Innate Pharma SA (IPHA) 2023 Q4 法說會逐字稿

(audio in progress) year 2023 financial results and business update call. Today's conference is being recorded, and all lines have been placed on mute to prevent any background noise. (Operator Instructions)

（音訊正在進行中）2023 年財務業績和業務更新電話會議。今天的會議正在錄製中，所有線路均已靜音，以防止任何背景噪音。（操作員說明）

Thank you, and I will now turn the conference over to Henry Wheeler, Vice President of Investor Relations. Mr. Wheeler, you may begin.

謝謝大家，我現在將會議交給投資人關係副總裁亨利‧惠勒 (Henry Wheeler)。惠勒先生，您可以開始了。

Thank you. Good morning, good afternoon, and welcome, everyone. This morning, Innate issued a press release for our full year 2023 financial results and business update. We look forward to highlighting the progress made during the year to date as well as addressing future goals and milestones. The press release and today's presentation are both available on the IR section of our website.

謝謝。早安，下午好，歡迎大家。今天上午，Innate 發布了 2023 年全年財務業績和業務更新的新聞稿。我們期待強調今年迄今取得的進展，並解決未來的目標和里程碑。新聞稿和今天的簡報均可在我們網站的投資者關係部分取得。

On slide 2, before we start, I'd like to remind you that we'll be making forward-looking statements regarding our financial outlook in addition to regulatory and product plan development. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted.

在投影片 2 上，在我們開始之前，我想提醒您，除了監管和產品計劃制定之外，我們還將就我們的財務前景做出前瞻性聲明。這些陳述存在風險和不確定性，可能導致實際結果與預測不同。

On slide 3, on today's call, we will be joined by Herve Brailly, our Interim Chief Executive Officer. Then we will hand over to Sonia Quaratino, our Chief Medical Officer, who will cover updates on lacutamab and IPH65.

在幻燈片 3 上，我們的臨時執行長 Herve Brailly 將參加今天的電話會議。然後我們將交給我們的首席醫療官 Sonia Quaratino，她將介紹 lacutamab 和 IPH65 的最新情況。

We will then hand to Yannis Morel, Chief Operating Officer, who will then discuss ANKET and ADC platform updates. Frederic Lombard, our CFO, will cover the financials. And we're very pleased to welcome Arvind Sood, EVP, US Operations, who will wrap up and close.

然後我們將交給營運長 Yannis Morel，他將討論 ANKET 和 ADC 平台的更新。我們的財務長 Frederic Lombard 將負責財務事宜。我們非常高興地歡迎美國營運部執行副總裁 Arvind Sood，他將結束演講。

Hervé, I now hand the call over to you.

Herve，我現在把電話交給你。

Thanks, Henry. Good morning, and good afternoon, everyone. I just like first to recall that Innate Pharma is a very important player on the field of NK cell pharmacology and innate immunity or manipulation. We address that through different mechanisms of actions where we have corresponding products.

謝謝，亨利。大家早安，下午好。我想先回顧一下 Innate Pharma 是 NK 細胞藥理學和先天免疫或操作領域非常重要的參與者。我們透過不同的行動機制來解決這個問題，並提供相應的產品。

It's, first, about engaging NK cells as cytotoxic effectors to tumor cells. And that's the approach that we implement with the ANKET platform, but also with the cytotoxic antibody, lacutamab.

首先，NK 細胞作為腫瘤細胞的細胞毒性效應器。這就是我們透過 ANKET 平台以及細胞毒性抗體 lacutamab 實施的方法。

We've also been pioneering the field of checkpoint inhibitors of NK cells with monalizumab, which is a checkpoint which is shared -- which is targeting the checkpoint which is shared by different classes of effector cells, both NK and T cells; and eventually, through addressing suppression of the cytotoxic immune response through IPH62 and 63, which addresses the adenosine pathway.

我們也利用莫那珠單抗（monalizumab）開創了NK 細胞檢查點抑制劑領域，這是一個共享的檢查點——它的目標是不同類別的效應細胞（NK 細胞和T 細胞）共享的檢查點；最終，透過 IPH62 和 63 解決細胞毒性免疫反應的抑制問題，從而解決腺苷途徑。

So that's it. What is the Innate Pharma strategy? Well, firstly, it's about creating near-term value. That's what we want to achieve with our most advanced proprietary asset, lacutamab, which is in development in T cell lymphoma.

就是這樣了。Innate Pharma 的策略是什麼？嗯，首先，它是為了創造短期價值。這就是我們希望透過我們最先進的專有資產 lacutamab 實現的目標，該資產正在 T 細胞淋巴瘤的開發中。

And actually, final CTCL and early PTCL data have been released by the end of '23 at ASH. And here, we do look forward to the next step, which will be the data on mycosis fungoides. And that will inform the future of this program for the late-stage development.

事實上，最終的 CTCL 和早期的 PTCL 數據已於 23 年底在 ASH 上發布。在這裡，我們確實期待下一步，即蕈樣肉芽腫的數據。這將為該項目的後期開發的未來提供資訊。

Second, we continue to fuel our innovative portfolio with both ANKET and antibody drug conjugates. ANKET is really a core asset. It's a platform which generated several molecules. And as you know, the first molecule in clinic has been advanced by our partner Sanofi, who published in '23 important first clinical data. We'll come back to that, of course, in greater details for the SAR443579.

其次，我們繼續透過 ANKET 和抗體藥物偶聯物來推動我們的創新產品組合。ANKET確實是一項核心資產。這是一個產生多個分子的平台。如你所知，臨床上的第一個分子是由我們的合作夥伴賽諾菲推進的，他在 '23 發表了重要的第一個臨床數據。當然，我們稍後會詳細討論 SAR443579。

But the ANKET portfolio is now expanding with other assets that have been further licensed in by Sanofi, but also, with the proprietary program that we recently announced [is now]. And this is the second generation of ANKET, which has now been brought to clinic in Phase 1 in lymphoma.

但 ANKET 投資組合現在正在透過賽諾菲進一步許可的其他資產進行擴展，而且還透過我們最近宣布的專有計劃進行擴展[就是現在]。這是第二代ANKET，目前已進入淋巴瘤治療一期臨床。

And beyond ANKET, we also advanced a second class of agents which are active as a single agent, potentially in tumor, with antibody drug conjugates, the first one being brought to -- we work on bringing it to IND in '24.

除了ANKET 之外，我們還開發了第二類藥物，它們作為單一藥物具有活性，可能與抗體藥物綴合物一起作用於腫瘤，第一個藥物被帶到- 我們致力於在24 年將其帶到IND。

Eventually, and this is through partnership, we have monalizumab, the checkpoint inhibitor in Phase 3. And AstraZeneca is pursuing this late-stage asset which will deliver in the next year's very important data.

最終，透過合作，我們獲得了 monalizumab，即處於第三階段的檢查點抑制劑。阿斯特捷利康正在追求這一後期資產，它將在明年提供非常重要的數據。

So that translates into the portfolio which is a combination of proprietary product and the partnered asset. I will now leave it to Sonia to detail the clinical stages and the clinical progress with those assets, especially and firstly, with lacutamab. Sonia?

因此，這轉化為專有產品和合作資產的組合的投資組合。現在，我將讓索妮亞詳細介紹這些資產的臨床階段和臨床進展，尤其是首先是 lacutamab。索尼婭？

Thank you very much, Herve. When we look at slide 7, I would like to summarize the progress we are making with lacutamab. And here in this space, we are pursuing a fast-to-market strategy for lacutamab in the niche setting of Sézary syndrome, where lacutamab was granted the US fast track designation and EU PRIME designation back in 2020.

非常感謝你，埃爾維。當我們看幻燈片 7 時，我想總結我們在 lacutamab 方面取得的進展。在這個領域，我們正在為 Sézary 綜合徵這一利基環境中的 lacutamab 尋求快速上市策略，lacutamab 早在 2020 年就獲得了美國快速通道指定和歐盟 PRIME 指定。

We have then expanded post Sézary syndrome to mycosis fungoides, where we have seen encouraging preliminary data from the Phase 2 TELLOMAK trial in patients that have a KIR3DL2 expression level above as well as below the threshold of 1%. And we expect to present this data to an upcoming conference later this year. Now the data in MF together with the data in SS will be shared with regulators to align on a path forward to maximize the value of lacutamab in CTCL, building on the existing fast track and orphan designation.

然後，我們將塞扎里綜合徵擴展到蕈樣肉芽腫，我們在 2 期 TELLOMAK 試驗中看到了令人鼓舞的初步數據，這些患者的 KIR3DL2 表達水平高於或低於 1% 的閾值。我們預計將在今年稍後召開的會議上展示這些數據。現在，MF 中的數據以及 SS 中的數據將與監管機構共享，以在現有的快速通道和孤兒藥指定的基礎上，在 CTCL 中最大化 lacutamab 的價值。

Now if we move to the PTCL space, today, we have announced that we are not going to reopen the recruitment of the Phase 1 testing lacutamab in monotherapy in PTCL, as the number of observed objective responses did not meet the pre-specified threshold for activity with lacutamab as a single agent.

現在，如果我們轉向 PTCL 領域，今天，我們宣布，我們不會重新招募 PTCL 單一療法中的 1 期測試 lacutamab，因為觀察到的客觀反應數量未達到預先指定的閾值。

However, based on the data presented at ASH last year, demonstrating the synergism between lacutamab and chemotherapy in preclinical models of PTCL, we remain committed to the development on PTCL and continue to enroll patients in the Phase 2 combination trial with chemotherapy, gemcitabine and oxaliplatin, where we believe the combination can offer additional benefit to patients.

然而，基於去年ASH 上公佈的數據，證明了lacutamab 和化療在PTCL 臨床前模型中的協同作用，我們仍然致力於PTCL 的開發，並繼續招募患者參加化療、吉西他濱和奧沙利鉑的2 期聯合試驗，我們相信這種組合可以為患者帶來額外的好處。

On the next slide, slide 8, we have a summary on the final Phase 2 data in Sézary that were presented at ASH last December in an oral presentation. This is a heavily pretreated post-mogamulizumab patient pool, with at least five median prior systemic line of therapies, including moga. And the global overall response rate was an encouraging 37.5%.

在下一張投影片（投影片 8）中，我們總結了 Sézary 的最終第 2 階段數據，這些數據是去年 12 月在 ASH 上以口頭簡報形式提出的。這是一個經過大量預處理的 mogamulizumab 後患者庫，其中至少有 5 種既往系統療法（包括 moga）。全球整體回覆率為令人鼓舞的 37.5%。

I would like to note the deepness of the partial responses, as you can see on the waterfall plot on the slide. We have also reported in this patient population an overall response rate of 46.4% in the skin and 48.2% in the blood; and overall, a clinical benefit rate of 87.5% and a median PFS of eight months, with a durability of response of 12.3 months. A favorable safety profile was also observed. And we look forward to sharing this data set along with the final data in mycosis fungoides cohort with the regulator later on.

我想指出部分響應的深度，正如您在幻燈片的瀑布圖上看到的那樣。我們也報告稱，在該患者群體中，皮膚總體緩解率為 46.4%，血液總體緩解率為 48.2%；整體而言，臨床受益率為 87.5%，中位 PFS 為 8 個月，緩解持續時間為 12.3 個月。也觀察到良好的安全性。我們期待稍後與監管機構分享該數據集以及蕈樣肉芽腫隊列的最終數據。

Now on slide 9, we can switch gear to our most advanced proprietary ANKET, which includes a detuned variant IL-2 to include activation and proliferation of NK cells in the tumor microenvironment. We were pleased to announce earlier this month that IPH65, the first of the second-generation aggregates which target CD20, has entered the clinic.

現在在幻燈片 9 上，我們可以切換到我們最先進的專有 ANKET，其中包括失諧變異體 IL-2，以包括腫瘤微環境中 NK 細胞的活化和增殖。我們很高興地在本月稍早宣布，第一個針對 CD20 的第二代聚合體 IPH65 已進入臨床。

And the first-in-human has started with the first patient being dosed in March. The trial will enroll patients with relapsed/refractory non-Hodgkin's lymphoma. And we will run in the US, Australia, and France.

首例人體試驗已從三月第一位患者接受給藥開始。該試驗將招募患有復發/難治性非何杰金氏淋巴瘤的患者。我們將在美國、澳洲和法國運行。

In B cell non-Hodgkin's lymphoma, compared to recent therapies including CAR-T and T cell engagers, IPH65 has a disruptive mechanism of action that eliminates cancer cell via profound activation and proliferation of the NK cells. And IPH65 differs from allogeneic NK therapies including CAR-NK, as it is an off-the-shelf therapy that drives the proliferation of the patient's own NK cells in non-Hodgkin's lymphoma and does not require any lymphodepletion as for other cell therapies.

在 B 細胞非何杰金氏淋巴瘤中，與包括 CAR-T 和 T 細胞接合劑在內的最新療法相比，IPH65 具有破壞性作用機制，可透過 NK 細胞的深度活化和增殖來消除癌細胞。IPH65 與包括CAR-NK 在內的同種異體NK 療法不同，因為它是一種現成療法，可以驅動非何杰金氏淋巴瘤患者自身NK 細胞的增殖，並且不需要像其他細胞療法那樣進行任何淋巴細胞清除。

Now, the IPH65 format also addresses the common challenges associated with the loss of CD16 by ensuring activation of intratumoral NK cells via the activation of NKp46. Finally, by stimulating the NK cell natural function, IPH65 has bystander effect that can cause the elimination of CD20-negative tumor cells, overcoming tumor heterogeneity or loss of tumor antigen.

現在，IPH65 格式還透過激活 NKp46 確保腫瘤內 NK 細胞的激活，解決了與 CD16 缺失相關的常見挑戰。最後，透過刺激NK細胞的天然功能，IPH65具有旁觀者效應，可導致CD20陰性腫瘤細胞的消除，克服腫瘤異質性或腫瘤抗原的流失。

Now I will turn to Yannis.

現在我要談談雅尼斯。

Thank you, Sonia. On slide 10, I wanted to highlight our proprietary first-in-class NK cell engager platform that we call ANKET. ANKET is a versatile technology made of antibody-derived building blocks, that is creating an entirely new class of multi-specific engagers to induce synthetic immunity against cancer.

謝謝你，索妮亞。在幻燈片 10 上，我想重點介紹我們專有的一流 NK 細胞接合平台，我們稱之為 ANKET。ANKET 是一種由抗體衍生構件組成的多功能技術，它正在創建一種全新的多特異性接合劑，以誘導針對癌症的合成免疫。

Leveraging our scientific expertise in the NK cell space, this platform is an engine for producing series of drug candidates addressing multiple tumor targets, both [inflamed] and solid tumors. The activating NK cell receptor called NKp46 is the backbone of our technology. And since it has a stable expression at the NK cell surface, even in the tumor microenvironment, it induces an optimal activation of the NK effector functions.

利用我們在 NK 細胞領域的科學專業知識，該平台是生產一系列針對多個腫瘤標靶（發炎）和實體瘤的候選藥物的引擎。稱為 NKp46 的活化 NK 細胞受體是我們技術的支柱。由於它在 NK 細胞表面穩定表達，即使在腫瘤微環境中，它也能誘導 NK 效應器功能的最佳活化。

We have also developed a second-generation version of the technology by incorporating a variant of interleukin-2 in order to induce NK cell proliferation. As you can see, our pipeline of ANKET molecule is significantly growing, with Sanofi having now licensed four molecules. Two are in the clinic, [inflamed], and two are at technical stage in solid tumor, including IPH67, which is the program for which Sanofi opted in December last year.

我們也開發了該技術的第二代版本，透過整合白介素-2 的變異來誘導 NK 細胞增殖。正如您所看到的，我們的 ANKET 分子管道正在顯著增長，賽諾菲現在已獲得四種分子的許可。兩個在診所，[發炎]，兩個在實體瘤方面處於技術階段，其中包括 IPH67，這是賽諾菲去年 12 月選擇的項目。

We are also very pleased to see our proprietary portfolio of ANKET progressing. The second-generation ANKET, IPH6501, is now in the clinic. And we continue to fuel our pipeline with new preclinical program against multiple targets.

我們也很高興看到我們專有的 ANKET 產品組合取得進展。第二代ANKET IPH6501現已進入臨床。我們繼續針對多個目標透過新的臨床前計劃來推動我們的研發進程。

On slide 11, you can see an overview of the clinical data presented by Sanofi last year at ASH for the ANKET IPH6101, also named SAR'579. In this dose escalation, we were encouraged to see initial preliminary single-agent activity and safety of SAR'579 in relapsed/recurrent AML patients.

在幻燈片 11 上，您可以看到賽諾菲去年在 ASH 上展示的 ANKET IPH6101（也稱為 SAR'579）臨床數據的概述。在這次劑量遞增中，我們很高興看到 SAR'579 在復發/復發 AML 患者中的初步單藥活性和安全性。

At the 1mg/kg dose, five complete responses were observed out of 15 patients, with three responders remaining in remission at data cutoff at over 7, 12, and 14 months of treatment. SAR'579 was well tolerated up to 6 mg/kg, with no dose-limiting toxicity observed and two grade 1 CRS observed out of 43 patients. The FDA awarded SAR'579 a fast track designation in May. And we look forward to seeing further updates from Sanofi in due course.

在 1mg/kg 劑量下，15 名患者中觀察到 5 名完全緩解，其中 3 名緩解者在治療超過 7、12 和 14 個月的數據截止時仍處於緩解狀態。SAR'579 在高達 6 mg/kg 的劑量下耐受性良好，未觀察到劑量限制性毒性，並且在 43 名患者中觀察到 2 例 1 級 CRS。FDA 於 5 月授予 SAR'579 快速通道資格。我們期待在適當的時候看到賽諾菲的進一步更新。

On slide 12, you can see a summary of our Sanofi alliance. In 2016, we signed an initial agreement for two ANKET molecules worth up to EUR400 million in milestone plus royalty, among which we announced EUR16 million to date. Both programs, SAR'579 and SAR'14, have progressed into Phase 1 clinical trials.

在幻燈片 12 上，您可以看到我們的賽諾菲聯盟的摘要。2016年，我們簽署了兩個ANKET分子的初步協議，價值​​高達4億歐元的里程碑加特許權使用費，其中我們迄今為止宣布了1600萬歐元。SAR'579 和 SAR'14 兩個項目都已進入一期臨床試驗。

In December '22, we signed a second agreement whereby Sanofi licensed the IPH62 ANKET program, targeting B7H3, a solid tumor target, and again, optioned for two other targets. In December last year, they opted in for one of these programs called IPH67, targeting an undisclosed tumor target in solid tumors, triggering a EUR15 million milestone and making EUR40 million, the total of payment received from the second agreement. Altogether, considering these two agreements, we are eligible for a total milestone package of up to EUR1.75 billion plus royalties.

22 年 12 月，我們簽署了第二份協議，賽諾菲授權 IPH62 ANKET 項目，針對實體瘤靶點 B7H3，並再次選擇其他兩個標靶。去年 12 月，他們選擇了其中一個名為 IPH67 的項目，針對實體瘤中未公開的腫瘤靶標，觸發了 1500 萬歐元的里程碑，並從第二項協議中收到的付款總額達到 4000 萬歐元。總而言之，考慮到這兩項協議，我們有資格獲得總計高達 17.5 億歐元的里程碑包以及特許權使用費。

Slide 13 highlights our growing antibody drug conjugate pipeline. As we continue to develop next-generation therapeutics having single-agent activity, utilizing our antibody-engineering platform, we find that for some tumor targets, we can generate antibodies with good internalizing property that, therefore, are well suited for ADC development. Our agreement with Takeda in the field provides a validation to this research approach and highlights our capability to generate differentiated ADC candidates.

幻燈片 13 重點介紹了我們不斷發展的抗體藥物偶聯物管道。隨著我們利用我們的抗體工程平台繼續開發具有單藥活性的下一代療法，我們發現對於某些腫瘤靶點，我們可以產生具有良好內化特性的抗體，因此非常適合 ADC 開發。我們與武田 (Takeda) 在該領域達成的協議驗證了這一研究方法，並強調了我們產生差異化 ADC 候選藥物的能力。

I will now cover updates on our lead proprietary ADC program, IPH45, on the next slide. Slide 14 highlights IPH45, which is our proprietary Nectin-4-targeted ADC, with a topo I inhibitor payload. We managed to create a differentiated product through multiple components.

現在，我將在下一張投影片上介紹我們領先的專有 ADC 計畫 IPH45 的更新。幻燈片 14 重點介紹了 IPH45，這是我們專有的 Nectin-4 靶向 ADC，具有拓撲 I 抑制劑有效負載。我們成功地透過多個組件創建了差異化產品。

First, we generated proprietary antibody with a differentiated epitope, non-overlapping with enfortumab, the antibody backbone of PADCEV. Then we selected the validated cleavable linker designed to be hydrophilic in order to counterbalance the hydrophobicity of the payload and to allow for a high drug-antibody ratio.

首先，我們產生了具有差異化抗原決定位點的專有抗體，與 PADCEV 的抗體骨架 enfortumab 不重疊。然後，我們選擇了經過驗證的親水性可裂解接頭，以平衡有效負載的疏水性並實現高藥物抗體比。

Finally, we selected a well-validated topo I inhibitor with bystander effect, allowing to bypass MMAE-related resistance mechanism and to address tumors with heterogeneous Nectin-4 expression. Altogether, these elements result in a differentiated Nectin-4 ADC, showing strong efficacy in preclinical models, including in PADCEV [refractory] PDX, as well as encouraging PK tox profile in the non-human primates.

最後，我們選擇了一種經過充分驗證的具有旁觀者效應的拓撲 I 抑制劑，可以繞過 MMAE 相關的抗藥性機制並解決具有異質 Nectin-4 表達的腫瘤。總而言之，這些元素產生了差異化的Nectin-4 ADC，在臨床前模型（包括PADCEV [難治性] PDX）中顯示出強大的功效，並在非人靈長類動物中顯示出令人鼓舞的PK 毒性特徵。

These clinical data have been selected for presentation at an oral session at AACR in the coming couple of weeks. We are looking forward to presenting them and to filing the IND for this product this year.

這些臨床數據已被選中在未來幾週內在 AACR 的口頭會議上發表。我們期待今年推出這些產品並提交該產品的 IND 申請。

On slide 15, I would like to remind you of monalizumab, the anti-NKG2A checkpoint inhibitor that we have licensed to AstraZeneca for oncology. In this slide, you can see an overview of the late-stage development plan for monalizumab in lung cancer.

在投影片 15 上，我想提醒您莫納珠單抗，這是我們已授權給阿斯特捷利康用於腫瘤學的抗 NKG2A 檢查點抑制劑。在這張投影片中，您可以看到莫那珠單抗治療肺癌的後期開發計劃的概述。

Mona is currently being investigated in a Phase 3 trial called PACIFIC-9. AstraZeneca started this Phase 3, evaluating the combinations of either mona or oleclumab plus durvalumab in the unresectable Stage 3 non-small cell lung cancer setting, who have not progressed after concurrent chemoradiotherapy based on the results of their Phase 2 COAST trial.

Mona 目前正在一項名為 PACIFIC-9 的第三階段試驗中進行調查。阿斯特捷利康啟動了這項3 期臨床試驗，在不可切除的3 期非小細胞肺癌環境中評估mona 或oleclumab 加durvalumab 的組合，根據2 期COAST 試驗的結果，這些患者在同步放化療後尚未出現進展。

COAST data were published in the Journal of Clinical Oncology in '22. And after a median follow-up of 11.5 months, PFS data showed a hazard ratio of 0.42 in favor of mona with lacutamab combination versus durvalumab alone. The results also showed an increase in the primary endpoints of confirmed overall response for monalizumab and durvalumab combination over durvalumab alone of 76% versus 18%, respectively.

COAST 數據於 22 年發表在《臨床腫瘤學雜誌》。中位追蹤 11.5 個月後，PFS 數據顯示，與單獨使用 durvalumab 相比，mona 與 lacutamab 組合的風險比為 0.42。結果也顯示，與單獨使用 durvalumab 相比，monalizumab 和 durvalumab 組合的主要終點已確認整體緩解率分別提高了 76% 和 18%。

The AstraZeneca-sponsored NeoCOAST-2 study is also underway in an earlier setting of lung cancer, evaluating mona plus durvalumab with chemo in the neoadjuvant non-small cell lung cancer patients. Based on Phase 2 data from the NeoCOAST study, which showed also superiority of the mona-plus-durvalumab combination over durvalumab in this neoadjuvant setting.

阿斯特捷利康贊助的 NeoCOAST-2 研究也在早期肺癌治療中進行，評估莫納加 durvalumab 合併化療對新輔助非小細胞肺癌患者的療效。基於 NeoCOAST 研究的 2 期數據，該研究還表明，在這種新輔助治療中，mona 加 durvalumab 組合優於 durvalumab。

I will now turn to Frederic for the financials.

我現在請弗雷德里克了解財務狀況。

Thank you, Yannis. On slide 16, the key elements of Innate's financial position and financial results as of the year ended December 31, 2023, is as follows.

謝謝你，雅尼斯。在投影片 16 上，Innate 截至 2023 年 12 月 31 日止年度的財務狀況和財務表現的關鍵要素如下。

Cash, cash equivalent, short-term investment, and financial assets amount to EUR102.3 million as of the end of last year, including financial instruments amounting to EUR9.8 million. This number does not include the EUR15 million payment received from Sanofi in January '24.

截至去年底，現金、現金等價物、短期投資和金融資產總額為1.023億歐元，其中金融工具總額為980萬歐元。該數字不包括 2024 年 1 月從賽諾菲收到的 1500 萬歐元付款。

Revenue and other income from continuing operations amounted to EUR61.6 million in '23, which mainly comprises revenue from collaboration and licensing agreements received pursuant to the agreements with AstraZeneca, Sanofi, and Takeda, and EUR9.7 million in research tax credit.

2023 年持續經營業務的收入和其他收入達 6,160 萬歐元，主要包括根據與阿斯特捷利康、賽諾菲和武田簽訂的協議獲得的合作和許可協議收入，以及 970 萬歐元的研究稅收抵免。

Operating expenses from continuing operations amounted to EUR74.3 million in '23, with R&D now making up 75% of the OpEx. Research and development expenses from continuing activities amounted to EUR56 million in '23, up 8.4% from prior year. The increase in R&D mainly results from an increase in direct research and development expenses, both clinical and nonclinical.

2023 年持續營運的營運支出達 7,430 萬歐元，其中研發費用目前佔營運支出的 75%。2023 年持續活動的研發費用達 5,600 萬歐元，較上年增長 8.4%。研發費用的增加主要是由於臨床和非臨床直接研發費用的增加。

General and administrative expenses amounted to EUR18.3 million, down by 18.5% on prior year due to the decrease in personnel expenses, non-scientific advisory fees, and other expenses, mainly resulting from efficiency measures applied by the company. The table in the press release summarized the IFRS consolidated financial adjustments as of and for the year ended December 31, 2023, including 2022 comparative information.

一般及行政費用為 1,830 萬歐元，較前一年下降 18.5%，這是由於公司採取的效率措施導致人事費用、非科學諮詢費和其他費用減少。新聞稿中的表格總結了截至 2023 年 12 月 31 日止年度的《國際財務報告準則》綜合財務調整，包括 2022 年的比較資訊。

I will now hand over to Herve.

現在我將把工作交給埃爾維。

Thank you, Frederic. I won't go through all the catalysts that we have listed on slide 17, but I'll spend a few minutes on some of the key clinical catalysts that we have noted on this slide. And then we'll provide a summary before we turn to your questions.

謝謝你，弗雷德里克。我不會詳細介紹我們在投影片 17 上列出的所有催化劑，但我將花幾分鐘時間介紹我們在這張投影片上註意到的一些關鍵臨床催化劑。然後，在回答您的問題之前，我們將提供摘要。

We are expecting the final data for a proprietary antibody lacutamab in mycosis fungoides imminently. And we look forward to presenting this data in detail at an upcoming medical meeting. Concurrent with that, we'll also commence interactions with the global regulatory agencies as we map out the next steps in its development.

我們期待很快能獲得專有抗體 lacutamab 治療蕈樣肉芽腫的最終數據。我們期待在即將召開的醫學會議上詳細介紹這些數據。同時，我們也將開始與全球監管機構互動，制定下一步的發展計畫。

Our antibody therapeutic NK cell engager program that was earlier referred to as the ANKET program, this continues to evolve. This program has received broad validation through the licensing of four programs to Sanofi.

我們的抗體治療 NK 細胞接合器計劃之前稱為 ANKET 計劃，該計劃仍在不斷發展。透過向賽諾菲授予四個項目許可，該項目已得到廣泛驗證。

We have recently taken a proprietary program emanating from this ANKET platform into the clinic ourselves by dosing the very first patient. This program, known as IPH6501, is targeting CD20 in B-cell non-Hodgkin's lymphoma.

最近，我們將源自此 ANKET 平台的專有程序引入診所，對第一位患者進行給藥。此計畫稱為 IPH6501，針對 B 細胞非何杰金氏淋巴瘤中的 CD20。

For monalizumab, our antibody targeting NKG2A, the Phase 3 trial called PACIFIC-9 is underway. This is a study looking at monalizumab plus durvalumab in non-small cell lung cancer. The thinking here is that the dual targeting of the PD-L1 and the NKG2A pathways through this combination will lead to enhanced antitumor activity versus single-agent therapy.

對於我們針對 NKG2A 的抗體 monalizumab，名為 PACIFIC-9 的 3 期試驗正在進行中。這是一項研究 monalizumab 合併 durvalumab 治療非小細胞肺癌的研究。這裡的想法是，透過這種組合對 PD-L1 和 NKG2A 途徑的雙重靶向將導致與單藥治療相比增強的抗腫瘤活性。

We continue to advance other agents targeting the adenosine pathway in the clinic. An example is IPH5201, which is currently in Phase 2 in combination with durvalumab and chemotherapy in treatment-naive patients with resectable early-stage non-small cell lung cancer.

我們持續在臨床上推進其他針對腺苷途徑的藥物。一個例子是 IPH5201，目前處於第 2 期臨床階段，與 durvalumab 和化療聯合治療可切除的早期非小細胞肺癌的初治患者。

So just to conclude, over the years, we have established a strong expertise in immunopharmacology. With definitive Phase 2 data in hand, we are mapping out the regulatory next steps for lacutamab.

總而言之，多年來，我們在免疫藥理學方面建立了強大的專業知識。有了明確的 2 期數據，我們正在製定 lacutamab 的後續監管步驟。

Our proprietary NK cell engager platform, ANKET, has the potential of addressing both hematologic malignancies and solid tumors. We are pursuing ADCs with a focus on differentiation with IPH45. This is our ADC-targeting Nectin-4, being a key example of our approach.

我們專有的 NK 細胞接合平台 ANKET 具有治療血液惡性腫瘤和實體腫瘤的潛力。我們正在開發專注於 IPH45 差異化的 ADC。這是我們的 ADC 標靶 Nectin-4，是我們方法的關鍵範例。

And lastly, we continue to retain a strong cash position to fund our operations well through the end of 2025. We are excited about our prospects for the future. And before I close, I would also like to thank the many employees at Innate, who work very hard in developing therapies for the potential benefit of patients.

最後，我們繼續保持強勁的現金狀況，為我們的營運提供資金直至 2025 年底。我們對未來的前景感到興奮。在結束之前，我還要感謝 Innate 的許多員工，他們為了病人的潛在利益而努力開發治療方法。

With that, we can open it up for questions.

這樣，我們就可以打開它來提問了。

(Operator Instructions) Yigal Nochomovitz, Citi.

（操作員指令）Yigal Nochomovitz，花旗銀行。

This is Amin, on for Yigal. Thank you for taking our questions. We had a couple; first on the PTCL program that you are not planning to reopen the Phase 1 monotherapy trial. Can you walk us through your thought process there and give us more details on that? And what was the internal bar for efficacy there?

這是阿明，替補伊格爾。感謝您接受我們的提問。我們有一對；首先，關於 PTCL 計劃，您不打算重新啟動 1 期單一療法試驗。您能否向我們介紹您的思考過程並提供更多詳細資訊？那裡的有效性的內部標準是什麼？

And then on the second -- again, unlike lacutamab, where are you standing within the process of finding a partner for the commercialization and development of the program? Are you expecting the upcoming data for MF to capitalize the partnership there?

然後，第二個問題——與 lacutamab 不同，您在尋找該專案商業化和開發合作夥伴的過程中處於什麼位置？您是否期待 MF 即將發布的數據能夠充分利用那裡的合作夥伴關係？

Right. Let me say that we have -- in PTCL, we have enrolled 20 patients. And the data around safety from 10 patients were presented at ASH last year. But per protocol, we have included a formal, let's say, interim analysis, where we define a minimum number of objective responses that needed to be observed prior to continuing the recruitment.

正確的。我想說的是，我們在 PTCL 招募了 20 位患者。去年 ASH 上公佈了 10 名患者的安全資料。但根據協議，我們包括了正式的，比如說，中期分析，其中我們定義了在繼續招募之前需要觀察的最少數量的客觀反應。

And despite we observed some objective responses in PTCL with lacutamab in monotherapy, this number of objective responses did not meet the minimum number preset by the protocol. As you understand, in PTCL, there are many different therapeutic options and many already provide quite a robust number of objective responses, and therefore, our threshold was quite high too much.

儘管我們在單一療法中觀察到 PTCL 中 lacutamab 的一些客觀反應，但客觀反應的數量並未達到方案預設的最低數量。如您所知，在 PTCL 中，有許多不同的治療選擇，並且許多已經提供了相當多的客觀反應，因此，我們的閾值相當高。

We remain, however, committed to the PTCL through the Phase 2 study in combination with chemotherapy, where we expect to see some synergism between lacutamab and chemotherapy and therefore, provide some meaningful clinical benefit to patients.

然而，我們仍然致力於透過與化療相結合的 2 期研究來進行 PTCL，我們期望看到 lacutamab 和化療之間的一些協同作用，從而為患者提供一些有意義的臨床益處。

The second question was around the partners. Is that correct? Is it?

第二個問題是關於合作夥伴的。那是對的嗎？是嗎？

The second question was on partnership, yes.

第二個問題是關於夥伴關係，是的。

Partnership. And around the partnership for lacutamab, we are actively looking for different options to pursue the next stage with lacutamab in the CTCL, either via partnership or alternative options.

合夥。圍繞著 lacutamab 的合作夥伴關係，我們正在積極尋找不同的選擇，以透過合作夥伴關係或替代方案，在 CTCL 中推進 lacutamab 的下一階段。

Okay, got it. That makes sense. And just one quick follow-up. Do you expect discontinuation of monotherapy to impact your plans on the partnership for this molecule?

好，知道了。這就說得通了。只需一個快速跟進。您預期單一療法的終止會影響您對該分子的合作計畫嗎？

Not really. I mean, the data on PTCL have no impact neither on the Phase 2 in PTCL in combination with chemo, but definitely not on the CTCL where we already have the data in-house.

並不真地。我的意思是，PTCL 的數據對 PTCL 聯合化療的第二階段沒有影響，但絕對不會對我們已經擁有內部數據的 CTCL 產生影響。

Okay, got it. Great. Thank you very much for taking our questions.

好，知道了。偉大的。非常感謝您接受我們的提問。

Daina Graybosch, Leerink Partners.

戴娜‧格雷博斯 (Daina Graybosch)，Leerink 合夥人。

Hi. I'm going to ask a follow-up on the one just asked on the single-agent activity. It's hard because we can't see it. And so is this, you had one response and you had a lot of shrinking -- stable disease? Or did you have three, and it just didn't meet your bar?

你好。我將詢問單一代理活動的後續問題。這很難，因為我們看不到它。這也是嗎，你有一種反應，但你有很多萎縮──穩定的疾病？或者您擁有三個，但它不符合您的標準？

And so I wonder if you could give us any more specific details, particularly because I think we'd like to -- what should make us confident, clinically, that this is going to prove out in GEMOX to be something more meaningful for patients and the unmet need compared to the therapeutic options here?

所以我想知道您是否可以給我們任何更具體的細節，特別是因為我認為我們希望——在臨床上，什麼能讓我們充滿信心，這將在GEMOX 中被證明對患者和患者來說更有意義與此處的治療方案相比，未被滿足的需求是什麼？

And this is the operator. I apologize. Did our presenters go on mute?

這就是操作員。我道歉。我們的主持人靜音了嗎？

All right. Ladies and gentlemen, please stand by. We are experiencing technical difficulties.

好的。女士們先生們，請稍候。我們遇到技術困難。

Ladies and gentlemen, I will put music back on while we wait for our speakers to reconnect. Thank you.

女士們先生們，當我們等待揚聲器重新連接時，我將重新播放音樂。謝謝。

Hello, Henry. This is Abby.

你好，亨利。這是艾比。

(inaudible - microphone inaccessible)

（聽不清楚 - 麥克風無法存取）

Okay, perfect. Give me just one moment. All right. And let me make a slide once again.

好的，完美。請給我一點時間。好的。讓我再製作一張投影片。

Ladies and gentlemen, thank you for your patience while we managed our technical difficulties. Ms. Graybosch, do you mind asking your question again, please?

女士們先生們，感謝您在我們解決技術難題時的耐心等待。Graybosch女士，您介意再問一次您的問題嗎？

(technical difficulty) question that came from Citi which is -- I wonder if you could give us any more details on the specific responses or any correlation with KIR3DL2 activity? What in the clinical data could we hang on to to be confident that we're going to see synergy in combination with chemotherapy next year?

（技術難度）花旗提出的問題是——我想知道您能否向我們提供有關具體反應或與 KIR3DL2 活動的任何相關性的更多詳細信息？我們可以依靠哪些臨床數據來確信明年我們將看到與化療結合的協同作用？

I suspect you are talking about the PTCL rather than the mycosis fungoides.

我懷疑你說的是 PTCL 而不是蕈樣肉芽腫。

Yes.

是的。

All right.

好的。

Yes.

是的。

Okay. Basically, in this study, we have recruited the patients to have an expression level of KIR3DL2 that is equal or above 1%. We did not, let's say, restricted to any subtype of PTCL. And we hope to present the data later on this year even if we are not going to reopen the study, and the sample size is relatively small because it's around 20 patients.

好的。基本上，在這項研究中，我們招募的患者的 KIR3DL2 表達量等於或高於 1%。可以說，我們並沒有限制 PTCL 的任何亞型。即使我們不打算重新進行這項研究，我們也希望在今年稍後公佈這些數據，而且樣本量相對較小，因為大約有 20 名患者。

So then what gives you confidence in the GEMOX combo will prove successful?

那麼，是什麼讓您對 GEMOX 組合將成功充滿信心呢？

This is an investigator-sponsored trial, and date of completion is predicted to be towards the end of 2025.

這是一項由研究者資助的試驗，預計完成日期為 2025 年底。

And yeah, but why do you think that this will be successful? Why continue with the IIIB?

是的，但是為什麼你認為這會成功呢？為什麼要繼續實施 IIIB？

Because at ASH last year, we have presented some data that demonstrate some synergism in preclinical model with lacutamab and chemotherapy.

因為在去年的 ASH 上，我們提供了一些數據，證明 lacutamab 和化療在臨床前模型中具有一定的協同作用。

Okay. Thank you for that.

好的。謝謝你。

So operator, I'll ask an offline question, and then maybe we can go back to the online questions. So I have an offline question from Justine Telliez at Kepler Cheuvreux.

那麼接線員，我會問一個線下問題，然後也許我們可以回到線上問題。我有一個來自 Kepler Cheuvreux 的 Justine Telliez 的線下問題。

On lacutamab, regarding the potential progress made with the regulatory authorities in Sézary syndrome, can you give us an update? And also, at what point are you regarding desired partner, which I think you covered already? So regulatory interactions.

關於 lacutamab，關於監管機構在 Sézary 症候群方面取得的潛在進展，您能給我們介紹一下最新情況嗎？另外，您在什麼時候考慮到所需的合作夥伴，我認為您已經涵蓋了？所以監管互動。

We are working -- now that we have the data in MF, and these data are promising, we are working for a fast forward alongside SS and MS. And a plan to maximize the value of lacutamab is going to be discussed with the regulators.

我們正在努力——現在我們有了 MF 的數據，而且這些數據很有希望，我們正在努力與 SS 和 MS 一起快速前進。將與監管機構討論最大化 lacutamab 價值的計劃。

Okay. Operator, next question, please.

好的。接線員，請下一個問題。

Arthur He, H.C. Wainwright.

何亞瑟，H.C.溫賴特。

Hey, good morning. This is Arthur, in for [RK]. Thanks for taking my question.

嗨，早安。這是亞瑟，為了[RK]。感謝您提出我的問題。

So I just want to follow-up on the regulatory question on lacutamab. So are you guys to go to the agent with the data, both with Sézary syndrome and the MF, or rather go for the Sézary syndrome data alone to talk to the agent to file the BLA? Just want to clarify that.

所以我只想跟進 lacutamab 的監管問題。那麼，你們是帶著 Sézary 綜合徵和 MF 的數據去找代理人，還是只索取 Sézary 綜合徵數據，與代理人交談以提交 BLA？只是想澄清這一點。

Sure. Originally, when we had the data of Sézary, there was the option of going to the regulators with Sézary data alone, where we had a fast track designation and PRIME.

當然。最初，當我們擁有 Sézary 的資料時，可以選擇僅將 Sézary 資料提交給監管機構，在那裡我們獲得了快速通道指定和 PRIME。

Now we can really plan to merge the data, as I said, to maximize the value of lacutamab, not only in Sézary that is a small subgroup of the CTCL, but maximize the value of the drug in the whole of CTCL, together, of course, with mycosis fungoides.

現在我們真的可以計劃合併數據，正如我所說，以最大化 lacutamab 的價值，不僅在 CTCL 的一個小亞組 Sézary 中，而且在整個 CTCL 中最大化該藥物的價值當然，還有蕈樣肉芽腫。

And of course, the option of asking for accelerated approval still remains. And as you know, in order to get accelerated approval any way, we need the 12-month durability of response that is needed for this. And of course, we need to align on what the registrational trial could look like.

當然，請求加速批准的選擇仍然存在。如您所知，為了以任何方式獲得加速批准，我們需要 12 個月的持續回應時間。當然，我們需要就註冊試驗的情況進行協調。

Thanks for that. Really helpful. Just quick on the ANKET program, it's great to see the progress along and the expanding of the portfolio.

感謝那。真的很有幫助。快速了解 ANKET 計劃，很高興看到進展和產品組合的擴展。

Specifically on the 6501, I'm just curious for the trial you're going to evaluate initially. Is there a CD20 color for the patient inclusion? And how about the dosing strategy there, if you can give additional color? Appreciate it.

特別是對於 6501，我只是對您最初要評估的試用感到好奇。患者內含物是否有 CD20 顏色？如果您可以提供額外的顏色，那麼那裡的劑量策略怎麼樣？欣賞它。

Sure. In the study, are going to be recruited the CD20 positive non-Hodgkin lymphoma, again, in every subtype. And this is a classic first-in-human trial. And therefore, we are the first cohort, as you can imagine, as the first patient was enrolled in March. It's a dose escalation study with expansion.

當然。在這項研究中，我們將再次招募每種亞型的 CD20 陽性非何杰金氏淋巴瘤患者。這是一場經典的首次人體試驗。因此，正如你可以想像的那樣，我們是第一個隊列，因為第一位患者是在三月入組的。這是一項擴展的劑量遞增研究。

Thanks. And how about the dosing wise? What's the dosing interval and the strategy for the dosing escalation?

謝謝。那麼劑量方面又如何呢？給藥間隔和劑量遞增策略是怎麼樣的？

Well, the dose escalation is guided by the safety signals that we see and, of course, by statistical consideration and appetite of the investigators, depending on the safety and the exposure that we observed at each cohort.

好吧，劑量遞增是由我們看到的安全信號指導的，當然，還有研究人員的統計考慮和興趣，這取決於我們在每個隊列中觀察到的安全性和暴露。

All right. Thanks. Thanks for the additional color.

好的。謝謝。感謝您提供額外的顏色。

Operator, are there any more questions?

接線員，還有問題嗎？

We have no further phone questions at this time. I would now like to turn the call back to Mr. Herve Brailly for any closing remarks.

目前我們沒有進一步的電話問題。現在我想將電話轉回給 Herve Brailly 先生，請他發表結束語。

Yeah. Thanks a lot for your questions. And we're looking forward to the next meeting. The next important steps will be the overall presentation at the AACR to present the features of ADC, CD, the IPH45, and then, of course, the general meeting taking place on May 21.

是的。非常感謝您的提問。我們期待著下一次會議。接下來的重要步驟將是在 AACR 上進行全面介紹，介紹 ADC、CD、IPH45 的功能，當然還有 5 月 21 日舉行的全體會議。

So we're looking forward to reconnecting with you all on those two opportunities. And I wish you a very good day. And looking forward to the next steps.

因此，我們期待著利用這兩個機會與大家重新建立聯繫。祝您有美好的一天。並期待下一步。

Great. Thank you, everybody.

偉大的。謝謝大家。

Ladies and gentlemen, this concludes today's call. And we thank you for your participation. You may now disconnect.

女士們、先生們，今天的電話會議到此結束。我們感謝您的參與。您現在可以斷開連線。