Vyne Therapeutics Inc (VYNE) 2021 Q3 法說會逐字稿

Good morning, and welcome to the VYNE Therapeutics conference call to discuss the third quarter 2021 financial results and corporate update. (Operator Instructions) Please be advised that this call is being recorded at the company's request.

早安，歡迎參加 VYNE Therapeutics 2021 年第三季財務業績和公司最新動態電話會議。（操作員指示）請注意，本次通話正在依照本公司要求進行錄音。

I will now turn the call over to John Fraunces of LifeSci Advisors. Please go ahead.

現在我將電話轉給 LifeSci Advisors 的 John Fraunces。請繼續。

Good morning, everyone, and thank you for joining us. Participating in this morning's call are Dave Domzalski, VYNE's President and Chief Executive Officer; Tyler Zeronda, VYNE's Chief Financial Officer; and Dr. Iain Stuart, the company's Chief Scientific Officer.

各位早安，感謝各位的參與。參加今天早上電話會議的有：VYNE 總裁兼執行長 Dave Domzalski；VYNE 財務長 Tyler Zeronda；以及公司首席科學官 Iain Stuart 博士。

Please note that there are slides to accompany Dr. Stuart's discussion. For those of you who dialed into the phone lines, in order to access these slides you will need to log on to the live webcast. The link can be found on the Investors & Media section of VYNE's corporate website under Events and Presentation. Slide presentation and a replay of this conference call will be archived on the company's website.

請注意，Stuart 博士的講解配有幻燈片。對於撥入電話線的各位，要存取這些投影片，您需要登入即時網路直播。您可以在 VYNE 公司網站的「投資者與媒體」版塊的「活動與演示」下找到該連結。本次電話會議的幻燈片簡報和錄音回放將存檔於公司網站。

Before we begin formal remarks, let remind you that some of the information in the press release issued this morning and on this conference call contain forward-looking statements that involve risks, uncertainties and assumptions that are difficult to predict including statements regarding VYNE's development programs and future plans and prospects as well as observations regarding ongoing operating expenses. These statements will include plans and expectations regarding strategic transactions and the success, timing and cost of clinical trials. Words that express and reflect optimism, satisfaction with current progress, prospects or projections as well as words such as believe, intend, expect, plan, anticipate and similar variations identify forward-looking statements, but their absence does not mean that a statement is not forward-looking.

在我們正式發言之前，請允許我提醒各位，今天上午發布的新聞稿和本次電話會議中的一些信息包含前瞻性陳述，這些陳述涉及難以預測的風險、不確定性和假設，包括有關 VYNE 開發計劃、未來計劃和前景的陳述，以及有關持續運營費用的觀察。這些聲明將包括有關策略交易的計劃和預期，以及臨床試驗的成功、時間和成本。表達和反映樂觀、對當前進展、前景或預測感到滿意的詞語，以及諸如相信、打算、期望、計劃、預計等詞語和類似變體，都可作為前瞻性陳述，但缺少這些詞語並不意味著某個陳述就不是前瞻性的。

Such forward-looking statements are not a guarantee of performance, and the company's actual results could differ materially from those contained in such statements. Several factors that could cause or contribute to such differences are described in detail in VYNE Therapeutics' filings with the SEC. These forward-looking statements speak only as of the date of today's press release and conference call, and the company undertakes no obligation to publicly update any forward-looking statements or supply new information regarding the circumstances after the date of this call.

此類前瞻性陳述並非績效保證，本公司的實際績效可能與此類陳述中所包含的績效有重大差異。VYNE Therapeutics 向美國證券交易委員會提交的文件中詳細描述了可能導致或促成此類差異的幾個因素。這些前瞻性聲明僅代表截至今天新聞稿和電話會議發布之日的信息，本公司不承擔在本次電話會議之後公開更新任何前瞻性聲明或提供有關情況的新信息的義務。

In addition, the financial portion of this call will include certain non-GAAP financial information. For additional disclosures relating to these non-GAAP financial measures, including a reconciliation to the most directly comparable GAAP measures, please see today's press release, which is posted on the Investor Relations section of our website.

此外，本次電話會議的財務部分將包含某些非GAAP財務資訊。有關這些非GAAP財務指標的更多披露信息，包括與最直接可比較的GAAP指標的調節表，請參閱今天發布的新聞稿，該新聞稿已發佈在我們網站的投資者關係部分。

At this time, I would like to turn the call over to Dave Domzalski. Dave, Please go ahead.

此時，我想把電話交給戴夫‧多姆札爾斯基。戴夫，請繼續。

Thank you, John, and good morning to everyone. On our previous earnings call, we announced our transformational decision to refocus our efforts toward developing new and innovative therapies for the treatment of immunoinflammatory diseases. Today, one quarter later, I'm pleased to report that we've achieved a number of important milestones as we continue to advance our proprietary pipeline through a series of near-term early-stage clinical catalysts over the next 12 to 18 months.

謝謝你，約翰，大家早安。在上一次財報電話會議上，我們宣布了一項變革性決定，即重新集中精力開發用於治療免疫發炎性疾病的新型創新療法。今天，時隔一個季度，我很高興地報告，我們取得了一些重要的里程碑，我們將繼續推進我們專有的產品線，並在未來 12 到 18 個月內透過一系列近期早期臨床催化劑來實現這一目標。

Without question, the catalytic event driving this transformation has been the licensing of our bromodomain and extra-terminal, or BET, inhibitor platform, which we announced in August. As a reminder, the BET inhibitor platform provides VYNE worldwide rights to a library of small molecule NCEs and a unique platform to develop both topical and oral BET inhibitor therapeutics for any indication. Because BET inhibitors have the ability to target multiple pro-inflammatory pathways, we believe this exciting new drug class could offer the opportunity for highly potent therapies. These therapies have the potential to address serious unmet medical needs with immunoinflammatory diseases. We are now poised to generate a series of exciting data-driven milestones that we believe will unveil the significant therapeutic potential of these assets.

毫無疑問，推動這一轉變的催化事件是我們在 8 月宣布的溴結構域和末端外結構域（BET）抑制劑平台的授權。提醒一下，BET 抑制劑平台為 VYNE 提供了一系列小分子 NCE 的全球權利，以及一個獨特的平台，用於開發針對任何適應症的局部和口服 BET 抑制劑療法。由於 BET 抑制劑能夠針對多種促發炎通路，我們相信這種令人興奮的新藥物類別可能為高效療法提供機會。這些療法有可能解決免疫發炎性疾病方面尚未滿足的嚴重醫療需求。我們現在準備推出一系列令人興奮的數據驅動型里程碑，我們相信這些里程碑將揭示這些資產的巨大治療潛力。

Our focus will be to advance our lead topical BET inhibitor product candidate VYN201 into the clinic in 2022. VYN201 is a first-in-class pan-BD BET inhibitor that is designed to reduce inflammation while mitigating systemic drug exposure. VYN201 is being developed for topical applications, potentially including rare dermatosis where there are significant unmet need due to a lack of indicated treatment options.

我們將重點推進我們領先的局部 BET 抑制劑候選產品 VYN201 在 2022 年進入臨床試驗階段。VYN201 是一種首創的泛 BD BET 抑制劑，旨在減少炎症，同時減輕全身藥物暴露。VYN201 正在開髮用於局部應用，可能包括罕見皮膚病，因為缺乏有效的治療方案，導致存在很大的未滿足需求。

As many of you know, we recently announced positive data showing that VYN201 was able to significantly reduce several key pro-inflammatory cytokines in both a preclinical model and in a human skin tissue model. Additionally, VYN201 demonstrated improvements in reducing fibrotic tissue mass and overall skin repair outcomes with no negative impact on healing time. These findings offer valuable insights into the evolving therapeutic profile of VYN201, suggesting that the drug may offer optimized efficacy and safety characteristics that could be highly differentiated. Our Chief Scientific Officer, Dr. Iain Stuart, will review the details from these studies later in the call.

正如你們許多人所知，我們最近公佈了積極的數據，表明 VYN201 能夠在臨床前模型和人體皮膚組織模型中顯著降低幾種關鍵的促炎細胞因子。此外，VYN201 在減少纖維化組織量和整體皮膚修復效果方面也表現出改善作用，且對癒合時間沒有負面影響。這些發現為 VYN201 不斷變化的治療特性提供了寶貴的見解，表明該藥物可能具有高度差異化的最佳化療效和安全性特徵。我們的首席科學官伊恩·斯圖爾特博士將在稍後的電話會議中詳細介紹這些研究。

In parallel with these efforts, we have been working diligently with our partner, In4Derm, on the development of the oral BET inhibitor VYN202. VYN202 is an orally delivered first-in-class BET inhibitor that is highly selective for bromodomain 2 or BD2, with the goal of having a more targeted anti-inflammatory effect with an improved benefit risk profile as compared to other oral non-selective BET inhibitors.

同時，我們與合作夥伴 In4Derm 密切合作，致力於開發口服 BET 抑制劑 VYN202。VYN202 是一種口服的首創 BET 抑制劑，對溴結構域 2 (BD2) 具有高度選擇性，旨在與其他口服非選擇性 BET 抑制劑相比，具有更有針對性的抗發炎作用和更優的獲益風險比。

Upon final candidate selection, we intend to commence an IND-enabling non-clinical safety program and enter the clinic. We are evaluating VYN202 for use in several potential indications with an initial focus on autoimmune conditions.

一旦最終確定候選藥物，我們將啟動一項可提交 IND 的非臨床安全性研究計劃，並進入臨床試驗階段。我們正在評估 VYN202 在幾種潛在適應症中的應用，初步重點是自體免疫疾病。

To further support our BET inhibitor programs, we recently formed our scientific advisory board, which will provide an important source of external scientific and medical expertise as we expand our BET inhibitor R&D activities. The members of our scientific advisory board are world-renowned experts specializing in immunological and inflammatory diseases, and we are incredibly fortunate to have these distinguished scientists and clinicians to help guide our BET inhibitor and other development programs.

為了進一步支持我們的 BET 抑制劑項目，我們最近成立了科學顧問委員會，這將為我們擴大 BET 抑制劑研發活動提供重要的外部科學和醫學專業知識來源。我們的科學顧問委員會成員都是世界知名的免疫和發炎疾病專家，我們非常幸運能有這些傑出的科學家和臨床醫生來指導我們的 BET 抑制劑和其他開發項目。

Turning to FMX114. We are encouraged by the progress we are making for our most advanced drug candidate. In October, we announced the first patient had enrolled in our Phase Ib/IIa clinical trial that will assess the safety and efficacy of FMX114 gel versus vehicle gel in patients with mild-to-moderate atopic dermatitis. In light of the FDA's recent review of the oral JAK inhibitor class for the treatment of several systemic autoimmune diseases, we believe it's important to characterize the preliminary safety and pharmacokinetic profile of FMX114. The Phase 1b portion of the study will generate meaningful data as we advance the product into the Phase IIa portion for broader safety and efficacy evaluation. We currently expect top line results from this study in the early part of first quarter of next year.

切換到FMX114。我們最先進的候選藥物取得了令人鼓舞的進展。10 月，我們宣布首位患者已入組我們的 Ib/IIa 期臨床試驗，該試驗將評估 FMX114 凝膠與賦形劑凝膠在輕度至中度異位性皮膚炎患者中的安全性和有效性。鑑於 FDA 最近對口服 JAK 抑制劑類藥物用於治療多種系統性自體免疫疾病進行了審查，我們認為有必要對 FMX114 的初步安全性和藥物動力學特徵進行表徵。研究的 1b 期部分將產生有意義的數據，以便我們將產品推進到 IIa 期部分，進行更廣泛的安全性和有效性評估。我們目前預計將於明年第一季初獲得該研究的初步結果。

As a reminder, FMX114 is a proprietary topical combination formulation of tofacitinib, a janus kinase inhibitor; and fingolimod, a sphingosine 1-phosphate receptor modulator, that is being evaluated for the treatment of mild-to-moderate atopic dermatitis. This program is an important part of our strategic transition to develop therapies for immunoinflammatory conditions. Atopic dermatitis is a chronic periodic inflammatory skin condition and is a multifactorial disease, which supports our thesis that a multimodal therapeutic is the ideal approach to achieve optimal clinical outcomes for patients.

提醒一下，FMX114 是一種專有的外用複方製劑，由 Janus 激酶抑制劑託法替尼和鞘氨醇 1-磷酸受體調節劑芬戈莫德組成，目前正在評估其治療輕度至中度異位性皮膚炎的療效。該計畫是我們策略轉型的重要組成部分，旨在開發針對免疫發炎性疾病的療法。異位性皮膚炎是一種慢性週期性發炎性皮膚病，是一種多因素疾病，這支持了我們的論點，即多模式治療是為患者實現最佳臨床療效的理想方法。

FMX114 has been designed with intracellular and extracellular mechanism of actions to address both the source and cause of inflammation in atopic dermatitis. As a JAK inhibitor, tofacitinib reduces inflammation by inhibiting the release of cytokines that promote inflammation in the skin. These cytokines negatively impact both skin barrier integrity and function, which are key components of the disease.

FMX114 的設計兼顧細胞內和細胞外作用機制，旨在解決異位性皮膚炎發炎的來源和原因。作為一種 JAK 抑制劑，託法替尼透過抑制促進皮膚發炎的細胞激素的釋放來減輕發炎。這些細胞激素會對皮膚屏障的完整性和功能產生負面影響，而皮膚屏障的完整性和功能是疾病的關鍵組成部分。

FMX114 second component, fingolimod, reduces inflammation by inhibiting the migration of inflammatory cells into the skin. Additionally, fingolimod upregulates flagrant, a protein which plays an important role in supporting skin barrier recovery. This successfully developed, we believe FMX114 has the potential to be the first topical combination product for the treatment of atopic dermatitis.

FMX114 的第二個成分芬戈莫德，透過抑制發炎細胞向皮膚遷移來減輕發炎。此外，芬戈莫德還能上調 flagrant 蛋白，在支持皮膚屏障恢復方面發揮重要作用。我們相信，FMX114 成功研發後，可望成為首個用於治療異位性皮膚炎的局部複方製劑。

Now I'd like to briefly touch on the planned sale of our topical minocycline franchise, which includes AMZEEQ, ZILXI, FCD105, which is our Phase III ready combination product, and the underlying MST platform. These are excellent products. And the responses from patients and healthcare providers continues to be very positive. AMZEEQ and ZILXI have generated nearly 165,000 prescriptions combined through September of this year.

現在我想簡單談談我們計劃出售的局部用米諾環素產品線，其中包括 AMZEEQ、ZILXI、FCD105（我們的 III 期組合產品）以及相關的 MST 平台。這些產品非常棒。來自患者和醫療服務提供者的回饋依然非常積極。截至今年9月，AMZEEQ 和 ZILXI 合計已產生近 165,000 張處方。

As noted in this morning's press release, our minocycline franchise is a high-quality commercial platform that has significant value. We continue to make progress on the sale of this franchise, and we are encouraged by the level of interest we have received. We will provide additional updates as our current discussions continue to advance.

正如今天早上的新聞稿所述，我們的米諾環素特許經營權是一個具有重大價值的高品質商業平台。我們在出售該特許經營權方面持續取得進展，並且我們對所收到的關注度感到鼓舞。隨著討論的深入，我們將提供更多最新消息。

With that, I'd now like to turn the call over to Tyler to cover the financials. Tyler?

接下來，我想把電話交給泰勒，讓他來介紹財務方面的狀況。泰勒？

Thanks, Dave, and good morning, everyone. Revenues in the third quarter 2021 totaled $4.1 million and consisted of $4 million of product sales from AMZEEQ and ZILXI and $0.1 million of royalty revenue. Our third quarter 2021 GAAP net loss was $21.3 million or $0.41 per share. When excluding $2.4 million of stock-based compensation expense, our third quarter 2021 adjusted net loss was $18.9 million or $0.36 per share.

謝謝你，戴夫，大家早安。2021 年第三季營收總計 410 萬美元，其中包括 AMZEEQ 和 ZILXI 的產品銷售額 400 萬美元和特許權使用費收入 10 萬美元。我們 2021 年第三季 GAAP 淨虧損為 2,130 萬美元，即每股虧損 0.41 美元。在扣除 240 萬美元的股票選擇權費用後，我們 2021 年第三季調整後的淨虧損為 1,890 萬美元，即每股虧損 0.36 美元。

For the third quarter 2021, adjusted operating expenses were $18.4 million, including adjusted SG&A expenses of $11.9 million and adjusted R&D expenses of $6.5 million. The third quarter adjusted operating expenses of $18.4 million were $1.9 million lower than the second quarter of 2021, reflecting our focus on cost control and resource prioritization.

2021 年第三季度，調整後的營運費用為 1,840 萬美元，其中包括調整後的銷售、一般及行政費用 1,190 萬美元及調整後的研發費用 650 萬美元。第三季調整後的營運支出為 1,840 萬美元，比 2021 年第二季減少了 190 萬美元，這反映了我們對成本控制和資源優先排序的重視。

As we continue to transition our focus and spend toward developing our pipeline, we expect to further reduce our adjusted operating expenses to a range of $10 million to $15 million in the fourth quarter of 2021, excluding the onetime $4 million milestone payment related to the exercise of the license agreement for the oral BET inhibitor VYN202.

隨著我們繼續將重點和支出轉向開發我們的產品線，我們預計在 2021 年第四季度將進一步減少調整後的營運支出，降至 1000 萬美元至 1500 萬美元之間，不包括與行使口服 BET 抑製劑 VYN202 的許可協議相關的 400 萬美元一次性付款。

Based on our current plans to conduct a Phase IIb trial for FMX114, assuming positive results in the Phase IIa trial and to progress both VYN201 and VYN202 into the clinic in 2022, we anticipate that our adjusted operating expenses will be approximately $10 million per quarter next year.

根據我們目前的計劃，並進行 FMX114 的 IIb 期試驗，假設 IIa 期試驗取得積極結果，並在 2022 年將 VYN201 和 VYN202 推進到臨床階段，我們預計明年調整後的營運費用約為每季 1000 萬美元。

Now turning to our balance sheet. Our cash position as of September 30 was approximately $53 million. We believe that this cash will be sufficient to fund our operations through the second quarter of 2022. This projection does not take into account any potential proceeds from the sale of the topical minocycline franchise, new business development transactions or additional financing activities.

現在來看我們的資產負債表。截至9月30日，我們的現金儲備約為5,300萬美元。我們相信這筆現金足以支持我們營運到 2022 年第二季。該預測並未考慮出售局部用米諾環素特許經營權、新的業務開發交易或額外融資活動可能帶來的任何收益。

Finally, our shares outstanding at September 30, 2021, totaled 53.5 million shares. For additional information regarding our third quarter results and prior period comparisons, please refer to today's earnings release and our Form 10-Q filed with the SEC.

最後，截至 2021 年 9 月 30 日，我們的流通股總數為 5,350 萬股。有關我們第三季度業績及前期比較的更多信息，請參閱今天發布的收益報告以及我們向美國證券交易委員會提交的 10-Q 表格。

With that, I will turn the call over to Iain, who will go through the progress we've made with our BET inhibitor program.

接下來，我將把電話交給伊恩，他將介紹我們在 BET 抑制劑專案方面的進展。

Thanks, Tyler. I'd like to start by providing a brief progress update on our BET inhibitor programs, which includes VYN201 and VYN202 that we are introducing today as the inhibit platform. I will then present a few slides covering recently announced preclinical data for VYN201, our topical pan bromodomain BET inhibitor project.

謝謝你，泰勒。首先，我想簡單介紹一下我們的 BET 抑制劑計畫的最新進展，其中包括我們今天推出的抑制平台 VYN201 和 VYN202。接下來，我將展示幾張投影片，介紹我們局部泛溴結構域 BET 抑制劑計畫 VYN201 最近發表的臨床前數據。

As a reminder, today's slide presentation is being presented via our live webcast, and these slides can also be found in our corporate presentation available on our website under the Investor Relations section.

再次提醒，今天的幻燈片簡報將透過我們的網路直播進行，這些幻燈片也可以在我們網站「投資者關係」欄位下的公司簡報中找到。

Beginning with VYN201. We have selected our topical formulation for this pan BET inhibitor and have already generated significant stage appropriate product characterization and stability information to support its development. In this past quarter, we have initiated the prerequisite preclinical safety program to support the product's regulatory submissions. I'm pleased to report that both formulation development and preclinical safety programs are progressing well to date.

從 VYN201 開始。我們已經選定了這種泛 BET 抑制劑的局部用製劑，並且已經生成了大量適合該階段的產品表徵和穩定性信息，以支持其開發。上個季度，我們啟動了必要的臨床前安全性計劃，以支持產品的監管申報。我很高興地報告，到目前為止，製劑開發和臨床前安全性研究計畫進展順利。

Moving now to VYN202, our bromodomain 2 selective oral BET inhibitor project. The lead optimization work is progressing well with our partner In4Derm to identify potential development candidates for this program. In4Derm have produced several drug light NCE candidates with potential class-leading potency and BD2 selectivity. Work is continuing to further characterize these molecules and adding new molecules to the platform of several hundred BET inhibitor examples.

接下來介紹 VYN202，我們的溴結構域 2 選擇性口服 BET 抑制劑計畫。我們與合作夥伴 In4Derm 的先導化合物優化工作進展順利，旨在為此專案確定潛在的開發候選藥物。In4Derm 已開發出幾種具有潛在領先同類效力和 BD2 選擇性的藥物輕型 NCE 候選物。目前仍在繼續進行工作，以進一步表徵這些分子，並將新分子添加到已有數百種 BET 抑制劑實例的平台中。

As Dave outlined earlier, we recently announced the formation of our scientific advisory board, and we convened our first meeting last month with this esteemed group of advisers. In brief, there was broad agreement and interest from the scientific advisory board members on the utility of the BET inhibitor platform across their respective specialties and enthusiasm for its first-in-class potential.

正如戴夫之前概述的那樣，我們最近宣布成立了科學顧問委員會，上個月我們與這群受人尊敬的顧問舉行了第一次會議。簡而言之，科學顧問委員會成員對 BET 抑制劑平台在其各自專業領域的實用性普遍表示贊同和興趣，並對其首創潛力充滿熱情。

Turning back to VYN201. We recently announced new data from 2 preclinical studies demonstrating the potential of VYN201 as a highly potent anti-inflammatory therapy for the treatment of various dermatoses with high unmet need.

回到 VYN201。我們最近公佈了 2 項臨床前研究的新數據，證明 VYN201 具有作為高效抗炎療法治療各種皮膚病的潛力，這些皮膚病目前存在著很高的未滿足需求。

Slide 3 presents data from a common mouse model of TH17 mediated inflammation. The differentiation and activity of TH17 immune cells drive inflammation in several autoimmune diseases, and are of particular relevance to rare skin diseases, we are currently investigating with VYN201. In this model, dose depleted mice will be topic or topically treated with imiquimod once-daily for 7 days to induce TH17 inflammatory dermal phenotype. Following this induction phase, VYN201 was applied once daily at several concentrations and compared to both vehicle and to the Class I superpotent glucocorticosteroid, clobetasol proprionate cream 0.05% over a 7-day treatment period. Topical imiquimod was also applied once-daily during the treatment period.

幻燈片 3 展示了來自 TH17 介導發炎的常見小鼠模型的數據。TH17 免疫細胞的分化和活性驅動多種自體免疫疾病的炎症，並且與我們目前正在使用 VYN201 進行研究的罕見皮膚病特別相關。在該模型中，劑量不足的小鼠將每天一次局部或局部用咪喹莫特治療 7 天，以誘導 TH17 發炎性皮膚表型。在誘導階段之後，每天使用一次不同濃度的 VYN201，並在 7 天的治療期內與賦形劑和 I 類超強效糖皮質激素丙酸氯倍他索乳膏 0.05% 進行比較。治療期間，每天也局部塗抹咪喹莫特一次。

The graph on the left of this slide presents change in Composite Inflammatory Severity Score of erythema and scaling severity for the treatment group over 7 days treatment period. Over the concentration range 0.001% to 0.1%, we observed a dose-dependent improvement in clinical signs of inflammation with VYN201 treated animals, culminating in a 94% reduction in clinical signs for VYN201 0.1% compared to vehicle at the end of treatment. Further, VYN201 0.1% was found to be comparable -- have a comparable positive impact on reducing clinical signs of inflammation when compared to the clobetasol product, indicative of our marked anti-inflammatory effect.

本投影片左側的圖表顯示了治療組在 7 天治療期內紅斑和鱗屑嚴重程度的綜合發炎嚴重程度評分的變化。在濃度範圍為 0.001% 至 0.1% 時，我們觀察到 VYN201 治療動物的發炎臨床症狀呈現劑量依賴性改善，最終 VYN201 0.1% 組在治療結束時的臨床症狀較對照組減少了 94%。此外，VYN201 0.1% 被發現具有可比性——與氯倍他索產品相比，在減少發炎的臨床症狀方面具有可比的正面影響，這表明我們具有顯著的抗發炎作用。

Moving to tolerability. The plot on the right of this slide presents mean change in animal body weights during the treatment phase. Change in body weight is used as an indicator of general tolerance to treatment. Here we compare body weight changes between VYN201 0.1%, vehicle, clobetasol cream and a healthy control animal group shown here in green. Animals treated with VYN201 0.1% continue to gain weight throughout the treatment phase and a similar manner to the healthy control animals and was well tolerated. However, animals treated with clobetasol experienced a 17% mean reduction in body weight throughout the treatment period compared to VYN201 0.1% treated animals. This is attributable to the negative impact glucocorticosteroids have on the endocrine system by causing hormonal imbalances that impact metabolism.

轉向耐受性。本投影片右側的圖表顯示了治療階段動物體重的平均變化。體重變化可作為衡量對治療整體耐受性的指標。在這裡，我們比較了 VYN201 0.1%、賦形劑、氯倍他索乳膏和健康對照動物組（圖中綠色部分）之間的體重變化。接受 VYN201 0.1% 治療的動物在整個治療階段體重持續增加，與健康對照動物的體重增加方式相似，且耐受性良好。然而，與接受 VYN201 0.1% 治療的動物相比，接受氯倍他索治療的動物在整個治療期間體重平均下降了 17%。這是由於糖皮質激素對內分泌系統產生負面影響，導致荷爾蒙失衡，進而影響新陳代謝所致。

Slide 4 presents the impact of VYN201 in reducing the expression of key cytokines that drive TH17-mediated inflammation. It should be noted that all of the cytokines presented here play a contributory roles in TH17 cell differentiation and inflammatory response in several autoimmune diseases. In this study, we observed a strong correlation between cytokine reduction and resolution of clinical signs of inflammation that I presented in the previous slide. Further, we observed a dose-dependent reduction in all 6 cytokines, culminating in a maximum effect at the VYN201 0.1% dose.

幻燈片 4 展示了 VYN201 在降低驅動 TH17 介導的發炎的關鍵細胞因子的表達方面的作用。值得注意的是，這裡提到的所有細胞激素在多種自體免疫疾病中對 TH17 細胞分化和發炎反應都起著促進作用。在本研究中，我們觀察到細胞激素減少與發炎臨床症狀消退之間存在很強的相關性，我在上一張投影片中展示了這一點。此外，我們觀察到所有 6 種細胞激素均呈現劑量依賴性降低，在 VYN201 0.1% 劑量下達到最大效果。

Slide 5 presents typical examples of photography at the end of this treatment. The left photograph is of an animal treated with VYN201 vehicle. As you can clearly see, there is still significant inflammation, redness and scaling present. The central photograph of an animal treated with VYN201 0.1%. The clinical signs of inflammation scaling have greatly subsided with this animal presenting as a more normal clinical phenotype at the end of treatment with no evidence of dermal intolerance to treatment.

投影片 5 展示了本篇教學結尾處的典型攝影範例。左圖為接受 VYN201 車輛治療的動物。正如你所看到的，仍然存在明顯的發炎、發紅和脫屑現象。中心照片為接受 VYN201 0.1% 治療的動物。發炎鱗屑的臨床症狀已大大減輕，治療結束時，該動物表現出更正常的臨床表型，沒有證據表明皮膚對治療不耐受。

The animal treated with clobetasol cream had experienced a significant reduction in clinical signs of dermal inflammation. However, the skin presents with marked dermal toxicity with clear evidence of fine and deep wrinkling, translucency and lack of elasticity. Although clearly undesirable, these phenomena are expected based on well-known skin toxicities from topically applied glucocorticosteroid treatment.

使用氯倍他索乳膏治療的動物，其皮膚發炎的臨床症狀明顯減輕。然而，皮膚表現出明顯的皮膚毒性，有明顯的細紋和深紋、半透明和缺乏彈性。雖然這些現象顯然是不受歡迎的，但根據局部應用糖皮質激素治療引起的眾所周知的皮膚毒性，這些現像是可以預期的。

Slide 6 presents with the effect of VYN201 on inhibiting the release of key inflammatory cytokines from human skin tissue in comparison with the JAK1/2 inhibitor ruxolitinib and the glucocorticosteroid, betamethasone. This ex vivo assay uses harvested human skin tissue that has been stimulated to produce a TH17 inflammatory phenotype through the impact of VYN201 on the release of several TH17 cytokines was evaluated in comparison to untreated controls.

幻燈片 6 展示了 VYN201 對抑制人體皮膚組織中關鍵發炎細胞因子釋放的影響，並與 JAK1/2 抑制劑魯索替尼和糖皮質激素倍他米松進行了比較。此離體試驗採用採集的人類皮膚組織，透過 VYN201 對幾種 TH17 細胞因子釋放的影響進行刺激，從而產生 TH17 發炎表型，並與未處理的對照組進行比較。

In these examples, cytokine release was inhibited by greater than 95% relative to untreated control. And in this graph, the example of Interleukin 17, the effect of VYN201 was demonstrated to be statistically superior to both active comparators. This confirms the findings from the preclinical model I presented earlier and demonstrates the potent inflammatory inhibitory potential of VYN201 for the treatment of diseases driven by TH17 immunology.

在這些例子中，與未處理的對照組相比，細胞激素釋放抑制率超過 95%。在該圖中，以白細胞介素 17 為例，VYN201 的效果在統計學上優於兩種活性對照藥物。這證實了我之前提出的臨床前模型的研究結果，並證明了 VYN201 在治療由 TH17 免疫驅動的疾病方面具有強大的發炎抑制潛力。

Now we move to the most recent announcement relating to the valuation of VYN201 in the preclinical model of skin healing. Although diverse in etiology, neutrophilic dermatosis commonly present as ulcers or readily compromise pustules or blisters in the skin. This requires rapid intervention to halt further tissue description and allow innate skin repair mechanisms to facilitate lesion healing and closure. As such, it's important to show that any potential treatment for these diseases does not interfere with these processes. So the primary objective of this study was to demonstrate that our topical VYN201 product would not delay skin tissue healing.

現在我們來看看與 VYN201 在皮膚癒合臨床前模型中的估值相關的最新公告。雖然病因各異，但嗜中性球性皮膚病通常表現為皮膚潰瘍或易損膿皰或水皰。這需要迅速乾預，以阻止進一步的組織損傷，並讓皮膚自身的修復機制促進病變癒合和閉合。因此，必須證明任何針對這些疾病的潛在治療方法都不會幹擾這些過程。因此，本研究的主要目的是證明我們的外用 VYN201 產品不會延緩皮膚組織癒合。

In this model, 2 identical incisions were made on either side of the flank of hairless mice under anesthesia. 3 treatment groups were treated topically once-daily with either VYN201 vehicle, VYN201 1% or a hydroalcoholic gel control that is known to delay lesion healing and closure.

在這個模型中，在麻醉狀態下，於無毛小鼠的側腹兩側各切開一個相同的切口。3 個治療組每天局部使用 VYN201 賦形劑、1% VYN201 或已知會延緩病灶癒合和閉合的水醇凝膠對照劑進行治療。

The graph on the left presents global external lesion healing score by treatment day. The global external lesion healing score is a composite score comprising of lesion length, width, degree of swelling and overall lesion visibility. It was anticipated that VYN201 1% would perform similarly to vehicle in this model and therefore, confirming that the BET inhibitor active ingredient would not impact on the time to -- for lesion healing and closure, unlike the hydroalcoholic gel control.

左側圖表顯示了按治療日期劃分的全球外部病變癒合評分。全球外部病灶癒合評分是一個綜合評分，包括病灶長度、寬度、腫脹程度和病灶整體可見度。預計 VYN201 1% 在此模型中表現與載體相似，因此證實 BET 抑制劑活性成分不會影響病變癒合和閉合的時間，這與水醇凝膠對照組不同。

As early as treatment day 5, there is a statistically significant improvement in lesion healing score for VYN201 1% compared to the hydroalcoholic gel, and this continues for the remainder of the treatment period. The meantime to heal for VYN201 1% and vehicle was 15.5 days, whereas the meantime to heal for the hydroalcoholic gel was approximately 5 days later. Based upon these results, VYN201 1% does not appear to negatively impact skin repair mechanisms.

早在治療第 5 天，VYN201 1% 與水醇凝膠相比，病變癒合評分就有了統計學上的顯著改善，並且這種改善一直持續到治療結束。VYN201 1% 和載體的平均癒合時間為 15.5 天，而水醇凝膠的平均癒合時間約為晚 5 天。根據這些結果，VYN201 1% 似乎不會對皮膚修復機制產生負面影響。

Moving to the graph on the right. This data represents the extent of fibrotic mass formed during the healing at the end of the treatment period. Excessive fibrotic tissue deposits in a healing lesion frequently results in a poor aesthetic outcome of the resultant scar. Fibrotic tissue mass was assessed on a 4-point severity scale. Findings from this study show that both vehicle and hydroalcoholic gel treatments resulted in a moderate amount of fibrotic tissue being identified in the lesion bed after the lesions had healed. However, in comparison, there was a much lower presence of fibrotic tissue mass in the VYN201 1% treatment group, which is indicative of the anti-fibrotic mechanism of action for BET inhibitors.

接下來看右邊的圖表。此數據代表治療期結束時癒合過程中形成的纖維化腫塊的程度。癒合病灶中過多的纖維組織沉積常常導致最終疤痕的美觀效果不佳。纖維化組織量以 4 分制嚴重程度評分。此研究結果表明，載體和水醇凝膠治療均導致病變癒合後病變床中出現中等量的纖維化組織。然而，相較之下，VYN201 1% 治療組中纖維化組織質量明顯較低，這表明 BET 抑制劑具有抗纖維化作用機制。

This slide presents typical examples of photography at the end of the treatment. The left photograph is of an animal treated with VYN201 vehicle. As you can see, there is residual swelling and the scars are still clearly visible. The central photograph is of an animal treated of VYN201 1%. There is little evidence of residual swelling, and the lesions are flatter and less distinct in comparison with the other treatment groups. On the right, animals treated with hydroalcoholic gel have clearly definable scars with significant residual swelling and scabbing still present.

此投影片展示了治療結束時拍攝的典型照片範例。左圖為接受 VYN201 車輛治療的動物。正如你所看到的，仍有殘留腫脹，疤痕仍然清晰可見。中心照片是接受 VYN201 1% 治療的動物。幾乎沒有殘餘腫脹的跡象，與其他治療組相比，病灶更扁平、更不明顯。右側，用含水酒精凝膠治療的動物身上有清晰可見的疤痕，但仍有明顯的殘留腫脹和結痂。

In conclusion, we are very satisfied with the preliminary data we have generated with VYN201. VYN201 significantly reduces the expression of several key pro-inflammatory cytokines relevant to TH17 mediated autoimmune diseases, and has demonstrated improvement in reducing fibrotic tissue mass and overall skin repair outcomes. These initial data validate our earlier belief of the broad utility and attractiveness of this platform, and is addressing disregular immune activity in several serious autoimmune diseases.

總之，我們對使用 VYN201 產生的初步數據非常滿意。VYN201 顯著降低了與 TH17 介導的自體免疫疾病相關的幾種關鍵促炎細胞因子的表達，並已證明可改善減少纖維化組織量和整體皮膚修復效果。這些初步數據證實了我們先前對該平台的廣泛實用性和吸引力的看法，並且正在解決幾種嚴重自體免疫疾病中的免疫活動異常問題。

We continue to work diligently to generate additional data on BET inhibitor pharmacology and epigenetics. The prerequisite IND-enabling non-clinical safety program is underway. And we intend to enter VYN201 into the clinic in 2022. We look forward to providing additional updates as the program progresses.

我們將繼續努力，以獲取更多關於 BET 抑制劑藥理學和表觀遺傳學的數據。提交 IND 申請所需的非臨床安全性研究計劃正在進行中。我們計劃在 2022 年將 VYN201 投入臨床試驗。隨著專案的推進，我們將提供更多最新消息。

With that, I will now pass the call back to Dave. Dave?

接下來，我會把電話轉回給戴夫。戴夫？

Thanks, Iain. We're very excited about the future direction of the company, and we are quickly building momentum across our pipeline of novel and highly differentiated candidates, each with the opportunity to address significant unmet medical need in immunoinflammatory diseases.

謝謝你，伊恩。我們對公司的未來發展方向感到非常興奮，我們正在迅速推進一系列新穎且高度差異化的候選藥物的研發，每一種都有機會解決免疫發炎疾病領域尚未滿足的重大醫療需求。

As I previously mentioned, we intend to leverage our existing development capabilities and strong network of discovery and preclinical science partners to develop products and advance a series of truly innovative new medicines through the clinic.

正如我之前提到的，我們打算利用我們現有的研發能力和強大的發現和臨床前科學合作夥伴網絡來開發產品，並透過臨床試驗來推進一系列真正創新的新藥。

Our key priorities are to complete the divestiture of the minocycline franchise and advance the pipeline. Over the next 12 to 18 months, we anticipate multiple milestones and early-stage development catalysts for our programs. As we move toward 2022, creating shareholder value remains front and center for our company, and we look forward to providing further updates on our progress.

我們的主要任務是完成米諾環素特許經營權的剝離，並推動產品線的開發。在接下來的 12 到 18 個月裡，我們預計我們的專案將迎來多個里程碑和早期發展催化劑。展望 2022 年，創造股東價值仍然是我們公司的首要任務，我們期待就我們的進展提供更多最新消息。

This concludes our prepared remarks. I will now turn the call back to the operator and open the call for questions. Thanks.

我們的發言稿到此結束。現在我將把通話轉回給接線員，並開放提問環節。謝謝。

(Operator Instructions) The first question comes from David Amsellem with Piper Sandler.

（操作說明）第一個問題來自 Piper Sandler 的 David Amsellem。

So I just had a few, starting with 201 and 202. And this is kind of a high-level question, but I thought it's important to ask. I mean, just given the underlying mechanism of these compounds, do you have a sense for what specific indications you think would be most appropriate for both 201 and 202? I know that's early, but wanted to just hear your thoughts on this sort of white space area.

所以我只有幾個，從 201 和 202 開始。這是一個比較宏觀的問題，但我認為有必要問一下。我的意思是，僅就這些化合物的潛在機製而言，您是否覺得 201 和 202 最適合用於哪些特定適應症？我知道現在問這個問題還為時過早，但我還是想聽聽你對這種空白領域的看法。

And to the extent that you move forward with both, should we think about sort of the topical being used in sort of a more mild-to-moderate disease setting and the oral being used in a more moderate-to-severe sort of disease setting as we see with other classes, like, for instance, the JAK inhibitors. So just help us understand your thought process there.

如果兩者都繼續推進，我們是否應該考慮將局部用藥用於輕度至中度疾病，將口服藥物用於中度至重度疾病，就像我們在其他類別（例如 JAK 抑制劑）中看到的那樣？所以，請您幫我們理解您的思考過程。

And then for 114, just understanding -- knowing what we know about the JAK inhibitors, I guess the question here is from a safety tolerability perspective, not just that, but also from an efficacy perspective, given the nature of the market. What do you have to really see to make a go, no-go decision after you get your data next year?

至於第 114 點，考慮到我們對 JAK 抑制劑的了解，我想這裡的問題不僅是從安全性和耐受性的角度來看，而且考慮到市場的性質，還要從療效的角度來看。明年拿到數據後，究竟需要看到什麼才能做出是否繼續前進的決定？

David, it's Dave. You're breaking up a bit. So if I can summarize and just tell me if this is what you're looking for. I think it was for 201 and 202 for our BET platform where the initial indications could potentially be, it's obviously early. We have some thoughts on that.

大衛，我是戴夫。你有點心不在焉。所以，我可以簡單總結一下嗎？請告訴我這是否符合您的需求。我認為那是我們 BET 平台的 201 和 202 版本，初步跡象可能表明，現在顯然還為時過早。我們對此有一些想法。

The second question, I believe, was whether or not we would take the topical into more mild-to-moderate disease states versus moderate-to-severe? And the third question, I believe you were looking for clarity on perhaps 114 relative to what's going on in the JAK class, but if you could confirm or let me know if there something else?

我認為第二個問題是，我們是否會將局部用藥應用於輕度至中度疾病狀態，而不是中度至重度疾病狀態？第三個問題，我相信您是想了解關於JAK級114號艦艇的情況，但如果您能確認一下或告訴我還有其他情況，那就太好了？

Yes. No, that's exactly right. Yes. Sorry for the bad connection.

是的。沒錯，完全正確。是的。抱歉，網路連線不好。

Okay. I will start with the JAK program and how we do our products. I don't know, Iain, you want to provide some color on how we see the benefits and the advantages of FMX114?

好的。我將從JAK專案以及我們產品的生產方式開始介紹。伊恩，我不知道，你想詳細說說我們如何看待FMX114的益處和優點嗎？

Sure. So in relation to 114 and how we see it, obviously, differentiating relative to others in the space and obviously, the recently approved topical JAK inhibitor from inside. So as Dave kind of covered also in the prepared remarks, we do see this as a -- the key benefits here being a multimodal impact on the disease stay itself. The top setting of the JAK inhibitor itself, we know obviously can have exquisite impact on down-regulating key cytokines to drive inflammation in the skin in atopic dermatitis. But also we see great utility and actually preventing some of these autoreactive lymphocytes CK immune cells from moving into the skin in the first place, where they actually unload the majority of these pro-inflammatory cytokines that drive the disease. So this is where fingolimod comes in. And fingolimod itself has the potential to inhibit and retain these autoreactive lymphocyte in the lymph nodes and therefore, prevent those cells moving into the skin in the first place. So this is the extracellular mechanism that Dave talked about in the prepared remarks.

當然。所以，就 114 而言，我們顯然要從內部看待它，因為它與該領域的其他藥物以及最近核准的局部 JAK 抑制劑有所不同。正如戴夫在準備好的演講稿中也提到的那樣，我們認為這是——這裡的主要好處是對疾病本身的多模式影響。我們都知道，JAK 抑制劑的最高濃度顯然可以對下調關鍵細胞因子以驅動異位性皮膚炎皮膚發炎產生顯著影響。但我們也看到了它的巨大作用，實際上可以阻止一些自體反應性淋巴細胞 CK 免疫細胞首先進入皮膚，因為它們會釋放大部分驅動疾病的促炎細胞因子。所以，芬戈莫德就派上用場了。芬戈莫德本身俱有抑制和保留淋巴結中這些自身反應性淋巴細胞的潛力，因此，從根本上阻止這些細胞進入皮膚。這就是戴夫在準備好的演講稿中提到的細胞外機制。

But what we've also found and others have found that fingolimod itself has the potential to up-regulate a key skin structure protein called filaggrin. That actually is really important in maintaining the epithelia and skin epidermis. Now we know that atopic dermatitis is really a skin -- a disease state where the epidermis is effectively missing. So the ability to prospectively support recovery of the epidermis as the anti-inflammatory effects of the treatments are working is a key component. And that's how we see it being quite differentiated away from any of the other topical products, whether it be our JAK inhibitor or others who certainly don't have that potential. I hope that answers your question on that.

但我們和其他人也發現，芬戈莫德本身有可能上調一種名為絲聚蛋白的關鍵皮膚結構蛋白。這對於維持上皮和皮膚表皮的健康至關重要。現在我們知道，異位性皮膚炎實際上是一種皮膚疾病，其特徵是表皮實際上缺失。因此，在治療發揮抗發炎作用的同時，能否促進表皮的恢復是一個關鍵因素。正因為如此，我們認為它與其他任何外用產品都截然不同，無論是我們的 JAK 抑制劑還是其他產品，它們肯定不具備這種潛力。希望這能解答你的疑問。

Yes. I'll just add to, obviously, we're in a middle of our Ib component of this Phase Ib/IIa study for 114. The Ib component will provide meaningful PK data, which obviously would be helpful, especially in light of the recent class labeling around JAK inhibitors. Yes, it certainly appears that even though it's class label for all JAKs that. This is really focusing -- or the view from the FDA was focusing primarily on systemic JAKs. Dermatologists who are prescribed these products, they're using these types of labels. And we feel obviously very good about the prospects of this product, assuming it gets all the way through the clinic. And we hope to have obviously the top line results in the early part of the first quarter of next year. The PK data we should have before the end of the year. So we're quite bullish on the prospects of this program.

是的。我還要補充一點，顯然，我們目前正處於 114 號藥物 Ib/IIa 期研究的 Ib 部分中期。Ib 成分將提供有意義的 PK 數據，這顯然會很有幫助，尤其是在最近 JAK 抑制劑類別標籤發布的情況下。是的，儘管它是所有 JAK 的類別標籤，但看起來確實如此。這確實非常關注——或者說，FDA 的觀點主要關注的是系統性 JAK 疾病。皮膚科醫生在開這些產品時，都會使用這類標籤。我們顯然對這款產品的前景非常樂觀，前提是它能順利通過臨床試驗。我們希望在明年第一季初獲得初步業績報告。我們應該在年底前獲得PK數據。因此，我們對這個專案的前景非常看好。

I think on the 201, 202 BET inhibitor programs, as we outlined, we're very early. The -- in development of both of these programs, the preclinical data that we've seen so far for 201, we're quite enthusiastic, quite pleased with. We're going to continue to take this model through a battery of additional animal models of biomarker studies that are ongoing. We're doing the prerequisite tox work for 201 now. There seems to be a significant level of enthusiasm from our scientific ad board and the general scientific community. We think that this program gives us a lot of utility. There's a lot of flexibility for where this product can go.

我認為，正如我們之前概述的那樣，關於 201、202 BET 抑制劑計劃，我們還處於非常早期的階段。——在這兩個計畫的開發過程中，我們目前看到的 201 的臨床前數據，我們感到非常振奮，非常滿意。我們將繼續利用一系列正在進行的生物標記研究的其他動物模型來驗證此模型。我們現在正在進行 201 課程的毒理學預備工作。我們的科學顧問委員會和整個科學界似乎都展現了極大的熱情。我們認為這個程式對我們很有幫助。這款產品的應用範圍非常廣泛。

We've talked about some of the more rare skin disease arenas. We've mentioned some pyoderma gangrenosum and others. We're going to hold off on putting a line or stand on where we're exactly going to take it. We're really excited about where it could go. I think there are several different arenas. Ultimately, we want to develop products that address unmet needs for patients. And we think that this platform could do that.

我們已經討論了一些比較罕見的皮膚病領域。我們提到了一些壞疽性膿皮症和其他疾病。我們暫且不劃定界線或立場，明確我們將採取什麼行動。我們對其未來的發展前景感到非常興奮。我認為有好幾個不同的領域。最終，我們希望開發出能夠滿足患者未被滿足的需求的產品。我們認為這個平台可以做到這一點。

So you can anticipate that. I don't -- I wouldn't characterize it, David, as being mild-to-moderate versus moderate-to-severe. I'd say ultimately, the data is going to drive where we go. But I think as we've shown, as Iain showed today, there's a potent anti-inflammatory effect from this BET inhibitor platform. And we think that gives us a lot of flexibility on where we can take this particular product.

所以你可以預料到這一點。我不認為——大衛，我會把它描述為輕度到中度，而不是中度到重度。我認為最終，數據將決定我們的發展方向。但我認為，正如我們已經展示的，正如伊恩今天所展示的，這個 BET 抑制劑平台具有強大的抗發炎作用。我們認為這讓我們在產品發展方向上擁有很大的彈性。

I think when it comes to 202, as we've mentioned when -- last quarter, I would envision we'd be looking at some of the more broader I&I indications. Again, without specifically locking in on a particular disease, we've talked about -- and our ad board saw that could have potential in RA, it could have the potential for IBD Crohn's, MS. Obviously, there's been work done in various oncology settings. Myeloproliferative diseases is, one, whether or not we would go there ourselves would yet to be determined. But again, I think that the utility of this platform is quite significant. So we're eager to advance both these programs. And as it gets further down the line, we'll obviously be able to lock-in on specifically where we take these programs for its first indication, both for a topical BETi as well as the oral BETi once we -- upon completion of final candidate selection. So hopefully, that helps, David.

我認為，就 202 而言，正如我們在上個季度提到的那樣，我設想我們會關註一些更廣泛的 I&I 指標。再次強調，雖然我們沒有具體針對某種疾病，但我們討論過——我們的顧問委員會也認為它可能對類風濕性關節炎、發炎性腸道疾病、克隆氏症和多發性硬化症都有潛在療效。顯然，在各種腫瘤治療領域也已經進行了相關研究。骨髓增生性疾病就是其中之一，至於我們是否會親自涉足其中，仍有待確定。但我仍然認為這個平台的實用性非常重要。因此，我們渴望推進這兩個項目。隨著研究的深入，一旦我們完成最終候選藥物的選擇，我們顯然就能確定這些項目最初的適應症，包括局部使用 BETi 和口服 BETi。希望這對你有幫助，大衛。

The next question comes from Louise Chen with Cantor Fitzgerald.

下一個問題來自 Cantor Fitzgerald 公司的 Louise Chen。

This is Carvey in for Louise. We have a few questions here. First, what is the breakdown of product sales? How much of it was coming from AMZEEQ? How much was it from ZILXI? We're interested in tracking the progress in these products.

這是卡維代替路易絲上場。我們這裡有幾個問題。首先，產品銷售組成是什麼？其中有多少來自AMZEEQ？ZILXI 的價格是多少？我們有興趣追蹤這些產品的進度。

Second, ahead of the Phase Ib/IIa POC data for 114, can you remind us how we should interpret the data once they come out? And lastly on 201, on the presentation, there's a lot of promising images of the mouse model compared to vehicles, steroid, alcohol gel, and you also included ex vivo analysis against a JAK inhibitor. So I just wanted to see if you have done the same mouse model testing against a JAK and see the comparison? If so, what are the takeaways there?

其次，在 114 的 Ib/IIa 期 POC 數據公佈之前，您能否提醒我們一下，一旦數據公佈，我們應該如何解讀這些數據？最後，在 201 節的簡報中，有許多關於小鼠模型與載體、類固醇、酒精凝膠相比的有前景的圖片，而且你還加入了針對 JAK 抑制劑的體外分析。所以我想看看你是否也對這款滑鼠模型進行了與JAK的對比測試，並比較了結果？如果真是如此，那麼我們能從中學到什麼教訓呢？

Breakdown of sales.

銷售明細。

Yes, sure. This is Tyler. I'll take the first question on the breakdown of sales. So for the quarter, we had $4 million of product sales for AMZEEQ and ZILXI. We have not historically disclosed the breakdown and haven't provided guidance on what the split between products is.

當然可以。這是泰勒。我先回答第一個關於銷售額組成的問題。因此，本季 AMZEEQ 和 ZILXI 的產品銷售額為 400 萬美元。我們歷來沒有揭露具體的細分數據，也沒有提供過關於各產品之間比例如何劃分的指導意見。

What I can point you to is if you take a look at the script data just from a relative proportion, that can give you a general direction. But at this point in time, we're not going to break the products down.

我可以告訴你的是，如果你只從相對比例的角度查看腳本數據，就能得到一個大致的方向。但目前我們不會對這些產品進行詳細拆解。

Iain, do you want to talk about the Ib/IIa related to 114 and…

伊恩，你想談談與 114 號化合物相關的 Ib/IIa 嗎？

So yes, the primary endpoint will be change in atopic dermatitis severity index. So maybe just back up to the design itself. So the Phase 1b patients will be -- 6 patients will be treated for 2 weeks. As Dave said earlier, we're primarily evaluating obviously safety and pharmacokinetic inflammation. The Phase 2a portion of the study is 4 weeks with an additional 2 weeks open-label study. Same endpoints there. So as I said, we're looking to report the data kind of in early part of Q1 next year.

所以，是的，主要終點將是異位性皮膚炎嚴重程度指數的變化。所以或許應該回到設計本身。因此，1b 期患者將有 6 名患者接受為期 2 週的治療。正如戴夫之前所說，我們主要評估的是安全性和藥物動力學發炎。研究的 2a 期部分為期 4 週，另加 2 週的開放標籤研究。終點相同。正如我所說，我們計劃在明年第一季初公佈相關數據。

And then I think, Carvey, your question was on comparative information in the animal models for the BET inhibitor, topical BET inhibitor. We haven't done that yet, although that is certainly something we will be focusing on. We traditionally use glucocorticosteroids as a control, but it's certainly something that will start to grow as we start to hone in on indications later.

然後我想，Carvey，你的問題是關於 BET 抑制劑、局部 BET 抑制劑的動物模型中的比較資訊。我們還沒有這樣做，但這無疑是我們將重點關注的事情。我們傳統上使用糖皮質激素作為對照，但隨著我們日後開始逐步明確適應症，它肯定會得到更廣泛的應用。

(Operator Instructions) The next question comes from Patrick Dolezal with LifeSci Capital.

（操作說明）下一個問題來自 LifeSci Capital 的 Patrick Dolezal。

So for the BET inhibitors asset class, just curious what safety effects have emerged clinically? And kind of what gives you confidence that these may be averted by a topical approach in the case of 201 and the selective BD2 approach in the case of 202? And then just perhaps if you could detail the items outstanding to IND submission for each of those. That would be helpful.

所以，對於BET抑制劑這類資產類別，我很好奇臨床上出現了哪些安全性問題？是什麼讓您確信，對於 201 號病例，局部治療方法可以避免這些問題；對於 202 號病例，採用選擇性 BD2 治療方法可以避免這些問題？然後，或許您可以詳細列出每項提交 IND 申請所需提交的項目。那會很有幫助。

Patrick, it's Iain. So as you know, the majority of BET inhibitors in development are pan BD. So they bind to BD1 and BD2. They're orally available and they are primarily for oncology indications although there's one in the cardiovascular space.

派崔克，我是伊恩。如您所知，目前正在研究的大多數 BET 抑制劑都是泛 BD 抑制劑。所以它們會與BD1和BD2結合。它們可口服，主要用於腫瘤治療，但也有一種用於心血管領域。

So why do we think ours are differentiated from there? I think we'll start with what the types of adverse events you can typically see for an orally available pan BD inhibitor. They tend to be things like thrombocytopenias, gastrointestinal toxicities, emesis, vomiting, that kind of thing, flushing.

那麼，我們為什麼認為我們的與他們的不同呢？我想我們先從口服泛BD抑制劑通常可能出現的不良反應類型開始說起。它們通常包括血小板減少症、胃腸道毒性、嘔吐、潮紅之類的症狀。

Moving to 201. So topical, but inherently, we have assumed we’ll have a reduced systemic exposure there. But I think primarily, we actually have factored in a metabolic liability into the molecule itself as part of the design principles from medicinal chemistry. So what that effectively means is that any 201 that is systemically exposed by the topical route will be rapidly cleared by the liver and inactivated. So that's a way where we're -- it's like a 1, 2 punch there, one go topical and one induced as soft drug approach where we're specifically and consciously introducing a metabolic liability.

搬到 201。所以，雖然這很應景，但從本質上講，我們一直認為在那裡的系統性暴露會減少。但我認為，主要原因在於，我們實際上已經將代謝缺陷作為藥物化學設計原則的一部分，納入了分子本身的考量。因此，這實際上意味著，任何透過局部途徑系統性暴露的 201 都會被肝臟迅速清除並失去活性。所以，這就是我們目前所採取的方法──就像一記組合拳，一記局部用藥，另一記誘導性軟性藥物療法，我​​們有意地、有意識地引入代謝缺陷。

On 202, the way we're addressing the pan BD toxicity question is that certainly evolving information from others and with our own data, that if you selectively bind to BD2, you tend to have an improved safety profile in general terms. Secondarily, it appears that majority of pro-inflammatory signaling or genes that are activated -- pro-inflammatory genes that are activating tend to be driven mostly through BD2 rather than BD1. BD1 has been implicated in driving the activation of genes and a lot of housekeeping genes. The work that In4Derm have done today, I covered off in the prepared remarks. We have exquisitely potent and highly, highly selective BD2 selected components already. And of course, we're developing additional work that goes on there.

關於 202，我們解決泛 BD 毒性問題的方法是，根據其他人提供的最新資訊以及我們自己的數據，如果選擇性地與 BD2 結合，則總體上往往會有更好的安全性。其次，大多數被活化的促炎訊號或基因——被活化的促炎基因——似乎主要透過 BD2 而不是 BD1 驅動。BD1 已被證實能夠活化基因和許多管家基因。In4Derm今天所做的工作，我在事先準備好的演講稿中已經介紹了。我們已經擁有效力極強、選擇性極高的 BD2 精選成分。當然，我們還在開發其他相關的工作。

So I think that we are really addressing that from 2 components to the 2 projects. One is about a metabolic liability and going topical with 201 and 202 going for a very selective BD2 inhibitor.

所以我認為我們正在從兩個組成部分到兩個專案來解決這個問題。其中之一是關於代謝缺陷，採用局部用藥，使用 201 和 202 作為非常選擇性的 BD2 抑制劑。

That's helpful. And just one follow-up. The preclinical data on composite inflammation severity in this med inflammation model looks solid, very comparable to steroids. Just curious, should we be thinking about the magnitude of effect observed here or more so just that it's directionally favorable? And then as it relates to the biomarker data, are there any biomarkers in particular that are known to be pathogenic in a given disease state or giving your excitement about future clinical development?

那很有幫助。還有一個後續問題。此藥物發炎模型中複合炎症嚴重程度的臨床前數據看起來很可靠，與類固醇非常相似。我只是好奇，我們應該考慮這裡觀察到的效應的大小，還是更應該考慮它在方向上是有利的？那麼，就生物標記數據而言，是否有任何已知的生物標記在特定疾病狀態下具有致病性，或者讓您對未來的臨床開發感到興奮？

Yes. So just on your last point there, the fact that we have significant impact and pretty much all cytokines that drive TH17 immunology is particularly exciting. You saw from the slide there, we -- I mean, obviously, we have significantly done rely in IL-17, IL-6 and others. So again, this speaks to the broad applicability as an anti-inflammatory agent.

是的。所以，就你剛才提到的最後一點而言，我們對幾乎所有驅動 TH17 免疫的細胞激素都產生了重大影響，這一點尤其令人興奮。從幻燈片中可以看到，我們——我的意思是，很顯然，我們已經在很大程度上依賴 IL-17、IL-6 和其他細胞因子。所以，這再次說明了它作為抗發炎劑的廣泛適用性。

Secondarily, we were effectively equipotent to a class 1 super potent steroid, which is quite rare for certainly newer generation of anti-inflammatory agents. So I think to your earlier question, you should think about the potential of having that super potent anti-inflammatory effect. But without the specific liabilities you would tend to see in long-term use of glucocorticosteroids.

其次，我們的藥物效力與 1 類超強效類固醇相當，這對新一代抗發炎藥物來說非常罕見。所以，對於你之前的問題，我認為你應該考慮一下它具有超強抗炎作用的潛力。但它沒有長期使用糖皮質激素可能帶來的特定副作用。

Yes. Just about piggyback on this, Patrick, clobetasol, Iain outlined, the super potent steroid, that's a far cry from the over-the-counter hydrocortisone and steroids that are out there, it's deemed a class 1, and there's a reason why it's called a super potent steroid because it's just that. And the fact that we -- again, obviously, this is early day in preclinical data. But the fact that we saw that level of response in line with what you see from clobetasol super potent steroids, yet initial -- tolerability data being very positive and encouraging, just gives us a lot of enthusiasm about the prospects of, obviously, this molecule and this program, but for the entire platform.

是的。派崔克，順便提一下，伊恩概述道，氯倍他索是一種超級強效的類固醇，它與市面上常見的非處方氫化可的松和類固醇截然不同，它被歸類為 1 類藥物，它被稱為超級強效類固醇是有原因的，因為它的確如此。而且，我們——再次強調，這顯然還處於臨床前數據的早期階段。但事實上，我們看到了與氯倍他索這種超強效類固醇類似的反應水平，而且初步的耐受性數據非常積極和令人鼓舞，這讓我們對這種分子和這個項目的前景充滿熱情，當然，也對整個平台的前景充滿熱情。

This concludes the question-and-answer session. I would now like to turn the conference back over to management for any closing remarks.

問答環節到此結束。現在我將會議交還給管理階層，請他們作總結發言。

Well, thank you, operator, and thanks to everyone that took time out of your schedules to join this call. We look forward to continuing to provide an update on the progress of our business, and we wish everyone an enjoyable holiday season that's coming up over the course of the next few weeks. We look forward to speaking with everyone soon. Thanks, and have a great rest of the week.

謝謝接線員，也感謝所有抽出時間參加本次通話的朋友們。我們期待繼續向大家報告公司業務進度，並祝福大家在接下來的幾週度過一個愉快的假期。我們期待盡快與大家交流。謝謝，祝你本週餘下的日子過得愉快。

This concludes today's conference call. You may disconnect your lines. Thank you for participating, and have a pleasant day.

今天的電話會議到此結束。您可以斷開線路。感謝您的參與，祝您有個愉快的一天。