Ensysce Biosciences Inc (ENSC) 2023 Q4 法說會逐字稿

Good morning, And welcome to the Ensysce Biosciences, Inc corporate update call. As a reminder, this conference call is being recorded. Your hosts today are Dr. Lynn Kirkpatrick, Chief Executive Officer; Dr. Bill Schmidt, Chief Medical Officer; and Dave Humphrey, Chief Financial Officer.

早安，歡迎撥打 Ensysce Biosciences, Inc 公司更新電話。謹此提醒，本次電話會議正在錄音中。今天的東道主是首席執行官 Lynn Kirkpatrick 博士； Bill Schmidt 博士，首席醫療官；和財務長戴夫漢弗萊。

And before we begin the formal presentation, I would like to remind everyone that the statements made on the call and webcast may include predictions, estimates or other information that might be considered forward looking. While these forward-looking statements represent our current judgment on what the future holds, they are subject to risks and uncertainties that could cause actual results to differ materially. You are cautioned not to place undue reliance on these forward-looking statements, which reflect our opinions only as of the date of this presentation. Please keep in mind that we are not obligating ourselves to revise or publicly release the results of any revision to these forward-looking statements in light of new information or future events throughout today's discussion, we will attempt to present some important factors relating to our business that may affect our predictions. You should also review our most recent Forms 10 Q and 10 K for a more complete discussion of these factors and other risks, particularly under the heading Risk Factors. At this time, I'd like to turn the call over to Chief Executive Officer, Dr. Lynn, Kirkpatrick. Lynn?

在我們開始正式演示之前，我想提醒大家，電話會議和網路廣播中的陳述可能包括預測、估計或其他可能被視為前瞻性的資訊。雖然這些前瞻性陳述代表了我們目前對未來的判斷，但它們受到風險和不確定性的影響，可能導致實際結果出現重大差異。請您注意不要過度依賴這些前瞻性陳述，這些陳述僅反映我們截至本簡報發布之日的觀點。請記住，我們沒有義務根據今天討論中的新資訊或未來事件來修改或公開發布對這些前瞻性陳述的任何修改結果，我們將嘗試提出與我們業務相關的一些重要因素這可能會影響我們的預測。您還應該查看我們最新的表格 10 Q 和 10 K，以更完整地討論這些因素和其他風險，特別是在「風險因素」標題下。現在，我想將電話轉給執行長林恩·柯克帕特里克博士。林恩？

Thank you, operator, and good morning, everyone, and thank you for joining us. I am pleased to welcome you to today's corporate update conference call. 2023 was a year of exceptional clinical progress for our next-generation analgesics as we move our programs toward commercialization.

謝謝您，接線員，大家早安，謝謝您加入我們。我很高興歡迎您參加今天的公司更新電話會議。 2023 年是我們下一代止痛藥取得非凡臨床進展的一年，我們將計畫推向商業化。

Before I get into the full background of the Company, I remind you that Encysive mission to provide safer therapeutics to treat severe pain to reduce abuse and to provide protection from overdose remains the core of our operations. Medicoe dichotomy exist between the treatment of severe pain with appropriate medication and the abuse and overdose that occurs with this class of drugs. Statistics suggest that the United States loses over 200 Americans every day to prescription of opioid overdose. Yet there are countless Americans with severe pain who cannot get access to the prescription medication. My insights team believes this is unacceptable, and we believe our novel TAP and impart opioid products provide a solution to address this dueling issue with opioids. For those of you new to our story, we are clinical-stage pharmaceutical companies seeking to develop innovative solutions. First the beer pain relief while reducing the potential for opioid misuse, abuse and overdose. We've used sophisticated chemistry in the development of our two technology platforms, TAPs and impart, providing opioid abuse deterrence and overdose protection, respectively. We've strategically positioned our products as next-generation opioids. It improves the delivery and effectiveness of analgesic prescription drugs while reducing abuse potential. In 2023, we focused on the execution and completion of a number of PF. six one four and PF. six one for NPR clinical trials, boosted capital resources and scale manufacturing procedures, which provided a solid operational foundation and resulted in favorable FDA discussions in early 2024. Following these valuable meeting, Insights is well positioned to enter the pivotal Phase three trials for PF 6.4 in the second half of 2024. I will take you through a review of our two technology platforms, and then Dr. Bill Schmidt, our Chief Medical Officer will expand on our clinical trial progress over the last year. Tap stands for triptan activated abuse protection, which is the chemical modification of an active medication designed to make it inactive until it is swallowed and reaches the small intestine where it's exposed to the natural enzyme. Tryptophan person only found in the small intestine and initiate the two-step process to effectively release the active opioid. In other words, our top prodrugs are activated or turned on a normal digestive enzymes that we use to digest our proteins in the small intestine. It's important to point out, the triptan is not found in other tissues through our chemistry limits our top opioids to oral administration, which in turns is a means to reduce abuse. The second step of the opioid release, which is designed into the chemistry determines whether our cap pro drugs provide either an immediate, our slow release profile as is preferred for drugs that are required 24 seven to treat pain. Based on this two-step release mechanism, we refer to tap as clever chemistry and from our clinical studies, we've shown it to work as designed to improve safety and overall drug efficacy. Additionally, TAP can be applied to other types of medicines to provide a delivery mechanism to the gut to improve safety or to simply make them more effective.

在全面了解公司背景之前，我提醒您，Encysive 的使命是提供更安全的治療方法來治療嚴重疼痛、減少濫用並提供藥物過量保護，這仍然是我們營運的核心。醫學上存在著用適當的藥物治療劇烈疼痛與濫用和過量使用此類藥物之間的分歧。統計數據顯示，美國每天有超過 200 名美國人因服用阿片類藥物過量而失去生命。然而，有無數患有劇烈疼痛的美國人無法獲得處方藥。我的見解團隊認為這是不可接受的，我們相信我們的新型 TAP 和賦予阿片類藥物產品提供了解決阿片類藥物這一相互矛盾問題的解決方案。對於那些不熟悉我們故事的人來說，我們是尋求開發創新解決方案的臨床階段製藥公司。首先，啤酒可以緩解疼痛，同時減少鴉片類藥物誤用、濫用和過量的可能性。我們在開發兩個技術平台 TAP 和 grant 時使用了複雜的化學技術，分別提供鴉片類藥物濫用威懾和過度保護。我們將我們的產品策略性地定位為下一代阿片類藥物。它改善了鎮痛處方藥的傳遞和有效性，同時減少了濫用的可能性。2023年，我們重點執行和完成了多項PF。六一四和PF。 NPR 臨床試驗的六一，增加了資本資源並規模化生產程序，這提供了堅實的營運基礎，並在 2024 年初引起了 FDA 的積極討論。在這些寶貴的會議之後，Insights 已做好準備，將於 2024 年下半年進入 PF 6.4 的關鍵第三階段試驗。我將帶您回顧我們的兩個技術平台，然後我們的首席醫療官 Bill Schmidt 博士將詳細介紹我們去年的臨床試驗進度。Tap 代表曲坦活化濫用保護，它是對活性藥物的化學修飾，旨在使其處於非活性狀態，直到吞嚥並到達小腸，在那裡它暴露於天然酶。色氨酸僅存在於小腸中並啟動兩步驟過程以有效釋放活性鴉片類藥物。換句話說，我們的頂級前藥被激活或打開我們用來消化小腸中蛋白質的正常消化酶。需要指出的是，曲坦類藥物在其他組織中並未發現，因為我們的化學物質限制了我們的頂級鴉片類藥物只能口服，這反過來又是減少濫用的一種手段。阿片類藥物釋放的第二步是在化學中設計的，這決定了我們的帽前藥物是否提供立即或緩慢釋放的特性，這對於治療疼痛所需的藥物來說是首選的 24 七 。基於這種兩步驟釋放機制，我們將 Tap 稱為巧妙的化學反應，並且從我們的臨床研究中，我們已經證明它可以按照設計的方式發揮作用，以提高安全性和整體藥物功效。此外，TAP 還可應用於其他類型的藥物，為腸道提供遞送機制，以提高安全性或簡單地使其更有效。

Our second technology platform, empower our multi pill abuse resistant is their smart overdose protection technology and industry. First, we've designed and par as a combination product of our TAP prodrugs with a small dose of triptan inhibitor called defense debt. This combination alone pain relief, coupled with overdose protection Empire, is designed to turn off the release of the active ingredient if more than the prescribed dose is consumed orally. This protection is smart since it only kicks in in an overdose situation. We have applied these highly novel technologies to sever opioids and specifically to oxycodone for our lead product, PF 6.4, we believe our entire TAP drug class is set to become the next generation of opioids to treat severe pain in a safer manner than ever existed for opioid analgesics. We believe that controlling severe pain appropriately may prevent it from spiraling into chronic pain, which frequently leads to the use of opioids long term, the initial role for our lead product, PF 6.4 may maybe an indication such as traumatic injuries or invasive surgeries. Additionally, we for CPS. 600 for future role in chronic pain because it additions such as treating osteo arthritis, pain in patients who cannot use or do not respond well to less effective anti-inflammatory analgesics and were high levels of pain negatively impact quality of life Series $0.06 or NPR with overdose protection is a follow-on product and we believe it will provide an extra layer of safety for treating both acute and chronic pain. In brief, our top and impart technologies have been developed to address and reduce both prescriptions, drug abuse and overdose. These are unique to the opioid class and provide a number of advantages over the currently marketed abuse deterrent formulated product advantages, which we believe will provide both patients and prescribers more confidence in the medicines safety. Although we've had focused on applying TAP and imparts opioid analgesics, we have explored applications with other classes of prescription drugs, which in turn provides substantial opportunities for future growth our current pipeline includes a number of TAP and NPR opioid tap and impart ADHD products and a discovery program of novel cap and in-park agents for the treatment of opioid use disorder. There is a brief summary of our programs before turning it over to Dr. Schmidt to provide more clinical details. PS. 600 for an oxygen code on TAP product is designed to replace OxyContin in the marketplace. The FDA has granted PF 600 for fast track status for the use in chronic pain, which suggests regulatory confidence that PF 600 for May fulfill an unmet therapeutic need. We have completed the nonclinical package for PO six and four. We've completed five clinical trials for safety, efficacy and abuse potential, and we've completed key manufacturing activities that position us two to initiate our Phase three program. Our accomplishments in 2023 include completion of PF 6.4104, a study that evaluated the oral abuse potential of PS. six and four, we reported positive results in April of last year. Importantly, the secondary endpoint take drug again was significantly lower at both low and mid doses of PS. six and four and was even numerically lower than comparator at the high dose, demonstrating that recreational drug users may be less motivated to abuse PF six one four compared to immediate release oxycodone, a second study, PF. six one four to a one was designed to measure the onset of pain relief for PF 6.4 in the cold presser test, establishing the time for drug onset was suggested by the FDA prior to initiating larger efficacy studies initiated in mid 2023 enrollment was rapid and the study was completed by year's end to support our end of Phase two meeting with the FDA in January, we have used the data from this study to support the design of our Phase three protocols, which were discussed at this end of Phase two meeting. This meeting provided feedback and support for our nonclinical package and enables a constructive discussion regarding Phase three clinical trial design for PF. six and four, as well as suggestions that we believe will support a successful new drug application or NDA. This end of Phase two meeting signifies a major step in the regulatory approval process of PF. six one four. As previously mentioned, the results and analyses from our completed Phase two studies have informed our strategy and design of Phase three studies, which are expected to begin in the second half of 2024 last year. We also completed a three-part Phase one study for our follow-on product PS. six for NPR that ultimately provided us with the first data, demonstrating the potential for preventing prescription drug oral overdose, something felt to be a holy grail for opioids. Because of our positive data, the FDA encouraged us to apply for breakthrough therapy designation in late 2023.

我們的第二個技術平台，使我們能夠抵抗多種藥物濫用，這是他們的智慧過量保護技術和產業。首先，我們設計了 TAP 前藥與小劑量曲坦類抑制劑（稱為「防禦債務」）的組合產品。這種單獨的止痛組合，加上帝國的過量保護，旨在在口服超過規定劑量時關閉活性成分的釋放。這種保護很聰明，因為它只在服藥過量的情況下才會發揮作用。我們已將這些高度新穎的技術應用於切斷阿片類藥物，特別是我們的主導產品PF 6.4 的羥考酮，我們相信我們的整個TAP 藥物類別將成為下一代阿片類藥物，以比以往更安全的方式治療嚴重疼痛。我們相信，適當控制劇烈疼痛可以防止其演變成慢性疼痛，慢性疼痛經常導致長期使用阿片類藥物，我們的主導產品 PF 6.4 的最初作用可能是外傷或侵入性手術等適應症。此外，我們也支持 CPS。 600 表示未來在慢性疼痛中的作用，因為它增加了治療骨關節炎、不能使用或對效果較差的抗炎鎮痛藥反應不佳的患者的疼痛以及高水平疼痛對生活質量產生負面影響系列0.06 美元或NPR 的過量防護是後續產品，我們相信它將為治療急性和慢性疼痛提供額外的安全保障。簡而言之，我們開發的頂級技術和傳授技術旨在解決和減少處方、藥物濫用和過量用藥。這些是鴉片類藥物所獨有的，與目前市售的防濫用配方產品相比具有許多優勢，我們相信這將使患者和處方者對藥物安全性更有信心。儘管我們一直專注於應用TAP 並賦予阿片類鎮痛藥，但我們也探索了其他類別處方藥的應用，這反過來又為未來的增長提供了巨大的機會。阿片類藥物TAP 和賦予ADHD 產品以及用於治療阿片類藥物使用障礙的新型上限和園區內藥物的發現計劃。在將其交給施密特博士以提供更多臨床細節之前，我們對我們的計劃進行了簡要總結。附言。 TAP 產品上的氧氣代碼 600 旨在取代市場上的奧施康定。FDA 已授予 PF 600 用於治療慢性疼痛的快速通道地位，這表明監管機構有信心 PF 600 可以滿足 5 月份未滿足的治療需求。我們已經完成了 PO 六和四的非臨床套件。我們已經完成了五項關於安全性、有效性和濫用可能性的臨床試驗，並且我們已經完成了關鍵的生產活動，使我們兩個人能夠啟動我們的第三階段計劃。我們在 2023 年的成就包括完成 PF 6.4104，這是一項評估 PS 口服濫用潛力的研究。第六和第四，我們在去年四月報告了積極的成果。重要的是，在低劑量和中劑量的 PS 下，再次服藥的次要終點顯著較低。 6 和 4，甚至在數字上低於高劑量的比較者，這表明與立即釋放羥考酮相比，娛樂性吸毒者濫用 PF 6 和 4 的動機可能較低，第二項研究 PF。六一四比一旨在測量冷壓試驗中PF 6.4 疼痛緩解的起效，FDA 建議在啟動更大規模的療效研究之前確定藥物起效時間，該研究於2023 年中期啟動，入組速度很快，並且研究已於年底完成，以支持我們一月份與FDA 舉行的第二階段會議，我們已使用這項研究的數據來支持我們第三階段方案的設計，該方案已在第二階段會議結束時進行了討論。這次會議為我們的非臨床方案提供了回饋和支持，並就 PF 三期臨床試驗設計進行了建設性討論。六和四，以及我們認為將支持成功的新藥申請或 NDA 的建議。第二階段會議的結束標誌著 PF 監管審批流程邁出了重要一步。六一四。如前所述，我們已完成的第二階段研究的結果和分析為我們第三階段研究的策略和設計提供了信息，第三階段研究預計於去年下半年開始。我們也為後續產品 PS 完成了由三個部分組成的第一階段研究。 NPR 的六次最終為我們提供了第一個數據，證明了預防處方藥口服過量的潛力，這被認為是阿片類藥物的聖杯。由於我們的正面數據，FDA 鼓勵我們在 2023 年底申請突破性療法認定。

On January 19th, 2024, we were informed that the FDA had granted us breakthrough therapy designation, which to date has only been provided to less than 300 drugs. Importantly, opioid analgesics have not previously been included in this exclusive drug classification. Breakthrough Therapy is a process designed to expedite the development and review of drugs that are intended to treat a serious condition. And that show preliminary clinical evidence of having a clear advantage over available therapies. We are highly encouraged by our innovative impart technology, which is truly groundbreaking and could save many lives strategically to broaden our portfolio in November 2023, we executed a letter of intent with Weeden based on present to explore a collaboration for the US development of view present, which is in Phase three clinical trials in the European Union you present is a non opioid lozenge to treat pain caused by oral mucositis. I can addition, resulting as a side effect of cancer therapies. We believe this collaboration could allow insights to diversify its pain like pipeline and discussions are continuing.

2024 年 1 月 19 日，我們獲悉 FDA 已授予我們突破性療法認定，迄今僅向不到 300 種藥物提供突破性療法認定。重要的是，阿片類止痛藥先前並未被納入此專有藥物分類。突破性療法是一個旨在加快治療嚴重疾病藥物的開發和審查的過程。這顯示了初步的臨床證據，顯示它比現有療法有明顯的優勢。我們對我們的創新傳遞技術感到非常鼓舞，該技術確實具有開創性，可以策略性地挽救許多人的生命。的意向書，探索在美國開發視圖禮物的合作，您目前正在歐盟進行第三期臨床試驗，它是一種非阿片類含片，用於治療口腔粘膜炎引起的疼痛。我也可以補充，這是癌症治療的副作用。我們相信，這種合作可以讓洞察力分散其痛苦，例如管道和討論仍在繼續。

Finally, I want to stress our programs are protected by our global intellectual property portfolio have over 100 patents issued in 25 countries, ensuring an opportunity to address the need for safer pain medication globally. We have built a strong, motivated and experienced team to assure our programs through each stage of development in an attempt to launch our next-generation products as quickly as possible.

最後，我想強調，我們的計畫受到我們的全球智慧財產權組合的保護，我們在 25 個國家/地區擁有 100 多項專利，確保有機會滿足全球對更安全止痛藥的需求。我們建立了一支強大、積極進取且經驗豐富的團隊，以確保我們的計劃貫穿每個開發階段，以盡快推出我們的下一代產品。

Now I'm pleased to turn over the call to Dr. Bill Smith, our Chief Medical Officer to further elaborate on our recent clinical study results. Phil?

現在我很高興將電話轉給我們的首席醫療官 Bill Smith 博士，以進一步詳細說明我們最近的臨床研究結果。菲爾？

Thank you, Len.

謝謝你，萊恩。

I'm pleased to provide an update on Encysive significant progress with our clinical program and further development of PF. six one four during 2023. We believe the results from our trials throughout the year have provided a formative structure as we advance to Phase three studies appear at six one four in 2024. As Lynne mentioned, we are developing a next-generation opioid analgesic, which provided which promises strong efficacy with less potential for abuse and overdose, something the industry and society really need. Over the past year, we've been perfecting our clinical package to ensure it will support a successful NDA in all. We have completed five clinical trials with PF six one for a single ascending dose study, also known as the SAD study, a multiple ascending dose study, also known as the MAD study that was combined with a bio equivalents arm, demonstrating that PF. six one four delivers oxycodone in a dose equivalent fashion, similar to actually cotton to support our use of the five or five b. to shorten regulatory pathway, two human abuse potential studies to support abuse deterrent labeling and most recently, an analgesic efficacy study that evaluated the time to onset of analgesia following oral dosing of PF six one four. The efficacy study at six one four dash two oh one was designed after receiving feedback from the FDA on our plan to explore F. six month for efficacy for the acute pain indication. Pf six one for dash two oh one was a Phase two study entitled A randomized, double-blind, placebo-controlled crossover study of PF. six one four on analgesic response in the cold presser test in healthy male subjects. It evaluated the time to efficacy onset for analgesia and measured pain intensity following two different oral doses of PF. six, one four versus placebo. The study was initiated and enrolled quickly to provide data for discussion with the FDA during our end-of-Phase two meeting early in 2024 study measured the onset of pain relief versus time in male subjects who submerged their non dominant hand in a two degree centigrade freezing ice water bath. This is a well-established method to measure pain and efficacy of novel pain products and provides a method to establish the time that the pain relief begins to occur.

我很高興向大家介紹 Encysive 在我們的臨床計劃和 PF 進一步開發方面取得的重大進展。 2023 年六零四。我們相信，我們全年的試驗結果已經為我們進入 2024 年六點四點的第三階段研究提供了一個形成性的結構。正如 Lynne 所提到的，我們正在開發一種下一代阿片類鎮痛藥，它具有強大的功效，並且濫用和過量的可能性較小，這是行業和社會真正需要的。在過去的一年裡，我們一直在完善我們的臨床方案，以確保它能夠支持新藥申請的成功。我們已經完成了五項 PF 六一單次遞增劑量研究（也稱為 SAD 研究）的臨床試驗，多項遞增劑量研究（也稱為 MAD 研究）與生物等效臂相結合，證明了 PF。六一四以劑量等效的方式提供羥考酮，類似於實際棉花以支持我們使用五或五b。為了縮短監管途徑，兩項人類濫用潛力研究支持濫用威懾標籤，最近一項鎮痛功效研究評估了口服 PF 六一四後鎮痛起效的時間。六一四衝二哦一的功效研究是在收到 FDA 關於我們計劃探索 F. 六個月急性疼痛適應症功效的反饋後設計的。Pf 六一代表破折號二哦一是一項名為「PF 的隨機、雙盲、安慰劑對照交叉研究」的第二階段研究。六一四關於健康男性受試者冷壓試驗中的鎮痛反應。它評估了鎮痛起效的時間，並測量了兩種不同口服劑量的 PF 後的疼痛強度。六、一、四與安慰劑相比。研究啟動並迅速入組，為 2024 年初第二階段結束會議期間與 FDA 的討論提供數據。水浴。這是一種行之有效的測量疼痛和新型止痛產品功效的方法，並提供了一種確定疼痛開始緩解的時間的方法。

Following completion of enrollment in November 2023 we reported results in December that reinforce the efficacy of PSX. one for demonstrating the time of analgesia onset and its ability to provide significant pain intensity reduction. The first ever measured for any type of opioid analgesics study. Pain endpoints matched all previous pharmacokinetic endpoints from prior clinical studies and supported the concept that Encysive TAP opioids deliver strong analgesia safely and effectively Importantly, this time of onset study provided data that aided the design of key elements of our Phase three studies that we are aiming to initiate in the second half of 2024. Early last year. We also completed enrollment of the final part of our first clinical trial to evaluate overdose protection, PF. six one for Dash and power dash one oh one study was undertaken in partnership with quotient sciences using their integrated translational pharmaceutics platform for the clinical testing of PF 600 for DASH and Par allowed us to complete this highly complicated study in record time. Final data from Part three of this trial confirm that consumption of increasing amounts of PF. 600 for dash Empire at the 25 milligram dose level resulted in protection from overdose if three or more capsules were taken simultaneously. This part of the trial was designed to deliver increasing amounts of PF. six one for dash Empire at the 25 milligram dosage. Specifically, we administered one two, three five or eight dose units at one time and measured resulting plasma levels of oxycodone. All of the subjects were now trucks en bloc for safety and the resulting Oxy codon released into their plasma was measured and compared to previous data generated with the delivery of increasing doses of PIP six one four without in-park protection data showed that delivery of one or two dose units of PF. six one four dash NPR provided analgesic level doses of oxycodone as designed once the dose units were increased to three or more, the amount of oxycodone release was reduced as compared to levels of unprotected PF. six one four at eight dose units that was significantly less plasma oxycodone. This is significant at P is less than 0.0033. And at the same dose of PF. six one four was delivered unprotected. These data were presented to the FDA and was the basis for the grant of our breakthrough therapy designation, something highly unique for an opioid product and something we are exceptionally proud of. Pf 600 for Empire is the first ever opioid analgesic with oral overdose protection. Finally, results from our intranasal human abuse potential study provided the fused first human data. It shows the intact prodrug PF. six one four when absorbed into the bloodstream does not convert to oxycodone. This confirms a key design feature of PF six one four. In that it requires exposure to the digestive enzyme trips and to convert to oxycodone. As Dr. Kirkpatrick mentioned, this can only occur in the human gastrointestinal tract. This information is important as it supports our contention that attempts to abuse PF. six one four by direct intravenous injection will be unsuccessful for supporting the habits of IV drug abusers.

2023 年 11 月完成招募後，我們在 12 月報告了結果，增強了 PSX 的功效。一種用於展示鎮痛開始時間及其顯著降低疼痛強度的能力。有史以來第一次測量任何類型的鴉片類鎮痛藥研究。疼痛終點與先前臨床研究中的所有藥物動力學終點相匹配，並支持Encysive TAP 鴉片類藥物安全有效地提供強效鎮痛作用的概念。於設計我們目標的第三期研究的關鍵要素將於 2024 年下半年啟動。去年年初。我們也完成了第一個臨床試驗的最後部分的入組，以評估過量用藥保護 PF。針對Dash 和power dash 的六一研究是與quotient sciences 合作進行的，使用他們的整合轉化製藥平台對PF 600 針對DASH 和Par 進行臨床測試，使我們能夠在創紀錄的時間內完成這項高度複雜的研究。該試驗第三部分的最終數據證實，PF 的消耗量不斷增加。如果同時服用三粒或更多膠囊，25 毫克劑量水平的 dash Empire 600 可以防止過量服用。這部分試驗的目的是提供越來越多的 PF。 6 1 為 dash Empire，劑量為 25 毫克。具體來說，我們一次施用一、二、三、五或八個劑量單位，並測量所得的羥考酮血漿濃度。為了安全起見，現在所有受試者都是卡車，測量了釋放到血漿中的氧密碼子，並與先前在沒有公園內保護的情況下增加劑量的PIP 六一四的遞送產生的數據進行比較，數據表明，遞送一或兩個劑量單位的 PF。六一四衝刺NPR按照設計提供了羥考酮的鎮痛水平劑量，一旦劑量單位增加到三個或更多，與未受保護的PF水平相比，羥考酮釋放量減少。八個劑量單位的六一四，血漿羥考酮明顯減少。當 P 小於 0.0033 時，這一點很顯著。且PF的劑量相同。六一四是在沒有保護的情況下交付的。這些數據已提交給 FDA，並成為授予我們突破性治療指定的基礎，這對於阿片類藥物產品來說是非常獨特的，也是我們感到非常自豪的。Empire 的 Pf 600 是有史以來第一種具有口服過量保護功能的鴉片類鎮痛藥。最後，我們的鼻內人類虐待潛力研究的結果提供了第一批融合的人類數據。它顯示了完整的前藥 PF。六一四吸收到血液中後不會轉化為羥考酮。這證實了 PF 六一四的關鍵設計特徵。因為它需要接觸消化酶並轉化為羥考酮。正如 Kirkpatrick 博士所提到的，這只能發生在人類胃腸道中。這些資訊很重要，因為它支持我們試圖濫用 PF 的論點。直接靜脈注射六一四對於支持靜脈注射藥物濫用者的習慣是不成功的。

I will now turn the call back over to Lynn.

我現在將把電話轉回給林恩。

Thank you, Bill. In February with breakthrough therapy designation granted for PS. 600 for NPR, we held a constructive meeting with the FDA. The meeting focused on the nonclinical data from our combination product that is designed for the treatment of severe pain integrated with multiple layers of safety. The FDA firm provided helpful feedback and advice on additional nonclinical studies that will be required for an eventual NDA submission and approval guidance will aid in streamlining the development plans for this innovative drug candidate.

謝謝你，比爾。2 月，PS 獲得突破性療法認定。 600 NPR，我們與 FDA 舉行了建設性會議。會議重點討論了我們的組合產品的非臨床數據，該組合產品專為治療嚴重疼痛而設計，並具有多層安全性。FDA 公司就最終 NDA 提交所需的其他非臨床研究提供了有用的反饋和建議，批准指南將有助於簡化這項創新候選藥物的開發計劃。

Looking ahead, the next stages for our key U.S. six one four and our PF. 600 for in-park clinical programs include more ambitious goals designed to enter the market as soon as possible and are outlined as follows.

展望未來，我們關鍵的美國六一四和我們的 PF 的下一階段。 600 園區內臨床計畫包括旨在盡快進入市場的更雄心勃勃的目標，概述如下。

Firstly, following FDA final review of our Phase three protocols and statistical analysis plans, we intend to initiate the first of the Phase three acute post-surgical pain studies, we have six one four Dash three oh one abdominoplasty or PF. 6,004 dash through two bunionectomy in the second half of 2024.

首先，在 FDA 對我們的第三階段方案和統計分析計劃進行最終審查後，我們打算啟動第一個第三階段急性術後疼痛研究，我們有六一四 Dash 三哦一腹部成形術或 PF。 2024 年下半年，將有 6,004 人完成兩次拇囊炎切除術。

Secondly, we aim to initiate our second study of PF. six and for NPR in the second half of 2024 as well as 6.4 m. or one or two will be a Phase Ib study intended to confirm that the higher 50 and 100 milligram dose units up to 6.4 m. are also provide overdose protection.

其次，我們的目標是啟動第二次 PF 研究。 6 和 NPR 2024 年下半年以及 640 萬。或者一兩項將是 Ib 期研究，旨在確認較高的 50 和 100 毫克劑量單位可達 6.4 m。還提供過量保護。

Thirdly, we are continuing to move our chemistry, manufacturing and controls activity towards commercial scale with additional drug substance and drug product development activities that have already been initiated in the first quarter of 2020.

第三，我們將繼續將我們的化學、製造和控制活動推向商業規模，並已於 2020 年第一季啟動了額外的原料藥和藥品開發活動。

For fourthly, given the expedited designations of both PF. 6.4 and PF. six one for Empire, we are continuing our regulatory package development and plan additional meetings with the FDA for both products in the second half of 2024.

第四，考慮到兩名 PF 的快速指定。 6.4 和PF。對於 Empire 來說，六一，我們正在繼續制定監管方案，並計劃在 2024 年下半年與 FDA 就這兩種產品舉行更多會議。

I now welcome our CFO, Dave Humphrey, for a short financial summary Dave potentially into 2023 with cash and cash equivalents of $1.1 million as of December 31st compared to 1.5 million as of September 30th, we have boosted our cash balance in early 2024 with cash proceeds of 2.1 million from the exercise of warrants to purchase 1.3 million shares of common stock that were issued in the fourth quarter of 2023. Additionally, in February, we received gross proceeds of $4.7 million from the exercise of warrants to purchase 3.6 million shares of common stock that were originally issued in May 2023. Funding under federal grants was 0.5 million for the fourth quarter of 23 compared to 1.4 million in the comparable 22 quarter. For the full year of 2023, funding of federal grants was 2.2 million compared to 2.5 million for the full year of 2022. These decreases were a result of the timing of research activities eligible for funding, particularly for the Empower program we're continuing to explore and non-dilutive government funding to support this program through the NIHCL. initiative, which stands for helping to end addiction long term. Our research and development expenses declined in 2023 totaling 2.2 million for the fourth quarter compared to 6.4 million for the same period in 2022. For the full year of 2023. R and D expenses were $7.6 million compared to 19.8 million for the full year 2022. The decreases were primarily the result of reduced external costs related to the clinical programs for PSX. one for MPS six, one for Empire, particularly regarding bioequivalents. And due to these potential studies for PS. 600 for conducted in 2022.

我現在歡迎我們的財務長戴夫漢弗萊(Dave Humphrey) 做簡短的財務摘要。 30 日則為150 萬美元。此外，2 月份，我們透過行使認股權證購買了最初於 2023 年 5 月發行的 360 萬股普通股，獲得了 470 萬美元的總收益。23 年第四季聯邦撥款額為 50 萬美元，而 22 年同期為 140 萬美元。2023 年全年，聯邦撥款 220 萬美元，而 2022 年全年為 250 萬美元。這些減少是由於有資格獲得資助的研究活動的時間安排造成的，特別是我們正在繼續探索的 Empower 計劃以及透過 NIHCL 支持該計劃的非稀釋性政府資金。倡議，代表幫助長期戒除毒癮。2023 年第四季我們的研發費用總計 220 萬美元，而 2022 年同期為 640 萬美元。2023 年全年。研發費用為 760 萬美元，而 2022 年全年為 1,980 萬美元。減少的主要原因是與 PSX 臨床項目相關的外部成本減少。一份用於 MPS 6，一份用於 Empire，特別是在生物等效物方面。由於這些潛在的 PS 研究。 2022 年進行 600 次。

General and administrative expenses were 1.4 million in the fourth quarter of 2023, a slight increase compared to $1.2 million for the same period of 2022. For the full year 2023 P. and A. expenses decreased 22% to 5.4 million compared to $6.9 million for the full year 2020. A slight increase in the quarter over quarter period was due to higher noncash stock-based compensation, while the full year decrease was a result of reduced consulting, legal liability, insurance and employee bonus expenses. Total other income or expense net was an expense of approximately 0.3 million for the fourth quarter of 23 compared to income of 0.7 million from the same period in 22. For full year total other income net was 92,000 in 2023 compared to 14,000 in 2022. These changes in other income expense are primarily due to non-cash better value adjustments for convertible notes and warrant net loss attributable to common stockholders for the fourth quarter of 2023 was 3.5 million compared to 5.5 million for the fourth quarter of 22 for the full year of 2023, our net loss was $10.6 million compared to $25.1 million for the full year of 2022 as a clinical-stage biotech company. Our continued research and development efforts toward regulatory approvals for our product candidates are expected to result in losses for the foreseeable future. Operator, we will now take questions.

2023年第四季一般及管理費用為140萬美元，較2022年同期的120萬美元略有增加。2023 年全年的 P. 和 A. 費用下降 22%，至 540 萬美元，而 2020 年全年為 690 萬美元。季度環比略有增長是由於非現金股票薪酬增加，而全年下降是由於諮詢、法律責任、保險和員工獎金費用減少。23 年第四季的其他收入或支出淨額總額約為 30 萬美元，而 22 年第四季的收入為 70 萬美元。2023 年全年其他淨收入總額為 92,000，而 2022 年為 14,000。其他收入費用的這些變化主要是由於可轉換票據和認股權證的非現金更好價值調整，2023 年第四季歸屬於普通股股東的淨虧損為350 萬美元，而22 年第四季全年為550 萬美元作為一家臨床階段的生物技術公司，到 2023 年，我們的淨虧損為 1,060 萬美元，而 2022 年全年的淨虧損為 2,510 萬美元。我們為候選產品獲得監管部門批准而持續進行的研發工作預計將在可預見的未來造成損失。接線員，我們現在開始提問。

(Operator Instructions) Ram Selvaraju, H.C. Wainwright.

（操作員說明）Ram Selvaraju, H.C.溫賴特。

Please proceed with your question.

請繼續你的問題。

Hello. What is the current pro forma cash?

你好。目前預計現金是多少？

Dave, would you like to take that?

戴夫，你願意接受嗎？

Sure. Our cash was about 1.1 million at the end of the year. And then we had some warrant exercises and in the first quarter. So our current funding allows us to fund operations into the third quarter of this year.

當然。年底我們的現金約110萬。然後我們在第一季進行了一些認股權證行使。因此，我們目前的資金使我們能夠為今年第三季的營運提供資金。

Do you currently have sufficient resources with which to start the Phase three trial of PF. six one four.

您目前是否有足夠的資源來啟動 PF 的第三階段試驗？六一四。

And right now we're working on preparatory preparation for Phase three trials and some additional work on our manufacturing of drug products, but we'd be looking to raise additional funding before we initiate the actual Phase three study.

目前，我們正在為第三階段試驗做準備，並為我們的藥品生產做一些額外的工作，但我們希望在啟動實際的第三階段研究之前籌集額外的資金。

Great.

偉大的。

Thank you.

謝謝。

First answering my questions.

首先回答我的問題。

Hunter Diamond, Diamond Equity.

獵人鑽石，鑽石股票。

Thank you. It was a fairly comprehensive call, so not many questions from me, but just a follow-up to the cash question on considering the advancements of PS. 600 for the exercise of the warrants and the issuances, maybe just to be approved, provide kind of an update on the burn rate and what you think milestones you can reach with the current capital?

謝謝。這是一次相當全面的電話會議，所以我提出的問題不多，只是關於考慮 PS 進步的現金問題的後續行動。 600 用於行使認股權證和發行，也許只是為了獲得批准，提供有關燃燒率的最新資訊以及您認為用當前資本可以達到的里程碑是什麼？

Sure. In terms of burn rate, we're in a phase right now where we're spending a little bit less. I think in the first half of this year, we'll probably continue R&D spending at about the rate we were in 2023, so maybe 1.5 to 2 million a quarter. I would expect that to begin to ramp up in the second half of the year once we initiate the Phase three clinical trials and depending on funding and as that ramps up, might reach levels more closely aligned with what we're doing in 2022 with some of our higher clinical activity in that year. So potentially 5 million or more a quarter and when fully ramped up for Phase three.

當然。就燒錢率而言，我們現在正處於支出稍微減少的階段。我認為今年上半年，我們可能會繼續以 2023 年的水平維持研發支出，因此每季可能為 150 至 200 萬美元。我預計，一旦我們啟動第三階段臨床試驗，這將在今年下半年開始加速，並且根據資金情況，隨著資金的增加，可能會達到與我們在2022 年所做的事情更加一致的水平，其中一些那一年我們更高的臨床活動。因此，當第三階段全面啟動時，每季可能會達到 500 萬或更多。

Great. Thank you.

偉大的。謝謝。

And that makes perfect sense and congratulations on all the progress.

這是完全合理的，祝賀所有的進展。

Okay.

好的。

Brad Sorensen, Zacks Small-Cap Research

Brad Sorensen，Zacks 小型股研究

Yes, thank you.

是的，謝謝。

Hi, Alan and the team a great update and we are very excited to hear about it and obviously a huge need for the country and read more about that this morning. And you mentioned some partnership opportunities in your partnership opportunity in Europe, I believe. And I was just wondering if you had pursued in the other side on the health of the pipeline with other partnership opportunities or additional government funding because this is a huge national problem, just those kinds of issues, either partner or government funding if there's any developments in that area.

嗨，艾倫和團隊，這是一個很棒的更新，我們很高興聽到這個消息，顯然這個國家有巨大的需求，今天早上閱讀了更多相關內容。我相信，您在歐洲的合作機會中提到了一些合作機會。我只是想知道您是否在另一邊透過其他合作機會或額外的政府資助來追求管道的健康，因為這是一個巨大的國家問題，只是這類問題，如果有任何進展，無論是合作夥伴還是政府資助在那個地區。

Thank you.

謝謝。

Thanks, Brad.

謝謝，布拉德。

And certainly, we appreciate the fact that you recognize the need that we're trying to fill. As we mentioned, we have explored a partnership really too expand our pipeline, and that is the partnership we spoke about with our strong presence. We are continuing to see that examine opportunities for all of our pLADD programs. Certainly the opioid products, which are more fully developed we have had discussions with some groups and we do have intellectual property in other areas. And the use of our TAP and impart platforms can be applied to other indications. So we've explored and have initiated discussions with that. It still have fairly long process, but we are in discussions for that and we are exploring other opportunities with the NIH. the Heald program, as Dave mentioned, as there is funding opportunities there for various programs and we will continue to tap into that as necessary.

當然，我們很感激您認識到我們正在努力滿足的需求。正如我們所提到的，我們已經探索了一種合作夥伴關係，以擴大我們的管道，這就是我們透過我們的強大影響力談到的合作夥伴關係。我們將繼續尋找我們所有 pLADD 專案的機會。當然，我們已經與一些團體進行了更充分開發的阿片類藥物產品的討論，並且我們確實在其他領域擁有知識產權。我們的 TAP 和 grant 平台的使用可以應用於其他適應症。因此，我們對此進行了探索並發起了討論。它仍然有相當長的過程，但我們正在對此進行討論，並且我們正在與 NIH 探索其他機會。正如戴夫所提到的，希爾德計劃，因為那裡有各種計劃的資助機會，我們將在必要時繼續利用這一機會。

Great. Thanks.

偉大的。謝謝。

Thank you. And we have reached the end of the question-and-answer session. And therefore, I would like to turn the call back over to Dr. Corey Passeri for her closing remarks.

謝謝。我們的問答環節已經結束了。因此，我想將電話轉回給科里·帕塞里 (Corey Passeri) 博士，讓她發表結束語。

Thank you, operator. As we think about pain. We know there are many different products on the market that deal with different types of pain. Many patients don't need an opioid to relieve their discomfort. Additionally, we know there is a significant push to tried to replace opioids with products that do not have their deleterious effect yet today this has not been a reality. There has been significant press recently about a new pain product, a NaV 1.8 inhibitor that purportedly it does not have the same potential for addiction as an opioid. However, we believe the data recently presented indicated that this new product was inferior to the opioid control arm for reducing pain in its recent Phase three clinical study. This new pain product may have great potential for some types of pain. But the study showed that severe postsurgical pain may still be better off treated with an opioid opioids have been used for thousands of years and still play a major role in health care. And I believe that tap and in-park opioid products will provide prescribers and patients with the next generation of safer opioid and the only opioid to date with oral overdose protection, we are working to bring these products to the market in a timely manner.

謝謝你，接線生。當我們思考疼痛時。我們知道市面上有許多不同的產品可以治療不同類型的疼痛。許多患者不需要阿片類藥物來緩解不適。此外，我們知道人們大力推動嘗試用沒有有害作用的產品取代鴉片類藥物，但如今這還沒有成為現實。最近有關於一種新的止痛產品 NaV 1.8 抑制劑的重大新聞報道，據稱它不具有與阿片類藥物相同的成癮潛力。然而，我們認為最近提供的數據表明，在最近的三期臨床研究中，該新產品在減輕疼痛方面不如阿片類藥物對照組。這種新的止痛產品對於某些類型的疼痛可能具有巨大的潛力。但研究表明，使用鴉片類藥物治療嚴重的術後疼痛可能仍然更好。我相信，自來水和公園內阿片類藥物產品將為處方者和患者提供下一代更安全的阿片類藥物，也是迄今為止唯一具有口服過量保護功能的阿片類藥物，我們正在努力將這些產品及時推向市場。

I would like to thank each of you for joining our corporate update conference call today. We are encouraged by the positive developments that have transpired in early 2024 for both our unique products. We look forward to continuing to provide progress updates as we initiate our Phase three studies in the year ahead. Thank you.

我要感謝大家今天參加我們的公司更新電話會議。我們對 2024 年初這兩種獨特產品所取得的正面進展感到鼓舞。我們期待在明年啟動第三階段研究時繼續提供進展更新。謝謝。

Thank you. This concludes today's conference, and you may disconnect your lines. Thank you for your participation.

謝謝。今天的會議到此結束，您可以掛斷電話了。感謝您的參與。