Brickell Biotech Inc (BBI) 2022 Q2 法說會逐字稿

Welcome, everyone, to the Brickell Biotech Second Quarter 2022 Financial Results Conference Call. (Operator Instructions)

歡迎大家參加 Brickell Biotech 2022 年第二季財務業績電話會議。 （操作員說明）

As a reminder, this conference call is being recorded. I would now like to turn the call over to Garth Russell from LifeSci Advisors, Garth?

謹此提醒，本次電話會議正在錄音中。我現在想將電話轉給 LifeSci Advisors 的 Garth Russell，Garth？

Thank you, operator, and good afternoon, everyone. Joining me on today's call are Brickell's Chief Executive Officer, Rob Brown; President and Chief Operating Officer, Andy Sklawer; Chief Financial Officer, Bert Marchio; Chief Medical Officer, Dr. Monica Luchi; and Chief R&D Officer, Deepak Chadha.

謝謝接線員，大家下午好。參加今天電話會議的還有 Brickell 執行長 Rob Brown；總裁兼營運長 Andy Sklawer；財務長伯特·馬爾基奧；首席醫療官 Monica Luchi 博士；和首席研發長 Deepak Chadha。

Before we begin, I would like to remind everyone that this conference call and webcast will contain forward-looking statements about the company. These statements are subject to risks and uncertainties that could cause actual results to differ. Please note that these forward-looking statements reflect our opinions only as of the date of this call. We will not undertake obligation to revise or publicly release the results of any revisions to these forward-looking statements in light of new information or future events.

在開始之前，我想提醒大家，本次電話會議和網路廣播將包含有關公司的前瞻性陳述。這些陳述存在風險和不確定性，可能導致實際結果有所不同。請注意，這些前瞻性陳述僅反映我們截至本次電話會議之日的觀點。我們不承擔根據新資訊或未來事件修改或公開發布這些前瞻性陳述的任何修改結果的義務。

Factors that could cause actual results or outcomes to differ materially from those expressed or implied by such forward-looking statements are discussed in greater detail in our most recent filings on Form 10-K and other periodic reports on Form 10-Q and 8-K filed with the SEC.

我們最近提交的表格 10-K 以及其他定期報告的表格 10-Q 和 8-K 中更詳細地討論了可能導致實際結果或結果與此類前瞻性陳述明示或暗示的結果存在重大差異的因素。向SEC 提交。

It is now my pleasure to turn the call over to the company's Chief Executive Officer, Rob Brown. Rob, the floor is yours.

現在我很高興將電話轉給公司執行長羅布·布朗。羅布，地板是你的。

Thanks, Garth. Good afternoon, everyone, and thanks for joining our call today. This is an exciting time for us as a company, as we continue to advance our development pipeline of cutting-edge autoimmune and inflammatory therapies. This is highlighted by BBI-02, our potent first-in-class DYRK1A inhibitor, BBI-10, a novel STING inhibitor and our platform of next-generation kinase inhibitors. These programs now define our company as we strive to transform patients' lives by developing innovative therapeutics and generate value for our shareholders.

謝謝，加斯。大家下午好，感謝您今天加入我們的電話會議。對於我們公司來說，這是一個激動人心的時刻，因為我們將繼續推進尖端自體免疫和發炎療法的開發管道。 BBI-02（我們強效的一流 DYRK1A 抑制劑）、BBI-10（一種新型 STING 抑制劑）和我們的下一代激酶抑制劑平台突顯了這一點。這些項目現在定義了我們公司，因為我們努力透過開發創新療法來改變患者的生活並為股東創造價值。

During the second quarter, we initiated an announced dosing of the first patient in a Phase I study of our lead DYRK1A inhibitor program, BBI-02. Advancement of BBI-02 into the clinic is a significant milestone for both our company and this novel target, as it marks the first time a DYRK1A inhibitor intended for patients with autoimmune diseases, has been orally administrated in humans. We are pleased with the progress in this study thus far and remain on track to report SAD and MAD top line results by early 2023. In addition, preclinical development activities are underway for BBI-10, our lead STING inhibitor candidate that we acquired earlier this year.

在第二季度，我們宣布對我們的主要 DYRK1A 抑制劑項目 BBI-02 的 I 期研究中的第一位患者進行給藥。 BBI-02 進入臨床對我們公司和這個新標靶來說都是一個重要的里程碑，因為它標誌著針對自體免疫疾病患者的 DYRK1A 抑制劑首次在人類中口服給藥。我們對這項研究迄今為止的進展感到高興，並將繼續按計劃在2023 年初報告SAD 和MAD 的頂線結果。早些時候獲得的主要STING 抑制劑候選藥物年。

Finally, I'd like to briefly touch on sofpironium bromide, or SB for short, for the treatment of primary axillary hyperhidrosis, which we sold to Botanix this past May. Botanix recently publicly stated that it plans to submit the NDA for SB gel 15% to the FDA in the third quarter of 2022. This is, of course, relevant to Brickell as we are eligible to receive various regulatory and sales milestone payments as well as tiered earnout payments ranging from high single digits to mid-teen digits on net sales of sofpironium bromide gel. We look forward to sharing any additional updates regarding this program as they become available.

最後，我想簡單介紹一下索吡溴銨（簡稱 SB），用於治療原發性腋窩多汗症，我們在今年 5 月將其出售給了 Botanix。 Botanix 最近公開表示，計劃在 2022 年第三季度向 FDA 提交 SB gel 15% 的 NDA。銷售額，分級支付報酬範圍從高個位數到中位數。我們期待分享有關此計劃的任何其他更新。

Now I'll pass it over to Monica to provide an update on our ongoing pipeline development activities. Monica?

現在我將把它交給莫妮卡，以提供我們正在進行的管道開發活動的最新資訊。莫妮卡？

Thanks, Rob, and good afternoon, everyone. We've had a very productive first half of 2022, and we look to continue delivering on this trend in the second half of the year. As Rob just mentioned, during the second quarter, we initiated the Phase I clinical trial of BBI-02, our potent, highly selective and orally bioavailable DYRK1A inhibitor. This randomized double-blind placebo-controlled trial is designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of BBI-02 capsules in both healthy volunteers and subjects with atopic dermatitis, or AD for short.

謝謝羅布，大家下午好。 2022 年上半年我們非常有成效，我們希望在下半年繼續實現這一趨勢。正如Rob剛才所提到的，在第二季度，我們啟動了BBI-02的I期臨床試驗，BBI-02是我們的強效、高選擇性和口服生物可利用的DYRK1A抑制劑。這項隨機雙盲安慰劑對照試驗旨在評估 BBI-02 膠囊在健康志願者和異位性皮膚炎（簡稱 AD）受試者中的安全性、耐受性、藥物動力學和藥效學。

The first part of the study consists of a single ascending dose, or SAD, assessment of BBI-02 capsules or placebo, which is expected to enroll up to 56 healthy volunteers followed by a multiple ascending dose, or MAD, assessment of BBI-02 capsules or placebo administered once daily over 14 days in approximately 33 healthy volunteers. The study is progressing as planned. As such, we expect to initiate the MAD part of the Phase II study next month and remain on track to report top line results from both the SAD and the MAD parts of the study by early next year.

研究的第一部分包括對 BBI-02 膠囊或安慰劑進行單次遞增劑量（SAD）評估，預計將招募多達 56 名健康志願者，然後對 BBI-02 進行多次遞增劑量（MAD）評估約33 名健康志願者在14 天內每天服用一次膠囊或安慰劑。該研究正在按計劃進行。因此，我們預計下個月啟動 II 期研究的 MAD 部分，並繼續在明年初報告研究的 SAD 和 MAD 部分的頂線結果。

In the second part of the Phase I study, we plan to compare BBI-02 to placebo in approximately 40 patients with moderate-to-severe atopic dermatitis over 28 days of dosing. This part of the study is expected to include a preliminary assessment of efficacy, which will serve as an initial model for the treatment of BBI-02 in immune-mediated disease. This design fits with our broader strategy for this program during the potential to develop BBI-02 for the treatment of a broad range of autoimmune and inflammatory diseases.

在 I 期研究的第二部分中，我們計劃在大約 40 名患有中度至重度異位性皮膚炎的患者中進行 28 天的給藥比較 BBI-02 與安慰劑。這部分研究預計將包括初步療效評估，這將作為 BBI-02 治療免疫介導疾病的初始模型。這種設計符合我們在開發 BBI-02 來治療廣泛的自體免疫疾病和發炎性疾病期間對該計劃的更廣泛策略。

Based on the scientifically robust data package and promising preclinical validation that's been observed with this compound to date, we believe that BBI-02's dual node of action modulating both the adaptive and the innate immune system could represent a paradigm shift in the way we currently treat these debilitating diseases. We are excited to continue to progress this program in the ongoing Phase I clinical study over the next coming months.

基於科學上可靠的資料包和迄今為止觀察到的該化合物有希望的臨床前驗證，我們相信 BBI-02 調節適應性和先天免疫系統的雙重作用節點可能代表了我們目前治療方式的範式轉移這些使人衰弱的疾病。我們很高興能在接下來的幾個月內繼續在正在進行的一期臨床研究中繼續推進該計劃。

With respect to our novel STING inhibitor program, BBI-10, in the first quarter of this year, we acquired exclusive global rights to BBI-10 and a portfolio of other novel, potent and orally available STING inhibitors from Carna Biosciences, an established drug discovery company in Japan. STING, which stands for Stimulator of Interferon Gene, is a well-known mediator of innate immune responses. Excessive signaling through STING is linked to a number of high unmet needs, such as systemic lupus erythematosus, nonalcoholic steatohepatitis or NASH and dermatomyositis as well as a series of rare genetic interferonopathies.

關於我們的新型 STING 抑制劑專案 BBI-10，今年第一季度，我們從 Carna Biosciences（一種成熟藥物）獲得了 BBI-10 以及其他新型、強效、口服 STING 抑制劑組合的全球獨家權利日本的發現公司。 STING 代表幹擾素基因刺激劑，是一種眾所周知的先天免疫反應介質。透過 STING 的過多訊號傳導與許多未滿足的需求有關，例如係統性紅斑狼瘡、非酒精性脂肪性肝炎或 NASH 和皮肌炎以及一系列罕見的遺傳性幹擾素疾病。

Several established pharmaceutical companies are currently investing in this space, and we are looking forward to developing these next-generation STING inhibitors that we believe are differentiated through their potent covalent inhibition of STING palmitoylation. Preclinical development activities are already underway for BBI-10, which has shown strong proof of mechanism resulting in significant reduction in key pro-inflammatory cytokines and a favorable initial pharmacokinetic toxicology and safety pharmacology profile. We expect to continue to conduct these development activities throughout the rest of this year to support starting IND-enabling studies thereafter.

幾家成熟的製藥公司目前正在投資這一領域，我們期待開發這些下一代 STING 抑制劑，我們相信這些抑制劑透過對 STING 棕櫚酰化的有效共價抑製而與眾不同。 BBI-10 的臨床前開發活動已經在進行中，該藥物已顯示出強有力的機制證據，可顯著減少關鍵的促炎細胞因子，並具有良好的初始藥物動力學毒理學和安全藥理學特徵。我們預計將在今年剩餘時間內繼續進行這些開發活動，以支持此後啟動 IND 支援研究。

Before I hand the call over to Bert to review the financials, I would like to briefly touch on our library of next-generation kinase inhibitors. This includes hundreds of new chemical entities that inhibit DYRK1A, LRRK2, TTK and KLK kinases. Importantly, inhibiting these kinases have shown promising outcomes in numerous models designed to mimic a broad range of different conditions within the autoimmune, neuroinflammatory oncology and rare disease spaces. We are conducting research to identify, characterize and optimize both brain penetrant and non-brain penetrant novel kinase inhibitors, with the goal of progressing them as potential treatment options for debilitating diseases within some of these high-impact fields.

在我將電話交給伯特審查財務狀況之前，我想先簡單介紹一下我們的下一代激酶抑制劑庫。其中包括數百種抑制 DYRK1A、LRRK2、TTK 和 KLK 激酶的新化學實體。重要的是，抑制這些激酶在許多旨在模擬自體免疫、神經發炎腫瘤和罕見疾病領域的各種不同條件的模型中顯示出了有希望的結果。我們正在進行研究，以識別、表徵和優化腦滲透性和非腦滲透性新型激酶抑制劑，目標是將它們發展為某些高影響領域內衰弱疾病的潛在治療選擇。

I'd now like to pass the call over to Bert to provide a financial review for the quarter. Bert?

我現在想將電話轉接給伯特，以提供本季的財務審查。伯特？

Thanks, Monica, and good day to everyone on the call. Before I provide a summary of the second quarter 2022 financial results, I want to encourage you to read our full consolidated financial statements and MD&A contained in our report on Form 10-Q, which can be accessed through the Investors section of our website once filed with the SEC.

謝謝莫妮卡，祝所有參加電話會議的人美好一天。在我提供 2022 年第二季財務績效摘要之前，我想鼓勵您閱讀 10-Q 表格報告中包含的完整合併財務報表和 MD&A，提交後可透過我們網站的投資者部分訪問與美國證券交易委員會。

Starting with cash, the company reported $14.5 million in cash and cash equivalents as of June 30, 2022. We expect that our cash and cash equivalents, combined with $2 million from expected near-term payments under the asset purchase agreement with Botanix will support our operations for at least the next 12 months. Revenue for the second quarter of '22 was approximately $4.3 million compared to $0.2 million for the second quarter of the prior year. Revenue for the second quarter of this year consisted primarily of contract revenue recognized under the asset purchase agreement with Botanix which includes an upfront payment from Botanix of $3 million, reimbursement from Botanix of $0.6 million in development expenditures, fees for consulting services the company provided under the transition services agreement of $0.4 million and sublicense income under the asset purchase agreement of $0.3 million.

從現金開始，截至2022 年6 月30 日，該公司報告的現金和現金等價物為1,450 萬美元。 200 萬美元，將支持我們的至少在未來 12 個月內繼續營運。 2022 年第二季的營收約為 430 萬美元，而去年第二季的營收為 20 萬美元。今年第二季的收入主要包括根據與 Botanix 的資產購買協議確認的合約收入，其中包括 Botanix 的 300 萬美元預付款、Botanix 償還的 60 萬美元的開發支出、公司根據40 萬美元的過渡服務協議和30 萬美元的資產購買協議下的再授權收入。

Revenue for the same period last year consisted of royalty revenue we recognize from the sales of ECCLOCK or SB gel 5% in Japan by Kaken Pharmaceuticals. R&D expenses were $1.9 million for the second quarter of '22 compared to $8.8 million for the second quarter of '21. This decrease was driven primarily by significant clinical expenses related to U.S. Phase III clinical program for SB gel 15%, which concluded in the fourth quarter of '21 versus the substantially lower clinical costs that relate to the start of our Phase I clinical trial of BBI-02 during the second quarter of '22.

去年同期的收入包括我們從 Kaken Pharmaceuticals 在日本銷售 ECCLOCK 或 SB gel 5% 所確認的特許權使用費收入。 22 年第二季的研發費用為 190 萬美元，而 21 年第二季的研發費用為 880 萬美元。這一下降主要是由於與 SB gel 15% 的美國 III 期臨床計劃相關的大量臨床費用，該計劃於 21 年第四季度結束，而與我們的 BBI I 期臨床試驗開始相關的臨床成本大幅降低- 02 在'22 年第二季。

G&A expenses were $3.9 million for the second quarter of '22 compared to $2.9 million for the same quarter of the prior year. The increase was primarily related to the sale of SB and higher legal compensation and other administrative fees. Our net loss for the second quarter was $1.1 million compared to $11.1 million for the same period last year.

2022 年第二季的一般管理費用為 390 萬美元，而去年同期為 290 萬美元。這一增長主要與出售 SB 以及更高的法律賠償和其他行政費用有關。我們第二季的淨虧損為 110 萬美元，而去年同期為 1,110 萬美元。

And with that, I'll turn the call back over to Rob for closing remarks. Rob?

然後，我會將電話轉回給 Rob，讓其結束語。搶？

Thanks for the financial recap, Bert. The first half of 2022 proved to be a defining period in our company's evolution as we shifted our focus towards the development of an exciting pipeline of novel candidates with broad potential in the fields of immunology and inflammation. As we look ahead to the next few quarters, there are several important milestones planned that we believe present a significant opportunity to start building value for our shareholders. This is highlighted by the SAD/MAD top line results from the BBI-02 Phase I study, which we expect to announce in early 2023 and the continued development and characterization of our other novel therapeutic candidates, including BBI-10 and our next-generation kinase inhibitor platform.

感謝伯特的財務回顧。事實證明，2022 年上半年是我們公司發展的決定性時期，我們將重點轉向開發一系列令人興奮的新型候選藥物，這些候選藥物在免疫學和發炎領域具有廣泛的潛力。展望未來幾個季度，我們計劃實現幾個重要的里程碑，我們相信這些里程碑為開始為股東創造價值提供了重要機會。 BBI-02 I 期研究的SAD/MAD 頂線結果突顯了這一點，我們預計在2023 年初宣布該研究結果，以及我們其他新型治療候選藥物（包括BBI-10 和我們的下一代）的持續開發和表徵激酶抑制劑平台。

This concludes today's prepared remarks. I'll now ask the operator to open the call up for questions. Operator?

今天準備好的發言到此結束。我現在請接線生打開電話詢問問題。操作員？

(Operator Instructions)

（操作員說明）

The first question comes from Tim Lugo of William Blair.

第一個問題來自威廉·布萊爾的提姆·盧戈。

As Lachlan on for Tim. Congrats on the progress in the quarter. So I was wondering, obviously, BBI-02 is the priority, and it sounds like BBI-10 is the next priority. But beyond that, how are you thinking about sort of prioritizing resources across the platforms and the various early-stage kinase inhibitors that you've got over, both through DYRK1A and STING deals you've done in the past year?

拉克蘭替補蒂姆。恭喜本季取得的進展。所以我想知道，顯然，BBI-02 是優先級，聽起來 BBI-10 是下一個優先級。但除此之外，您如何考慮跨平台的資源優先順序以及您透過過去一年完成的 DYRK1A 和 STING 交易獲得的各種早期激酶抑制劑？

And then second of all, yes, after you get the SAD/MAD data in, say, early next year, what kind of turnaround is it to then initiate Part 2 of the study in patients with atopic derm?

其次，是的，在明年初獲得 SAD/MAD 數據後，在特異性皮膚患者中啟動研究的第 2 部分會帶來什麼樣的轉變？

Great. Well, let me answer the second one first and then we'll -- then we can talk in broader terms about the early pipeline. The real answer is, we're going to need the data from the SAD/MAD portion of the study to inform us about our future plans and the time lines. This is -- you got to remember, this is the first time this drug has been in man -- it's the first time DYRK1A -- oral DYRK1A has been studied in man for autoimmune diseases. And that just leads to a series of questions you've got to answer as you go forward. So we're not giving guidance at this time on when we'll start Part 2 of that study. Obviously, we'd like to start it as soon after as we can, but we need to take the time to understand the data that we generate in the SAD/MAD so we can do the best work we can in making that next study really, really valuable.

偉大的。好吧，讓我先回答第二個問題，然後我們可以更廣泛地討論早期的管道。真正的答案是，我們需要研究的 SAD/MAD 部分的數據來告知我們未來的計劃和時間表。這是——你必須記住，這是這種藥物首次用於人類——這是 DYRK1A——口服 DYRK1A 第一次在人類中研究用於治療自體免疫疾病。這只會引出一系列你在前進過程中必須回答的問題。因此，我們目前不會就何時開始研究的第二部分提供指導。顯然，我們希望盡快開始，但我們需要花時間了解我們在 SAD/MAD 中產生的數據，以便我們能夠盡最大努力使下一項研究真正開展起來。

On the first question about the pipeline. Maybe I'll ask Monica to opine on that a little bit. But needless to say, the vast majority of our time and our focus and our resources as an organization are on BBI-02 and then BBI-10. We are starting to characterize the library of assets we acquired through the 2 transactions. But again, the majority of our time is being spent on those first 2 assets. Monica, would you like to add any color to the pipeline?

關於第一個問題，關於管道。也許我會請莫妮卡對此發表一點意見。但不用說，我們作為一個組織的絕大多數時間、重點和資源都集中在 BBI-02 和 BBI-10 上。我們開始描述透過兩次交易獲得的資產庫的特徵。但同樣，我們大部分的時間都花在了前兩項資產上。莫妮卡，你想為管道添加一些顏色嗎？

Sure. I can add a bit and then, of course, Deepak can add some as well. So we've been sorting through this -- the various molecules that we have in that pipeline. Quite a bit of characterization work has been done already, but not quite enough to move completely into -- I'm sorry, there was a bit of feedback there, so I apologize for that. Actually, Deepak and his team are actively waiting for the various molecules. We'll identify which of these has the most favorable characteristics for going forward. Deepak, do you want to give any extra information on that?

當然。我可以添加一些，當然，迪帕克也可以添加一些。所以我們一直在對管道中的各種分子進行分類。相當多的特徵描述工作已經完成，但還不足以完全進入 - 很抱歉，那裡有一些反饋，所以我對此表示歉意。事實上，迪帕克和他的團隊正在積極等待各種分子。我們將確定其中哪些具有最有利於未來發展的特徵。 Deepak，您想提供任何額外資訊嗎？

I think, Monica, you provided the highlights, but just to add, so our focus right now is in terms of understanding physical and chemical (technical difficulty) over next-gen kinases. We are very much interested because during our update, we mentioned that really neuroinflammatory side of things. So based on our next-gen kinases, we are really focused on understanding whether those compounds they even have the blood-brain-barrier-penetrating properties. So we are very focused in exploring that aspect, which opens up the whole inflammatory side of things. And again, we are planning to first understand the chemical and physical characteristics of these compounds. But the next step will be -- we will be doing some PK exposure studies, and we'll be very interested to understand the blood-brain-barrier-penetrating properties. And then we will look into starting some of the in vitro preclinical work. So there is a lot on the table for the next 12 to 18 months on the next-gen kinase as part of the pipeline.

我想，莫妮卡，你提供了要點，但只是補充一下，所以我們現在的重點是了解下一代激酶的物理和化學（技術難度）。我們非常感興趣，因為在更新過程中，我們提到了真正的神經發炎方面。因此，基於我們的下一代激酶，我們真正專注於了解這些化合物是否具有血腦屏障穿透特性。所以我們非常專注於探索這個方面，這揭示了事情的整個煽動性的一面。同樣，我們計劃首先了解這些化合物的化學和物理特性。但下一步我們將進行一些 PK 暴露研究，我們將非常有興趣了解其血腦障壁穿透特性。然後我們將考慮開始一些體外臨床前工作。因此，作為管道的一部分，未來 12 到 18 個月內，下一代激酶將有很多工作要做。

The next question comes from Ram Selvaraju of H.C. Wainwright.

下一個問題來自 H.C. 的 Ram Selvaraju。溫賴特。

This is Mitchell on for Ram. The first one is on the BBI-02 program and the strategy there. Could you just give us an update on what you're thinking after atopic dermatitis? What goes into the decision to pick an indication? I know you'll have to look at a bunch of different cytokines and other markers. But is there a decision tree you can kind of walk through that, broadly speaking, you're analyzing and thinking about as you go forward with this program?

這是米切爾為拉姆出場。第一個是關於 BBI-02 計劃及其策略。您能否告訴我們您在異位性皮膚炎之後的最新想法？選擇適應症的決定取決於什麼？我知道您必須查看一堆不同的細胞因子和其他標記。但是，從廣義上講，您在推進該計劃時是否有一個可以分析和思考的決策樹？

Sure. Thanks, Mitchell. Let me start with that, then Monica, let me ask you to jump in as well. First, it's important to remember that we have picked atopic dermatitis as the indication that we're going to look at in this part 2 of the study. But it doesn't necessarily mean we're going to focus on atopic dermatitis long term. We think that it's the ideal vehicle, if you will, to help us with a proof of mechanism, if you will, of the drug and see how it's working because it's a skin disease, and we can measure a variety of different endpoints and understand. We think what's happening in the human body, atopic dermatitis patients better. That's really why we're focusing on that. That data is really what then drives how we decide what to do next. And maybe, Monica, if I can turn it over to you for a minute to share a little more insight into that.

當然。謝謝，米切爾。讓我從這個開始，然後莫妮卡，讓我也請你也加入進來。首先，重要的是要記住，我們選擇異位性皮膚炎作為我們將在研究的第二部分中研究的適應症。但這並不一定意味著我們將長期關注異位性皮膚炎。我們認為它是理想的工具，如果你願意的話，可以幫助我們證明藥物的機制，並了解它是如何發揮作用的，因為它是一種皮膚病，我們可以測量各種不同的終點並了解。我們認為人體發生了什麼，異位性皮膚炎患者的情況比較好。這就是我們關注這一點的真正原因。這些數據確實決定了我們下一步該做什麼。也許，莫妮卡，我可以把它交給你一分鐘，讓你分享更多對此的見解。

Sure. So because this molecule is the first time in humans, as you know, and I have learned more about the pharmacokinetics and the pharmacodynamics and safety, we're going to be assessing a wide variety of endpoints in the AD study that would be extrapolatable to other autoimmune disorders. So of course, we're going to be measuring cytokine trends that's going to be important to us (technical difficulty). We'll also be looking at various cellular markers. We'll be looking at cell markers ex vivo. We'll be also looking at in situ cellular populations in the actual space of inflammation via biopsies that I'm talking about, so we'll be able to identify what types of cells are present pretreatment, what types of cells are present after treatment and inform ourselves about how DYRK1A inhibition actually affects this chemotaxis into the tissues.

當然。因此，如您所知，由於這種分子是首次在人類中使用，而且我對藥物動力學、藥效學和安全性有了更多了解，因此我們將評估AD 研究中的各種終點，這些終點可以推論為其他自體免疫疾病。因此，當然，我們將測量對我們很重要的細胞激素趨勢（技術難度）。我們還將研究各種細胞標記。我們將研究離體細胞標記。我們還將透過我所說的活檢來觀察發炎實際空間中的原位細胞群，因此我們將能夠識別治療前存在哪些類型的細胞，治療後存在哪些類型的細胞並了解DYRK1A 抑制實際上如何影響組織的趨化性。

We'll also be looking at tape stripping, which will give us some idea about any impact on RNA. So we have a wide variety of information, which will give us data on both inflammatory disease applicability and autoimmune disease applicability. And depending on the trends and what we see in that data, that's going to probably shift us one way or the other as being the most beneficial. There's so much information that we're going to be getting in I can't stress that enough, and it will help to shape the future direction. If the AD data is stellar, of course, we'll think about that as well. Does that help?

我們還將研究膠帶剝離，這將使我們了解對 RNA 的影響。因此，我們擁有各種各樣的信息，這將為我們提供有關發炎性疾病適用性和自體免疫疾病適用性的數據。根據趨勢和我們在數據中看到的內容，這可能會以一種最有利的方式改變我們。我們將獲得大量信息，我怎麼強調都不為過，這將有助於塑造未來的方向。當然，如果 AD 數據非常出色，我們也會考慮這一點。這樣有幫助嗎？

Yes, absolutely. That was very thorough. And then on BBI-10, could you just talk about the strategy there? And what are the next updates we can expect as you move towards the clinic?

是的，絕對是。那是非常徹底的。然後在 BBI-10 上，您能談談那裡的策略嗎？當您走向診所時，我們可以期待哪些後續更新？

Sure. Deepak, would you like to talk about that?

當然。迪帕克，你想談談這個嗎？

Sure. Sure. Happy to answer. So as mentioned, BBI-10 or the STING inhibitor compound is just getting out of discovery into preclinical. Our focus for next 12 months is very much in understanding more into the in vitro side of things. So we have already planned to carry out some of the in vitro metabolism study, solubility. We are really interested to get an early read on SIP inhibition, induction, plasma protein binding. So that's just the gamut of data is going to help us starting the IND-enabling study next year.

當然。當然。很高興回答。如前所述，BBI-10 或 STING 抑制劑化合物剛從發現階段進入臨床前階段。我們未來 12 個月的重點是更多地了解體外方面的情況。所以我們已經計劃進行一些體外代謝、溶解度的研究。我們非常有興趣儘早了解 SIP 抑制、誘導、血漿蛋白結合的情況。因此，這一系列數據將幫助我們明年開始 IND 支持研究。

So short answer, next 6 months in vitro work, and then once we move into 2023, we are going to embark on the IND-enabling tox studies. And then subsequently, as we move the asset forward, clearly, like sometime around 2024, we'll be looking into starting first-in-human, but a lot of preclinical work to be done in the next 12 to 18 months.

簡而言之，接下來 6 個月的體外工作，然後一旦進入 2023 年，我們將開始進行 IND 毒性研究。隨後，隨著我們推進該資產，顯然，例如 2024 年左右的某個時候，我們將考慮開始首次人體試驗，但在未來 12 到 18 個月內需要完成大量臨床前工作。

Great. And last question for me. Just wanted to ask about what more needs to be done on the Botanix side to get that submission into that NDA submission in for sofpironium bromide?

偉大的。還有我的最後一個問題。只是想問一下 Botanix 方面還需要做哪些工作才能將該提交提交到索匹羅溴銨的 NDA 提交中？

Yes. This is Rob. Obviously, we're excited that they're on the cusp of getting that done and they have stated publicly that they'll get it done in this quarter. And I think we probably ought to leave it for them to provide any more information on that. But obviously, we're tracking. We're working with them. Our team is helping in the preparation of that submission. But I'll leave it to them to provide any more guidance on timing.

是的。這是羅布。顯然，我們很高興他們即將完成這項工作，並且他們已公開表示將在本季完成這項工作。我認為我們可能應該讓他們提供更多相關資訊。但顯然，我們正在追蹤。我們正在與他們合作。我們的團隊正在幫助準備該提交內容。但我會讓他們在時間安排上提供更多指導。

The next question comes from Leland Gershell from Oppenheimer.

下一個問題來自奧本海默的利蘭·格謝爾。

This is Rohan Mathur speaking on behalf of Leland. Congrats on another great quarter and appreciate you taking my questions. Just a couple of questions on the BBI-10 portfolio. So in light of the recent Carna/STING inhibitor portfolio acquisition, have you made any progress in determining what kind of indications in neuro inflammation might be of interest? And what particular stages of the disease would you be looking at? And moreover, are there any diseases that you feel STING inhibitors would have a competitive advantage over other therapeutics? And just a follow up on that. How do we think R&D expenses will look as trials pick up and we move into the clinic? And also, are there any plans to get some kind of partnership funding involved?

我是羅漢馬圖爾 (Rohan Mathur) 代表利蘭 (Leland) 發言。恭喜又一個偉大的季度，並感謝您回答我的問題。關於 BBI-10 投資組合的幾個問題。那麼，鑑於最近收購的 Carna/STING 抑制劑組合，您在確定可能感興趣的神經發炎適應症方面是否取得了任何進展？您會關注疾病的哪些特定階段？此外，您認為 STING 抑制劑在哪些疾病中比其他療法具有競爭優勢？這只是後續行動。隨著試驗的進行和進入臨床，我們認為研發費用將如何？另外，是否有計劃參與某種合作夥伴資金？

Great. Well, let me answer the first part, the first questions on R&D expenses first, and then we'll talk about BBI-10 briefly. I think the quarter is, as you see, far more representative of what our spend going forward will look like. R&D expenses of $1.9 million in the second quarter, and that's pharma representative of what it will look like, plus or minus some as we do this Phase I work. So very, very different, obviously, than the sofpironium bromide expenses we were spending a year ago or even a couple of quarters ago. So this last quarter is probably not a bad barometer to use for the next few quarters.

偉大的。那我先回答第一部分，第一個問題，關於研發費用，然後我們簡單講BBI-10。正如您所看到的，我認為這個季度更能代表我們未來的支出狀況。第二季的研發費用為 190 萬美元，這是製藥公司的代表，在我們進行第一階段工作時加上或減去一些費用。顯然，這與我們一年前甚至幾季前花費的溴化索吡溴銨費用非常非常不同。因此，最後一個季度可能是未來幾季的一個不錯的晴雨表。

On the BBI-10 portfolio, it's really too early, I think, for us to opine on which indications and what stages of the diseases that might make sense for this at this time. We're excited about the broad potential for this product. There's a number of really interesting diseases with unmet needs. But it's probably a little too early for us to find too much. In terms of advantages, Monica, I don't know if you have any sense for where the STING might have an advantage versus other treatments that are out there and provide any thought on that.

我認為，就 BBI-10 投資組合而言，我們現在就哪些適應症以及疾病的哪些階段可能對此有意義發表意見還為時過早。我們對該產品的廣泛潛力感到興奮。有許多非常有趣的疾病，其需求尚未被滿足。但現在我們發現太多可能還太早。就優勢而言，莫妮卡，我不知道您是否知道 STING 與現有的其他治療方法相比可能具有哪些優勢，並對此提供任何想法。

Well, STING is very clearly related to the interferon pathway and particularly in autoimmune diseases but also in auto-inflammatory diseases. There's clear overdrive of the interferon pathway. So I think because these are so focused on the interferon pathway, that gives us an advantage over the more broad-based immunomodulatory modalities, more focus targeted.

嗯，STING 與幹擾素途徑非常明顯相關，特別是在自體免疫疾病中，而且在自體發炎性疾病中也有相關性。幹擾素途徑明顯超速。所以我認為，由於這些藥物如此專注於幹擾素途徑，這使我們比基礎更廣泛、更有針對性的免疫調節方式更具優勢。

The next question comes from Thomas Flaten of Lake Street.

下一個問題來自湖街的托馬斯·弗拉頓。

Just a quick one for Bert. The cash runway of at least 12 months, is that an accounting at least 12 months or should we think 12 to 15 months from that perspective?

對伯特來說只是一個快速的。至少 12 個月的現金跑道，是會計至少 12 個月還是我們應該從這個角度考慮 12 到 15 個月？

That's at least 12 months from an accounting perspective, which also means we've got to have the cash to go out that far.

從會計角度來看，這至少需要 12 個月，這也意味著我們必須有足夠的現金來支付這麼長時間。

Right. And Monica, I'm struggling with how to really word this question intelligently, so please bear with me. So given that you're taking a look at atopic dermatitis for BBI-02, is there a kind of decision tree that you already have in mind if you see certain PD dynamics that will drive you towards a certain other autoimmune indication versus a different one. I'm trying to understand how that decision tree really works once you get that data in hand? Are there particular pathways that are preestablished if you see a certain grouping of PD markers, you'll know that you should go down this path versus that path? Or do you have to wait to see what the totality of the data is before really making up your mind on that?

正確的。莫妮卡，我正在努力思考如何明智地表達這個問題，所以請耐心等待。因此，鑑於您正在研究 BBI-02 的異位性皮膚炎，如果您看到某些 PD 動態會驅使您走向某種其他自體免疫適應症而不是其他適應症，您是否已經想到了一種決策樹。我試圖了解一旦您掌握了數據，決策樹實際上是如何運作的？如果您看到一組特定的 PD 標記物，是否存在預先建立的特定路徑，您就會知道您應該走這條路徑而不是那條路徑？或者您必須等待查看全部數據後才能真正做出決定？

Yes, it's a difficult question to answer specifically. The DYRK1A pathway is a new target, as you know. So we're learning about how intervention within -- with that target actually behaves in the human. Obviously, we're going to need to take safety in regards and what kinds of risk-benefit ratios that we have when we're looking -- deciding on different diseases, that's one thing we need to think about. We'll need to see how well we do in terms of being able to shift the cytokine flow from pro-inflammatory cytokines to lower levels of inflammatory cytokines if we hit some more than others.

是的，這是一個很難具體回答的問題。如您所知，DYRK1A 通路是一個新標靶。因此，我們正在了解針對該目標的干預實際上如何在人類身上表現。顯然，我們需要考慮到安全性，以及當我們在尋找不同的疾病時我們有什麼樣的風險效益比，這是我們需要考慮的一件事。如果我們對某些細胞因子的打擊比其他細胞因子多，我們需要看看我們在將細胞因子流從促炎細胞因子轉移到較低水平的發炎細胞因子方面做得如何。

Obviously, there are some diseases that are driven a little bit more by some cytokines. You look at IL-6 diseases, for instance, the TNF-alpha-driven diseases, which often overlap, but differentiate slightly. If we see an impact on Th2 cells. When we look at our cellular populations that might take us down one path. If we have more of an impact on Th17, that might take us a different pathway. So unfortunately, there are so many unknowns that I can't say that we have a definitive path right now to say if we see this, then we should have this. There's just too many different balls in the air. We'll have to see how they all line up, and then, I guess, see where they lie and make our decisions then. I'm sorry, I can't be more specific. It's a little bit early.

顯然，有些疾病較多是由某些細胞激素所驅動的。例如，IL-6 疾病，TNF-α 驅動的疾病，它們經常重疊，但略有不同。如果我們看到對 Th2 細胞的影響。當我們觀察我們的細胞群時，可能會帶我們走上一條路。如果我們對 Th17 產生更大的影響，那可能會帶我們走一條不同的路。不幸的是，有太多的未知因素，我不能說我們現在有一個明確的路徑，如果我們看到這個，那麼我們應該有這個。空中有太多不同的球。我們必須看看他們是如何排列的，然後，我想，看看他們在哪裡，然後做出我們的決定。抱歉，我不能說得更具體。時間有點早了。

Yes. No, that's absolutely fine. And then one final one. Is there a -- or what is the risk, if any, that 28 days of treatment simply isn't enough to see an early efficacy signal or see the pharmacodynamics that you'd be hoping for or some of the downstream consequences of treatment?

是的。不，那絕對沒問題。然後是最後一張。是否存在 28 天的治療不足以看到早期療效訊號或看到您所希望的藥效學或治療的一些下游後果的風險（如果有）？

It's a great question, a really good question and one I can't answer. As you all know, there are that AD that there are drugs that will give you an impact already 2 to 4 weeks, and there are some that you have to wait 8 to 12 weeks. And ultimately, it's a chronic long-term diseases. And if you get the best outcome and it takes you a little bit longer to get there. Sometimes patients are waiting to -- wait for that in order to get to the better outcome. So we don't know how, obviously, DYRK1A is going to show its impact, and we'll learn a little bit about that with the AD program, but we were sensitive to that question, and that's why we very consciously have said all along that this will give us a preliminary assessment of efficacy. We don't want for ourselves -- we don't want to think that if we don't get the biggest bang for the buck after 4 weeks that this is not a good way to go. So we're very conscious of the fact that 28 days is a limiting factor, and that's why we're going to be starting our -- actually, our subclinical tox is going to be starting imminently, the longest 3 months.

這是一個很好的問題，一個非常好的問題，但我無法回答。眾所周知，有些藥物會在 2 到 4 週內產生影響，有些藥物則需要等待 8 到 12 週。最終，這是一種慢性長期疾病。如果你得到了最好的結果，但你需要更長的時間才能到達那裡。有時患者會等待，以便獲得更好的結果。因此，顯然，我們不知道 DYRK1A 將如何顯示其影響，我們將透過 AD 計劃了解一些相關信息，但我們對這個問題很敏感，這就是為什麼我們非常有意識地說了所有這些這將為我們提供初步的功效評估。我們不想為自己——我們不想認為如果我們在 4 週後沒有得到最大的回報，這不是一個好方法。因此，我們非常清楚 28 天是一個限制因素，這就是為什麼我們要開始——實際上，我們的亞臨床毒性即將開始，最長的 3 個月。

We've reached the end of our question-and-answer session. I'd like to turn the call back over to Mr. Rob Brown for closing remarks.

我們的問答環節已經結束。我想將電話轉回給羅布·布朗先生做總結發言。

Thank you for taking the time this afternoon to listen to our update. We're enthused about what the future holds for Brickell as a biotech exploring cutting-edge treatment alternatives for patients suffering from debilitating, autoimmune and inflammatory conditions. We look forward to sharing additional updates on our development progress moving forward. As always, please feel free to reach out to us at any time if you have further questions. Have a great day.

感謝您今天下午抽出時間來收聽我們的最新動態。我們對 Brickell 作為一家生技公司的未來充滿熱情，為患有衰弱、自體免疫和發炎性疾病的患者探索尖端的治療替代方案。我們期待分享更多有關我們未來開發進展的最新資訊。一如既往，如果您有其他問題，請隨時與我們聯繫。祝你有美好的一天。

Thank you. That concludes today's teleconference. You may now disconnect your lines at this time. We thank you for your participation today.

謝謝。今天的電話會議到此結束。此時您可以斷開線路。我們感謝您今天的參與。