句話。他們非常清楚，這是一件全球性的重大事件。美國疾病管制與預防中心估計，長期新冠疫情影響了全球約 4 億人，每年造成的經濟影響約 1 兆美元。這相當於全球經濟的1%左右。

Why is that? Well, there's a higher incidence in adults 18 to 64 as compared with 65 plus. If we think about acute COVID, the primary issue, there is the elderly when it comes to Long COVID. And what we believe is the reactivation of secondary viruses. It's actually more present prevalent in the working population. Hence the economic impact associated with this particular illness in the US. We estimate that 6.5% of the non institutionalized us adult population has experienced long COVID since the introduction of COVID back in 2019 or 2020.

這是為什麼？嗯，18 至 64 歲的成年人的發病率比 65 歲以上的成年人更高。如果我們考慮急性 COVID，即主要問題，那麼當涉及長期 COVID 時，老年人就是主要問題。我們認為這是繼發性病毒的重新活化。事實上，這種現像在勞動人口中更為普遍。因此，這種特殊疾病會為美國帶來經濟影響。我們估計，自 2019 年或 2020 年出現 COVID 以來，6.5% 的非住院美國成年人口經歷了長期 COVID。

As you're probably aware, there's nothing approved to treat long COVID by the food and drug administration. And to date therapeutic research has exhibited very little progress. Notably pfizer's palod, which people have high hopes for failed in its one long COVID trial. We think that's rational because we don't think long COVID is associated with the SARS virus, which is the focus of palod. We believe it's the reactivation of secondary herpes viruses which are delivering the Symp and the sequeli that are associated with LCO.

您可能知道，食品藥物管理局尚未批准任何藥物用於治療長期 COVID。迄今為止，治療研究進展甚微。值得注意的是，人們對輝瑞公司寄予厚望的帕洛迪德在其長期 COVID 試驗中失敗了。我們認為這是合理的，因為我們不認為長期 COVID 與 SARS 病毒有關，而 SARS 病毒是 palod 的重點。我們認為，繼發性皰疹病毒的重新活化導致了與 LCO 相關的症狀和後遺症。

The bat results are shortly forthcoming and we believe one of the unique benefits of the formation of Dogwood is that enables us ample time to consider the value enhancing development pathways that sit before us both traditional financing and non diluted funding options to advance I MC two into phase two to phase two B development for the treatment of long COVID illness.

臨床試驗結果即將公佈，我們相信 Dogwood 成立的獨特優勢之一是，它使我們有充足的時間來考慮擺在我們面前的增值發展途徑，包括傳統融資和非稀釋融資選項，以推進 IMC 2 進入第二階段至第二階段 B 階段的開發，用於治療長期 COVID 疾病。

And really just to summarize on our next updates, we believe this pipeline has very significant value creation potential. The long COVID data are due in the middle of this month. We're very excited to report that out in the next week or so. The fibromyalgia program I MC one is poised to progress into phase three and we'll do an update on partnership in the first half of next year. And as Mike went through very nicely, we have the phase to be interim data from the hell neuron C I MP program due in the second half of next year with that background to the program. Let me open it up to questions. So back to you as our operator.

總結一下我們的下一次更新，我們相信這條管道具有非常顯著的價值創造潛力。長期 COVID 數據將於本月中旬公佈。我們非常高興能在下週左右報告這一消息。I MC 一號的纖維肌痛症計畫即將進入第三階段，我們將在明年上半年更新合作關係。正如 Mike 所介紹的，我們目前處於一個階段性階段，即在明年下半年獲得地獄神經元 C I MP 計劃的中期數據，並將以此作為該計劃的背景。讓我來回答大家的問題。那麼回到你作為我們的操作員。

Thank you. At this time, we'll be conducting our question and answer session.

謝謝。此時，我們將進行問答環節。

If you would like to ask a question, please press star one on your telephone keypad.

如果您想提問，請按電話鍵盤上的星號 1。

The confirmation tone will indicate your line is in the question queue and you may press star two. If you would like to remove your question from the queue for participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys.

確認音將表示您的線路已進入問題佇列，您可以按星號二。如果您想從使用揚聲器裝置的參與者群組中刪除您的問題，則可能需要在按星號鍵之前拿起聽筒。

One moment please. While we pull for questions.

請稍等。當我們提出問題時。

Thank you. Our first question is coming from Jason mccarthy with Maxim group. Your line is live.

謝謝。我們的第一個問題來自 Maxim 集團的 Jason McCarthy。您的線路處於通電狀態。

Hi guys. Thanks for taking the questions. Greg, maybe you guys could talk a little bit about the how neuron a little bit more rather durability of response when patients stopped taking drugs, you know, was how far out did that go? Kind of what do you? And is there a dose response high versus low that's associated with that? And what do you hypothesize might be the reason for it?

嗨，大家好。感謝您回答這些問題。格雷格，也許你們可以稍微談談當患者停止服藥時，神經元的反應持久性如何，你知道，這種情況持續了多久？你是什​​麼樣子？是否有與此相關的高劑量反應和低劑量反應？您認為造成這種情況的原因是什麼？

Well, Jason, thank you for joining today and I'm going to turn the question over to Doctor General who's best placed to answer that question for you?

好吧，傑森，感謝您今天的加入，我將把問題交給最適合為您回答這個問題的將軍博士？

Sure, Jason. So in terms of durability of response. The study that was conducted that had durability information was that cancer related pain study, we showed the median response time or the actually average response time was 57 days for the hell neuron group and 10.5 days for the placebo group among responders. So if they were initial responders in three weeks, they were followed to see how long that response lasted.

當然，傑森。因此就響應的持久性而言。具有耐久性資訊的研究是癌症相關疼痛研究，我們表明，在響應者中，地獄神經元組的中位反應時間或實際平均反應時間為 57 天，安慰劑組的中位反應時間或實際平均反應時間為 10.5 天。因此，如果他們在三週內出現最初的反應，我們會對他們進行跟踪，以觀察這種反應持續了多長時間。

No, that's due to that's from a single cycle of four, you know, four days of injections twice a day for four days.

不，那是因為這是一個四次注射的週期，你知道，四天注射兩次，持續四天。

We don't, we will not necessarily plan in long term to only use this for four days. This is if it's an analgesic, it can be repeated. And one of the questions we will be looking at as we progress development is how often should this treatment be repeated? How many injec injections do you need subsequently and so on. So, we, we see hints of durability well beyond four days and whether it needs to be a week, two weeks, four weeks, eight weeks, how long it needs to last before we repeat is one of the questions we'll be looking at in terms of your question about dose response in the chemotherapy induced neuropathic pain study. Three doses were looked at there was a quite low dose and mid dose and high dose. The results were best with the high dose. So we did see a dose response both in terms of efficacy and adverse events. And that result has led us to go with that high dose, which is what we're taking forward into the two B study that's being planned right now.

我們不會，也不一定會長期計劃只使用它四天。如果這是一種止痛藥，則可以重複使用。隨著我們不斷推進開發，我們將要研究的一個問題是，這種治療應該多久重複一次？隨後您需要注射多少次等等。因此，我們看到了遠超四天的持久性的跡象，以及是否需要一周、兩週、四周、八週，需要持續多長時間才能重複，這是我們在關於化療引起的神經性疼痛研究中的劑量反應的問題方面要研究的問題之一。研究了三種劑量：低劑量、中劑量和高劑量。高劑量時效果最佳。因此，我們確實看到了療效和不良事件的劑量反應。這項結果促使我們採用高劑量，這也是我們目前正在計劃的兩項 B 類研究中採用的方法。

Yeah, Jason, I, all I would add is we do think there may be something structurally or some kind of reset going on with the nerve transmission. And that is something we're exploring right now to see if we can't tease that out through forward research. But it is pretty clear, this effect is doing something that's providing a very durable effect.

是的，傑森，我想補充的是，我們確實認為神經傳遞過程中可能存在某種結構性問題或某種重置。我們現在正在探索這個問題，看看是否可以透過前瞻性研究來解決這個問題。但很明顯，這種效應正在產生非常持久的影響。

And hopefully, we can find out a way to show that through either pre clinical work, animal work or human clinical trials. And we'll endeavor to do so.

希望我們能夠找到一種方法來透過臨床前工作、動物實驗或人體臨床試驗來證明這一點。我們將盡力做到這一點。

And just in terms of the state profile, I think I caught it earlier from the B ID to the QD.

就狀態概況而言，我認為我早些時候就從 B ID 到 QD 發現了它。

It was a better tolerability profile and I know they're unrelated mechanisms between opioids and neuron. But are any of those tolerability issues related to respiration?

它具有更好的耐受性，而且我知道阿片類藥物和神經元之間的機制並不相關。但這些耐受性問題是否與呼吸有關？

We did not see a respiratory adverse event signal in these studies. So the doses we're using quite low doses. So the doses we're employing are not, do not appear to be sufficient to cause major respiratory suppression as you would get with a very high dose. The in terms of going from twice a day to once a day, we did see a better tolerability profile with once a day and we didn't see any meaningful change in efficacy with once a day dosing versus twice. So it became a pretty obvious choice to go with once a day dosing.

我們在這些研究中沒有看到呼吸不良事件訊號。所以我們使用的劑量相當低。因此，我們所採用的劑量似乎不足以像高劑量那樣造成嚴重的呼吸抑制。就從每天兩次改為每天一次而言，我們確實看到每天一次的耐受性更好，我們沒有看到每天一次與兩次相比在療效上有任何顯著變化。因此，每天服用一次就成了顯而易見的選擇。

And just last question quick as part of, oh, sorry guys.

最後一個問題，哦，抱歉，各位。

No, not at all. I was just, I was going to just add to my comments that one of the things that was attractive to us about home. There is a specific focus on the 1.7 modulator as opposed to other targets, there are n target spread throughout the body. As Mike said 171,819 are primarily focused on pain signaling. And so that actually pull through when you take a look at the tolerability data, I didn't mean to cut off the follow up question.

不，一點也不。我只是，我只是想補充我的評論，那就是家對我們有吸引力的事情之一。與其他目標相比，特別關注 1.7 調節器，並且有 n 個目標分佈在整個身體中。正如麥克所說，171,819 主要關注的是疼痛信號。因此，當您查看耐受性數據時，實際上就會明白，我並不是想要打斷後續問題。

Got it last last question really quick. You had mentioned that 50% or so of T I patients do use opioids because there is nothing else that FDA asked or do you think they'll ask for any information coming out of your trial on any reduction in the scripts or opioids or maybe opioid based rescue for any patients that might be having more severe pain.

很快就回答了最後一個問題。您曾提到，大約 50% 的 T I 患者確實使用阿片類藥物，因為 FDA 沒有提出其他要求，或者您是否認為他們會要求提供試驗中得出的任何信息，以了解處方或阿片類藥物的減少情況，或者針對可能出現更嚴重疼痛的任何患者進行阿片類藥物救援的情況。

They will be interested to see if you have a reduction in rescue with treated patients versus control patients. We, we don't at this point plan to pursue a opioid sparing claim. And if you don't pursue a sparing claim, then they're not going to insist you show a reduction in usage. That's a very complicated issue to chase because the reasons people change opioid doses are, are complicated. It's not just your treatment. And it's from a clinical trial standpoint, it's better to try and keep all the ancillary treatment, medications constant throughout your, your study. This is going going to be a four week study. So we're going to try and keep, if they're on opioids, we're going to keep those constant as much as we can. If they need rescue, we're going to use a, a different rescue than a straight opioid. So we're going to try and not have opioid be a major variable in interpreting the results we get once we treat patients with H&M.

他們會感興趣的是看看接受治療的患者與接受對照治療的患者相比搶救的次數是否減少了。我們目前不打算提出阿片類藥物節約要求。如果你不追求節約，那麼他們就不會堅持要你證明使用量的減少。這是一個非常複雜的問題，因為人們改變鴉片類藥物劑量的原因很複雜。這不僅僅是你的治療。從臨床試驗的角度來看，最好在整個研究過程中保持所有輔助治療和藥物的一致性。這將是一項為期四週的研究。因此，如果他們正在服用鴉片類藥物，我們會盡力保持其劑量不變。如果他們需要救援，我們將使用不同於直接使用鴉片類藥物的救援方法。因此，我們將嘗試不讓阿片類藥物成為我們用 H&M 治療患者的結果解釋的主要變數。

Got it. Thank you guys.

知道了。謝謝你們。

Thank you, Jason. We appreciate you joining this morning.

謝謝你，傑森。感謝您今天上午的參與。

Thank you. Our next question is coming from Dave Bouts with Zacks small Cap research. Your line is life.

謝謝。我們的下一個問題來自 Zacks 小型股研究部門的 Dave Bouts。你的路線就是生命。

Hey, good morning, everyone. I was wondering if you could provide a few details on this, the phase two B trial for how neuron And if you can provide in that regard and then what are the steps that you need to go through if any before that trial can get going underway?

嘿，大家早安。我想知道您是否可以提供一些有關這方面的詳細信息，即關於神經元的第二階段 B 試驗，如果您可以提供這方面的詳細信息，那麼在開始該試驗之前您需要經歷哪些步驟（如果有的話）？

David. Good morning. This is Greg. Thank you for attending this morning. I'll turn it over to Mike who's spearheading not just the clinical piece of this, but the regulatory piece as well to talk through a little bit about the process we're undertaking before we start dosing patients in quarter one, which is our goal.

大衛。早安.這是格雷格。感謝大家今天上午的出席。我會把時間交給麥克，他不僅負責臨床部分，還負責監管部分，他將向我們簡單介紹一下我們在第一季開始為患者用藥之前正在進行的流程，這是我們的目標。

Sure. So, you know, hell no. And has been used in Cinp before and that dose ranging proof of concept study I mentioned we're going to use that as a background. The study we're designing the two B study we're designing is significantly larger. We are using the, the high dose dose once a day. So it's a somewhat different design than we've used before. But it's actually consistent with what the FDA has seen before. And we think going to once a day dosing actually will be attractive in terms of, since we, we see better tolerability once a day versus twice a day. Arguably we're going to go in with a trial design that FDA is going to think is, you know, better tolerated, potentially safer in terms of the study itself. It's a four week long study. We will be dosing. We'll be given the same eight doses that's been used historically, in the past, it was four days of twice a day dosing. We're going to go to once a day dosing for eight days. It'll be spread over up to two weeks. So the same amount of total drug delivery will happen just in a different dosing format. We will primary end point will be a week four at which point, patients will exit the study. It'll be 1 to 1 randomization against placebo of traditional design with an interim analysis. As we have talked about scheduled for the second half of 2025 we anticipate we'll have roughly 40 to 50% of our targeted enrollment in the patient for in the study for that interim analysis. Again, the primary endpoint is going to be reduction in pain over time. We'll be looking at what fraction of patients have significant improvement and how long it lasts within the context of the four week study. That that's to set us up for a phase three program where we, we already have some agreements with FDA about what a phase three would look like in this indication. But this is our really proof of concept to do proper power calculations and get a handle on what it would take to, to get this through the approval process.

當然。所以，你知道，絕對不行。並且之前已在 Cinp 中使用過，並且我提到的劑量範圍概念驗證研究我們將使用它作為背景。我們正在設計的研究，即兩項 B 類研究，規模要大得多。我們每天使用一次高劑量。所以它與我們以前使用的設計有些不同。但這實際上與 FDA 之前看到的情況一致。我們認為，每天服用一次實際上會很有吸引力，因為我們發現每天服用一次比每天服用兩次的耐受性更好。可以說，我們將採用 FDA 認為耐受性較好、就研究本身而言可能更安全的試驗設計。這是一項為期四週的研究。我們將進行劑量控制。我們將使用與以往相同的八劑藥物，過去，我們每天服用兩次，總共四天。我們將每天服用一次，持續八天。這個過程將持續兩週。因此，僅以不同的劑量形式輸送相同量的藥物。我們的主要終點將是第四周，此時患者將退出研究。它將採用傳統設計的 1 比 1 隨機化方法，與安慰劑進行對比，並進行中期分析。正如我們之前談到的 2025 年下半年計劃，我們預計在此次中期分析研究中，我們的目標入組患者人數將達到約 40% 至 50%。再次強調，主要終點是隨著時間的推移疼痛的減輕。我們將在為期四週的研究中觀察有多少比例的患者病情有顯著改善以及這種改善持續多長時間。這是為了為我們開展第三階段計劃做好準備，我們已經與 FDA 就這一適應症的第三階段計劃達成了一些協議。但這是我們真正的概念證明，即進行適當的功率計算並掌握需要什麼才能通過審批流程。

I should mention Dave as we do with all this stuff that's obviously subject to FDA input. But I think there's a very good logical flow for the transition to this particular study and very high hopes for Helmo is a really important new treatment.

我應該提到戴夫，因為我們對所有這些顯然要接受 FDA 輸入的東西都這樣做。但我認為，這項特定研究的過渡有一個非常好的邏輯流程，人們對 Helmo 寄予厚望，因為它是一種非常重要的新療法。

Okay, great. Appreciate the details there. And lastly what are if any, the conditions that need to be met to get that second tranche of money in February of 2025.

好的，太好了。感謝那裡的細節。最後，如果有的話，需要滿足哪些條件才能在 2025 年 2 月獲得第二筆資金。

There are really no material obligations to meet, to get that that money in quarter one to make sure the intention is certainly to do so. As long as we maintain a good, consistent listing standards and all those other things that are required as a public entity, we don't see any, any impede impediments, excuse me, to getting the additional $3 million.

實際上沒有實質的義務需要滿足，在第一季獲得這筆錢以確保目的確實如此。只要我們保持良好、一致的上市標準以及作為公共實體所需的所有其他事項，我們就不會看到任何阻礙，對不起，不會有任何阻礙我們獲得額外的 300 萬美元。

Okay. Ultimately taking, yeah. So PLS is very excited about this program. I don't think it's too much to say that having a very good stable institutional shareholder strategic in its own right, as one of our large and soon to be our largest shareholder is anything but a good fact. And so they're very committed to the asset and look forward to moving that asset forward.

好的。最後還是接受了，是的。因此 PLS 對這個計畫感到非常興奮。我認為，擁有一個非常好的、穩定的機構股東策略本身並不為過，作為我們最大的股東之一，並且很快就會成為我們最大的股東，這絕不是什麼好事。因此，他們非常重視這項資產，並期待推動該資產向前發展。

All right, great. Thanks for taking the questions.

好的，太好了。感謝您回答這些問題。

Thank you, David.

謝謝你，大衛。

Thank you as we have no further questions in queue at this time, I'd like to turn it back over to Mr Duncan for any closing remarks.

謝謝，由於我們目前沒有其他問題，我想將發言權交還給鄧肯先生，請他做最後發言。

Yeah. First off, thank you for those of you who joined this morning. Hopefully, you can tell we believe the formation of dog with therapeutics last month represents a very transformational event for us. And in particular, the expansion of our pipeline to include how neuron as a complement to I MC one and I MC two.

是的。首先，感謝今天早上參加的各位。希望您能明白，我們相信上個月治療犬的形成對我們來說是一個非常具有變革意義的事件。特別是，我們的管道擴展包括如何將神經元作為 I MC 一和 I MC 二的補充。

The concurrent strategic financing by CKLS is affiliate, the former owner of Wex Pharmaceutical provides us with this nice tranche of operating capital to get through the end of next year inclusive of the readout for the hel neuron phase to be studied the interim readout specifically, it is our view that this is a win win for Legacy Bureau shareholders and CKLS shareholders with both short term and medium term potential value creation opportunities associated with the forthcoming long COVID phase two data for I MC two and the phase two B data next year. For Hell Neuron, we look forward to updating you on all of our progress in a very timely manner starting with sharing results from our recently completed BHC long COVID phase two study in the next week or so. We want to thank you for your time and attention today.

CKLS 同時進行的策略性融資是附屬公司，Wex Pharmaceutical 的前所有者為我們提供了這筆不錯的營運資金，以幫助我們度過明年年底，其中包括要研究中期讀數的 hel 神經元階段的讀數，我們認為，對於 Legacy Bureau 股東和 CKLS 股東來說，這是一個雙贏的數據局面，即將發布的 I MC two 的短期數據和長期數據的短期數據創造明年對於 Hell Neuron，我們期待及時向您通報我們的所有進展，首先在下週左右分享我們最近完成的 BHC 長期 COVID 第二階段研究的結果。我們要感謝您今天的時間和關注。

Thank you, ladies and gentlemen, this concludes today's conference and you may disconnect your lines at this time and we thank you for your participation.

謝謝各位，女士們、先生們，今天的會議到此結束，各位可以掛斷電話了，感謝您的參與。