Evelo Biosciences Inc (EVLO) 2022 Q4 法說會逐字稿

Good morning, and welcome to Evelo Biosciences Conference Call to discuss its fourth quarter and full year 2022 financial results and business updates. (Operator Instructions) Please be advised this call is being recorded at the company's request.

早上好，歡迎參加 Evelo Biosciences 電話會議，討論其第四季度和 2022 年全年財務業績和業務更新。 （操作員說明）請注意，本次通話是應公司要求進行錄音的。

At this time, I'd like to turn the call over to (inaudible) of Evelo. Please proceed.

此時，我想將電話轉給（聽不清）Evelo。請繼續。

Thank you. This morning, we issued our fourth quarter and full year 2022 financial results and business updates. This release is available at evelobio.com under the Investors tab.

謝謝。今天早上，我們發布了 2022 年第四季度和全年財務業績和業務更新。此版本可在 evelobio.com 的“投資者”選項卡下獲取。

Today, on the call we have [Balkrishan Gill], Chief Executive Officer; Marella Thorell, Chief Financial Officer; and Mark Bodmer, Chief Scientific Officer.

今天，首席執行官 [Balkrishan Gill] 參加了電話會議； Marella Thorell，首席財務官；和首席科學官馬克·博德默。

Before we begin, I would like to remind everyone that statements made during this conference call that do not relate to matters of historical fact, including statements about our objectives and anticipated clinical milestones, the impact of any of our product candidates and the timing and results of any clinical trials should be considered forward-looking statements, including within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements are intended to be subject to the safe harbor protection provided by the Reform Act and all other applicable law. Actual results could differ materially from those indicated by the forward-looking statements due to the impact of many factors.

在開始之前，我想提醒大家，本次電話會議期間發表的聲明與歷史事實無關，包括有關我們的目標和預期臨床里程碑、我們任何候選產品的影響以及時間和結果的聲明任何臨床試驗的結果均應被視為前瞻性陳述，包括 1995 年《私人證券訴訟改革法案》含義內的前瞻性陳述。此類前瞻性陳述旨在受到《改革法案》和所有其他適用法案提供的安全港保護的約束。法律。由於許多因素的影響，實際結果可能與前瞻性陳述所示的結果存在重大差異。

Participants are directed to the risk factors set forth in Evelo's annual report on Form 10-K for the period ended December 31, 2022, and the company's other filings with the Securities and Exchange Commission.

參與者請參閱 Evelo 截至 2022 年 12 月 31 日的 10-K 表格年度報告以及該公司向美國證券交易委員會提交的其他文件中列出的風險因素。

Any forward-looking statements made today speak only to Evelo's operations as of today. Evelo disclaims any duty to provide updates to its forward-looking statements even if subsequent events cause the company's views to change.

今天發表的任何前瞻性聲明僅涉及 Evelo 截至目前的運營情況。即使後續事件導致公司觀點發生變化，Evelo 也不承擔任何更新其前瞻性陳述的義務。

I will now hand the call over to Simba.

我現在將電話轉交給辛巴。

Thanks (inaudible). Good morning, everyone, and thank you for joining us. We wanted to spend some time reviewing our progress over 2022, our current status and key milestones [in] 2023.

謝謝（聽不清）。大家早上好，感謝您加入我們。我們想花一些時間回顧 2022 年的進展、目前的狀態以及 2023 年的關鍵里程碑。

I'll begin by highlighting an important advance, which we announced in February. The progress of EDP2939, the first bacterial extracellular vesicle product candidate. EDP2939 has begun dosing in patients with moderate psoriasis. EDP2939 cleared safety and tolerability in healthy volunteers initial therapeutic dose (technical difficulty) escalating dose stages of the Phase I (technical difficulty).

首先我要強調我們在二月份宣布的一項重要進展。第一個細菌細胞外囊泡候選產品EDP2939的進展。 EDP​​2939 已開始在中度銀屑病患者中給藥。 EDP​​2939在健康志願者的初始治療劑量（技術難度）和I期劑量遞增階段（技術難度）中清除了安全性和耐受性。

Psoriasis patients are now receiving EDP2939 in the Phase II study at the initial therapeutic dose. As far as we know, this is the first Phase II for an orally delivered microbial extracellular vesicle being investigated for the treatment of a systemic (technical difficulty). We expect data from the Phase II study with EDP2939 to be available in the (technical difficulty) this year. A reminder that EDP2939 is the EV product candidate that is derived as a pure active substance from EDP1815. The science and preclinical (technical difficulty) EDP2939 strongly suggests the potential to drive greater efficacy than EDP1815 (technical difficulty) safety and tolerability.

銀屑病患者目前正在 II 期研究中以初始治療劑量接受 EDP2939。據我們所知，這是第一個口服微生物細胞外囊泡的第二階段研究，用於治療全身性疾病（技術困難）。我們預計 EDP2939 的 II 期研究數據將於今年（技術難度）提供。請注意，EDP2939 是 EV 候選產品，是從 EDP1815 衍生而來的純活性物質。科學和臨床前（技術難度）EDP2939 強烈表明，與 EDP1815（技術難度）安全性和耐受性相比，其具有提高療效的潛力。

Mark will review more on our extracellular vesicle program (technical difficulty) another potential for EDP2939 build on clinical experience with EDP1815. Beyond progress on our EV program, I wanted to recap a few highlights from last year. In late 2021, we reported that our Phase II mild-to-moderate psoriasis study on EDP1815 significantly (technical difficulty) versus placebo at the end of the 16-week treatment period. PASI-50 or greater responses were 25% to 32% versus 12% for placebo with statistical significance of p value less than 0.05 (technical difficulty) active cohorts.

Mark 將詳細回顧我們的細胞外囊泡計劃（技術難度）以及 EDP2939 的另一個潛力，該潛力建立在 EDP1815 的臨床經驗基礎上。除了我們的電動汽車計劃的進展之外，我還想回顧一下去年的一些亮點。 2021 年末，我們報導了 EDP1815 的 II 期輕至中度銀屑病研究在 16 周治療期結束時與安慰劑相比顯著（技術難度）。 PASI-50 或更高的反應率為 25% 至 32%，而安慰劑為 12%，p 值的統計顯著性小於 0.05（技術難度）活躍隊列。

Into early 2022, we continued to follow (technical difficulty) 24 additional weeks after they ceased treatment with EDP1815 in Part B of the study. Clinical responses were maintained or even improved off treatment. Specifically, 50% patients in Part B with a PASI-50 response or greater maintained this response with no (technical difficulty). All these 45% of patients who had an initial improvement from (technical difficulty) between 50% to 75% experienced a deepening of response to PASI-75 is greater in the follow-up period.

到 2022 年初，我們在研究 B 部分中停止 EDP1815 治療後繼續跟踪（技術難度）24 週。治療後臨床反應得以維持甚至改善。具體來說，B 部分中 50% 具有 PASI-50 反應或更高反應的患者在沒有（技術困難）的情況下維持了這種反應。所有這 45% 的患者（技術難度）最初從 50% 改善到 75%，在隨訪期間對 PASI-75 的反應加深。

This durability of clinical effect is differentiated from standard of care anti-inflammatory medicines. It is consistent with the mechanism of action that we have elucidated showing that SINTAX (technical difficulty) locally in the small intestine to activate a nonclinical (technical difficulty) regulatory T cell population. This is a fundamental breakthrough in the treatment of inflammatory diseases, which suggests great potential for SINTAX medicines.

這種臨床效果的持久性不同於標準護理抗炎藥物。這與我們已經闡明的作用機制一致，表明 SINTAX（技術難度）在小腸局部激活非臨床（技術難度）調節性 T 細胞群。這是炎症性疾病治療的根本性突破，表明 SINTAX 藥物具有巨大潛力。

In November 2022, we published a scientific review in frontiers of immunology, explaining the science behind the small (technical difficulty) based on this growing understanding of the mechanism of action of SINTAX medicines.

2022 年 11 月，我們在免疫學前沿發表了一篇科學評論，基於對 SINTAX 藥物作用機制日益深入的了解，解釋了小事（技術難度）背後的科學。

(technical difficulty) EDP1815 program goal for 2022 was to advance interactions with regulators regarding a potential (technical difficulty) for EDP1815 in psoriasis. (technical difficulty) completed with the FDA, EMA and MHRA over the past few months, providing a path to Phase III. Advancing EDP1815 (technical difficulty) dependent on ability to finance (technical difficulty) prioritization.

（技術困難）2022 年 EDP1815 計劃目標是就 EDP1815 治療銀屑病的潛在（技術困難）問題促進與監管機構的互動。 （技術難度）在過去幾個月裡與 FDA、EMA 和 MHRA 完成，為進入 III 期提供了途徑。推進 EDP1815（技術難度）取決於融資能力（技術難度）優先級。

As you know, we are also investigating the potential of EDP1815 in the Phase II atopic dermatitis study. The first 3 cohorts of this study (technical difficulty) primary endpoint due to an unusually high placebo rate, which we cannot explain. The fourth cohort (technical difficulty) using the faster release capsule are expected in the second quarter of 2023.

如您所知，我們還在研究 EDP1815 在特應性皮炎 II 期研究中的潛力。本研究的前 3 個隊列（技術難度）的主要終點是由於安慰劑率異常高，我們無法解釋。使用更快釋放膠囊的第四批（技術難度）預計將於 2023 年第二季度上市。

Beyond clinical (technical difficulty), I would want to also remind everyone of our accomplishments on the financial side in 2022. In May 2022, we raised $79.2 million through a Registered Direct Offering with participation from the key (technical difficulty) investors.

除了臨床（技術難度）之外，我還想提醒大家我們 2022 年在財務方面取得的成就。2022 年 5 月，我們通過主要（技術難度）投資者參與的註冊直接發行籌集了 7920 萬美元。

In December 2022, we refinanced our existing $45 million debt of (technical difficulty) agreement with Horizon Technology Finance (technical difficulty) 3 years of interest-only payments followed by a 2-year amortization period.

2022 年 12 月，我們與 Horizo​​n Technology Finance（技術難度）協議的現有 4500 萬美元債務進行了再融資（技術難度），為期 3 年的只付利息，隨後是 2 年攤銷期。

I'll now turn over to our Chief Scientific Officer and President of R&D, Mark Bodmer, to provide more detail on our EV platform and report recent updates from our EDP2939 clinical program.

現在，我將請我們的首席科學官兼研發總裁 Mark Bodmer 提供有關我們 EV 平台的更多詳細信息，並報告我們 EDP2939 臨床項目的最新更新。

Thank you, Simba. Bacterial extracellular vesicles, or EVs, are naturally occurring the (technical difficulty) bacteria also be the main means of communication amongst bacteria -- between bacteria and (technical difficulty) cells. (technical difficulty) them well suited as potential drugs engaging the small intestinal access when given orally to induce regulatory (technical difficulty) inflammation throughout the body, and this leads to striking efficacy that has matched anticytokine biologics and JAK inhibitors (technical difficulty) studies.

謝謝你，辛巴。細菌細胞外囊泡（EV）是（技術難度）細菌自然產生的，也是細菌之間——細菌和（技術難度）細胞之間通訊的主要手段。 （技術難度）它們非常適合作為潛在藥物，口服時參與小腸通路，誘導全身調節性（技術難度）炎症，這導致了與抗細胞因子生物製劑和 JAK 抑製劑（技術難度）研究相匹配的驚人療效。

As Simba mentioned, the EV product EDP2939 derives from EDP1815. They're both prepared from fermentation of the same single (technical difficulty) bacteria. EDP1815 (technical difficulty) microbial product prepared from the cell pole of the fermentation, EDP2939 is the EV product (technical difficulty).

正如 Simba 所說，EV 產品 EDP2939 源自 EDP1815。它們都是由相同的單一（技術難度）細菌發酵而成。 EDP​​1815（技術難度）是發酵細胞極製備的微生物產品，EDP2939是EV產品（技術難度）。

Now EDP1815 provided proof of concept of the underlying SINTAX (technical difficulty) the drug action in the small intestine could lead to clinical benefit (technical difficulty) result of biologics and JAK inhibitors, those are the results that Simba described earlier.

現在，EDP1815 提供了基本 SINTAX（技術難度）的概念證明，即小腸中的藥物作用可能導致生物製劑和 JAK 抑製劑的臨床益處（技術難度）結果，這些是 Simba 之前描述的結果。

However, the overall level of response that we've seen in clinical studies so far has actually not been as great as (technical difficulty). And we propose that this is most likely due to limitations in the dose response that can be achieved with EDP1815. The critical factor in understanding why we expect EDP2939 to improve on the EDP1815 in psoriasis this experimental evidence to the main active substance EDP1815 is the EVs that (technical difficulty) in the drug substance. That is EDP1815 can (technical difficulty) as well as on microbial content. Preparations of EVs like 2939 with (technical difficulty) cells have consistently shown higher preclinical potency of up to 2 orders of magnitude in preclinical experiments.

然而，迄今為止我們在臨床研究中看到的總體反應水平實際上並沒有（技術難度）那麼高。我們認為這很可能是由於 EDP1815 所能實現的劑量反應的限制。理解為什麼我們期望 EDP2939 在銀屑病方面優於 EDP1815 的關鍵因素是主要活性物質 EDP1815 的實驗證據是原料藥中的 EV（技術難度）。也就是說EDP1815可以（技術難度）以及微生物含量。在臨床前實驗中，使用（技術難度）細胞製備的 EV（如 2939）始終顯示出高達 2 個數量級的更高臨床前效力。

(technical difficulty) that could mean clinically, published first response modeling of tofacitinib, with oral JAK inhibitor in psoriasis (technical difficulty) suggests there's about fivefold range dose from no response for the maximum response at a maximum tolerated. The fivefold range is actually much smaller than the range that we think we can achieve with the potency improvements between EDP2939 and EDP1815 (technical difficulty) efficacy that Simba described, we saw with EDP1815 in the Phase II psoriasis study was evidence (technical difficulty) dose response curve for the clinical response. So on the basic principles of pharmacology, the increase (technical difficulty) EDP2939 is predicted to be more than adequate for a meaningful shift of that dose response curve. (technical difficulty) EDP2939 enables the possibility of improved clinical activity while maintaining the potential for the placebo-like safety and tolerability that we saw (technical difficulty).

（技術困難）這可能意味著在臨床上，發表的第一個託法替布與口服 JAK 抑製劑治療銀屑病的反應模型（技術困難）表明，從無反應到最大耐受的最大反應，劑量範圍約為五倍。五倍範圍實際上比我們認為通過 Simba 描述的 EDP2939 和 EDP1815（技術難度）功效之間的效力改進可以實現的範圍要小得多，我們在 II 期銀屑病研究中看到 EDP1815 是證據（技術難度）劑量臨床反應的反應曲線。因此，根據藥理學的基本原理，預計 EDP2939 的增加（技術難度）足以實現劑量反應曲線的有意義的轉變。 （技術難度）EDP2939 能夠改善臨床活性，同時保持我們所看到的類似安慰劑的安全性和耐受性的潛力（技術難度）。

The 2 clinical developments reported last month from EDP2939 in its (technical difficulty) milestones and the progress of the product candidate. The first that Simba mentioned was the outcome of Phase I safety cohort of EDP2939 (technical difficulty) in the human volunteers at the initial therapeutic dose level. The trial safety review committee determined that EDP2939 met the safety and tolerability criteria at the therapeutic post-proposed progression to Phase II in patients with moderate psoriasis (technical difficulty) recruitment of psoriasis patients (technical difficulty) study is not progressing well. Based on the current recruitment round, we anticipate reporting with the psoriasis results in the second half of 2023.

上個月 EDP2939 報告的 2 項臨床進展包括其（技術難度）里程碑和候選產品的進展。 Simba 提到的第一個是 EDP2939（技術難度）在人類誌願者中在初始治療劑量水平下的 I 期安全隊列結果。試驗安全審查委員會確定 EDP2939 在治療後擬進展至中度銀屑病患者 II 期（技術難度）時符合安全性和耐受性標準，銀屑病患者招募（技術難度）研究進展不佳。根據當前的招募輪次，我們預計將於 2023 年下半年報告銀屑病結果。

The safety review was important. EDP2939 is differentiated from (technical difficulty) prior generation microbial product candidates by the higher intensive potency of (technical difficulty) and the number of concentration of EVs that can be packed into a single capsule. This first safety evaluation (technical difficulty) at the proposed therapeutic dose EDP2939 with these potencies maintains for the placebo safety and tolerability we previously observed with EDP1815.

安全審查很重要。 EDP​​2939 與（技術難度）上一代微生物產品候選者的區別在於（技術難度）更高的強化效力以及可裝入單個膠囊中的 EV 濃度數量。在提議的治療劑量 EDP2939 上進行的首次安全性評估（技術難度）具有這些效力，維持了我們之前在 EDP1815 中觀察到的安慰劑安全性和耐受性。

I'll now hand back to Simba.

現在我將把事情交還給辛巴。

Thanks, Mark. (technical difficulty) of the current environment for small-cap biotech at a time of (technical difficulty) bringing EDP2939 to the clinic is the culmination of years of discovery in the lab, building on our previous experience with EDP1815. Working out new modalities based on new (technical difficulty) some challenging and some offering the potential for great advances all I think (technical difficulty) of the pharmacology of bacterial EVs as is an example of the latter, a step change in opportunity and potential value for (technical difficulty)

謝謝，馬克。將 EDP2939 推向臨床（技術難度）時小型生物技術當前環境的（技術難度）是基於我們之前在 EDP1815 方面的經驗，在實驗室中多年發現的成果。基於新的（技術難度）制定新的模式，一些具有挑戰性，一些提供了巨大進步的潛力，我認為細菌電動汽車的藥理學（技術難度）就是後者的一個例子，機會和潛在價值的一步變化對於（技術難度）

In closing, I'd like to thank patients involved in our studies, our partners, our shareholders and our remarkable team for their commitment and efforts to enable the progress we have discussed today.

最後，我要感謝參與我們研究的患者、我們的合作夥伴、我們的股東和我們傑出的團隊，感謝他們的承諾和努力，使我們今天討論的進展得以實現。

I'll now open the call for questions.

我現在開始提問。

(Operator Instructions) Our first question comes from the line of Gary Nachman with BMO.

（操作員說明）我們的第一個問題來自 BMO 的 Gary Nachman。

First, for the fourth cohort in the atopic derm trial, looking at the faster release capsule, was there anything you were able to do to modify that cohort to manage the high placebo response you saw with the first 3 cohorts? Or was that locked already? So is there anything you were able to do to modify it?

首先，對於特應性皮膚試驗中的第四個隊列，觀察更快釋放的膠囊，您是否可以採取任何措施來修改該隊列，以管理您在前 3 個隊列中看到的高安慰劑反應？還是已經鎖了？那麼您可以做些什麼來修改它嗎？

Gary, so -- 2 things. One, we obviously have engaged very deeply with the sites at which the study has been run to ensure as much as possible that the study is being run according to protocol that patients are respecting (technical difficulty). I raised that because one of the possible explanations for the high placebo rate could be (technical difficulty) use of topical steroids for example, in placebo patients. So we've done that. Beyond that, the study was -- the fourth cohort was already underway and we (technical difficulty)

加里，所以——有兩件事。第一，我們顯然與進行研究的地點進行了非常深入的接觸，以盡可能確保研究按照患者遵守的方案進行（技術難度）。我提出這一點是因為安慰劑率高的可能解釋之一可能是（技術困難）在安慰劑患者中使用局部類固醇。所以我們已經做到了。除此之外，這項研究——第四組已經在進行中，我們（技術難度）

Okay. Great. And then depending on the results of the fourth cohort, are there any other tweaks you could potentially do to the faster release capital, if necessary, if you don't have the exact data that you're hoping for? Or is that profile fully optimized? And if the fast release capsule looks good in atopic derm, is there anything you would need to do before using it in a Phase III psoriasis trial, assuming that's still the plan?

好的。偉大的。然後，根據第四組的結果，如果您沒有所需的確切數據，如果有必要，您是否可以對更快地釋放資本進行任何其他調整？或者該配置文件是否已完全優化？如果快速釋放膠囊在特應性皮膚中看起來效果很好，假設這仍然是計劃，那麼在將其用於 III 期銀屑病試驗之前，您需要做些什麼嗎？

Yes. So let me take those in reverse order. If we (technical difficulty) with the faster release, there's nothing further that we need to do to take it into the Phase III trial in psoriasis. In terms of whether or not it's optimized, the clinical (technical difficulty), as you know, remind everybody else, in humans on the release profile with the faster releases, is very positive. So we're releasing the vast majority of product in the right place in the proximal small intestine with the current capsule release. So I think it is very well positioned. There's always a (technical difficulty) will need them.

是的。那麼讓我以相反的順序來看這些。如果我們（技術上的困難）能夠更快地釋放，那麼我們不需要做任何進一步的事情就可以將其納入銀屑病的 III 期試驗。就其是否優化而言，正如您所知，臨床（技術難度）提醒其他人，在人類中以更快的釋放速度進行釋放，是非常積極的。因此，我們通過當前的膠囊釋放將絕大多數產品釋放到近端小腸的正確位置。所以我認為它的定位非常好。總會有（技術困難）需要它們。

Okay. And you guys are breaking up a little bit, but I think you had said that you wouldn't be able to start the Phase III in psoriasis and so you have the appropriate financing. So maybe just comment, Simba, about partnership discussions if those are ongoing for both 1815 or 2939 and the timing of that potentially? And then just what's the expected cash burn for this year given what you have in front of you?

好的。你們有點分手了，但我想你們說過你們無法啟動牛皮癬的第三階段，所以你們有適當的融資。那麼辛巴，也許只是評論一下合作夥伴關係討論是否在 1815 年或 2939 年進行，以及可能的時間安排？那麼考慮到您所面臨的情況，今年的預期現金消耗是多少？

I'll take the question on partnering, and then I'll hand over to Marella, our Chief Financial Officer, to discuss cash burn. So on partner in a significant number of discussions around different partnering possibilities that fall into the obvious buckets. So on (technical difficulty) 1815 from a clinical development and commercialization perspective, both in psoriasis as well as (technical difficulty) and then partnership discussions on EDP2939 and the broader EV platform. So multiple discussions going on across the breadth. Our fundamental goal is to get a partnership over the course of this year.

我將回答有關合作的問題，然後交給我們的首席財務官 Marella 討論現金消耗問題。因此，就屬於明顯類別的不同合作可能性進行大量討論。等等（技術難度）1815，從臨床開發和商業化的角度來看，無論是銀屑病還是（技術難度），然後是關於 EDP2939 和更廣泛的 EV 平台的合作夥伴討論。因此，廣泛的討論正在進行中。我們的基本目標是在今年內建立合作夥伴關係。

So I think I'll hand over to Marella to talk about the cash burn.

所以我想我會交給 Marella 來討論現金消耗問題。

Thanks for the question. So we have (technical difficulty) this year and following a number of the cash preservation (technical difficulty) this year, we are prioritizing our investment in our 2 key clinical programs and milestones this year (technical difficulty) program and advancing 2939 in the moderate psoriasis study (technical difficulty) in the second half of this year.

謝謝你的提問。所以我們今年有（技術難度），繼今年有一些現金保值（技術難度）之後，我們優先投資我們的2個關鍵臨床項目和今年的里程碑（技術難度）項目，並在適度的情況下推進2939今年下半年的牛皮癬研究（技術難度）。

Our next question comes from the line of Vikram Purohit with Morgan Stanley.

我們的下一個問題來自 Vikram Purohit 與摩根士丹利的對話。

This is Gospel on for Vikram. We have 2 questions. So for the AD data expected in 2Q, I guess, what is the efficacy hurdle that you are looking to cross? And then also to same for the 2939 data in psoriasis expected in the second half, what do you see as the bar for success in terms of efficacy and safety?

這對維克拉姆來說是福音。我們有 2 個問題。因此，對於第二季度預計的 AD 數據，我想，您希望跨越的功效障礙是什麼？預計下半年將有 2939 份銀屑病數據，您認為在功效和安全性方面成功的標準是什麼？

So on the AD data, we've given previous guidance but on the (technical difficulty) we'd be looking for around 40% of PASI-50 -- sorry, EASI-50 (technical difficulty) patients on active with EASI-50 or greater or placebo separation of 15%. So a separation in terms of percentage of patients with EASI-50 or greater of 15%.

因此，根據 AD 數據，我們之前已經給出了指導，但在（技術難度）方面，我們會尋找大約 40% 的 PASI-50——抱歉，EASI-50（技術難度）患者正在積極使用 EASI-50或更高或安慰劑分離 15%。因此，EASI-50 或更高的患者百分比分離為 15%。

(technical difficulty) on the cohort 4 data. And that's been consistent guidance for some time possible. On the (technical difficulty) data with EDP2939 (technical difficulty) the remainder of the integrated profile but underpins everything we're doing. Very uniquely, the potentially (technical difficulty) drug that is very safe and well tolerated and has meaningful efficacy and can be priced with flexibility.

（技術難度）第 4 組數據。這在一段時間內一直是一致的指導。關於（技術難度）數據與 EDP2939（技術難度）集成配置文件的其餘部分，但支撐了我們正在做的一切。非常獨特的是，這種潛在的（技術難度）藥物非常安全、耐受性良好，具有有意義的療效，並且可以靈活定價。

What (technical difficulty) is something that has a Tesla-like efficacy or greater with safety and tolerability and (technical difficulty) level or greater would be a big win. You're aware, Gospel, you guys have a forecast for (technical difficulty) but I think it's most people consider on track to be a $3 billion a year drug with significant tolerability issues.

什麼（技術難度）是具有類似特斯拉的功效或更高，並且安全性和耐受性以及（技術難度）水平或更高的東西將是一個巨大的勝利。你知道，福音，你們對（技術難度）有一個預測，但我認為大多數人認為這是一種每年 30 億美元的藥物，但存在嚴重的耐受性問題。

So (technical difficulty) efficacy with safety and tolerability, we've got a major drug. We're very close to that level of efficacy (technical difficulty) and I think we have strong conviction that, that is a likely result. (technical difficulty) even more exciting is what Mark talked about because of the fact that preclinically, we're seeing (technical difficulty) or biologic (technical difficulty) there's a big range between (technical difficulty) efficacy engaged at that level. But anywhere in that range is a win for us with EDP2939.

所以（技術難度）功效與安全性和耐受性，我們已經有了一種主要藥物。我們非常接近這個效率水平（技術難度），我認為我們堅信，這是一個可能的結果。 （技術難度）更令人興奮的是馬克所說的，因為在臨床前，我們看到（技術難度）或生物學（技術難度）在該水平上的（技術難度）功效之間存在很大的差異。但在這個範圍內的任何地方，EDP2939 都是我們的勝利。

Our next question comes from the line of Kristen Kluska with Cantor.

我們的下一個問題來自克里斯汀·克魯斯卡（Kristen Kluska）和康托爾（Cantor）的對話。

I just have one this morning. So I understand you haven't necessarily discovered what has caused the high response in placebo, but I'm curious if there's anything that you're able to rule out at this time?

我今天早上只有一個。所以我知道你不一定發現是什麼導致了安慰劑的高反應，但我很好奇你現在是否可以排除什麼？

(technical difficulty) So we have essentially ruled out the obvious possibility that there was a mixup in supplier drug (technical difficulty) patients took active instead of placebo in place versa (technical difficulty) and we've worked through all of that, that does not seem to be (technical difficulty). So that's the one (technical difficulty).

（技術困難）因此，我們基本上排除了供應商藥物中存在混淆的明顯可能性（技術困難）患者採取了活性藥物而不是安慰劑，反之亦然（技術困難）並且我們已經解決了所有這些問題，這確實似乎不是（技術難度）。這就是（技術難度）。

(Operator Instructions) Our next question comes from the line of (technical difficulty) with Cowen.

（操作員說明）我們的下一個問題來自 Cowen 的（技術難度）路線。

I guess just to start out, could you discuss what gives you the confidence to move forward with the lower dose in the psoriasis patients? And did you see any evidence of target engagement or biomarker changes in healthy volunteers in that study, in the 2939?

我想首先，您能否討論一下是什麼讓您有信心在銀屑病患者中繼續使用較低劑量？在 2939 年的研究中，您是否看到健康志願者的目標參與或生物標誌物變化的任何證據？

I'll let Mark take those questions.

我會讓馬克回答這些問題。

So we've used actually a very conservative scaling factor to get from preclinical studies (technical difficulty) clinical is the (technical difficulty) particles of the exposure (technical difficulty) actually, based on the staining volume, if you know your PK/PD and pharmacology (technical difficulty) that's 100x higher than would be predicted.

因此，我們實際上使用了一個非常保守的縮放因子，從臨床前研究（技術難度）中獲得，臨床實際上是暴露（技術難度）的（技術難度）顆粒，基於染色量，如果您知道您的 PK/PD和藥理學（技術難度）比預期高 100 倍。

The ability to do that is actually based on the small size of the EVs (technical difficulty) and that's a big part of the (technical difficulty) as you go back to (technical difficulty) a moment ago to the question about the expected outcome in (technical difficulty) EDP2939 actually the whole point of what I was saying was to do with the estimated probability of getting above that (technical difficulty) baseline level of efficacy based on very, very basic (technical difficulty) with pharmacology in terms of potency and (technical difficulty) goes forward. So the (technical difficulty) we spent a lot of time for baking how do we pick a single dose for a (technical difficulty) study for a Phase IIa and the answer is we went (technical difficulty) cost. We went way above what we thought was likely to be the minimum effective dose.

做到這一點的能力實際上是基於電動汽車的小尺寸（技術難度），這是（技術難度）的很大一部分，因為你回到（技術難度）剛才關於預期結果的問題（技術難度）EDP2939 實際上我所說的重點是基於非常非常基本的（技術難度）藥理學在效力和（技術難度）繼續前進。因此，（技術難度）我們花了很多時間來研究如何為 IIa 期（技術難度）研究選擇單劑量，答案是我們去了（技術難度）成本。我們的劑量遠遠超出了我們認為可能的最低有效劑量。

Great. And did you guys see a target engagement or biomarket changes in the healthy volunteers?

偉大的。你們是否看到健康志願者的目標參與度或生物市場變化？

We didn't do that. So actually, you need to get me for an hour separately. So these drugs work in (technical difficulty) stage (technical difficulty) it's not to see unless there's inflammation going on. It's the same with these. So in the healthy volunteers, we don't even look at that because (technical difficulty)

我們沒有那樣做。所以實際上，你需要單獨給我一個小時。所以這些藥物在（技術難度）階段（技術難度）起作用，除非有炎症發生，否則是看不到的。這些也是一樣的。所以在健康志願者中，我們甚至不考慮這一點，因為（技術難度）

Great. And then I guess, just could you kind of explain whether -- how you're thinking currently on whether you move forward with EDP1815 assuming the funding or a partnership deal is reached or would you kind of wait for a readout from EDP2939 in the second half of this year?

偉大的。然後我想，您能否解釋一下，如果資金或合作協議達成，您目前如何考慮是否繼續推進 EDP1815，或者您是否會等待第二次 EDP2939 的讀數今年一半？

Yes. So we're working through all of that because there's a couple of key components you touched on both of the (technical difficulty)

是的。所以我們正在解決所有這些問題，因為您觸及了兩個（技術難度）的關鍵組件

Sorry, you broke up a little there. Do you mind repeating that for me?

抱歉，你們在那里分手了一點。你介意為我重複一遍嗎？

Sorry, (technical difficulty). Actually, you broke up, so can you say that again?

抱歉，（技術難度）。其實你們已經分手了，你能再說一遍嗎？

Sorry. So never mind, I'll take it offline.

對不起。所以沒關係，我會把它離線。

That concludes today's question-and-answer session. I'd like to turn the call back to Simba Gill for closing remarks.

今天的問答環節到此結束。我想將電話轉回辛巴·吉爾（Simba Gill），讓其致閉幕詞。

Thank you very much, everyone. Appreciate everybody continuing to follow us. This is a very exciting time for us. And we look forward to updating further on our clinical programs. And as we've talked about on this call, updates on EDP2939 in the EV (technical difficulty) next level of efficacy and beyond. Thanks very much, everyone.

非常感謝大家。感謝大家繼續關注我們。這對我們來說是一個非常激動人心的時刻。我們期待進一步更新我們的臨床計劃。正如我們在本次電話會議中討論的那樣，EDP2939 在 EV（技術難度）下一個級別的功效及更高級別的更新。非常感謝大家。

This concludes today's conference call. Thank you for participating. You may now disconnect.

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連接。