HOOKIPA Pharma Inc (HOOK) 2022 Q4 法說會逐字稿

Good morning, and thank you for joining the Hookipa Pharma fourth-quarter and full-year 2022 earnings and 2023 outlook conference call. (Operator Instructions) I will now pass the call over to Matthew Beck, Executive Director of Investor Relations. Please go ahead.

早上好，感謝您參加 Hookipa Pharma 第四季度和全年 2022 年收益和 2023 年展望電話會議。 （操作員說明）我現在將電話轉給投資者關係執行總監馬修貝克。請繼續。

Thank you. A slide deck accompanying today's call is available through the webcast and in the Events section of the Hookipa website. Please manually advance the slides as we prompt you through them.

謝謝。可通過網絡廣播和 Hookipa 網站的“活動”部分獲取今天電話會議的幻燈片。請在我們提示您瀏覽幻燈片時手動推進幻燈片。

Joining me today are Chief Executive Officer, Joern Aldag; Chief Financial Officer, Reinhard Kandera; and Chief Medical Officer, Katia Schlienger.

今天加入我的是首席執行官 Joern Aldag；首席財務官 Reinhard Kandera；和首席醫療官 Katia Schlienger。

During today's call, we will be making certain forward-looking statements. These statements may include statements regarding, among other things, the efficacy, safety, and intended utilization of investigational agents; our clinical and non-clinical plans; our plans to present or report additional data; the anticipated conduct in the source of future clinical trials, regulatory plans, future research, and development; and possible intended use of cash and investments.

在今天的電話會議中，我們將做出某些前瞻性陳述。這些陳述可能包括關於研究藥物的功效、安全性和預期用途等方面的陳述；我們的臨床和非臨床計劃；我們展示或報告額外數據的計劃；未來臨床試驗、監管計劃、未來研究和開發來源的預期行為；現金和投資的可能預期用途。

These forward-looking statements are based on current information, assumptions, and expectations that are subject to change and involve risks and uncertainties that may cause the actual results to differ materially from those contained in the forward-looking statements.

這些前瞻性陳述基於可能發生變化的當前信息、假設和預期，並涉及可能導致實際結果與前瞻性陳述中包含的結果存在重大差異的風險和不確定性。

These and other risks are described in our periodic filings made with the SEC, including our quarterly and annual reports. You are cautioned not to place undue reliance on these forward-looking statements, which are only made as of today's date. The company disclaims any obligation to update such statements.

這些風險和其他風險在我們定期向美國證券交易委員會提交的文件中有所描述，包括我們的季度和年度報告。請注意不要過分依賴這些前瞻性陳述，這些陳述僅在今天發布。公司不承擔任何更新此類聲明的義務。

For today's call, Joern will provide opening remarks, Reinhard will offer high-level comments on our financials, and then we'll open the call to Q&A. With that, I'll pass the call to Joern.

對於今天的電話會議，Joern 將發表開場白，Reinhard 將就我們的財務狀況發表高層評論，然後我們將開始電話問答。有了這個，我會把電話轉給 Joern。

Okay. Good morning, everyone. I'd like to focus first on our accomplishments in 2022 and, second, highlight what's coming in 2023. At Hookipa, we're leveraging our arenaviral platform to create therapies that deliver unprecedented antigen-specific CD8 T cells to combat disease.

好的。大家，早安。我想首先關注我們在 2022 年取得的成就，其次，強調 2023 年將發生的事情。在 Hookipa，我們正在利用我們的 arenaviral 平台創造療法，提供前所未有的抗原特異性 CD8 T 細胞來對抗疾病。

In 2022, we saw progress both in and toward the clinic across four different programs in areas of considerable unmet need. Please go to Slide 3, which is our portfolio slide.

2022 年，我們在四個不同的項目中看到了診所在大量未滿足需求領域取得的進展。請轉到幻燈片 3，這是我們的投資組合幻燈片。

Key developments in '22 were the progress of our HPV-positive cancer drug, HB-200, in a Phase 2 single-arm cohort in combination with pembrolizumab; the acceptance of an IND for 300, a prostate cancer therapeutic targeting self-antigens; a material collaboration with Roche for a novel approach to targeting shared new antigens in cancers for lung, pancreas, and colon cancers with KRAS mutations; and achieving Phase 1 readiness for our Gilead-partnered hepatitis B therapeutic vaccine.

22 年的主要進展是我們的 HPV 陽性抗癌藥物 HB-200 在與 pembrolizumab 聯合進行的 2 期單臂隊列研究中取得的進展；接受針對自身抗原的前列腺癌治療藥物 300 的 IND；與羅氏（Roche）進行實質性合作，以開發一種新方法來靶向具有 KRAS 突變的肺癌、胰腺癌和結腸癌中共有的新抗原；並為我們與 Gilead 合作的乙型肝炎治療性疫苗實現第一階段準備。

Let me give you a bit more background on these major achievements. Our Phase 1 dose escalation study showed that HB-200 was generally well tolerated, rapidly induced a high magnitude of tumor-specific T cells and showed early anti-tumor activity in difficult-to-treat patients as a monotherapy.

讓我為您提供更多有關這些重大成就的背景信息。我們的 1 期劑量遞增研究表明，HB-200 總體耐受性良好，可迅速誘導大量腫瘤特異性 T 細胞，並在難以治療的患者中顯示出早期抗腫瘤活性作為單一療法。

We progressed to testing HB-200 in HPV16-positive head and neck squamous cell carcinoma patients in Phase 2. We're currently enrolling patients in three dose-expansion cohorts: a cohort in the non-randomized first-line setting in combination with pembro, a cohort in the nonrandomized second-line setting and second-line-plus setting in combination with pembro, and a cohort of patients in the post-standard-of-care setting at the recommended Phase 2 dose.

我們在第 2 階段對 HPV16 陽性頭頸部鱗狀細胞癌患者進行了 HB-200 測試。我們目前正在三個劑量擴展隊列中招募患者：一個隊列在非隨機一線環境中聯合 pembro ，一組在非隨機二線環境和二線+環境中與 pembro 聯合使用的隊列，以及一組在推薦的 2 期劑量下接受標準治療後環境的患者。

Regarding the HB-200 trial, I reaffirm our Q2 data guidance. We will disclose data from 10 to 20 patients each in the first- and second-line settings in combination with pembro, and we will provide an update on our monotherapy dose-escalation cohort.

關於 HB-200 試驗，我重申我們的第二季度數據指導。我們將在與 pembro 聯合使用的一線和二線環境中披露 10 至 20 名患者的數據，我們將提供我們的單藥劑量遞增隊列的更新。

We will present an update on this trial and all three cohorts in a press release and an investor call in the second quarter and inform about the likely path forward. As a reminder, our HB-200 trial, which targets an oncoviral antigen, supports the first pillar of our three-part strategy in oncology.

我們將在第二季度的新聞稿和投資者電話會議中介紹該試驗和所有三個隊列的最新情況，並告知可能的前進道路。提醒一下，我們針對腫瘤病毒抗原的 HB-200 試驗支持我們腫瘤學三部分戰略的第一支柱。

The second pillar in our oncology strategy is targeting self-antigens, which we are pursuing with our HB-300 program in prostate cancer. The trial is now open for enrollment as per our guidance to start the trial in Q1 2023.

我們的腫瘤學戰略的第二個支柱是針對自身抗原，我們正在通過我們的 HB-300 前列腺癌項目追求這一點。根據我們在 2023 年第一季度開始試驗的指南，該試驗現已開放註冊。

Targeting new antigens is the third pillar of our oncology strategy. In October, we announced a collaboration in this field with Roche to advance our HB-700 asset targeting KRAS mutations in multiple indications and an option to develop a second undisclosed candidate.

針對新抗原是我們腫瘤學戰略的第三大支柱。 10 月，我們宣布與羅氏在該領域開展合作，以推進我們針對多種適應症中 KRAS 突變的 HB-700 資產，並可選擇開發第二個未公開的候選藥物。

We're pleased by the progress across our oncology portfolio as well as the acceptance by the FDA last July of our drug master file. The information from that master file can be used to support new IND filings using our platform, leading to reduced pre-clinical cycle times.

我們對我們的腫瘤產品組合取得的進展以及 FDA 去年 7 月接受我們的藥物主文件感到高興。該主文件中的信息可用於支持使用我們平台的新 IND 申請，從而縮短臨床前週期時間。

Regarding our Gilead collaboration, much progress has been made. After restarting the HIV program, HB-500, under our control to bring it to the end of Phase 1b, we're working with our academic collaborators and plan an IND filing in 2023.

關於我們與吉利德的合作，已經取得了很大進展。在我們控制下重啟 HIV 項目 HB-500 以使其進入 1b 階段結束後，我們正在與我們的學術合作者合作，併計劃在 2023 年提交 IND 申請。

The hepatitis B program progressed well. As planned, we completed the Hookipa contributions for IND preparations in 2022, triggering a $5 million milestone payment. Gilead guided to a start of the trial of this HPV program in 2023.

乙型肝炎項目進展順利。按照計劃，我們在 2022 年完成了 Hookipa 對 IND 準備工作的貢獻，觸發了 500 萬美元的里程碑付款。吉利德（Gilead）指導於 2023 年開始對該 HPV 計劃進行試驗。

So what's in our plans for '23? The readout of all three HB-200 Phase 2 expansion cohorts in the second quarter of 2023 shall guide our decision to move into a randomized HB-200 trial in combination with pembro versus pembro alone. We have Fast Track designation for such a trial and a supply agreement for pembro with Merck US.

那麼我們對 23 年的計劃是什麼？ 2023 年第二季度所有三個 HB-200 2 期擴展隊列的讀數將指導我們決定進入隨機 HB-200 試驗結合 pembro 與 pembro 單獨試驗。我們為此類試驗指定了快速通道，並與美國默克公司簽訂了 pembro 供應協議。

In our HB-300 Phase 1 trial targeting prostate cancer, we're recruiting now, and we'll start dosing patients. Expect initial data in the first half of 2024.

在我們針對前列腺癌的 HB-300 1 期試驗中，我們現在正在招募患者，我們將開始對患者進行給藥。預計 2024 年上半年的初步數據。

We had a good start into 2023 with two significant milestone payments, reflecting significant progress in our collaborations, plus one $5 million from Gilead for the completion and delivery of a regulatory support package for their Phase 1 clinical trial of a therapeutic cure for chronic hepatitis B using HB-400; and the second, a $10 million payment from Roche for starting GMP manufacturing of the KRAS therapeutic, an important step before filing the IND, which we expect to happen in the first half of 2024.

我們在 2023 年有了一個良好的開端，獲得了兩筆重要的里程碑付款，反映了我們在合作方面取得的重大進展，另外還有吉利德 (Gilead) 提供的 500 萬美元，用於完成和交付用於治療慢性乙型肝炎的 1 期臨床試驗的監管支持包使用 HB-400；第二，羅氏支付 1000 萬美元用於開始 KRAS 療法的 GMP 生產，這是提交 IND 之前的重要一步，我們預計這將在 2024 年上半年進行。

We expect to file our HB-500 HIV therapeutic cure candidate IND in 2023. We will continue our work for Roche, both on the KRAS therapeutic as well as on the option package for an additional target, which Roche may decide to exercise in 2024.

我們預計將在 2023 年提交我們的 HB-500 HIV 治療候選藥物 IND。我們將繼續為羅氏工作，包括 KRAS 治療以及羅氏可能決定在 2024 年實施的額外目標的選項包。

In summary, we've made significant progress in 2022, and we are positioned for an exciting 2023, with material [in those four] to come from our key programs.

總而言之，我們在 2022 年取得了重大進展，我們為激動人心的 2023 年做好了準備，[這四個] 的材料來自我們的關鍵項目。

Finally, I'd like to highlight that we have significantly strengthened our cash balance with $113 million at year-end 2022. We're well-funded for many major data readouts.

最後，我想強調的是，到 2022 年底，我們的現金餘額已顯著增加，達到 1.13 億美元。我們有充足的資金來讀取許多主要數據。

With that, I'll turn the call over to our CFO for more financial details. Reinhard?

有了這個，我會把電話轉給我們的首席財務官，了解更多財務細節。萊因哈特？

Thanks, Joern. Good morning, everyone. So I want to give you a few highlights of our financial results for the fourth quarter and the full-year 2022.

謝謝，喬恩。大家，早安。因此，我想向您介紹我們第四季度和 2022 年全年財務業績的一些亮點。

As shown on Slide 4 of our presentation, we ended the year with a strong quarter in revenues, which amounted to $7.8 million and included the milestone payments from Gilead and the start of the recognition of the $25 million upfront payment received under the Roche collaboration.

如我們演示文稿的幻燈片 4 所示，我們以強勁的季度收入結束了這一年，總計 780 萬美元，其中包括吉利德的里程碑付款以及開始確認在羅氏合作下收到的 2500 萬美元預付款。

Our Q4 spending was very much in line with the average of the previous quarters, leading to a quarterly net loss of $12.3 million for Q4.

我們第四季度的支出與前幾個季度的平均水平非常一致，導致第四季度的季度淨虧損為 1230 萬美元。

For the 2022 results, I want to start by pointing out our significantly strengthened cash position, which we achieved through our $75 million capital raise in the first quarter and cash inflows from partnering, including [$19 million] from Gilead and $25 million from Roche.

對於 2022 年的業績，我想首先指出我們顯著增強的現金狀況，這是通過第一季度 7500 萬美元的融資和來自合作夥伴的現金流入實現的，包括吉利德的 [1900 萬美元] 和羅氏的 2500 萬美元。

I'm also proud to report that we were able to achieve a significant 2022 R&D progress that Joern has just detailed at a 17% lower spend compared to 2021. Our G&A expenses moderately increased, but the increase was more than offset by higher grant and interest income.

我也很自豪地報告，我們能夠在 2022 年取得重大研發進展，Joern 剛剛詳細說明，與 2021 年相比，支出減少了 17%。我們的 G&A 費用適度增加，但增加的資金被更高的撥款和利息收入。

Bottom line, we reported a full-year 2022 net loss of slightly less than $65 million, which is 14% below 2021. We continue to manage our burn rate tightly and to rely on partnerships to support our spending. We expect to moderately increase our expenses in 2023 as the pipeline progresses.

總而言之，我們報告的 2022 年全年淨虧損略低於 6500 萬美元，比 2021 年低 14%。我們繼續嚴格管理我們的消耗率，並依靠合作夥伴來支持我們的支出。隨著管道的進展，我們預計將在 2023 年適度增加支出。

The financial contributions from partnerships were already evidenced in the first quarter of 2023 by the receipt of a total of $15 million in milestone payments.

2023 年第一季度已收到總計 1500 萬美元的里程碑付款，證明了合作夥伴的財務貢獻。

With a cash balance of $113.4 million at the end of 2022, plus the $15 million in partner milestone income already achieved in 2023, we consider ourselves well-funded to reach beyond important upcoming pipeline catalysts.

憑藉 2022 年底 1.134 億美元的現金餘額，加上 2023 年已經實現的 1500 萬美元合作夥伴里程碑收入，我們認為自己有充足的資金來超越即將到來的重要管道催化劑。

With that, I'd like to hand back to Joern for some closing remarks.

說到這裡，我想請 Joern 做一些結束語。

Thanks, Reinhard. We're coming to the end of this call. I'm indeed very proud of our talented people and their drive to support the company's and our shareholders' objectives throughout this difficult capital market environment. We're laser focused to produce and present to you our clinical data updates throughout the year.

謝謝，萊因哈特。我們即將結束本次電話會議。我確實為我們的人才以及他們在這個艱難的資本市場環境中支持公司和股東目標的動力感到非常自豪。我們專注於製作並向您展示我們全年的臨床數據更新。

With that, I'd like to re-open the line for Q&A. Operator?

有了這個，我想重新打開問答熱線。操作員？

Thank you. (Operator Instructions) Brian Abrahams, RBC Capital Markets.

謝謝。 （操作員說明）RBC 資本市場的 Brian Abrahams。

Hi, guys. Thanks. It's Leo on for Brian. Congrats on another quarter, and thanks for taking our question. How are you thinking about the bar for HB-200, and what's achievable? If the response rates fall in the 25% to 35% range, how are you thinking about next steps for the program, and what's your sense of where standard of care is for each line and what docs would find meaningful?

嗨，大家好。謝謝。這是獅子座對布賴恩。祝賀另一個季度，感謝您提出我們的問題。您如何看待 HB-200 的標準，可以達到什麼標準？如果響應率落在 25% 到 35% 的範圍內，您如何考慮該計劃的後續步驟，您對每條線的護理標準以及哪些文檔會覺得有意義有何看法？

I mean, would you add more patients to tease that response, or would you pivot and look to modify the program depending on what you see? And maybe I'll have a follow-up after that. Thanks.

我的意思是，你會增加更多的病人來挑逗這種反應，還是你會根據你看到的情況來調整和修改程序？也許在那之後我會有一個跟進。謝謝。

[I think Katia can] give you more specifics to it, but in general, we know that the standard of care to pembrolizumab and in the second line has a response rate -- objective response rate of 15%; and in the first line, an objective response rate of 20%.

[我認為 Katia 可以] 給你更多細節，但總的來說，我們知道 pembrolizumab 和二線治療的標準治療有反應率——客觀反應率為 15%；在第一線，客觀響應率為 20%。

And we consider it a success if we're able to double these, meaning that we reach around 40% objective response on with the combination of HB-200 together with standard-of-care pembrolizumab.

如果我們能夠將這些翻倍，我們認為它是成功的，這意味著我們通過 HB-200 與標準護理 pembrolizumab 的組合達到了大約 40% 的客觀響應。

Yes. And adding a little bit to that, we will look at the totality of the data. So if we are in the gray zone or if it's not [clear to] -- [on there], we would look at other marker of efficacy, we would look into immunogenicity, and we will then decide if we want to start the trial or not.

是的。再加上一點，我們將查看數據的整體性。因此，如果我們處於灰色地帶，或者如果它不是 [clear to] - [on there]，我們會查看其他功效標記，我們會查看免疫原性，然後我們將決定是否要開始試驗或不。

So in brief, if we make 40% objective response rate, that's clear go-ahead signal that we will be looking at the totality of the data in making that final decision because you know that this is going to be a Phase 3 trial with a fairly significant investment.

所以簡而言之，如果我們的客觀響應率為 40%，那麼這是一個明確的信號，表明我們將在做出最終決定時查看全部數據，因為你知道這將是一個 3 期試驗相當大的投資。

Got it. Thanks. And then maybe just a quick follow-up on that. Have you talked about how much follow-up you'll be expecting for the patients that you present at the upcoming data cut?

知道了。謝謝。然後可能只是對此進行快速跟進。您是否談過您期望在即將到來的數據削減中為您呈現的患者進行多少次隨訪？

Is it going to be only patients in more than two scans? And you mentioned you'll be presenting the data in a press release. Are you still looking at a medical meeting submission around that same time. Thanks. I'll hop back in the queue.

是否只會接受超過兩次掃描的患者？你提到你將在新聞稿中展示數據。你還在看大約同一時間的醫學會議提交嗎？謝謝。我會跳回到隊列中。

Yes, we will -- [we intend at this point in time] to have a press release and also an investor event. So we'll substantially detail the data and be at a medical conference some point after the summer. Katia?

是的，我們將 - [我們打算在這個時間點] 發布新聞稿和投資者活動。因此，我們將詳細說明數據，並在夏季過後的某個時候參加醫學會議。卡蒂亞？

Yes. No, nothing -- not to add to that, exactly that. Of course, we will present [at the] scientific conference afterwards.

是的。不，沒什麼——不是要添加，就是這樣。當然，我們將在之後 [在] 科學會議上介紹。

Vikram Purohit, Morgan Stanley.

Vikram Purohit，摩根士丹利。

Hi, everyone. This is Will on for Vikram. Thanks for taking our questions, and congrats on the quarter. And Just kind of the same vein as Leo's question, how are you -- how would you frame expectations for the initial data expected for HB-300 -- the first half? Could you just give us a sense of what we can expect to see in terms of the data points and what you would consider a win?

大家好。這是維克拉姆的意志。感謝您提出我們的問題，並祝賀本季度。就像 Leo 的問題一樣，你如何 - 你如何構建對 HB-300 預期初始數據的預期 - 上半年？您能否讓我們了解一下我們可以期望在數據點方面看到什麼以及您認為什麼是勝利？

(Multiple speakers) We're looking at a self-antigen clearly establishing immunogenicity against the antigens that we've chosen. It would be a significant win in the first half of 2024. Katia?

（多位發言者）我們正在研究一種自身抗原，它可以清楚地建立針對我們選擇的抗原的免疫原性。這將是 2024 年上半年的重大勝利。卡蒂亞？

No, exactly that. I think it's our [system with that] as well as the general safety profile. We don't expect a lot of surprise based on -- there's an excellent safety profile that we have demonstrated with the 200 program using exactly the same vector. So all these information will come in 2024.

不，正是這樣。我認為這是我們的 [系統] 以及一般安全概況。我們預計不會有太多驚喜——我們已經使用完全相同的向量在 200 程序中展示了出色的安全性。所以所有這些信息都將在 2024 年到來。

Okay, great. And is that going to be just a press release, or is that going to be associated with medical conference as well?

好的，太好了。那隻是一份新聞稿，還是也與醫學會議有關？

It depends on the timing of data availability versus a major conference, which we could present. It's not decided yet.

這取決於數據可用性與我們可以展示的主要會議的時間安排。還沒有決定。

Okay. Well, thanks for the color. I appreciate it. Congrats again.

好的。嗯，謝謝你的顏色。我很感激。再次恭喜。

You're welcome.

不客氣。

Thanks.

謝謝。

Alec Stranahan, Bank of America.

亞歷克·斯特拉納漢，美國銀行。

Hey, guys, thanks for taking our question. Just a couple from us. We appreciate the additional color on the 2Q update for the 200 program.

嘿，伙計們，謝謝你提出我們的問題。我們只有一對夫婦。我們感謝 200 計劃的 2Q 更新的額外顏色。

And as we're thinking through the to the historical controls, obviously, those are in a broader head-and-neck population. Is there any reason to think that KEYTRUDA monotherapy would perform better or worse than an HPV16 positive population? I'm just trying to think if that's apples to apples.

當我們考慮歷史控制時，顯然，這些控制在更廣泛的頭頸人群中。是否有任何理由認為 KEYTRUDA 單一療法會比 HPV16 陽性人群表現更好或更差？我只是想想想這是否是蘋果對蘋果。

And then, just on the capital allocation priorities next 12 months, starting a few new studies; obviously, you've got some partner funding as well. So I guess, where does that put you guys in terms of runway, and where is your main focus in terms of capital allocation? Thanks.

然後，就未來 12 個月的資本配置優先事項，開始一些新的研究；顯然，你也有一些合作夥伴的資金。所以我想，就跑道而言，這將你們置於何處？在資本配置方面，你們的主要關注點在哪裡？謝謝。

Katia, will you take the KEYTRUDA monotherapy question?

Katia，你會回答 KEYTRUDA 單一療法的問題嗎？

Yes. Yes, absolutely. So [KEYNOTE-048], which is a randomized Phase 3 trial that led to pembrolizumab approval in first line for patients with head-and-neck squamous cell carcinoma, no known difference between those patients with HPV-positive or HPV-negative head and neck. And so, that's to answer the first question. But were you thinking of something specific along that question?

是的。是的，一點沒錯。因此 [KEYNOTE-048]，這是一項隨機 3 期試驗，導致 pembrolizumab 被批准用於頭頸部鱗狀細胞癌患者的一線治療，HPV 陽性或 HPV 陰性的頭部和頸部鱗狀細胞癌患者之間沒有已知差異脖子。所以，這就是回答第一個問題。但是你有沒有想過這個問題的具體內容？

No, I think that's helpful. (Multiple speakers)

不，我認為這很有幫助。 （多個揚聲器）

Okay. So on the capital allocation, clearly, the key priority at this point is moving HB-200 along. HB-300, from a strategic perspective, is important because for targeting and self-antigen. And if we're able to generate significant T-cell immune responses against self-antigens, and by that, breaking tolerance, we're clearly in a pretty good camp. So that is our priority number two, strategically important.

好的。因此，在資本配置方面，顯然，此時的關鍵優先事項是推動 HB-200。從戰略角度來看，HB-300 很重要，因為它用於靶向和自身抗原。如果我們能夠針對自身抗原產生顯著的 T 細胞免疫反應，並由此打破耐受性，那麼我們顯然處於一個非常好的陣營。所以這是我們的第二優先事項，具有戰略重要性。

Clearly also important from a capital allocation perspective are HB-500, which is the HIV program, which we are running until after the end of Phase 1b or if Gilead has an option to take it in; and the very interesting KRAS program that we're running with Roche. But both these programs are basically funded through payments that we're receiving from Gilead and Roche.

從資本配置的角度來看，顯然也很重要的是 HB-500，它是 HIV 項目，我們將一直運行到 1b 階段結束之後，或者如果 Gilead 可以選擇接受它；以及我們與羅氏一起運行的非常有趣的 KRAS 程序。但這兩個項目基本上都是通過我們從吉利德和羅氏收到的付款來資助的。

So your question actually addresses the [key spend], and that's obviously HB-200 and its progression and where we have various avenues to take it forward, including the [HB-200] randomized trial and HB-300.

所以你的問題實際上解決了[關鍵支出]，這顯然是 HB-200 及其進展，我們有各種途徑來推進它，包括 [HB-200] 隨機試驗和 HB-300。

Regarding the cash runway, I would like to have Reinhard answer that question.

關於現金跑道，我想讓 Reinhard 回答這個問題。

Yes. Given the uncertainty of the business and the dependence on R&D outcomes, we don't give specific numbers, but I can give you some orientation. I've mentioned that our R&D costs is going to increase moderately.

是的。鑑於業務的不確定性和對研發成果的依賴，我們不給出具體數字，但我可以給你一個方向。我已經提到我們的研發成本將適度增加。

On the other hand, we have two big partnerships with Roche and with Gilead that provide increasing support from partnership revenue to cover that cost. So by and large, expect our net loss in the current year to be similar. Then in the previous year, around $65 million.

另一方面，我們與羅氏和吉利德建立了兩大合作夥伴關係，它們從合作夥伴收入中提供越來越多的支持，以支付該費用。所以總的來說，預計我們今年的淨虧損是相似的。然後在前一年，大約 6500 萬美元。

As I've mentioned, we have more than $113 million in cash at year end. There is another $15 million that already came in from partnerships in the first quarter. So I'll let you do the math of where this takes us approximately in terms of cash runway.

正如我所提到的，到年底我們有超過 1.13 億美元的現金。第一季度還有 1500 萬美元來自合作夥伴關係。因此，我將讓您根據現金跑道計算一下這將把我們帶到什麼地方。

Great. Thank you. Looking forward to the update.

偉大的。謝謝。期待更新。

Thanks a lot.

多謝。

Arthur He, H.C. Wainwright.

何亞瑟, H.C.溫賴特。

Hi. Hello, everyone, and thanks for taking my question. Just for the HB-200 program, regarding the randomized study, could you give us [a more specific] regarding the study initiation and when could we expect the data from the randomized Phase 2 study for the first-line patients?

你好。大家好，感謝您提出我的問題。僅針對 HB-200 計劃，關於隨機研究，您能否給我們[更具體]關於研究啟動的信息，以及我們什麼時候可以期待來自一線患者的隨機 2 期研究的數據？

For the first point, obviously, a lot of preparation has been done. We have manufactured HB-200 product. We have a clinical protocol in place that we can apply. We have had discussions with some of the relevant CROs that would support the clinical trial.

對於第一點，顯然已經做了很多準備。我們生產了HB-200產品。我們有一個可以應用的臨床方案。我們已經與一些支持臨床試驗的相關 CRO 進行了討論。

And we have to make the decision and inform folks that we would make that decision based on information that is coming from our clinical trial, which is currently ongoing and running, which we will be reporting about June. So more specific timelines you will hear when we do the data release.

我們必須做出決定並告知人們，我們將根據來自我們臨床試驗的信息做出該決定，該試驗目前正在進行中，我們將在 6 月份報告。因此，當我們發布數據時，您會聽到更具體的時間表。

Katia, maybe a flavor on initial data from the 200 program, the randomized trial, and [how it] gets started.

Katia，也許是對 200 計劃的初始數據、隨機試驗以及 [它] 的啟動方式的一種啟發。

Yes. And just as a reminder, we have Fast Track designation of [this] that we have received from the FDA. For that study, we have a supply agreement with Merck.

是的。提醒一下，我們已經從 FDA 收到了 [this] 的快速通道指定。對於這項研究，我們與默克公司簽訂了供應協議。

We have already discussed the design of our trial with the FDA, and we just would like to have a deep look into our data from the [HB-201] data. It's a single-arm cohort to make basically the decision to move ahead. So is that helpful, Arthur, or should I answer something else?

我們已經與 FDA 討論了我們的試驗設計，我們只是想深入了解 [HB-201] 數據中的數據。這是一個單臂隊列，基本上可以做出前進的決定。那麼這有幫助嗎，Arthur，還是我應該回答其他問題？

No. That's helpful. Yes, that makes sense anyway. So for your upcoming presentation at the [ACR], it's quite interesting for the target. Could you elaborate more on that particular candidate?

不，這很有幫助。是的，無論如何這是有道理的。因此，對於您即將在 [ACR] 上進行的演示，它對目標來說非常有趣。你能詳細說明那個特定的候選人嗎？

We do know that a significant number of immunotherapies are suboptimally working with regard to efficacy because they're lacking T cells at the site of the tumor. For that reason, we were claiming that we're able to drive very high levels of antigen-specific T cells, and that this ability to drive these antigen-specific T cells towards the tumor could actually help a number of different immunotherapies to work.

我們確實知道，大量免疫療法在療效方面效果欠佳，因為它們在腫瘤部位缺乏 T 細胞。出於這個原因，我們聲稱我們能夠驅動非常高水平的抗原特異性 T 細胞，並且這種將這些抗原特異性 T 細胞驅動到腫瘤的能力實際上可以幫助許多不同的免疫療法發揮作用。

You may remember that last year at ACR, we demonstrated the combination with some 4-1BB. In this ACR presentation, you will be looking at a different immunotherapeutic, I02, which we think has a significant promise in combination with HB-200 as well.

你可能記得去年在 ACR 上，我們展示了一些 4-1BB 的組合。在此 ACR 演示中，您將看到一種不同的免疫治療藥物 I02，我們認為它與 HB-200 結合使用也具有重要前景。

And what we're trying to show, albeit preclinical for the time being, is that with these types of combinations, we can actually significantly enhance therapeutic effect in cancer patients across many different diseases. And we're very pleased that at ACR, we have a mini symposium, so [another] presentation of that data that you're referring to.

我們試圖展示的是，儘管目前還處於臨床前階段，但通過這些類型的組合，我們實際上可以顯著提高對許多不同疾病的癌症患者的治療效果。我們很高興在 ACR 上，我們舉辦了一個小型研討會，因此 [另一個] 介紹了您所指的數據。

Great. Thanks for the additional color, and congrats on the progress. [Talk to you soon].

偉大的。感謝您提供額外的顏色，並祝賀您取得的進步。 [以後再聊]。

Thank you.

謝謝。

Thank you.

謝謝。

Asthika Goonewardene, Truist Securities.

Asthika Goonewardene，Truist 證券。

Hi, guys. Thanks for taking my questions. I want to go back to the first question asked about the bar here in the [difficult-to-treat] patients, what [data they're] looking forward during the second quarter. You told us the bar in response rate. But as we know, [I/O] also shows -- the [I/O works]. You have nice durable response.

嗨，大家好。感謝您回答我的問題。我想回到第一個問題，關於[難以治療]患者的酒吧，他們在第二季度期待什麼[數據]。你告訴我們響應率吧。但正如我們所知，[I/O] 也表明——[I/O 有效]。你有很好的持久反應。

What do you think is the bar for duration of response in both these cohorts that you're planning on presenting? And I've got a couple of follow-ups on that.

您認為在您計劃展示的這兩個隊列中，反應持續時間的標準是什麼？我對此進行了一些跟進。

Yes, absolutely. So are we planning on -- to look at the numbers from other efficacy endpoints like disease control rate. Indeed, sometimes, we have shown that with our vector as a single agent. We see some patients with stable disease for months. And so, we are planning to report that as well.

是的，一點沒錯。因此，我們是否計劃 - 查看來自疾病控制率等其他療效終點的數字。事實上，有時候，我們已經用我們的向量作為單一代理人證明了這一點。我們看到一些病情穩定數月的患者。因此，我們也計劃報告這一點。

In terms of duration of response, this will be -- which will have -- knowing that we have started, and [we'll include patients] at the beginning of 2022. So we will put the maximum of data that we have at this point. We guided to 10 to 20 patients in first line and 10 to 20 patients in second-line plus.

就反應持續時間而言，這將是——這將是——知道我們已經開始，並且 [我們將包括患者] 在 2022 年初。所以我們將把我們擁有的最大數據放在這觀點。我們指導了 10 到 20 名一線患者和 10 到 20 名二線患者。

Katia, maybe I'll ask it more directly. Do you think the duration of response data will be mature enough to see a signal when you present this data in the second quarter? Or would we need more follow-up to really understand what the median duration of response is in these cohorts?

Katia，也許我會更直接地問它。當您在第二季度提供這些數據時，您認為響應數據的持續時間是否足夠成熟，可以看到信號？或者我們是否需要更多的後續行動才能真正了解這些隊列中的中位反應持續時間？

Yes, we will probably need to continue to show adoption rates quite frequent for this data update, something [done regularly] at each of the conference. So we will continue to follow-up the patient no matter what. This would be a first release, but we will continue to follow-up the patient and provide regular updates at scientific conference.

是的，我們可能需要繼續非常頻繁地顯示此數據更新的採用率，這在每次會議上都[定期]進行。所以無論如何我們都會繼續跟進病人。這將是第一次發布，但我們將繼續跟踪患者並在科學會議上提供定期更新。

And so, I think it is important to note -- yes, sorry, Katia.

因此，我認為重要的是要注意——是的，對不起，Katia。

No, no. Go ahead, Joern.

不，不。去吧，喬恩。

Yes, it's important to note that the median progression-free survival, for example, for pembro alone is very short and why we will not have data that has fully matured across the entire data set of patients. You will be able to see how we compare against the median progression-free survival of pembro alone.

是的，重要的是要注意，例如，僅 pembro 的中位無進展生存期非常短，以及為什麼我們沒有在整個患者數據集中完全成熟的數據。您將能夠看到我們如何與單獨使用 pembro 的中位無進展生存期進行比較。

Okay. And then, when you're looking at this at the more longer-term follow up, let's say, hopefully later this year or maybe early next year, what is the bar then for progression-free survival or duration of response that you would like to see, given that you said that you're looking for double the ORR? Would you want to see double the median PFS or double the duration?

好的。然後，當你在更長期的隨訪中觀察這個問題時，比方說，希望在今年晚些時候或明年初，你想要的無進展生存期或反應持續時間的標準是什麼看看，鑑於你說你正在尋找雙倍的 ORR？您希望看到雙倍的 PFS 中值還是雙倍的持續時間？

So I can take that. We know that [finding] oncology PFS is not necessarily the best primary endpoint. We know that for pembrolizumab, for example, it's three months in first line and [two months] in second-line plus, and that does not reflect the huge [rest] advantage that is provided in first line, in second line for those patients.

所以我可以接受。我們知道，[發現]腫瘤 PFS 不一定是最好的主要終點。我們知道，例如，對於 pembrolizumab，一線是三個月，二線加 [兩個月]，這並沒有反映一線、二線為這些患者提供的巨大 [休息] 優勢.

So I would like just to caution that yes, we will provide on what we have. The PFS is not necessarily the right measure for immuno-oncology projects.

所以我想提醒一下，是的，我們將提供我們所擁有的。 PFS 不一定是免疫腫瘤學項目的正確衡量標準。

In terms of duration of response, so this is measuring the time on treatment with a progression in patients who are responding since we take [several] months to assess, and we will probably provide an update later on through scientific conference abstract and presentation.

就反應持續時間而言，這是衡量反應患者的治療時間，因為我們需要 [幾個月] 的時間進行評估，我們可能會在稍後通過科學會議摘要和演示文稿提供更新。

Got it. Okay. And then, just lastly, just bigger picture here. Previously, in our discussions, and we felt this too, the really strong immunogenic response that you were generating with HB-200 in the platform, that was really attractive. And it made sense that adding something like PD-1 was a logical step to making this work.

知道了。好的。然後，最後，這裡是更大的圖景。之前，在我們的討論中，我們也感受到了這一點，您在平台中使用 HB-200 產生的真正強大的免疫原性反應非常有吸引力。添加 PD-1 之類的東西是實現這項工作的合乎邏輯的步驟是有道理的。

Given what you know today and the emergence of other data, preclinical and otherwise, how do you feel about that? And if there's anything that you would like to add to a combo, what would that be?

鑑於您今天所知道的以及其他臨床前和其他數據的出現，您對此有何看法？如果您想將任何東西添加到組合中，那會是什麼？

I am not clear about what you specifically want to find out here, but could you just specify your question a bit more?

我不清楚你具體想在這裡找到什麼，但你能再詳細說明一下你的問題嗎？

Yes. I mean, I'm just wondering. Do you need to -- you're getting the immunogenic response with HB-200. You're getting checkpoint blockade with the PD-1.

是的。我的意思是，我只是想知道。您是否需要——您正在使用 HB-200 獲得免疫原性反應。你正在用 PD-1 封鎖檢查點。

Is there anything else from an immunological perspective that you think would be useful to add to this combination, maybe like [you did] things like getting more danger signals with chemotherapy?

從免疫學的角度來看，您認為是否還有其他任何東西可以添加到這種組合中，比如 [您做過] 諸如通過化療獲得更多危險信號之類的事情？

What do you think is the next logical component that you might want to add to this type of therapy here from an immunological perspective?

從免疫學的角度來看，您認為下一個您可能想要添加到此類療法中的邏輯組成部分是什麼？

[It may be] interesting to look at the data that we will present at ACR, but I'll let Katia answer the question.

查看我們將在 ACR 上展示的數據 [可能] 很有趣，但我會讓 Katia 回答這個問題。

Yes. So certainly, like we know -- so what we saw in monotherapy, we saw that we were able to see clinical response and stable disease in some patients. We saw a huge immunogenicity injection with very high level of T cells specific to the tumor antigen into circulation.

是的。所以當然，就像我們知道的那樣——所以我們在單一療法中看到的，我們看到我們能夠看到一些患者的臨床反應和穩定的疾病。我們看到大量免疫原性注射液進入循環，其中含有非常高水平的腫瘤抗原特異性 T 細胞。

We saw that those T cells are fully functional and that they do infiltrate the tumor. So we would like to continue to develop those data in monotherapy and in combination with pembrolizumab over the [next months then].

我們看到這些 T 細胞功能齊全，並且它們確實浸潤了腫瘤。因此，我們希望在 [接下來的幾個月] 中繼續開發單藥治療和與 pembrolizumab 聯合治療的這些數據。

To tell you exactly what we will show and what it means, I think [Joern and the team's] looking for a general correlation between the immunogenicity and efficacy. And we will definitely look at that and report what we find.

為了準確地告訴你我們將展示什麼以及它意味著什麼，我認為 [Joern 和團隊] 正在尋找免疫原性和功效之間的一般相關性。我們一定會查看並報告我們的發現。

Awesome, guys. Thanks. I look forward to it and look forward to your updates at ACR as well.

太棒了，伙計們。謝謝。我很期待，也期待您在 ACR 的更新。

Great.

偉大的。

Thank you.

謝謝。

Roy Buchanan, JMP Securities.

JMP 證券公司的 Roy Buchanan。

Hey, great. Thanks for taking the questions. Just a few quick ones. First one for Reinhard, can you just remind me if Gilead has a timeframe they need to make the purchase of stock? I think there's 30 million. They're still eligible to purchase. Is there a certain timeframe on that?

嘿，太好了。感謝您提出問題。只是一些快速的。 Reinhard 的第一個問題，你能否提醒我 Gilead 是否有他們需要購買股票的時間表？我認為有3000萬。他們仍然有資格購買。有特定的時間框架嗎？

Yes, there is a timeframe. We have actually the choice to draw that additional equity, and it is until end of 2023.

是的，有一個時間表。實際上，我們可以選擇提取額外的股權，直到 2023 年底。

Okay, great. Thank you. And then, has Gilead had said if the Phase 1 in hepatitis B is going to be in patients or healthy volunteers?

好的，太好了。謝謝。然後，吉利德（Gilead）是否說過乙型肝炎的第一階段是針對患者還是健康志願者？

Katia, [we haven't disclosed] that yet, and I don't think we can. We have to leave that to Gilead.

Katia，[我們還沒有透露]，我認為我們不能。我們必須把它留給吉利德。

Okay. Fair enough. And then, just the last one. Can partners use the drug master file? Like, can Roche use it for the KRAS program?

好的。很公平。然後，只是最後一個。合作夥伴可以使用藥品主檔案嗎？比如，羅氏可以將它用於 KRAS 程序嗎？

Yes. We can use it as we're preparing the Phase 1b and we're doing the IND work. And we can use that drug master file from HB-200 and 300 in that context as well.

是的。我們可以在準備 1b 階段和進行 IND 工作時使用它。在這種情況下，我們也可以使用 HB-200 和 300 的藥物主文件。

Okay, great. What about partners that are doing the Phase 1 themselves? Can they use it?

好的，太好了。那些自己進行第一階段的合作夥伴呢？他們可以使用它嗎？

Katia, can you answer this?

卡蒂亞，你能回答這個問題嗎？

Yes. They can certainly use it once they [use our product]. These could be some things that they can use when they file an IND in projects that are related to those -- the ones that [they] are using in Gilead's [investigations] and the ones that we're using in oncology.

是的。一旦他們[使用我們的產品]，他們當然可以使用它。這些可能是他們在與這些相關的項目中提交 IND 時可以使用的一些東西——[他們] 在 Gilead 的 [調查] 中使用的那些以及我們在腫瘤學中使用的那些。

So that master file was done for the two vectors replicating, which is different from the 400 technology. So depending on what our partner will use, so for example, for Roche, absolutely. This will be used for the IND submission as well.

所以主文件是為兩個複制的載體完成的，這與400技術不同。因此，這取決於我們的合作夥伴將使用什麼，例如，絕對是羅氏。這也將用於 IND 提交。

Great, okay.

太好了，好吧。

So just very, very briefly. Yes, they can use it. At this point in time, no one is doing it in Phase 1 with our program -- [with the arenavirus program].

所以非常非常簡短。是的，他們可以使用它。在這個時間點，沒有人在第一階段使用我們的程序 - [使用沙粒病毒程序]。

Got it. Thank you.

知道了。謝謝。

Great.

偉大的。

Suzanne van Voorthuizen, Kempen.

Suzanne van Voorthuizen，肯彭。

Hi, Suzanne.

嗨，蘇珊娜。

Hi. Good afternoon, and thanks for taking my question. I just wanted to circle back to the Q2 update on HB-200 program. I'm not sure I heard it right.

你好。下午好，謝謝你提出我的問題。我只想回到 HB-200 計劃的第二季度更新。我不確定我沒聽錯。

So can you clarify what you will include in terms of duration data in the press release? Would it include both duration of response and PFS, and what conference in the latter half of the year are you targeting to get the data presentation? And then, I'll follow up as well.

那麼，您能否澄清一下您將在新聞稿中包含哪些持續時間數據？它是否包括響應持續時間和 PFS，以及您打算在下半年的哪個會議上獲得數據演示？然後，我也會跟進。

Katia?

卡蒂亞？

Yes. So in terms of duration of response, generally, the challenge would be to obtain a million. On patients, probably, we would not have a million at that time, but I was just speculating.

是的。因此，就響應持續時間而言，一般來說，挑戰是獲得一百萬。在病人身上，我們當時可能不會有一百萬，但我只是在猜測。

The duration of response for pembrolizumab is 22 months. So it's difficult to know if we will be able to reach a median at that time. We will disclose on what we have in terms of objective response rate and the controlled rate and associated efficacy endpoint.

派姆單抗的反應持續時間為 22 個月。所以很難知道我們是否能夠在那個時候達到中位數。我們將披露我們在客觀反應率、控制率和相關療效終點方面的情況。

We will disclose the full safety profile and immunogenicity data that we will have at that time. Is that helpful, or --

我們將披露我們屆時將擁有的完整安全概況和免疫原性數據。這有幫助嗎，或者——

Yes, for sure. Thank you. And what conference in the latter half of year are you targeting for presentation?

是肯定的。謝謝。您打算在下半年的什麼會議上發表演講？

So we did not decide yet, and we will release it when we are ready.

所以我們還沒有決定，等我們準備好了再發布。

Got it. All right. And then, a follow-up is on a different topic with now Gilead and the addition of Roche as partners for Hookipa.

知道了。好的。然後，跟進是一個不同的話題，現在是吉利德（Gilead）和羅氏（Roche）作為 Hookipa 的合作夥伴。

How are you looking at potential further [BD]? I just would like to hear your considerations and preferences in terms of type of deals, oncology or infectious diseases, development stage or platform deals, yes, just some thoughts that you can share there.

您如何看待進一步的潛力 [BD]？我只是想听聽您在交易類型、腫瘤學或傳染病、開發階段或平台交易方面的考慮和偏好，是的，只是您可以在那里分享的一些想法。

Yes. So any collaboration is actually quite a complex undertaking. Working with bigger pharma companies like Gilead and Roche does trigger a lot of activity, organizational and otherwise, within an organization. And adding business development activities has to take account of that. So we -- at this point in time, we'd like to retain value in our programs and not partner them away.

是的。因此，任何合作實際上都是一項相當複雜的工作。與吉利德和羅氏等更大的製藥公司合作確實會引發組織內部的大量活動，無論是組織活動還是其他活動。添加業務開發活動必須考慮到這一點。所以我們 - 在這個時間點，我們希望保留我們計劃的價值，而不是與他們合作。

Having said that, we have a technology platform, and we know that there are many different antigens that we're currently not tackling, which we could if a pharma company was interested in it. And clearly, the development of capital markets, the way we're seeing them today may also trigger one or the other thought about interesting deal structures that provide -- that would provide funding capital to the company.

話雖如此，我們有一個技術平台，而且我們知道我們目前沒有處理許多不同的抗原，如果一家製藥公司對此感興趣，我們就可以處理。很明顯，資本市場的發展，我們今天看到的方式，也可能引發一種或另一種關於有趣的交易結構的想法——這將為公司提供融資資本。

So you're asking a complex question. At this point in time, we're very, very happy about our collaborations with Roche and Gilead.

所以你問的是一個複雜的問題。在這個時候，我們對與羅氏和吉利德的合作感到非常非常高興。

We can see that as our data sets mature and the strength of the technology gets more and more proven, other people could be interested, and we would not be averse to partnering. At the same time, we do know that retaining value in the company is important. And therefore, we would have to look at it at the moment that such partnership discussions come up.

我們可以看到，隨著我們的數據集越來越成熟，技術的實力越來越得到證實，其他人可能會感興趣，我們也不會反對合作。同時，我們確實知道在公司保留價值很重要。因此，我們必須在出現此類合作夥伴關係討論時查看它。

Got it. Thanks a lot.

知道了。多謝。

And there are no further questions at this time. I would like to turn the conference back over to management for any additional or closing remarks.

目前沒有其他問題。我想將會議轉回管理層，以獲得任何補充或結束語。

Very briefly, I think we've had a great year 2022. We're gearing up to some important value inflection points and milestones and are looking forward and curious to see the outcome of all of this and would basically tell our shareholders that we're doing our utmost to keep our burn low up until better times at capital markets to really progress the company to big value inflection points that will change its valuation and, with that, the future.

簡而言之，我認為我們在 2022 年度過了美好的一年。我們正在為一些重要的價值轉折點和里程碑做準備，並且期待並好奇地看到所有這一切的結果，並且基本上會告訴我們的股東我們'我們正在盡最大努力保持低燒錢，直到資本市場出現更好的時機，才能真正將公司推向巨大的價值拐點，這將改變其估值，進而改變未來。

Thanks a lot and talk to you soon. Bye-bye.

非常感謝，很快就會和你談談。再見。

And that does conclude today's conference. Thank you for your participation. You may now disconnect.

今天的會議到此結束。感謝您的參與。您現在可以斷開連接。