F-Star Therapeutics Inc (FSTX) 2022 Q1 法說會逐字稿

Greetings and welcome to the F-star first quarter 2022 earnings conference call. (Operator Instructions) As a reminder, this conference is being recorded. I would now like to turn the conference over to your host, John Fraunces, Managing Director of LifeSci Advisors. Please proceed, sir.

您好，歡迎參加 F-star 2022 年第一季度財報電話會議。 （操作員指示）謹此提醒，本次會議正在錄製中。現在我想將會議交給主持人、LifeSci Advisors 董事總經理約翰·弗朗西斯 (John Fraunces)。請繼續，先生。

Good morning everyone. And thank you for joining us. With me today is the Chief Executive Officer of F-star Therapeutics, Eliot Forster; and Chief Financial Officer, Darlene Deptula-Hicks.

大家，早安。感謝您加入我們。今天和我在一起的是 F-star Therapeutics 公司的首席執行官艾略特·福斯特 (Eliot Forster)；首席財務官達琳·德普圖拉-希克斯 (Darlene Deptula-Hicks)。

We announced financial results pre-market today for the quarter ended March 31, 2022. You can access the press release on the investor relations page of our website at fstar.com. Before we get started, let's quickly run through the forward looking statements. Please note that as a part of our discussion today, management will be making forward looking statements. These statements are not guarantees of future performance and therefore you should not place undue reliance on them. Investors are also cautioned that statements that are not strictly historical constitute forward looking statements. Such forward looking statements are subject to a number of risks and uncertainties that could cause the actual results to differ materially from those anticipated. These risks include risks and uncertainties detailed in F-stars filings with the SEC. The company undertakes no obligation to update any forward looking statements in order to reflect events or circumstances that may arise after the date of this conference call With that, I'll hand the call over to Eliot.

我們今天在盤前公佈了截至 2022 年 3 月 31 日的季度的財務業績。您可以在我們網站 fstar.com 的投資者關係頁面上訪問新聞稿。在開始之前，讓我們快速瀏覽一下前瞻性陳述。請注意，作為我們今天討論的一部分，管理層將做出前瞻性聲明。這些聲明並不是對未來業績的保證，因此您不應過度依賴它們。投資者還應注意，非嚴格歷史性的陳述構成前瞻性陳述。此類前瞻性陳述受到許多風險和不確定性的影響，可能導致實際結果與預期存在重大差異。這些風險包括 F-stars 向 SEC 提交的文件中詳述的風險和不確定性。該公司沒有義務更新任何前瞻性陳述，以反映本次電話會議之後可能發生的事件或情況。因此，我將把電話轉交給艾略特。

Thank you, John. And thank you and good morning, everyone. As ever, it's a pleasure to speak with you today and review F-star's first quarter of this year. It's only been 8 weeks since we last met, but every new month brings increased confidence in our portfolio. We're pleased with progress across all 4 programs and in particular their performance in the clinic. Against the backdrop of a tough ongoing biotech market, we're getting on with the job at hand. Our mission is, of course, to transform the lives of patients and ultimately achieve a future that's free from cancer.

謝謝你，約翰。謝謝大家，早上好。一如既往，很高興今天與您交談並回顧 F-star 今年第一季度的情況。距離我們上次見面才過去了 8 週，但每個新月都會讓我們對自己的投資組合充滿信心。我們對所有 4 個項目的進展，特別是它們在臨床中的表現感到滿意。在生物技術市場持續嚴峻的背景下，我們正在繼續做好手頭的工作。當然，我們的使命是改變患者的生活並最終實現沒有癌症的未來。

Looking back over the first 3 months of the year, I'm pleased report that we've continued to build momentum across each of our programs. All 4 are progressing well in the clinic. In the last quarter for each of our 3 tetravalent bispecific (inaudible) FS118, FS222, and FS120 — we've increased the number of clinical research sites and added new countries. So, as well as the patients enrolled in the US, we've also dosed our first FS118 and FS120 patients in Europe. We're very excited about the 4 set of important clinical data coming this year. As you recall, our preferences [is]? to release data at scientific conferences where possible. We strengthened our drug development capabilities by welcoming James Sandy to our company's chief development officer. With more than 3 decades of clinical development experience, James brings valuable additional expertise to the team and accelerating cancer treatment programs through early stage and late stage development. And that will greatly benefit our clinical development strategy. We are pleased to present a poster on FS118's mechanism of action at the American Association for Cancer Research annual meeting in April. Our data reveals the unique tetra structure of FS118 plays a crucial role in driving LAG-3 shedding and cell surface reduction on tumor infiltrating lymphocytes, enabling FS118 to overcome compensatory upregulation of LAG-3 induced by PDL or [PDL]? or PD-L1 blockade. And with the positive news from the field, including the recent approval of BMSs LAG-3 antibody in combination with PD-1, LAG-3 has become the defacto third checkpoint inhibitor.

回顧今年的前 3 個月，我很高興地報告說，我們的每個項目都繼續保持勢頭。所有 4 人在診所均進展順利。在上個季度，對於我們的 3 個四價雙特異性（聽不清）FS118、FS222 和 FS120 中的每一個，我們增加了臨床研究地點的數量並添加了新的國家/地區。因此，除了在美國入組的患者外，我們還在歐洲對首批 FS118 和 FS120 患者進行了給藥。我們對今年即將推出的 4 組重要臨床數據感到非常興奮。您還記得嗎，我們的偏好是？盡可能在科學會議上發布數據。我們歡迎 James Sandy 擔任我們公司的首席開發官，從而增強了我們的藥物開發能力。 James 擁有 3 多年的臨床開發經驗，為團隊帶來了寶貴的額外專業知識，並通過早期和後期開發加速了癌症治療項目。這將極大有利於我們的臨床開發策略。我們很高興在四月份的美國癌症研究協會年會上展示 FS118 作用機制的海報。我們的數據揭示了 FS118 獨特的四重結構在驅動腫瘤浸潤淋巴細胞上的 LAG-3 脫落和細胞表面減少方面發揮著至關重要的作用，使 FS118 能夠克服 PDL 或 [PDL]? 誘導的 LAG-3 代償性上調？或 PD-L1 阻斷。隨著該領域的積極消息，包括最近批准 BMS 的 LAG-3 抗體與 PD-1 聯合用藥，LAG-3 已成為事實上的第三種檢查點抑製劑。

Our partnerships continue to advance well. In this past quarter, Merck KGaA, Darmstadt, Germany,, exercised a fourth licensing option to develop another bispecific program under our ongoing immune oncology collaboration. I guess, just as a reminder, the potential revenue from this collaboration is up to approximately $765 million in milestone payments. This is just one of the more than 20 partner programs that are advancing this year based on the discovery capabilities of the F-star platform. Also this quarter, the US patent and trademark offers granted a patent protecting the composition of matter for FS118.

我們的合作夥伴關係繼續良好發展。在上個季度，德國達姆施塔特的默克公司行使了第四種許可選擇權，在我們正在進行的免疫腫瘤學合作下開發另一個雙特異性項目。我想提醒一下，這次合作的潛在收入高達約 7.65 億美元的里程碑付款。這只是今年基於 F-star 平台發現能力推進的 20 多個合作夥伴計劃之一。同樣在本季度，美國專利和商標局授予了 FS118 物質成分保護專利。

This new patent is expected to provide F-star with exclusivity for FS118 to at least August 2038. We also held a 2-day meeting of our scientific advisory board in the last quarter. It's always time well spent to discuss our programs and hear the views and gain support from these internationally [renowned] experts for our future development plans. Now, by the way, I was particularly struck by one of our advisors reminding us that 5 in every 6 patients with head and neck cancer continues to face the most difficult conversations about their futures. And despite the remarkable progress of immune oncology treatment over the past decade, we are very mindful of the majority of patients who are running out of options. We also continued with a busy program of meetings with existing shareholders and potential new investors. We're greatly encouraged by the interest shown in our programs across the portfolio and grateful for the opportunity to share information with those investors. As ever, it was a pleasure to present our programs at several investor conferences and, and thanks to our analysts for arranging those.

這項新專利預計將至少在 2038 年 8 月之前為 F-star 提供 FS118 的獨家經營權。我們還在上個季度舉行了為期 2 天的科學顧問委員會會議。花時間討論我們的計劃、聽取這些國際[知名]專家的意見並獲得對我們未來發展計劃的支持總是值得的。順便說一句，現在，我們的一位顧問提醒我們，每 6 名頭頸癌患者中就有 5 名繼續面臨著關於他們未來的最困難的對話，這讓我印象特別深刻。儘管過去十年免疫腫瘤治療取得了顯著進展，但我們非常關注大多數別無選擇的患者。我們還繼續與現有股東和潛在新投資者舉行繁忙的會議。我們對整個投資組合中的項目表現出的興趣感到深受鼓舞，並感謝有機會與這些投資者分享信息。一如既往，我們很高興在幾次投資者會議上展示我們的計劃，並感謝我們的分析師安排這些計劃。

So bispecifics have huge potential to deliver different and better outcomes for patients with cancer. This is backed up by our own data and by that of others. Bispecifics really are now coming of age. They behave differently from monoclonal antibodies and even combinations of monoclonal antibodies. It's this difference that brings hope for improvement, treatment options beyond first generation checkpoint inhibitors, particularly for hard to treat cancers and patients with few other options. The promise of next generation immune oncology is reflected by the extraordinary amount of capital being invested in bispecific drug development. Bispecifics now represent nearly 20% of the clinical antibody pipeline, and new collaborations account for more than 18 billion in deal value over the past 2 years — for example, the AstraZeneca Harbour Biomed deal worth 25 million upfront further reinforces the growing importance of bispecifics. Toda, 4 bispecific drugs have already been approved. And without question, we expect the pace of investment and future approvals for bispecifics only to accelerate over time.

因此，雙特異性藥物具有為癌症患者帶來不同且更好結果的巨大潛力。這得到了我們自己和其他人的數據的支持。雙特異性現在確實已經成熟了。它們的行為不同於單克隆抗體，甚至不同於單克隆抗體的組合。正是這種差異帶來了改善的希望，以及第一代檢查點抑製劑之外的治療選擇，特別是對於難以治療的癌症和幾乎沒有其他選擇的患者。下一代免疫腫瘤學的前景體現在雙特異性藥物開發上投入的巨額資金。雙特異性抗體目前佔臨床抗體產品線的近 20%，過去 2 年新合作的交易價值超過 180 億美元——例如，價值 2500 萬美元的阿斯利康 Harbour Biomed 交易進一步強化了雙特異性抗體日益增長的重要性。截至目前，已有 4 個雙特異性藥物獲得批准。毫無疑問，我們預計雙特異性藥物的投資和未來批准的步伐只會隨著時間的推移而加快。

We firmly believe our teal tetra-valent bispecifics are amongst the best in class. Our plug and play platform enables the rapid creation of natural full length human bispecific antibodies [that are designed] for safe, potent immune activation in the tumor microenvironment. Here, you can see a model of the natural human IgG1 molecule with 2 natural binding sites at the top of the antibody highlighted in blue. We make our bispecifics by introducing 2 new binding sites at the bottom of the antibody structure highlighted in green. These are spatially closer together and in a more constrained structure, pointing outwards, enabling binding to both targets. To achieve these new binding sites, we're not adding additional loops or domains, but rather making direct changes to those amino acids in a highly conservative and effective manner. We're not disrupting the antibody structure and functions, but rather in an elegant way, making it tetravalent — that is 2 binding sites for one target and 2 for the other, evoking novel biology, we summarize as cross-linking, clustering, and conditionality. On top of all of this, with so few changes to the natural human antibody format, manufacturing is a straightforward process, giving us antibody like yields and stability. All of this is protected by more than 500 patents granted and pending.

我們堅信我們的青色四價雙特異性抗體是同類中最好的。我們的即插即用平台能夠快速創建天然全長人類雙特異性抗體[設計]，以在腫瘤微環境中安全、有效地激活免疫。在這裡，您可以看到天然人 IgG1 分子的模型，其抗體頂部有 2 個天然結合位點（以藍色突出顯示）。我們通過在以綠色突出顯示的抗體結構底部引入 2 個新的結合位點來製造雙特異性抗體。它們在空間上更接近，並且結構更受限制，指向外側，從而能夠與兩個目標結合。為了實現這些新的結合位點，我們沒有添加額外的環或結構域，而是以高度保守和有效的方式直接改變這些氨基酸。我們並沒有破壞抗體的結構和功能，而是以一種優雅的方式，使其成為四價——即一個靶標有 2 個結合位點，另一個靶標有 2 個結合位點，這引發了新的生物學，我們總結為交聯、聚類和條件性。最重要的是，由於對天然人類抗體形式的改變很少，製造過程非常簡單，為我們提供了類似抗體的產量和穩定性。所有這些均受到 500 多項已授予和正在申請的專利的保護。

This is our most significant year as a clinical stage company with data expected from all 4 programs before year end. These are the most important value drivers for F-star. Success in just one of our 4 programs, and of course we open anticipate for success in more than one, will be transformative for patients, the company, our shareholders, and for the field of immunotherapy. I'll now talk through our program, starting with FS118. FS118 targets 2 clinically validated inhibitory checkpoints: PD-L1 and LAG-3. It's currently being tested in 2 different patient settings, checkpoint inhibitor, naiïve patients, in non-small cell lung cancer and diffuse large b-cell lymphoma, and in head and neck cancer patients with PD-1 acquired resistance. For the head and neck cancer patient group, which commenced additional patient enrolment in Europe to account for fewer available biopsies than initially planned and. In anticipation of the expansion of the proof of concept trial. As the war in Ukraine continues, our thoughts are with all of those affected, including the medical and patient community there. As we said in our last earnings call, the checkpoint inhibitor naive non-small cell component of the FS118 trials was affected by the conflict, but I'm pleased to say that the contingency plan we mentioned at the time is now being implemented.

作為一家臨床階段公司，這是我們最重要的一年，所有 4 個項目預計將在年底前獲得數據。這些是 F-star 最重要的價值驅動因素。我們的 4 個項目中只有一個取得成功，當然，我們預計多個項目都會取得成功，這將為患者、公司、我們的股東以及免疫治療領域帶來變革。我現在將介紹我們的程序，從 FS118 開始。 FS118 針對 2 個經過臨床驗證的抑制檢查點：PD-L1 和 LAG-3。目前正在 2 種不同的患者環境中進行測試：檢查點抑製劑、初次接受治療的患者、非小細胞肺癌和瀰漫性大 B 細胞淋巴瘤以及具有 PD-1 獲得性耐藥性的頭頸癌患者。對於頭頸癌患者組，該組開始在歐洲招募更多患者，以解決可用活檢數量少於最初計劃的情況。預計概念驗證試驗將擴大。隨著烏克蘭戰爭的繼續，我們的心與所有受影響的人在一起，包括那裡的醫療和患者社區。正如我們在上次財報電話會議中所說，FS118 試驗的檢查點抑製劑初始非小細胞部分受到了衝突的影響，但我很高興地說，我們當時提到的應急計劃現在正在實施。

We remain confident about the prospects for FS118. And I look forward to updating you on preliminary data from the head and neck study in the coming few months, FS222 continues to promise best in class data. And we're encouraged by how well it continues to progress in the clinic. FS222 is designed to target a wide range of patients, including those with PD-L1 high and PD-L1 low [expression] tumors. It benefits from all of the unique aspects of our platform technology. The program has the potential to be truly transformational for those patients who are not getting the full benefit of first generation of immuno-oncology therapies. It's worth highlighting that in pre-clinical studies, we observed 100% survival and tumor clearance with FS222, and that's without having to combine with PD-1 inhibitors. As we've previously described FS222 is designed for avidity, and as such balances the affinity profile against both the costimulatory CD137 and the inhibitory PD-1 targets. This leads to dose dependent PD-L1 driven CD137 t-cell redirection and activation. We look forward to sharing the data from part a of the phase one trial, including safety and any early science of efficacy in the coming few months.

我們對 FS118 的前景仍然充滿信心。我期待在未來幾個月內向您更新頭頸部研究的初步數據，FS222 繼續承諾提供一流的數據。我們對它在臨床上的持續進展感到鼓舞。 FS222 旨在針對廣泛的患者，包括 PD-L1 高表達和 PD-L1 低表達腫瘤的患者。它受益於我們平台技術的所有獨特方面。該計劃有可能為那些沒有從第一代免疫腫瘤療法中充分受益的患者帶來真正的變革。值得強調的是，在臨床前研究中，我們觀察到 FS222 的存活率和腫瘤清除率為 100%，而且無需與 PD-1 抑製劑聯合使用。正如我們之前所描述的，FS222 專為親合力而設計，因此平衡了共刺激 CD137 和抑制性 PD-1 靶標的親和力。這導致劑量依賴性 PD-L1 驅動的 CD137 T 細胞重定向和激活。我們期待在未來幾個月分享第一階段試驗 A 部分的數據，包括安全性和任何早期的功效科學。

First in class FS120, with its triple immune activation, aims to improve checkpoint inhibitor or chemotherapy treatment outcomes for patients. Being tumor agnostic it builds on the potential of current standards of care. FS120 co-stimulates OX40 and CD137 to key targets found on the surface of t-cells. The start of a combination trial of FS120 with Merck's pembrolizumab is on track. And we look forward to updating you on progress later this year. And finally, SB 11285 our next generation intravenously administered novel STING agonist. Dose escalation is still ongoing successfully in phase one clinical trial. We look forward to sharing more clinical data with you later this year. Furthermore, we were pleased to read independent commentary from Dr. Michael Curran from the MD Anderson Cancer Center in Houston, who pointed out that SB11285 may have the best therapeutic window amongst systemic STING agonists currently under clinical evaluation. Under the terms of the contingent value rights agreement for SP11285, we continue to explore partnering options for the program as a further source of non-dilutive funding for the company. We're also pleased with the high level of interest in next generation STING therapies at the recent AACR. Discovery work also continues in the lab, of course, and we'll share news on this later in the year. We continue to benefit from growing and growing partnership income. It's clear that partnerships will continue to be part of our company's future, building on those we have today and bringing non-dilutive capital and further patient benefit from our extensive antibody discovery technology.

FS120 是同類產品中的首創，具有三重免疫激活功能，旨在改善患者的檢查點抑製劑或化療治療結果。由於與腫瘤無關，它建立在當前護理標準的潛力之上。 FS120 共同刺激 OX40 和 CD137 到達 T 細胞表面的關鍵靶點。 FS120 與默克公司的 pembrolizumab 的聯合試驗正在按計劃啟動。我們期待在今年晚些時候向您通報最新進展情況。最後，SB 11285 是我們下一代靜脈注射的新型 STING 激動劑。一期臨床試驗中劑量遞增仍在成功進行。我們期待在今年晚些時候與您分享更多臨床數據。此外，我們很高興閱讀來自休斯頓 MD 安德森癌症中心的 Michael Curran 博士的獨立評論，他指出，SB11285 可能在目前正在進行臨床評估的系統性 STING 激動劑中具有最佳的治療窗口。根據 SP11285 或有價值權利協議的條款，我們繼續探索該計劃的合作選擇，作為公司非稀釋資金的進一步來源。我們還對最近的 AACR 上對下一代 STING 療法的高度興趣感到高興。當然，實驗室中的發現工作也在繼續，我們將在今年晚些時候分享這方面的消息。我們繼續受益於不斷增長的合夥收入。顯然，合作夥伴關係將繼續成為我們公司未來的一部分，以我們今天的合作夥伴關係為基礎，並帶來非稀釋資本，並從我們廣泛的抗體發現技術中進一步使患者受益。

Here's a summary of the milestones we anticipate over the next 2 years from our programs. As you can see, we're entering a data-rich period, which we believe will generate multiple value driving catalysts. Our confidence in our portfolio grows day by day. And on this basis, we look forward to sharing clinical data from all 4 programs in the coming months. At the same time, we'll share with investors our plans to deliver on our future ambitions. It's been a pleasure to share this corporate update with you and we'll continue our outreach to the investment community, providing insight into how we both plan to help more patients with cancer live longer and better lives and unlock long term shareholder value. And with that, I'll hand over to our CFO, Darlene, to give you an update on our financials. Darlene.

以下是我們預計未來兩年的計劃里程碑的摘要。正如您所看到的，我們正在進入一個數據豐富的時期，我們相信這將產生多種價值驅動催化劑。我們對我們的投資組合的信心與日俱增。在此基礎上，我們期待在未來幾個月內分享所有 4 個項目的臨床數據。與此同時，我們將與投資者分享我們實現未來雄心的計劃。很高興與您分享這一公司最新動態，我們將繼續與投資界接觸，深入了解我們計劃如何幫助更多癌症患者活得更長、更好，並釋放長期股東價值。接下來，我將交給我們的首席財務官達琳，向您介紹我們財務狀況的最新情況。達琳。

Thank thanks, Eliot, and good morning, everyone. As you've just heard, it's been a busy first quarter of 2022 for the company as we continue to build on the momentum we've carried through from last year. We're excited to be making great progress in all 4 clinical programs. And just as a reminder, success in any one of these 4 programs would be absolutely transformative for the financial performance of the company and for our shareholders.

謝謝艾略特，大家早上好。正如您剛剛聽說的，對於公司來說，2022 年第一季度是忙碌的，我們將繼續鞏固去年的勢頭。我們很高興在所有 4 個臨床項目中取得了巨大進展。提醒一下，這 4 個項目中任何一個的成功都絕對會對公司和股東的財務業績產生革命性的影響。

I'll now go through the financial results for the first quarter ending March 31, 2022, which demonstrates strong financial performance. As we execute against our strategy, we'll be happy to take questions at the end. Cash and cash equivalence as of March 31, 2022, were $68.8 million as compared to $78.5 million at December 31, 2021. As part of our partnering strategy Merck KGaA also took their fourth licensing option during this first quarter. We expect our cash and cash equivalents will be sufficient to fund our projected operating plans, including multiple clinical milestones across all 4 programs through the first quarter of 2023. Revenue for the first quarter of 2022 was 2.6 million as compared with 2.9 million for the same period in the prior year. In both periods, Merck exercised their option to acquire [IP] rights to their third and fourth molecules under our license and collaboration agreement.

我現在將查看截至 2022 年 3 月 31 日的第一季度的財務業績，該業績展示了強勁的財務業績。當我們執行我們的策略時，我們很樂意在最後回答問題。截至 2022 年 3 月 31 日，現金和現金等價物為 6,880 萬美元，而 2021 年 12 月 31 日為 7,850 萬美元。作為我們合作戰略的一部分，默克公司還在第一季度採取了第四次許可選擇。我們預計我們的現金和現金等價物將足以為我們的預計運營計劃提供資金，包括到 2023 年第一季度所有 4 個項目的多個臨床里程碑。2022 年第一季度的收入為 260 萬美元，而 2022 年第一季度的收入為 290 萬美元。上一年期間。在這兩個時期，默克公司都根據我們的許可和合作協議行使了獲得第三和第四種分子的[知識產權]的選擇權。

Total R&D expenses were $8 million for the 3 months ended March 31, 2022, as compared to 7.1 million for the prior year first quarter. This $900,000 increase is primarily due to an increase in clinical CRO costs of $1.4 million resulting from an increased number of patients on trials on our 4 clinical trials, an increase of $1.2 million of R&D staff related costs, primarily to support clinical operations, and an increase of $0.4 million of other costs, all of which are offset by decreases in manufacturing costs of $0.4 million, due to the timing of batch manufacturing activities, and a $1.7 million increase in the UK research and development tax credit, which is recorded as a reduction of R&D costs. The total R&D expenses include 0.5 million and 0.4 million of non-cash stock-based compensation expense for both the first quarter of 2022 and 2021 respectively. Total G&A expenses were 5.7 million for the 3 months ended March 31, 2022, as compared to 6.4 million for the prior year first quarter.

截至 2022 年 3 月 31 日的三個月，研發費用總額為 800 萬美元，而去年第一季度的研發費用為 710 萬美元。增加 90 萬美元主要是由於 4 項臨床試驗的患者數量增加導致臨床 CRO 成本增加 140 萬美元，研發人員相關成本增加 120 萬美元（主要用於支持臨床運營），以及其他成本增加 40 萬美元，所有這些都被批量生產活動時間安排導致的製造成本減少 40 萬美元以及英國研發稅收抵免增加 170 萬美元所抵消。降低研發成本。研發費用總額分別包括2022年第一季度和2021年第一季度50萬美元和40萬美元的非現金股票補償費用。截至 2022 年 3 月 31 日的三個月，一般管理費用總額為 570 萬美元，而去年第一季度為 640 萬美元。

This $0.7 million decrease is primarily due to a decrease in stock compensation expense of 0.8 million, a decrease in legal and professional cost of 0.4 million, which is due to cost incurred in the prior year quarter for work related to the share exchange agreement with Spring Bank Pharmaceuticals. These decreased costs were offset by increases of $0.4 million in facilities in IT-related expenses and other general costs of 0.1 million. Total G&A expense also includes 1 million and 1.8 million of non-cash stock-based compensation expense for Q1 22 and 2021, respectively. Net loss for the first quarter of 2022 was 12.1 million or 0.57 cents per basic and diluted share, compared with a net loss of 9.7 million or $1.07 per basic and diluted share for the first quarter of 2021.

減少 70 萬美元主要是由於股票補償費用減少 80 萬美元，法律和專業成本減少 40 萬美元，這是由於上一季度與 Spring 的股份交換協議相關的工作產生的成本銀行製藥。這些減少的成本被 IT 相關設施費用增加 40 萬美元和其他一般成本增加 10 萬美元所抵消。總管理及行政費用還包括 22 年第一季度和 2021 年分別為 100 萬美元和 180 萬美元的非現金股票補償費用。 2022 年第一季度的淨虧損為 1210 萬美元，即每股基本和稀釋股份 0.57 美分，而 2021 年第一季度的淨虧損為 970 萬美元，即每股基本和稀釋股份 1.07 美元。

In closing, the first quarter of 22 has brought growing momentum and increased confidence in our portfolio. We're well positioned to deliver on our strategy in the coming months. And we're very excited by the important data readouts across all 4 of our programs expected later this year. With bispecifics coming of age, it's a very important time for F-star as can continue to pioneer bispecifics to help more people with cancer live longer and better lives. With that, operator, we'll open the call for questions now. Thank you.

最後，22 年第一季度給我們的投資組合帶來了增長動力和信心。我們已做好充分準備，可以在未來幾個月內實施我們的戰略。我們對今年晚些時候預計將在所有 4 個項目中讀出的重要數據感到非常興奮。隨著雙特異性技術的成熟，對於 F-star 來說這是一個非常重要的時刻，因為它可以繼續開拓雙特異性技術，幫助更多的癌症患者活得更久、生活得更好。接線員，我們現在就開始提問。謝謝。

(Operator Instructions) Our first question is from Daina Graybosch with SVB Securities.

（操作員指令）我們的第一個問題來自 SVB 證券的 Daina Graybosch。

One sort of process question and one science question for me. On the process side on FS118 specifically, you know, you're guiding to preliminary data from phase 2, sort of in the midyear, but also guiding to medical conferences. And I wonder if you could give us any more details on what potential medical conferences you would be submitting to and about how many patients we could expect. And then on the science side, in your recent AACR poster, perhaps the most intriguing thing was the difference in the LAG-3 cleavage dynamics for t-cells in the tumor versus the blood. And I wonder if you could describe that and what you think is mechanistically driving the difference in those 2 compartments.

對我來說，一種過程問題和一種科學問題。具體來說，在 FS118 的流程方面，您知道，您正在指導第二階段（大約在年中）的初步數據，而且還指導醫學會議。我想知道您是否可以向我們提供更多詳細信息，說明您將參加哪些潛在的醫學會議以及我們預計會有多少患者。然後在科學方面，在您最近的 AACR 海報中，也許最有趣的事情是腫瘤中 T 細胞與血液中 LAG-3 裂解動力學的差異。我想知道您是否可以描述一下這一點以及您認為在機械上驅動這兩個隔間差異的原因。

Good morning, Daina, thanks for both of those questions. So just to pick off the process one first: as a company in common with many our preferences is typically to go to shareholder — sorry to technical or medical conferences in order to present new data. clearly that's only if the timing of those conferences work with the timing of the delivery of the data. For FS118 we're working towards the reporting of the proof of concept study, as you mentioned, in head and neck, and we'll make a judgment over the coming few weeks as to where that data will be presented. So either at a conference, or we'll use a company press release and conference call associated with that. And we're not far away from it in my judgment right now. We've guided in the past that we're looking for a minimum of 10 evaluable patients — so that's patients who have the right co-expression of LAG-3 and PD-L1 with the head and neck acquired resistance profile. And again, we'll be working to ensure we have at least that number available to present.

早上好，戴娜，謝謝你提出這兩個問題。因此，首先要挑出一個流程：作為一家與我們的許多偏好相同的公司，通常是去股東那裡——抱歉，為了提供新數據而召開技術或醫學會議。顯然，前提是這些會議的時間與數據交付的時間一致。對於 FS118，我們正在努力報告概念驗證研究的報告，正如您提到的，在頭頸方面，我們將在未來幾週內就將在何處呈現這些數據做出判斷。因此，要么在會議上，要么我們將使用與此相關的公司新聞稿和電話會議。根據我的判斷，我們現在離它並不遙遠。我們過去曾指導過，我們正在尋找至少 10 名可評估的患者，即 LAG-3 和 PD-L1 正確共表達且頭頸部獲得性耐藥情況的患者。再次，我們將努力確保我們至少有這個數字可供展示。

And then for the second question, which relates to the AACR paper: the difference between LAG expression on the TILs versus in the blood. We're actually in the process of drafting a paper around this. So I'm going to be reasonably cagey on, the mechanism. But I guess, I think, as you'd understand, with the crosslinking and clustering in particular, in the cell to cell environment, you'd expect to see in the tumor dramatic regulation. And I think as far as I can go right now in the blood is to say that there is a possibility of compensatory mechanisms with respect to LAG-3 expressions. So that's one of the reasons we're potentially seeing some differences there. But we're, as I say, we're working on that manuscript. But, you know, I guess fundamentally the key being we're seeing the drop in LAG-3 in TILs in patients.

然後是與 AACR 論文相關的第二個問題：TIL 上的 LAG 表達與血液中的 LAG 表達之間的差異。實際上，我們正​​在起草一份有關此問題的論文。所以我會對這個機制保持相當謹慎的態度。但我想，正如你所理解的，特別是在細胞間環境中的交聯和聚集，你會期望在腫瘤中看到戲劇性的調節。我認為，就我目前在血液中所能達到的程度而言，LAG-3 表達可能存在補償機制。這就是我們可能會看到一些差異的原因之一。但正如我所說，我們正在研究這份手稿。但是，我想從根本上來說關鍵是我們看到患者 TIL 中 LAG-3 的下降。

Our next question comes from Matt Phipps with William Blair.

我們的下一個問題來自馬特·菲普斯和威廉·布萊爾。

This is Rob Andrew for Matt Phipps here. Just wanted to return to the comments on the FS118 trial as well here. The addition of more trial science and anticipation of expansion definitely seems like a positive set. Could you just remind us, have you specifically disclosed the bar for expanding that study and how are you kind of accounting for the fact that you p been able to get biopsy samples from all those patients, when you're thinking about the bar there — did I catch it right that those patients without biopsies are not going to be considered among the 10 evaluable patients she described? And then, you know, secondly, just a kind of a broader question: clearly the FDA is kind of focusing on the [early] stage clinical development and dose optimization with project [optimist]. We saw the FDA host a 2 day panel on the subject of dose optimization last week in which, you know, some immunotherapies were kind of used as examples of where dose optimization could have been better in early stage development. So just kind of how you're thinking about that in the whole context of your own pipeline in terms of how to best satisfy FDA, the sufficient dose optimization has been carried out in these kind of phase one studies across the pipeline. Thanks.

我是羅布·安德魯（Rob Andrew），代表馬特·菲普斯（Matt Phipps）。只是想在這裡回到對 FS118 試驗的評論。增加更多的試驗科學和對擴展的預期絕對看起來是一個積極的組合。您能否提醒我們，您是否具體披露了擴大該研究的標準？當您考慮那裡的標準時，您如何解釋您能夠從所有這些患者身上獲取活檢樣本的事實 -我是否理解正確的是，那些沒有進行活檢的患者不會被納入她描述的 10 名可評估患者之中？然後，你知道，第二，只是一個更廣泛的問題：顯然 FDA 正在關注[早期]階段的臨床開發和項目[樂觀]的劑量優化。上週，我們看到 FDA 舉辦了一個為期 2 天的關於劑量優化主題的小組會議，其中，您知道，一些免疫療法被用作劑量優化在早期開發中可以更好的例子。因此，您在自己的管道的整個背景下如何考慮如何最好地滿足 FDA 的要求，在整個管道的此類第一階段研究中已經進行了足夠的劑量優化。謝謝。

Great. Thanks very much, Rob. And thanks for question. Good morning. So, with respect to biopsies, what we've been doing is collecting biopsies, and then we have (inaudible) defined a retrospective analysis of the PD-L1 LAG-3 positivity in the biopsies. And we're looking in reverse, as it were, to see how the patients do who have that appropriate biomarker profile with the head and neck cancer. What we haven't stated, as you rightly say, is what the bar for success is. However, what we have been doing over the past quarter is adding more patients through our site in Europe to this. And of course the other FS118 trials that are ongoing. And so I guess what we're going to ensure is that we have the right level of availability.

偉大的。非常感謝，羅布。謝謝你的提問。早上好。因此，就活檢而言，我們一直在收集活檢，然後（聽不清）定義了對活檢中 PD-L1 LAG-3 陽性的回顧性分析。我們正在反向觀察，看看那些具有適當的頭頸癌生物標誌物特徵的患者的表現如何。正如您所說，我們沒有說明的是成功的門檻是什麼。然而，我們在過去一個季度一直在做的是通過我們在歐洲的網站增加更多的患者。當然還有正在進行的其他 FS118 試驗。所以我想我們要確保的是我們擁有適當的可用性水平。

And I think it's right to be prepared for success and hence why we're prepping for the second part of the study at the same time. So with respect to Optimus Optus, really, I think this is a measure of ensuring we have a kind of lowest effective dose for FS118, we're pretty comfortable given — and some of this is about to be published in a full manuscript — we're pretty comfortable that we've now got what will be defined as an appropriate selected dose, obviously still to be discussed with the FDA. For the other programs, it also brings sort of new ways of thinking about the program. So FS222 and FS120, because we've got drugs that are really well tolerated — and we can continue to escalate the dose — what you'll see from us is that we've explored more than one dose level for each of those programs as we've gone through the early stages of development, really with a mind to being able to ultimately discuss with the FDA at a kind of end of phase one, or pre phase 2 meeting as to whether they want us to carry one or maybe 2 doses forward. And we're building a biological and patient rationale around each of those considerations. It's more pertinent for the FS222 and the FS120, where we pretty comfortable. We've got a package of data that gives us confidence in the dose level we're at great.

我認為為成功做好準備是正確的，因此我們同時為研究的第二部分做準備。因此，關於 Optimus Optus，實際上，我認為這是確保我們對 FS118 擁有最低有效劑量的一種措施，考慮到其中一些即將以完整手稿的形式發表，我們對此感到非常滿意。很高興我們現在已經確定了合適的選定劑量，顯然仍有待與 FDA 討論。對於其他程序來說，它也帶來了一些新的程序思考方式。所以 FS222 和 FS120，因為我們已經有了耐受性非常好的藥物——而且我們可以繼續增加劑量——你會從我們身上看到的是，我們已經為每個項目探索了不止一種劑量水平，我們已經經歷了開發的早期階段，真正的目的是能夠最終在第一階段結束時或第二階段會議之前與 FDA 討論他們是否希望我們攜帶一個或兩個劑量向前。我們正在圍繞這些考慮因素建立生物學和患者的基本原理。它與 FS222 和 FS120 更相關，我們對此感到非常滿意。我們獲得了一系列數據，使我們對當前的劑量水平充滿信心。

Our next question comes from Hartaj Singh with Oppenheimer.

我們的下一個問題來自哈塔吉·辛格和奧本海默。

When you're at the end of your rope, you just tie a knot and hold on, somebody once said, in this environment. But really looking forward to these readouts. Just a quick question on head and neck with FS118, you know, the [Bristol combo] has been approved for a while now, or at least a few months — but of course in melanoma. Any insights that you've gotten more so from that — I know it's a different tumor — as to what gives you line of sight into FS118, the head and neck read out, and then what exactly are you looking for, or what would the parameters, or what you're looking for in order to move the project forward? And then I just got a quick follow up.

有人曾經說過，在這種環境下，當你走到了繩子的盡頭時，你只需打個結並抓住即可。但真的很期待這些讀數。關於 FS118 的一個簡單問題，您知道，[布里斯托爾組合] 已經獲得批准一段時間了，或者至少幾個月了，但當然是針對黑色素瘤。您從中獲得的任何見解 - 我知道這是一種不同的腫瘤 - 是什麼讓您能夠看到 FS118，頭部和頸部讀數，然後您到底在尋找什麼，或者什麼是參數，或者您正在尋找什麼來推動項目向前發展？然後我就得到了快速跟進。

Yes, sure. So, Hey, Hartaj, good morning. And we're lucky in the sense that we have 4 ropes to hang onto. And so, so that's great. However, just let's go to the BMS data. So, you know, we are interested as you know, from previous conversations in the LAG-3 expression, and my response to Rob's question about biopsies, we follow that through, and that's true, not just in the head neck setting, but also in the 2 checkpoint naive settings of non-small cell lung cancer and diffused large b-cell lymphoma. And that's really the central thread that's run through the working clinical hypotheses you put together what we draw. Interestingly, you've got to sort of go back to the fundamental mechanism of PD1 one PD-L1 [axis] and LAG-3 axis . And what we've demonstrated previously, and it's actually been shown by others, is if you suppress the PD1-PD-L1 axis and the LAG-3 axis with a combination, what you in effect do is cause an upregulation of the expression of both of those receptors. And so, in effect, even if a patient going into a combination study is an initial, in inverted commas, low expressor of LAG-3, during the course of their treatment, even though they'll be getting under control because they've got an [antagonists] in place, their baseline level of LAG-3 will grow. And so for us, understanding that mechanism and understanding the fact that we because of [crosslinking] (inaudible) cleave the LAG-3 and don't see upregulation in the tumor microenvironment through the TILs really gives us a point of difference, but also the confidence that LAG-3 expression and then the inhibition of its function — in our case through cleavage — becomes central to that kind of working hypothesis.

是的，當然。所以，嘿，Hartaj，早上好。我們很幸運，因為我們有 4 根繩子可以抓住。所以，那就太好了。不過，讓我們看看 BMS 數據。所以，你知道，正如你所知，我們對 LAG-3 表達式的先前對話以及我對 Rob 關於活檢問題的回答很感興趣，我們會遵循這一點，這是事實，不僅在頭頸設置中，而且在在非小細胞肺癌和瀰漫性大 B 細胞淋巴瘤的 2 個檢查點初始設置中。這確實是貫穿我們所繪製的工作臨床假設的中心線索。有趣的是，你必須回到 PD1、PD-L1 [軸] 和 LAG-3 軸的基本機制。我們之前已經證明了，實際上其他人也已經證明了，如果你聯合抑制 PD1-PD-L1 軸和 LAG-3 軸，你實際上會導致這兩個受體。因此，實際上，即使進入聯合研究的患者是 LAG-3 低表達的初始患者，在治療過程中，即使他們會得到控制，因為他們已經有了[拮抗劑]，他們的 LAG-3 基線水平就會提高。因此，對我們來說，了解這一機制並了解我們由於[交聯]（聽不清）裂解 LAG-3 並且沒有通過 TIL 在腫瘤微環境中看到上調這一事實確實給我們帶來了一點不同，但也LAG-3 表達以及隨後對其功能的抑制（在我們的例子中是通過裂解）的信心成為這種工作假設的核心。

So that's where we are with LAG-3. We haven't disclosed on the second question what our hurdle rate is. Clearly this is a patient group who have a few other options having been through checkpoint, their often third or sometimes fourth line of treatment, when they come — when they're on our trials. And there's a relatively low bar, but of course we want to get much higher than that ourselves in order to give us confidence to go forwards: one confidence, to go further forward in this proof of concept study and head and neck, but also planning for you know a kind of basket trial in which we would look at other acquired resistant patient settings. Of course, unfortunately, head and neck is not the only cancer in which patients who've been treated with PD1 and have a response then become refractory. And we're interested around that LAG-3 hypothesis but interested in those patient groups as well. So that's where we'll be going next. You said you had a follow up, Hartaj.

這就是 LAG-3 的現狀。我們還沒有透露第二個問題我們的最低門檻是多少。顯然，這是一個已經通過檢查點的患者群體，當他們來參加我們的試驗時，他們通常是第三線或有時是第四線治療，他們有一些其他選擇。有一個相對較低的標準，但我們當然希望比我們自己更高，以便給我們前進的信心：一個信心，在概念驗證研究和頭頸方面進一步前進，但也規劃因為你知道一種籃子試驗，我們會研究其他獲得性耐藥患者的情況。當然，不幸的是，頭頸癌並不是唯一一種接受過 PD1 治療並產生反應的患者變得難治的癌症。我們對 LAG-3 假說感興趣，但也對那些患者群體感興趣。這就是我們下一步要去的地方。你說過你有後續行動，哈塔傑。

Yes. Thank you, Eliot. Yes, no that's great. Thank you so much for detail answer. And just that question of Darlene, which is that, again, kudos for managing your, your P&L really well — these kind of small, but stepwise increases as your clinical activity increases, but generally, you know, assuming you have one, 2 or 3 of these kind of top line readouts important to the company that (inaudible) material readout in the next 6, 12 months, how to think about your R&D um, burn rate, basically over the next year or 2 years. Thank you.

是的。謝謝你，艾略特。是的，不，那太好了。非常感謝您的詳細解答。就達琳的問題而言，再次感謝您能夠很好地管理您的損益表 - 這些金額雖小，但隨著您的臨床活動的增加而逐步增加，但一般來說，您知道，假設您有一個、兩個或其中 3 種頂線讀數對公司很重要，（聽不清）未來 6、12 個月內的材料讀數，如何考慮您的研發嗯，燒錢率，基本上是在未來一年或兩年內。謝謝。

Yes. Hi, Hartaj. Well, as we said, we do expect that we have enough cash to get us well through the first quarter of next year and moving forward with all these programs and all these readouts. Now, obviously, as we take more patients on trial, costs will increase over time. So you're sort of seeing kind of level spending now with a little bit of build over the remain of the year and into next year. So it will build some while I expect G&A will sort of stay flat to potentially even come down just a tad. But again, it's really kind of driven by patients on trial.

是的。嗨，哈塔傑。好吧，正如我們所說，我們確實希望有足夠的現金來讓我們順利度過明年第一季度，並推進所有這些計劃和所有這些讀數。現在，顯然，隨著我們接受更多患者進行試驗，成本會隨著時間的推移而增加。因此，您現在可以看到支出處於一定水平，並且在今年剩餘時間和明年會有一些增加。因此，它會增加一些，而我預計一般行政費用將保持平穩，甚至可能略有下降。但同樣，這確實是由試驗中的患者驅動的。

Great, Darlene. Do you give any updates as to your partner revenue? I mean, how does that affect your burn — your revenue run rate through the first quarter of next year?

太棒了，達琳。您是否提供有關合作夥伴收入的最新信息？我的意思是，這對你的燒錢——明年第一季度的收入運行率有何影響？

Yes, so we have not given guidance on that unless — until it happens, but we do have visibility into some of that, and that is factored into our cash flow projections. There's certain milestones that we — that are shorter term and others that are longer term, and as they become more — closer to solidified, we definitely run that through our cash projections, but we have not disclosed that. And not disclosed what those milestones are based on confidentiality with our partners. I can say too, that one of the unique features in the UK is that they actually have these R&D research development tax refunds, not just credits, but they're refunds. So, we're in the process of doing the calculations and submitting those now, but that can be in the millions of dollars, and that's you know, that's a definite if you will, at least for the time being, so that's a nice thing. It's not just a tax credit. It's actually a tax refund. So we've got that built into the model as well.

是的，所以我們沒有就此給出指導，除非 - 直到它發生，但我們確實了解其中的一些內容，並將其納入我們的現金流預測中。我們有一些里程碑——短期的和長期的，隨著它們變得越來越接近鞏固，我們肯定會通過我們的現金預測來實現這一點，但我們尚未披露這一點。基於對我們合作夥伴的保密，沒有透露這些里程碑是什麼。我也可以說，英國的獨特之處之一是他們實際上有這些研發研究開發退稅，不僅僅是抵免，而是退款。所以，我們現在正在計算並提交這些數據，但這可能是數百萬美元，這就是你知道的，如果你願意的話，這是確定的，至少暫時是這樣，所以這是一個很好的選擇事物。這不僅僅是稅收抵免。其實就是退稅。所以我們也將其內置到模型中。

Our next question comes from Patrick Trucchio with H.C. Wainwright.

我們的下一個問題來自 Patrick Trucchio 和 H.C.溫賴特。

This is Jason on for Patrick. And my first question is just around SB 11285. And we were just wondering in terms of kind of benchmarking the potentials of SB 11285. And should we be looking at more of like Mercks or [GSKs] and will it be a potential guide for the path forward? And I have a follow up question after that?

這是傑森替帕特里克發言。我的第一個問題是關於 SB 11285 的。我們只是想知道 SB 11285 潛力的基準測試。我們是否應該更多地關注像 Mercks 或 [GSKs] 這樣的公司，它是否會成為 SB 11285 的潛在指南？前進的道路？之後我還有一個後續問題？

Great morning, Jason. Thanks very much for your question. So you know, we sit squarely in the kind of second generation of STING so we [we] can be given intravenously and we gave an update at the end of last years, a few months ago, saying that to date the ascending — the accelerate — the ascending parts of the dose had been going well and was safe and well tolerated, some early signs of STING. I think where we've tended to benchmark ourselves is against other second generations. So we'd — of the 2 you've selected, we were kind of more point towards the [GSK] molecule, and certainly, you know, we're looking forward to seeing any data from that organization as it moves. One of the challenges of first generation, of course, was there was a kind of step wise function in biological response to STING agonism, and it was a kind of all or nothing.

早上好，傑森。非常感謝你的提問。所以你知道，我們正處於第二代 STING 中，這樣我們就可以進行靜脈注射，我們在去年年底，幾個月前進行了更新，說迄今為止，上升 - 加速— 劑量的上升部分進展順利，安全且耐受性良好，是 STING 的一些早期跡象。我認為我們傾向於將自己與其他第二代人進行比較。因此，在您選擇的兩個中，我們更傾向於 [GSK] 分子，當然，您知道，我們期待看到該組織的任何變化數據。當然，第一代的挑戰之一是對 STING 激動的生物反應存在一種逐步的功能，這是一種全有或全無的感覺。

And we were, you know, really interested to see Prof. Currans' work out of MD Anderson, who's been doing analysis of the current clinical STING — [assets] of STING that are in the clinic. And, and he had some positive things to say about [SB 1125] with respect to its kind of gradual uptake — uptick, my apology uptick in STING agonism. So we we're excited about what's going on in the clinic. We'll certainly report more in the later part of the show from that study as a monotherapy and in combination with the (inaudible).

你知道，我們非常有興趣看到 Currans 教授在 MD 安德森的工作，他一直在分析當前的臨床 STING——臨床上的 STING [資產]。而且，他對 [SB 1125] 的逐漸接受程度有一些積極的看法——上升，我對 STING 激動的道歉上升。所以我們對診所發生的事情感到興奮。我們肯定會在節目的後半部分報告更多該研究作為單一療法以及與（聽不清）的結合。

Okay. Yes, that's really helpful to know. And just kind of building off the last point that you just said: in terms of data being released later this year, can you remind us, is this for the part A or part B or — and just, again, to clarify, which is the part A in part B of the phase one study?

好的。是的，了解這一點確實很有幫助。就您剛才所說的最後一點而言：就今年晚些時候發布的數據而言，您能否提醒我們，這是 A 部分還是 B 部分，或者——再次澄清一下，這是第一階段研究的 A 部分和 B 部分？

Of SB 11285, Jason, just to be clear?

SB 11285，Jason，需要澄清一下嗎？

Yes, yes. For SB12185. Yes.

是的是的。對於SB12185。是的。

Yes, yes. So it's in 2 parts: there's a combina — sorry, part A is just a simple monotherapy, ascending dose standard 3 plus 3, and part B is in combination with a flat dose of atlizumab, flat standard dose atlizumab. And I would anticipate will be — tens of patients, maybe 30 to 40 patients worth of data will be reporting towards the end of this year. So we're excited about what we're seeing and looking forward to more data.

是的是的。所以它分為兩部分：有一個組合 - 抱歉，A部分只是簡單的單一療法，遞增劑量標準3加3，B部分與固定劑量的atlizumab，固定標準劑量的atlizumab組合。我預計，到今年年底，將會有數十名患者，也許 30 到 40 名患者的數據報告。因此，我們對所看到的感到興奮，並期待更多數據。

Our next question comes from Ahu Demir with Ladenburg.

我們的下一個問題來自 Ahu Demir 和 Ladenburg。

My first question is on the FS118 program. Just to follow up on the AACR presentation: knowing the tumor [infiltrating] lymphocyte aspects, do you plan to implement that and do you expect patients with higher TIL expression to respond? And are we expecting any maybe clinical data on that side?

我的第一個問題是關於 FS118 計劃的。只是跟進 AACR 的演示：了解腫瘤[浸潤]淋巴細胞方面，您是否計劃實施該方案，以及您是否期望 TIL 表達較高的患者做出反應？我們是否期待這方面的任何臨床數據？

Hey morning, nice to speak with you. Just to repeat, you just broke up slightly in there. So for the TIL LAG-3 expression?

早上好，很高興與你交談。再說一遍，你們剛剛在那里分手了。那麼對於 TIL LAG-3 表達式呢？

Yes. Happy to sorry, Eliot. No, no worries. Given the knowledge on the TILs, are we expecting to see perhaps better response rate with patients who have higher TIL expression? And do you plan to show more data on that? What are the implementation on the clinical side?

是的。高興又抱歉，艾略特。不，不用擔心。鑑於對 TIL 的了解，我們是否期望看到 TIL 表達較高的患者的緩解率更高？您打算展示更多這方面的數據嗎？臨床方面有哪些實施？

Yes, sure. So, I mean, this really comes back to our fundamental hypothesis that, you know, LAG-3 and PD-L1 expression in the post checkpoint setting, and indeed in the checkpoint naive setting, is really, really important. And I think, if you look at the phase one data, then what we saw was a correlation between expansion of TIL activity post-treatment with disease control and indeed one unconfirmed and one confirmed PR, with high expression of LAG-3 and PD-L1. And we expect to see that in the phase 2 proof of concept. It's a great question to try and get me to kind of spill the beans before we announce the data. But we're excited to look at the correlation between LAG-3 expression and clinical benefit in the head and neck proof concept study.

是的，當然。所以，我的意思是，這確實回到了我們的基本假設，即，你知道，LAG-3 和 PD-L1 在檢查點後設置中的表達，實際上在檢查點初始設置中，非常非常重要。我認為，如果你看一下第一階段的數據，那麼我們看到的是治療後 TIL 活性的擴大與疾病控制之間的相關性，實際上與一項未經證實和一項確診的 PR 之間存在相關性，其中 LAG-3 和 PD- 的高表達L1。我們期望在第二階段概念驗證中看到這一點。在我們公佈數據之前，嘗試讓我透露一些秘密是一個很好的問題。但我們很高興在頭頸證明概念研究中了解 LAG-3 表達與臨床獲益之間的相關性。

Thanks, Eliot. I have one more question on the 4-1BB site: you have 2 asset targeting 4-1BB. Is there a particular one you are more excited about, and given that we'll see (inaudible), preliminary efficacy data on the 22,2 program, I'm curious to hear if there are any other programs in the near term that perhaps investors can place more confidence for 4-1BB as a target, maybe during (inaudible) or any other presentation. Just would like to get more information on that as well.

謝謝，艾略特。我在 4-1BB 網站上還有一個問題：您有 2 項資產定位為 4-1BB。有沒有一個讓您更興奮的項目，鑑於我們將看到（聽不清）22,2 計劃的初步功效數據，我很想知道短期內是否還有其他計劃可能投資者可以對 4-1BB 作為目標更有信心，也許是在（聽不清）或任何其他演示期間。我也想獲得更多相關信息。

Well, I've often asked by investors in particular which is my favorite child. And I always argue that they're, they're all lovely, but all different. And I think for the 2 4-1BB molecules, FS222 and FS120, you know, they fall into that lovely and different category. It is true that FS222 will be reporting preliminary data in the coming few months. And we're very excited about what we're seeing with that. We've been particularly impressed by how the preclinical data have translated into the clinic. And I would say for that molecule in particular, we've got some reasonable benchmarks from which we'll need to differentiate given some of the competitors who are also developing PD-L1, 4-1BB, you know, in the non-clinical setting, we saw complete disease control without the need for a combination with a PD1.

嗯，我經常被投資者特別問到我最喜歡的孩子是哪一個。我總是認為他們都很可愛，但又各不相同。我認為對於 2 個 4-1BB 分子，FS222 和 FS120，你知道，它們屬於那個可愛且不同的類別。確實，FS222 將在未來幾個月內報告初步數據。我們對所看到的一切感到非常興奮。臨床前數據如何轉化為臨床給我們留下了特別深刻的印象。我想說的是，特別是對於該分子，我們有一些合理的基準，我們需要根據這些基准進行區分，因為一些競爭對手也在開發 PD-L1、4-1BB，你知道，在非臨床領域在這種情況下，我們看到了疾病的完全控制，而不需要與 PD1 聯合使用。

And, you know, we're happy to see that beginning to translate into the clinic. In addition to that, of course, we're going after both high and low PD-1 expressing tumors and non-clinically, we observe no sign of the so-called bell shaped or hook effect that has been present with some of the competitors. So we know the kind of pillars of differentiation that we're aiming for. And we're excited to bring FS222 data forward in the coming few months. You may, from all of that conclude that that is my favorite child, but it's lovely but different from FS120, and as you know FS120 is a first in-class dual agonist. It's a really potent molecule. We're very excited to be combining it with pembrolizumab from Merck.

而且，你知道，我們很高興看到這一點開始轉化為臨床。當然，除此之外，我們正在研究高表達和低表達 PD-1 的腫瘤，並且在非臨床方面，我們沒有觀察到某些競爭對手存在的所謂鐘形或鉤狀效應的跡象。因此，我們知道我們的目標是什麼，是差異化的支柱。我們很高興能在未來幾個月內提供 FS222 數據。從所有這些你可能會得出結論，那是我最喜歡的孩子，但它很可愛，但與 FS120 不同，正如你所知，FS120 是同類中的第一個雙重激動劑。這是一種非常有效的分子。我們非常高興將其與默克公司的 pembrolizumab 相結合。

And we'll talk about what we're doing beyond that towards the end of this year. But this is a, this is a molecule that is kind of tumor type agnostic, and the way in which it can be used is in this combination. So pembro is approved in about 17 indications if I recall of late. And so of course we can go into any of those settings and some of our non-clinical data with 3 different types of chemo (inaudible). So some real important synergies. So, I would say in a different sort of way, 120 is a really important and exciting molecule for us as well than 222.

我們將在今年年底討論除此之外我們正在做的事情。但這是一種與腫瘤類型無關的分子，它的使用方式就是在這種組合中。如果我最近記得的話，pembro 大約有 17 種適應症被批准。因此，我們當然可以使用 3 種不同類型的化療（聽不清）來研究任何這些設置和一些非臨床數據。所以一些真正重要的協同效應。所以，我會以不同的方式說，120 對我們來說是一個比 222 更重要、更令人興奮的分子。

(Operator Instructions) Our next question comes from Yale Jen with Laidlaw & Co.

（操作員說明）我們的下一個問題來自 Yale Jen 和 Laidlaw & Co.。

The first question I have is about 222. My understanding is that you might have 2 data reporting. In other words, another one after your initial one in this year, is that correct? So that would be my first one.

我的第一個問題是關於222。我的理解是你可能有2個數據報告。換句話說，今年繼第一屆之後，又是另一屆，對嗎？所以這將是我的第一個。

Yes. So, 222 is going very well. And what we've done is managed to bring some of the data that we were planning to update much later this year sooner. So we'll do that in the coming few months. And we'll then have a look and see what else emerges beyond that. So, there'll be more data in this first report that than we'd anticipated. Clearly we continue to explore the full spectrum of activity for FS222 in that both in those PD-L1 low and PD-L1 high settings. We also hope, which we haven't disclosed yet, but we're also particularly interested in seeing some intriguing data in the clinic from another biomarker that we've been using in combination with that PD-L1 expression level as well. And, we almost certainly we'll be talking more about that in the months to come.

是的。所以，222 進展順利。我們所做的就是設法提供一些我們計劃在今年晚些時候更新的數據。所以我們將在未來幾個月內做到這一點。然後我們將看看除此之外還會出現什麼。因此，第一份報告中的數據將比我們預期的要多。顯然，我們將繼續探索 FS222 在 PD-L1 低和 PD-L1 高設置下的全譜活性。我們也希望，這一點我們尚未透露，但我們也特別有興趣在臨床中看到來自另一種生物標誌物的一些有趣的數據，我們也一直在與 PD-L1 表達水平結合使用該生物標誌物。而且，幾乎可以肯定，我們將在未來幾個月內更多地討論這一問題。

So should I interpret that as that you will have the first data report with a much more enriched data and (inaudible) probably has a second one or otherwise it will be maybe push the second data readout into next year?

那麼我是否應該將其解釋為您將擁有第一個包含更豐富數據的數據報告，並且（聽不清）可能有第二個數據報告，否則可能會將第二個數據讀數推到明年？

Yes, I think your interpretation of a much enriched update in the coming few months is a good way of interpreting that. And we'll guide once we're through that as to when the next set of data will be coming.

是的，我認為您對未來幾個月內更加豐富的更新的解釋是解釋這一點的好方法。一旦完成，我們將指導下一組數據何時到來。

Okay. Maybe a quick follow up in terms of 118 — that I know the announcements are long and DL, PCL enrolment has some issues there in terms of the Ukraine situation. What kind of remedial work currently you try to resolve this issue?

好的。也許是關於 118 的快速跟進——我知道公告很長，而且 DL、PCL 註冊在烏克蘭局勢方面存在一些問題。目前你們正在採取哪些補救措施來解決這個問題？

Yes, I like — and, you know, I'll repeat what I said. You know, what we are doing is trivial compared to the suffering of the people of Ukraine, but we also need to keep our programs moving forward to benefit patients that we can. And so what we've done and we did it pretty much immediately is added additional sites to the countries we were already open in, and then quickly looked for feasibility in new countries. So, and that was part of our contingency planning around the war in Ukraine. And as I reported a little while ago, we are pleased to say that those contingencies are coming into place. I think the reality is that for data output, the diffused large c-cell lymphoma should still be first quarter of next year. So, that should be fully on track. And we think current estimates suggest we may lose about a quarter with the head and neck — non-small cell, sorry, non-small cell lung cancer study apologies. And that will be then to the second quarter of next year. Though, we'll do everything we can to pull that forward. Of course.

是的，我喜歡——而且，你知道，我會重複我說過的話。你知道，與烏克蘭人民的苦難相比，我們正在做的事情微不足道，但我們還需要繼續推進我們的項目，盡可能造福患者。因此，我們所做的，而且我們幾乎是立即做的，就是在我們已經開放的國家/地區添加更多站點，然後迅速在新的國家/地區尋找可行性。所以，這是我們圍繞烏克蘭戰爭制定的應急計劃的一部分。正如我不久前報導的那樣，我們很高興地說這些意外情況正在發生。我認為現實情況是，就數據輸出而言，瀰漫性大C細胞淋巴瘤應該仍然是明年第一季度。所以，這應該完全步入正軌。我們認為，目前的估計表明，我們可能會失去大約四分之一的頭部和頸部——非小細胞肺癌，抱歉，非小細胞肺癌研究道歉。那將是到明年第二季度。不過，我們將盡一切努力推動這一進程。當然。

Our next question comes from Justin Walsh with B. Riley Securities.

我們的下一個問題來自 B. Riley Securities 的 Justin Walsh。

I know that you can't provide specific details that haven't been announced, but I was wondering if you can maybe provide some color on what Merck KGaA has found so consistently attractive about the Appstar development platform.

我知道您無法提供尚未公佈的具體細節，但我想知道您是否可以提供一些關於 Merck KGaA 認為 Appstar 開發平台始終如此有吸引力的方面的信息。

Yes, that's a great question, morning, Justin. So look, I think one of the things that big pharma in particular are interested in is thinking about how to get a molecule to market. And if you look at our bispecific platform — it's the thing we kind of mentioned in passing often, but it actually is really important — is that we can make these drugs in a really simple way. You know, you take a standard, cell line put the sequence in, and 9 months later, you are good to go with high yields, good stability, low aggregation, just like making, you know, monoclonals in the kind of 1990s. So I think that becomes really compelling. So, so in the background, the big check box for big pharma is — and big biotech is we've got something that's easy to manufacture as a platform.

是的，這是一個很好的問題，早上好，賈斯汀。所以，我認為大型製藥公司特別感興趣的事情之一就是考慮如何將分子推向市場。如果你看看我們的雙特異性平台——這是我們經常提到的，但實際上非常重要——我們可以用一種非常簡單的方式來製造這些藥物。你知道，你採用一個標準的細胞系，將序列放入其中，9 個月後，你就可以得到高產量、良好穩定性、低聚集性，就像 20 世紀 90 年代製造單克隆抗體一樣。所以我認為這變得非常引人注目。因此，在後台，大型製藥公司的重要復選框是——大型生物技術是我們擁有易於製造的平台。

The second then of course is the hunting down of that biology that we're looking for in bispecifics. And, you know, as I mentioned in the earnings call about, you know, 20% of all clinical activities now heading into — is s in bispecifics, which is terrific. And of the bispecifics, obviously we believe ours is, you know, one of the best, if not the best, format because we get — with these simple changes, we get the tetravalency and the potency associated with that, and this novel biology, some of which we've reported already for FS118, which is the cleavage of LAG-3 from the surface of TIL. And there's much more of that follow from it and the other programs. And I think, combining manufacturability simplicity with that unique combination of crosslinking clustering in a conditional way seems to be the thing that has consistently attracted Merck as a partner. And we were really excited by the way to see what we used to call FS122. I don't recall what Merck called it now, but their data on that first program published at (inaudible) last year.

第二個當然是尋找我們正在尋找的雙特異性生物。而且，正如我在財報電話會議中提到的，現在所有臨床活動的 20% 都是雙特異性藥物，這非常棒。對於雙特異性，顯然我們相信我們的格式，即使不是最好的，也是最好的格式之一，因為我們通過這些簡單的改變，獲得了四價性和與之相關的效力，而這種新穎的生物學，其中一些我們已經報導過 FS118，即 LAG-3 從 TIL 表面的裂解。它和其他程序還有更多的內容。我認為，將可製造性的簡單性與有條件的交聯聚類的獨特組合相結合似乎是一直吸引默克作為合作夥伴的原因。看到我們過去稱之為 FS122 的東西，我們真的很興奮。我現在不記得默克公司稱之為什麼，但他們去年在（聽不清）上發布了第一個程序的數據。

Great, thanks. One more question for me. I was wondering if you could provide some color on any feedback from scientists, KOLs, and others working in the space on the AACR presentation for the FS118 differentiated MOA.

十分感謝。還有一個問題要問我。我想知道您是否可以就 FS118 差異化 MOA 的 AACR 演示中的科學家、KOL 和其他工作人員的反饋提供一些信息。

Yes. So I think there's growing body of evidence to tie kind of LAG-3 shedding hypothesis today together. So, so one is there is a correlation between lack of effect with a checkpoint inhibitor and expression of (inaudible), this is a cleavage mechanism for LAG-3 from the surface. It's also clear that LAG-3 — the expression of LAG-3 is a poor prognostic factor from — for outcome for the checkpoint inhibitors. And of course, one of the things that we have been showing in the clinic and elsewhere is this cleavage mechanism. And certainly, people like (inaudible) who are, you know, leaders in the field are very excited about this is a mechanism compared to others — where, as I said, in the very first response, I think to Daina, we see this change in upregulation of LAG-3 and PD-L1, if you're using just monotherapies in combination. And indeed interestingly, and this was published in our AACR paper, is that you still see some upregulation if you use a PDL — sorry a PD1 and LAG-3, our difference being PD-L1 and LAG-3, given that crosslink in clustering and that shedding. So, you get this kind of hierarchy of expression of LAG-3, which is a really important player in exhaustion pathways. And I think, that — so landing on that hypothesis is really where our [SAB] got pretty excited, as well as obviously talking about specific diseases where we believe we can bring benefit.

是的。所以我認為現在有越來越多的證據將 LAG-3 脫落假說聯繫在一起。因此，檢查點抑製劑缺乏作用與（聽不清）的表達之間存在相關性，這是 LAG-3 從表面裂解的機制。同樣清楚的是，LAG-3（LAG-3 的表達是檢查點抑製劑的不良預後因素）。當然，我們在診所和其他地方展示的內容之一就是這種裂解機制。當然，像（聽不清）這樣的人，你知道，是該領域的領導者，與其他人相比，他們對這種機制感到非常興奮——正如我所說，在第一個回應中，我想對戴娜來說，我們看到了這一點如果您僅聯合使用單一療法，LAG-3 和 PD-L1 的上調會發生變化。事實上，有趣的是，這發表在我們的 AACR 論文中，如果您使用 PDL，您仍然會看到一些上調 - 抱歉，PD1 和 LAG-3，考慮到聚類中的交聯，我們的區別是 PD-L1 和 LAG-3和那種脫落。因此，你得到了 LAG-3 的這種表達層次，它在耗竭途徑中起著非常重要的作用。我認為，我們的 [SAB] 非常興奮的是，我們的 [SAB] 非常興奮地提出了這一假設，並且顯然正在談論我們認為可以帶來益處的特定疾病。

Ladies and gentlemen, we have reached the end of the question answer session, and I would now like to turn the call back over to Eliot Forster for closing remarks.

女士們、先生們，我們的問答環節已經結束，現在我想將電話轉回給艾略特·福斯特（Eliot Forster），讓其作結束語。

Great. Well, thanks everyone for the questions and appreciate you joining this morning and, and the thoughtfulness that goes into that question and answer session. Clearly 2022 is an important job for us at F-star and probably our most significant one as a clinical stage company, given the data coming from all 4 of the programs. We believe that success in any one of these is real potential to deliver significant value to shareholders and of course transform the lives of patients with cancer. Our partnership strategy also brings the opportunities to patients, as well as delivering that important non-dilutive cash. There really is a lot to look forward to back to part backed up by the emerging data. And I'd like to thank the F-star team, our partners, and shareholders for your ongoing support. I'd also like to thank the patients participating in our trials and our expert clinical investigators. And with that, thank you and goodbye.

偉大的。好的，感謝大家提出的問題，感謝您今天早上的加入，以及問答環節中的深思熟慮。顯然，2022 年對我們 F-star 來說是一項重要的工作，考慮到來自所有 4 個項目的數據，這可能是我們作為一家臨床階段公司最重要的工作。我們相信，其中任何一項的成功都具有真正的潛力，可以為股東帶來巨大的價值，當然也可以改變癌症患者的生活。我們的合作夥伴戰略還為患者帶來了機會，並提供了重要的非稀釋性現金。新興數據支持的部分確實有很多值得期待的地方。我要感謝 F-star 團隊、我們的合作夥伴和股東的持續支持。我還要感謝參與我們試驗的患者和我們的臨床研究專家。就這樣，謝謝你，再見。

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

今天的會議到此結束。此時您可以斷開線路。感謝您的參與。