Exscientia PLC (EXAI) 2024 Q1 法說會逐字稿

Hello, everyone. My name is Sarah, and I will be your conference operator today. At this time, I would like to welcome everyone to Exscientia's business update call for the first quarter 2024. (Operator Instructions) At this time, I would like to introduce Chin Okeke, Associate Director of Strategy and Investor Relations. Chin, you may begin.

大家好。我叫莎拉，今天我將擔任你們的會議操作員。此時此刻，我歡迎大家參加 Exscientia 2024 年第一季的業務更新電話會議。（操作員須知）這時我想介紹一下策略與投資人關係副總監Chin Okeke。欽，你可以開始了。

Thank you, operator, and welcome, everyone, to Exscientia's first quarter 2024 financial results. And business update conference call. A press release and 6-K were issued this morning with our first quarter 2024 financial results and business update. These documents can be found on our website at investors.exscientia.ai along with the presentation for today's webcast.

謝謝業者，歡迎大家關注 Exscientia 2024 年第一季的財務表現。以及業務更新電話會議。今天早上發布了一份新聞稿和 6-K，其中介紹了我們 2024 年第一季的財務業績和業務更新。這些文件以及今天網路廣播的簡報可以在我們的網站 Investors.exscientia.ai 上找到。

Before we begin, I'd like to remind you that we may make forward-looking statements on our call. These may include statements about our projected growth, revenue, business models, preclinical and clinical progress and results, and business activities and performance, as well as our anticipated cash runway. Actual results may differ materially from those indicated by these statements. Unless required by law, Exscientia does not undertake any obligation to update these statements regarding the future or to confirm these statements in relation to actual results.

在開始之前，我想提醒您，我們可能會在電話會議中做出前瞻性陳述。這些可能包括有關我們預計成長、收入、業務模式、臨床前和臨床進展和結果、業務活動和業績以及我們預期現金跑道的聲明。實際結果可能與這些陳述所示的結果有重大差異。除非法律要求，Exscientia 不承擔任何更新這些有關未來的聲明或根據實際結果確認這些聲明的義務。

On today's call, I'm joined by Dr. Dave Hallett, Interim Chief Executive Officer and Chief Scientific Officer; and Ben Taylor, Chief Financial Officer and Chief Strategy Officer. And with that, I will now turn the call over to Dave.

臨時執行長兼首席科學官 Dave Hallett 博士也參加了今天的電話會議。財務長兼首席策略長 Ben Taylor。現在，我將把電話轉給戴夫。

Thank you, Chin. While the first quarter of 2024 has been my first officially leading Exscientia, the turn of the year marked the beginning of my fifth year as a senior executive at the company. With this experience and perspective in mind, I firmly believe that 2024 will be a year of opportunity for Exscientia to continue making substantial progress on our mission to shift the curve of the pharmaceutical industry. The tangible benefits of our investments in platform and infrastructure are gaining pace.

謝謝你，欽。雖然 2024 年第一季是我第一次正式領導 Exscientia，但新年伊始標誌著我在該公司擔任高階主管的第五年的開始。考慮到這些經驗和觀點，我堅信 2024 年將是 Exscientia 有機會繼續在我們改變製藥業曲線的使命上取得實質進展的一年。我們在平台和基礎設施方面的投資的實際效益正在不斷顯現。

When we at Exscientia refer to shifting the curve, we are referring to reducing the cost and time lines of contemporary drug discovery, design, and development, while also increasing the probability of success. We have already demonstrated a repeated ability to lower the cost and time in the discovery phase of drug design projects. Our clinical pipeline has multiple shots on goal this year to start to improve upon the low probability of success historically seen by the wider industry.

當 Exscientia 提到改變曲線時，我們指的是降低當代藥物發現、設計和開發的成本和時間，同時增加成功的可能性。我們已經反覆證明了在藥物設計專案的發現階段降低成本和時間的能力。我們的臨床管道今年有多個目標，以開始改善更廣泛行業歷史上成功機率較低的情況。

These include our most advanced program, GTAEXS-617 or 617 for short, a potential best-in-class CDK7 inhibitor. We expect to present top line clinical data from the dose escalation phase of the elucidate Phase 1/2 study in the second half of this year. The XS4318 or 4318, a selective PKC Theta inhibitor designed by Exscientia and in-licensed by Bristol Myers Squibb for immunology and inflammation indications. 4318 has shown positive early results in its Phase 1 study has the potential to be a first-in-class immunology drug.

其中包括我們最先進的項目 GTAEXS-617 或簡稱 617，它是一種潛在的同類最佳 CDK7 抑制劑。我們預計將在今年下半年提供闡明 1/2 期研究的劑量遞增階段的主要臨床數據。XS4318 或 4318 是一種選擇性 PKC Theta 抑制劑，由 Exscientia 設計，並獲得百時美施貴寶 (Bristol Myers Squibb) 許可，用於免疫學和發炎適應症。 4318 在其 1 期研究中顯示出積極的早期結果，有潛力成為一流的免疫學藥物。

There's two compounds designed for Sumitomo Pharma, which are currently in psychiatric disease that could read out this year. All these candidates were created by Exscientia because traditional methods have resulted in compounds with major developmental issues. Initial data from several programs will begin to demonstrate, but our design solutions can significantly improve probability of success in the clinic.

有兩種為住友製藥設計的化合物，目前正在治療精神疾病，今年可能會獲得批准。所有這些候選藥物都是由 Exscientia 創建的，因為傳統方法產生的化合物存在重大發育問題。來自多個專案的初始數據將開始證明，但我們的設計解決方案可以顯著提高臨床成功的可能性。

Today, we are providing updates for our highly differentiated LSD1 inhibitor the XS74539, or 539, which continues its progression towards a Phase 1 clinical trial in acute myeloid leukemia patients. And for the first time announcing our plans for our MALT1 inhibitor, XS73565 or 565 as a potential treatment for B-cell lymphomas, including chronic lymphocytic leukemia.

今天，我們為高度差異化的 LSD1 抑制劑 XS74539 或 539 提供更新，該抑制劑繼續在急性髓系白血病患者中進行 1 期臨床試驗。並首次宣布我們的 MALT1 抑制劑 XS73565 或 565 計劃作為 B 細胞淋巴瘤（包括慢性淋巴細胞白血病）的潛在治療方法。

We have built a platform with a focus on the efficient discovery, design, and development of highly differentiated small molecule compounds. Our first-of-its-kind automation lab, integrating our AI design capabilities with automated design, make test loops launch towards the middle of last year. We have already transitioned three programs over to the facility, and we'll continue to add more during 2024. Prior to the opening of the lab, ever compound we have designed has been synthesized at the CRO or by our partners.

我們建立了一個專注於高效發現、設計和開發高度差異化小分子化合物的平台。我們的首個自動化實驗室將我們的人工智慧設計能力與自動化設計相結合，在去年年中啟動了測試循環。我們已經將三個項目轉移到該設施，並且我們將在 2024 年繼續添加更多項目。在實驗室開放之前，我們設計的所有化合物都已在 CRO 或我們的合作夥伴處合成。

We have analyzed synthesis data from these legacy campaigns and believe that at least 75% of these multistep compounds and 90% of the overall reaction types are automatable and could have been run through our facility. This is important as we aim to push through the logistical and time bottlenecks of working with third parties and reduce the CRO costs associated with these activities. We are already starting to see an initial positive impact from a studio with like-for-like biology resource requirements coming down by at least 75%, and in many cases, by more than 90%.

我們分析了這些遺留活動的合成數據，並相信至少 75% 的這些多步驟化合物和 90% 的整體反應類型是可自動化的，並且可以透過我們的設施運作。這一點很重要，因為我們的目標是突破與第三方合作的後勤和時間瓶頸，並降低與這些活動相關的 CRO 成本。我們已經開始看到工作室的初步正面影響，同類生物資源需求下降了至少 75%，在許多情況下下降了 90% 以上。

We develop it and optimize assays directly on the platform rather than through an intermediate step. We have started to run unattended overnight assays are executing multiple assays on the same plate and providing the teams with greater opportunity to collect data. The active learning driven nature of our entire approach from AI to design through automation and across the entire experimentation cycle means we can accelerate the discovery process even further than before and at a more cost effective manner for Exscientia. We are seeing operational efficiencies from the multiyear investments into our integrated platform.

我們直接在平台上開發並優化檢測，而不是透過中間步驟。我們已經開始運行無人值守的過夜檢測，在同一板上執行多個檢測，為團隊提供更多收集數據的機會。我們從人工智慧到設計、自動化以及整個實驗週期的整個方法的主動學習驅動性質意味著我們可以比以前更進一步加速發現過程，並以更具成本效益的方式為 Exs​​cientia 提供幫助。我們看到了對我們整合平台的多年投資所帶來的營運效率。

With these developments in mind, we are continuing to shape our business around the automation of the design, make test learn loop, and ramping of activity through the automation lab. Our laser focus on this process corrects the necessity to scale back or discontinued legacy activities that are not directly aligned with our core transformative purpose. Automation, advancing our design platform, pipeline development, and partnerships. As part of this process, we intend to anchor our precision medicine capabilities on those aspects that directly influence our pipeline or contribute to our discovery and translational activities.

考慮到這些發展，我們將繼續圍繞設計自動化塑造我們的業務，建立測試學習循環，並透過自動化實驗室擴大活動。我們對這一過程的高度關注糾正了縮減或停止與我們核心變革目標不直接一致的遺留活動的必要性。自動化，推動我們的設計平台、管道開發和合作夥伴關係。作為這個過程的一部分，我們打算將我們的精準醫療能力錨定在那些直接影響我們的產品線或有助於我們的發現和轉化活動的方面。

As a result of the sharpened operational emphasis, we expect to make a total reduction in headcount of somewhere between 20% and 25% of global staff, including reduced activities at our Vienna sites. These changes will result in at least $40 million of annualized savings beginning in 2025. These changes are the natural progression for a technologically driven company and reflect our deep rooted commitment to efficiency, not only with respect to what we do, but critically how we execute and deliver it.

由於營運重點更加突出，我們預計全球員工總數將減少 20% 至 25%，其中包括減少維也納工廠的活動。從 2025 年開始，這些變化將帶來至少 4000 萬美元的年度節省。這些變化是一家技術驅動型公司的自然發展，反映了我們對效率根深蒂固的承諾，不僅涉及我們所做的事情，更重要的是我們如何執行和交付它。

Importantly, this step reaffirms our commitment to the key value drivers of our business, meaning our pipeline, our partnerships on our design and automation capabilities. As I've already mentioned, we will share a few key updates across our pipeline as we look to build long-term value for our business. Starting with 539, our LSD1 inhibitors.

重要的是，這一步驟重申了我們對業務關鍵價值驅動因素的承諾，這意味著我們的管道、我們在設計和自動化能力方面的合作夥伴關係。正如我已經提到的，當我們希望為我們的業務創造長期價值時，我們將分享我們管道中的一些關鍵更新。從我們的 LSD1 抑制劑 539 開始。

As a reminder, we believe that in 539, we have designed the first LSD1 inhibitor that uniquely combines a reversible mechanism of action with an appropriate half-life and CNS penetration. CNS penetration is an important property because it has the potential to address brain metastases, which are prevalent in advanced disease. We believe that having a reversible mechanism of action is important because irreversibly deactivating LSD1 can contribute to poor control of platelet levels.

提醒一下，我們相信在 539 中，我們設計了第一個 LSD1 抑制劑，它獨特地將可逆作用機制與適當的半衰期和 CNS 滲透結合起來。中樞神經系統滲透是一個重要的特性，因為它有可能解決晚期疾病中常見的腦轉移問題。我們認為，具有可逆的作用機制很重要，因為不可逆地使 LSD1 失去活性可能導致血小板水平控制不良。

Having a long half-life has the potential to have the same effect and so the pharmacokinetic properties of the compound are also important. We have previously demonstrated in rodent studies that platelet levels are able to recover even with super efficacious doses of 539, whereas they remain depleted even for intermittently dose irreversible LSD1 inhibitors. This unique combination of properties offers 539 best in class potential.

半衰期長有可能產生相同的效果，因此化合物的藥物動力學特性也很重要。我們先前已在囓齒動物研究中證明，即使使用超有效劑量的 539，血小板水平也能夠恢復，而即使使用間歇劑量的不可逆 LSD1 抑制劑，血小板水平仍然處於耗盡狀態。這種獨特的屬性組合提供了 539 種同類最佳的潛力。

The stoplight chart on this slide is color-coded to show how close a profile compound is to an optimized target product profile. Green represents no deviation from the ideal property range. Amber, a minor deviation, and red, a major deviation. The column on the right hand side represents 539, which is green for all profile properties. The first two columns represent two LSD1 inhibitors developed by other companies, both compounds have major deviations, both have long human half-lives, and neither a CNS penetrant.

此投影片上的紅綠燈圖表採用顏色編碼，以顯示設定檔與最佳化的目標產品設定檔的接近程度。綠色表示與理想性能範圍沒有偏差。琥珀色表示較小偏差，紅色表示較大偏差。右側的欄位代表 539，所有設定檔屬性均為綠色。前兩列代表其他公司開發的兩種LSD1抑制劑，兩種化合物都存在重大偏差，都具有較長的人體半衰期，且都不是中樞神經系統滲透劑。

The Phase 1/2 compound also irreversibly deactivate the enzyme compounding a long half-life and presenting a challenge to managing platelet levels. What is interesting is that despite these deviations, the Phase 1/2 compound has been able to achieve proof-of-concept in an AML study, achieving complete responses in 33% of patients. On the face of it, this is a good result. However, it should be noted that to achieve this patients had to be dosed intermittently and even then high rates of grade 3 and 4 platelet count decreases were seen.

1/2 相化合物也會不可逆地使酵素失活，從而延長半衰期，並對管理血小板水平提出了挑戰。有趣的是，儘管存在這些偏差，1/2 期化合物仍能夠在 AML 研究中實現概念驗證，在 33% 的患者中實現完全緩解。從表面上看，這是一個很好的結果。然而，應該指出的是，為了實現這一目標，患者必須間歇性給藥，即使如此，仍會出現 3 級和 4 級血小板計數下降的高比例。

We have previously shown data that demonstrates 539 preclinical efficacy is comparable to this compound. If this activity translates into the clinic 539 has the potential to be just as efficacious, but with a better safety profile. With this in mind, we plan to submit an IND to support a Phase 1/2 trial in AML in the third quarter of this year with the aim of opening the first clinical trial site across the end of 2024. We retain an interest in the development of 539 for solid tumors, including small cell lung cancer.

我們先前的數據顯示 539 的臨床前功效與該化合物相當。如果這項活動轉化為臨床，539 有可能同樣有效，但安全性更高。考慮到這一點，我們計劃在今年第三季提交 IND 以支持 AML 的 1/2 期試驗，目標是在 2024 年底開設第一個臨床試驗中心。我們仍然對開髮用於實體瘤（包括小細胞肺癌）的 539 感興趣。

By entering AML first, we are de-risking our program where clinical proof of concept has already been established. We believe we can leverage what we learned from this regulatory process for future opportunities for 539 in other indications. This Phase 1/2 trial will initially have a monotherapy dose escalation phase to help us identify the appropriate dose for testing, followed by a seamless Phase 2 dose expansion to assess safety and efficacy at that dose. Throughout this, we will continue to pursue our precision medicine approach to help support with biomarker selection and patient response prediction.

透過先進入 AML，我們正在降低我們已經建立了臨床概念驗證的項目的風險。我們相信，我們可以利用從這個監管流程中學到的經驗，為 539 在其他適應症方面的未來機會提供幫助。這項 1/2 期試驗最初將有一個單藥劑量遞增階段，以幫助我們確定合適的測試劑量，然後是無縫的 2 期劑量擴展，以評估該劑量的安全性和有效性。在此過程中，我們將繼續追求精準醫學方法，以幫助支持生物標記選擇和患者反應預測。

In addition to 539, I'm also going to provide updates about 565, our MALT1 inhibitor. 565 has been specifically designed to be highly selective, including over the enzyme UGT1A1. UGT1A1 mediates bilirubin glucose [validation] and in addition contributes to hyperbole [rube] anemia.

除了 539 之外，我還將提供有關我們的 MALT1 抑制劑 565 的更新。 565 經過專門設計，具有高度選擇性，包括對 UGT1A1 酶的選擇性。UGT1A1 介導膽紅素葡萄糖[驗證]，此外也導致誇張[rube]貧血。

Hy's law is the assessment of high fatality risks from drug-induced liver injury that is based on elevated levels of liver enzymes and total bilirubin in the absence of other factors. For example, viral hepatitis or alcohol abuse. Many of the current standard of care treatment options that could be used in rational combination with a [novel] inhibitor such as BTK inhibitors, are known to cause drug induced liver injury with concomitant elevations of liver enzymes.

海定律是在不考慮其他因素的情況下，根據肝臟酵素和總膽紅素水平升高來評估藥物性肝損傷的高死亡風險。例如，病毒性肝炎或酗酒。目前許多標準護理治療方案可以與[新型]抑制劑（例如 BTK 抑制劑）合理組合使用，但已知會導致藥物性肝損傷，並伴隨肝酵素升高。

This would make combination with BTK inhibitors difficult in practice for those MALT1 inhibitors that do not share 565 selectivity profile. We previously shared data at [Asmode] late last year, showing in vivo activity of 565 as a monotherapy and in combination. The combinations with ibrutinib demonstrated tumor growth regression in animal models. We have also recently generated compelling data in house for combinations with next-generation BTK inhibitors, which we look forward to sharing at a medical meeting later this year.

對於那些不具有 565 選擇性特徵的 MALT1 抑制劑來說，這將使與 BTK 抑制劑的組合在實踐中變得困難。我們在去年年底在 [Asmode] 上分享了數據，顯示 565 作為單一療法和聯合療法的體內活性。與依魯替尼的組合在動物模型中證明了腫瘤生長的消退。我們最近還在內部產生了與下一代 BTK 抑制劑組合的令人信服的數據，我們期待在今年稍後的醫學會議上分享這些數據。

565 is currently progressing through IND enabling studies, and we plan to launch a clinical trial for patients with B-cell lymphomas, including chronic lymphocytic leukemia in early 2025. It has been demonstrated from preclinical data that there are synergies between MALT1 inhibition and current standard of care treatment options.

565目前正在進行IND支持研究，我們計畫在2025年初針對B細胞淋巴瘤（包括慢性淋巴球白血病）患者啟動臨床試驗。臨床前數據已證明，MALT1 抑制與目前標準護理治療方案之間存在協同作用。

It has even been demonstrated that MALT1 combinations have the potential to overcome standard of care treatment resistant for some B-cell lymphomas. As you can see from this slide, there are approximately 22,000 B-cell lymphoma patients that fall into the second line of treatment each year. Our clinical development strategy will lay the groundwork for our ultimate goal of using 565 in combination with current standard of care treatment options. We will take the first step towards this by submitting either an IND or CTA application before the end of this year.

甚至已經證明，MALT1 組合有可能克服某些 B 細胞淋巴瘤的標準護理治療抗藥性。正如您從這張投影片中看到的，每年約有 22,000 名 B 細胞淋巴瘤患者接受二線治療。我們的臨床開發策略將為我們將 565 與目前標準護理治療方案相結合的最終目標奠定基礎。我們將在今年年底前提交 IND 或 CTA 申請，從而邁出第一步。

I will now hand over to Ben. So walk us through the business and financial updates.

我現在將交給本。請向我們介紹一下業務和財務最新情況。

Thank you, Dave. Partnerships have been and will continue to be an important part of our business model. We have brought in almost $230 million from partnerships over the last few years and expect to generate significant additional near-term cash inflows. Our Sanofi collaboration is showing strong progress across multiple programs and the Merck KGAA collaboration now has all of the programs in early discovery.

謝謝你，戴夫。合作夥伴關係已經並將繼續成為我們商業模式的重要組成部分。過去幾年，我們從合作關係中獲得了近 2.3 億美元的收入，預計短期內將產生大量額外現金流入。我們與賽諾菲的合作在多個項目上顯示出強勁的進展，而與默克 KGAA 的合作現在所有項目都處於早期發現階段。

Drug discovery and early development are under pressure across the industry, and we believe Exscientia has the ideal solution? When the main industry problems is that approximately 50% of drugs fail in Phase 1. These failures are usually tied to safety and dosing. These are two areas where the Exscientia platform accelerates beyond traditional methods.

整個產業的藥物發現和早期開發都面臨壓力，我們相信 Exscientia 擁有理想的解決方案？該行業的主要問題是大約 50% 的藥物在第一階段失敗。這些失敗通常與安全性和劑量有關。Exscientia 平台在這兩個領域超越了傳統方法。

In addition, the integration of our AI based design and our automation lab can enable a new level of speed and cost efficiency. The impact we create is being demonstrated by our PKC Theta inhibitor that is partnered with BMS. It recently achieved positive early results in its Phase 1 study and has the potential to be a first-in-class immunology drug.

此外，我們基於人工智慧的設計和自動化實驗室的整合可以將速度和成本效率提升到新的水平。我們與 BMS 合作的 PKC Theta 抑制劑證明了我們所創造的影響。它最近在 1 期研究中取得了積極的早期結果，有潛力成為一流的免疫學藥物。

PKC Theta is a target where over the last 15 years, more than a dozen biopharma companies have tried and failed to create a potent and selective inhibitor using traditional design methods. We were able to move from design initiation to identifying the development candidate in less than 12 months, delivering a better quality drug with balanced properties faster.

PKC Theta 是一個目標，在過去 15 年裡，十幾家生物製藥公司嘗試使用傳統設計方法創建有效的選擇性抑制劑，但都以失敗告終。我們能夠在不到 12 個月的時間內從設計啟動到確定開發候選藥物，從而更快地提供具有平衡特性的更優質藥物。

I will now take a minute to close with highlights from our financial results. Full results are detailed in our press release and Form 6-K. I will review the results in US dollars using the constant currency rate of [1.26] to the pound. We ended the quarter with $417 million in cash, providing us with a cash runway well into 2027 without additional business development. This enables us to deliver on a multitude of pipeline and platform milestones during that time.

現在，我將花一點時間介紹我們的財務表現亮點。完整結果詳見我們的新聞稿和表格 6-K。我將使用 [1.26] 兌英鎊的恆定匯率來查看美元結果。截至本季末，我們擁有 4.17 億美元現金，為我們提供了直至 2027 年無需進行額外業務開發的現金跑道。這使我們能夠在此期間實現多個管道和平台里程碑。

You can see the impact of our improving efficiencies and disciplined spending through the 29% decrease in operating cash burn from $55 million in the first quarter of last year to $39 million in the first quarter of 2024. We did this while moving CDK7 forward in the clinic, bringing two new drugs into IND prep, executing on our partnerships, launching our automation lab, and setting the standard for small molecule design technology.

營運現金消耗從去年第一季的 5,500 萬美元減少到 2024 年第一季的 3,900 萬美元，減少了 29%，您可以看到我們提高效率和嚴格支出的影響。我們在做到這一點的同時，推動了CDK7 在臨床上的發展，將兩種新藥帶入IND 準備階段，執行我們的合作夥伴關係，啟動我們的自動化實驗室，並為小分子設計技術設定標準。

Today, we have evolved our business again to recognize the benefits of technological efficiency and in doing so expect to realize annual cash savings from 2025 onwards of more than $40 million. We have a strong track record of delivering business development, and that has supported us since our IPO. We are focused on achieving those pipeline and collaboration milestones that will validate the substantial leadership position we have built with our platform.

今天，我們再次發展我們的業務，認識到技術效率的好處，並期望從 2025 年起每年實現超過 4000 萬美元的現金節省。我們在業務發展方面擁有良好的記錄，自首次公開募股以來，這一直為我們提供支援。我們專注於實現這些管道和合作里程碑，這將驗證我們透過我們的平台建立的實質領導地位。

And with that, I will turn it back over to Dave.

這樣，我會將其轉回給戴夫。

Thank you, Ben. Our foundational work leveraging an AI-driven precision trial design has culminated in the development of a focused high-value oncology pipeline, which we believe has the potential to dramatically improve patient outcomes. We expect to be providing data this year from at least one program, namely CDK7. Our platform that drives both the pipeline and partnerships is working and we believe with the integration of automation has the potential to drive extraordinary efficiencies to our business.

謝謝你，本。我們利用人工智慧驅動的精確試驗設計的基礎工作最終開發了一個專注的高價值腫瘤學管道，我們相信它有潛力顯著改善患者的治療結果。我們預計今年將提供至少一個項目的數據，即 CDK7。我們推動管道和合作夥伴關係的平台正在發揮作用，我們相信透過自動化的整合有潛力為我們的業務帶來非凡的效率。

The changes we announced today result in annualized savings of $40 million from 2025 and beyond. These changes will help us achieve our medium- to long-term goals. These are delivering efficacy data for our current clinical programs, CDK7, LSD1, MALT1, and PKC Theta; delivering hundreds of millions of dollars in milestones from our partnership; advancing the next generation of automation supported projects into the clinic; and quantifiably demonstrating the full use case of integrating generative AI with automated experimentation. We believe this will cement our position as the leader in technology driven drug design.

我們今天宣布的變革將使 2025 年及以後每年節省 4000 萬美元。這些變化將幫助我們實現中長期目標。這些為我們目前的臨床項目 CDK7、LSD1、MALT1 和 PKC Theta 提供功效數據；透過我們的合作關係實現了數億美元的里程碑；將下一代自動化支援的項目推進到臨床；並量化地展示將生成式人工智慧與自動化實驗結合的完整用例。我們相信這將鞏固我們作為技術驅動藥物設計領導者的地位。

And with that we will open the call for questions and answers.

接下來，我們將開始提問和解答徵集活動。

(Operator Instructions) Alec Stranahan, Bank of America.

（操作員指示）Alec Stranahan，美國銀行。

Hey, guys. Thanks for taking our questions. Just a couple from us. First for CDK7, how should we be thinking about activity with mono versus combos here? And anything in terms of safety profile you'd like to see in terms of gauging combinability? And given the announced cost reductions, how are you balancing executing on your partnerships while driving your pipeline forward? Any color around the balance of efforts here would be great.

嘿，夥計們。感謝您回答我們的問題。只有我們幾個人。首先對於 CDK7，我們該如何考慮單聲道與組合的活動？在衡量可組合性方面，您希望看到什麼安全性方面的內容？鑑於已宣布的成本削減，您如何平衡執行合作夥伴關係並推動管道向前發展？圍繞這裡的努力平衡的任何顏色都會很棒。

Thank you for that question. I'll let Ben take the first question was about CDK7 and then I'll follow on with that with your question around the balance of the pipeline and partnerships.

謝謝你提出這個問題。我會讓 Ben 回答關於 CDK7 的第一個問題，然後我將繼續回答您關於通路和合作夥伴關係平衡的問題。

Hey, Alec, thanks for the questions. So CDK7, we would expect to see some level of monotherapy activity. This is both a cytostatic and a cytotoxic mechanism. However, in clinical use, it will almost certainly always be used in combination. And so what we're looking at right now, and we'll have more on this in the near future is what's the right next step. So it's in a monotherapy dose escalation and that will be the data that is coming out later on this year, and then we'll look at the appropriate combination to put that into for probably a brief escalation and then an expansion into that area.

嘿，亞歷克，謝謝你的提問。因此，CDK7，我們預計會看到一定程度的單一療法活性。這既是一種細胞抑制機制，也是一種細胞毒性機制。但在臨床使用中，幾乎肯定會合併使用。因此，我們現在正在考慮的以及在不久的將來我們將對此進行更多討論，這就是下一步正確的步驟。因此，這是單一療法劑量遞增的情況，這將是今年稍後公佈的數據，然後我們將研究適當的組合，將其放入可能短暫的劑量遞增中，然後擴展到該領域。

We've seen some good track record of CDK7, CDK4, other CDKs that have been out in the clinic. And I think we feel really good about our profile. The critical issue that you really have to manage with CDK7 is toxicity. GI tox will definitely be a big part of it. You both lose patients as well as have variable absorption if you do have GI toxicities. And so that's something that I would definitely be focused on.

我們已經看到 CDK7、CDK4 和其他已在臨床上使用的 CDK 的一些良好記錄。我認為我們對自己的個人資料感覺非常好。使用 CDK7 時真正需要解決的關鍵問題是毒性。胃腸道毒素肯定是其中的重要組成部分。如果確實有胃腸道毒性，您不僅會失去患者，而且吸收也會改變。所以這肯定是我會關注的事情。

But if you remember the profile of our inhibitor, it was specially designed to have a -- to get around an issue that a number of the other competitive molecules have, which is being transporter substrate. So we think we've got a really nice advantage in there. And hopefully, you'll be able to see that in the data. Because if we can get a nice safe profile, this is a mechanism that clearly should work, and there's a number of different combination opportunities for it.

但如果您還記得我們的抑制劑的概況，它是專門設計來解決許多其他競爭性分子所存在的問題的，即轉運蛋白底物。所以我們認為我們在這方面有非常好的優勢。希望您能夠在數據中看到這一點。因為如果我們能夠獲得一個良好的安全配置文件，那麼這顯然是一種應該起作用的機制，並且它有許多不同的組合機會。

Thank you, Ben. Part of your question, partnerships will remain a cornerstone of our business. The reasons that Ben highlighted, one of those, they've brought substantial cash inflows into the organization. As I mentioned in my remarks, is that the potential for the current collaborations over the next two to three years is to bring in hundreds of millions of dollars of potential milestones. More importantly, or just as importantly, they allow us an opportunity for our platform to learn and [seeking] to leverage the capacity that we've created.

謝謝你，本。你的問題的一部分是，合作夥伴關係仍將是我們業務的基石。本強調的原因之一是，他們為該組織帶來了大量現金流入。正如我在演講中提到的，目前的合作在未來兩到三年內有望帶來數億美元的潛在里程碑。更重要的是，或者同樣重要的是，它們為我們的平台提供了學習和[尋求]利用我們所創建的能力的機會。

The Sanofi partnership, for example, is also making great progress. In those last couple of quarters, we've not only announced the addition of a new program with enhanced economics that started out life within Exscientia, but more recently that the first kind of discovery stage milestones from that collaboration. The new collaborations are also benefiting from utility of our automation platform. So whether it be BMS or Merck or Sanofi or Gates or Rallybio, all our partnerships are important to us.

例如，賽諾菲的合作關係也取得了巨大進展。在過去的幾個季度中，我們不僅宣布了在 Exscientia 內啟動的一項具有增強經濟效益的新計劃，而且最近還宣布了該合作的第一個發現階段里程碑。新的合作也受惠於我們自動化平台的實用性。因此，無論是 BMS、默克、賽諾菲、蓋茲或 Rallybio，我們所有的合作關係對我們都很重要。

Great. That's very helpful. Thank you.

偉大的。這非常有幫助。謝謝。

Vikram Purohit, Morgan Stanley.

維克拉姆‧普羅希特，摩根士丹利。

Hi, good morning. Thanks for taking the question. We had two, one on partnerships and one on the pipeline. So revisiting the topic of partnerships, could you speak a bit about how you're kind of thinking about and pushing through opportunities for biopharma partnerships versus more tech-focused partnerships and kind of how your appetite for each of those could evolve throughout the year, and what you'd be looking for from each different type of partnership?

嗨，早安。感謝您提出問題。我們有兩個項目，一個是合作夥伴關係，另一個是正在籌備中。因此，重新審視合作夥伴關係的話題，您能否談談您如何思考和推動生物製藥合作夥伴關係與更多以技術為重點的合作夥伴關係的機會，以及您對這些合作夥伴關係的興趣在一年中會如何變化，您希望從每種不同類型的合作關係中尋找什麼？

And secondly on the pipeline, are you mentioned in your prepared remarks that the PKC [data-data], the initial data has been promising. Just wondering if you could share a bit more about what you've learned with that compound and what the next public facing communications on that program can look like? Thank you.

其次，關於管道，您在準備好的發言中是否提到 PKC [數據-數據]，初始數據很有希望。只是想知道您是否可以更多地分享您從該化合物中學到的東西以及該項目下一個面向公眾的通信會是什麼樣子？謝謝。

I would come and let me start with your second part first, if that's okay. Immensely kind of proud of the progress that PKC Theta has made. This has been a very challenging project over the course of the last kind of probably last decade. I estimate that kind of more than 10 companies have tried and failed to try and bring an orally bioavailable selective potent inhibitor into the clinic and they pretty much all fail to do that.

如果可以的話，我會過來讓我先從你的第二部分開始。對 PKC Theta 所取得的進步感到非常自豪。在過去（可能是過去十年）的過程中，這是一個非常具有挑戰性的專案。我估計有超過 10 家公司嘗試將口服生物可利用的選擇性強效抑制劑引入臨床，但都以失敗告終，而且他們幾乎都未能做到這一點。

I think this is proof of the first evidence of what we've spoken about for many quarters now about the capabilities of our design platform to deliver where others have failed. PKC Theta remains within the BMS portfolio. It has progressed and go through Phase 1. We can't say anymore at this stage, but we are working with BMS to be able to tell you more in the coming quarters.

我認為，這是我們在許多季度中所談論的第一個證據，證明我們的設計平台有能力在其他平台失敗的地方提供服務。PKC Theta 仍屬於 BMS 產品組合。它已經取得進展並進入第一階段。現階段我們無法透露更多信息，但我們正在與 BMS 合作，以便能夠在未來幾季告訴您更多。

In terms of partnerships, is that, we continue to look for both target kind of based kind of partnerships, whether they be the kind of collaborations that we've done historically with Sanofi, for example. But I think what the automation platform is allowing us to do in terms of the efficiencies and the kind of changing cost base and also to potentially attract kind of early-stage collaborators like biotechs or even startups. So that's kind of one area there where business development kind of conversations are taking place at the moment.

在合作關係方面，我們繼續尋找基於目標的合作關係，無論它們是否是我們歷史上與賽諾菲進行的那種合作。但我認為自動化平台使我們能夠提高效率和改變成本基礎，並有可能吸引生技公司甚至新創公司等早期合作者。因此，這是目前正在進行業務開發對話的領域。

In terms of technology conversations, that we have and continue to have with the major technology players, are really about the excitement we're generating in terms of the investment we've made into our automation studio. I think a lot of people that have been fortunate enough to visit that sites have recognized the potential and the value of actually bringing together the computational world and with the real world of kind of engineering and that [kind] of test environments.

就技術對話而言，我們已經並將繼續與主要技術參與者進行對話，實際上是關於我們對自動化工作室的投資所產生的興奮感。我認為許多有幸造訪這些網站的人已經認識到將計算世界與現實世界的工程和測試環境真正結合在一起的潛力和價值。

So the kind of conversations that we're having with kind of technology partners are really around how best can they help us support that going forward. And so we will update you as -- of course, over the course of the next couple of quarters. But I'm confident we'll see progress on both aspects of our business in that regard.

因此，我們與技術合作夥伴的對話實際上是圍繞著他們如何最好地幫助我們支持未來的發展。當然，我們將在接下來的幾季內向您通報最新情況。但我相信我們在這方面的業務的兩個方面都會取得進展。

Understood. Thank you.

明白了。謝謝。

Peter Lawson, Barclays.

彼得·勞森，巴克萊銀行。

Great. Thanks so much. I guess initially it's just a question on CDK7, the combination agent you're thinking of using them and the initial datasets, what indications we should be thinking about?

偉大的。非常感謝。我想最初這只是關於 CDK7 的問題，您正在考慮使用它們的組合代理和初始資料集，我們應該考慮哪些跡象？

Thank you, Peter. I'll pass that question over to Ben.

謝謝你，彼得。我會把這個問題轉給本。

Sure. So we still have some flexibility, but I'll give you a few ideas of where we could go with it because I think there's some really interesting avenues. The most common path here would be to go after ER-positive HER2-negative CDK4/6 refractory breast cancer patients. And that may seem like a tough patient population for CDK inhibitors, but actually, we've seen some positive early data out of Pfizer's CDK4 showing that even if you're going after CDK4 after 4/6, you can have good positive responses as well as some early signs out of CDK7.

當然。所以我們仍然有一定的靈活性，但我會給你一些關於我們可以去哪裡的想法，因為我認為有一些非常有趣的途徑。最常見的途徑是治療 ER 陽性、HER2 陰性 CDK4/6 難治性乳癌患者。對於CDK 抑制劑來說，這似乎是一個艱難的患者群體，但實際上，我們已經從輝瑞的CDK4 中看到了一些積極的早期數據，表明即使您在4/6 後使用CDK4，您也可以獲得良好的正面反應，以及 CDK7 的一些早期跡象。

I think we just have a lot better overall balanced profile than the inhibitors that are out there on the market. And as we've talked about before, we think the CDK7 as a class could really have some advantages over some of the other CDKs. So I think we will be able to obviously explore that area if we wanted to. But because of our safety profile that also opens up some other areas. There's a lot of great preclinical data showing that CDK7 can be beneficial with immunotherapies.

我認為我們比市場上現有的抑制劑具有更好的整體平衡特性。正如我們之前討論過的，我們認為 CDK7 作為一個類別確實比其他一些 CDK 有一些優勢。所以我認為如果我們願意的話我們顯然能夠探索這個領域。但由於我們的安全性，也開闢了其他一些領域。有大量臨床前數據顯示 CDK7 對免疫療法有益。

And that is often not been pursued or the clinical trials haven't been very successful because of toxicity. And part of the reason there might be, they have very different toxicity profiles. And so you put them together, you can get an overwhelming tox burden. But if we're able to manage that CDK7 toxicity better, there should be very complementary activity.

但由於毒性，這一點往往沒有落實，或者臨床試驗並不十分成功。部分原因可能是它們具有截然不同的毒性特徵。所以你把它們放在一起，你會得到壓倒性的毒性負擔。但如果我們能夠更好地控制 CDK7 毒性，那麼應該會有非常互補的活性。

So that's another example of how our profile and what we're able to do with our platform actually could open up markets that other drugs are unable to reach. So there's a number of different places that you could go with CDK7 because it is a more fundamental mechanism. But that gives you an example of what we're thinking about.

這是另一個例子，說明我們的概況以及我們能夠利用我們的平台做些什麼實際上可以打開其他藥物無法到達的市場。因此，CDK7 可以用於許多不同的地方，因為它是一種更基本的機制。但這給了你一個我們正在思考的例子。

Thank you. And then the combination agents with CDK7, immunotherapy, I guess, is one potential.

謝謝。然後，我認為與 CDK7 聯合使用的免疫療法是一種潛力。

So it will really depend on where you go. So if you went with that ER-positive, HER2-negative CDK4/6 resistant breast cancers, you'd probably be with [Aserd]. Fulvestrant is obviously a pretty common standard of care there. If you went after something like a lung cancer indication, you may go with a PD-L1. There are obviously other indications you could go after.

所以這實際上取決於你去哪裡。因此，如果您患有 ER 陽性、HER2 陰性 CDK4/6 抗藥性乳癌，您可能會[阿瑟德]。氟維司群顯然是那裡相當常見的護理標準。如果您想要尋找肺癌等適應症，您可以選擇 PD-L1。顯然還有其他跡象可供您追蹤。

And it really depends on the standard of care. I think we would need to start around second line in most indications, but that could give you a good sense,

這實際上取決於護理標準。我認為在大多數情況下我們需要從第二線開始，但這可以給你一個很好的感覺，

Thank you. Then any (technical difficulty) around cash burn expectations for Q2, and how that kind of measures out to financial year '24?

謝謝。那麼，關於第二季現金消耗預期的任何（技術困難），以及如何衡量 24 財年的情況？

Sure. I'll keep going on that one. So obviously -- hopefully, it was noticed we had a 29% decrease year over year despite a lot of execution in our first quarter results. I think we intend to continue that into the year. Our guidance had been the cash burn -- the operational cash burn this year will be less than last year, and we're still holding to that. I think with what we announced today that puts our cash runway well into 2027.

當然。我會繼續做下去。很明顯——希望人們注意到，儘管我們在第一季的業績中執行了大量的工作，但我們的業績同比下降了 29%。我認為我們打算將這種情況延續到今年。我們的指導是現金消耗——今年的營運現金消耗將少於去年，我們仍然堅持這一點。我認為我們今天宣布的消息使我們的現金跑道可以順利進入 2027 年。

You may remember our previous guidance was well into 2026. That's actually a really important 12-month period, not only because it gives us more control over our own destiny, which is always a good thing. But that also means that we have the ability without additional BD or financing to get through things like CDK7 Phase 2 data and/or initial Phase 1 data on LSD1 and/or MALT1.

您可能還記得我們之前的指導意見已經到了 2026 年。這實際上是非常重要的 12 個月，不僅因為它讓我們能夠更好地掌控自己的命運，這總是一件好事。但這也意味著我們有能力在沒有額外 BD 或融資的情況下獲得 CDK7 第 2 階段數據和/或 LSD1 和/或 MALT1 的初始第 1 階段數據等數據。

Plus, there's a lot that should happen in our partnered pipeline over that time period. And obviously, we'd get to see the automation really play out well. So there's a lot going on over the next couple of years and we wanted to make sure that we were in full control over that time period.

另外，在此期間，我們的合作管道中應該會發生很多事情。顯然，我們會看到自動化確實發揮了良好的作用。因此，接下來的幾年會發生很多事情，我們希望確保我們能夠完全控制這段時間。

Great. Thanks.

偉大的。謝謝。

(Operator Instructions) There are no further questions at this time. I will turn the call to Dave Hallett for closing remarks.

（操作員說明） 目前沒有其他問題。我將把電話轉給戴夫·哈利特（Dave Hallett），讓他致閉幕詞。

Thank you, operator, and thank you to everyone on the call today for your continued support of Exscientia. In closing, let me reiterate why we are in a strong position for the future. The positive results for our [partner], PKC Theta inhibitor program, the upcoming Phase 1 data for CDK7, and the progression of our LSD1 and MALT1 inhibitor programs into the clinic, all provide meaningful advancements of our pipeline.

謝謝接線員，也感謝今天通話中的所有人對 Exscientia 的持續支持。最後，讓我重申為什麼我們在未來處於有利地位。我們的[合作夥伴] PKC Theta 抑制劑計畫的正面結果、即將發布的 CDK7 一期數據，以及我們的 LSD1 和 MALT1 抑制劑計畫進入臨床的進展，都為我們的管道提供了有意義的進展。

The integration of our AI lead drug design capabilities, now supercharged by experimental automation will help us drive towards maximum speed, quality, and ultimately autonomous truck design. We continue our journey to truly transform how drugs will be invented in the future. Finally, leveraging technology advancements and streamlining operations to realize annual savings of $40 million. We'll extend our cash runway well into 2027 and help Exscientia deliver on our mid- and long-term goals.

我們的人工智慧主導藥物設計能力的整合，現在透過實驗自動化得到增強，將幫助我們實現最高速度、品質和最終的自主卡車設計。我們將繼續努力，真正改變未來藥物的發明方式。最後，利用技術進步和簡化運營，每年節省 4000 萬美元。我們將把我們的現金跑道延長到 2027 年，並幫助 Exscientia 實現我們的中長期目標。

Operator, you may now disconnect.

接線員，您現在可以斷開連接了。

Thank you. This concludes today's conference call. Thank you for joining. You may now disconnect your lines.

謝謝。今天的電話會議到此結束。感謝您的加入。現在您可以斷開線路。