Regulus Therapeutics Inc (RGLS) 2022 Q3 法說會逐字稿

Hello, and welcome to the Regulus Therapeutics Inc. Q3 2022 Earnings Conference Call. (Operator Instructions)

您好，歡迎參加 Regulus Therapeutics Inc. 2022 年第三季度收益電話會議。 （操作員說明）

Please note this event is being recorded.

請注意此事件正在被記錄。

I would now like to turn the conference over to Chief Financial Officer, Cris Calsada. Please go ahead.

我現在想將會議交給首席財務官 Cris Calsada。請繼續。

Thank you, and good afternoon, and thank you for joining us to discuss Regulus Therapeutics Third quarter 2022 financial results and corporate highlights. .

謝謝您，下午好，感謝您與我們一起討論 Regulus Therapeutics 2022 年第三季度財務業績和公司亮點。 。

Joining me on today's call is Jay Hagan, President and Chief Executive Officer; and Dr. Dennis Drygin, Chief Scientific Officer. Jay will provide opening remarks and share progress on our ADPKD program, and I will review the financial results before we open the line for questions.

與我一起參加今天電話會議的是總裁兼首席執行官傑伊·哈根 (Jay Hagan)；和首席科學官 Dennis Drygin 博士。 Jay 將致開幕詞並分享我們 ADPKD 計劃的進展，我將在開始提問之前審查財務結果。

Before we begin, I'd like to remind you that this call will contain forward-looking statements concerning Regulus Therapeutics future expectations, plans, prospects, corporate strategy and performance, which constitute forward-looking statements for the purposes of the safe harbor provision under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in our filings with the SEC.

在我們開始之前，我想提醒您，本次電話會議將包含有關 Regulus Therapeutics 未來預期、計劃、前景、公司戰略和業績的前瞻性陳述，這些前瞻性陳述構成了安全港條款的前瞻性陳述。 1995年《私人證券訴訟改革法案》。由於各種重要因素（包括我們向美國證券交易委員會提交的文件中討論的因素），實際結果可能與這些前瞻性陳述所示的結果存在重大差異。

In addition, any forward-looking statements represent our views only as of the date of this webcast and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligations to update such statements.

此外，任何前瞻性陳述僅代表我們截至本網絡廣播之日的觀點，不應被視為代表我們在任何後續日期的觀點。我們明確聲明不承擔更新此類聲明的義務。

I will now turn the call over to Jay.

我現在將把電話轉給傑伊。

Thanks, Cris, and welcome, everyone, to our third quarter earnings call and business update. I'll begin with a general update on our ADPKD program. We continue to make progress in the clinic with RGLS8429. In September, we announced positive top line safety and PK data from our Phase I single ascending dose, or SAD, clinical trial of RGLS8429. RGLS8429 was well tolerated with no serious adverse events reported. Among the 32 subjects treated with RGLSA429 or placebo, there were only 9 adverse events, all of which were mild, except one, a sinus infection, which was graded moderate in severity. In addition, importantly, preliminary results suggest that plasma exposure is approximately linear across the 4 dose levels tested and is similar to the PK data from the first generation compound RGLS4326.

謝謝克里斯，歡迎大家參加我們的第三季度財報電話會議和業務更新。我將首先介紹我們的 ADPKD 計劃的一般更新。我們通過 RGLS8429 繼續在臨床上取得進展。 9 月，我們宣布了 RGLS8429 的 I 期單劑量遞增（SAD）臨床試驗的積極頂線安全性和 PK 數據。 RGLS8429 耐受性良好，未報告嚴重不良事件。在接受 RGLSA429 或安慰劑治療的 32 名受試者中，僅發生 9 例不良事件，除 1 例鼻竇感染（嚴重程度為中度）外，所有不良事件均為輕度。此外，重要的是，初步結果表明，在測試的 4 個劑量水平中，血漿暴露量近似呈線性，並且與第一代化合物 RGLS4326 的 PK 數據相似。

Last week, we announced the dosing of our first patient in our Phase Ib multiple ascending dose or MAD study of RGLS8429. Since then, we've enrolled the second patient and have several more in screening at the 6 sites that are now currently active. The study is a double-blind, placebo-controlled, multiple ascending dose study to assess safety, tolerability and pharmacokinetics of RGLS8429 in adult patients with ADPKD.

上週，我們宣布了 RGLS8429 的 Ib 期多次遞增劑量或 MAD 研究中第一位患者的給藥。從那時起，我們招募了第二名患者，並在目前活躍的 6 個站點對更多患者進行了篩查。該研究是一項雙盲、安慰劑對照、多劑量遞增研究，旨在評估 RGLS8429 在 ADPKD 成年患者中的安全性、耐受性和藥代動力學。

The study will evaluate the safety and efficacy of treatment with 4329 -- excuse me, 8429 across 3 different dose levels, including measuring changes in [PolySystems], cystic kidney volume or high adjusted total kidney volume and overall kidney function. The first cohort is being dosed at 1 milligram per kilogram of RGLSA429 or placebo every other week for 3 months.

該研究將評估 4329（對不起，8429）在 3 個不同劑量水平下治療的安全性和有效性，包括測量 [PolySystems]、囊性腎體積或高調整總腎體積和整體腎功能的變化。第一個隊列的劑量為每公斤 1 毫克 RGLSA429 或安慰劑，每隔一周服用一次，持續 3 個月。

Top line data from the first cohort of patients are now anticipated in mid-2023. Switching gears, during the 3 months ended September 30, 2022, we sold and settled approximately 2.2 million shares for net proceeds of $4.5 million under our ATM facility. Almost all the shares were sold to a new institutional investor. With the completion of this transaction, we believe our cash, cash equivalents and short-term investments will now fund current planned activities through 2023.

目前預計第一批患者的主要數據將於 2023 年中期獲得。換個角度，在截至 2022 年 9 月 30 日的三個月內，我們通過 ATM 設施出售並結算了約 220 萬股股票，淨收益為 450 萬美元。幾乎所有股票都賣給了新的機構投資者。隨著本次交易的完成，我們相信我們的現金、現金等價物和短期投資現在將為當前計劃的活動提供資金直至 2023 年。

Last week, we presented data at the American Society of Nephrology Kidney Week meeting in Orlando. The poster presentation was titled Discovery of next-generation anti-miR-17 oligonucleotide RG-429 for the treatment of autosomadominant polycystic kidney disease, and it highlighted data supporting the potential of A429 in this important disease.

上週，我們在奧蘭多舉行的美國腎髒病學會腎臟週會議上公佈了數據。海報展示的標題是發現下一代抗 miR-17 寡核苷酸 RG-429 用於治療常染色體顯性多囊腎病，並強調了支持 A429 在這一重要疾病中潛力的數據。

We are excited about our progress as well as the attention RGLS8429 receives in the marketplace, which helps validate the effort our team is putting forth each day to advance this therapy and its potential to improve the current standard of care.

我們對我們的進展以及 RGLS8429 在市場上受到的關注感到興奮，這有助於驗證我們的團隊每天為推進這種療法所付出的努力及其改善當前護理標準的潛力。

With that, I will turn the call back over to Cris for an update on our financials. Cris?

這樣，我會將電話轉回克里斯，以了解我們財務狀況的最新情況。克里斯？

Thanks, Jay. Turning to our financial results. As of September 30, 2022, our cash, cash equivalents and short-term investments totaled approximately $45. 3 million. We expect our cash runway to extend through 2023. Research and development expenses for the third quarter of 2022 totaled $5.3 million compared to $5. 9 million in the same period in 2021.

謝謝，傑伊。轉向我們的財務業績。截至 2022 年 9 月 30 日，我們的現金、現金等價物和短期投資總計約為 45 美元。 3百萬。我們預計我們的現金跑道將延續到 2023 年。2022 年第三季度的研發費用總計 530 萬美元，而去年同期為 5 美元。 2021年同期為900萬。

These amounts reflect the internal and external costs associated with advancing our ADPKD program and other research efforts within our pipeline. General and administrative expenses for the third quarter of 2022 totaled $2.3 million compared to $2.5 million for the same period in 2021. These amounts reflect related and ongoing general business operating costs. Net loss for the third quarter of 2022 was $7.6 million compared to a net loss of $8.6 million for the same period in 2021. Basic and diluted net loss per share for the third quarter of 2022 was $0.50 per share compared to basic and diluted net loss of $0.99 per share for the same period in 2021.

這些金額反映了與推進我們的 ADPKD 項目和我們管道內的其他研究工作相關的內部和外部成本。 2022 年第三季度的一般和管理費用總計 230 萬美元，而 2021 年同期為 250 萬美元。這些金額反映了相關和持續的一般業務運營成本。 2022 年第三季度的淨虧損為760 萬美元，而2021 年同期的淨虧損為860 萬美元。與基本和稀釋的淨虧損相比，2022 年第三季度的基本和稀釋每股淨虧損為每股0.50 美元2021 年同期每股收益為 0.99 美元。

With that, I will turn the call back over to Jay.

這樣，我會將電話轉回給傑伊。

Thanks, Chris. At this time, we'd be happy to take any questions. Operator, please open the line. .

謝謝，克里斯。目前，我們很樂意回答任何問題。接線員，請開通線路。 。

(Operator Instructions) Our first question today comes from Whitney Adam with Canaccord.

（操作員說明）我們今天的第一個問題來自 Canaccord 的 Whitney Adam。

The question I have, I guess, is around expectations headed into the data mid next year. Can you remind us what you saw in animal studies with slightly extended dosing? I know the 3 months of dosing here versus a slightly shorter course in the first [gen] compound. So curious what you saw with longer dosing in animal studies, and if you think there's read through there to what we should be expecting from the clinical data readout next year.

我想我的問題是對明年中期數據的預期。您能否提醒我們您在稍微延長劑量的動物研究中看到了什麼？我知道這裡的 3 個月給藥時間與第一個 [gen] 化合物的療程稍短。很好奇您在動物研究中看到的較長劑量的情況，以及您是否認為已經閱讀了我們應該從明年的臨床數據讀出中期待的內容。

Yes. Maybe I'll touch on the clinical part, and I ask Denis to comment on dosing duration in a variety of animal models, which depending on the animal model some are more rapid than others offering less opportunity to dose for extended periods.

是的。也許我會談談臨床部分，我請丹尼斯評論一下各種動物模型的給藥持續時間，根據動物模型的不同，有些動物模型比其他模型更快，提供了較少的長時間給藥機會。

But just to remind folks that at the 1 milligram per kilogram dose level that we're testing currently with our next-gen compound we saw a statistically significant increase in both Polysystem 1 and Polysystem 2 from baseline of approximately 60% and 40% increases in those at that dose level. And as I mentioned earlier, the PK between the molecules is very similar. So we anticipate with this next-gen compound to see similar types of effects. And if you recall, the trajectory of the change from baseline would suggest that with continued dosing, higher levels of Polysystem could be achieved prior to it plateauing once we reach steady state in the kidney. So that's what we'll be looking for in the clinic. And Denis, I don't know if you want to comment on duration of dosing in animals.

但只是想提醒大家，在我們目前使用下一代化合物測試的每公斤 1 毫克劑量水平下，我們發現 Polysystem 1 和 Polysystem 2 均較基線有統計顯著性增加，分別增加了約 60% 和 40%。那些處於該劑量水平的人。正如我之前提到的，分子之間的 PK 非常相似。因此，我們預計這種下一代化合物會看到類似的效果。如果您還記得的話，相對於基線的變化軌跡表明，通過持續給藥，可以在腎臟達到穩定狀態之前達到更高水平的 Polysystem。這就是我們在診所尋找的東西。丹尼斯，我不知道你是否想評論動物的給藥持續時間。

Thank you, Jay. Indeed, as Jay mentioned earlier, the majority of the models for ADPKD are quite aggressive and do not allow extended period of treatment.

謝謝你，傑伊。事實上，正如 Jay 之前提到的，大多數 ADPKD 模型都非常具有侵略性，並且不允許延長治療時間。

However, we did test first generation molecule in a longer [nonphoto] model where the treatment was for 7 weeks. And with longer treatment, there was more and more evidence of the incubation of (inaudible) expansion and growth.

然而，我們確實在較長的[非照片]模型中測試了第一代分子，其中治療時間為 7 週。隨著治療時間的延長，越來越多的證據表明（聽不清）擴張和生長正在醞釀之中。

(Operator Instructions) The next question comes from Yanan Zhu with Wells Fargo Securities.

（操作員指令）下一個問題來自富國銀行證券的朱亞楠。

I mainly have a question about enrollment and time line for the data from different cohorts. So I think the -- previously, the data expectation for the first dose cohort might have been first half '23, please correct me if I'm wrong, and this time, we hear midyear.

我主要有一個關於不同群體數據的註冊和時間線的問題。所以我認為——之前，第一劑隊列的數據預期可能是 23 年上半年，如果我錯了，請糾正我，而這一次，我們聽到年中。

Could you elaborate on this might be a small change first half versus midyear, but any changes in your expectations for enrollment, speed or any other factors? And also for the additional cohorts, do you have any suggestion on potential time line for the data from those cohorts?

您能否詳細說明一下，這可能是上半年與年中相比的一個小變化，但您對入學率、速度或任何其他因素的期望有什麼變化嗎？對於其他隊列，您對這些隊列數據的潛在時間表有什麼建議嗎？

Sure. So the guidance that we provided for data from the first cohort in the first half of '23 dates back to when we did our financing in October, November last year, outlining at that time, our expectation for both initiation of the SAD and then initiation to MAD.

當然。因此，我們為 23 年上半年第一批數據提供的指導可以追溯到去年 10 月、11 月我們進行融資時，概述了當時我們對啟動 SAD 和隨後啟動的預期瘋狂。

And as often the case, as you work through these processes, sometimes things take a little bit longer to get up and going. So we chose to update our guidance in terms of when we would have data. Now that the MAD is actually initiated, we're a year after that initial guidance was provided, where we're taking a look at what -- how quickly we think we're going to enroll the study. And I think guidance of mid '23 is more accurate than the first half which includes the first quarter.

通常情況下，當您完成這些流程時，有時事情需要更長的時間才能啟動和進行。因此，我們選擇更新我們何時獲得數據的指導。現在，MAD 已實際啟動，距提供初步指導已經一年了，我們正在研究我們認為要以多快的速度參加這項研究。我認為 23 年中期的指導比上半年（包括第一季度）更準確。

So effectively, we're saying in the first quarter is likely out, we'd have to be done enrollment this month probably to hit the first quarter. And enrollment is obviously a forward-looking statement. Actual results may differ. We're pleased with the progress the team is making thus far in getting now 6 sites up and a good pipeline of patients in screening and 2 now in the study of the total 12 that we're targeting for the first cohort.

因此，實際上，我們說第一季度可能會結束，我們必須在本月完成註冊才能進入第一季度。而招生顯然是一個前瞻性聲明。實際結果可能有所不同。我們對團隊迄今為止所取得的進展感到高興，在我們針對第一批隊列的 12 名患者中，目前已建立了 6 個站點，並有良好的患者篩選渠道，其中 2 個正在研究中。

And so guidance for mid '23 feels more appropriate and accurate with how we project enrollment is going to go. When the last patient is initiated, we know quite clearly the time it will take them to complete that. They're going to have 3 months of dosing and 1 month of follow-up after which we've got the analytical work that's needed. So that is formed the basis of the overall time line for the first cohort. As far as the subsequent cohorts, I mentioned earlier that we have 6 sites up.

因此，23 年中期的指導對於我們預計招生的進展方式感覺更加合適和準確。當最後一名患者開始治療時，我們非常清楚他們需要多長時間才能完成。他們將進行 3 個月的給藥和 1 個月的隨訪，之後我們將進行所需的分析工作。這就是第一批總體時間表的基礎。至於後續的群組，我之前提到過我們有 6 個站點。

We're targeting up to 25 total sites currently. And so as more sites come up, then obviously more potential patients will come into the queue geographically and otherwise. And so while it's premature to estimate the time of enrollment of subsequent cohorts, one can anticipate that it could go more quickly than the first cohort just given more sites up and active. So what we've guided to for data from the second cohort is the second half of '23.

目前我們的目標網站總數最多為 25 個。因此，隨著更多站點的出現，顯然更多的潛在患者將在地理位置和其他方面進入隊列。因此，雖然現在估計後續隊列的註冊時間還為時過早，但可以預見的是，只要有更多的網站上線和活躍，它可能會比第一批的註冊速度更快。因此，我們對第二批數據的指導是 23 年下半年。

Congrats on the progress. .

祝賀取得的進展。 。

(Operator Instructions) Seeing no further questions, I would like to turn the conference back over to Jay Hagan for any closing remarks.

（操作員指示）由於沒有其他問題，我想將會議轉回傑伊·哈根 (Jay Hagan) 進行閉幕致辭。

Great. Thank you, operator, and thanks, everyone, for joining us today and for your support of Regulus. We look forward to providing you with future updates as the program advances. Take care. .

偉大的。謝謝運營商，也謝謝大家今天加入我們以及對 Regulus 的支持。隨著計劃的進展，我們期待為您提供未來的更新。小心。 。

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.

會議現已結束。感謝您參加今天的演講。您現在可以斷開連接。