Biora Therapeutics Inc (BIOR) 2024 Q2 法說會逐字稿

Welcome to the Biora Therapeutics second quarter 2024 financial results call. (Operator Instructions). As a reminder, this conference is being recorded.

歡迎參加 Biora Therapeutics 2024 年第二季財務業績電話會議。（操作員指令）。提醒一下，本次會議正在錄音。

I will now turn the call over to Chuck Padala, Managing Director with LifeSci Advisors, Biora's Investor Relations firm. Please go ahead.

現在，我將把電話轉給 Biora 投資者關係公司 LifeSci Advisors 的董事總經理 Chuck Padala。請繼續。

Thank you, operator. Good afternoon and welcome to the Biora Therapeutics second quarter 2024 corporate update and financial results conference call. Joining me on the call are Adi Mohanty, Chief Executive Officer; and Eric d'Esparbes, Chief Financial Officer.

謝謝您，接線生。下午好，歡迎參加 Biora Therapeutics 2024 年第二季公司更新與財務業績電話會議。參加電話會議的還有執行長 Adi Mohanty；艾瑞克‧德斯帕布 (Eric d'Esparbes)，財務長。

Before I turn the call over to Mr. Mohanty, I would like to remind you that today's call will include forward-looking statements within the meaning of the federal securities laws, including, but not limited to, the types of statements identified as forward-looking in our quarterly report on Form 10-Q that we filed or will file later today and our subsequent reports filed with the SEC, which are available on our website in the Investors section.

在我將電話轉給 Mohanty 先生之前，我想提醒您，今天的電話會議將包括聯邦證券法所定義的前瞻性陳述，包括但不限於我們今天提交或將稍後提交的 10-Q 表季度報告以及我們隨後向美國證券交易委員會提交的報告中確定的前瞻性陳述類型，這些報告可在我們網站的「投資者」部分查閱。

These forward-looking statements represent our views only as of the date of this call and involve substantial risks and uncertainties, including many that are beyond our control. Please note that actual results could differ materially from those expressed in the forward-looking statements.

這些前瞻性陳述僅代表我們截至本次電話會議之日的觀點，涉及重大風險和不確定性，包括許多我們無法控制的風險和不確定性。請注意，實際結果可能與前瞻性陳述中表達的結果有重大差異。

For a further description of the risks and uncertainties that could cause actual results to differ materially from those expressed in the forward-looking statements as well as risks related to our business, please see the company's periodic reports filed with the SEC.

有關可能導致實際結果與前瞻性陳述中表達的結果存在重大差異的風險和不確定因素以及與我們的業務相關的風險的進一步描述，請參閱公司向美國證券交易委員會提交的定期報告。

With that, I will now turn the call over to Adi Mohanty, CEO of Biora Therapeutics. Adi?

說完這些，我現在將電話轉給 Biora Therapeutics 的執行長 Adi Mohanty。阿迪？

Thanks, Chuck, and thank you, everyone, for joining us. It's been a very productive and busy quarter for Biora with the announcement of our successful Phase 1 clinical trial for the BT-600 program using our NaviCap platform and significant work and progress with partners on the BioJet platform.

謝謝查克，也謝謝大家加入我們。對於 Biora 來說，這是一個非常有效率且忙碌的季度，我們宣布使用 NaviCap 平台成功進行了 BT-600 計畫的第一階段臨床試驗，並與合作夥伴在 BioJet 平台上開展了重大工作並取得了進展。

I'll begin with our NaviCap platform. We were pleased to see the large number of people who joined our recent KOL event, which was cohosted by Dr. Bruce Sands of Mount Sinai; and Dr. Brian Feagan, of the University of Western Ontario.

我將從我們的 NaviCap 平台開始。我們很高興看到有大量的人參加我們最近的 KOL 活動，該活動由西奈山的 Bruce Sands 博士共同主持；以及西安大略大學的 Brian Feagan 博士。

These two physicians are legends in the treatment of IBD. And if you look at many of the major clinical trials in UC therapies, you'll see both these names appear over-and-over, including as principal investigators. It was great to have them help us present and contextualize our clinical trial results for BT-600.

這兩位醫生是 IBD 治療領域的傳奇人物。如果你觀察一下 UC 治療領域的許多主要臨床試驗，你會發現這兩個名字反覆出現，有時還作為首席研究員。非常高興他們能幫助我們展示和闡述 BT-600 的臨床試驗結果。

BT-600 is being developed for the treatment of ulcerative colitis, which is an inflammatory disease that affects the mucosal and submucosal layers of the colon. It's largely a local disease of the colon tissue. Despite knowing for over 30-years that UC is the disease of the colon tissue, even now patients are treated by receiving powerful drugs systemically in an attempt to reach therapeutic levels in the colon.

BT-600 正在開發用於治療潰瘍性結腸炎，這是一種影響結腸黏膜和黏膜下層的發炎性疾病。這主要是結腸組織的局部疾病。儘管 30 多年來人們都知道 UC 是一種結腸組織疾病，但直到現在，患者仍然透過系統性地使用強效藥物進行治療，以期達到結腸的治療水平。

Research shows that UC patients with higher drug exposure in the colon tissue have significantly better responses to therapy. Although several attempts have been made, there has not been a reliable way to achieve colon tissue targeted delivery of therapeutics.

研究表明，結腸組織中藥物暴露較高的 UC 患者對治療的反應明顯較好。儘管已經進行了多次嘗試，但目前還沒有可靠的方法來實現結腸組織標靶治療。

With our approach, we aim to achieve higher drug exposure and activity in colon tissue by delivering drug directly to the site of disease. Our Phase 1 clinical trial was a very big step forward in demonstrating the NaviCap platform's ability to achieve this direct topical delivery to colon and we're incredibly pleased to have met all our objectives with this study.

透過我們的方法，我們的目標是透過將藥物直接輸送到疾病部位來實現結腸組織中更高的藥物暴露和活性。我們的第一階段臨床試驗向前邁出了一大步，證明了 NaviCap 平台能夠實現直接局部輸送到結腸，我們非常高興透過這項研究實現了我們的所有目標。

Looking at the pharmacokinetic data, we achieved a PK profile consistent with drug delivery in the colon. The timing of when tofacitinib shows up in the blood at about six hours compared to 30 minutes for conventional oral therapy is an indicator of the drug entering systemic circulation via the colon.

透過查看藥物動力學數據，我們獲得了與結腸中藥物傳輸一致的 PK 曲線。託法替尼在血液中出現的時間約為 6 小時，而傳統口服療法則為 30 分鐘，這表示藥物會經由結腸進入全身循環。

With this delivery approach, we wanted to see lower levels in systemic circulation and we did. Systemic levels were three to four times lower than with conventional oral delivery. We believe this could help reduce toxicity risks, which are known issue with many UC drugs, including JAK inhibitors.

透過這種輸送方式，我們希望看到體循環中濃度降低，而我們確實做到了。全身性濃度比傳統口服給藥低三至四倍。我們相信這有助於降低毒性風險，這是許多 UC 藥物（包括 JAK 抑制劑）的已知問題。

We also wanted to get some data on colon tissue exposure to tofacitinib. As you may recall, NaviCap has been programmed to deliver at the entry to the colon. We wanted to confirm that drug travels from the proximal colon to the distal or far side of the colon as we saw with payload delivery in several previous device function studies.

我們也想獲得一些關於結腸組織暴露於託法替尼的數據。您可能還記得，NaviCap 已被編程為在結腸入口處進行輸送。我們想要確認藥物從近端結腸移動到結腸的遠端或遠端，就像我們在先前的幾項設備功能研究中看到的有效載荷輸送一樣。

Our Phase 1 results did indeed confirm this with tofacitinib detected across all three biopsy sites in the distal colon. We anticipated that tissue levels of these biopsy sites could be quite low because of a trial design that required performing those biopsies at 24 hours or four to five half-lives after the final dose along with extensive colon prep before the procedure.

我們的第一階段結果確實證實了這一點，在遠端結腸的所有三個活檢部位均檢測到了託法替尼。我們預計這些活檢部位的組織水平可能非常低，因為試驗設計要求在最後一次服藥後 24 小時或四到五個半衰期進行活檢，並在手術前進行大量的結腸準備。

Despite the late timing of the biopsy, we observed drug tissue concentrations above the IC50 level for all three locations. This is especially notable since we studied daily doses of 5 mgs and 10 mgs in this trial, which are a quarter to half of the approved doses for conventional tofacitinib.

儘管活檢時間較晚，我們仍觀察到三個位置的藥物組織濃度均高於 IC50 水平。這一點尤其值得注意，因為我們在這次試驗中研究的是 5 毫克和 10 毫克的每日劑量，這相當於傳統託法替尼批准劑量的四分之一到二分之一。

The data also showed a strong correlation between plasma and tissue levels. And because of this correlation, we were able to model tissue concentrations at earlier time points, which predicts that tissue levels should exceed IC90 through at least 16 hours after dosing. Across both study arms, we saw greater than 95% accuracy of release in the colon with no early release before colon entry, which is excellent performance. We also saw excellent safety data in the trial.

數據也顯示血漿和組織水平之間存在很強的相關性。由於這種相關性，我們能夠在早期時間點模擬組織濃度，從而預測給藥後至少 16 小時內組織水平應超過 IC90。在兩項研究中，我們發現結腸釋放的準確率超過 95%，且在進入結腸之前沒有出現早期釋放，這是非常出色的表現。我們還在試驗中看到了出色的安全數據。

A lot of the details were included in our KOL presentation. If you haven't viewed that event yet, I invite you to watch the replay, where our Chief Medical Officer, Dr. Ariella Kelman, who did an amazing job leading this clinical trial, presents the data.

我們的 KOL 演示中包含了許多細節。如果您還沒有觀看該活動，我邀請您觀看重播，其中我們的首席醫療官 Ariella Kelman 博士展示了數據，她在領導這項臨床試驗方面做得非常出色。

Patients with UC continue to experience tremendous difficulties in achieving and sustaining remission. And we remain focused on this serious unmet need. Despite the many approved advanced therapies, a therapeutic ceiling exists at about 30% above placebo.

潰瘍性結腸炎患者在實現和維持緩解的過程中仍然面臨巨大的困難。我們將繼續關注這項尚未滿足的嚴重需求。儘管已有許多先進療法獲得批准，但治療效果仍有上限，比安慰劑高出約 30%。

A delta of 15% to 30% induction efficacy simply isn't good enough for a condition that causes tremendous suffering for so many. We believe the NaviCap platform is important because it has the potential to break this therapeutic ceiling through several approaches.

對於這種給許多人帶來巨大痛苦的疾病來說，15% 到 30% 的誘導效力的差異根本不夠好。我們認為 NaviCap 平台很重要，因為它有可能透過多種方法突破這種治療上限。

First, we think this platform can optimize JAK inhibitor therapy by achieving better therapeutic outcomes while reducing safety risks. Our Phase 1 data demonstrate a proof of mechanism for this. Second, research shows that colon targeted delivery could also improve outcomes for other drug classes such as TNF inhibitors and integrin inhibitors. We believe the NaviCap platform could deliver those molecules and we ultimately envision a portfolio of optimized UC therapies. Third, leading physicians talk about the importance of enabling combination therapy for UC in order to target multiple inflammatory pathways. We believe the NaviCap platform would be very well positioned to facilitate combination therapies.

首先，我們認為該平台可以優化JAK抑制劑療法，實現更好的治療效果，同時降低安全風險。我們的第一階段數據證明了這個機制。其次，研究表明，結腸標靶給藥還可以改善其他類別藥物（如 TNF 抑制劑和整合素抑制劑）的效果。我們相信 NaviCap 平台可以提供這些分子，我們最終設想了一系列優化的 UC 療法。第三，領先的醫生談到了對 UC 進行聯合治療以針對多種發炎途徑的重要性。我們相信 NaviCap 平台將非常適合促進聯合療法。

In the near-term, our Phase 1 results clearly support a clinical development plan that moves us into a clinical study in UC patients. Our objective with that study is to confirm the PK profile in UC patients and to inform dose selection for a subsequent induction efficacy trial.

短期內，我們的第一階段結果明確支持臨床開發計劃，該計劃將使我們進入針對 UC 患者的臨床研究階段。我們進行研究的目的是確認 UC 患者的 PK 特徵，並為後續誘導療效試驗的劑量選擇提供資訊。

Everything we have seen indicates that our approach should lead to improved response and reduced toxicity for UC patients and we're eager to continue with clinical development to prove that out. We're also looking forward to the American College of Gastroenterology's Annual Meeting in October, where we will be presenting data from our Phase 1 clinical trial to the medical community.

我們所看到的一切都表明，我們的方法應該可以改善 UC 患者的反應並降低毒性，我們渴望繼續進行臨床開發來證明這一點。我們也期待十月的美國胃腸病學會年會，我們將在會上向醫學界展示我們第一階段臨床試驗的數據。

Moving on to our BioJet systemic therapeutics platform. The BioJet platform continues to exceed its performance targets and shows outstanding promise to solve the challenge of oral delivery of large molecules, which has been called the holy grail of drug delivery.

繼續我們的 BioJet 系統治療平台。BioJet 平台不斷超越其性能目標，並在解決大分子口服給藥難題方面展現出卓越的前景，這被稱為藥物輸送的聖杯。

Our goal with BioJet is to provide an alternative to needle-based delivery of complex molecules. The platform could also enable those molecules to more efficiently reach the liver, which is difficult with other oral delivery methods.

我們對 BioJet 的目標是提供一種替代透過針頭輸送複雜分子的方法。該平台還可以使這些分子更有效地到達肝臟，這對於其他口服給藥方法來說是困難的。

As I shared with you last quarter, we established a defined partnering process with interested pharma parties, and during the past quarter, we've made significant steps forward with that. Our goal was to achieve a critical mass of data and to have partner-stated interest confirmed by mid-year. We met that goal. And we're currently in active partnership discussions with more than one large pharma company. We anticipate bringing at least one of these through to completion in the near-term.

正如我上個季度與您分享的那樣，我們與感興趣的製藥方建立了明確的合作流程，並且在過去一個季度中，我們在這方面取得了重大進展。我們的目標是取得足夠的數據，並在年中之前獲得合作夥伴的確認。我們實現了這個目標。目前我們正與多家大型製藥公司積極洽談合作事宜。我們預計其中至少有一項將在近期完成。

I'm unable to provide details until we conclude, but I can say that we remain on track to achieve our partnership goal for 2024. This progress has also been recognized by several of our large shareholders, who are stepping up to support our operations while we conclude our partnership process. Eric will speak a little more about that shortly.

在達成協議之前我無法提供詳細信息，但我可以說，我們仍在按計劃實現 2024 年的合作目標。這項進展也得到了我們幾家大股東的認可，他們在我們完成合作進程的同時加大了對我們的營運的支持。艾瑞克稍後會就此進一步談一談。

In June, we shared an update at an industry meeting, the Next Gen Peptide Formulation & Delivery Summit, where our Head of Research, Dr. Sharat Singh, presented on a panel discussion alongside his peers from Lilly, Merck, and Novo Nordisk who are all pursuing oral delivery of peptides such as GLP-1 receptor agonist. Dr. Singh also presented a session focused solely on the BioJet platform, where he shared our continued progress in demonstrating category-leading bioavailability across multiple complex molecules, including antibodies, peptides and antisense oligonucleotides.

6 月份，我們在行業會議「下一代勝肽配方與交付高峰會」上分享了最新進展，我們的研究主管 Sharat Singh 博士與來自禮來、默克和諾和諾德的同行一起參加了小組討論，他們都在致力於 GLP-1 受體激動劑等勝肽的口服交付。Singh 博士也發表了一場專注於 BioJet 平台的演講，分享了我們在展示多種複雜分子（包括抗體、勝肽和反義寡核苷酸）的領先生物利用度方面取得的持續進展。

We remain encouraged by the interest in BioJet platform's ability to deliver multi milligram payloads using existing liquid formulations and its potential to enable liver-targeted delivery of large molecules. With all of these competitive advantages, we're in an excellent position with the BioJet platform and we look forward to evolving our plans as we bring on pharma partners.

我們仍然對 BioJet 平台利用現有液體配方輸送多毫克有效載荷的能力及其實現大分子肝臟靶向輸送的潛力感興趣。憑藉所有這些競爭優勢，我們在 BioJet 平台上處於有利地位，我們期待在引入製藥合作夥伴的同時不斷發展我們的計劃。

To summarize our anticipated milestones. For our NaviCap platform, we continue to share results from our successful Phase 1 clinical trial for BT-600. We will next be presenting trial data at the American College of Gastroenterology Annual Meeting in October. We anticipate initiating a clinical study with BT-600 in UC patients towards the end of the year. For our BioJet platform, we're in active partnership discussions with more than one large pharma company as part of our defined process. We remain on track toward our goal of partnership for the BioJet platform in 2024.

總結我們預期的里程碑。對於我們的 NaviCap 平台，我們繼續分享 BT-600 成功的第一階段臨床試驗的結果。我們接下來將在十月的美國胃腸病學會年會上展示試驗數據。我們預計將在今年底啟動針對 UC 患者的 BT-600 臨床研究。對於我們的 BioJet 平台，作為我們既定流程的一部分，我們正在與多家大型製藥公司進行積極的合作討論。我們仍在朝著 2024 年與 BioJet 平台合作的目標邁進。

With that I'll now turn the call over to Eric for a review of our financial results and capital market activities.

現在我將把電話轉給 Eric，讓他審查我們的財務表現和資本市場活動。

Thanks, Adi, and good afternoon, everyone. Earlier today, we announced a capital raise that provides crucial funding for the company. We're happy to see the continued support from investors as we progress towards important milestones for Biora.

謝謝，阿迪，大家下午好。今天早些時候，我們宣布增加資本，為公司提供關鍵資金。在 Biora 邁向重要里程碑的過程中，我們很高興看到投資者的持續支持。

I'll first cover our financial results and then provide more background on the transaction. Operating expenses during the second quarter, excluding stock-based compensation expenses were $14.5 million with continued investment in device development, preclinical and clinical activities.

我將首先介紹我們的財務業績，然後提供有關交易的更多背景資訊。第二季的營業費用（不包括股票薪酬費用）為 1,450 萬美元，繼續投資於設備開發、臨床前和臨床活動。

To break this down further, G&A expenses in the second quarter, excluding stock-based compensation expenses were $7.5 million of which approximately 60% was core activity spend leaving nearly 40% of G&A costs associated with legacy matters which we are working to eliminate by the end of the year.

進一步細分，第二季的一般及行政管理費用（不包括股票薪酬費用）為 750 萬美元，其中約 60% 為核心活動支出，剩下近 40% 的一般及行政管理成本與遺留事項有關，我們正在努力在年底前消除這些遺留事項。

R&D expenses excluding stock-based compensation expenses were $7 million. As a result Biora's core OpEx spend was $11.7 million in Q2. With the majority of the spend allocated to our R&D programs, including the execution of our clinical development with NaviCap and BT-600 and preclinical work with BioJet with our pharma collaborators.

不包括股票薪酬費用的研發費用為 700 萬美元。因此，Biora 第二季的核心營運支出為 1,170 萬美元。大部分支出都用於我們的研發項目，包括使用 NaviCap 和 BT-600 進行臨床開發以及與我們的製藥合作夥伴一起用 BioJet 進行臨床前工作。

I'd like to remind investors that our financial results include many noncash items, which is why we also refer to operating expenses excluding those elements for better guidance on our actual operating cash burn. We also have other non-cash items in our income statement, including changes in derivative and warrant liabilities. As a result, we are posting a $6.5 million net income position for the second quarter of 2024.

我想提醒投資者，我們的財務結果包括許多非現金項目，這就是為什麼我們還參考不包括這些因素的營運費用，以便更好地指導我們的實際營運現金消耗。我們的損益表中還有其他非現金項目，包括衍生性商品和認股權證負債的變動。因此，我們預計 2024 年第二季的淨收入為 650 萬美元。

Moving on to our capital raise announced this afternoon. We made a series of transactions last year and in early 2024, where we substantially reduced our outstanding notes balance, but more importantly, we brought in $19.8 million in new investments from a core group of large institutions.

我們將繼續討論今天下午宣布的融資事宜。我們去年和 2024 年初進行了一系列交易，大幅減少了未償還票據餘額，但更重要的是，我們從一群核心大型機構引入了 1,980 萬美元的新投資。

We are happy to see these same institutions adding an additional $16 million to their capital commitment to Biora. The transaction is structured as an additional $16 million contribution from our noteholders to the existing facility to be provided in tranches of $4 million increments as needed by the company. This allows us to raise complementary capital from other sources if available and preserve this funding as required.

我們很高興看到這些機構向 Biora 額外增加了 1,600 萬美元的資本承諾。此交易的結構為，我們的票據持有人將向現有融資工具額外注資 1,600 萬美元，並將根據公司需要以 400 萬美元的增量分期提供。這樣，我們就可以從其他可用來源籌集補充資金，並根據需要保留這些資金。

In addition, there's a large equity component to this capital raise from convertible features and warrants allocation, highlighting a strong focus on the future value of our stock. We and our investors view and structure this transaction as a bridge to an anticipated pharma partnership and we're excited about what lies ahead for Biora.

此外，此次融資的股權部分很大一部分來自可轉換功能和認股權證分配，凸顯了我們對股票未來價值的高度關注。我們和我們的投資者將此次交易視為預期的製藥合作的橋樑，我們對 Biora 的前景感到興奮。

With that, I will now turn the call back over to Adi.

說完這些，我現在將電話轉回給阿迪。

Thanks, Eric. We're actively working towards completing our first pharma partnership for the BioJet platform and we look forward to sharing more. And for BT-600 and the NaviCap platform, we're preparing for the next stage of clinical development as we work to break the therapeutic ceiling in UC.

謝謝，埃里克。我們正在積極致力於完成 BioJet 平台的第一個製藥合作，並期待分享更多。對於 BT-600 和 NaviCap 平台，我們正在為下一階段的臨床開發做準備，致力於突破 UC 的治療天花板。

Operator, we're now ready for questions.

接線員，現在我們可以回答問題了。

(Operator Instructions).

（操作員指令）。

John Vandermosten, Zacks.

約翰‧范德莫斯滕 (John Vandermosten)，Zacks。

Good afternoon, Adi and Eric. I'll start out with a question on just the topics of negotiation with your partnership. I know you can't say too much about it, but is it revolving around market assumption, pricing, penetration, technical execution or I'm just wondering kind of how the talks are going? And what are the main areas of focus?

下午好，阿迪和埃里克。我將首先提出一個有關與你們的合作關係進行談判的議題的問題。我知道你不能透露太多，但它是否圍繞市場假設、定價、滲透、技術執行，或者我只是想知道談判的進展？主要關注領域有哪些？

Hi, John. Yeah, the discussions are narrowing. So they did start very broad with all the things you're talking about. But they are starting to narrow and we're trying to figure out the best way to work with potentially more than one partner and how that would work. So we're getting there. We'd love to tell you more, but it's kind of difficult. We're really close to the end of it. And so hopefully we'll be able to share fairly soon.

你好，約翰。是的，討論範圍正在縮小。因此，他們確實從廣泛的角度開始討論您所談論的所有事情。但它們的範圍開始縮小，我們正在嘗試找出與潛在多個合作夥伴合作的最佳方法以及如何開展工作。所以我們快到了。我們很想告訴你更多信息，但這有點困難。我們真的快要結束了。因此希望我們很快就能分享。

Great. Exciting times for that. And then a couple of technical questions about the results from the BT-600 trial. When we look at the uptake of the drug from the oral versus when it's given through the pill, in one way, it's getting to the tissue through the vasculature, and the other way, it's through direct contact with the tissue. And I'm wondering if there's any, if you looked at that at all and have anything to say about the difference in the way it kind of gets to where it needs to go?

偉大的。那是令人興奮的時刻。然後是關於 BT-600 試驗結果的幾個技術問題。當我們觀察口服藥物的吸收與透過藥丸給藥的情況時，一方面，藥物透過血管到達組織，另一種方式是直接與組織接觸。我想知道，您是否仔細觀察過這個問題，並對其到達目的地的方式有何不同有何看法？

Interesting question because for us, that is the core of why we believe we can do what they have not been able to do, which is get a lot more tissue I mean drug where it matters. So Xeljanz or oral tofacitinib basically gets absorbed just after the stomach in that small GI tract, which is where a lot of these oral medications get absorbed, lots of vasculature. It goes into the entire blood system. And certainly, the blood circulates everywhere, including the colon.

這是一個有趣的問題，因為對我們來說，這就是為什麼我們相信我們能夠做到他們無法做到的事情的核心，那就是獲得更多的組織，我的意思是在重要的地方使用藥物。因此，Xeljanz 或口服託法替尼基本上是在胃部的小胃腸道中被吸收的，許多口服藥物也是在這裡和許多血管中被吸收的。它進入整個血液系統。當然，血液循環到處，包括結腸。

So it comes in through the blood into the colon, and you get to a certain quantity. And all the published data shows what quantities they get to. So we are able to compare because there's enough publications that show, hey, if you had a 10 mg dose and if you had it twice a day, how much do you get in the tissue. And the difficulty there is if you want to increase that, how do you do that, and they've tried. So on our KOL event, I think, it was Dr. Feagan who also mentioned that, look, people who did these drug trials also tried 30 mgs and got better outcomes response, however, with the toxicity, the adverse events were worse. And so the approved label is 10 twice a day, so 20 mgs and not 30.

因此它通過血液進入結腸，並達到一定的數量。所有已發布的數據都顯示了它們的數量。因此我們能夠進行比較，因為有足夠多的出版物顯示，如果你服用 10 毫克劑量並且每天服用兩次，那麼組織中會攝取多少。而困難的是如果你想增加這個數字，你該怎麼做，他們已經嘗試過了。因此，在我們的 KOL 活動中，我認為 Feagan 博士也提到，進行這些藥物試驗的人也嘗試了 30 毫克，並獲得了更好的結果反應，但是，由於毒性，不良事件更嚴重。因此核准的標籤是每天兩次，每次十粒，也就是 20 毫克，而不是 30 毫克。

All of these telling you, look, through the blood, you get to the colon, but in order to get enough, we just cannot dose high enough. We get past the small intestine into the colon. And when we drop the drug along the colon, one of the concerns was, would you actually have uptake in the tissue. So when it goes through the tissue, again, in that KOL event, there's actually some really nice how it works, presentation done by Dr. Sands as well as there are some pictures. So if you look it up, it goes through the tissue and comes out some of it into the blood.

所有這些都告訴你，看，通過血液，你到達結腸，但為了獲得足夠的劑量，我們不能劑量足夠大。我們穿過小腸進入結腸。當我們將藥物滴入結腸時，我們擔心的問題之一是藥物是否真的會被組織吸收。因此，當它再次穿過組織時，在那個 KOL 活動中，它實際上有一些非常好的工作原理，由 Sands 博士進行了演示，並且有一些圖片。如果你查看一下，你會發現它會穿過組織，然後其中一些進入血液。

And so our -- what we noticed first time is about six hours into the dose that you start seeing drug in the blood and then it peaks around 8 to 10 hours. So it's over time, getting more and more absorbed in the tissue and coming out in the blood.

因此，我們第一次注意到，服藥後約六小時，你開始在血液中看到藥物，然後在大約 8 到 10 小時達到高峰。隨著時間的推移，它會越來越多地被組織吸收並隨血液排出。

Being in the blood systemically is not great. You need just a really small amount, not the high amounts. So we can get large quantities into that tissue that we need to reach without having to get a lot into the blood. And that was the beauty of it. So if you look at it, there is some information in clinical trials already that says more would give you better outcomes.

系統性地存在於血液中並不好。您只需要非常少量，不需要大量。因此，我們可以將大量的藥物輸送到需要到達的組織中，而不需要將大量的藥物輸送到血液中。這就是它的美妙之處。所以如果你看一下，你會發現臨床試驗中已經有一些資訊顯示更多的資訊會帶來更好的結果。

And you can compare with other JAK inhibitors also where they keep dosing higher and higher, response is great. It's the adverse reactions they have to stop. So the fact that we can get extremely high tissue exposure with very small systemic exposure is a big deal. And we did walk through how we got that information partly in the KOL, partly in the [Dex]. So I encourage people to look it up. It's really exciting. We were thrilled with what we saw, exactly what we hoped for.

您也可以將其與其他 JAK 抑制劑進行比較，它們的劑量越來越高，反應很好。他們必須阻止的是不良反應。因此，我們能夠以非常小的系統暴露獲得極高的組織暴露，這一事實意義重大。我們確實介紹瞭如何從 KOL 和[德克斯]。因此我鼓勵人們去查一下。這真是令人興奮。我們對所見所聞感到非常興奮，這正是我們所希望的。

Great. And that was a good technical description there. And then kind of on the same line, when you take the oral product that's already approved, the entire amount of drug is processed to the body. But when you're using the mechanical pill, not all of it is really processed. Some of it passes through. Have you done any work to estimate how much of the drug kind of passes through and not and doesn't touch upon the body at all or is that something that's very difficult to measure?

偉大的。那是一個很好的技術描述。同樣，當您服用已獲批准的口服產品時，全部藥物都會被身體吸收。但當你使用機械藥丸時，並非所有的東西都真正被處理了。有些會通過。您是否做過任何工作來估計有多少藥物通過了身體，而沒有接觸到身體，或者這是否很難測量？

Interesting question. So we do have some of that information. So we collected all these different things and we'll be sharing more information. Majority of it does get absorbed in the colon. Some of it in sometimes does come out the other end without getting absorbed, but we did collect that information. We know because we dropped the load at the beginning entry to the colon. And over time, it crosses the entire colon.

有趣的問題。所以我們確實有一些這樣的資訊。因此我們收集了所有這些不同的東西，我們將分享更多資訊。大部分確實被結腸吸收。有些資訊有時確實會從另一端出來而未被吸收，但我們確實收集了這些資訊。我們知道，因為我們在剛進入結腸時就把負荷卸了下來。隨著時間的推移，它會穿過整個結腸。

And remember, we took biopsies. So we know it went all the way to the end of the colon. The majority of it does get absorbed and the small quantities that come out. And we'll share some more of that data in the coming conference as we mentioned. So we do have that and we'll continue to collect more of that information to see how much of this drug goes in the tissue and what if any comes out the other end.

請記住，我們進行了活檢。所以我們知道它一直到達了結腸末端。大部分都會被吸收，少量則會被排出。正如我們所提到的，我們將在即將舉行的會議上分享更多數據。所以我們確實有這個，並且我們將繼續收集更多這方面的信息，以了解有多少藥物進入組織，以及如果有的話，有多少從另一端出來。

Great. All right.

偉大的。好的。

Great. All right. We're looking forward to it. Thank you, Adi.

偉大的。好的。我們對此充滿期待。謝謝你，阿迪。

Joseph Pantginis, H.C. Wainwright.

約瑟夫·潘吉尼斯（H.C.）溫賴特。

Hey, everybody. Good afternoon and thanks for taking the question. So two questions. First, is a logistics question and second is a perspective question. So on the logistics front, in anticipation of more advanced clinical studies, whether in your hands or in a partner's hands, I was hoping you could discuss your relative current capacity and intermediate needs for device availability and manufacturing.

嘿，大家好。下午好，感謝您回答這個問題。所以有兩個問題。首先是一個物流問題，其次才是觀點問題。因此，在物流方面，為了進行更先進的臨床研究，無論是在您手中還是在合作夥伴手中，我希望您可以討論您目前的相對產能以及設備可用性和製造的中間需求。

Yeah. So you're talking about NaviCap?

是的。所以您說的是 NaviCap？

Yeah.

是的。

Yes. So NaviCap, which is being used in our BT-600 for the UC trial, we have some contract manufacturers already that we work with. We have our internal team that has the expertise to build like a handful of these. But we even already work with some contract manufacturers that we could make several hundred and we've planned to be able to make several thousand. We're ready to do that in the short period of time.

是的。因此，我們在 BT-600 中為 UC 試驗採用的 NaviCap 已經與一些合約製造商進行了合作。我們擁有自己的內部團隊，他們擁有建立此類產品的專業知識。但我們甚至已經與一些合約製造商合作，我們可以生產幾百個，並且我們計劃生產數千個。我們已準備好在短時間內完成這項目標。

But in the meantime, we're working on further automation so that when we need them, we'll be able to make plenty of these. So all of that is in motion for the next short period of time, which would be 12 to 18 months. The ability to make a few thousand of these pills exists. And we have those vendors and contract manufacturers set up to go.

但同時，我們正在致力於進一步實現自動化，以便當我們需要它們時，我們能夠生產大量這樣的產品。所以所有這些都將在接下來的短時間內進行，也就是 12 到 18 個月。目前，我們有能力生產數千顆這樣的藥丸。我們已經準備好這些供應商和合約製造商。

So we don't see that as a huge thing, down the road, though, we do need to do a little more work as we have started building the automation required to build to be able to make the hundreds of thousands that we would need to down the road.

因此，我們並不認為這是一件大事，但是，從長遠來看，我們確實需要做更多的工作，因為我們已經開始建立所需的自動化系統，以便能夠生產未來所需的數十萬台。

That's very helpful. Thanks for that. And then the perspective question is, I was hoping you can provide some information because, obviously, with BioJet, the bioavailability is one of the key attributes of the asset. Now some of the data or a lot of the data that you put out there, and you talked about in your press release also as a reminder, you're seeing in the range of 40% bioavailability. So I was hoping you could offer up some perspective as to how that really compares to IV formulations of drugs.

這非常有幫助。謝謝。然後問題是，我希望您能提供一些信息，因為顯然，對於 BioJet 來說，生物利用度是該資產的關鍵屬性之一。現在，您發布的部分數據或大量數據以及您在新聞稿中提到的提醒都表明，生物利用度在 40% 左右。所以我希望您能提供一些觀點，說明這與靜脈注射藥物相比有何不同。

Wow. Yeah, it's really interesting. So I could just look back to this when our Head of Research, Sharat, was presenting. There were others on that panel. They were from a lot of large pharma companies. They were all talking about the most commonly used methods of trying to make these available through permeability enhancers, through entire coating, all of those they end up being sort of single-digits or mid-single digits. And it's really hard to get that beyond. There are some technologies that have claimed to have higher numbers. But there's nothing that has consistently shown the ability to reach even double-digits.

哇。是的，真的很有趣。因此，當我們的研究主管 Sharat 進行演講時，我可以回顧這一點。該小組還有其他人。他們來自許多大型製藥公司。他們都在談論最常用的方法，試圖透過滲透增強劑、整個塗層來實現這些目標，而這些方法最終都達到了個位數或中等個位數。但要超越這一點真的非常困難。有些技術聲稱擁有更高的數字。但沒有哪支球隊能夠持續展現達到兩位數的能力。

So it's basically comparing to under 10% for things that potentially could be done reliably and for us to be able to have a technology, which is what BioJet is the platform where we can essentially take your formulation that you currently use in your needle-based delivery system and get close to 40%. So when you compare to IV. IV being the gold standard, subcu injection ranges in sort of 50% to 60% of IV. And so getting to 40% of IV, it's almost as good as a subcu injection.

因此，這基本上相當於低於 10% 的可能可靠完成的事情，並且我們能夠擁有一項技術，這就是 BioJet 平台，我們基本上可以將您目前在基於針頭的輸送系統中使用的配方提高到接近 40%。因此當你與 IV 進行比較時。靜脈注射是黃金標準，皮下注射範圍約為靜脈注射的 50% 到 60%。因此，達到靜脈注射的 40% 幾乎與皮下注射一樣好。

We think that's phenomenal and so do our collaborators. And the fact that we can do this with such minimal manipulation of whatever formulation you have is another big advantage. Over time, we see this as being applicable to so many places. We just got to get to that step one and step two, which is coming up really in the near-term.

我們和我們的合作者都認為這是非凡的。事實上，我們可以透過對現有配方進行最少的調整來實現這一點，這是另一個巨大的優勢。隨著時間的推移，我們發現這適用於許多地方。我們只需進入第一步和第二步，這實際上將在近期實現。

So thanks for that question. Perspective-wise, we're thrilled. We keep looking at all these different places for others to show a broadly applicable platform that could do even double-digits and it's hard to see. We don't see them.

感謝您的提問。從視角來看，我們感到非常興奮。我們一直在尋找不同的地方來展示一個可以廣泛應用的平台，甚至可以達到兩位數，但這很難實現。我們沒有看到它們。

Great. Thanks for the added details.

偉大的。感謝您補充詳細資訊。

Thank you. As there are no further questions, I would now like to hand the conference over to Adi for closing comments.

謝謝。由於沒有其他問題，我現在想將會議交給阿迪進行最後評論。

Well I want to thank everyone for joining us. We look forward to keeping you updated as we continue to advance our programs. Good afternoon.

我想感謝大家的參與。我們期待在我們繼續推進專案的過程中及時向您通報最新情況。午安.

Thank you. This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation.

謝謝。今天的電話會議到此結束。現在您可以斷開您的線路。感謝您的參與。