XBiotech Inc (XBIT) 2017 Q1 法說會逐字稿

Good day, ladies and gentlemen and welcome to the XBiotech's First Quarter 2017 Earnings Conference Call. (Operator Instructions) As a reminder, this conference is being recorded.

女士們、先生們，美好的一天，歡迎參加 XBiotech 2017 年第一季財報電話會議。 （操作員指示）謹此提醒，本次會議正在錄製中。

I would now like to introduce your host for today's conference, Ashley Otero. You may begin.

現在我想介紹今天會議的主持人 Ashley Otero。你可以開始了。

Thank you, operator. Before turning the call over to our CEO, John Simard, I would like to make the following remarks. During this call, forward-looking statements including declarations regarding management's beliefs and expectations will be made. In some cases, you can identify forward-looking statements by terminologies such as may, will, should, would, could, expects, plans, contemplates, anticipates, believes, estimates, predicts, projects, intends, or continue or the negative of such terms or other comparable terminology, although not all forward-looking statements contain these identifying words.

謝謝你，接線生。在將電話轉給我們的執行長約翰·西馬德之前，我想發表以下評論。在本次電話會議中，將做出前瞻性聲明，包括有關管理層信念和期望的聲明。在某些情況下，您可以透過「可能」、「將」、「應該」、「將」、「可能」、「預期」、「計劃」、「考慮」、「預期」、「相信」、“估計」、「預測」、「項目」、「打算」、「繼續」或「繼續」等術語或這些術語的否定來識別前瞻性陳述。術語或其他類似術語，儘管並非所有前瞻性陳述都包含這些辨識詞。

Thank you for the introduction and thanks to all those attending the call this morning. I will speak to the status of our ongoing marketing authorization application first here this morning and then give a more general background of the other operations that are ongoing.

感謝您的介紹，也感謝今天早上參加電話會議的所有人員。今天早上我將首先在這裡談論我們正在進行的營銷授權申請的狀態，然後提供正在進行的其他操作的更一般背景。

As we already publically announced, on April 20, an oral explanation in support of our marketing authorization application was given to the EMA at its headquarters in London, England. In our opinion, an overwhelming body of evidence was presented that confirmed our True Human antibody works through specifically target tumor associated information and that this activity results in an important therapeutic benefit for patients with advanced colorectal cancer.

正如我們已經公開宣布的那樣，4 月 20 日，我們向位於英國倫敦總部的 EMA 提供了支持我們行銷授權申請的口頭解釋。我們認為，大量證據證實我們的 True Human 抗體透過專門針對腫瘤相關資訊發揮作用，而該活性可為晚期大腸直腸癌患者帶來重要的治療益處。

At the April 20 meeting, we've actually presented unambiguous findings from our Phase 3 pivotal study that our antibody therapy controlled a combination of key symptoms associated with advanced cancer and in particular advanced colorectal cancer. These symptoms included pain, fatigue, anorexia and muscle loss. Each of these measures were in fact established with the EMA's scientific group as the primary endpoint of the clinical study. And to be clear, we did in fact meet the planned primary outcome of the study. The symptoms we measured each are of critical importance to the patient's well being. That is in fact why the combined endpoint was considered so relevant as a measure of our drug's activity.

在 4 月 20 日的會議上，我們實際上提出了 3 期關鍵研究的明確發現，即我們的抗體療法控制了與晚期癌症，特別是晚期結直腸癌相關的一系列關鍵症狀。這些症狀包括疼痛、疲勞、厭食和肌肉損失。事實上，每項措施都是由 EMA 科學小組作為臨床研究的主要終點制定的。需要明確的是，我們實際上確實達到了該研究計劃的主要結果。我們測量的每項症狀對於患者的健康至關重要。事實上，這就是為什麼綜合終點被認為與衡量我們藥物活性的指標如此相關。

At the request of the EMA, we spent a long time investigating what we could learn about what these symptoms told us about the patient's disease. These findings were also groundbreaking. Our analysis showed that the symptoms [we then] used as an endpoint for the clinical study with far more relevant measures of prognosis than the longstanding use of tumor measures.

應 EMA 的要求，我們花了很長時間調查我們可以從這些症狀中了解到有關患者疾病的資訊。這些發現也是開創性的。我們的分析表明，[我們隨後]將症狀用作臨床研究的終點，與長期使用的腫瘤指標相比，其預後指標的相關性要高得多。

Our findings showed that patients which achieved the primary endpoint, in other words, patients which had achieved stabilization or improvement with these combination of symptoms also had dramatic increase in overall survival, reduced tumor progression in substantially fewer disease related serious adverse events.

我們的研究結果表明，達到主要終點的患者，換句話說，這些症狀組合已實現穩定或改善的患者，總體生存率也顯著提高，腫瘤進展減少，疾病相關的嚴重不良事件大大減少。

What was equally remarkable was that the safety and tolerability of the therapy was unprecedented for oncology. In the double-blinded placebo controlled Phase 3 study, doctors actually attributed more adverse events to placebo than to the antibody therapy. The findings with the therapy not only met our planned endpoints, but the new endpoints exceeded all of our expectations for its value as a measure of disease progression.

同樣值得注意的是，該療法的安全性和耐受性對於腫瘤學來說是前所未有的。在雙盲安慰劑對照三期研究中，醫生實際上將更多的不良事件歸因於安慰劑，而不是抗體療法。該療法的結果不僅達到了我們計劃的終點，而且新終點超出了我們對其作為疾病進展衡量標準的價值的所有預期。

At our invitation, the London meeting was attended by renowned oncologists that have used the antibody therapy in their clinics to treat colorectal cancer patients. These oncologists were Andrew Hendifar from the UCLA's Cedars-Sinai Cancer Center, Alexander Knuth, Professor Emeritus and Former Chief of Oncology, University of Zurich Hospital; Marii Sklodowskiej, Professor of Oncology in Warsaw; and Mark Saunders, Clinical Oncologist from the NHS Foundation Trust in the UK who came together with this research (inaudible).

應我們的邀請，著名的腫瘤學家參加了倫敦會議，他們在診所中使用抗體療法來治療大腸直腸癌患者。這些腫瘤學家包括來自加州大學洛杉磯分校雪松-西奈癌症中心的 Andrew Hendifar、蘇黎世大學醫院榮譽教授、前腫瘤科主任 Alexander Knuth； Marii Sklodowskiej，華沙腫瘤學教授；英國 NHS 基金會信託基金的臨床腫瘤學家 Mark Saunders 參與了這項研究（聽不清楚）。

Finally, we had a patient with us that has been in the Phase 3 study receiving antibody therapy for about two years. These extraordinary people convened in London to share their various experiences and the common belief that the antibody therapy serves a dire unmet medical need in advanced cancer. Their dedication, expertise and support was indeed inspirational.

最後，我們有一位患者已經接受抗體治療大約兩年了，處於第三階段研究。這些傑出人士齊聚倫敦，分享他們的各種經驗和共同信念，即抗體療法滿足了晚期癌症中未被滿足的嚴峻醫療需求。他們的奉獻精神、專業知識和支持確實令人鼓舞。

Unfortunately, we seemed unable to engage the CHMP committee members in any meaningful way to evaluate the data presented or to consider the important clinical benefits of the therapy. The presentation made at the meeting has been filed as an 8-K document and is available for download. Upon careful review of this presentation, I believe those knowledgeable in the field will conclude that the negative positions taken by the CHMP are in conflict with the scientific data reported.

不幸的是，我們似乎無法以任何有意義的方式讓 CHMP 委員會成員參與評估所提供的數據或考慮該療法的重要臨床益處。會議上的簡報已歸檔為 8-K 文件並可供下載。經過仔細閱讀本次演講，我相信該領域的知識淵博的人會得出結論，CHMP 所採取的負面立場與報告的科學數據相衝突。

It remains at present impossible for us to determine where the source of this conflict comes from. Although the design was based on explicit regulatory guidance provided by the EMA, the study did however represent a new way to evaluate an anti-cancer agent. Focusing on the use of symptoms as a measure of disease progression goes against tradition, against the use of tumor measures that have been used to evaluate anti-tumor activity of cancer agents for 60 years. Yet, the EMA's published guidance states that symptom control and I quote: If related to anti-tumor effects, is a valid measure of therapeutic activity and may serve as a primary endpoint in late line therapy studies, end quote. Moreover, key aspects of the study design used in the Phase 3 trial [rolls] out of an extensive collaborative process between the company and the EMA's own Scientific Advice Working Party.

目前我們還無法確定這場衝突的根源來自何處。儘管該設計是基於 EMA 提供的明確監管指導，但該研究確實代表了評估抗癌藥物的新方法。專注於使用症狀作為疾病進展的衡量標準違背了傳統，也違背了60年來一直用於評估癌症藥物抗腫瘤活性的腫瘤衡量標準。然而，EMA 發布的指南指出，症狀控制，我引用：如果與抗腫瘤作用相關，則是治療活性的有效衡量標準，並且可以作為後期治療研究的主要終點，引用結束。此外，第三階段試驗中使用的研究設計的關鍵方面是由該公司與 EMA 自己的科學建議工作小組之間的廣泛合作過程產生的。

Although the endpoints were new, we expected that these formal guidance and engagement activities with the EMA in the study design will provide the necessary institutional support for positive findings later to come. However, the outcome of the oral explanation leaves no doubt that the CHMP committee does not properly appreciate the importance of either the clinical approach or the data that was generated from the Phase 3 study. We must continue to work to help the EMA gain a better understanding, a better perspective of the data and the importance of the therapy for the unmet medical need for advanced colorectal cancer.

儘管終點是新的，但我們預計研究設計中 EMA 的這些正式指導和參與活動將為以後的積極發現提供必要的機構支持。然而，口頭解釋的結果無疑表明 CHMP 委員會沒有正確認識到臨床方法或 3 期研究產生的數據的重要性。我們必須繼續努力幫助 EMA 更好地理解、更好地看待數據以及治療對於晚期結直腸癌未滿足的醫療需求的重要性。

In these circumstances, EMA regulations provide for a reexamination procedure that can give us the opportunity to work further towards this aim. In summary, the reexamination procedure with the EMA is as follows. Within 15 calendar days, after receiving a final opinion, we are to submit a written notice to the EMA requesting reexamination. Within 60 days from the opinion, a further detailed explanation justifying the need for a reexamination must be provided. And within 60 days from receiving the detailed explanation, the EMA shall complete its reexamination process of its original opinion. During this period, the company may also seek additional input from the EMA Scientific Advice group or from an ad hoc group of experts to further support the reexamination process.

在這種情況下，EMA 法規規定了重新審查程序，使我們有機會進一步努力實現這一目標。綜上所述，EMA 的複審程序如下。在收到最終意見後 15 個日曆日內，我們將向 EMA 提交書面通知，要求重新審查。在提出意見後 60 天內，必須提供進一步詳細的解釋，證明需要重新審查。 EMA應在收到詳細解釋之日起60天內完成對原意見的複審程序。在此期間，公司還可以尋求 EMA 科學建議小組或特設專家小組的額外意見，以進一步支持複審過程。

A final opinion is expected after the CHMP convenes during its routine meeting in mid-May. It must be emphasized that we have not yet received the final opinion on our marketing authorization application. We received only a trending vote that took place immediately following the meeting. While the EMA has not shared the details and reasoning behind the trending vote, it was explained to us that the trend indicated that there would be a lack of support for an approval once the official vote is to be taken at the scheduled meeting in May. Hence, the immediate communication with you on the result of that trend.

預計 CHMP 在 5 月中旬召開例行會議後將得出最終意見。必須強調的是，我們尚未收到有關我們的行銷授權申請的最終意見。我們只收到了會議結束後立即進行的趨勢投票。雖然 EMA 沒有分享趨勢投票背後的細節和理由，但它向我們解釋說，該趨勢表明，一旦在 5 月的預定會議上進行正式投票，將缺乏對批准的支持。因此，我們會立即與您溝通該趨勢的結果。

We do however trust that through the remaining procedures available to us, it will be possible to build a consensus around the positive data and [the crucial] importance of our antibody therapy for treating advanced colorectal cancer. We are vigorously pursuing these activities.

然而，我們確實相信，透過我們可用的剩餘程序，將有可能圍繞積極數據和我們的抗體療法治療晚期結直腸癌的[至關重要]重要性達成共識。我們正在積極地進行這些活動。

It's important to know that this situation has happened in the recent past with other drugs. Since 2009, 18 products have undergone reexamination through this appeal process. The CHMP has reversed their original negative opinion to positive outcomes in seven of these cases.

重要的是要知道這種情況在最近的過去也曾在其他藥物中發生過。自2009年以來，已有18種產品透過上訴程序接受了複審。 CHMP 在其中 7 個案例中將最初的負面意見轉變為正面結果。

In May 2016, the anti-cancer agent, a tyrosine-kinase inhibitor developed by the Japanese pharmaceutical company, Takeda, was denied approval for the treatment of multiple myeloma. Denial of approval was after the drug showed significant improvement in progression free survival, but could not demonstrate extension of life in patients with advanced disease.

2016年5月，日本武田製藥公司開發的抗癌藥物酪胺酸激酶抑制劑用於治療多發性骨髓瘤的申請被拒絕。該藥物顯示無惡化存活期顯著改善，但無法證明晚期疾病患者的生命延長，因此被拒絕批准。

A reexamination was requested and the drug was eventually granted marketing authorization in November 2016. Crucial to the reexamination process appears to be the widespread support of the drug that it received among multiple myeloma advocacy groups across Europe.

有人要求重新審查，該藥物最終於 2016 年 11 月獲得上市許可。重新審查過程的關鍵似乎是該藥物在歐洲多發性骨髓瘤倡導團體中獲得了廣泛支持。

In another example, in 2014, the EMA rejected approval of a new treatment for Duchenne muscular dystrophy. The rejection was based on the fact that the pivotal study to demonstrate efficacy failed to meet its primary endpoint. This of course is a significant failure. The decision was appealed and post-hoc data analysis was accepted that showed that the drug was more effective in a subset of patients involved in the clinical study and based on this post-hoc data and the presence of another ongoing Phase 3 study, in May 2014, the EMA changed its decision and conditionally approved the drug.

另一個例子是，2014 年，EMA 拒絕批准杜氏肌肉營養不良症的新療法。拒絕的理由是證明療效的關鍵研究未能達到其主要終點。這當然是重大失敗。該決定被上訴，事後數據分析被接受，分析顯示該藥物對參與臨床研究的一部分患者更有效，並且基於事後數據和 5 月份另一項正在進行的 3 期研究2014年，EMA改變決定，有條件批准該藥物。

Again important in the decision by the EMA to grant conditional approval of the widespread backing of patient groups that demanded new treatments for muscular dystrophy.

對於 EMA 決定有條件批准對要求肌肉營養不良症新療法的患​​者群體的廣泛支持的決定來說，這一點也很重要。

There are at least 43 patient organizations spread across the 32 European countries that advocate for the right needs of colorectal cancer sufferers. Our plan is to get support from each and every one of these organizations and to deliver the support to the EMA.

歐洲 32 個國家至少有 43 個病患組織倡議滿足大腸直腸癌患者的正確需求。我們的計劃是獲得每個組織的支持並向 EMA 提供支援。

My personal experience with patients and patient advocates has been extraordinary. I believe we can garner patient support unlike any other cancer drug before us. That is because our treatment is unlike any other cancer drug before and how it makes patients feel better while it attacks the disease. This is enormously important to patients and the fact that the drug was derived of a natural human antibody gives patients a great deal of comfort in receiving the therapy.

我與患者和患者倡導者打交道的個人經歷非同尋常。我相信我們能夠獲得患者的支持，這與我們之前的任何其他抗癌藥物不同。這是因為我們的治療方法不同於以前任何其他癌症藥物，而且它如何讓患者在攻擊疾病時感覺更好。這對患者來說非常重要，而且該藥物源自天然人類抗體這一事實使患者在接受治療時感到非常舒適。

Every situation is different and there are complex to multiple variables involved in this approval process. But in our case, we achieved our primary endpoint for a study that we designed together with the EMA and we demonstrated unequivocal benefits for patients receiving the therapy. We have a therapy that patients and clinicians are screaming for. I must believe that our well grounded appeal strenuously supported by all the stakeholders involved will be appropriately received in the reexamination process by the EMA. Again, we will vigorously pursue this reexamination process.

每種情況都不同，審批過程中涉及的變數也很複雜。但在我們的案例中，我們實現了與 EMA 共同設計的一項研究的主要終點，並且我們向接受治療的患者展示了明確的益處。我們有一種患者和臨床醫生都渴望的療法。我必須相信，我們的上訴有理有據，得到了所有相關利益相關者的大力支持，EMA 將會在復審過程中得到適當的接受。再次，我們將大力推進這項複審進程。

While we continue to pursue our EU marketing authorization, other important clinical programs are not affected. Our global Phase 3 study is ongoing, that has completed enrollment with 640 patients having received treatment with either our antibody therapy or placebo in advanced colorectal cancer population. Although this study is in a similar patient population to that conducted in Europe, the endpoint differs from the EMA study.

雖然我們繼續尋求歐盟行銷授權，但其他重要的臨床項目不受影響。我們的全球 3 期研究正在進行中，已完成 640 名在晚期結直腸癌人群中接受我們的抗體療法或安慰劑治療的患者的入組。儘管這項研究的患者群體與歐洲進行的研究相似，但終點與 EMA 研究不同。

The global Phase 3 study under our fast tracked FDA regulatory path has a conventional objective of demonstrating overall survival as the primary endpoint. In other words, the placebo controlled randomized double blinded study must show a significant improvement in overall survival between the treatment and placebo groups.

我們快速追蹤 FDA 監管路徑下的全球 3 期研究的傳統目標是證明總體存活率作為主要終點。換句話說，安慰劑對照的隨機雙盲研究必須顯示治療組和安慰劑組之間的總存活率有顯著改善。

The second interim analysis is scheduled for mid-June. And the second interim will be similar to the first in that there will be three possible outcomes. Completion of the study because of the successful demonstration of the primary endpoint, a continuation of the study to collect more survival data or a halting of the study if we fail to meet the statistical significance for the survival effect. We will of course report on the outcome of this analysis when it becomes available.

第二次中期分析定於六月中旬進行。第二個過渡期將與第一個過渡期類似，因為將出現三種可能的結果。由於主要終點的成功論證而完成研究，繼續研究以收集更多生存數據，或者如果我們未能達到生存效應的統計顯著性，則停止研究。當然，我們會在分析結果可用時進行報告。

To discuss our development pipeline beyond oncology, I will briefly mention two other clinical programs for which we are in the planning stages for registration studies. We are in the process of developing Phase 3 pivotal study protocols for both our dermatology and our infectious disease programs. As soon as possible, we will be submitting registration plans to the FDA for what is known as a special protocol assessment or SPA for both the dermatology and infectious disease therapies.

為了討論我們在腫瘤學之外的開發管線，我將簡要提及我們正處於註冊研究規劃階段的另外兩個臨床項目。我們正在為我們的皮膚科和傳染病計畫制定第三階段關鍵研究方案。我們將盡快向 FDA 提交註冊計劃，以進行皮膚科和傳染病治療的特殊方案評估或 SPA。

These SPAs will enable the agency to review and help guide the development of the clinical protocols so that we are in better agreement on what will be sufficient data to seek product registration. We expect to have agency feedback for each of these pivotal study designs around the same quarter of 2017.

這些 SPA 將使該機構能夠審查並幫助指導臨床方案的製定，以便我們就尋求產品註冊所需的足夠數據達成更好的一致性。我們預計將在 2017 年同一季度收到每項關鍵研究設計的機構回饋。

When I speak of our dermatology program in this context, I'm speaking of Hidradenitis Suppurativa. And our recent findings from our Phase 2 study showed that our antibody therapy for Hidradenitis significantly improved the disease including in patients that were refractory to other best known therapies such as Remicade or Humira.

當我在這種情況下談到我們的皮膚科計畫時，我指的是化膿性汗腺炎。我們最近的 2 期研究結果表明，我們針對汗腺炎的抗體療法顯著改善了這種疾病，包括對其他最著名療法（如 Remicade 或 Humira）難治的患者。

Importantly, while our therapy improved the skin lesions, it also worked under the skin to reduce the underlying vascularization of the lesions. 60% of the patients treated had meaningful improvement in the disease according to the accepted heart score rating system that is used to assess disease severity in Hidradenitis. The devastating nature of the disease, the lack of treatment options and the high incidence of diseases in the public made the treatment response that we saw to our therapy all the more important.

重要的是，雖然我們的治療改善了皮膚病變，但它也在皮下發揮作用，減少病變的潛在血管化。根據公認的用於評估汗腺炎疾病嚴重程度的心臟評分系統，60% 的接受治療的患者的疾病得到了有意義的改善。這種疾病的破壞性、治療選擇的缺乏以及公眾中疾病的高發病率使得我們看到的治療反應變得更加重要。

But what we also saw in terms of reduction in vascularization of the skin lesions was tremendously important in terms of the potential durability in the treatment and how it confirmed a fundamental mechanism of action that has wide ranging implications for this antibody therapy.

但我們也看到，皮膚病變血管化的減少對於治療的潛在持久性以及它如何證實對這種抗體療法具有廣泛影響的基本作用機製而言非常重要。

We know that the target of the antibody is a potent inducer of angiogenesis but we have not previously had the clinical study designs, which allowed us to capture these kinds of results. So this activity goes beyond skin disease and speaks to a very fundamental mechanism that could be at work for patients that are treated with the antibody in other diseases too like cancer where inhibiting tumor angiogenesis has been a duty of oncologists for decades.

我們知道抗體的標靶是血管生成的有效誘導劑，但我們之前沒有臨床研究設計，這使我們能夠獲得此類結果。因此，這項活動超越了皮膚病的範圍，並說明了一種非常基本的機制，該機制可能對接受該抗體治療的其他疾病（例如癌症）的患者起作用，幾十年來，抑制腫瘤血管生成一直是腫瘤學家的職責。

In summary, our findings in Hidradenitis suggest a very important therapy for patients suffering from this disease which is estimated to affect as many as 4% of the population. Our treatment for Hidradenitis will have important impact on this disease for sure. But our results in dermatology as a whole including psoriasis and acne suggest that Hidradenitis is the tip of the iceberg and that an approval to Hidradenitis will be a gateway to proving that our antibody therapy is the most important new treatment approach in development today for our inflammatory skin disorders.

總之，我們在汗腺炎方面的研究結果表明，對於患有這種疾病的患者來說，這是一種非常重要的治療方法，據估計，這種疾病影響了多達 4% 的人口。我們對汗腺炎的治療肯定會對這種疾病產生重要影響。但我們在包括牛皮癬和痤瘡在內的整個皮膚病學方面的結果表明，汗腺炎只是冰山一角，汗腺炎的批准將成為證明我們的抗體療法是當今正在開發的針對我們的炎症的最重要的新治療方法的門戶。皮膚疾病。

I would like now to say a few words about our infectious disease program. Our discovery approach to deriving antibody therapeutics of individuals with natural immunity to disease has the potential for treating a new generation of therapies for infectious disease. We're pleased with the [goal] or the speed at which we can identify a candidate therapy from an individual that has antibodies to neutralize a deadly infectious agent.

我現在想談談我們的傳染病項目。我們對具有疾病天然免疫力的個體進行抗體治療的發現方法具有治療新一代傳染病療法的潛力。我們對[目標]或從具有中和致命傳染原的抗體的個體中識別出候選療法的速度感到滿意。

With our FDA Fast Track program to treat staphylococcus aureus, we showed that the very precise immunity so cleverly engineered by one person's immune system can be used to protect others even from bacteria evolved to evade the body's defenses. A recent clinical finding is therefore from our staph aureus therapy were a homerun.

透過 FDA 治療金黃色葡萄球菌的快速通道計劃，我們表明，由一個人的免疫系統巧妙設計的非常精確的免疫力可以用來保護其他人，甚至免受進化來逃避人體防禦的細菌的侵害。因此，最近的一項臨床發現表明我們的金黃色葡萄球菌療法取得了成功。

Let me give you a little background on the study. We knew from the start that our antibody therapy was unique. (Inaudible) attempts to treat staph infections, we found for the first time an antibody that targets the bacteria at a key virulence factor. It's allowed the bacteria to escape the body's immune system and to cause devastating disease. We fully expect that the antibody can neutralize blood-borne staph infections and to do it as safely as if it were a natural antibody already present in the person's body.

讓我向您介紹一下這項研究的背景。我們從一開始就知道我們的抗體療法是獨一無二的。 （聽不清楚）在治療葡萄球菌感染的嘗試中，我們首次發現了一種針對細菌關鍵毒力因子的抗體。它使細菌逃離人體的免疫系統並引起毀滅性的疾病。我們完全期望該抗體能夠中和血源性葡萄球菌感染，並且像人體內已經存在的天然抗體一樣安全。

What we knew less about though was who and where would we find these infections. We wanted to demonstrate activity in patients who needed help the most. That is those with bacteria that had spread into the blood and had significant risk of dying from the infection. We had good ideas from the literature about who were the most likely patients to have this infection and we consulted extensively with medical experts to determine where this drug might -- most commonly be used. But as with all complex problems, it took real world experience to actually learn the most about the patient population, who is in need of this antibody therapy. The recent clinical studies with dozens of hospitals [to] have our antibody on the shelf to treat people urgently in need of therapy.

但我們不太了解的是我們會在哪裡發現這些感染。我們希望在最需要幫助的患者中展示活動。這些細菌已經擴散到血液中，並且有很大的死於感染的風險。我們從文獻中得到了關於誰最有可能感染這種感染的患者的好主意，並且我們廣泛諮詢了醫學專家，以確定這種藥物最常使用的地方。但與所有複雜問題一樣，需要現實世界的經驗才能真正了解需要這種抗體療法的患者群體。最近與數十家醫院進行的臨床研究使我們的抗體上架，以治療急需治療的人。

As it turned out, the lead doctor at the clinic -- for all the clinics was a surgeon that treated trauma victims. That is the investigator treated patients who came into the emergency ward after serious or life-threatening events. Patients at the center had been in car accidents, had head injuries, required emergency surgery for chronic diseases or the like. These patients who are subject to invasive procedures and the otherwise severely weakened by their injuries. They appeared to be the most susceptible to the blood infections with staph aureus.

事實證明，該診所的首席醫生——所有診所都是一位治療創傷受害者的外科醫生。這是研究者治療在嚴重或危及生命的事件後進入急診室的患者。中心的病人曾遭遇車禍、頭部受傷、因慢性疾病需要緊急手術等。這些患者遭受侵入性操作，並且因受傷而嚴重虛弱。他們似乎最容易受到金黃色葡萄球菌血液感染。

A key endpoint in this study, we however -- the duration of hospitalization and the incidence of serious adverse events. As we saw the complicated nature of the background illnesses of the patient's blood staph bacteremia, it became concerning whether or not we could see ultimately a reduction in hospitalization or serious adverse events by treating only the bacteremia. In other words, there was so much background noise related to the bacteremia that treating the infectious disease, although serious and life-threatening, might not give us a clear enough signal of the drug effect. So it was quite extraordinary.

然而，這項研究的關鍵終點是住院時間和嚴重不良事件的發生率。當我們看到患者血葡萄球菌菌血症的背景疾病的複雜性時，我們開始考慮是否可以透過僅治療菌血症來最終減少住院或嚴重不良事件。換句話說，與菌血症相關的背景噪音如此之多，以至於治療這種傳染病雖然嚴重且危及生命，但可能無法向我們提供足夠清晰的藥物作用訊號。所以這是非常不尋常的。

Once the study completed, it was unblinded to find that there was about half as many serious adverse events overall in patients receiving antibody and nearly 60% reduction in serious adverse events that were deemed to be related to infection. As well, hospitalization time was reduced by about one-third in those receiving the antibody. This was exactly the signal that we were hoping for. And it came in spite of a patient population that had so much background illness, it made us uncertain of the outcome.

研究完成後，我們發現，接受抗體治療的患者的嚴重不良事件總數約為一半，並且被認為與感染相關的嚴重不良事件減少了近 60%。此外，接受抗體的患者的住院時間也減少了約三分之一。這正是我們所希望的訊號。儘管患者群體有如此多的背景疾病，但它還是出現了，這讓我們對結果感到不確定。

In the clinical testing of the (inaudible), it is essential that you demonstrate a treatment effect that shows an impact, a positive impact on the patient's well-being. Reducing serious adverse events or hospitalized days is just such an effect. This is how we plan to approach the pivotal study for registration of the product.

在（聽不清楚）的臨床測試中，必須證明治療效果能對患者的健康產生正面的影響。減少嚴重不良事件或住院天數就是這樣的效果。這就是我們計劃進行產品註冊關鍵研究的方式。

We are now developing a pivotal study plan that will enable us to seek market registration for our 514G3 antibody therapy to treat life-threatening staphylococcus aureus infections. As I mentioned before, the first step would be getting the study proposal to the FDA and getting their detailed feedback on the plan and the endpoints. Once this is achieved, we would be prepared to launch an approval study. We will give you more information on the timing of this program as we progress.

我們現在正在製定一項關鍵研究計劃，該計劃將使我們能夠為 514G3 抗體療法尋求市場註冊，以治療危及生命的金黃色葡萄球菌感染。正如我之前提到的，第一步是將研究提案提交給 FDA，並獲得他們對計劃和終點的詳細回饋。一旦實現這一目標，我們將準備啟動一項批准研究。隨著我們的進展，我們將向您提供有關該計劃時間表的更多資訊。

To help us with all of this scientific and clinical development, we recently announced the formalization of a scientific advisory board, which now includes leading physicians and researchers with a broad range of expertise relating to the [age] of the company's product pipeline, including oncology, dermatology, infectious disease and Type 2 diabetes. We have put brief biographies of these extremely talented and dedicated physicians on our website. I encourage those that are interested in learning more about some of these doctors involved to go ahead and have a look at the XBiotech website.

為了幫助我們完成所有這些科學和臨床開發，我們最近宣布成立一個科學顧問委員會，該委員會現在包括領先的醫生和研究人員，他們擁有與公司產品線[年齡]相關的廣泛專業知識，包括腫瘤學、皮膚科、傳染病和第2型糖尿病。我們在我們的網站上放置了這些極其有才華和敬業的醫生的簡介。我鼓勵那些有興趣了解更多有關其中一些醫生的信息的人繼續訪問 XBiotech 網站。

I want to say just a few words about our ongoing groundbreaking discovery work. In general, our technology enables us to capture the essence of protective immunity from its individual and share it with others. The potential safety and benefits from this approach I think are quite intuitive. But what is a really remarkable opportunity, an unmet need for these kinds of therapies is with our ageing population. Antibodies play a crucial role in eliminating infectious disease before they can become a problem. As we age, our immune system diminish. By the time we reach retirement age, the quality and quantity of our antibody defense has significantly diminished.

我想簡單談談我們正在進行的突破性發現工作。總的來說，我們的技術使我們能夠捕捉到個體的保護性免疫力的本質，並與他人分享。我認為這種方法的潛在安全性和好處是非常直觀的。但真正令人矚目的機會是，我們的人口老化對此類療法的需求尚未得到滿足。在傳染病成為問題之前，抗體在消除傳染病方面發揮著至關重要的作用。隨著年齡的增長，我們的免疫系統會減弱。當我們達到退休年齡時，我們的抗體防禦的品質和數量都顯著下降。

This diminishing antibody immunity cannot be overcome by immunization and just simply isn't the machinery in place any longer to produce the kinds of antibodies that we give at one point in our lives.

這種抗體免疫力的下降無法透過免疫來克服，而且它根本就不再是產生我們在生命中某個時刻所產生的抗體的機制。

Consequently, infectious disease agents that were once easily controlled begin to outpace and outmaneuver our antibody system. Diseases like C. difficile, herpes-zoster and Influenza are prime examples of infectious agents once well-controlled that begin to represent an existential threat to a body no longer defended by a strong antibody system.

因此，曾經容易控制的傳染病病原體開始超越我們的抗體系統。艱難梭菌、帶狀皰疹和流感等疾病是傳染源的主要例子，一旦得到良好控制，它們就會開始對不再受到強大抗體系統防禦的身體構成生存威脅。

So what we are able to do in essence is to replace that diminishing antibody response with those that have been lost. When we search the healthy human population for natural antibodies against disease, we are finding those natural protectors that have been lost with age. We can make it and we can synthesize those antibodies in large quantities to use to reinvigorate the [eroding] immune system.

因此，我們本質上能夠做的就是用已經失去的抗體反應來取代正在減弱的抗體反應。當我們在健康人群中尋找針對疾病的天然抗體時，我們發現了那些隨著年齡的增長而失去的天然保護劑。我們可以製造它，我們可以大量合成這些抗體，用於重振[正在惡化的]免疫系統。

With the ageing demographics in our industrial societies, the need for this approach is both massive and growing every day. And to me, it is the most sensible use of biological therapy that one can imagine.

隨著工業社會人口老化，對這種方法的需求不僅巨大而且每天都在增長。對我來說，這是人們能想像到的最明智的生物療法用途。

Within this platform, we are furthering innovation to find unique approaches to make these therapies as effective and as useful as possible. You may remember that we are working towards development of the first oral monoclonal antibody therapy, which we will use to try and prevent the terrible intestinal infections caused by C. difficile.

在這個平台上，我們正​​在進一步創新，尋找獨特的方法，使這些療法盡可能有效和有用。您可能還記得，我們​​正在努力開發第一種口服單株抗體療法，我們將用它來嘗試預防由艱難梭菌引起的可怕腸道感染。

In hundreds of thousands of elderly people each year in the United States, Europe and Japan [awaiting] antibody immunity that protects their intestine from uncontrolled colonization by this bacteria allows the disease to manifest with a high degree of morbidity and deadly consequences. We have found antibodies in healthy volunteers that target the exact ranges of the bacteria we believe are involved in its attachment to the lining of the intestine. We've also found antibodies that target parts of the bacteria involved in its motility. We believe these antibodies are involved in protecting healthy immunocompetent individuals from developing disease. And we are extremely excited about the potential to bring these antibodies into the clinic to supplement the immunity of our ageing population and relieve the considerable human suffering that these infections cause today.

在美國、歐洲和日本，每年有數十萬老年人等待抗體免疫，以保護他們的腸道免受這種細菌不受控制的定植，從而導致這種疾病表現出高發病率和致命後果。我們在健康志願者體內發現了抗體，這些抗體針對我們認為與腸道內壁附著有關的細菌的確切範圍。我們也發現了針對細菌運動相關部位的抗體。我們相信這些抗體有助於保護健康的免疫功能正常的個體免受疾病的侵害。我們對將這些抗體引入臨床以補充老齡化人口的免疫力並減輕這些感染今天給人類帶來的巨大痛苦的潛力感到非常興奮。

Our True Human antibody candidates targeting C. difficile are now being developed for production cell lines that will enable us to manufacture products and support final stages of preclinical research and to support clinical trials and distribution to the market. Because this is an oral antibody therapy and not administrated directly into the bloodstream, it gives us opportunities to reduce some of the downstream production steps normally used in the manufacturing of antibodies.

我們針對艱難梭菌的 True Human 候選抗體目前正在開髮用於生產細胞系，這將使我們能夠生產產品並支持臨床前研究的最後階段，並支持臨床試驗和市場分銷。由於這是一種口服抗體療法，不會直接施用到血液中，因此它使我們有機會減少通常用於抗體製造的一些下游生產步驟。

We will therefore be innovating further in our manufacturing process to further reduce the cost and complexity of the production process for this therapy. We will submit these details along with the protocol to the FDA to gain their early feedback for all aspects of this program and I will keep you appraised as this important therapy advances closer to the clinic.

因此，我們將進一步創新我們的製造工藝，以進一步降低該療法生產過程的成本和複雜性。我們將把這些詳細資訊連同方案一起提交給 FDA，以獲得他們對該計劃各個方面的早期反饋，隨著這項重要療法越來越接近臨床，我將隨時對您進行評估。

The development of our True Human antibody therapies for Influenza and herpes zoster is also proceeding. Antibody candidates against herpes zoster have now been shortlisted and will undergo in vitro testing for efficacy soon.

我們針對流感和帶狀皰疹的 True Human 抗體療法的開發也在進行中。針對帶狀皰疹的候選抗體現已入圍，並將很快進行體外療效測試。

Our search for broadly neutralizing antibodies for Influenza are continuing, but to date, we have not been satisfied with the breadth of activity we can achieve with the antibodies we have found so far. Because of the variations between Influenza, finding an antibody that can protect against many different strains would be ideal for the product. And to achieve this kind of broadly neutralizing activity, we will have to continue to screen the candidate molecules we have found to date.

我們仍在繼續尋找流感的廣泛中和抗體，但迄今為止，我們對迄今為止發現的抗體所能實現的活性廣度並不滿意。由於流感之間存在差異，因此找到一種可以針對多種不同病毒株提供保護的抗體將是該產品的理想選擇。為了實現這種廣泛的中和活性，我們必須繼續篩選迄今為止發現的候選分子。

As we have talked about in the past, we were recently granted GMP certification by the EMA to enable our production of antibody for the market. This manufacturing infrastructure is a cornerstone that will enable our drug production needs for all of our clinical trials and commercial programs, including oncology, dermatology and infectious disease programs. We continue to build on our operational capabilities in our new manufacturing facility and our first full-scale manufacturing runs that support registration of the facility began already in the first quarter and will continue. We still have work to do to bring that facility online.

正如我們過去談到的，我們最近獲得了 EMA 的 GMP 認證，使我們能夠為市場生產抗體。該製造基礎設施是滿足我們所有臨床試驗和商業項目（包括腫瘤學、皮膚病學和傳染病項目）的藥物生產需求的基石。我們繼續增強新製造工廠的營運能力，支援該工廠註冊的首次全面製造運作已於第一季開始並將繼續進行。我們仍有工作要做才能使該設施上線。

I will now summarize briefly our financial position today. From inception through March 31, 2017, the company has accumulated a deficit of approximately $257 million. During the first quarter of 2017, the company had about $10.9 million in operating expenses, which is about $700,000 above our operating expenses during the first quarter of 2016. As of March 31, 2017, XBiotech had cash and cash equivalents of approximately $54.6 million. Our biggest cash needs during the quarter were in the [supported] contract and clinical operations where we spent about $3.8 million.

我現在簡要地總結一下我們今天的財務狀況。從成立到2017年3月31日，該公司已累計赤字約2.57億美元。 2017年第一季度，該公司的營運費用約為1,090萬美元，比2016年第一季的營運費用高出約70萬美元。截至2017年3月31日，XBiotech擁有現金和現金等價物約5,460萬美元。本季我們最大的現金需求是[支援的]合約和臨床業務，我們花了約 380 萬美元。

Overall, personnel costs for the quarter were our second biggest cost center, where we spent approximately $2.7 million. We spent an additional $1.2 million in laboratory supplies and some trailing costs related to our construction and manufacturing amounted to about $1.5 million.

總體而言，本季的人員成本是我們的第二大成本中心，我們花費了約 270 萬美元。我們在實驗室用品上額外花費了 120 萬美元，與我們的建設和製造相關的一些後續成本約為 150 萬美元。

As you already know on the last quarter, we raised about $32 million in a registered direct offering. This means that we sold shares directly without a broker or an underwriter and without any of the associated fees and that these shares were registered in tradable securities. The company has, based on its current burn rate, cash to operate into the third quarter of 2018.

正如您在上個季度已經知道的那樣，我們透過註冊直接發行籌集了約 3,200 萬美元。這意味著我們直接出售股票，沒有經紀人或承銷商，也沒有任何相關費用，而這些股票以可交易證券的形式登記。根據目前的燒錢率，該公司擁有足夠的現金營運至 2018 年第三季。

With that, I will wrap up this portion of the quarterly update and remind listeners that we will have Q&A session and I do look forward to trying to answer any of the thoughts or questions you may have. Operator, thank you. Please open the call to Q&A.

至此，我將總結季度更新的這一部分，並提醒聽眾，我們將舉行問答環節，我確實期待著嘗試回答您可能有的任何想法或問題。接線員，謝謝。請打開問答電話。

(Operator Instructions) Our first question comes from Kumar Raja of Noble Capital. Your line is open.

（操作員說明）我們的第一個問題來自Noble Capital 的Kumar Raja。您的線路已開通。

So the ongoing US colorectal trial, can that be leveraged for re-examination by the EMA. And also when you guys released Phase 2 data for staph aureus, there were some imbalances in the arm. And for the Phase 3 trial, what is the expectation in terms of how large a trial in terms of how many patients you would need and what can be done in that trial to reduce these imbalances?

因此，正在進行的美國結直腸試驗是否可以被 EMA 用來重新審查。而且，當你們發布金黃色葡萄球菌的第二階段數據時，手臂也出現了一些不平衡。對於 3 期試驗，您對試驗規模（需要多少患者）的期望是什麼？在該試驗中可以採取哪些措施來減少這些不平衡？

Hi. Thanks for the question. Thanks for calling in today. Mike, do you want to start with the second question?

你好。謝謝你的提問。感謝您今天打電話來。麥克，你想從第二個問題開始嗎？

Sure. Regarding the imbalances, as I'm sure you're aware, the patient numbers in the Phase 1/2 trial were 36 and 16. So 36 patients treated with the antibody and 16 with placebo. 30 of those were at the highest dose level and we did this design in this way in order to evaluate different dose levels not only for the potential for dose limiting toxicity, but also for the dose effect.

當然。關於不平衡，我相信您也知道，1/2 期試驗中的患者人數分別是 36 人和 16 人。因此，36 名患者接受了抗體治療，16 名患者接受了安慰劑治療。其中 30 個處於最高劑量水平，我們以這種方式進行設計是為了評估不同劑量水平，不僅評估劑量限制毒性的潛力，而且評估劑量效應。

So what we had was a study with relatively small numbers, which we had great results we feel, but there was this imbalance that we saw in the number of deaths. So, the way we would handle this and the way we will handle this moving forward is the same way anyone else would and that is with larger numbers, [I mean with our] Phase 3 pivotal trial, it's going to take quite a bit more than 52 patients, so larger numbers and one-to-one randomization that should account for any potential additional imbalances.

因此，我們進行的研究人數相對較少，我們認為取得了很好的結果，但我們在死亡人數中看到了這種不平衡。因此，我們處理這個問題的方式以及我們未來處理這個問題的方式與其他人一樣，而且是在數量更大的情況下，[我的意思是，在我們的]第三階段關鍵試驗中，這將需要更多的時間超過 52 名患者，因此更大的數量和一對一的隨機化應該可以解釋任何潛在的額外不平衡。

Does that answer your questions on that?

這能回答你的問題嗎？

Yes. And on the leveraging the US trial for re-examination by the EMA for the (multiple speakers) --

是的。關於利用美國的審判，讓 EMA 重新審查（多位發言者）——

Yes. I was going to answer that, as I gave an given example, the study in muscular dystrophy which failed on the first pass and to be granted approval, when they came back for the re-examination, they apparently did discuss and used the Phase 3 data that was ongoing in the separate study as part of the arguments to support the conditional approval that they ultimately achieved.

是的。我要回答的是，正如我舉的一個例子，肌肉營養不良症的研究在第一次通過時失敗並獲得批准，當他們回來重新審查時，他們顯然確實討論並使用了第三階段另一項研究中正在進行的數據，作為支持他們最終獲得有條件批准的論點的一部分。

So I think if history is any guide, with this re-examination process, it seems that anything could potentially be on the table. It's really up to the examiners at that time to decide what they think is relevant. This Phase 3 study could be viewed as relevant, but on the other hand, it's not really necessary. We did achieve the primary endpoint. The purpose of this study in Europe was to show improvement in a [stabilization] and the collection of symptoms that are unquestionably clinically relevant, pain, fatigue, anorexia and muscle mass, we demonstrated that and I think we want to focus on that, it's independent of the US study. And in our case, I'm not sure that we need the US study to be successful in our appeal.

所以我認為，如果以歷史為鑑的話，透過這個重新審視的過程，似乎任何事情都有可能擺在桌面上。這實際上取決於當時的審查員來決定他們認為相關的內容。這項第三階段的研究可以被視為相關的，但另一方面，它並不是真正必要的。我們確實達到了主要終點。這項在歐洲進行的研究的目的是顯示[穩定性]的改善以及毫無疑問與臨床相關的症狀的收集，疼痛，疲勞，厭食和肌肉質量，我們證明了這一點，我認為我們想要關注這一點，這是獨立於美國的研究。就我們而言，我不確定我們是否需要美國的研究才能成功上訴。

Thank you. (Operator Instructions) At this time, I'm showing no other callers in the queue for questions. So I'll turn the call back over to management for closing remarks.

謝謝。 （操作員說明） 目前，我沒有在隊列中顯示其他來電者詢問問題。因此，我將把電話轉回給管理層，讓其結束語。

We have no further remarks, but we do thank again everyone for coming on the call this morning. That will wrap up the session.

我們沒有進一步的評論，但我們再次感謝大家今天早上參加電話會議。會議就此結束。

Ladies and gentlemen, thank you for your participation in today's conference. You may disconnect. Have a wonderful day.

女士們、先生們，感謝你們參加今天的會議。您可以斷開連線。祝你有美好的一天。