Altimmune Inc (ALT) 2023 Q3 法說會逐字稿

Good day, ladies and gentlemen, and welcome to Altimmune, Inc., third-quarter 2023 financial results conference call. (Operator Instructions). As a reminder, this call is being recorded.

女士們、先生們，美好的一天，歡迎參加 Altimmune, Inc. 2023 年第三季財務業績電話會議。 （操作員說明）。提醒一下，此通話正在錄音。

I would now like to introduce your host for today's conference call Rich Eisenstadt, Chief Financial Officer of Altimmune. Rich, you may begin.

現在我想介紹一下今天電話會議的主持人 Altimmune 財務長 Rich Eisenstadt。里奇，你可以開始了。

Thank you, Olivia, and good morning, everyone. Thank you for participating in Altimmune's third-quarter 2023 financial results and business update conference call. Members of Altimmune team joining me on the call today are Vipin Garg, our Chief Executive Officer; Scot Roberts, our Chief Scientific Officer; and Scott Harris, our Chief Medical Officer.

謝謝你，奧莉維亞，大家早安。感謝您參加 Altimmune 2023 年第三季財務業績和業務更新電話會議。今天與我一起參加電話會議的 Altimmune 團隊成員包括我們的執行長 Vipin Garg；斯科特·羅伯茨，我們的首席科學官；和我們的首席醫療官斯科特哈里斯 (Scott Harris)。

Following the prepared remarks, we will hold a question-and-answer session. A press release with our third quarter 2023 financial results was issued this morning and can be found on the Investor Relations section of the company's website.

在準備好的發言之後，我們將舉行問答環節。今天早上發布了我們 2023 年第三季財務業績的新聞稿，可以在公司網站的投資者關係部分找到。

Before we begin, I would like to remind everyone that remarks about future expectations, plans and prospects constitute forward-looking statements for purposes of Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995.

在開始之前，我想提醒大家，有關未來預期、計畫和前景的言論構成前瞻性陳述，符合 1995 年《私人證券訴訟改革法案》中的安全港條款。

Altimmune cautions that these forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those indicated. For discussion of some of the risks and factors that could affect the company's future results and operations. Please see the risk factors and other cautionary statements contained in the company's filings with the SEC.

Altimmune 警告說，這些前瞻性陳述存在風險和不確定性，可能導致實際結果與所示結果有重大差異。討論可能影響公司未來業績和營運的一些風險和因素。請參閱該公司向 SEC 提交的文件中包含的風險因素和其他警示性聲明。

I will also direct you to read the forward-looking statement disclaimer in our press release issued this morning and now available on our website. Any statements made on this conference call speak only as of today's date, Tuesday, November 7, 2023, and the company does not undertake any obligation to update any of these forward-looking statements to reflect events or circumstances that occur on or after today's date.

我還將指導您閱讀今天上午發布的新聞稿中的前瞻性聲明免責聲明，該聲明現已在我們的網站上發布。本次電話會議上發表的任何聲明僅代表今天（2023 年 11 月 7 日星期二）的情況，本公司不承擔更新任何這些前瞻性聲明以反映今天或之後發生的事件或情況的義務。

As a reminder, this conference call is being recorded and will be available for audio replay on Altimmune's website. With that, I will now turn the call over to Dr. Vipin Garg, Chief Executive Officer of Altimmune. Vipin?

謹此提醒，本次電話會議正在錄製中，並將在 Altimmune 網站上進行音訊重播。現在，我將把電話轉給 Altimmune 執行長 Vipin Garg 博士。維賓？

Thank you, Rich, and good morning, everyone. We appreciate you joining us today for the discussion of our third quarter 2023 financial results and business update. We are excited about the continued advancement of our lead product candidate pemvidutide, a GLP-1/glucagon dual receptor agonist in development for both obesity and NASH.

謝謝你，里奇，大家早安。感謝您今天加入我們討論 2023 年第三季財務業績和業務更新。我們對我們的主要候選產品pemvidutide的持續進步感到興奮，pemvidutide是一種正在開髮用於治療肥胖和NASH的GLP-1/胰高血糖素雙受體激動劑。

The last subject completed this past September. In our Phase 2 MOMENTUM, pemvidutide subjects with obesity or overweight. We remain on target to announce top line 48 week results this quarter. Recall the MOMENTUM data showed weight loss of 10.7% at the 2.4 milligram dose after only 24 weeks of treatment.

最後一科於去年九月完成。在我們的 2 期 MOMENTUM 中，pemvidutide 受試者患有肥胖或超重。我們的目標仍然是公佈本季 48 週的頂線業績。回想一下，MOMENTUM 數據顯示，僅治療 24 週後，2.4 毫克劑量的體重減輕了 10.7%。

These robust reductions in body weight, together with waist circumference of the serum lipids, blood pressure without any advance or without clinically meaningful increases at heart rate or other cardiovascular signals suggest that if approved and we do guide maybe an important treatment option for patients with obesity, especially those with NAFLD or dyslipidemia.

這些體重的大幅下降，加上血脂、血壓的腰圍沒有任何進展，或者心率或其他心血管信號沒有臨床意義的增加，表明如果獲得批准並且我們確實指導可能是肥胖患者的重要治療選擇，尤其是患有NAFLD 或血脂異常的患者。

It is important to point out that these two conditions are prevalent in approximately 70% up to obesity population. In our NASH program we recently announced that the FDA has granted Fast Track designation to digitize for the treatment NASH. Fast Track designation is designed to facilitate the development and expedite the review of drugs intended to treat serious conditions and address unmet medical needs.

需要指出的是，這兩種情況在大約 70% 的肥胖人群中普遍存在。在我們的 NASH 計畫中，我們最近宣布 FDA 已授予 NASH 治療數位化快速通道指定。快速通道指定旨在促進用於治療嚴重疾病和解決未滿足的醫療需求的藥物的開發和加快審查。

NASH is a growing public health concern and there are currently two treatments. The FDA decision was informed in part by the results of our two newest Phase 1b randomized placebo-controlled trials of [pemvidutide] in subjects with nonalcoholic fatty liver disease.

NASH 是一個日益嚴重的公共衛生問題，目前有兩種治療方法。 FDA 的決定部分是基於我們在非酒精性脂肪肝患者中進行的兩項最新 1b 期隨機安慰劑對照試驗的結果。

We have a relative reduction in liver fat content up to 76% combined with significant weight loss were achieved. The efficacy and safety of packaging guided ash should be evaluated and impact our Phase 2b randomized, placebo-controlled biopsy-based trial.

我們的肝臟脂肪含量相對減少了 76%，並且實現了顯著的體重減輕。應評估包裝引導灰燼的功效和安全性，並影響我們的 2b 期隨機、安慰劑對照活檢試驗。

Given the compelling [great] data from our Phase 1b trial, we expect to achieve significant rates of NASH resolution and fibrosis improvement and data readout, which is anticipated the Q1 2025, as also announced new clinical data and phenotype factory and anti-fibrotic effects are digitized. We'll be presented at a late-breaking abstract at [ASL, ASLD]. We refer to a prior press release posted on our website and the details of that relation.

鑑於我們1b 期試驗中令人信服的[偉大]數據，我們預計將在2025 年第一季實現NASH 消退、纖維化改善和數據讀出的顯著速度，同時也宣布了新的臨床數據和表型工廠以及抗纖維化效果數位化。我們將在 [ASL、ASLD] 上看到最新的摘要。我們參考了我們網站上發布的先前新聞稿以及該關係的詳細資訊。

Finally, we expect to have a data readout from our Phase 2b clinical trial of HepTcell in chronic hepatitis B in the first quarter of 2024. We call that this trial is designed to show evidence of Altimmune model effects against hepatitis B virus and establish the role of HepTcell in combination therapy for the three significant progress FMP do type (inaudible) and HepTcell at the upcoming results of these ongoing trials.

最後，我們預計將在 2024 年第一季獲得 HepTcell 治療慢性乙型肝炎的 2b 期臨床試驗的數據。我們稱該試驗旨在顯示 Altimmune 模型對抗乙型肝炎病毒的作用證據，並確定其作用HepTcell 在FMP do 型（聽不清楚）和HepTcell 聯合治療中的三個重大進展即將公佈這些正在進行的試驗的結果。

With that, I'll now turn the call over to our Chief Medical Officer, Dr. Scott Harris to discuss our clinical plans. Scott?

現在，我將把電話轉給我們的首席醫療官 Scott Harris 博士，討論我們的臨床計劃。史考特？

Thank you, Vipin, and good morning, everyone. I'll start off with our Phase 2 MOMENTUM trial, pemvidutide in obesity. The MOMENTUM trial enrolled 391 subjects with obesity or overweight with at least one co-morbidity, but without diabetes, Dr. Louis Aronne from Weil Cornell Medical School, a leading authority in obesity and obesity clinical trials is serving as the principal investigator.

謝謝你，Vipin，大家早安。我將從我們的 2 期 MOMENTUM 試驗開始：pemvidutide 治療肥胖症。 MOMENTUM 試驗招募了 391 名肥胖或超重且至少有一種共病但沒有糖尿病的受試者，肥胖和肥胖臨床試驗領域的權威權威威爾康奈爾醫學院的 Louis Aronne 博士擔任首席研究員。

Subjects were randomized 1:1:1:1 to 1.2 milligram, 1.8 milligram, 2.4 milligram pemvidutide or placebo administered weekly for 48 weeks in conjunction with diet and exercise. A prespecified interim analysis was performed when 160 subjects completed 24-weeks of treatment, weight losses of 10.7% at the 2.4 milligram dose and 9.4% at the 1.8 milligram dose were achieved compared to a 1.0 weight loss in subjects receiving placebo.

受試者以 1:1:1:1 的比例隨機分配至 1.2 毫克、1.8 毫克、2.4 毫克培維肽或安慰劑，每週服用 48 週，同時結合飲食和運動。當160 名受試者完成24 週的治療時，進行了預先指定的中期分析，與接受安慰劑的受試者體重減輕1.0 相比，2.4 毫克劑量的體重減輕了10.7%，1.8 毫克劑量的體重減輕了9.4%。

Approximately 50% of the subjects achieved at least 10% weight loss and approximately 20% of subjects achieved at least a 15% weight loss by week 24 at the 2.4 milligram and 1.8 milligram doses. Significant improvements or positive trends in cardiometabolic risk factors were observed. Importantly, these effects were achieved without a arrhythmias clinically meaningful heart rate increases or other safety signals.

在2.4毫克和1.8毫克劑量下，到第24週時，約50%的受試者實現了至少10%的體重減輕，約20%的受試者實現了至少15%的體重減輕。觀察到心臟代謝危險因子的顯著改善或正面趨勢。重要的是，這些效果是在沒有心律不整、有臨床意義的心率增加或其他安全訊號的情況下實現的。

These results are impactful in view of the data readouts from our from other compounds in the obesity space. At 24 weeks, the placebo-adjusted weight loss achieved by [semaglutide] in [tripeptide] were approximately 8% and 12%, respectively, with pemvidutide occupying the middle of this range at approximately 10% weight loss.

考慮到我們從肥胖領域其他化合物中讀出的數據，這些結果是有影響力的。 24 週時，[三肽] 中的[索馬魯肽] 實現的安慰劑調整體重減輕分別約為 8% 和 12%，而培維肽佔據該範圍的中間位置，體重減輕約為 10%。

It should also be pointed out that at the 24 week time point, the magnitude of LDL-cholesterol reduction, on tends to do tight treatment with several fold better than that achieved by [semaglutide] or pemvidutide in a similar population at the conclusion of their trials, but at 68 weeks and 72 weeks, respectively.

還應該指出的是，在 24 週時間點，LDL-膽固醇降低的幅度往往比在相似人群中使用[索馬魯肽]或培維肽在治療結束時所達到的效果好幾倍。試驗，但分別在68 週和72 週時進行。

We believe it is the action of the glucagon receptor agonism present intent to do tied, but not in semaglutide or pemvidutide. That leads to the improved effects of lipids and differentiates pemvidutide do time. The important reductions in lipid based cardiovascular risk factors suggests that pemvidutide has the potential to achieve even greater reductions in cardiovascular risk than those observed in the recently completed select cardiovascular outcomes trial.

我們認為這是胰高血糖素受體激動劑的作用，但與索馬魯肽或培維肽無關。這會改善脂質的作用並延長培維肽的作用時間。基於脂質的心血管危險因子的顯著降低表明，與最近完成的精選心血管結果試驗中觀察到的結果相比，培維肽有可能實現更大的心血管風險降低。

Of important note, pemvidutide type has not been associated with minimal heart rate increases in any of our trials to date by contrast, other GLP-1 based multi agonist containing glucagon had been associated with these increases and in one case arrhythmias, this may prove to be an important differentiator as cardiac effects may be may not be tolerated in a population with higher cardiovascular risk such as elderly individuals or individuals with pre-existing cardiovascular disease.

值得注意的是，迄今為止，在我們的任何試驗中，培維肽類型均未與最小心率增加相關，相比之下，其他含有胰高血糖素的基於GLP-1 的多激動劑與這些增加有關，在一種情況下，可能會導致心律不整，這可能證明是一個重要的區分因素，因為心血管風險較高的人群（例如老年人或患有心血管疾病的個體）可能無法耐受心臟效應。

We see the obesity marketplace is becoming highly segmented based on these different patient needs and profiles with tempted to type fulfilling the need for the large segment with elevated lipids or liver fat content, which we estimate to be approximately 70% of the obesity marketplace. And today may also provide the opportunity to initiate to established therapy without dose titration, which we believe may be a highly attractive option to primary care physicians.

我們看到，根據這些不同的患者需求和情況，肥胖市場正在變得高度細分，試圖透過類型來滿足血脂或肝臟脂肪含量升高的大部分市場的需求，我們估計這部分市場約佔肥胖市場的70%。今天也可能提供在不調整劑量的情況下開始既定治療的機會，我們相信這對初級保健醫生來說可能是一個非常有吸引力的選擇。

As the obesity market grows beyond specialty clinical settings, we believe pemvidutide type profile may be an ideal treatment for many patients and physician segments and may ultimately capture a significant portion of the obesity market. We look forward to the top-line 48 week results from the MOMENTUM trial later this quarter.

隨著肥胖市場的發展超越了專業臨床環境，我們相信培維肽類型可能是許多患者和醫生群體的理想治療方法，並可能最終佔據肥胖市場的很大一部分。我們期待本季稍後 MOMENTUM 試驗的 48 週頂線結果。

It should be noted that the placebo-adjusted weight loss achieved by semaglutide in tripeptide at 48 weeks were approximately 12% and 17%, respectively and based on our analysis of the 24-week interim data we believe that tend to do tight could achieve weight loss in the mid-teens at the 48 week time point. As discussed previously by Dr. Aronne, our lead investigator in the MOMENTUM trial.

值得注意的是，三肽索馬魯肽在 48 週時實現的安慰劑調整體重減輕分別約為 12% 和 17%，根據我們對 24 週中期數據的分析，我們認為傾向於緊縮可以實現體重減輕在48 週時間點，損失在十幾歲左右。正如我們 MOMENTUM 試驗的首席研究員 Aronne 博士之前所討論的。

This represents an important benchmark for reversal of most, if not all, of the key morbidities of obesity. Importantly, it should be pointed out that semaglutide and tripeptide exhibited continued weight loss from week 48 through weeks 68 weeks and 72 weeks, respectively. And that the weight loss curves generated in recent trials with glucagon containing compounds suggest that the weight loss with pemvidutide may continue beyond the 48-week time point.

這代表了逆轉大多數（如果不是全部）肥胖關鍵發病率的重要基準。重要的是，應該指出的是，索馬魯肽和三肽分別從第48週到第68週和第72週表現出持續的體重減輕。在最近使用含胰高血糖素的化合物進行的試驗中產生的體重減輕曲線表明，培維肽的體重減輕可能會持續超過 48 週的時間點。

This gives us confidence that the weight loss beyond that weight loss beyond the mid-teens could be achieved as subjects were to be treated for longer durations. We are optimistic about the pending results and look forward to ongoing discussions with FDA about the design of our Phase 3 program, which we hope to commence with a partner in the second half of 2024.

這讓我們相信，當受試者接受更長的治療時，可以達到超過十幾歲的體重減輕。我們對即將公佈的結果持樂觀態度，並期待與 FDA 就我們的 3 期專案的設計進行持續討論，我們希望與合作夥伴在 2024 年下半年開始該專案。

Now let me talk about our impact Phase 2b NASH trial. This biopsy driven NASH trial is being conducted at approximately 60 sites in the US with Dr. Stephen Harrison, Medical Director of Clinical Research and adjunct professor of medicine Oxford University, serving as the principal investigator, we're planning for approximately 190 subjects, both with and without diabetes to be enrolled.

現在讓我談談我們的 2b 期 NASH 試驗的影響。這項活檢驅動的 NASH 試驗正在美國大約 60 個地點進行，臨床研究醫學主任兼牛津大學醫學兼職教授 Stephen Harrison 博士擔任首席研究員，我們計劃對大約 190 名受試者進行研究患有和不患有糖尿病的患者均納入。

Subjects were randomized to pemvidutide 1.2 milligrams, pemvidutide 1.8 milligrams or placebo in 1:2:2 ratio and will be stratified for fibrosis stage in the presence or absence of diabetes. Therefore, approximately 38 subjects are expected to receive pemvidutide 1.2 milligrams, 76 subjects, pemvidutide 1.8 milligrams and 76 subjects placebo.

受試者以 1:2:2 的比例隨機接受 1.2 毫克派維肽、1.8 毫克派維肽或安慰劑，並根據是否患有糖尿病對纖維化階段進行分層。因此，預計約 38 名受試者接受培維肽 1.2 毫克，76 名受試者接受培維肽 1.8 毫克，76 名受試者接受安慰劑。

This trial will enroll subjects with a BMI of at least 27 kilograms per meter squared, liver fat content of at least 10%, 8% as measured by MRI-PDFF, a natural D score of at least four on a pre-treatment biopsy and either F2 or F3 fibrosis with at least 50% of subjects required to have F3 fibrosis.

該試驗將招募體重指數至少為每平方公尺 27 公斤、肝臟脂肪含量至少為 10%、MRI-PDFF 測量為 8%、治療前活檢中自然 D 評分至少為 4 的受試者，並且F2 或F3 纖維化，至少50% 的受試者需要患有F3 纖維化。

The primary efficacy endpoints of the IMPACT trial will be the dual endpoints of achieving either NASH resolution with no worsening of fibrosis or fibrosis improvement with no worsening of NASH with the primary treatment comparison being the 1.8 milligram dose versus placebo.

IMPACT 試驗的主要療效終點將是實現 NASH 消退且纖維化不惡化或纖維化改善但 NASH 不惡化的雙重終點，主要治療比較是 1.8 毫克劑量與安慰劑。

Secondary endpoints, which will include achievement of both NASH resolution and fibrosis improvement, liver fat reduction by MRI-PDFF corrected T1 response rate, serum lipids and other non-invasive markers of disease. Importantly, weight loss will also be assessed as a key endpoint, as we believe this will be an important differentiator with respect to the majority of NASH therapeutics in development.

次要終點，包括實現 NASH 消退和纖維化改善、透過 MRI-PDFF 校正的 T1 反應率減少肝臟脂肪、血脂和其他非侵入性疾病標記。重要的是，體重減輕也將作為關鍵終點進行評估，因為我們相信這將是與大多數正在開發的 NASH 療法的一個重要區別。

All efficacy endpoints will be evaluated week 24 of treatment and subjects will continue to be dosed and followed for an additional 24 weeks to a total of 48 weeks for safety and additional biomarker responses. As a reminder, the 24-week data from our NAFLD trials suggests of greater than 75% relative reduction in liver fat at 24 weeks.

所有療效終點將在治療第 24 週進行評估，受試者將繼續給藥並追蹤另外 24 週，總計 48 週，以確保安全性和其他生物標記反應。提醒一下，我們的 NAFLD 試驗的 24 週數據表明，24 週時肝臟脂肪相對減少了 75% 以上。

With over 50% of subjects achieving the high bar of normalization of liver fat at the 1.8 milligram dose. We also achieved significant reduction in serum ALT and MRI base corrected T1 imaging, both important markers of NASH improvement. As we've mentioned, new clinical data on the anti-inflammatory and anti-fibrotic effects of pemvidutide will be presented as a late-breaking abstract at [AASLD].

超過 50% 的受試者在 1.8 毫克劑量下達到了肝臟脂肪正常化的高標準。我們也實現了血清 ALT 和 MRI 基礎校正 T1 影像的顯著降低，這兩者都是 NASH 改善的重要指標。正如我們所提到的，關於培維肽抗發炎和抗纖維化作用的新臨床數據將作為最新摘要在 [AASLD] 上發布。

We believe that a robust reduction in NASH activity combined with fibrosis improvement and leading meaningful weight loss will be essential for a competitive product in the NASH marketplace. Also, as we have previously announced, we have completed the enrollment in our Phase 2 multicenter clinical trial of HepTcell patients with chronic hepatitis B.

我們相信，NASH 活性的大幅降​​低、纖維化的改善以及有意義的減肥對於 NASH 市場上具有競爭力的產品至關重要。此外，正如我們先前宣布的，我們已經完成了慢性乙型肝炎 HepTcell 患者的 2 期多中心臨床試驗的入組。

Chronic hepatitis B continues to represent a serious unmet need in the United States and worldwide and represents a significant commercial opportunity. HepTcell is an immunotherapeutic designed to activate HepTcell to fight the hepatitis B virus infection. HepTcell trial was designed to enroll 80 subjects with an active chronic hepatitis B and low hepatitis B surface antigen.

慢性B型肝炎仍然是美國和全世界未滿足的嚴重需求，並且代表著重要的商業機會。 HepTcell 是一種免疫治療藥物，旨在活化 HepTcell 以對抗乙型肝炎病毒感染。 HepTcell 試驗旨在招募 80 名患有活動性慢性B型肝炎且B型肝炎表面抗原較低的受試者。

The primary endpoint of this trial is 1-log reduction or clearance of the hepatitis B surface antigen. We expect to announce the results of this trial in the first quarter of 2024. Once all subjects complete the six-month treatment period, it is generally believed in an infected then an effective therapy for chronic hepatitis B will require both direct-acting antivirals in immunotherapy, and we believe that HepTcell is highly differentiated and may provide a functional cure of chronic hepatitis B infection when combined with novel direct acting antivirals. I will now hand the call over to Richard, to give an update on our third quarter financial results, Rich?

此試驗的主要終點是乙型肝炎表面抗原的 1 個對數減少或清除。我們預計在 2024 年第一季公佈這項試驗的結果。一旦所有受試者完成六個月的治療期，人們普遍認為，慢性乙型肝炎的有效治療將需要兩種直接作用的抗病毒藥物免疫療法，我們相信HepTcell 具有高度分化性，與新型直接作用抗病毒藥物聯合使用可以提供慢性乙型肝炎感染的功能性治癒。我現在將電話轉交給理查德，介紹我們第三季財務業績的最新情況，里奇？

Thank you, Scott, and good morning again, for today's call, I'll be providing a brief update on Altimmune's third quarter 2023 financial and operating results. More comprehensive information will be available in our Form 10-Q to be filed with the SEC later today.

謝謝你，斯科特，再次早上好，在今天的電話會議中，我將提供有關 Altimmune 2023 年第三季度財務和運營業績的簡短更新。今天稍後向 SEC 提交的 10-Q 表格中將提供更全面的資訊。

Auto-immune ended the third quarter of 2023 with approximately $140.8 million of cash, cash equivalents and short-term investments compared to $184.9 million at the end of 2022.

截至 2023 年第三季末，Auto-immune 擁有約 1.408 億美元的現金、現金等價物和短期投資，而 2022 年底為 1.849 億美元。

Research and development expenses were $18.6 million in the third quarter of 2023 compared to 20.3 million in the same period in 2022. Approximately $12 million of this total for the third quarter of 2023, were direct expenses for the conduct of our clinical programs, including $10.4 million in direct costs related to development activities for pemvidutide and $1.6 million in direct costs related to development activities for HepTcell.

2023 年第三季的研發費用為 1,860 萬美元，而 2022 年同期為 2,030 萬美元。2023 年第三季的研發費用總額中約 1,200 萬美元是開展臨床項目的直接費用，其中包括 10.4 美元與pemvidutide開發活動相關的直接成本為160 萬美元，與HepTcell 開發活動相關的直接成本為160 萬美元。

We anticipate a brief We anticipated a brief and small increase in research and development expenses during the ramp of our IMPACT trial. As we completed the in-life portion of our MOMENTUM trial. Looking ahead, we expect the increase in expenses related to IMPACT trial will be offset in part by reductions in expenses the MOMENTUM trial winds down.

我們預計在 IMPACT 試驗期間，研發費用會短暫而小幅增加。當我們完成 MOMENTUM 試驗的現實部分。展望未來，我們預計與 IMPACT 試驗相關的費用增加將被 MOMENTUM 試驗結束後費用的減少部分抵消。

General and administrative expense were consistent period over period at $4.5 million for the three months ended September 30, 2023, and 2022, approximately $2.9 million for quarterly operating expenses. Non-cash expense, primarily stock compensation.

截至 2023 年 9 月 30 日和 2022 年的三個月，一般和管理費用與上期持平，為 450 萬美元，季度營運費用約為 290 萬美元。非現金費用，主要是股票報酬。

Interest income was $1.9 million in the third quarter of 2023 compared to $1.1 million in the same period in 2022. Net loss for the three months ended September 30, 2023, was $20.7 million or $0.39 net loss per share compared to net loss of $23.5 million or $0.48 net loss per share for the third quarter of 2022. We estimate that our existing cash funds us through the 24-week biopsy results from our IMPACT Phase 2b NASH trial expected in the first quarter of 2025.

2023 年第三季的利息收入為190 萬美元，而2022 年同期為110 萬美元。截至2023 年9 月30 日止三個月的淨虧損為2,070 萬美元，即每股淨虧損0.39 美元，而淨虧損為2,350 萬美元或2022 年第三季每股淨虧損0.48 美元。我們估計，我們現有的現金可以為我們提供預計在2025 年第一季進行的IMPACT 2b 期NASH 試驗的24 週活檢結果。

Operator that concludes our formal remarks, and we would like to open the lines to take questions. Could you please instruct the audience on the Q&A procedure?

接線員結束了我們的正式發言，我們想打開線路來回答問題。您能指導一下觀眾的問答程序嗎？

Certainly, ladies and gentlemen, to ask a question, (Operator Instructions)

當然，女士們先生們，請提問，（操作員說明）

Yasmeen Rahimi, Piper Sandler. (Operator Instructions).

亞斯明·拉希米，派珀·桑德勒。 （操作員說明）。

Good morning, team, and thank you so much for all the great updates. And to the extent you can comment on in for the MOMENTUM data, like I know it's set for this quarter, enrollment finished in September. Any chance this is going to potentially come around this month or next month. So to the extent you could provide a little bit color on when in this quarter, we should be expecting it.

早安，團隊，非常感謝你們提供的所有精彩更新。就您可以評論的 MOMENTUM 數據而言，就像我知道的那樣，該數據是在本季度設定的，註冊已於 9 月完成。這有可能在本月或下個月發生。因此，如果您能提供有關本季度時間的一些信息，我們應該對此有所期待。

I know in the past. Second question is in the past you guys spoken about also at the top line to provide some modeling analysis to be able to look at the curve of weight loss. I just wanted to make sure that's still occurring as we head into the top-line data.

我知道過去。第二個問題是，你們過去也曾在頂行提到提供一些模型分析，以便能夠查看減肥曲線。我只是想確保當我們研究最重要的數據時這種情況仍然發生。

And then maybe the third question is just some cadence on given that impact has a weight loss and a really desirable product profile and what is the enthusiasm among sites and patients as they have eligibility to be part of the study. So appreciate if you could tackle those three for me, and I'll jump back into the queue.

然後，也許第三個問題只是一些節奏，因為影響有減肥和真正理想的產品概況，以及站點和患者的熱情是什麼，因為他們有資格參與這項研究。如果您能為我解決這三個問題，我將不勝感激，我將重新加入隊列。

Thanks, [Yasmeen], and thank you for the questions.(multiple speakers)

謝謝，[Yasmeen]，也謝謝你提出的問題。（多位發言者）

Scott Harris, do you want to take this?

史考特哈里斯，你想接受這個嗎？

Yes, I can take those. So Yasmeen, the data, we can provide at the current time is that we finished enrollment, we finished dosing in September, there's obviously a safety follow-up period after that of approximately four weeks, there's time for data cleaning.

是的，我可以接受這些。所以Yasmeen，我們目前可以提供的數據是，我們完成了註冊，我們在9月份完成了給藥，顯然之後有一個大約四個星期的安全隨訪期，有時間進行數據清理。

So as we said, we're really headed towards the readout this quarter. And at this time, that's about as much information as I can provide. But I think the arithmetic is there and you can do the calculation back based on the information in the public domain?

正如我們所說，我們確實將在本季公佈結果。目前，我能提供的資訊就這麼多了。但我認為算術已經存在，你可以根據公共領域的資訊來計算？

Well, regarding the modeling analysis, yes, as I said, weight loss is expected to continue beyond 48 weeks based on the shape of the curve of other compounds, particularly glucagon containing compound. And we will model that and tried to provide with weight loss would look like a patient been followed for the 68 weeks to 72 weeks of other compounds.

嗯，關於模型分析，是的，正如我所說，根據其他化合物（特別是含胰高血糖素的化合物）的曲線形狀，體重減輕預計將持續超過 48 週。我們將對此進行建模，並嘗試提供減肥效果，就像對患者進行 68 週至 72 週的其他化合物追蹤一樣。

I would emphasize there's been a great deal of enthusiasm from not only patients but also sites. And in particular, Dr. Aronne, who is the principal investigator in the trial as he echoed during the reading of our 24-week weight loss. He thinks that this is an extremely important drug based on its differentiated profile the fact that the marketplace will be segmented with different needs for weight loss, serum lipids, liver fat reduction, these particularly interest in an absence of the need to dose titrate because he feels very strongly that the great majority of this marketplace for move to primary care.

我想強調的是，不僅患者而且網站也都表現出了極大的熱情。特別是 Aronne 博士，他是該試驗的主要研究者，他在閱讀我們的 24 週減肥情況時也做出了回應。他認為這是一種極其重要的藥物，因為它具有差異化特徵，市場將根據減肥、血脂、肝臟脂肪減少的不同需求進行細分，這些在不需要劑量滴定的情況下特別令人感興趣，因為他非常強烈地感覺到這個市場的絕大多數人都轉向初級保健。

In the absence of really the need to achieve [Pheno bariatric] surgery type weight loss in patients. We think these sites feel and patients feel as well based on their reactions that this is going to be a very successful product.

在沒有真正需要實現[Pheno減重]手術減重的患者中。我們認為這些網站和患者根據他們的反應也感覺這將是一個非常成功的產品。

And Scott, there was also a question about the enrollment IMPACT trial based on the weight loss properties. Could you elaborate on that as well?

Scott，還有一個關於基於減肥特性的 IMPACT 試驗的問題。能詳細說明一下嗎？

Yes, sure. So, we are seeing very brisk enrollment and impact we're very pleased with it. And the comments reading from patients and investigators is that you've got the drug out there in NASH trials that's not only treating NASH, which for most patients is invisible, they have a condition in the liver. What they're really coming to draw for is the weight loss. And we think that their reaction in the IMPACT trial will reflect the uptake pemvidutide in the marketplace when it finally gets approved.

是的，當然。因此，我們看到入學人數非常活躍，影響也非常大，我們對此感到非常滿意。從患者和研究人員那裡讀到的評論是，你已經在NASH 試驗中找到了這種藥物，它不僅可以治療NASH（對於大多數患者來說，NASH 是看不見的），他們還患有肝臟疾病。他們真正的目的是為了減肥。我們認為，當培維肽最終獲得批准時，他們在 IMPACT 試驗中的反應將反映其在市場上的接受度。

Okay. Thank you so much. I'll jump back in the queue.

好的。太感謝了。我會跳回到隊列中。

Corinne Jenkins, Goldman Sachs. (Operator Instructions)

科琳·詹金斯，高盛。 （操作員說明）

Hi, this is [Omari], on for Corinne. So first question is, what do you view as successful outcome for that 48-week momentum readout with respect to weight loss? And then what can you contextualize for us how that positions pemvidutide given both the safety and efficacy considerations?

大家好，我是 [Omari]，為 Corinne 發言。所以第一個問題是，您認為 48 週減肥動力讀數的成功結果是什麼？那麼，考慮到安全性和有效性，您可以為我們介紹一下培維肽的定位嗎？

Well, thank you, [Omari]. All I'll answer both of those question.

好吧，謝謝你，[奧馬裡]。我將回答這兩個問題。

Yes. So [Omari], you know, we as we've said, we feel comfortable that we could achieve weight loss in the mid-teens, which, as Dr. Aronne pointed out, is key for moving most of not all of the comorbidities of obesity. And we feel comfortable that we'll be in that range and that also will continue to see weight loss beyond that.

是的。因此，[Omari]，正如我們所說，我們對能夠在十幾歲左右實現體重減輕感到放心，正如阿龍博士指出的那樣，這是消除大多數（而非全部）合併症的關鍵肥胖症。我們感到很放心，我們將處於這個範圍內，並且還將繼續看到體重減輕超過這個範圍。

So if you recall, the weight loss achieved by tripeptide and semaglutide at 48 weeks was less than it achieved at 48 weeks at 72 weeks or 68 weeks and 72 weeks. Now we'll continue to see weight loss or what have continued to see weight loss beyond the 48-week time point. And as I mentioned in my response, as we will model that for investors and estimate what we think the weight loss would be at extended time points.

因此，如果您還記得的話，三肽和索馬魯肽在 48 週時實現的體重減輕少於 48 週、72 週或 68 週和 72 週時實現的體重減輕。現在我們將繼續看到體重減輕或在 48 週時間點之後繼續看到體重減輕。正如我在回覆中提到的，我們將為投資者建立模型，並估計我們認為在較長時間點的減肥效果。

We see this drug extremely well positioned in the obesity marketplace, especially fitting the segment of patients who need to get further reduction in their serum lipids reduction in their liver fat content, both important risk factors for cardiovascular disease, but most importantly, achieving it safely.

我們認為這種藥物在肥胖市場中定位非常好，特別適合需要進一步降低血脂和肝臟脂肪含量的患者，這兩者都是心血管疾病的重要危險因素，但最重要的是，安全地實現這一目標。

And I want to emphasize that we have not seen the heart rate increases, we have not seen meaningful heart rate increases with pemvidutide or arrhythmias that's been seen in other compounds, especially the compounds, the dual agonist that contain a glucagon.

我想強調的是，我們還沒有看到心率增加，我們還沒有看到在其他化合物，特別是含有胰高血糖素的雙重激動劑的化合物中觀察到培維肽或心律不整有意義的心率增加。

So we think the safety profile, the good solid weight loss effects on serum and the [hepatic] lipids and especially in primary care, which we believe is going to dominate the obesity marketplace in the future the convenience of not having dose titration at least at the 1.8 milligram dose.

因此，我們認為安全性、對血清和[肝]脂質的良好固體減肥效果，特別是在初級保健中，我們相信這將在未來主導肥胖市場，至少在不進行劑量滴定的便利性1.8毫克劑量。

Thank you. Roger Song, Jefferies. (Operator Instructions)

謝謝。羅傑·宋，杰弗里斯。 （操作員說明）

Great, congrats for the progress, and thanks for the update. Few questions from us. So the first one is regarding the you know, assuming the MOMENTUM Phase 2 data meeting your expectation and how, what is your current thinking around the Phase 3 design, particularly around the dosing and the titration given you know, we see it a bit higher discontinued due to AI, in Phase 2, which is similar to other Phase 2.

太好了，祝賀您取得的進展，並感謝您的更新。我們提出的問題很少。所以第一個是關於你知道的，假設MOMENTUM 第2 階段的數據滿足你的期望，以及你目前對第3 階段設計的想法是什麼，特別是在劑量和滴定方面，你知道，我們認為它有點高由於 AI 在第 2 階段中止，這與其他第 2 階段類似。

But in Phase 3, you probably want a lower data rate for Phase 2. Just remind us of what is your current thinking at, for the design portion? And second question is related to that partnership, so I think on the call you mentioned you will start a Phase 3 in second half next year with a partner.

但在第 3 階段，您可能希望第 2 階段具有較低的資料速率。請提醒我們，您目前對設計部分的想法是什麼？第二個問題與合作夥伴關係有關，所以我認為您在電話中提到您將在明年下半年與合作夥伴啟動第三階段。

Maybe just, can you give us some color around the panel discussion at this point, particularly with the MOMENTUM for the 48-week data hall and when will trigger additional discussion to make this material? Thank you.

也許只是，您能否就目前的小組討論給我們一些說明，特別是 48 週數據大廳的動量，以及何時會引發更多討論來製作此材料？謝謝。

Roger, I'll answer the first question.

羅傑，我來回答第一個問題。

Scott, you want to take the first question? Yeah, go ahead.

史考特，你想回答第一個問題嗎？是的，繼續吧。

Yeah, Roger, I'll answer the first question. I'll turn the microphone over to Vipin, for the second question. So the ultimate design of the Phase 3 trial will be set in discussion with partners and also in discussions with the FDA and we anticipate having an end-of-Phase 2 discussion with FDA in 2024, based on the results of the MOMENTUM trial.

是的，羅傑，我來回答第一個問題。我將把麥克風交給 Vipin，回答第二個問題。因此，3 期試驗的最終設計將在與合作夥伴以及 FDA 的討論中確定，我們預計根據 MOMENTUM 試驗的結果，在 2024 年與 FDA 進行第 2 期臨床試驗的結束討論。

We see all of the current doses as being viable going forward the 1.2 milligram and 1.8 milligram doses are given without dose titration. And currently the 2.4 milligram dose is given with a very short before we titration. That's about one-fifth the duration of [tripeptide] dosing and even lower than that, which prolong titration that are being used beyond half a year in other programs or will be used in Phase 3 programs.

我們認為目前所有劑量在未來都是可行的，1.2 毫克和 1.8 毫克劑量無需劑量滴定。目前，2.4毫克的劑量是在我們滴定之前很短的時間內給予的。這大約是[三肽]給藥持續時間的五分之一，甚至更低，這將其他項目中使用的滴定時間延長了半年以上，或將在第三階段項目中使用。

So we see those doses moving forward. As you mentioned, there was a higher than we expected adverse event discontinuation rate at the 2.4 milligram dose. But as you pointed out, it was the same, if not less than the adverse events discontinuations that have been seen in other Phase 2 programs like the semaglutide program appetite, Phase 2 programs and that they made the necessary adjustments going into Phase 3 to get their adverse events down towards where they are right now in the single digits.

所以我們看到這些劑量正在向前推進。正如您所提到的，2.4 毫克劑量的不良事件停藥率高於我們的預期。但正如您所指出的，這與其他第2 階段項目（如索馬魯肽項目食慾、第2 階段項目）中出現的不良事件中斷情況相同，甚至更少，並且他們在進入第3 階段時進行了必要的調整，以獲得他們的不良事件減少到了現在的個位數。

We have a lot of opportunity to do that. We have, as you said, we could modify dose titration. But a very important difference from the other trials is that we did not allow dose reduction and as I mentioned before, in the tripeptide and [semaglutide] trials as much as 30% of those patients either never got up to the highest dose or dose reduce once they got there.

我們有很多機會可以這樣做。正如您所說，我們可以修改劑量滴定。但與其他試驗的一個非常重要的區別是，我們不允許減少劑量，正如我之前提到的，在三肽和[索馬魯肽]試驗中，多達30% 的患者要么從未達到最高劑量，要么減少了劑量一旦他們到達那裡。

And consequently, you can see that by putting a dose reduction scheme, we're more flexibility in the up-titration in our study, we really think that we can get that adverse event rate down even without having to dose titrate any further than we are right now. Vipin, would you like to answer the second question about the partnership?

因此，您可以看到，透過制定劑量減少方案，我們在研究中的滴定上調方面更加靈活，我們確實認為，即使無需比我們進一步滴定劑量，我們也可以降低不良事件發生率。現在。 Vipin，您願意回答關於合作關係的第二個問題嗎？

Yeah, thanks, Scott. So Roger, as we have said before, obviously this 48-week data moving our partnership discussions forward, we've already received multiple discussions out there. And our goal is to be Phase 3 ready by the second half of next year. And that gives us enough time plenty of time to also line up a partner to initiate that Phase 3 program.

是的，謝謝，斯科特。所以羅傑，正如我們之前所說，顯然這個 48 週的數據推動了我們的合作夥伴關係討論，我們已經收到了多次討論。我們的目標是在明年下半年之前完成第三階段的準備。這給了我們足夠的時間來安排合作夥伴來啟動第三階段計畫。

So that's really what we are executing to. We feel that with the data that we are expecting at 48-week readout and that would give us the best opportunity to line up the partner to move forward into Phase 3

這就是我們正在執行的目標。我們認為，根據我們預期的 48 週讀數數據，這將為我們提供最佳機會，讓合作夥伴進入第 3 階段

Excellent, thank you, that's it from me.

太好了，謝謝，這就是我的。

Thank you. Mayank Mamtani, B. Riley. (Operator Instructions)

謝謝。 Mayank Mamtani，B.Riley。 （操作員說明）

Hi, this is [William Wood] on for Mayank today. Congratulations on the on your quarter. So couple of questions from us thinking about your upcoming Phase 2 momentum top line readout, are there any datasets that you've recently prioritized and decided to include possibly body composition or lean muscle?

大家好，我是 [William Wood] 今天為 Mayank 做的節目。恭喜您的季度。因此，我們對即將到來的第二階段動量頂線讀數提出了幾個問題，您最近是否優先考慮並決定包括可能的身體組成或瘦肌肉的任何數據集？

Yeah, William, the readout that we're going to have this quarter will be in many ways, similar to the parameters that we read out before 24 weeks. So let me repeat that. It will include body weight loss to include our waist circumference, that will include serum lipids. It will include readout on vital signs, which we think are very important in differentiating and will include glycemic control and also reported adverse events within data included on the discontinuations.

是的，William，我們本季將得到的讀數在許多方面都與我們在 24 週之前讀出的參數類似。讓我重複一遍。它將包括體重減輕，包括我們的腰圍，這將包括血脂。它將包括生命體徵的讀數，我們認為這對於區分非常重要，並將包括血糖控制以及在停藥數據中報告的不良事件。

We also expect to have data on reduction in liver fat. We are doing body composition measurements of this trial. At this point, we do not think that we're going to have them for the top line results because they require more analysis than just liver fat analyses. So that additional readout on, say lean body mass will probably come sometime after the top line results.

我們還期望獲得有關減少肝臟脂肪的數據。我們正在對這次試驗進行身體組成測量。在這一點上，我們認為我們不會將它們作為頂線結果，因為它們需要更多的分析而不僅僅是肝臟脂肪分析。因此，額外的讀數（例如去脂體重）可能會在頂線結果之後的某個時間出現。

Got it. And then you mentioned and you've previously reported that you have a presentation coming up this weekend or early next week on you mentioned that just going to be new data on anti-inflammatory and anti-fibrotic properties of the thought.

知道了。然後你提到，你之前已經報道過，你在本週末或下週初將有一個演講，你提到這將是關於該想法的抗炎和抗纖維化特性的新數據。

Do you think you could go into a little bit more color on what we may expect to see and how we should view that data feeding into the FDA decision granting FTD, and then obviously your IMPACT trial?

您是否認為您可以對我們可能期望看到的情況以及我們應該如何看待 FDA 批准 FTD 決定的數據以及您的 IMPACT 試驗的數據進行更多的闡述？

Thank you, William. I cannot discuss the data in that poster because it's embargoed by ASLG role since late breaking abstracts. But as you can see the FDA, so all of the data, including the data that the additional data that we'll present additional data on not only anti-inflammatory properties of pemvidutide, but even more importantly, the anti-fibrotic properties of pemvidutide.

謝謝你，威廉。我無法討論該海報中的數據，因為自從最新的摘要以來它就受到 ASLG 角色的禁運。但正如您所看到的 FDA 的所有數據，包括我們將提供的附加數據，不僅涉及培維肽的抗炎特性，更重要的是，培維肽的抗纖維化特性。

And they are well aware of all that when they fall saw the Fast Track application and granted that designation to Altimmune. We believe that pemvidutide, this very high reduction in liver fat content and class-leading effects on anti-fibrotic anti-inflammatory markers will results in important improvements of fibrosis, and the abstract will highlight the observations that we've made to date on the latter point.

他們很清楚這一切，當他們看到快速通道申請並授予 Altimmune 頭銜時。我們相信，pemvidutide，這種肝臟脂肪含量的高度降低和抗纖維化抗發炎標誌物的領先作用將導致纖維化的重要改善，摘要將強調我們迄今為止在後一點。

Appreciate it. And then one last quick one on your IMPACT trial is enrolling F2, F3 patients, I believe you said 50% have to be F3, given the difficulties we've seen recently in F4 at the current time, do you foresee pemvidutide to be run in that F4 population?

欣賞它。然後，您的 IMPACT 試驗的最後一項快速任務是招募 F2、F3 患者，我相信您說過 50% 必須是 F3，考慮到我們最近在 F4 中看到的困難，您是否預計將進行培維肽在F4 群體中？

It's a great question, William. That's something we're obviously taking a very good look at. We haven't made any announcements on that to date. Right now, we're concentrating on the F2, F3 population, but we're certainly taking a very good look at [cirrhosis] and the possibility of engaging that population in a separate clinical trial.

這是一個很好的問題，威廉。顯然，我們正在認真研究這一點。迄今為止我們尚未就此發布任何公告。目前，我們專注於 F2、F3 族群，但我們當然正在仔細研究[肝硬化]以及讓該族群參與單獨臨床試驗的可能性。

Appreciate it. Thanks very much for taking my questions and congratulations again.

欣賞它。非常感謝您再次提出我的問題並表示祝賀。

Thank you.

謝謝。

Jonathan Wolleben, JMP Securities. (Operator Instructions)

喬納森·沃勒本，JMP 證券。 （操作員說明）

Hi, thanks for taking the questions. I guess two for me. One, a follow-up from an earlier question. How do you think about an acceptable tolerability profile than in the upcoming MOMENTUM readout, given in the tweaks, Scott, you just discussed you can make going into Phase 3, and then can you also discuss the differentiation from peptide to other GLP-1/glucagon dual agonist and [Bi] compounds, either structurally or even from the data we've seen. And we've gotten pretty good benefits from all three at this point, I think there would be helpful to hear. Thanks.

您好，感謝您提出問題。我猜對我來說有兩個。一，之前問題的後續。與即將到來的MOMENTUM 讀數相比，您如何看待可接受的耐受性概況，在調整中給出，斯科特，您剛剛討論過您可以進入第3 階段，然後您是否也可以討論肽與其他GLP-1/ 的區別胰高血糖素雙重激動劑和[Bi]化合物，無論是在結構上還是從我們所看到的數據來看。目前我們已經從這三個方面獲得了相當好的好處，我認為聽到這些會有幫助。謝謝。

Yeah. So, you know, we have to point out that any tolerability data that's been generated to date has been in the absence of dose titration and the fact that we can achieve comparable safety and tolerability is really it's a complement to the drug. And we believe that arises from the pharmacokinetics of pemvidutide with a slow entry into the bloodstream.

是的。所以，你知道，我們必須指出，迄今為止產生的任何耐受性數據都是在沒有劑量滴定的情況下進行的，而我們能夠實現相當的安全性和耐受性的事實實際上是對藥物的補充。我們認為這是由於派維度勝肽緩慢進入血液的藥物動力學所致。

And remember that at the 1.2 milligram and 1.8 milligram doses, the adverse event rates leading to discontinuation were low. And again, the 1.8 was given without dose titration and still achieved a 9.4% weight loss at that point in time, which is as good as [semaglutide] at the same time point and you look at it on a placebo adjusted basis, obviously, there is a lot of opportunity to tweak the dosing any way we wish in order to get that profile down even better than it is right now.

請記住，在 1.2 毫克和 1.8 毫克劑量下，導致停藥的不良事件發生率較低。同樣，1.8 的給藥沒有劑量滴定，但在該時間點仍然實現了9.4% 的體重減輕，這與同一時間點的[索馬魯肽]一樣好，並且你在安慰劑調整的基礎上看它，顯然，我們有很多機會以任何我們希望的方式調整劑量，以便比現在更好地降低這種情況。

And as I mentioned before, Jonathan, we think we can do that without dose, without adjusting the dose titration by simply allowing for dose reduction in future trials. So we're obviously optimistic about that.

正如我之前提到的，喬納森，我們認為我們可以在沒有劑量的情況下做到這一點，而無需調整劑量滴定，只需在未來的試驗中減少劑量即可。所以我們顯然對此持樂觀態度。

Regarding the other compounds, starting from the structural viewpoint, as one knows that in addition to the Viewpoint domain, which we think is unique and conveys special pharmacokinetics to the drug. We also have a 1:1 ratio of GLP-1/glucagon agonism, which has the highest concentration of glucagon and glucagon dual agonist that are available to date. In contrast, [Marcus] announced that it's about two to one bias towards GLP-1, and the [placebo] compound pemvidutide is 8:1.

至於其他化合物，從結構角度出發，眾所周知，除了 Viewpoint 結構域之外，我們認為該結構域是獨特的，並且向藥物傳達了特殊的藥物動力學。我們還有 1:1 比例的 GLP-1/胰高血糖素激動劑，這是迄今為止濃度最高的胰高血糖素和胰高血糖素雙重激動劑。相較之下，[Marcus] 宣布其對 GLP-1 的偏見約為二比一，而[安慰劑]化合物 pemvidutide 的比例為 8:1。

We believe that it's the higher glucagon content that conveys the properties that we've seen. But it's also important to note that these compounds have both been associated with heart rate increases and that we're not seeing these heart rate increases in our program, and we think that's a very important differentiator.

我們相信更高的胰高血糖素含量體現了我們所看到的特性。但同樣重要的是要注意，這些化合物都與心率增加有關，我們在我們的計劃中沒有看到這些心率增加，我們認為這是一個非常重要的區別因素。

We have not seen any liver fat data with the [boehringer] compound. Some discussion has taken place around meetings that they're not seeing changes in serum lipids. We think that reflects the low glucagon compound content in that compound and the market data, they are some seeing relatively comparable reductions in liver fat, which we speak to the glucagon activity in both compounds.

我們尚未看到[勃林格殷格翰]化合物的任何肝臟脂肪數據。會議上進行了一些討論，他們沒有看到血脂發生變化。我們認為這反映了該化合物和市場數據中胰高血糖素化合物含量較低，他們看到肝臟脂肪的相對可比的減少，我們所說的是兩種化合物中的升糖素活性。

Thanks for the color, Scott.

謝謝你的顏色，斯科特。

Thank you.

謝謝。

Patrick Trucchio, H.C. Wainwright. (Operator Instructions)

特魯基奧 (Patrick Trucchio)，H.C.溫賴特。 （操作員說明）

Good morning, everyone. This is Louise, for Patrick. Thank you for taking our questions. I'm going to change gears here and talk a little bit about the HepTcell and the way that the field has been looking at immune modulation as an asset to its necessity in the HBV cure.

大家，早安。這是派崔克的路易絲。感謝您接受我們的提問。我將在這裡換個話題，談談 HepTcell 以及該領域一直將免疫調節視為其在 HBV 治療中的必要性的資產的方式。

For HBV cure, so can you talk about how your treatment is progressing towards a functional cure that could achieve this mechanism, this immune modulation mechanism where others don't have that?

對於乙型肝炎的治愈，您能談談您的治療是如何朝著功能性治愈方向發展的嗎？這種功能性治愈可以實現這種機制，這種免疫調節機制，而其他人沒有這種機制？

Sure. I appreciate that question, you know we've already demonstrated with HepTcell is that the therapeutic, which is HepTcell immunotherapeutic meant to them to boost that HepTcell response over there to the resistance enhanced testing and HBV antigens.

當然。我很欣賞這個問題，你知道我們已經用 HepTcell 證明了這種療法，即 HepTcell 免疫療法，旨在增強 HepTcell 對抗藥性增強測試和 HBV 抗原的反應。

We've demonstrated in our Phase 1 studies that it's very safe and that it's able to significantly increase the T-cell response to our HBV antigens. And so the next step, we felt it was important since this is going to be used as a combination therapy, most likely with direct-acting antivirals like SIRNA. or monoclonal antibodies or oligonucleotides against the surface antigen, for example, to show that the compound has activity on its own.

我們在第一階段研究中證明它非常安全，並且能夠顯著增強 T 細胞對 HBV 抗原的反應。因此，下一步，我們認為這很重要，因為這將被用作聯合療法，最有可能與 SIRNA 等直接作用抗病毒藥物一起使用。例如，針對錶面抗原的單株抗體或寡核苷酸，以顯示該化合物本身俱有活性。

And so that's with this Phase 2 study that's currently ongoing and we'll report out in the first quarter of next year is meant to show. The advantages of HepTcell have to do with the focus of the T-cell response against antigens that are known to be important for a functional response.

這就是目前正在進行的第二階段研究，我們將在明年第一季發布報告。 HepTcell 的優勢與 T 細胞針對抗原的反應重點有關，已知這些抗原對功能反應很重要。

And that is a glamorous antigen and core antigen. The hepatitis that was selected and represented and HepTcell are highly invariant there, hydrophobic in nature. And so they're unlikely to mutate in response to the immune pressure that will be generated.

那就是魅力抗原和核心抗原。選擇並代表的肝炎和 HepTcell 在那裡具有高度不變性，本質上是疏水性的。因此，它們不太可能因產生的免疫壓力而發生突變。

So what we have is an immunotherapeutic that is expected to be active against all of the circulating genotypes of HBV. And with combination with the add to intent that we are using IC31, which is a preclinically looked very encouraging and in our Phase 1 study was shown to be important for these T-cell responses, we feel that we're going to be able to generate a very robust response with surface antigen and other measures of HBV replication, that will then set us up for partnering discussions with companies that have these direct antivirals. It allows us to do then Phase two 2 in combination therapies.

因此，我們擁有的是一種免疫療法，預計對所有循環的 HBV 基因型都有活性。結合我們使用 IC31 的意圖，這是一種臨床前看起來非常令人鼓舞的藥物，並且在我們的 1 期研究中被證明對這些 T 細胞反應很重要，我們認為我們將能夠與表面抗原和乙肝病毒複製的其他措施產生非常強烈的反應，這將使我們能夠與擁有這些直接抗病毒藥物的公司進行合作討論。它使我們能夠進行聯合療法的第二階段。

That's sounds great. And do you plan to stratify patients based on surface antigen at baseline I. We've seen that with the Phase 3 program. Can you discuss more the baseline characteristics of the Phase 2 trial? And if you're successful if you're going to implement that threshold of surface antigen at baseline going forward?

聽起來不錯。您是否計劃根據基線 I 的表面抗原對患者進行分層。我們已經在第 3 階段計劃中看到了這一點。您能否更深入討論 2 期試驗的基線特徵？如果您打算在未來的基線上實現表面抗原的閾值，那麼您是否會成功？

Sure, that's a great question. And that's really one of the unique design elements of that of the Phase 2 study that site that's currently ongoing and report out here shortly is that we've selected patients that are referred to as inactive carriers, basically these folks have low surface antigen levels compared to many on chronically infected individuals.

當然，這是一個很好的問題。這確實是第二階段研究的獨特設計元素之一，該網站目前正在進行並很快在這裡報告，我們選擇了被稱為非活動攜帶者的患者，基本上這些人的表面抗原水平較低。對許多慢性感染者來說。

And we felt that would represent a population that has received direct-acting antivirals has had the surface antigen reduced by the mechanism site that I referred to earlier and then created a better environment for the immunotherapeutic to work and boost the T-cell response.

我們認為，這代表接受直接作用抗病毒藥物的人群的表面抗原通過我之前提到的機制位點減少，然後為免疫療法發揮作用並增強 T 細胞反應創造了更好的環境。

So going forward, you know, we don't see selecting patients with low surface antigens. We think that the combination therapy, the first part of that with the direct ending direct-acting antivirals will accomplish that goal and then HepTcell will work as it is in this study. So the study is really meant to look forward towards the combination studies and how the patients would present themselves for treatment with HepTcell.

所以，展望未來，我們不會選擇表面抗原低的患者。我們認為聯合療法，即直接結束直接作用抗病毒藥物的第一部分，將實現這一目標，然後 HepTcell 將像本研究中一樣發揮作用。因此，這項研究的真正目的是展望聯合研究以及患者如何接受 HepTcell 治療。

It sounds great, can you just remind me quickly, is this with or without interferon? And do you plan to have an arm with and without interferon in the combination setting.

聽起來不錯，你能不能快點提醒我，這個是加乾擾素還是不加干擾素？您是否計劃在組合設定中使用含有或不含幹擾素的手臂？

So the current study does not include interferon in the treatment for whom going forward. I think that there's any number of combination approaches that can be envisioned, and that's something that we'll talk more about as we get a little further down the road.

因此，目前的研究並未將幹擾素納入未來的治療中。我認為可以設想多種組合方法，當我們進一步深入時，我們將更多地討論這一點。

Sounds good, thank you so much.

聽起來不錯，非常感謝。

Thank you. And I see no further questions in the queue at this time. I will now turn the call back over to Dr. Vipin Garg, for any closing remarks.

謝謝。目前我在隊列中沒有看到更多問題。我現在將把電話轉回給 Vipin Garg 博士，請其發表結束語。

Thank you, everyone, for participating today. We appreciate the opportunity to share our results and outlook with you and thank you for your continued interest. Have a nice day.

謝謝大家今天的參與。我們很高興有機會與您分享我們的成果和前景，並感謝您的持續關注。祝你今天過得愉快。

Ladies and gentlemen, that does conclude our conference for today. Thank you for your participation. You may now disconnect.

女士們、先生們，今天的會議到此結束。感謝您的參與。您現在可以斷開連線。