Palvella Therapeutics Inc (PVLA) 2022 Q1 法說會逐字稿

Good day, and welcome to our Pieris Pharmaceuticals, Inc. First Quarter Earnings Call. (Operator Instructions) At this time, it is my pleasure to turn the floor over to Tom Bures, CFO. Sir, the floor is yours.

美好的一天，歡迎參加我們的 Pieris Pharmaceuticals, Inc. 第一季財報電話會議。 （操作員說明） 現在，我很高興將發言權交給財務長 Tom Bures。先生，地板是你的了。

Thank you, and good morning, everyone, and thank you for joining us for our first quarter 2022 conference call and corporate update.

謝謝大家，大家早安，謝謝您參加我們的 2022 年第一季電話會議和公司最新動態。

On the call today, we have Steve Yoder, our President and CEO, who will provide a corporate overview and outline on our pipeline. Tim Demuth, our Chief Medical Officer; Hitto Kaufmann, our Chief Scientific Officer; and Shane Olwill, our Chief Development Officer, will also be available for Q&A. You can access the press release released this morning on the Investor Relations page of our website at www.pieris.com.

在今天的電話會議上，我們的總裁兼執行長 Steve Yoder 將提供公司概況和我們的管線摘要。 Tim Demuth，我們的首席醫療官； Hitto Kaufmann，我們的首席科學長；我們的首席開發長 Shane Olwill 也將出席問答環節。您可以在我們網站 www.pieris.com 的投資者關係頁面上造訪今天早上發布的新聞稿。

Before we begin, I'd like to caution that comments made during this conference call may contain forward-looking statements involving risks and uncertainties regarding the operations and future results of operations of Pieris, including statements relating to the timing and progress of our clinical trials and preclinical programs, our partnerships and our financial position, and actual results or events may differ materially from those expressed or implied by such forward-looking statements.

在我們開始之前，我想提醒您，本次電話會議期間發表的評論可能包含涉及 Pieris 營運和未來營運結果的風險和不確定性的前瞻性陳述，包括與我們臨床試驗的時間和進展有關的陳述和臨床前計劃、我們的合作夥伴關係和我們的財務狀況以及實際結果或事件可能與此類前瞻性陳述明示或暗示的內容有重大差異。

Factors that might cause such differences are described in our filings with the SEC, including our annual, quarterly and current reports. The information being presented is only accurate as of today, and Pieris undertakes no obligation to update any statements to reflect future events or circumstances. I will now turn the call over to Steve.

我們向 SEC 提交的文件中描述了可能導致此類差異的因素，包括我們的年度報告、季度報告和當前報告。所提供的資訊僅截至今日準確，Pieris 不承擔更新任何聲明以反映未來事件或情況的義務。我現在將把電話轉給史蒂夫。

Thank you, Tom, and thank you to everyone for joining us today for our first quarter 2022 earnings call. My update will address key developments within our pipeline and across our R&D alliances before I turn it back to Tom, who will speak to our financial results in the context of the present capital markets, which we believe reflect the value of having significant support from our biopharma partners and access to alternative sources of capital funding such as grant funding.

謝謝湯姆，也謝謝大家今天參加我們的 2022 年第一季財報電話會議。我的更新將解決我們的管道和整個研發聯盟的關鍵發展，然後我將其轉回湯姆，他將在當前資本市場的背景下談論我們的財務業績，我們相信這反映了獲得我們的大力支持的價值。生物製藥合作夥伴以及獲得其他資金來源（例如贈款資金）的機會。

We'll then open the call for your questions. In the first quarter, we focused our resources on our 4 most advanced assets, with 2 belonging to our inhaled biologics respiratory franchise and the other 2 within our immuno-oncology bispecific franchise. The lead asset in our respiratory franchise is PRS-060 or AZD1402 where a crucial Phase IIa study in moderate to severe asthma is being driven by AstraZeneca.

然後我們將開始電話詢問您的問題。在第一季度，我們將資源集中在 4 項最先進的資產上，其中 2 項屬於我們的吸入生物製劑呼吸專營權，另外 2 項屬於我們的免疫腫瘤學雙特異性專營權。我們呼吸系統特許經營權的主要資產是 PRS-060 或 AZD1402，阿斯特捷利康正在推動一項針對中度至重度氣喘的關鍵 IIa 期研究。

Next is our fully proprietary pulmonary fibrosis program, PRS-220, which we continue to advance towards a first-in-human study later this year as a high priority. Our 2 IO bispecifics are both clinical stage. And in the first quarter, we initiated the Phase II study of our most advanced program, cinrebafusp alpha, also known as CINRA, which targets HER2-expressing gastric cancers.

接下來是我們完全專有的肺纖維化專案 PRS-220，我們將在今年稍後繼續優先推進該專案的首次人體研究。我們的 2 個 IO 雙特異性抗體均處於臨床階段。在第一季度，我們啟動了我們最先進的計畫 cinrebafusp alpha（也稱為 CINRA）的 II 期研究，該計畫針對錶達 HER2 的胃癌。

We continue building momentum for our second program, PRS-344 or S095012 having received IND acceptance to enroll patients in the U.S., alongside our co-development partner, Servier, who holds ex-U.S. rights for this program. So I'm now going to provide further details on our progress within these programs together with a snapshot of anticipated catalysts in the coming quarters, beginning with our respiratory assets followed by our IO assets.

我們繼續為我們的第二個專案PRS-344 或S095012 建立動力，該專案已獲得IND 接受，可在美國招募患者，與我們的共同開發合作夥伴施維雅（Servier）一起，施維雅持有美國以外的藥物。該程序的權利。因此，我現在將提供有關這些計劃進展的更多詳細信息，以及未來幾個季度預期催化劑的快照，首先是我們的呼吸資產，然後是我們的 IO 資產。

Our lead respiratory program, PRS-060, is an inhaled IL-4 receptor alpha inhibitor that we are developing with AstraZeneca for the treatment of moderate to severe asthma. In the first quarter, AstraZeneca initiated the efficacy portion of the Phase IIa study with the dry powder inhaler formulation given twice a day on top of the standard of care regimen of medium-dose inhaled corticosteroids and long-acting beta agonist or ICS LABA in moderate uncontrolled asthmatic patients, which is randomized 1:1:1 across the 1 milligram and 3-milligram dose levels plus a placebo arm.

我們主要的呼吸系統計畫 PRS-060 是一種吸入性 IL-4 受體 α 抑制劑，我們正在與阿斯特捷利康合作開發，用於治療中度至重度氣喘。第一季度，阿斯特捷利康啟動了 IIa 期研究的功效部分，在中等劑量吸入性皮質類固醇和長效 β 激動劑或 ICS LABA 的標準護理方案基礎上，每天給予乾粉吸入劑製劑兩次。不受控制的氣喘患者，以1:1:1 隨機分配1 毫克和3 毫克劑量等級以及安慰劑組。

We previously announced the successful completion of the safety portion of both the 1 milligram and the 3-milligram dose cohorts in Part 1 of the study which consisted of 31 moderate asthmatics controlled on standard of care asthma therapy. Having established the safety of the DPI formulation at the 1 milligram and 3-milligram dose levels, AstraZeneca is also enrolling the safety portion of the 10-milligram dose level, which is randomized 2:1 treatment to placebo.

我們先前宣布，該研究第 1 部分中 1 毫克和 3 毫克劑量組的安全部分已成功完成，該組由 31 名接受標準氣喘護理治療的中度氣喘患者組成。在確定了 1 毫克和 3 毫克劑量水平的 DPI 製劑的安全性後，阿斯特捷利康還招募了 10 毫克劑量水平的安全部分，該部分是隨機 2:1 治療與安慰劑的。

Our earlier guidance for this study readout included reporting top line efficacy data by the end of the year. Now given the geopolitical situation, along with the broader challenges amidst the ongoing pandemic, there is a heightened risk that more time will be required to deliver the top line study results by the end of the year. AstraZeneca is currently in the process of conducting a thorough time line reforecast and working on strategies to mitigate any potential delays. An announcement of top line results from this study, along with receiving a formal development plan and budget from AstraZeneca would trigger an opt-in decision for this program by Pieris. We will then have 30 days to make our opt-in decision for co-development at 1 of 2 levels, neither of which includes an option exercise fee.

我們早期對這項研究讀數的指導包括在年底前報告頂線療效數據。現在，考慮到地緣政治局勢，以及當前大流行中更廣泛的挑戰，到今年年底需要更多時間來提供最重要的研究結果的風險更大。阿斯特捷利康目前正在對時間表進行徹底的重新預測，並制定策略以減少任何潛在的延誤。這項研究的主要結果的公佈，以及收到阿斯特捷利康的正式開發計劃和預算，將觸發 Pieris 對該專案的選擇加入決定。然後，我們將有 30 天的時間在 2 個層級中的一個層級做出共同開發的選擇決定，這兩個層級均不包含選擇權行使費。

At the first level, we would be responsible for 25% of the cost share through regulatory approval with a predetermined cost cap. At this level, for the lifetime of this product, we would receive sales royalties from single digit up to the high teens plus the potential for multibillion-dollar sales milestones. We would also stand to receive development milestones that would represent approximately half of the captive development costs, making this an attractive and affordable investment opportunity.

在第一級，透過監管部門批准，我們將承擔 25% 的成本份額，並設定預定的成本上限。在這個水準上，在該產品的生命週期中，我們將收到從個位數到十幾歲的銷售特許權使用費，並且有可能實現數十億美元的銷售里程碑。我們還將獲得相當於自有開發成本約一半的開發里程碑，這使其成為一個有吸引力且負擔得起的投資機會。

The second opt-in level would be at a 50% cost share without a cost cap, but it would enhance our economics, allowing us to receive a gross margin share in the mid-20% range for the lifetime of product sales. And in addition to an independent of the co-development options I just mentioned, it's worth reminding everyone that we also have the option to co-commercialize this program in the United States.

第二個選擇加入水準將是 50% 的成本份額，沒有成本上限，但這將提高我們的經濟效益，使我們能夠在產品銷售生命週期內獲得 20% 左右的毛利率份額。除了我剛才提到的獨立的共同開發選項之外，值得提醒大家的是，我們還可以選擇在美國共同商業化這個專案。

Looking to our earlier respiratory pipeline, we continue to jointly work with AstraZeneca on 3 discovery stage programs, for which we retain co-development and co-commercialization options for 2 of those programs. And moving beyond our AstraZeneca alliance, we continue to advance our wholly owned respiratory asset, PRS-220 towards the clinic, which remains on track to enter Phase I this year. PRS-220 is an inhaled Anticalin protein targeting CTGF or connective tissue growth factor for the treatment of idiopathic pulmonary fibrosis or IPF for which we reported encouraging preclinical data last year.

回顧我們早期的呼吸產品管線，我們繼續與阿斯特捷利康合作 3 個發現階段項目，其中我們保留其中 2 個項目的共同開發和共同商業化選項。除了我們的阿斯特捷利康聯盟之外，我們繼續將我們的全資呼吸資產 PRS-220 推向臨床，該計畫今年仍有望進入第一階段。 PRS-220是一種吸入性Anticalin蛋白，針對CTGF或結締組織生長因子，用於治療特發性肺纖維化或IPF，我們去年報告了令人鼓舞的臨床前數據。

As a reminder, we received a $17 million government grant from the Bavarian government to support early stage development of PRS-220 to also evaluate the program for the treatment of post-covid pulmonary fibrosis. We also had the pleasure of hosting the President of the Bavarian State Ms. Ilse Aigner at our German facility this past quarter in association with this grant.

提醒一下，我們從巴伐利亞政府獲得了 1700 萬美元的政府撥款，用於支持 PRS-220 的早期開發，並評估該治療新冠肺炎後肺纖維化的計劃。上個季度，我們還很榮幸地在我們的德國工廠接待了巴伐利亞州總統伊爾莎·艾格納 (Ilse Aigner) 女士，以配合這筆贈款。

IPF is a devastating pulmonary disease, impacting between 3 million and 5 million patients worldwide with a mean survival time from diagnosis of just 2 to 5 years. Currently available treatments have achieved greater than $3 billion in sales despite modest benefits and substantial side effects. We believe patients need more effective treatment options with better tolerability, which is why we are excited for PRS-220 to enter Phase I development in healthy subjects later this year.

IPF 是一種毀滅性的肺部疾病，影響全球 300 萬至 500 萬名患者，診斷後平均存活期僅 2 至 5 年。儘管療效有限且副作用較大，但目前可用的治療方法的銷售額已超過 30 億美元。我們相信患者需要更有效且耐受性更好的治療方案，這就是為什麼我們對 PRS-220 今年稍後在健康受試者中進入 I 期開發感到興奮。

I would now like to give an update on our immuno-oncology pipeline. CINRA is a wholly owned 4-1BB/HER2 bispecific in Phase II development for the treatment of HER2 high and separately HER2-low gastric cancer. The Phase II study is a 2-arm study evaluating CINRA in these different HER2 settings. The first arm is evaluating CINRA in combination with the standard of care regimen of ramucirumab and paclitaxel in 20 patients who have HER2-high gastric cancer. For this arm, we have a clear go/no go criteria of an ORR objective response rate of at least 50%, 5-0 and in addition to clinically meaningful duration of response and good safety and tolerability to continue further development of this program. We expect to report data from this arm of the trial in 2023.

我現在想介紹一下我們的免疫腫瘤學管道的最新情況。 CINRA 是全資擁有的 4-1BB/HER2 雙特異性藥物，處於 II 期開發中，用於治療 HER2 高胃癌和 HER2 低胃癌。 II 期研究是一項雙組研究，在這些不同的 HER2 設定中評估 CINRA。第一組正在 20 名 HER2 高胃癌患者中評估 CINRA 與雷莫蘆單抗和紫杉醇標準治療方案的組合。對於該臂，我們有明確的通過/不通過標準，即ORR 客觀緩解率至少為50%、5-0，此外還具有臨床意義的緩解持續時間以及良好的安全性和耐受性，以繼續進一步開發該項目。我們預計在 2023 年報告該試驗的數據。

The second arm is evaluating CINRA in combination with the small molecule HER2 inhibitor tucatinib, in 20 HER2-low gastric cancer patients. For this arm, we would like to see an ORR of at least 40% paired with clinically meaningful duration of response and good safety and tolerability to continue further development of this program. Although our initial projections for this arm included top line data this year, more time is needed for the enrollment of the HER2 low arm, and we have revised our guidance now aiming to provide data on 20 patients in 2023 as we are guiding for the HER2-high arm.

第二組正在 20 名 HER2 低胃癌患者中評估 CINRA 與小分子 HER2 抑制劑 tucatinib 的合併治療。對於該臂，我們希望看到至少 40% 的 ORR、具有臨床意義的反應持續時間以及良好的安全性和耐受性，以繼續進一步開發該項目。儘管我們對該臂的初步預測包括今年的頂線數據，但HER2 低臂的入組還需要更多時間，並且我們現在修訂了指南，目標是在2023 年提供20 名患者的數據，因為我們正在指導HER2 - 高臂。

Because CINRA will be the first targeted therapy to address HER2-low gastric cancer, education of the clinical community is required to properly engage this emerging subpopulation of what is classically HER2 negative patients. We are working closely with sites and investigators to interrogate the potential of this drug candidate in an area of truly great unmet medical need.

由於 CINRA 將是第一個治療 HER2 低胃癌的標靶療法，因此需要對臨床界進行教育，以正確吸引這一新興的經典 HER2 陰性患者亞群。我們正在與研究中心和研究人員密切合作，探討該候選藥物在真正未滿足醫療需求的領域的潛力。

Turning to our next IO program. Enrollment is progressing in our global open-label Phase I/II dose escalation study of PRS-344 and also known as S0950012, a 4-1BB PD-L1 bispecific in patients with advanced solid tumors. As a reminder, PRS-344 uses the same 4-1BB engager as in CINRA, which has shown single-agent activity in clinical studies.

轉向我們的下一個 IO 程式。 PRS-344（也稱為 S0950012）是一種針對晚期實體瘤患者的 4-1BB PD-L1 雙特異性藥物，其全球開放標籤 I/II 期劑量遞增研究的入組工作正在進行中。提醒一下，PRS-344 使用與 CINRA 相同的 4-1BB 接合劑，CINRA 已在臨床研究中顯示出單藥活性。

Thanks to the learnings from CINRA as well as emerging data from the ongoing Phase I study outside the U.S. for PRS-344 we received FDA authorization to dose patients in our Phase I study at a higher dose than was originally permitted for CINRA and in a manner that allows seamless enrollment across U.S. and ex U.S. sites.

由於CINRA 的經驗教訓以及美國境外正在進行的PRS-344 I 期研究的新數據，我們獲得了FDA 的授權，可以在我們的I 期研究中以比CINRA 最初允許的劑量更高的劑量對患者進行給藥，並以某種方式允許在美國和美國以外的站點進行無縫註冊。

As a reminder, we have exclusive commercialization rights for PRS-344 in the United States, and we stand to receive royalties on potential ex U.S. sales through our partnership with Servier. Beyond 344, Servier continues the development of PRS-352 or S095025 which is an OX40/PD-L1 bispecific for which we jointly presented preclinical data at AACR last month. PRS-352 has demonstrated superior potency to both mono anti-PD-L1 in combination OX40 and PD-L1 therapy in marks in different in vitro assays. It also inhibits the PD-1, PD-L1 pathway with comparable potency to anti-PD-L1 antibodies stimulates human CD4 cells drives T cell stimulation in ex vivo cynomolgus monkey assays and demonstrated an antibody like PK in vivo.

提醒一下，我們擁有 PRS-344 在美國的獨家商業化權利，並且我們將透過與施維雅的合作獲得潛在的美國境外銷售的特許權使用費。除了 344 之外，施維雅還在繼續開發 PRS-352 或 S095025，這是一種 OX40/PD-L1 雙特異性藥物，我們上個月在 AACR 上聯合展示了其臨床前數據。在不同的體外試驗中，PRS-352 在 OX40 和 PD-L1 聯合治療中顯示出優於單抗 PD-L1 的功效。它還抑制 PD-1、PD-L1 通路，其效力與抗 PD-L1 抗體相當。在離體食蟹猴試驗中刺激人類 CD4 細胞驅動 T 細胞刺激，並在體內證明了類似 PK 的抗體。

As a reminder, we believe that the design of PRS-352 may improve upon the limited OX40 pathway activation and antitumor effects shown by OX40 agonist antibodies currently in development, which rely on Fc-gamma receptor cross-linking for OX40 activation.

提醒一下，我們相信 PRS-352 的設計可能會改善目前正在開發的 OX40 激動劑抗體所顯示的有限 OX40 途徑活化和抗腫瘤作用，這些抗體依賴 Fc-γ 受體交聯來活化 OX40。

Before turning the call over to Tom for a financial update, I would like to provide a brief update on some of our other collaborations. Boston Pharmaceuticals continues to advance PRS-342, or BOS 342, which is a 4-1BB/GPC3 bispecific towards the clinic, and we expect an IND to be filed within the next 12 months for this program.

在將電話轉給 Tom 詢問財務更新之前，我想先簡單介紹一下我們其他一些合作的最新情況。波士頓製藥公司繼續推進 PRS-342 或 BOS 342，這是一種面向臨床的 4-1BB/GPC3 雙特異性藥物，我們預計該計畫將在未來 12 個月內提交 IND。

Additionally, we continue to execute well on our multi-program collaboration announced last year with Genentech for the discovery development and commercialization of locally delivered therapies for respiratory and ophthalmology diseases, further bolstering our respiratory pipeline while expanding the therapeutic applications for our Anticalin technology and platform.

此外，我們繼續良好地執行去年與基因泰克宣布的多項目合作，以發現開發和商業化本地提供的呼吸系統和眼科疾病療法，進一步增強我們的呼吸系統管道，同時擴大我們的Anticalin 技術和平台的治療應用。

We have 2 active programs within our CGEN collaboration, including 1 that has been successfully turned over to CGEN and one that is ongoing in a joint collaboration phase. This concludes my prepared remarks, and I would now like to hand the call back over to Tom.

我們的 CGEN 合作中有 2 個活躍項目，其中 1 個已成功移交給 CGEN，另一個正在聯合合作階段進行。我準備好的演講到此結束，現在我想將電話轉回湯姆。

Thanks, Steve, and good morning again, everyone. We recognize it's been a very challenging time within the capital markets and biotech sector in general. Valuations are down significantly across the board. And with that, we continue to be mindful of how we continue to deploy capital to build value based upon our broad program pipeline. First, I wanted to report that we have cash, cash equivalents and investments totaling $100.3 million for the quarter ended March 31, 2022, compared to a cash and cash equivalents balance of $117.8 million for the year ended December 31, 2021. The decrease, of course, was attributed to funding operations in the first quarter.

謝謝史蒂夫，大家早安。我們認識到，對於資本市場和生物技術產業來說，這是一個非常具有挑戰性的時期。估值全面大幅下跌。因此，我們將繼續關注如何繼續部署資本，以基於我們廣泛的專案管道創造價值。首先，我想報告的是，截至2022 年3 月31 日的季度，我們的現金、現金等價物和投資總額為1.003 億美元，而截至2021 年12 月31 日的年度現金和現金等價物餘額為1.178 億美元。當然，這歸因於第一季的資金運作。

Next, I wanted to remind everyone of the key role that our partners and government grants play in the efficient structuring of our program spending. AstraZeneca is fully funding the development of PRS-060 through at least the ongoing Phase IIa study subject to our opt-in decision. Servier funds approximately half of the development cost of PRS-344 where we retain the U.S. rights and the generous grant support from the Bavarian government funds more than 50% of the clinical readiness and forthcoming Phase I study for PRS-220. Cinrebafusp alfa is the only program that we are fully funding and we have efficiently designed the 20 patient per arm 2-arm study to utilize the same sites.

接下來，我想提醒大家，我們的合作夥伴和政府撥款在我們的計畫支出的有效結構中發揮關鍵作用。阿斯特捷利康至少透過正在進行的 IIa 期研究為 PRS-060 的開發提供全額資助，但取決於我們的選擇決定。施維雅資助了 PRS-344 大約一半的開發成本，我們保留了美國的權利，並且巴伐利亞政府的慷慨資助資助了 PRS-220 超過 50% 的臨床準備和即將進行的 I 期研究。 Cinrebafusp alfa 是我們全額資助的唯一項目，我們有效地設計了每組 20 名患者的 2 組研究，以利用相同的地點。

Additionally, we have set clear and high bars to govern go/no-go development decisions and further cost commitments on that program. Considering the ongoing development plans for our lead assets, which include some of the cost reimbursement structures that I've just described, we believe reported cash is sufficient to fund operations into the fourth quarter of 2023. The R&D expenses were $14.1 million for the quarter ended March 31, 2022, compared to $16.6 million for the quarter ended March 31, 2021.

此外，我們還制定了明確且高的標準來管理繼續/不繼續的開發決策以及該計劃的進一步成本承諾。考慮到我們主要資產的持續開發計劃（包括我剛才描述的一些成本補償結構），我們認為報告的現金足以為 2023 年第四季度的運營提供資金。該季度的研發費用為 1,410 萬美元截至2022年3月31日的季度營收為1,660萬美元，而截至2021年3月31日的季度營收為1,660萬美元。

The decrease is due to lower program costs on PRS-060 as work related to our sponsored Phase I trial was largely complete in 2021 and lower manufacturing costs for cinrebafusp alfa both partially offset by higher clinical costs for cinrebafusp alfa and higher clinical and manufacturing costs for PRS-344 as we moved into Phase I development. Separately, higher personnel costs due to higher headcount was partially offset by a reduction in consulting and other professional service costs.

下降的原因是PRS-060 的項目成本較低，因為與我們贊助的I 期試驗相關的工作已於2021 年基本完成，並且cinrebafusp alfa 的製造成本降低，部分被cinrebafusp alfa 較高的臨床成本和cinrebafusp alfa 較高的臨床和製造成本所抵消。PRS-344，我們進入第一階段開發。另外，諮詢和其他專業服務成本的減少部分抵消了因員工人數增加而導致的人員成本上升。

Moving on to G&A expenses. Those were $4.4 million for the quarter ended March 31, 2022, compared to $4.1 million for the quarter ended March 31, 2021. The period-over-period increase was driven primarily by higher noncash amortization of deferred costs related to collaboration revenue earned this quarter, partially offset by slightly lower legal and audit costs.

接下來是一般行政費用。截至2022 年3 月31 日的季度為440 萬美元，而截至2021 年3 月31 日的季度為410 萬美元。同比增長主要是由於與本季度獲得的協作收入相關的遞延成本攤銷增加所致。 ，部分被法律和審計成本略有下降所抵消。

For the quarter ended March 31, 2022, $2.1 million of grant income was recorded on PRS-220. And finally, net loss was $5.1 million or a $0.07 loss per share for the quarter ended March 31, 2022, which compared to a net loss of $4.2 million or also a $0.07 loss per share for the quarter ended March 31, 2021.

截至 2022 年 3 月 31 日的季度，PRS-220 記錄了 210 萬美元的補助收入。最後，截至 2022 年 3 月 31 日的季度淨虧損為 510 萬美元，即每股虧損 0.07 美元，而截至 2021 年 3 月 31 日的季度淨虧損為 420 萬美元，即每股虧損 0.07 美元。

And with that, I'll turn the call back over to Steve.

然後，我會將電話轉回給史蒂夫。

Thank you, Tom. Before taking everyone's questions, I would like to reiterate those points about our success in partnering and grand procurement, which has enabled us to leverage a significant amount of nondilutive capital to advance a broad and diversified pipeline while retaining significant or fully proprietary commercial rights in these programs. We continue to advance our innovative pipeline, and we are looking forward to adding PRS-220 as our fourth clinical stage program later this year. We believe that upcoming data readouts for these programs will bring us closer to getting our therapies to the patients who need them most. The current biotech landscape is not without its challenges right now, but we believe we have the right pipeline the right partners and the right people to deliver on our mission.

謝謝你，湯姆。在回答大家的問題之前，我想重申一下我們在合作和大採購方面取得的成功，這使我們能夠利用大量非稀釋資本來推進廣泛和多元化的管道，同時保留這些領域的重要或完全專有的商業權利。程序。我們將繼續推進我們的創新產品線，並期待在今年稍後將 PRS-220 添加為我們的第四個臨床階段項目。我們相信，即將公佈的這些項目的數據將使我們更接近為最需要的患者提供治療方法。目前的生物技術領域並非沒有挑戰，但我們相信我們擁有正確的管道、正確的合作夥伴和正確的人員來實現我們的使命。

We look forward to keeping you apprised of our ongoing progress. And with that, thank you for joining us on the call today. And now we'd like to open the call to your questions.

我們期待讓您隨時了解我們的持續進展。感謝您今天加入我們的電話會議。現在我們想開始回答您的問題。

(Operator Instructions) We'll take our first question today from Jon Miller with Evercore.

（操作員說明）今天我們將回答 Evercore 的 Jon Miller 提出的第一個問題。

This is Jessica on for Jon Miller. Two questions. First one, given the possible pushback of the PRS-060 -- Phase IIa trial next year, is there any chance that we'll see more data from the Phase I portion this year? Like what about like the Phase I portion of the 10-milligram dose? And then secondly, is the slower enrollment of the HER2 low combo with PRS-343, a function of site selection and trial conduct. Or is there a lack of underlying demand for more trials in the space, put another way, how tough is the competition for these patients given the landscape of HER2 development?

這是傑西卡為喬恩·米勒配音。兩個問題。首先，考慮到明年 PRS-060 IIa 期試驗可能會被推遲，今年我們是否有機會看到更多來自 I 期部分的數據？例如 10 毫克劑量的 I 期部分呢？其次，HER2 低組合與 PRS-343 的註冊速度較慢，這是位點選擇與試驗進行的函數。或者是否缺乏對該領域進行更多試驗的潛在需求，換句話說，考慮到 HER2 開發的前景，對這些患者的競爭有多激烈？

Thanks for the 2 questions. So I'll start with the first question and then highlight maybe high level the second and maybe turn it over to Tim Demuth to answer more details on the HER2 low question. Your first question, I think, concerned the timing for any data for the PRS-060 study with AstraZeneca, whether that's the efficacy data or the safety data, particularly the high dose safety cohort that's being enrolled in parallel to the first 2 doses in efficacy trial. I mean, as we mentioned, AstraZeneca is undertaking currently a thorough reforecast for the entire trial. This includes both the efficacy arm and the safety arm.

謝謝你的2個問題。因此，我將從第一個問題開始，然後突出顯示第二個問題，可能是高級別問題，也許會將其交給 Tim Demuth，以回答有關 HER2 低級別問題的更多詳細資訊。我認為你的第一個問題涉及阿斯特捷利康 PRS-060 研究的任何數據的時間安排，無論是療效數據還是安全數據，特別是與前 2 劑療效平行入組的高劑量安全隊列審判。我的意思是，正如我們所提到的，阿斯特捷利康目前正在對整個試驗進行徹底的重新預測。這包括功效臂和安全臂。

We had mentioned in prior communications that we did rely quite a lot on Ukraine for the safety part of Part 1a, and we would have relied on them as well for Part 1b. And so that obviously is something we can't do given the unfortunate situation that everyone knows about in Ukraine.

我們在先前的溝通中提到，我們確實非常依賴烏克蘭來完成第 1a 部分的安全部分，我們也會在第 1b 部分中依賴它們。鑑於烏克蘭眾所周知的不幸局勢，這顯然是我們不能做的事情。

So that's one thing to keep in mind. We're going to just let AstraZeneca work through a very thorough reforecast and would expect that we'll be able to provide an update across the board in our next orderly corporate update on the next earnings call, which will be in August.

所以這是需要記住的一件事。我們將讓阿斯特捷利康進行一次非常徹底的重新預測，並希望我們能夠在下一次財報電話會議（將於 8 月舉行）的有序公司更新中提供全面的更新。

For the Second question about HER2 low. As we mentioned, in addition to just ongoing challenges of enrolling patients in the pandemic environment, we do have nuances with the HER2-low arm in that this is an emerging subpopulation being characterized that is otherwise been known for a long time as HER2 negative. And so we're working through bringing additional sites on board on plan beyond the U.S., and we're also working on education of how to best been or yes, delineate patients between who have -- what we're calling HER2 high as well as in HER2 low, which would go into 1 of the 2 different arms.

關於 HER2 低的第二個問題。正如我們所提到的，除了在大流行環境下招募患者的持續挑戰之外，我們確實對 HER2 低臂有細微差別，因為這是一個新興的亞群，長期以來被稱為 HER2 陰性。因此，我們正在努力在美國以外的地區開展更多站點的計劃，我們也致力於教育如何最好地做到這一點，或者是的，將患者劃分為具有我們所說的 HER2 高水平的患者。如HER2 low，它將進入2 個不同組中的1 個。

Tim can provide a bit more color if you want to, Tim, but that's at a high level, it's a composite of factors.

如果你願意的話，蒂姆可以提供更多的色彩，蒂姆，但那是高水平的，它是多種因素的綜合。

Yes. Maybe just to quickly reiterate HER2-negative gastric cancer, it's a great, great unmet medical need. And as Steve pointed out, the HER2 low population we're looking at is really, if he wants a subpopulation of HER2 negative that is defined by the IHC score that is standardly reported by pathologists and the education piece that we're currently very actively engaging in is just talking with investigators, study nurses, et cetera. to make them aware of that particular definition of HER2 low by IHC score and help them to pinpoint patients and make patients aware of this clinical trial.

是的。也許只是為了快速重申 HER2 陰性胃癌，這是一個巨大的、巨大的未滿足的醫療需求。正如 Steve 指出的那樣，如果他想要 HER2 陰性的亞群（由病理學家標準報告的 IHC 評分和我們目前非常積極的教育文章來定義），那麼我們正在研究的 HER2 低人群確實是這樣。參與只是與研究人員、研究護士等交談。讓他們了解 IHC 評分對 HER2 低的特定定義，並幫助他們找出患者並使患者了解這項臨床試驗。

So we feel good about these education efforts that we're expanding about adding a plant sites and geographies to deliver that study to patients who need open gastric cancer.

因此，我們對這些教育工作感到滿意，我們正在擴大這些教育工作，增加工廠地點和地理位置，以便向需要開放性胃癌的患者提供這項研究。

For our next question, we'll turn to Roger Song with Jefferies.

對於我們的下一個問題，我們將請傑弗里斯的羅傑·宋 (Roger Song) 回答。

So the first question also relates to 060. Given this kind of uncertainty around the enrollment and the time that they read out pushouts. So is that possible you will read out a separate case for your current dose cohort when 3 versus 10 later on because I think the initial plan i,s, we will be everything together. So just curious about the potential kind of data readout strategy there?

所以第一個問題也與 060 相關。考慮到註冊和他們宣讀退出的時間的這種不確定性。那麼，當 3 比 10 稍後時，您是否有可能會為您當前的劑量組讀出一個單獨的案例，因為我認為最初的計劃是，我們將一切都在一起。那麼只是對潛在的資料讀取策略感到好奇嗎？

Roger, your connection wasn't maybe perfect. But just to make sure I got your question, you were asking in light of the, again, the potential, the heightened risk for a delay in the top line readout for efficacy, you were asking, I think, if there's a potential to separately read out different arms of the efficacy portion as opposed to waiting for all in one go. Is that correct?

羅傑，你的連結可能並不完美。但為了確保我明白你的問題，你再次詢問，考慮到延遲頂線療效讀數的可能性和增加的風險，你問，我認為，是否有可能單獨讀出功效部分的不同部分，而不是一次性等待全部。那是對的嗎？

Yes, that's right.

恩，那就對了。

No problem. Listen, I think, again, we're going to wait for a thorough reforecast and then leave all options open right now. And we're, of course, going to be collaborating closely with AstraZeneca Ultimate, who ultimately has the final say, but I trust that they will act reasonably because this is, of course, a very high priority program for them from our vantage point.

沒問題。聽著，我想，我們將再次等待徹底的重新預測，然後立即保留所有選項。當然，我們將與阿斯特捷利康 Ultimate 密切合作，後者擁有最終決定權，但我相信他們會採取合理行動，因為從我們的角度來看，這對他們來說當然是一個非常高度優先的計劃。

I would just say that we don't want to do anything that will jeopardize the integrity of the trial. So we wouldn't want to rush anything if it meant that it would compromise all of the great efforts that are going into this very large global study with significant resources being invested by Astra as a priority program. So we'll see, but I wouldn't want to set an expectation that that's what we would do. We have to wait. We have to wait and see what the outcome is of the reforecast first.

我只想說，我們不想做任何有損審判公正性的事情。因此，如果這意味著會損害阿斯特拉作為優先項目投入大量資源的這項大型全球研究的所有巨大努力，我們不想倉促行事。所以我們拭目以待，但我不想設定我們會這麼做的期望。我們必須等。我們必須先等待，看看重新預測的結果如何。

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。

Steve, you obviously did give us a little warning on the fourth quarter about geopolitical risk around the 060 trial?

史蒂夫，你顯然在第四季度就 060 試驗周圍的地緣政治風險向我們發出了一些警告？

But -- it does seem like the language is stronger in this quarter's press release. Is that a fair statement? And then looking at the trial action on control (inaudible) , which I realize is not always the most up-to-date there were a number of new sites that began recruiting in late March, I updated in late March, but across multiple countries. But since then, it doesn't seem like there's been any additional sites recruiting, is that up to date? Or are there -- how spread out is the current recruitment geographically?

但是，本季的新聞稿中的措辭似乎更為強烈。這是一個公平的說法嗎？然後看看控制方面的試驗行動（聽不清楚），我意識到這並不總是最新的，有許多新網站在 3 月底開始招募，我在 3 月底更新，但跨越多個國家。但從那以後，似乎沒有其他網站在招聘，這是最新的嗎？或者目前的招募在地理上分佈有多大？

So Matt, your first question was, is there a change may be in risk appraisal between the fourth quarter earnings call of last year in the first quarter. And I would say, yes, it's fair to say there is. And that's based on, again, ongoing situation in Ukraine. Ongoing real-time assessment of enrollment in still a COVID environment in a post-COVID environment where there's still quite a lot of masks and some of those general challenges of enrolling respiratory studies across so many different geographies given the pandemic. So yes, there is an increased risk. We're not changing. We're just (inaudible) of risk and again, waiting for a very thorough reforecast to better inform a more definitive guidance later in probably the next earnings call.

馬特，你的第一個問題是，去年第四季財報電話會議與第一季之間的風險評估是否可能會改變。我想說，是的，可以公平地說是存在的。這也是基於烏克蘭當前的局勢。在新冠疫情後的環境中，仍在對新冠疫情環境下的入學情況進行持續的實時評估，那裡仍然有相當多的口罩，鑑於大流行，在如此多的不同地區進行呼吸系統研究面臨著一些普遍的挑戰。所以是的，風險增加了。我們沒有改變。我們只是（聽不清楚）風險，再次等待非常徹底的重新預測，以便在下一次財報電話會議上更好地提供更明確的指導。

With respect to the ongoing operations of the trial, I mean AstraZeneca is driving that. We're very confident in their ability. They have many, many sites that they'll be continuing to activate and used for recruiting on a global basis. As you mentioned, ct.gov is updated in real time. There is a regular cadence. I would say it's approximately on a monthly or no less than bimonthly update typically by AstraZeneca, but they are working really hard to onboard sites and get all the necessary supply chain elements in place, which is also something that we have to work through in a supply chain constrained environment.

關於試驗的持續進行，我的意思是阿斯特捷利康正在推動這項進程。我們對他們的能力非常有信心。他們有很多很多網站，他們將繼續啟動這些網站並用於在全球範圍內進行招募。正如您所提到的，ct.gov 是即時更新的。有規律的節奏。我想說的是，阿斯特捷利康通常大約每月一次或不少於每兩個月更新一次，但他們正在非常努力地登錄網站並讓所有必要的供應鏈要素就位，這也是我們必須在整個過程中解決的問題。供應鏈環境受限。

So I'd say keep your eyes on ct.gov. It's not real time. But you can think about that as being active on a monthly or bimonthly basis in general.

所以我建議大家密切關注 ct.gov。這不是實時的。但您可以將其視為一般每月或每兩個月活躍一次。

Okay. And switching to CTGF, we're going to see the first clinical readouts from FibroGen's IV antibody against CTGF in non-IPF indications, pancreatic cancer and DMD, which are obviously very different diseases, different endpoints, but do have fibrotic components to them.

好的。轉向 CTGF，我們將看到 FibroGen 針對 CTGF 的 IV 抗體在非 IPF 適應症、胰腺癌和 DMD 中的第一個臨床讀數，這顯然是非常不同的疾病，不同的終點，但確實具有纖維化成分。

So do you think there's any read-through on really just more proof of mechanism for CTGF inhibition from these trials? Or are you just really waiting until the IPF trial, which they recently guided to, I think, mid next year readout?

那麼您認為這些試驗是否有任何關於 CTGF 抑制機制的更多證據的通讀？或者你真的只是在等待 IPF 審判，我認為他們最近指導了明年年中的判決？

Yes. I mean I don't want to rule out a read through or a -- read-through from indication to indication. What we're looking at are 2 key points is that we really think the data from the Phase IIa study in IPF with pamrevlumab are real was pretty large, it was randomized. And from our vantage point and the number of advisers that we continuously talk to people believe this data are real. And also, I believe that the pamrevlumab IPF trial has now been fully enrolled, and we would expect very meaningful data in that indication study to be available next year. And that, to us, will be the most relevant of all of the areas where pamrevlumab is being clinically studied. I think even within IPF, there are many important nuances, including the benefit potentially of local engagement of 220 versus pamrevlumab. And also many other benefits from convenience and even patient selection that we're still working on.

是的。我的意思是，我不想排除從一個指示到另一個指示的通讀或通讀。我們正在研究的兩個關鍵點是，我們確實認為 pamrevlumab 治療 IPF 的 IIa 期研究的數據是真實的，數據相當大，而且是隨機的。從我們的有利位置以及我們不斷與人們交談的顧問數量來看，我們相信這些數據是真實的。而且，我相信 pamrevlumab IPF 試驗現已完全入組，我們預計明年將獲得此適應症研究中非常有意義的數據。對我們來說，這將是 pamrevlumab 臨床研究的所有領域中最相關的。我認為即使在 IPF 中，也存在許多重要的細微差別，包括 220 與 pamrevlumab 相比局部參與的潛在益處。還有我們仍在努力的便利性甚至患者選擇帶來的許多其他好處。

I would say that we'll keep our eye on it and we'll certainly assess potential impact. But I wouldn't be able to tell you beyond that today, if we think that there is a meaningful readout to say, the answer is no.

我想說我們會密切關注它，我們一定會評估潛在的影響。但今天我無法告訴你更多的內容，如果我們認為有一個有意義的讀數可以說，那麼答案是否定的。

This concludes our question-and-answer session. I would now like to turn the call back over to Mr. Yoder for closing remarks.

我們的問答環節到此結束。我現在想將電話轉回給約德先生，讓其致閉幕詞。

Thank you so much. I have nothing really to add other than to say thank you, everyone, for your attention today and for your continued support of Pieris. Thanks so much for joining us today, and have a great day.

太感謝了。我沒有什麼要補充的，只是感謝大家今天的關注以及對 Pieris 的持續支持。非常感謝您今天加入我們，祝您有美好的一天。

Bye-bye.

再見。

This does conclude today's teleconference. We thank you again for your participation. You may disconnect your lines at this time, and have a great day.

今天的電話會議到此結束。我們再次感謝您的參與。此時您可以斷開線路，祝您有個愉快的一天。