Bioatla Inc (BCAB) 2023 Q4 法說會逐字稿

Greetings, and welcome to the BioAtla's fourth quarter and full year 2023 earnings call. At this time, all participants are in a listen-only mode. A brief question-and-answer session will follow the formal presentation. (Operator Instructions) As a reminder, this conference is being recorded. It's now my pleasure to introduce your host, Bruce Mackle with LifeSci Advisors. Thank you. Mr. Michael, you may begin.

大家好，歡迎參加 BioAtla 第四季和 2023 年全年財報電話會議。此時，所有參與者都處於只聽模式。正式演講後將舉行簡短的問答環節。（操作員指示）謹此提醒，本次會議正在錄製中。現在我很高興向您介紹主持人，LifeSci Advisors 的 Bruce Mackle。謝謝。麥可先生，您可以開始了。

Thank you, operator, and good afternoon, everyone. With me today on the phone from BioAtla are Dr. Jay Short, Chairman, CEO, and Co-Founder; and Richard Waldron, Chief Financial Officer. Following today's call, Dr. Eric Sievers, Chief Medical Officer; and Sheri Lydick, Chief Commercial Officer, will join Jay and Rich for a short Q&A. Earlier this afternoon, BioAmber released financial results and a business update for the fourth quarter and full year ended December 31, 2023.

謝謝接線員，大家下午好。今天與我通電話的是 BioAtla 董事長、執行長兼聯合創辦人 Jay Short 博士；和財務長理查德·沃爾德倫。在今天的電話會議之後，首席醫療官 Eric Sievers 博士表示：首席商務官 Sheri Lydick 將與 Jay 和 Rich 一起進行簡短的問答。今天下午早些時候，BioAmber 發布了截至 2023 年 12 月 31 日的第四季度和全年的財務表現和業務更新。

A copy of the press release and corporate presentation are available on the Company's website and before we begin, I'd like to remind everyone that statements made during this conference call will include forward looking statements, including but not limited to, statements regarding BioAtlas' business plans and prospects and whether its clinical trials will support registration plans to form collaborations and other strategic partnerships for selected assets, results, conduct progress and timing of its research and development programs and clinical trials, expectations with respect to enrollment and dosing in US clinical trials, plans and expectations regarding future data updates, clinical trials, regulatory meetings and regulatory submissions.

新聞稿和公司簡報的副本可在公司網站上獲取，在我們開始之前，我想提醒大家，本次電話會議期間發表的聲明將包括前瞻性聲明，包括但不限於有關 BioAtlas 的聲明業務計劃和前景，以及其臨床試驗是否將支持註冊計劃，以就選定的資產形成合作和其他戰略夥伴關係、結果、其研發計劃和臨床試驗的進展和時間安排、對美國臨床註冊和劑量的期望有關未來數據更新、臨床試驗、監管會議和監管提交的試驗、計劃和期望。

The potential regulatory approval path for its product candidates, expectations about the sufficiency of its cash and cash equivalents to fund operations and expected R&D expenses. These statements are subject to various risks, assumptions and uncertainties that can cause actual results to differ materially and are described in the filings made with the SEC, including the most recent annual report on Form 10 K and subsequent quarterly reports on Form 10 Q. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of today, March 26th, 2024, and BioAmber disclaims any obligation to update such statements to reflect future information, events or circumstances, except as required by law. With that, I'd like to turn the call over to Jay Short, Jay?

其候選產品的潛在監管批准路徑、對其現金和現金等價物是否足以資助營運的預期以及預期的研發費用。這些陳述受到各種風險、假設和不確定性的影響，可能導致實際結果存在重大差異，並在向SEC 提交的文件中進行了描述，包括表格10 K 中的最新年度報告和表格10 Q 中的後續季度報告。請注意不要過度依賴這些前瞻性陳述，這些陳述僅截至今天（2024 年3 月26 日），BioAmber 不承擔任何更新此類陳述以反映未來資訊、事件或情況的義務，除非法律要求。說到這裡，我想把電話轉給傑伊·肖特，傑伊？

Thank you, Bruce, and thanks, everyone, for joining us for our Fourth Quarter Full Year 2023 BioAmber Earnings Call. Bi-level is the inventor and leader in the development of novel therapies using a proprietary conditionally active biologics or CAPS platform with improved selectivity for attacking tumor cells while avoiding healthy cells, thereby addressing critical unmet needs in oncology to improve patients' lives, we made considerable progress in 2023 across all of our ongoing clinical programs, including the Phase two trials for our first in class cab ADC product candidates be a 30 11 NDA 30 21, targeting multiple solid tumor types, our CAB CTLA-4 IO antibody, and our first dual cam bispecific, Abcam CD. three T cell engager.

謝謝 Bruce，也謝謝大家參加我們的 2023 年第四季全年 BioAmber 財報電話會議。Bi-level 是開發新型療法的發明者和領導者，該療法使用專有的條件活性生物製劑或CAPS 平台，提高了攻擊腫瘤細胞的選擇性，同時避免健康細胞，從而解決腫瘤學中未滿足的關鍵需求，以改善患者的生活。到2023 年，我們所有正在進行的臨床項目都將取得重大進展，包括我們的同類首個cab ADC 產品候選產品30 11 NDA 30 21、針對多種實體瘤類型的二期試驗、我們的CAB CTLA-4 IO 抗體和我們的CAB CTLA-4 IO 抗體。第一個雙凸輪雙特異性抗體，Abcam CD。三個 T 細胞接合者。

We continue the positive trajectory into 2024, focused on further advancing our prioritized CAP programs, generating data sets that potentially enable us to move into one or more registrational trials in the second half of the year. We believe that these near-term inflection points also support the formation of one or more strategic collaborations with major pharmaceutical partners this year, which can accelerate the development of selected assets and maximize their market opportunities. Additional details related to what I'm going to provide are available in today's press release and our updated company presentation, both of which are available on our website.

我們將繼續保持積極的軌跡進入 2024 年，重點是進一步推進我們的優先 CAP 計劃，產生數據集，這些數據集可能使我們能夠在今年下半年進入一項或多項註冊試驗。我們相信，這些近期拐點也支持今年與主要製藥合作夥伴形成一項或多項策略合作，這可以加速選定資產的開發並最大化其市場機會。與我將要提供的內容相關的更多詳細資訊可以在今天的新聞稿和我們更新的公司簡報中找到，這兩者都可以在我們的網站上找到。

I will now review our latest updates beginning with our CAB CTLA-4 antibody D, a 30 71, which is applicable in areas of high unmet need across multiple solid tumor indications both for refractory and for first line patients and represents a sizable commercial opportunity. We are pleased to report that our Phase two data at 350 milligrams flat dose continues to near our Phase one dose escalation data in terms of low incidence and severity of immune-related adverse events. In addition, I'm happy to report that we have cleared a higher dose of 700 milligrams with tislelizumab for the first two cycles and are now evaluating the unprecedented one gram dose level.

我現在將回顧我們的最新更新，從我們的CAB CTLA-4 抗體D（a 30 71）開始，該抗體適用於難治性和一線患者的多種實體瘤適應症的高度未滿足需求領域，代表著巨大的商業機會。我們很高興地報告，就免疫相關不良事件的低發生率和嚴重程度而言，350 毫克固定劑量的第二階段數據繼續接近我們的第一階段劑量遞增數據。此外，我很高興地報告，我們已經在前兩個週期中使用替雷利珠單抗清除了 700 毫克的更高劑量，現在正在評估前所未有的 1 克劑量水平。

This is important since previous studies demonstrated improved overall survival in metastatic cancers, including melanoma, with higher levels of CTLA-4 inhibition. As a result, we are now enrolling patients at 700 milligrams in the first-line melanoma patients and in a significant targeted first-line non-small cell lung cancer population in combination with PD-1 for readouts later this year. These data are also anticipated to position the company for one or more potentially registrational trials in first-line indications in the second half of this year.

這一點很重要，因為先前的研究表明，較高水平的 CTLA-4 抑制可以提高轉移性癌症（包括黑色素瘤）的整體存活率。因此，我們現在正在招募 700 毫克的一線黑色素瘤患者和重要的靶向一線非小細胞肺癌患者，並與 PD-1 聯合用於今年稍後的讀數。預計這些數據也將使該公司在今年下半年進行一項或多項第一線適應症的潛在註冊試驗。

In addition, as part of our evaluation of safety and tolerability of BA. 30 71, we are completing the Phase two expansion in treatment refractory melanoma and carcinoma with an initial data readout of approximately 20 patients in the second quarter. As already noted, the safety and efficacy data from the Phase one study, demonstrating both the confirmed partial response and the confirmed complete response for two out of six patients is encouraging using the 350 milligram dose and now we are enrolling the remaining patients at the 700 milligram dose with our evolving clinical data. We believe DA. 30 71 has the potential to be best in class CTLA-4 as it holds the promise to be used as often as a PD-1 inhibitor and potentially expand the indications where combined immune checkpoint inhibition can be effective.

此外，作為我們評估 BA 的安全性和耐受性的一部分。 30 月 71 日，我們即將完成難治性黑色素瘤和癌症治療的第二階段擴展，第二季將讀取約 20 名患者的初始數據。如前所述，第一階段研究的安全性和有效性數據表明，使用350 毫克劑量時，六名患者中的兩名患者已確認部分緩解和確認完全緩解，這令人鼓舞，現在我們正在以700 毫克劑量招募其餘患者毫克劑量與我們不斷變化的臨床數據。我們相信DA。 30 71 有潛力成為 CTLA-4 類藥物中最好的，因為它有望與 PD-1 抑制劑一樣頻繁使用，並有可能擴大聯合免疫檢查點抑制有效的適應症。

In addition, the emerging safety profile suggests that be a 30 71 with PD1 immune modulation may be suitable for further combining with CAB ADC therapies that target actual end or were to achieve synergistic durable tumor control.

此外，新出現的安全性表明，具有 PD1 免疫調節功能的 30 71 可能適合與針對實際終點或實現協同持久腫瘤控制的 CAB ADC 療法進一步結合。

Now turning to our cab war to ADCSSDA. 30 21 for our ongoing Phase two trials in treatment refractory were two agnostic patient populations. We previously reported encouraging responses in the Phase two melanoma and squamous cell carcinoma of the head neck studies. As part of today's update, we now have both 28 melanoma patients and 12 head-and-neck patients dosed using the 1.8 milligram per kilogram Q. two W. regimen and 20 head and neck patients dose using the more intense two Q. three W. regimen for a total of 32 head and neck patients. We anticipate having two plus gains in the melanoma cohort next month and two plus scans in the head and neck cohort in May with anticipated top line data readouts for both during our Q1 earnings call in May.

現在轉向我們與 ADCSSDA 的計程車大戰。 30 21 我們正在進行的難治性治療第二期試驗涉及兩個不可知的患者群體。我們先前曾報道過頭頸部黑色素瘤和鱗狀細胞癌第二期研究的令人鼓舞的反應。作為今天更新的一部分，我們現在有 28 名黑色素瘤患者和 12 名頭頸患者使用每公斤 1.8 毫克的 Q.2 W. 方案，還有 20 名頭頸患者使用強度更高的 2Q.3 W 方案。 .總共32 名頭頸部患者的治療方案。我們預計下個月黑色素瘤隊列將獲得兩次以上的收益，五月頭頸隊列的掃描將獲得兩次以上的收益，預計在5 月份第一季財報電話會議期間將公佈這兩項數據的頂線數據。

Given the encouraging emerging datasets, we believe the A. 32 one is well positioned for global strategic collaboration to maximize potential of this cab ADC. across multiple solid tumor indications onto our CAB axle ADCBA. 30 11 our Phase two potentially registrational study for undifferentiated polymorphic sarcoma or UPS is on track to complete enrollment of approximately 20 as for diagnostic patients at the 1.8 milligram per kilogram two Q. three W. regimen next month with encouraging compliance and manageable safety. We anticipate having multiple scans across the patient group, potentially enabling a meeting with the FDA to discuss the remaining portion of the potentially registrational study in the second half of this year. We also reported clinically meaningful antitumor activity among patients with treatment refractory bone and soft tissue sarcomas.

鑑於令人鼓舞的新興數據集，我們相信 A.32 已做好全球戰略合作的準備，以最大限度地發揮這一 cab ADC 的潛力。跨越多種實體腫瘤適應症到我們的 CAB 軸 ADCBA 上。 30 11 我們針對未分化多形性肉瘤或UPS 的第二期潛在註冊研究預計將在下個月完成約20 名診斷患者的入組，採用每公斤1.8 毫克的二Q. 3 W. 方案，並具有令人所鼓舞的依從性和可控制的安全性。我們預計會對整個患者組進行多次掃描，從而有可能在今年下半年與 FDA 舉行會議，討論潛在註冊研究的剩餘部分。我們也報告了難治性骨骼和軟組織肉瘤患者中具有臨床意義的抗腫瘤活性。

Which remain a profound and tractable unmet need for new treatment options. We presented these data from Phase two part one cohort enrollment as an oral presentation at the as most common rare cancers meeting earlier this month and showed disease control at 12 weeks for 43% of the 87 patients treated with BA. 30 11 monotherapy using the less intense regimen of 1.8 milligram per kilogram Q. two W. We believe this represents a promising disease control rate for patients with treatment refractory sarcomas. In the osteosarcoma cohort, we observed two partial responses out of 11 efficacy evaluable patients. The treatment was well tolerated associated with a manageable safety profile with no new safety signals to report.

這仍然是對新治療方案的深刻且易於處理的未滿足的需求。我們在本月稍早舉行的最常見罕見癌症會議上以口頭報告形式展示了第二階段第一部分隊列入組的這些數據，並顯示接受BA 治療的87 名患者中有43% 在12 週時得到了疾病控制。 30 11 單一療法使用每公斤 1.8 毫克 Q.2 W 的強度較低的方案。我們相信這對難治性肉瘤患者來說代表著有希望的疾病控制率。在骨肉瘤群組中，我們觀察到 11 名可評估療效的患者中有 2 名部分緩解。此治療的耐受性良好，安全性可控，沒有新的安全訊號需要報告。

Now regarding our Phase two study in non-small cell lung cancer. Last quarter, we reported multiple durable clinical responses with a differentiated safety profile among a challenging actual positive treatment refractory lung cancer population, specifically, among 15 patients with EGFR wild-type tumors who had received prior PD-1 treatment. We observed five partial responses with a median duration of response of approximately five months using 1.8 milligrams per kilogram Q. two W. every other week, dosing toxicity was manageable and few high grade related treatment emergent AEs were reported. We believe multiple responses in a treatment refractory actual positive poor prognostic group such as this one is clinically meaningful and relevant, particularly since these patients have experienced failure of a median of three prior lines of therapy as part of today's update.

現在談談我們對非小細胞肺癌的第二階段研究。上個季度，我們報告了在具有挑戰性的實際陽性治療難治性肺癌人群中，特別是在15 名既往接受過PD-1 治療的EGFR 野生型腫瘤患者中，出現了多種持久的臨床反應，並且具有差異化的安全性。我們每隔一週使用 1.8 毫克每公斤 Q. 2 W. 觀察到 5 例部分緩解，中位緩解持續時間約為 5 個月，給藥毒性是可控的，並且很少報告高級相關治療緊急 AE。我們相信，在治療難治性實際陽性預後不良組（例如本組）中的多重反應具有臨床意義和相關性，特別是因為作為今天更新的一部分，這些患者之前經歷了中位數三線治療的失敗。

We have enrolled 33 target agnostic patients using the more intense 1.8 milligram per kilogram two Q. three W. regimen across both squamous and non-squamous patients. We are on track to evaluate clinical benefit in the target agnostic non-small cell lung cancer non-squamous population in the second quarter of this year.

我們已經招募了 33 名目標不可知的患者，使用更強度的 1.8 毫克每公斤 2 Q. 3 W. 方案，針對鱗狀和非鱗狀患者。我們預計在今年第二季度評估目標不可知的非小細胞肺癌非鱗狀細胞群的臨床效益。

Next onto our potentially first-in-class dual cab bispecific T-cell engager antibody cab, EpCAM cab CD. three or VA. 31 82. Epcam is a ubiquitous target expressed on the surface of cancer cells, which requires the use of our TAP technology to achieve optimal selectivity and safety. Our Phase one two dose escalation study continues to progress and is on track. We anticipate completion of the Phase one study with a full data readout anticipated in the second half of this year with potential initiation of a Phase two study also in the second half of this year is shown to be safe and effective in lung cancer patients enrolled. Our CAB enabled T cell engager has the potential to treat patients with a wide range of metastatic tumors, including cancers of colon, lung breast, pancreas and prostate, among others.

接下來是我們潛在的一流雙 cab 雙特異性 T 細胞接合抗體 cab，EpCAM cab CD。三個或VA。31 82.Epcam是癌細胞表面表達的常見的靶標，這需要使用我們的TAP技術來實現最佳的選擇性和安全性。我們的一期二期劑量遞增研究持續取得進展並步入正軌。我們預計第一期研究將在今年下半年完成，並公佈完整的數據，並有可能在今年下半年啟動第二期研究，結果顯示該研究對於入組的肺癌患者是安全有效的。我們的 CAB 啟用 T 細胞接合器有潛力治療患有多種轉移性腫瘤的患者，包括結腸癌、肺癌、乳腺癌、胰腺癌和前列腺癌等。

As we have previously discussed, ADCs are a promising treatment modality with broad applicability across multiple tumor types to further reduce the potential risk associated with neutropenia from off-target toxicities. We developed a novel next-gen carbohydrate linker system was superior serum stability, solubility and tumor-specific payload release yielding our first glyco conjugate, CADx Nectin-4 ADC, PA. 33 to 61 at the upcoming ACR meeting in April, efficacy data will be presented demonstrating complete tumor regression in xenograph models, including a superior efficacy compared to the photomask. The Dayton analog and the patient derived pancreatic cancer model.

正如我們先前所討論的，ADC 是一種有前景的治療方式，在多種腫瘤類型中具有廣泛的適用性，可進一步降低與脫靶毒性引起的中性粒細胞減少症相關的潛在風險。我們開發了一種新型的下一代碳水化合物連接體系統，具有卓越的血清穩定性、溶解度和腫瘤特異性有效負載釋放，從而產生了我們的第一個糖綴合物CADx Nectin-4 ADC，PA 。 4 月 33 日至 61 日，在即將舉行的 ACR 會議上，將公佈療效數據，證明異種移植模型中的腫瘤完全消退，包括與光掩模相比具有優越的功效。代頓類似物和患者衍生的胰臟癌模型。

We will also present both PK and toxicology data in nonhuman primates as well as the influence of our linker technology and specific cancer models. These data indicate that our next-gen CAB Nectin-4 ADC petition is a more effective treatment with reduced toxicity. We plan to submit the IND and ample. And finally, I'm pleased to report our progress with the medical and scientific communities, an important ongoing communications with numerous publications and presentations, including conferences such as asthma, sarcoma and rare cancers. Since the spring and the ACR Annual Meeting in April, which can be found on our website.

我們還將展示非人靈長類動物的 PK 和毒理學數據，以及我們的接頭技術和特定癌症模型的影響。這些數據表明我們的下一代 CAB Nectin-4 ADC 申請是一種更有效且毒性更低的治療方法。我們計劃提交 IND 和充足的材料。最後，我很高興地報告我們與醫學界和科學界的進展，以及與許多出版物和演講的重要持續溝通，包括氣喘、肉瘤和罕見癌症等會議。自春季和四月的 ACR 年會以來，這可以在我們的網站上找到。

With that, I would now like to turn the call over to Rick to review the fourth quarter and full year 2023 financials. Rick?

現在，我想將電話轉給 Rick，讓他審查 2023 年第四季和全年的財務狀況。瑞克？

Thank you, Jane. Research and development expenses were $22.7 million for the quarter ended December 31st, 2023, compared to $21.9 million for the same quarter in 2022. The increase of $0.8 million was due to clinical development expenses primarily related to the launch of our CA 30 11 UPS, our potentially registrational trial in 2023 and overall accelerated enrollment across our clinical trials in 2023, offset by a decrease in expense for our preclinical programs in selected clinical indications due to our program prioritization in 2023, we expect our R&D expenses to decrease overall in the first half of 2024 due to recently completed enrollment in clinical trials for data set expected to enable potentially registrational trials for our ADC programs, VA 30 21 and VA 30 11 general and administrative expenses were $5.9 million for the quarter ended December 31, 2023, compared to $6.7 million for the same quarter in 2022.

謝謝你，簡。截至 2023 年 12 月 31 日的季度，研發費用為 2,270 萬美元，而 2022 年同一季度的研發費用為 2,190 萬美元。增加 80 萬美元的原因是臨床開發費用主要與 CA 30 11 UPS 的推出、2023 年潛在的註冊試驗以及 2023 年臨床試驗的總體加速註冊相關，但被我們臨床前項目費用的減少所抵消由於我們在2023 年的計劃優先考慮，在選定的臨床適應症中，我們預計我們的研發費用將在2024 年上半年總體減少，因為最近完成了數據集的臨床試驗註冊，預計將為我們的ADC 項目（ VA 30）進行潛在的註冊試驗截至 2023 年 12 月 31 日的季度的 VA 30 11 和 VA 30 11 一般及管理費用為 590 萬美元，而 2022 年同一季度為 670 萬美元。

The $0.8 million decrease was primarily due to lower stock-based compensation and D&O insurance premiums. Net loss for the quarter ended December 31st, 2023 was $26.9 million compared to a net loss of $27.6 million for the same quarter in 2022. Net cash used in operating activities for the full year ended December 31st, 2023 was $104 million compared to net cash used in operating activities of $90.4 million for the same period in 2022. Our cash use for the quarter ended December 31st, 2023 was $29.8 million. Cash and cash equivalents as of December 31st, 2023 were $111.5 million compared to $215.5 million as of December 31st, 2022 we expect our cash utilization to decrease in the first half of 2024, allowing our current cash and cash equivalents fund operations into the second half of 2025 and now back to Jay.

減少 80 萬美元主要是因為股票薪酬和 D&O 保險費減少。截至 2023 年 12 月 31 日的季度淨虧損為 2,690 萬美元，而 2022 年同一季度的淨虧損為 2,760 萬美元。截至 2023 年 12 月 31 日的全年經營活動所使用的現金淨額為 1.04 億美元，而 2022 年同期經營活動所使用的現金淨額為 9,040 萬美元。截至 2023 年 12 月 31 日的季度，我們的現金使用量為 2,980 萬美元。截至2023 年12 月31 日的現金和現金等價物為1.115 億美元，而截至2022 年12 月31 日的現金和現金等價物為2.155 億美元，我們預計2024 年上半年的現金利用率將下降，從而使我們目前的現金和現金等價物基金業務能夠進入下半年2025 年，現在回到傑伊。

Thank you, Rick. All other made considerable progress in 2020 through cross our ongoing clinical trials targeting various tumor types, and we look forward to the multiple important milestones in the second quarter of this year, including initial data readout from our Phase two CTLA-4 IO antibody, Phase two in both melanoma and head and neck cancer on the evaluation of clinical benefit and Axl agnostic patients in our Phase two non-small cell lung cancer study. We are encouraged by the compelling clinical efficacy and safety that continues to emerge highlighting our differentiated cap technology across multiple therapeutic targets. With that, we will turn it back to the operator to take your questions.

謝謝你，瑞克。透過我們正在進行的針對各種腫瘤類型的臨床試驗，所有其他藥物在2020 年都取得了相當大的進展，我們期待今年第二季度的多個重要里程碑，包括我們的二期CTLA-4 IO 抗體、二期臨床試驗的初步數據讀出在我們的二期非小細胞肺癌研究中，對黑色素瘤和頭頸癌的臨床獲益和 Axl 不可知患者進行了兩項評估。我們對不斷出現的引人注目的臨床療效和安全性感到鼓舞，突顯了我們在多個治療標靶上的差異化帽技術。這樣，我們會將其轉回給接線員以回答您的問題。

(Operator Instructions) Kelly Shi, Jefferies.

（操作員說明）Kelly Shi，Jefferies。

I Hi. This is Dave on for Kelly Shi. I have a couple of questions. One on three zero one one in UPS. Maybe if you can talk about your expectation and what you anticipate from the meeting from the FDA meeting that you plan in second half also, will you be discussing additional indication or will it be only for you?

我嗨。我是凱莉·施 (Kelly Shi) 的戴夫 (Dave)。我有一些問題。UPS 中的一對三零一一。也許如果您能談談您的期望以及您對下半年計劃的 FDA 會議的預期，您會討論其他適應症還是只針對您？

Yes, Sherri, do you want to it's about 1 billion and choice.

是的，Sherri，你想要大約 10 億美元和選擇嗎？

Thank you for the question. And Dave, in terms of the second, I'll take the second part of your question. So the meeting would be focused on UPS. And this is our, a potentially registrational trial. So it was enough to discuss the data set that we had generated with the first 20 patients in terms of efficacy and tolerability. And I think I would pass the first part of your question over to Eric for additional comments.

感謝你的提問。戴夫，關於第二個問題，我將回答你問題的第二部分。因此，會議的重點將是 UPS。這是我們的一個潛在的註冊試驗。因此，討論我們為前 20 名患者產生的數據集的療效和耐受性就足夠了。我想我會將你問題的第一部分轉交給艾瑞克以徵求更多意見。

Sure. I'm happy to say that. Thank you, Sherry. So our goals with the FDA meeting are really to plot out together and agreeable registration path. And I think we've guided previously that that would be based on an overall response rate with a certain durability on. We'll also be talking with the agency about Project Optimus and whether the multiple different dosing regimens that we've explored in UPS are sufficient to achieve the Project Optimus guidelines, and we then hope to be able to provide guidance on on our path forward after that meeting.

當然。我很高興這麼說。謝謝你，雪莉。因此，我們與 FDA 會議的目標實際上是共同規劃一致的註冊路徑。我認為我們之前已經指導過，這將基於整體回應率和一定的持久性。我們還將與該機構討論 Optimus 項目，以及我們在 UPS 探索的多種不同劑量方案是否足以實現 Optimus 項目指南，然後我們希望能夠為我們的前進道路提供指導那次會議之後。

Great. Thank you for taking our question.

偉大的。感謝您提出我們的問題。

Thank you.

謝謝。

Thank you.

謝謝。

Kaveri Pohlman, BTIG.

卡維裡·波爾曼，BTIG。

Yes, good evening. Congrats on the progress and thanks for taking my question, I foresee VLA-4 Any additional color you can provide on the first line, melanoma and non-small cell lung cancer trials? Are these going to be single-arm trials and how many patients you plan to enroll?

是的，晚上好。恭喜進展並感謝您提出我的問題，我預計 VLA-4 您可以在第一線、黑色素瘤和非小細胞肺癌試驗中提供任何其他顏色嗎？這些是單臂試驗嗎？您計劃招募多少患者？

Well, you want to I'll start with that one.

好吧，你想的話我就從那個開始吧。

Sure. And thank you for very beginning. So we would expect to enroll about 15 to 20 patients in each of our first-line melanoma cohort and the first line targeted non-small cell lung cancer by the end of the second half of 2024. We hope that this data set both in melanoma and non-small cell lung cancer will help guide next steps for us. And I also want to emphasize, as Jay did that we've passed the 700 milligram dose which is equivalent to a 10 per kilo dosing and are now evaluating one gram. So we're really on the belief that a higher dose levels will be very important and extending survival as other studies have shown.

當然。謝謝你的開始。因此，我們預計到 2024 年下半年末，我們的一線黑色素瘤隊列和一線靶向非小細胞肺癌隊列各招募約 15 至 20 名患者。我們希望黑色素瘤和非小細胞肺癌的數據集將有助於指導我們下一步的行動。我還想強調，正如 Jay 所做的那樣，我們已經通過了 700 毫克劑量，相當於每公斤 10 毫克的劑量，現在正在評估 1 克。因此，我們確實相信，正如其他研究表明的那樣，更高的劑量水平將非常重要，並且可以延長生存期。

And I think I'll just add, I think our goal here is from these studies is to inform us and allow the positioning for registrational trials which in that case would be randomized studies.

我想我只想補充一點，我認為這些研究的目標是通知我們並允許註冊試驗的定位，在這種情況下，這些試驗將是隨機研究。

That's helpful.And for EpCAM CD. three bispecific trial, I understand it is for multiple solid tumors, but are you enriching or have you seen an enrichment for patients with certain tumor types? And can you set some expectations for what we will be seeing in second half?

這對 EpCAM CD 很有幫助。三個雙特異性試驗，我知道它是針對多種實體瘤的，但是您是否正在豐富或您是否看到了針對某些腫瘤類型患者的豐富？您能否對我們下半年看到的情況設定一些期望？

And what would good data look like but the I think, obviously adenocarcinoma, but I think we're seeing some colorectal patients that we would expect to see continuation along those lines as we go through the different dose layers as to the ultimate dose selection level and what our goal is to report out on those with multiple scales, very much similar to what we did with CTLA-4 in December with that readout as we position for Phase two studies. Erik, do you want to add anything to that?

好的數據會是什麼樣子，但我認為，顯然是腺癌，但我認為我們正在看到一些結直腸患者，當我們通過不同的劑量層以最終選擇劑量水平時，我們希望看到這些患者繼續沿著這些路線發展我們的目標是報告多尺度的數據，這與我們在 12 月對 CTLA-4 所做的非常相似，我們為第二階段研究定位時的讀數。艾瑞克，你想補充什麼嗎？

I think that covers it from a more than 70% of tumors are adenocarcinomas. So where we think we have plenty of coverage with this approach. And compared to your question, we're not needing to arm specifically up pick patients based on target expression of EpCAM is so robustly expressed by tumors that we think that just using the adenocarcinoma approach, we'll be getting patients likely to benefit.

我認為這涵蓋了超過 70% 的腫瘤是腺癌。因此，我們認為這種方法有足夠的覆蓋範圍。與你的問題相比，我們不需要根據腫瘤強烈表達的 EpCAM 目標表達來專門挑選患者，我們認為僅使用腺癌方法，我們將使患者可能受益。

Got it. Thanks for taking my question.

知道了。感謝您提出我的問題。

Thank you.

謝謝。

(Operator Instructions) Arthur He, H.C. Wainwright.

（操作員指令） Arthur He, H.C.溫賴特。

As you know, Jay and team, thanks for taking my questions. So I just wanted to get your for the 30 30, 71 and the 30 21 update that will be all together at the first quarter earnings call. Notably, our expectation of 30 21 will we will be giving top-line updates and key updates for 37?

如您所知，傑伊和團隊，感謝您回答我的問題。所以我只是想了解 30 30、71 和 30 21 的更新，這些更新將在第一季的財報電話會議上一起發布。值得注意的是，我們對 30 21 的預期是否會提供頂線更新和 37 的關鍵更新？

The one well, that could be an update on the dose escalation up to it. We won't know for sure to get a few weeks at further down the road here since we're enrolling at the one gram level right now, but the first part of that as a possibility there, but we'll see as we get closer to time. I think for the readout of the monotherapy Phase two study with approximately 20 patients where we look set a majority have been recruited at three 50 milligram flat dose and just a few remaining patients at the 700 milligram dose that will be sometime in June and latter part of June.

好吧，這可能是劑量升級的最新情況。由於我們現在正在以一克的水平進行註冊，因此我們不確定未來幾週的情況，但第一部分是可能的，但我們會看到我們得到的結果距離時間更近。我認為，對於大約20 名患者的單一療法第二期研究的讀數，我們認為大多數患者已被招募，接受3 次50 毫克的固定劑量，只有少數患者接受700 毫克的劑量，這將在6 月和下半年的某個時候進行六月。

I'm estimating because we want to give us much scan data, if you remember back on 30 70 well, you definitely want to see two scans because you're and initiating the immune system so that we know we're going to give it just a little more time, but all pretty much gone very far away, quite frankly, coming quickly.

我估計是因為我們想給我們很多掃描數據，如果你還記得 30 70，你肯定想看到兩次掃描，因為你正在啟動免疫系統，這樣我們就知道我們要提供它只是多了一點時間，但坦白說，一切都已經過去了很遠，來得很快。

Got you. Got you. Thanks for that. And my second question is and so regarding the next candidate. I just curious to us tried to pick your brain is why another ADC not a TC. T cell engager? That's one. And the second is on why Nectin-4 as a target. Thanks for that.

明白你了。明白你了。感謝那。我的第二個問題是關於下一位候選人的問題。我只是好奇我們試圖問你為什麼是另一個 ADC 而不是 TC。T 細胞接合器？這是一個。第二個是為什麼 Nectin-4 作為目標。感謝那。

Well, I think two things we have both we have an ADC that just happened to be ready first. And then we also have a bispecific, which I believe we've reported on in previous conferences. But I think that there are a couple of reasons why Nectin-4, number one, there is an associated toxicity with the current marketed Nectin-4 that limits its applicability.

嗯，我認為有兩件事我們都有，我們有一個恰好首先準備好的 ADC。然後我們還有一個雙特異性，我相信我們在之前的會議中已經報導過。但我認為，有幾個原因導致 Nectin-4（第一）與目前市售的 Nectin-4 有相關毒性，這限制了其適用性。

Secondly, as we're going to report on in April at a CR, we're seeing efficacy in tumors that were not addressable with the current marketed drugs so we see an opportunity to move expand indications and also improve on existing indications. And that's driven, of course, by a novel, but still on a carbohydrate linker, which reduces off-target levels of off-target toxicity. That is a result of the payload coming off prior to entering the the cancer cell. And so in general, we see both of these assets having an important opportunity for validated targets.

其次，正如我們將在 4 月的 CR 報告中所報告的那樣，我們看到了對目前上市藥物無法治療的腫瘤的療效，因此我們看到了擴大適應症並改善現有適應症的機會。當然，這是由一種新穎但仍然基於碳水化合物連接體驅動的，它可以降低脫靶毒性的脫靶水平。這是有效負荷在進入癌細胞之前脫落的結果。因此，總的來說，我們認為這兩種資產都為經過驗證的目標提供了重要機會。

I will generalize. But what is optically? I mean, you could ask the same question of CTLA-4. You know, here's a drug with incredible opportunity, but the toxicity has been very difficult to manage and has been used in very limited extent, relative to what its potential is. And I think we can make that argument across several different targets when we apply our CAM technology, which improves that selectivity between for the cancer cell and protects the normal cell.

我會概括一下。但什麼是光學呢？我的意思是，你可以對 CTLA-4 提出同樣的問題。您知道，這是一種具有令人難以置信的機會的藥物，但其毒性非常難以控制，並且相對於其潛力而言，其使用範圍非常有限。我認為，當我們應用 CAM 技術時，我們可以在幾個不同的目標上進行論證，該技術提高了癌細胞和保護正常細胞之間的選擇性。

I think, Ben, thanks for the additional color. So if I may. Can I squeeze one more? Just curious, I just quickly noticed the ACR on plantation. You're going to you're going to be doing it in April or could you tell us more on the tetravalent T-cell engager Type B, I believe that B7-H3 targets. What's the what's the special of these design? I'm just curious.

我想，本，謝謝你提供的額外顏色。所以如果可以的話。我可以再擠一張嗎？只是好奇，我很快就注意到了種植園上的 ACR。您將在 4 月進行，或者您能否告訴我們更多關於 B 型四價 T 細胞接合劑的信息，我相信 B7-H3 的目標。這些設計有何特別之處？我只是好奇。

Well, I think it's a good or we refer to as tenants butterfly design. In other words, we have two arms of the antibody that both can bind to the tumor cells against the tumor cell engager. And then we also have two arms to that come off the light chains that combined to the CD. three receptor. Now we sense at least in terms of the Abcam drug. Now that were binding to a single CD. three arm at a time, whereas we can still bind to two different antigens on the tumor cell.

嗯，我認為這是一個很好的或我們稱之為租戶蝴蝶設計。換句話說，我們有兩個抗體臂，它們都可以與腫瘤細胞結合，對抗腫瘤細胞接合器。然後我們還有兩條從輕鏈上脫落下來的臂，與 CD 結合在一起。三個受體。現在我們至少在 Abcam 藥物方面有所感覺。現在，它們被綁定到一張 CD 上。一次三個臂，而我們仍然可以結合腫瘤細胞上的兩種不同抗原。

So but this certainly increases your ability to it increases the potency of the drug to have this Tetra available structure, even in the case where one arm combined at a time like in season three on certainly is going to get not only affinity, but also avidity and tumor targeting portion. So it's a very nice design from that perspective. And secondly, because there's only one form of this antibody that can be generated and bearing manufacturing and simplifies manufacturing and reduces cost of goods, which is also an advantage that you think will shake out competition.

所以，但這肯定會增加你的能力，它會增加藥物具有這種Tetra 可用結構的效力，即使在像第三季那樣一次組合一隻手臂的情況下，肯定不僅會獲得親和力，而且還會獲得親和力和腫瘤靶向部分。所以從這個角度來看，這是一個非常好的設計。其次，因為這種抗體只有一種形式可以產生，並且可以簡化製造並降低產品成本，這也是您認為將擺脫競爭的優勢。

Reni Benjamin, Citizen's GMP.

Reni Benjamin，公民 GMP。

Good afternoon, guys. Thanks for taking the questions. As I think about 30 71, I have one question is, you know, now you're looking at the one gram dose level. At what point do you kind of stop dosing higher or can you just continue to go higher until you on reach of DLT. And then I guess the second question is when I'm thinking about the melanoma non-small cell combination with pembro cohort for which we'll have data a data readout in the second half of this year?

下午好，夥計們。感謝您提出問題。當我想到 30 71 時，我有一個問題是，你知道，現在你正在考慮一克劑量水平。在什麼時候你可以停止更高的劑量，或者你可以繼續更高的劑量，直到你達到 DLT。然後我想第二個問題是當我考慮黑色素瘤非小細胞與 pembro 隊列的組合時，我們將在今年下半年獲得數據讀出？

And can you talk roughly kind of metrics that you might need to to me, like, for example, in melanoma, should I be thinking about you guys beating or trying to beat nivo plus Yervoy from both an efficacy and safety perspective? Or are you more concerned about on the safety aspect and the same kind of question for now. So if you want to start on this one for sure.

您能否粗略地談談您可能需要向我提供的指標，例如，在黑色素瘤中，我是否應該考慮從功效和安全性的角度來看，你們擊敗或試圖擊敗 nivo 加 Yervoy？或者您現在更關心安全方面和同類問題。因此，如果您確實想從這一個開始。

I think I'll take a start and then hand to Sheri. You had a really interesting question about really how high to go with CTLA-4 inhibition on. It's really striking to look back at earlier randomized trials of, if you remember, at 10 per kilo versus three per kilo and the survival benefits are really quite striking at multiple years of follow-up. However, ipi 10 per kilo was associated with considerable toxicity. So on most of sponsors that are pursuing CTLA-4 antibody, you really want to push the dose and to achieve high exposures. And then we also want on a good high on a concentration trough and our pharmacokinetics. So that CTLA-4 blockade lingers for the full three weeks between doses. And so our current plan is to treat the patients at one gram every three weeks, and we don't plan to go higher.

我想我會先開始，然後交給 Sheri。您有一個非常有趣的問題，關於 CTLA-4 抑製到底要達到多高。如果你還記得的話，回顧一下早期的隨機試驗，每公斤 10 個與每公斤 3 個相比，確實令人震驚，而且在多年的隨訪中，生存獲益確實相當驚人。然而，每公斤 IPI 10 會產生相當大的毒性。因此，對於大多數尋求 CTLA-4 抗體的申辦者來說，您確實希望提高劑量並實現高曝光。然後我們還想要一個好的高濃度谷和我們的藥物動力學。因此，CTLA-4 阻斷作用會在兩次給藥之間持續整整三週。因此，我們目前的計劃是每三週為患者治療一克，我們不打算更高。

We felt that that represents 14.2 milligrams per kilogram if you compare to the ipi dosing. And I think I think we can use that and just have a broad goal of giving as much CTLA-4 blockade as early in our cancer patients treatment as possible and make this something that based on tolerability and its efficacy would be reach for us often as a PD-1 inhibitor. Sherry, do you want to address the questions of regarding what we would see in the context of melanoma and non-small cell lung cancer?

我們認為，如果與 IPI 劑量進行比較，這代表每公斤 14.2 毫克。我認為我們可以利用這一點，並有一個廣泛的目標，即在我們的癌症患者治療中儘早給予盡可能多的CTLA-4 阻斷，並使其基於耐受性和療效，我們通常可以達到這一點PD-1抑制劑。雪莉，您想回答一下我們在黑色素瘤和非小細胞肺癌的背景下會看到什麼的問題嗎？

Sure. Sure. Thank you, Eric, and thank you, Ben, for your question. And I think basically what we would like is to be meaningfully better then on the current marketed standard of care as to what that means is meaningfully better and not only in terms of efficacy, but also tolerability. So providing a regimen that helps we'll allow a patient to we really experienced the full benefit of of the therapy. And so in the context of melanoma, don't know whether that means being meaningfully better than and up to lag in terms of efficacy are meaningfully better than a pivotal year. I believe we aim to be meaningfully better than it's regimens currently.

當然。當然。謝謝你，艾瑞克，謝謝你，本，提出問題。我認為基本上我們想要的是比目前市場上的護理標準明顯更好，這意味著不僅在功效方面而且在耐受性方面都明顯更好。因此，提供一種有幫助的治療方案，我們將使患者真正體驗到治療的全部益處。因此，在黑色素瘤的背景下，不知道這是否意味著在療效方面明顯好於或落後於關鍵一年。我相信我們的目標是比目前的治療方案更有意義。

Got it. And I and I and what about for non-small cell? As you know, both of those just out and jump in here for a second. As you noticed, we mentioned that we're doing a targeted population with a significantly large population, but a subset of all non-small cell lung cancer patients. And we're going to talk a bit more about that in a future conference because at the moment, we're just simply keeping that at a high level at this point.

知道了。而我和我，對於非小型基地台又如何呢？如你所知，這兩個人都只是出去並跳到這裡來。正如您所注意到的，我們提到我們正在研究一個目標人群，其人群數量非常大，但只是所有非小細胞肺癌患者的子集。我們將在未來的會議上更多地討論這一點，因為目前我們只是將其保持在高水準。

Okay. And just maybe just going back to <unk> and Eric's answer, just in regards to the 14.2 mix for QiG significantly higher than what's been evaluated on prior. Do you have a sense as to kind of the there PKPD. at this point and how much sort of receptor occupancy or blocking we're already getting any sort of color there would be first, I'll just jump in for a moment. I think that a lot of the studies that were done prior with ipilimumab have shown that you do continue to get it advantage up to 10 migs per kg. We don't have the data of 14.2 megs per kg, but we'll definitely be comparing the 10 to the 14.2.

好的。也許只是回到 和 Eric 的答案，只是就 QiG 的 14.2 混合而言，它明顯高於先前評估的值。你對 PKPD 有什麼感覺嗎？在這一點上，以及我們已經獲得了某種顏色的受體佔據或阻斷的程度，我將先介紹一下。我認為之前使用 ipilimumab 進行的許多研究表明，您確實可以繼續獲得每公斤 10 毫克的優勢。我們沒有 14.2 兆每公斤的數據，但我們肯定會比較 10 和 14.2。

And our belief is we may not have quite a saturated it yet at all of the 10. But the data is pretty clear when you compare one going one three and up to 10 migs per kilo that you continue to get benefits. So I think though Your point is reasonable, it's a reasonable question at what point does that our efforts start to become saturated. And I think so certainly there's plenty of incentive to check out this one gram level. And well, we'll hope to report out on that in the future.

我們相信，這 10 個國家可能還沒有完全飽和。但當您比較一比一三和每公斤 10 公尺時，數據非常清楚，您將繼續獲得好處。所以我認為雖然你的觀點是合理的，但我們的努力從什麼時候開始變得飽和是一個合理的問題。我認為肯定有足夠的動力來檢查這一克水平。好吧，我們希望將來能對此進行報告。

And then maybe I'll jump in here with your question about the PK. So as these are conditionally binding antibodies, we would need to do tumor biopsies to explore receptor occupancy because the antibody was designed to explicitly not bind in the periphery. So it turns out to be a more challenging question to answer and one that we haven't done those biopsies in humans to characterize receptor occupancy.

然後也許我會在這裡提出你關於 PK 的問題。因此，由於這些是有條件結合的抗體，我們需要進行腫瘤活檢來探索受體佔據情況，因為抗體被設計為明確不在周邊結合。因此，這是一個更具挑戰性的問題，我們還沒有對人體進行活組織檢查來表徵受體佔用情況。

And then your question about PK. is that it is really behaving in a in a pretty standard on manner there really no PK surprises to date.

然後是關於PK的問題。是它的表現確實非常標準，迄今為止確實沒有出現任何 PK 驚喜。

Excellent. Thanks, guys for taking the questions. Thank you.

出色的。謝謝你們提出問題。謝謝。

Yes, thank you.

是的，謝謝。

There are no further questions at this time. I would like to turn the floor back over to Jay Short for any closing comments.

目前沒有其他問題。我想將發言權交還給傑伊·肖特（Jay Short）以徵求結束意見。

Both So everyone for your attention and looking forward to a very exciting second quarter. We'll be talking to you soon. Thank you.

請大家關注並期待非常令人興奮的第二季。我們很快就會與您交談。謝謝。

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

今天的電話會議到此結束。此時您可以斷開線路。感謝您的參與。