Bioatla Inc (BCAB) 2024 Q1 法說會逐字稿

Greetings and welcome to the BioAtla First Quarter 2024 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.

您好，歡迎參加 BioAtla 2024 年第一季財報電話會議。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。

It is now my pleasure to introduce your host, Bruce Mackle, with LifeSci Advisors. Thank you, Bruce. You may begin.

現在我很高興向您介紹主持人 Bruce Mackle 和 LifeSci Advisors。謝謝你，布魯斯。你可以開始了。

Thank you, operator, and good afternoon, everyone. With me today on the phone from BioAtla are Dr. Jay Short, Chairman, CEO and Co-Founder; Dr. Eric Sievers, Chief Medical Officer; Sheri Lydick, Chief Commercial Officer; and Richard Waldron, Chief Financial Officer. Following today’s call the team will participate in a short Q&A. Earlier this afternoon, BioAtla released financial results and a business update for the first quarter ended March 31, 2024. A copy of that press release and corporate presentation are available on the company’s website.

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； Eric Sievers 博士，首席醫療官； Sheri Lydick，商務長；和財務長理查德·沃爾德倫。在今天的電話會議之後，團隊將參加一個簡短的問答。今天下午早些時候，BioAtla 發布了截至 2024 年 3 月 31 日的第一季財務表現和業務更新。該新聞稿和公司簡報的副本可在該公司網站上取得。

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 BioAtla’s business plans and prospects and whether it’s clinical trials will support registration, plans to form collaborations and other strategic partnerships for selected assets; achievements of milestones, results, conduct, progress and timing of its research and development programs in clinical trials; expectations with respect to enrollment and dosing in its clinical trials, plans and expectations regarding future data updates, clinical trials, regulatory meetings and regulatory submissions, the potential regulatory approval path for its product candidates; expectations about the sufficiency of its cash and cash equivalents to fund operations and expectations regarding R&D expenses and cash burn.

在我們開始之前，我想提醒大家，本次電話會議期間所做的陳述將包括前瞻性陳述，包括但不限於有關 BioAtla 的業務計劃和前景以及它是否是臨床的陳述試驗將支持選定資產的註冊、建立合作和其他策略夥伴關係的計劃；其臨床試驗研發計劃的里程碑成就、結果、實施、進度和時間表；對臨床試驗入組和劑量的期望、對未來數據更新、臨床試驗、監管會議和監管提交的計劃和期望、候選產品的潛在監管批准路徑；對現金和現金等價物是否足以滿足營運資金的預期以及對研發費用和現金消耗的預期。

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 quarterly report on Form 10-Q. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of today, May 14, 2024, and BioAtla disclaims any obligation to update such statements to reflect future information, events or circumstances, except as required by law.

這些陳述受到各種風險、假設和不確定性的影響，可能導致實際結果出現重大差異，並在向 SEC 提交的文件中進行了描述，包括最新的 10-Q 表季度報告。請您注意不要過度依賴這些前瞻性陳述，這些陳述僅截至今天，即 2024 年 5 月 14 日，BioAtla 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。

With that, I’d like to turn the call over to Jay Short. Jay?

說到這裡，我想把電話轉給傑伊·肖特。傑伊？

Thank you, Bruce, and thanks to everyone for joining us for our first quarter 2024 BioAtla earnings call. Additional details related to what we will share today are available in today’s press release and our updated company presentation, both of which are available on our website. We continue to make considerable progress across all of our ongoing clinical programs. We are pleased to share our recent encouraging data readouts for our CAB-ROR2-ADC and highly treatment refractory head and neck cancer patients, who had a median of three prior lines of treatment.

謝謝你，Bruce，也謝謝大家加入我們參加我們的 2024 年第一季 BioAtla 財報電話會議。與我們今天分享的內容相關的更多詳細資訊可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。我們所有正在進行的臨床項目繼續取得重大進展。我們很高興分享我們最近為 CAB-ROR2-ADC 和高度治療難治性頭頸癌患者提供的令人鼓舞的數據，這些患者之前接受過三種治療的中位數。

As illustrated in the best overall response slide of our corporate presentation, many patients achieved rapid and deep tumor control with 38% of patients responding. Having observed an 86% disease control rate, we believe these findings support use in earlier line settings. In addition, in view of the manageable safety profile, this holds considerable promise for future combination therapies. Given the strength of the data we observed with CAB-ROR2-ADC, especially at the more intensive 2Q3W dosing regimen. We plan to meet with the FDA in the second half of this year for guidance on a potentially registrational trial. We obtained multiple responses in encouraging clinical benefit using the less intense Q2W dose of our CAB-ROR2-ADC and melanoma.

正如我們公司演示的最佳整體反應幻燈片所示，許多患者實現了快速、深度的腫瘤控制，其中 38% 的患者有反應。觀察到 86% 的疾病控制率後，我們相信這些發現支持在早期生產線設定中的使用。此外，鑑於可控的安全性，這為未來的聯合療法帶來了巨大的希望。鑑於我們使用 CAB-ROR2-ADC 觀察到的數據強度，特別是在更密集的 2Q3W 給藥方案中。我們計劃在今年下半年與 FDA 會面，尋求潛在註冊試驗的指導。使用較低強度的 Q2W 劑量的 CAB-ROR2-ADC 和黑色素瘤，我們在鼓勵臨床獲益方面獲得了多種反應。

However, we did not meet our internal bar. We do believe, though, that our CAB-ROR2-ADC at the more intensive regimen has potential in melanoma and other indications, including triple negative breast cancer, where we observed tumor reduction in our earlier Phase 1 study. However, due to our ongoing prioritization, we do not plan to explore the more intensive regimen at this time.

然而，我們並沒有滿足我們內在的要求。不過，我們確實相信，我們的 CAB-ROR2-ADC 在更強化的方案中具有治療黑色素瘤和其他適應症的潛力，包括三陰性乳癌，我們在早期的 1 期研究中觀察到腫瘤減少。然而，由於我們持續優先考慮，目前不打算探索更強化的治療方案。

Next, I will cover our ongoing Phase 1/2 trial with our CAB CTLA-4 IO antibody. Our Phase 1 study, which was expanded to a higher dose due to the encouraging safety results, is progressing well. We’ve more than doubled the number of treated patients since our first data disclosure late last year, and we have observed multiple responses at the 350 milligram dose in combination with PD-1. We are pleased to report that our ongoing Phase 2 study echoes our earlier report as very few immune-related adverse events have been observed to date, which is consistent with the anticipated benefits of our conditional binding technology.

接下來，我將介紹我們正在進行的 CAB CTLA-4 IO 抗體的 1/2 期試驗。由於令人鼓舞的安全性結果，我們的一期研究進展順利，因此擴大了劑量。自去年年底首次披露數據以來，我們的治療患者數量增加了一倍多，並且我們觀察到 350 毫克劑量與 PD-1 聯合使用時出現多種反應。我們很高興地報告，我們正在進行的 2 期研究與我們先前的報告相呼應，因為迄今為止觀察到的免疫相關不良事件很少，這與我們條件結合技術的預期益處一致。

In addition, the observed safety profile also continues to hold now that we are treating patients at the 700 milligram flat dose or approximately 10 milligram per kilogram. We also remain on track to clear the DLT observation period with the unprecedented 1 gram dose later this quarter. The manageable safety at this high dose allows us to approach the maximum activity for a CTLA-4 inhibitor in the tumor, which has not previously been achieved in the clinic. As for our CAB AXL ADC, we completed dosing patients in the first portion of our potentially registrational trial in undifferentiated pleomorphic sarcoma in April. We also remain on track to evaluate clinical benefit of the AXL ADC in target agnostic cancer patients later this quarter.

此外，現在我們以 700 毫克的固定劑量或大約每公斤 10 毫克的劑量治療患者，觀察到的安全性也持續維持。我們也將繼續在本季稍後以史無前例的 1 克劑量清除 DLT 觀察期。這種高劑量的可控安全性使我們能夠達到 CTLA-4 抑制劑在腫瘤中的最大活性，這在臨床上以前從未實現過。至於我們的 CAB AXL ADC，我們在 4 月在未分化多形性肉瘤潛在註冊試驗的第一部分中完成了患者給藥。我們也將繼續在本季稍後評估 AXL ADC 在目標不可知癌症患者中的臨床益處。

Finally, the Phase 1 dose escalation trial with our first dual CAB biospecific EpCAM CD3 T cell engager remains on track for readout in the second half. As we are now into the second quarter of 2024, we are focused on finalizing data readouts and reports for our ROR2 and CTLA-4 assets for meetings with the FDA to obtain guidance on one or more potentially registrational trials in the second half of this year. In addition, we are advancing our discussions with potential pharmaceutical partners on selected preclinical and clinical assets to both accelerate their development and maximize their market potential.

最後，我們的第一個雙 CAB 生物特異性 EpCAM CD3 T 細胞接合器的 1 期劑量遞增試驗仍按計劃在下半年進行讀數。目前已進入 2024 年第二季度，我們的重點是最終確定 ROR2 和 CTLA-4 資產的數據讀數和報告，以便與 FDA 舉行會議，以獲得今年下半年一項或多項潛在註冊試驗的指導。此外，我們正在與潛在的製藥合作夥伴就選定的臨床前和臨床資產進行討論，以加速其開發並最大限度地發揮其市場潛力。

I will now turn the call over to Eric, who will provide additional insights and details on our ROR2 and CTLA-4 assets. Eric?

我現在將把電話轉給 Eric，他將提供有關我們的 ROR2 和 CTLA-4 資產的更多見解和詳細資訊。艾瑞克？

Thank you, Jay. Beginning with our CAB-ROR2-ADC ozuriftabmab vedotin in the target agnostic head and neck cancer indication, we have enrolled a total of 33 patients, who had a median of three prior treatment regimens. Ranging from one to six prior lines of treatment, 21 received more intensive day 1 and 8 dosing in three week cycles, and twelve received every other week dosing. Among the 29 who were valuable for response assessment, eleven responses were documented and five responses are now confirmed to date. Notably, four of five confirmed responses occurred in patients, who received the ADC as second or third line therapy. Further follow up will be required to provide a reliable estimate of the response duration.

謝謝你，傑伊。從我們的 CAB-ROR2-ADC ozuriftabmab vedotin 用於目標不可知的頭頸癌適應症開始，我們總共招募了 33 名患者，他們之前接受過三種治療方案。在先前接受 1 到 6 條治療線的情況下，21 名患者在三週的週期中在第 1 天和第 8 天接受了更密集的給藥，12 名患者每隔一周接受一次給藥。在對響應評估有價值的 29 名響應者中，有 11 名響應已被記錄，5 名響應目前已被確認。值得注意的是，五分之四的確診緩解發生在接受 ADC 作為二線或三線治療的患者身上。需要進一步跟進以提供響應持續時間的可靠估計。

Importantly, responses were observed regardless of ROR2 target expression from pre-treatment tumor biopsies evaluated by immunohistochemistry. As of the safety data cut in March, only one patient discontinued treatment due to a treatment related adverse event, which was peripheral neuropathy. Collectively, these data support advancing to earlier lines of therapy, potentially in combination with PD-1 inhibition in the first-line setting. A meeting with the FDA is anticipated in the second half of the year to discuss potential registrational trial approaches.

重要的是，無論透過免疫組織化學評估的治療前腫瘤活檢中的 ROR2 標靶表達如何，都觀察到了反應。截至三月的安全資料削減，只有一名患者因治療相關不良事件（週邊神經病變）而停止治療。總的來說，這些數據支持推進早期治療，可能與第一線治療中的 PD-1 抑制相結合。預計今年下半年將與 FDA 舉行會議，討論潛在的註冊試驗方法。

Moving now to our CAB CTLA-4 antibody evalstotug. Over the past 25 years, multiple lines of clinical evidence have shown that increased exposure of CTLA-4 blockade in combination with PD-1 inhibition drives long-term survival benefits. At the same time, most oncologists prescribe currently approved CTLA-4 blocking antibodies at relatively low doses because a high rate of immune-related adverse events limit tolerability. We designed evalstotug to preferentially bind CTLA-4 in the acidic tumor microenvironment to avoid binding in normal healthy tissues and lymph nodes. We believe evalstotug will be better tolerated, enabling more patients to receive clinical benefit from CTLA-4 inhibition.

現在轉向我們的 CAB CTLA-4 抗體 evalstotug。在過去 25 年中，多項臨床證據表明，增加 CTLA-4 阻斷劑暴露與 PD-1 抑制相結合可帶來長期存活獲益。同時，大多數腫瘤學家以相對較低的劑量開出目前已批准的 CTLA-4 阻斷抗體，因為免疫相關不良事件發生率較高，限制了耐受性。我們設計的 evalstotug 在酸性腫瘤微環境中優先結合 CTLA-4，以避免在正常健康組織和淋巴結中結合。我們相信 evalstotug 將具有更好的耐受性，使更多患者能夠從 CTLA-4 抑制中獲得臨床效益。

Last quarter, we announced confirmed responses for two of six treatment refractory patients using the 350 milligram dose in combination with PD-1 antibody. As part of today’s update another response has now been achieved in a melanoma patient, whose evalstotug dose was increased from 70 milligrams to 350 milligrams given every three weeks, providing additional evidence that higher doses drive clinical benefit.

上個季度，我們宣布使用 350 毫克劑量與 PD-1 抗體聯合治療，六名難治性患者中的兩名患者獲得了確認的緩解。作為今天更新的一部分，一名黑色素瘤患者現在已經取得了另一項緩解，其evalstotug 劑量從每三週一次的70 毫克增加到350 毫克，這提供了更多證據表明更高的劑量可帶來臨床益處。

As Jay mentioned, patients are tolerating the unprecedented 1 gram dose level that we are presently evaluating as a part of our continued dose escalation. We continue to enroll in the Phase 2, first-line melanoma and non-small cell lung cancer combination cohorts at the 700 milligram flat dose. We are on track for additional data readouts later this year. Investigators are enthusiastic to use a CTLA-4 inhibitor at higher doses in highly treatment refractory cancer patients, and we will report a Phase 1 update at ASCO on June 1.

正如 Jay 所提到的，患者正在耐受前所未有的 1 克劑量水平，我們目前正在評估該劑量水平，作為我們持續劑量遞增的一部分。我們繼續以 700 毫克固定劑量入組 2 期一線黑色素瘤和非小細胞肺癌聯合隊列。我們預計在今年稍後獲得更多數據。研究人員熱衷於在高度治療難治性癌症患者中使用更高劑量的 CTLA-4 抑制劑，我們將於 6 月 1 日在 ASCO 上報告 1 期更新。

Shifting to our registration plans, we are now focused on the marked, unmet need among patients with newly diagnosed metastatic or unresectable, BRAF-mutated melanoma, who account for approximately half of patients with melanoma. Our strategy is informed by three key findings from large prospective clinical trials. First, BRAF patients should receive checkpoint inhibitor treatment before BRAF inhibitors. Second, combined use of CTLA-4 and PD-1 blockade helps drive both progression-free and overall survival. Third, higher CTLA-4 doses meaningfully and specifically improve overall survival.

轉向我們的註冊計劃，我們現在專注於新診斷的轉移性或不可切除的 BRAF 突變黑色素瘤患者中明顯的、未滿足的需求，這些患者約佔黑色素瘤患者的一半。我們的策略是基於大型前瞻性臨床試驗的三個關鍵發現。首先，BRAF患者應在接受BRAF抑制劑之前接受檢查點抑制劑治療。其次，合併使用 CTLA-4 和 PD-1 阻斷劑有助於提高無惡化存活率和整體存活率。第三，較高的 CTLA-4 劑量有意義且特別能提高整體存活率。

Notably, improved progression-free survival for this patient subgroup first appeared at just three months, suggesting that adding CTLA-4 inhibition quickly achieves tumor control for these BRAF melanoma patients. We believe that our conditionally binding CTLA-4 antibody can safely achieve high, unprecedented levels of CTLA-4 blockade in the tumor microenvironment, while largely avoiding CTLA-4 inhibition in normal tissues. We are now designing an efficient, blinded, randomized, pivotal trial employing evalstotug plus pembrolizumab for newly diagnosed patients with BRAF-mutated metastatic or unresectable melanoma. We anticipate FDA feedback in the second half of this year, positioning us to initiate the potentially registrational trial by year’s end.

值得注意的是，該患者亞群在短短三個月內首次出現無惡化存活期的改善，顯示添加 CTLA-4 抑制劑可以快速實現這些 BRAF 黑色素瘤患者的腫瘤控制。我們相信，我們的條件結合 CTLA-4 抗體可以在腫瘤微環境中安全地實現前所未有的高水平 CTLA-4 阻斷，同時很大程度上避免正常組織中的 CTLA-4 抑制。我們現在正在設計一項高效、盲法、隨機、關鍵試驗，採用 evalstotug 聯合派姆單抗治療新診斷的 BRAF 突變轉移性或不可切除黑色素瘤患者。我們預計 FDA 將在今年下半年收到回饋，使我們能夠在年底前啟動可能的註冊試驗。

I would now like to turn the call over to Sheri to provide a few comments on the market opportunities for these agents. Sheri?

我現在想把電話轉給 Sheri，就這些代理商的市場機會提供一些評論。雪莉？

Thank you, Eric. And good afternoon everyone.

謝謝你，埃里克。大家下午好。

Continuing with our CAB CTLA-4 antibody, evalstotug, based on our evolving Phase 1 data, we continue to believe evalstotug has the potential to be better best-in-class CTLA-4 that 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. There is tremendous opportunity across many solid tumors for evalstotug, but we are focused initially on BRAF-mutated metastatic melanoma as a potential efficient path to approval with a high likelihood of success.

繼續我們的 CAB CTLA-4 抗體 evalstotug，根據我們不斷發展的 1 期數據，我們仍然相信 evalstotug 有潛力成為更好的同類最佳 CTLA-4，有望與 PD 一樣經常使用-1 抑製劑，並可能擴大合併免疫檢查點抑制有效的適應症。evalstotug 在許多實體瘤中存在巨大的機會，但我們最初關注 BRAF 突變的轉移性黑色素瘤，將其視為一種潛在的有效審批途徑，成功的可能性很高。

The current worldwide therapeutic market size of metastatic melanoma is approximately eight billion annually and is expected to grow to over 11 billion by 2028. BRAF mutations are present in approximately 50% of malignant melanoma patients and first line standard of care remains immunotherapy regardless of BRAF status. As Eric noted earlier, documented clinical benefits of adding an anti-CTLA-4 to a PD-1 inhibitor are particularly striking in BRF mutated patients and we believe that the combination of evalstotug with a PD-1 inhibitor, has the potential to become the standard of care for these patients.

目前全球轉移性黑色素瘤治療市場規模每年約 80 億，預計到 2028 年將成長到超過 110 億。大約 50% 的惡性黑色素瘤患者存在 BRAF 突變，無論 BRAF 狀態如何，一線治療標準仍然是免疫療法。正如 Eric 先前指出的，已記錄的在 PD-1 抑制劑中添加抗 CTLA-4 的臨床益處在 BRF 突變患者中尤其引人注目，我們相信 evalstotug 與 PD-1 抑制劑的組合有潛力成為這些患者的護理標準。

Onto our CAB ROR2 ADC ozuriftamab vedotin. We are encouraged with the single agent clinical profile that is emerging in multi refractory, heavily pretreated head and neck cancer. The worldwide prevalence and mortality rate for this population are significant, and despite recent advances, there remains a profound unmet need, particularly for patients who have progressed on first line treatment options. Therapies available for these refractory patients are limited and have suboptimal clinical benefits.

關於我們的 CAB ROR2 ADC ozuriftamab vedotin。我們對多難治性、經過大量預先治療的頭頸癌中出現的單藥臨床概況感到鼓舞。該族群在全球範圍內的盛行率和死亡率很高，儘管最近取得了進展，但仍然存在巨大的未滿足的需求，特別是對於在一線治療方案中取得進展的患者。可用於這些難治性患者的治療方法有限，且臨床效益不佳。

The current worldwide therapeutic market size of head and neck cancer is approximately 3.5 billion annually and is expected to grow significantly to nearly 5 billion over the next five years. Given the encouraging emerging data set in head and neck cancer, we believe ozuriftamab vedotin could represent a significant commercial opportunity for BioAtla. We also believe ozuriftamab vedotin is well positioned for a strategic collaboration that will expand the potential of this CAB ADC across multiple solid tumor indications.

目前全球頭頸癌治療市場規模每年約35億，預計未來五年將大幅成長至近50億。鑑於頭頸癌方面令人鼓舞的新興數據集，我們相信 ozuriftamab vedotin 可能為 BioAtla 帶來重要的商業機會。我們也相信 ozuriftamab vedotin 已做好戰略合作的準備，這將擴大該 CAB ADC 在多種實體瘤適應症中的潛力。

Given the combined prevalence of head and neck cancer and BRAF-mutated melanoma, we believe these assets and indications represent potentially meaningful value creating opportunities for BioAtla with the potential to redefine standard-of-care for patients with these devastating diseases.

鑑於頭頸癌和 BRAF 突變黑色素瘤的綜合盛行率，我們相信這些資產和適應症代表了 BioAtla 潛在的有意義的價值創造機會，有可能重新定義患有這些破壞性疾病的患者的護理標準。

With that, I would now like to turn the call back over to Jay.

有了這個，我現在想把電話轉回給傑伊。

Thank you, Sheri.

謝謝你，雪莉。

Next, a few words in our potentially first-in-class, dual CAB, bispecific T-cell engager antibody CAB-EpCAM, CAB-CD3. EpCAM is a ubiquitous target expressed on the surface of cancer cells, which requires the use of our CAB technology to achieve optimal selectivity and safety. We are on track to report the full data set from the Phase 1 study in the second half of this year, with a potential Phase 2 study initiating also in the second half of this year. The T-cell engager space offers tremendous opportunity for more effective therapies and in particular, our CAB enabled EpCAM 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，簡單介紹一下我們潛在的一流雙 CAB 雙特異性 T 細胞接合抗體 CAB-EpCAM、CAB-CD3。EpCAM 是癌細胞表面表達的普遍靶點，需要使用我們的 CAB 技術來實現最佳選擇性和安全性。我們預計在今年下半年報告第一階段研究的完整數據集，第二階段研究也可能在今年下半年啟動。T 細胞接合器空間為更有效的治療提供了巨大的機會，特別是，我們的CAB 支持EpCAM 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、胰腺癌和癌症前列腺等。

BioAtla has developed a novel NextGen carbohydrate linker system to further reduce the potential risks associated with neutropenia from off target toxicity used in our CAB Nectin-4 ADC. This ADC has the potential for broad applicability, including for do indications such as pancreatic cancer. We recently presented compelling antitumor activity, PK and toxicology data last month at the AACR annual meeting that indicates CAB Nectin-4 ADC is potentially a more effective treatment with reduced toxicity. As part of today’s update, we have received FDA IND clearance for this agent and are evaluating several options as we continue to focus our resources on our later stage clinical programs.

BioAtla 開發了一種新型 NextGen 碳水化合物連接體系統，以進一步降低 CAB Nectin-4 ADC 中使用的脫靶毒性與嗜中性白血球減少症相關的潛在風險。此 ADC 具有廣泛的應用潛力，包括胰腺癌等適應症。我們最近在上個月的 AACR 年會上展示了引人注目的抗腫瘤活性、PK 和毒理學數據，顯示 CAB Nectin-4 ADC 可能是更有效且毒性更低的治療方法。作為今天更新的一部分，我們已獲得 FDA 對該藥物的 IND 批准，並正在評估多種選擇，同時我們將繼續將資源集中在後期臨床項目上。

With that, I would now like to turn the call over to Rick to review the first quarter 2024 financials. Rick?

現在，我想將電話轉給 Rick，讓他審查 2024 年第一季的財務狀況。瑞克？

Thank you, Jay. Research and development expenses were $18.9 million for the quarter ended March 31, 2024, compared to $21.7 million for the same quarter in 2023. The decrease of $2.8 million was primarily due to completion of preclinical development related to our Nectin-4 IND and prioritization of our clinical programs in 2023.

謝謝你，傑伊。截至 2024 年 3 月 31 日的季度，研發費用為 1,890 萬美元，而 2023 年同一季度的研發費用為 2,170 萬美元。減少 280 萬美元主要是因為完成了與 Nectin-4 IND 相關的臨床前開發以及 2023 年臨床計畫的優先順序。

We expect our R&D expenses to continue to decrease in the near-term due to recently completed enrollment in clinical trials for datasets expected to enable potentially registrational trials for our ADC programs.

我們預計我們的研發費用在短期內將繼續減少，因為最近完成了資料集臨床試驗的註冊，預計將為我們的 ADC 專案提供潛在的註冊試驗。

General and administrative expenses were $5.6 million for the quarter ended March 31, 2024, compared to $7.2 million for the same quarter in 2023. The $1.6 million decrease was primarily due to lower stock-based compensation and professional fees.

截至 2024 年 3 月 31 日的季度一般及管理費用為 560 萬美元，而 2023 年同一季度為 720 萬美元。減少 160 萬美元主要是因為股票薪酬和專業費用的減少。

Net loss for the quarter ended March 31, 2024 was $23.2 million, compared to a net loss of $27.4 million for the same quarter in 2023. Cash and cash equivalents as of March 31, 2024 were $80.6 million, compared to $111.5 million as of December 31, 2023.

截至 2024 年 3 月 31 日的季度淨虧損為 2,320 萬美元，而 2023 年同一季度的淨虧損為 2,740 萬美元。截至 2024 年 3 月 31 日，現金及現金等價物為 8,060 萬美元，而截至 2023 年 12 月 31 日，現金及現金等價物為 1.115 億美元。

Net cash used in operating activities for the quarter ended March 31, 2024 was $30.8 million, compared to net cash using operating activities of $22.7 million for the same period in 2023. Our cash used for the quarter ended March 31, 2024 included approximately $5 million in annual payments that typically occur during our first fiscal quarter.

截至 2024 年 3 月 31 日的季度經營活動使用的現金淨額為 3,080 萬美元，而 2023 年同期經營活動使用的現金淨額為 2,270 萬美元。截至 2024 年 3 月 31 日的季度使用的現金包括約 500 萬美元的年度付款，這些付款通常發生在我們的第一個財季。

We expect our operating cash burn to be approximately $20 million for the quarter ending June 30, 2024, and to continue to decrease in the second half of the year as we complete treatments in our ADC clinical trials, allowing our current cash and cash equivalents to fund operations into the second half of 2025.

我們預計，截至2024 年6 月30 日的季度，我們的營運現金消耗約為2000 萬美元，並且隨著我們完成ADC 臨床試驗中的治療，該現金消耗將在下半年繼續減少，從而使我們當前的現金及現金等價物能夠基金營運至2025年下半年。

And now, back to Jay.

現在，回到傑伊。

Thank you, Rick. We are pleased with the considerable progress we have made to date and our cumulative results across our CAB pipeline targeting solid tumors. We look forward to the multiple important milestones this year, including several planned meetings with the FDA to discuss our potentially registrational trial with ROR2 in head and neck cancer, guidance on the remaining portion of the registrational trial in UPS with AXL, and guidance for a potentially registrational trial with CTLA-4 in BRAF mutated melanoma.

謝謝你，瑞克。我們對迄今為止的巨大進展以及針對實體腫瘤的 CAB 管道的累積成果感到高興。我們期待今年實現多個重要的里程碑，包括計劃與 FDA 舉行的幾次會議，討論我們在頭頸癌中使用 ROR2 的潛在註冊試驗、對 UPS 與 AXL 註冊試驗的剩餘部分的指導，以及對CTLA-4治療BRAF 突變黑色素瘤的潛在註冊試驗。

With that, we will turn it back to our operator to take your questions.

這樣，我們會將其轉回給我們的接線生來回答您的問題。

Thank you. We will now be conducting a question-and-answer session. (Operator Instructions)

謝謝。我們現在將進行問答環節。（操作員說明）

Brian Cheng, JPMorgan.

布萊恩鄭，摩根大通。

Hey guys, thanks for taking our question this afternoon. Can you elaborate on the duration of the confirmed responses that you’re seeing with your raw two ADC in head and neck today? And what is your expectation on the duration response as the data set mature?

大家好，感謝您今天下午提出我們的問題。您能否詳細說明一下您今天在頭部和頸部的原始兩個 ADC 中看到的確認反應的持續時間？隨著資料集成熟，您對持續時間回應的期望是什麼？

Thanks, Brian. I’ll let Eric take a crack at this one. Thank you.

謝謝，布萊恩。我會讓埃里克嘗試一下這個。謝謝。

Thanks, Brian. So we definitely need further follow-up to estimate our duration of response, but I will refer you to Slide 29 of our updated corporate deck, the swimmers plot gives you a sense of the confirmed responses and addresses the question you asked, particularly the patients that were treated at the every other week dosing.

謝謝，布萊恩。因此，我們肯定需要進一步的後續行動來估計我們的回應持續時間，但我將向您推薦我們更新的公司幻燈片的幻燈片29，游泳者圖讓您了解已確認的回應並解決了您提出的問題，特別是患者每隔一週給藥一次進行治療。

I will note that those patients were dosed first and then after completing that effort, we then went on to employ the days one and aid regimen. So, we have a bit longer follow-up for the patients in blue on Slide 29.

我要指出的是，這些患者首先接受了給藥，然後在完成工作後，我們繼續採用第一天和輔助方案。因此，我們對幻燈片 29 上藍色的患者進行了更長的追蹤。

And I’ll just add there are eight patients still on treatment and that are ongoing of which two have responses that could confirm, and there’s also two with decreasing tumor volume.

我只想補充一下，有八名患者仍在接受治療，並且正在進行中，其中兩名患者的反應可以確認，還有兩名患者的腫瘤體積正在縮小。

Great. And then maybe can you help us also frame the expectation of response level and also the duration of response with the current standard of care in head and neck today in second line and also third line.

偉大的。然後，也許您可以幫助我們根據當前二線和三線頭頸護理標準制定響應水平的預期以及響應持續時間。

Yes. So I think when you look at the later lines, we’re thinking if you could get four months plus in these -- keep in mind, we’re fourth line here, three prior line -- median three prior lines. So this is really out there. The bar is exceptionally low, especially when you look at second line, where you’re getting on, from a response rate standpoint 13% on average. And so there you would like to see, I think five months plus, obviously, go to first line, you’d like to see a half a year plus. But I think given the late lines we’re in, I think that it’s encouraging.

是的。所以我認為，當你看後面的幾行時，我們會想你是否可以在這些行中獲得四個月以上的時間- 請記住，我們這裡是第四行，前面的三行- 中間是前面的三行。所以這確實存在。這個標準非常低，尤其是當你看第二線時，從平均回覆率 13% 的角度來看，你正在進步。所以你想看到，我想五個月以上，顯然，轉到第一行，你想看到半年以上。但我認為，考慮到我們排的很晚，我認為這令人鼓舞。

Great. Thank you so much.

偉大的。太感謝了。

Kelly Shi, Jefferies.

施凱莉，傑弗里斯。

Hi everyone, thank you for taking our question. This is Dev on for Kelly Shi, and congratulations on the progress. I have a couple of questions on AXL. Can you provide any color on median follow-up that you might need before you meet with the FDA in second half? And also, do you expect to start the next stage of recruiting in 2024? Or it could be in early 2025. Thank you.

大家好，感謝您提出我們的問題。這是凱莉·施 (Kelly Shi) 的開發人員，祝賀您的進展。我有幾個關於 AXL 的問題。您能否提供下半年與 FDA 會面之前可能需要的中位追蹤情況？另外，您預計在 2024 年開始下一階段的招募嗎？或者可能是在 2025 年初。謝謝。

Thank you. Yes. Because we’ve completed the dosing that we intended for the first portion of the potentially registrational trial, our main goal here is to achieve multiple scans for each of those patients, which we think should readily occur in the second half of this year. And so our current thinking, assuming we got encouraging -- continue to get encouraging data that we would have an opportunity to start that next portion of the -- remaining portion of the registrational trial in late 2024.

謝謝。是的。因為我們已經完成了潛在註冊試驗第一部分的給藥劑量，所以我們的主要目標是對每位患者進行多次掃描，我們認為這應該很容易在今年下半年實現。因此，我們目前的想法是，假設我們得到令人鼓舞的數據，繼續獲得令人鼓舞的數據，我們將有機會在 2024 年底開始註冊試驗的剩餘部分的下一部分。

And one more on non-small cell lung cancer randomized Phase 3 trial. Can you remind whether you started those trial in second line or third line, or do you need any more alignment with the FDA?

還有一項關於非小細胞肺癌隨機 3 期試驗。您能否提醒一下您是否在二線或三線開始了這些試驗，或者您是否需要與 FDA 進行更多協調？

Well, on the non-small cell lung cancer, if I recall correctly, median of three prior lines there. So it was pretty late, very refractory patients, and we reported that out in December of last year, and we’ve done an extension to that study to look at the target agnostic patients. So we’ll give -- we’ll have that data in still later this quarter, and we’re going to pick an appropriate way to communicate that data once we get to the end of this quarter.

好吧，對於非小細胞肺癌，如果我沒記錯的話，是之前三行的中位數。所以當時已經很晚了，對於非常難治的患者，我們在去年 12 月就報告了這一點，並且我們對該研究進行了擴展，以觀察目標不可知論的患者。因此，我們將在本季稍後獲得這些數據，並且在本季末時我們將選擇適當的方式來傳達這些數據。

And so -- and then I think from there, I think we’ve already got feedback from the FDA on how to proceed if one goes into a second line or a third line, which obviously is earlier than what our data comes from. So we feel that with that final data, we’ll be well-positioned to layout the final strategy for that, either independently or with partners.

因此，我認為從那裡開始，我認為我們已經從 FDA 獲得了關於如何進入第二線或第三線的反饋，這顯然早於我們的數據來源。因此，我們認為，有了最終數據，我們將能夠獨立或與合作夥伴共同製定最終策略。

Okay. Thank you. Thanks for taking our question.

好的。謝謝。感謝您提出我們的問題。

Kaveri Pohlman, BTIG

卡維裡·波爾曼，BTIG

Great. Good evening. Congrats on the progress and thanks for taking my questions. For ROR2 ADC in head and neck. Can you tell us what feedback you received from physicians on this data? And were there any patients who had seen any other vedotin ADC as prior line of therapy, whether it’s PADCEV or Tivdak. Also, how you are thinking about the competitive landscape in general.

偉大的。晚安.恭喜您的進展，並感謝您提出我的問題。適用於頭部和頸部的 ROR2 ADC。您能告訴我們您從醫生那裡收到了關於這些數據的什麼回饋嗎？是否有患者曾接受過其他 vedotin ADC 作為先前的治療方案，無論是 PADCEV 還是 Tivdak。另外，您如何看待整體競爭格局。

Thanks, Kaveri. It’s Eric answering. So, first, your question about the feedback we’ve gotten from physicians, I’ll just give you some anecdotes. We received a call from the PI at USC indicating how pleased he was to report a complete response, and that’s now confirmed and enabling the patient to go back to work.

謝謝，卡維裡。是埃里克接聽的。因此，首先，關於我們從醫生那裡得到的反饋的問題，我將向您提供一些軼事。我們接到了南加州大學 PI 的電話，表示他很高興報告完整的答复，現在已經得到確認，使患者能夠重返工作崗位。

And that’s a patient that we review in our corporate deck. We were also pleased to hear from Memorial Sloan Kettering, where two of the investigators spoke about several patients on treatment, particularly emphasizing the tolerability and the rapidity of response. They felt that it really was serving an unmet need in this second, third and fourth line, head and neck cancer, which is exceptionally challenging, and so many patients having clinical progression as they’re getting these therapies.

這就是我們在公司資料庫中審查的患者。我們也很高興聽到紀念斯隆凱特琳醫院的消息，其中兩名研究人員談到了幾名正在接受治療的患者，特別強調了耐受性和反應的速度。他們認為，它確實滿足了二線、三線和四線頭頸癌中未滿足的需求，這是極具挑戰性的，而且許多患者在接受這些療法時出現了臨床進展。

And then you asked the question about did prior treatment with one of the other auristatin based ADCs. When I looked through the prior treatments, all patients had received a PD-1 blocking agent. Many received either a platinum or -- and/or a taxane regimen. I didn’t see any anecdotes of people that had received prior ADCs, but it’s certainly an interesting question with regard to the studies that are ongoing.

然後您問了有關之前使用其他一種基於 auristatin 的 ADC 進行治療的問題。當我查看先前的治療時，所有患者都接受了 PD-1 阻斷劑。許多人接受了鉑類藥物或—和/或紫杉烷治療方案。我沒有看到任何關於之前接受過 ADC 的人的軼事，但這對於正在進行的研究來說無疑是一個有趣的問題。

Yes. And Kaveri, this is Sheri. I can -- if I could take the question on the competitive landscape. Obviously, within the existing competitive landscape, there remains a profound unmet need and patients who fail frontline options, as you know, in second line cetuximab is often used with an ORR 13%. So we think -- within the existing therapeutic landscape that there remains an unmet need. And even if you look at the future competitive landscape, we have a different mechanism of action than those that are in development. And we think that the profile that’s emerging in this very heavily pre-treated patient population, really, really provides the opportunity for us to benefit patients in the second line setting within the existing as well as the future competitive landscape.

是的。卡維裡，這是謝裡。我可以——如果我能回答有關競爭格局的問題的話。顯然，在現有的競爭格局中，仍然存在巨大的未滿足的需求，並且一線選擇失敗的患者，如您所知，二線西妥昔單抗的 ORR 通常為 13%。因此我們認為，在現有的治療領域中，仍有未滿足的需求。即使你看看未來的競爭格局，我們的行動機制也與正在開發的機制不同。我們認為，在這個接受過大量治療的患者群體中出現的情況確實為我們提供了機會，使我們能夠在現有和未來的競爭格局中使二線患者受益。

Got it. That’s very helpful. And maybe a question on the dosing regimen, I guess, this is for both active and ROR2 ADC. You’ve tested different regimens from your initial schedule of Q2W to 2Q3W. Is this just for Project Optimus? Can you tell us what has been learned regarding the profile of the drug from these studies, whether you saw any significant PK/PD differences with these regimen and how you are thinking about dosing schedule going forward?

知道了。這非常有幫助。我想，這可能是關於劑量方案的問題，這適用於活性 ADC 和 ROR2 ADC。您已經測試了從最初的第二季到第二季第三週的不同治療方案。這只是為了擎天柱計畫嗎？您能否告訴我們從這些研究中對該藥物的概況了解了什麼，您是否發現這些方案有任何顯著的 PK/PD 差異，以及您如何考慮未來的給藥方案？

I’ll just start off by saying and I’ll let Eric finish this, but I just want to say, I’ll remind us all that we did use the 2Q3W in Phase 1, so it’s not that new. It’s certainly one we’ve looked at. But with respect to 2Q3W, certain characteristics, I’ll let Eric add to this.

我首先會說，我會讓 Eric 完成這個任務，但我只想說，我會提醒我們所有人，我們在第一階段確實使用了 2Q3W，所以事實並非如此新的。這當然是我們已經研究過的一個。但對於 2Q3W 的某些特徵，我會讓 Eric 補充一下。

Sure. Thanks, Jay. So I’ll emphasize that both of the regimens, I think, are exceptionally well tolerated. I’ll refer everyone to Slide 35 of our corporate deck, where we’ve summarized the every other week dosing the 2Q3W, which is days one and eight of a three week cycle, and then for melanoma as well. And in here, we’re having very few instances of related AEs leading to treatment discontinuation. And so tolerability is excellent with both regimens.

當然。謝謝，傑伊。因此，我要強調的是，我認為這兩種療法的耐受性都非常好。我將向大家推薦我們公司投影片 35，其中我們總結了每隔一周服用 2Q3W 的情況，即三週週期的第一天和第八天，然後也是黑色素瘤的情況。在這裡，導致治療中斷的相關 AE 實例非常少。因此這兩種方案的耐受性都非常好。

We are seeing in the head and neck data in particular, I think you can see from the spider plot on Slide 28 just a sense that we get more rapid disease control in the red, which is the more intensive regimen than the blue. And it is interesting with the blue patients, they did have longer exposure because we did those patients first. There are quite a few patients. There are the two instances of patients that are at many, many weeks of therapy, one passing 35 weeks and one passing 45 weeks on study. So, I think both regimens well tolerated and the PK/PD, no surprises there. So, looking good.

我們特別在頭部和頸部數據中看到，我認為您可以從幻燈片28 上的蜘蛛圖看出，我們在紅色中獲得了更快速的疾病控制，這是比藍色更密集的治療方案。有趣的是，藍色患者的暴露時間確實更長，因為我們首先對這些患者進行了治療。病人還不少。有兩例患者已經接受了許多週的治療，一名患者已經接受了 35 週的治療，另一名患者已經接受了 45 週的研究。因此，我認為這兩種治療方案的耐受性都很好，而且 PK/PD 也沒有什麼意外。所以，看起來不錯。

That’s helpful. Thanks for taking my questions.

這很有幫助。感謝您回答我的問題。

Arthur He, H.C. Wainwright.

何亞瑟，H.C.溫賴特。

Hey, Jay and team. Good afternoon. Thanks for taking my question and congrats on the data in the head and neck. I just had a couple of questions for the head and neck data. So first -- so I record you mentioned you want to go for a first line for these ROR2 ADC. First, I just want to get gauging your priority here for the future or still depending on the discussion with the FDA in the second half.

嘿，傑伊和團隊。午安.感謝您提出我的問題，並對頭部和頸部的數據表示祝賀。我只是對頭部和頸部數據有幾個問題。首先，我記錄下您提到的您想要為這些 ROR2 ADC 選擇第一行。首先，我只是想衡量你未來的優先事項，還是仍然取決於下半年與 FDA 的討論。

Thank you, Arthur. I appreciate it. We haven’t made a formal decision about whether we’re going to target first or second or both yet. Our vision is that we’d like to go to the agency and discuss trial designs for both. For the first line, I think that the auristatin based ADCs park pair remarkably well with PD-1 blockade. And so I think it’d be really an excellent combination with PD-1 antibody in the first line patients that received just the PD-1 antibody alone. And then we could, of course, do a Phase 1 evaluation in combination with platinum PD-1 to further enable that.

謝謝你，亞瑟。我很感激。我們還沒有就是否要瞄準第一目標、第二目標或兩者兼而有之做出正式決定。我們的願景是，我們願意前往該機構討論兩者的試驗設計。對於第一條線，我認為基於 auristatin 的 ADC 與 PD-1 阻斷效果非常好。因此，我認為對於僅接受 PD-1 抗體治療的第一線患者來說，這確實是與 PD-1 抗體的絕佳組合。當然，我們可以結合鉑金 PD-1 進行第一階段評估，以進一步實現這一目標。

Moving to second and beyond. Second and beyond line, there’s an enormous unmet need, and we see a relatively straightforward trial design where we would compare either against cetuximab monotherapy or potentially a limited number of chemotherapy or cetuximab choices for the investigator with a PFS endpoint that might possibly enable an early review of the trial data and accelerated approval, and then with an OS endpoint that would confirm in the same trial. So these are the possibilities that we are looking forward to exploring with the agency.

進入第二名以上。其次，還有一個巨大的未滿足的需求，我們看到了一個相對簡單的試驗設計，我們將與西妥昔單抗單藥療法或潛在的有限數量的化療或西妥昔單抗選擇進行比較，為研究者提供可能的PFS 終點能夠儘早審查試驗數據並加速批准，然後使用將在同一試驗中確認的 OS 終點。因此，我們期待與該機構一起探索這些可能性。

Thanks, Eric. Very helpful. And regarding the data, it seems like the 2Q3W has a better response compared to the Q2W. And I’m just curious, have you looking into the HPV expression marker in these patients, is there any correlation regarding the response rate with the HPV expression there?

謝謝，埃里克。很有幫助。從數據來看，2Q3W 的反應似乎比 Q2W 更好。我只是好奇，您是否研究過這些患者的 HPV 表達標記物，反應率與那裡的 HPV 表達有任何相關性嗎？

Yes, it’s a great question, Arthur. We have not seen a correlation with HPV expression. It’s something that we’re going to continue to look at very closely. Those patients receive therapy that’s a little bit different. There’s some recent data suggesting they can deescalate the aggressive early therapy. And so we’ve been guided by our investigators to think of them as a little bit different than the HPV negative population. But right now, not seeing any obvious correlations. And I’ll just add that we’re also not seeing obvious correlations with the ROR2 expression, because that’s often a question that people ask us, and so we’re not needing a companion diagnostic at this time.

是的，這是一個很好的問題，亞瑟。我們尚未發現與 HPV 表現的相關性。我們將繼續密切關注這一問題。這些患者接受的治療略有不同。最近的一些數據表明，它們可以減弱積極的早期治療。因此，我們在研究人員的指導下認為他們與 HPV 陰性族群略有不同。但目前，沒有看到任何明顯的相關性。我想補充一點，我們也沒有看到與 ROR2 表達的明顯相關性，因為人們經常問我們這個問題，所以我們目前不需要伴隨診斷。

Got you. If I may, for the CTLA4 program for the upcoming data for the monotherapy this quarter, could you give us a little bit more color on the cancer type for those 20 patients as well as of now, what’s the medium cycle number as patient received the drug?

明白你了。如果可以的話，對於本季度即將發布的單一療法數據的 CTLA4 計劃，您能否為我們提供有關這 20 名患者以及現在的癌症類型的更多信息，中間週期數是多少患者收到藥物了嗎？

Okay. So moving to the conditionally binding CTLA-4 and you’re asking about the monotherapy. We open the doors very wide to melanomas and relapsed, refractory carcinomas. So I would anticipate a very broad number of different one single patients with different unusual cancer diagnoses that sometimes weren’t eligible for other clinical trials that were participating in the monotherapy experience.

好的。因此，轉向有條件結合的 CTLA-4，您會詢問單一療法。我們對黑色素瘤和復發難治性癌症敞開大門。因此，我預計會有大量不同的單一患者患有不同的異常癌症診斷，這些患者有時不符合參與單一療法經驗的其他臨床試驗的資格。

Our overall goal with the monotherapy was to clearly characterize the safety profile at both 300 and 700 milligrams. And I’m also happy to say that today we treated the third patient at the 1-gram dosing level. So we’ve now infused all three of the individuals at the very high dose level of 1-gram, which is 14.2 milligrams per kilogram based on a 70-kilo adult. So we’re looking forward to the ASCO presentation on June 1st and then a subsequent presentation to describe the outcome of these monotherapy patients that you’ve just asked about.

我們單一療法的總體目標是清楚描述 300 毫克和 700 毫克的安全性特徵。我還很高興地說，今天我們以 1 克劑量水平治療了第三位患者。因此，我們現在為所有三個人注射了 1 克的極高劑量水平，以 70 公斤重的成年人計算，即每公斤 14.2 毫克。因此，我們期待 6 月 1 日的 ASCO 演示，以及隨後的演示，以描述您剛才詢問的這些單一療法患者的結果。

Great. Thanks, Eric. Thanks for taking my question.

偉大的。謝謝，埃里克。感謝您提出我的問題。

Tony Butler, EF Hutton.

東尼·巴特勒，EF·赫頓。

Yes. Thanks very much. I’d like to go back to the previous question, if I may, and part a, again, this is with CTLA-4. Will there be or do you anticipate, I assume you will that the combination with pembro at 1-gram will have been sufficiently -- have sufficient duration before you make a decision about moving forward. In the BRAF mutated melanoma study that’s part one.

是的。非常感謝。如果可以的話，我想回到上一個問題，a 部分，再一次，這是關於 CTLA-4 的。是否會有或您是否預期，我假設您會認為與 1 克的 pembro 的組合將已經足夠 - 在您做出繼續前進的決定之前有足夠的持續時間。這是 BRAF 突變黑色素瘤研究的第一部分。

And part two of that is apparently from the comparator arm, you’re making some judgments that there may be other types of agents that could be utilized other than pembro. And I’m just curious, does this end up simply being physicians' choice and frontline? And then I have one more follow up, if I may? Thank you.

其中第二部分顯然來自比較器臂，您正在做出一些判斷，除了 pembro 之外，可能還有其他類型的代理可以使用。我只是好奇，這最終只是醫生的選擇和前線嗎？然後我再跟進一次，可以嗎？謝謝。

So why don’t I take these in sequence? The very first question you asked is, will we have sufficient follow up? And we believe we will. So I want to affirm that we are currently dosing patients with newly diagnosed melanoma, metastatic or unresectable melanoma, and presently, without regard to BRAF mutation, it to gain additional experience at this dose level. So these are first line patients. I just want to emphasize that, because that is then going to then lead into the proposed pivotal trial.

那我為什麼不按順序考慮這些呢？您問的第一個問題是，我們會有足夠的後續行動嗎？我們相信我們會的。因此，我想確認的是，我們目前正在對新診斷的黑色素瘤、轉移性或不可切除的黑色素瘤患者進行給藥，目前，不考慮BRAF 突變，這是為了在該劑量水平上獲得更多經驗。所以這些都是第一線患者。我只是想強調這一點，因為這將導致擬議的關鍵試驗。

Your second question is a really interesting one, and I think that agency feedback will be necessary here. I want to remind everyone that there are four strategies that could be employed for newly diagnosed metastatic or unresectable melanoma, and they include nivolumab, pembrolizumab both of those as monotherapy, opdualag or the combination of nivolumab plus ipilimumab.

你的第二個問題非常有趣，我認為機構的回饋在這裡是必要的。我想提醒大家，有四種策略可用於新診斷的轉移性或不可切除的黑色素瘤，其中包括納武單抗、派姆單抗（均為單一療法）、opdualag 或納武單抗加伊匹單抗的組合。

And so vision presently is that we’d like to run a blinded, randomized study against pembrolizumab because it represents a currently labeled opportunity. And it’s notable that several other sponsors are using pembrolizumab monotherapy as the comparator arm in their frontline melanoma trials.

因此，目前我們的願景是針對派姆單抗進行一項盲法隨機研究，因為它代表了目前已標記的機會。值得注意的是，其他幾位申辦者正在其一線黑色素瘤試驗中使用派姆單抗單一療法作為比較組。

Eric, thank you for the follow-up or the commentary.

埃里克，感謝您的跟進或評論。

My follow-up question is on the Nectin-4 ADC with the carbohydrate linker. Just mechanistically, does the carbohydrate linker limit the number of the payload that you can actually add to the antibody? And if you say no, that’s fine. But the question is, what is the DAR today? Is that the most optimal payload for the Nectin-4 ADC? Thanks very much.

我的後續問題是關於帶有碳水化合物連接器的 Nectin-4 ADC。從機制上講，碳水化合物連接體是否限制了您實際可以添加到抗體中的有效負載的數量？如果您說不，也沒關係。但問題是，今天的 DAR 是什麼？這是 Nectin-4 ADC 的最佳有效負載嗎？非常感謝。

I’ll take that one, Tony. Basically, the actual design of our carbohydrate linker system allows us to increase above the DAR 4. So actually that current Nectin-4 ADC is DAR 6. And we’ve seen very good safety profile. We think it’s going to add to the safety profile because if it’s going to help us to reduce off target talks. In addition, it’s also a cab, so further reduces on target talks. So we’re really bringing these two pieces together and in a very specific way because Nectin-4 the marketed compound is known to have various toxicities, and one of those is significant is a rash.

我要那個，東尼。基本上，我們的碳水化合物連接系統的實際設計使我們能夠提高 DAR 4 以上。所以實際上目前的 Nectin-4 ADC 是 DAR 6。我們已經看到了非常好的安全狀況。我們認為這將增加安全性，因為如果它能幫助我們減少偏離目標的對話。此外，它也是一輛計程車，因此進一步減少了目標對話。因此，我們確實以一種非常具體的方式將這兩部分結合在一起，因為已知市售化合物 Nectin-4 具有多種毒性，其中最重要的毒性之一是皮疹。

And so we, at least from the animal data and for modeling, suggest that we have a therapeutic index that should allow us to be able to reduce, if not totally eliminate the rash, and we’ll just have to see the data further. We’re kind of -- we’re excited about this drug because we’ve also noticed that we’ve been enabled -- had the ability to enable additional targets not traditionally associated with Nectin-4 activity, and one of those is pancreatic cancer.

因此，至少從動物數據和建模角度來看，我們建議我們有一個治療指數，該指數應該使我們能夠減少（如果不能完全消除）皮疹，並且我們只需要進一步查看數據。我們對這種藥物感到興奮，因為我們也注意到我們已經能夠實現傳統上與 Nectin-4 活性無關的其他目標，並且其中一個包括胰腺癌。

And we do know that this observation is linked in part to our carbohydrate linker and the cab and carbohydrate linker working together. However, in saying all of this, I want to emphasize that there’s no way, I think, is saying that the carbohydrate linker is better than what we’ve seen at the peptide linker and AXL and ROR2 because we had a very specific toxicity to resolve Nectin-4. We are seeing very safe profile without those kind of toxicities with our AXL and ROR2 drugs.

我們確實知道這一觀察結果部分與我們的碳水化合物連接體以及出租車和碳水化合物連接體一起工作有關。然而，在說這一切時，我想強調的是，我認為，不可能說碳水化合物連接體比我們在勝肽連接體以及 AXL 和 ROR2 中看到的更好，因為我們有具有非常特異性的毒性來分解Nectin-4。我們發現我們的 AXL 和 ROR2 藥物非常安全，沒有此類毒性。

So I think, in a way we came in to this program with a very specific purpose to address a very clearly defined toxicity. And so in combination you have a chance here to go into an indication with a very low bar with safety that could potentially allow this drug to go quite wide. And I’ll just add, I think one nice thing about it is that you should get these results very quickly because there’s a known level of dosing. And so with Phase 1, you should learn both your safety and your efficacy adequate to really validate this compound, so an exciting asset.

所以我認為，在某種程度上，我們進入這個計畫是有一個非常具體的目的，就是為了解決一個非常明確定義的毒性。因此，結合起來，您有機會進入一個安全標準非常低的適應症，這可能會讓這種藥物的應用範圍相當廣泛。我想補充一點，我認為它的一個好處是您應該很快就能得到這些結果，因為劑量水平是已知的。因此，在第一階段，您應該充分了解您的安全性和功效，以真正驗證這種化合物，這是一項令人興奮的資產。

Jay, it’s fantastic. Thanks very much.

傑伊，太棒了。非常感謝。

Thank you. There are no further questions at this time. I’d like to hand the floor back over to Jay Short, CEO, for closing comments.

謝謝。目前沒有其他問題。我想將發言權交還給執行長傑伊·肖特 (Jay Short)，讓其發表結束評論。

Thank you everyone for your attendance today and continued interest in BioAtla. We’re obviously very encouraged by our data and very hopeful and a lot of drugs that I think are on the precipice of being able to bring to market. So hopefully it continues. And thank you for your attention.

感謝大家今天的出席以及對 BioAtla 的持續關注。我們顯然對我們的數據感到非常鼓舞，並且充滿希望，我認為許多藥物即將推向市場。所以希望它能繼續下去。感謝您的關注。

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。