Rani Therapeutics Holdings Inc (RANI) 2022 Q4 法說會逐字稿

Hello, and welcome to Rani Therapeutics fourth quarter and full year 2022 financial results and corporate update conference call. (Operator Instructions) As a reminder, this call is being recorded today, wednesday, March 22, 2023. I would now like to turn the conference over to Lawrence Watts of Gilmartin Group. Please go ahead, sir.

您好，歡迎參加 Rani Therapeutics 第四季度和 2022 年全年財務業績和公司更新電話會議。 （操作員說明）謹此提醒，本次通話將於今天（2023 年 3 月 22 日星期三）進行錄音。我現在想將會議轉交給 Gilmartin Group 的 Lawrence Watts。請繼續，先生。

Thank you, operator. Joining us on the call today from Rani Therapeutics are Chief Executive Officer, Talat Imran, Chief Financial Officer, Svai Sanford, and Chief Scientific Officer, Mir Hashim. During this conference call, management will make forward-looking statements that are subject to risks, uncertainties, and assumptions such as but not limited to those discussed in the Risk Factors section of the company's filings with the Securities and Exchange Commission, including its annual report on Form 10-K and quarterly reports on Form 10-Q, which identify the specific factors that may cause actual events or results to differ materially from those described in these forward-looking statements.

謝謝你，接線員。 Rani Therapeutics 首席執行官 Talat Imran、首席財務官 Svai Sanford 和首席科學官 Mir Hashim 參加了今天的電話會議。在本次電話會議期間，管理層將做出前瞻性聲明，這些聲明受到風險、不確定性和假設的影響，例如但不限於公司向美國證券交易委員會提交的文件（包括其年度報告）的風險因素部分中討論的內容表 10-K 中的季度報告和表 10-Q 中的季度報告，確定了可能導致實際事件或結果與這些前瞻性聲明中描述的內容存在重大差異的具體因素。

These statements may include, without limitation, statements regarding product development, clinical trials, product potential device progress and performance, potential impact on patients, regulatory environments, manufacturing progress, certain business strategies, capital resources or operating performance. Actual results and the timing of events could differ materially from those projected in such forward-looking statements.

這些陳述可能包括但不限於有關產品開發、臨床試驗、產品潛在器械進展和性能、對患者的潛在影響、監管環境、製造進展、某些業務策略、資本資源或運營績效的陳述。實際結果和事件發生的時間可能與此類前瞻性聲明中的預測存在重大差異。

With that, I will turn the call over to Talat Imran, Chief Executive Officer of Rani. Talat?

接下來，我將把電話轉給 Rani 首席執行官塔拉特·伊姆蘭 (Talat Imran)。塔拉特？

Thank you, Laurence. Good afternoon, everyone, and thank you for joining our fourth quarter and full year 2022 financial results conference call. I'm delighted to share the highlight of Rani Therapeutics' strong performance in 2022, during which the company achieved numerous milestones in the progression of its pipeline program and improvements in device performance. I would like to start by reviewing the important milestones that Rani achieved throughout the year.

謝謝你，勞倫斯。大家下午好，感謝您參加我們的 2022 年第四季度和全年財務業績電話會議。我很高興與大家分享 Rani Therapeutics 在 2022 年強勁業績的亮點，在此期間，該公司在管道項目的進展和設備性能的改進方面取得了許多里程碑。首先，我想回顧一下拉尼在這一年中取得的重要里程碑。

Last year, we made significant enhancements to the RaniPill platform, highlighted by the unveiling of our high-capacity RaniPill HC device, and continued improvement in both the manufacture and performance of our RaniPill GO device.

去年，我們對 RaniPill 平台進行了重大改進，特別是推出了高容量 RaniPill HC 設備，並持續改進了 RaniPill GO 設備的製造和性能。

In February 2022, Rani announced the development of the RaniPill HC, capable of administering 500% plus higher payloads than our standard RaniPill GO. While the RaniPill GO is designed to deliver drugs with a daily dose of up to three milligrams, the RaniPill HC can potentially deliver up to 20 milligrams per pill. We are currently in preclinical studies with the RaniPill HC. Importantly, with this new device, we now have the potential to target a much larger market of molecules such as pembrolizumab, etanercept, trastuzumab, secukinumab.

2022 年 2 月，Rani 宣布開發 RaniPill HC，其有效負載比我們的標準 RaniPill GO 高出 500% 以上。 RaniPill GO 的設計每日劑量高達 3 毫克，而 RaniPill HC 每粒藥片的劑量可能高達 20 毫克。我們目前正在進行 RaniPill HC 的臨床前研究。重要的是，通過這種新設備，我們現在有潛力瞄準更大的分子市場，例如派姆單抗、依那西普、曲妥珠單抗、蘇金單抗。

Concurrent with the development of the RaniPill HC, we have continued to make improvements in the development of the RaniPill GO, which is being utilized across our current internal development pipeline. We have progressed our manufacturing scale-up and automation efforts, and I'm happy to report that we are now capable of supporting a Phase 2 program in the second half of this year. With our current manufacturing line, we also plan to support three additional Phase 1 clinical studies of other pipeline programs concurrently in 2023.

在開發 RaniPill HC 的同時，我們繼續改進 RaniPill GO 的開發，該產品正在我們當前的內部開發流程中使用。我們已經在製造規模擴大和自動化方面取得了進展，我很高興地報告說，我們現在有能力在今年下半年支持第二階段計劃。利用我們現有的生產線，我們還計劃在 2023 年同時支持其他管道項目的另外三項一期臨床研究。

In addition, subtle but important improvements in our manufacturing processes resulted in our latest iteration of the RaniPill GO achieving a 92% drug delivery success rate in our recently completed Phase 1 study of RT-102. Beyond the improvement in device performance, the Phase 1 study of RT-102 met all of its endpoints. RT-102 delivered PTH with 300% to 400% higher bioavailability for 20 micrograms and 80 micrograms of PTH, respectively, when compared to 20 micrograms of Forteo delivered via subcutaneous injection.

此外，我們的製造工藝進行了微妙但重要的改進，使我們最新版本的 RaniPill GO 在我們最近完成的 RT-102 一期研究中實現了 92% 的藥物輸送成功率。除了設備性能的改進之外，RT-102 的第一階段研究還達到了所有終點。與通過皮下注射遞送的 20 微克 Forteo 相比，RT-102 遞送的 PTH 的生物利用度分別高出 300% 至 400%（20 微克和 80 微克 PTH）。

In addition, RT-102 was well tolerated, and no serious adverse events were reported in this study. Of the few minor adverse events reported, all were deemed mild to moderate and resolved on their own. The Phase 1 study results add to our robust and growing body of data supporting the safety and performance of the RaniPill. We are very pleased with the favorable safety profile demonstrated by the RaniPill capsule to date. We have now dosed nearly 100 human subjects in clinical studies with no serious adverse events to report.

此外，RT-102耐受性良好，本研究中未報告嚴重不良事件。在報告的少數輕微不良事件中，所有不良事件均被視為輕度至中度並自行解決。第一階段的研究結果補充了我們強大且不斷增長的數據，支持 RaniPill 的安全性和性能。我們對 RaniPill 膠囊迄今為止所表現出的良好安全性感到非常滿意。目前，我們已在臨床研究中對近 100 名人類受試者進行了給藥，沒有出現嚴重不良事件報告。

As we plan for the initiation of our first Phase 2 clinical trial in the second half of 2023, I would like to remind everyone about our recent interactions with the FDA, particularly the feedback received during our pre-IND meetings for RT-102. Based on guidance from the FDA, we believe that the 505(b)(2) pathway is suitable for RT-102, our PTH analog program. We appreciate the interactions we have had to date with regulators, and will continue to take their input into account as we progress our development program.

由於我們計劃在 2023 年下半年啟動第一個 2 期臨床試驗，我想提醒大家我們最近與 FDA 的互動，特別是在 RT-102 的 IND 前會議期間收到的反饋。根據 FDA 的指導，我們認為 505(b)(2) 途徑適合我們的 PTH 類似物項目 RT-102。我們感謝迄今為止與監管機構的互動，並將在我們推進開發計劃時繼續考慮他們的意見。

Turning to the development of RT-111, we were pleased to recently announce our partnership with Celltrion. Under this partnership, Celltrion will exclusively supply to Rani to execute on our biosimilar drug substance, CT- P43 required for RT-111. Rani has been granted an exclusive license to use CT- P43 in the development and commercialization of RT-111. And Celltrion in turn has been granted a right of first negotiation to acquire worldwide rights to RT-111 following a Phase 1 clinical trial. We believe our partnership with Celltrion, a leader in biosimilars and biologics manufacturing, validates the strength of our RaniPill oral drug delivery platform. We are delighted to be working with Celltrion, and look forward to potentially broadening our partnership over time.

談到 RT-111 的開發，我們很高興最近宣布與 Celltrion 建立合作夥伴關係。根據這一合作夥伴關係，Celltrion 將獨家向 Rani 供應 RT-111 所需的生物仿製藥 CT-P43。 Rani 已獲得在 RT-111 的開發和商業化中使用 CT-P43 的獨家許可。 Celltrion 又獲得了在 1 期臨床試驗後獲得 RT-111 全球權利的優先談判權。我們相信，我們與生物仿製藥和生物製劑製造領域的領導者 Celltrion 的合作驗證了我們 RaniPill 口服給藥平台的實力。我們很高興與 Celltrion 合作，並期待隨著時間的推移擴大我們的合作夥伴關係。

Lastly, before I turn it over to Mir Hashim to cover our preclinical and clinical data in more detail, I would like to remind you of our anticipated near-term milestones, which include initiating a Phase 2 clinical trial with RT-102 in the second half of 2023, and initiating three additional Phase 1 studies with pipeline molecules, RT-105 containing an adalimubab biosimilar, RT-110 containing PTH for hypoparathyroidism, and RT-111 containing Celltrion's ustekinumab biosimilar.

最後，在我將其交給 Mir Hashim 更詳細地介紹我們的臨床前和臨床數據之前，我想提醒您我們預期的近期里程碑，其中包括在第二個階段啟動 RT-102 的 2 期臨床試驗2023年下半年，並啟動另外三項管道分子1 期研究，包括含有阿達木巴生物仿製藥的RT-105、含有治療甲狀旁腺功能減退症的PTH 的RT-110 和含有Celltrion 的ustekinumab 生物仿製藥的RT-111。

With that, let me now turn the call over to Mir Hashim to discuss our preclinical and clinical updates in more detail. Mir?

現在，讓我將電話轉給 Mir Hashim，更詳細地討論我們的臨床前和臨床更新。米爾？

Thank you, Talat, and thank you, everyone, for joining us. Let me begin by highlighting some of the updates we have provided for RT-102, which is being developed for the treatment of osteoporosis. RT-102 is the RaniPill capsule containing PTH(1-34), also known as teriparatide. As you all know, we initiated a Phase 1 clinical study of RT-102 in Australia in March of 2022, and released top-line data for part one of the study in August and part two of the study in December of [2019].

謝謝你，塔拉特，也謝謝大家加入我們。首先讓我重點介紹一下我們為 RT-102 提供的一些更新，RT-102 正在開髮用於治療骨質疏鬆症。 RT-102是含有PTH(1-34)的RaniPill膠囊，也稱為特立帕肽。眾所周知，我們於2022年3月在澳大利亞啟動了RT-102的1期臨床研究，並於[2019]8月發布了研究第一部分的頂線數據，並於[2019]12月發布了研究第二部分的頂線數據。

In part one of the study, we evaluated the safety, tolerability, reliability, and pharmacokinetics of RT-102 in healthy adult female volunteers at a single dose of either 20 micrograms or 80 micrograms. In part two of the study, the same parameters were evaluated with repeat dosing of RT-102 at 20 micrograms for up to seven days. In part one, 15 subjects received RT-102 at a dose of 20 micrograms, while 14 subjects received RT-102 at a dose of 80 micrograms. A control group of 10 participants received a single 20 microgram subcutaneous injection of Forteo, which is the commercial formulation of teriparatide approved for subcutaneous administration.

在該研究的第一部分中，我們評估了健康成年女性志願者單劑量 20 微克或 80 微克 RT-102 的安全性、耐受性、可靠性和藥代動力學。在該研究的第二部分中，通過重複服用 20 微克 RT-102 長達 7 天來評估相同的參數。在第一部分中，15 名受試者接受了 20 微克劑量的 RT-102，而 14 名受試者接受了 80 微克劑量的 RT-102。由 10 名參與者組成的對照組接受了單次 20 微克皮下注射 Forteo，這是批准用於皮下注射的特立帕肽商業製劑。

RT-102 was well-tolerated in both dose groups and delivered PTH with bioavailability estimated to be up to three to four-fold higher than that of subcutaneous Forteo. There were no serious adverse events reported in this study at any dose. Now in part two of the study, ten healthy female volunteers, five of whom were postmenopausal, received RT-102 20 micrograms once daily for seven consecutive days. On the seventh day, complete pharmacokinetic profiles of RT-102 were obtained for each subject. We again observed that RT-102 was generally well tolerated with no serious adverse events noted during the study. And in fact, none of the participants withdrew from the study due to any adverse event related to the RaniPill capsule.

RT-102 在兩個劑量組中均具有良好的耐受性，並且所遞送的 PTH 的生物利用度估計比皮下注射 Forteo 高出三到四倍。本研究中任何劑量均未報告嚴重不良事件。現在，在該研究的第二部分中，10 名健康女性志願者（其中 5 名已絕經）連續 7 天每天接受 RT-102 20 微克治療。第七天，獲得了每位受試者 RT-102 的完整藥代動力學特徵。我們再次觀察到 RT-102 總體耐受性良好，研究期間沒有發現嚴重不良事件。事實上，沒有任何參與者因與 RaniPill 膠囊相關的任何不良事件而退出研究。

The bioavailability of RT-102 was high relative to subcutaneous Forteo, again confirming the data from part one of the study. And importantly, as Talat indicated earlier, the overall reliability or success rate of RT-102 delivery was 92%.

RT-102 的生物利用度相對於皮下注射的 Forteo 較高，再次證實了該研究第一部分的數據。重要的是，正如 Talat 之前指出的那樣，RT-102 遞送的總體可靠性或成功率為 92%。

Additionally, we were also pleased to have received preliminary feedback and guidance from the FDA on our RT-102 development plans. Overall, for RT-102, we are enthusiastic about the progress we have made so far. And we believe that the safety, reliability, and pharmacokinetic data that we collected to both parts of the Phase 1 study support the initiation of a Phase 2 trial of RT-102 in osteoporosis, which we anticipate beginning in the second half 2023.

此外，我們還很高興收到 FDA 對我們 RT-102 開發計劃的初步反饋和指導。總的來說，對於 RT-102，我們對迄今為止所取得的進展感到興奮。我們相信，我們在1 期研究的兩個部分中收集的安全性、可靠性和藥代動力學數據支持啟動RT-102 治療骨質疏鬆症的2 期試驗，我們預計該試驗將於2023 年下半年開始。

Beyond our RT-102 program, we are also pleased with our ongoing progress in the development of RT-111, RaniPill capsule containing ustekinumab biosimilar for the treatment of inflammatory conditions. And we look forward to the initiation of a Phase 1 study for RT-111 later this year. We believe that RT-111 has the potential to make a real difference for patients by providing them with an oral alternative to the current injectable standard of care.

除了我們的 RT-102 項目之外，我們還對 RT-111 的開發不斷取得進展感到高興，RT-111 是含有烏特克單抗生物仿製藥的 RaniPill 膠囊，用於治療炎症。我們期待今年晚些時候啟動 RT-111 的一期研究。我們相信 RT-111 有潛力為患者帶來真正的改變，為他們提供當前註射標準護理的口服替代方案。

Overall, we are delighted with the ongoing clinical and preclinical development of our pipeline programs. Advancements in our core programs reiterate our commitment to delivering the RaniPill capsule as an effective oral alternative that could change the treatment paradigm for the millions of patients currently taking injections for their chronic disease conditions.

總的來說，我們對我們的管道項目正在進行的臨床和臨床前開發感到高興。我們核心項目的進展重申了我們的承諾，即提供 RaniPill 膠囊作為一種有效的口服替代品，這可能會改變目前數百萬接受注射治療慢性疾病的患者的治療模式。

Now I will turn it over to Svai to go over the financial results for the fourth quarter and year end 2022. Svai?

現在我將把它交給 Svai 來審核第四季度和 2022 年年底的財務業績。Svai？

Thank you, Hashim, and good afternoon, everyone. In addition to the financial results summarized in our press release that was issued earlier today, I will briefly share some key financial highlights on this call. You can also find additional information on our Form 10-K for the year ended December 31, 2022. Cash, cash equivalents, and marketable securities as of December 31, 2022 totaled $98.5 million, compared to $117.5 million as of December 31, 2021. Without additional financing, we expect the current in cash, cash equivalents, and marketable securities to sufficiently fund our operation to mid-2024.

謝謝哈希姆，大家下午好。除了今天早些時候發布的新聞稿中總結的財務業績之外，我還將在本次電話會議上簡要分享一些關鍵的財務亮點。您還可以在我們截至2022 年12 月31 日的年度10-K 表格中找到更多信息。截至2022 年12 月31 日，現金、現金等價物和有價證券總計9,850 萬美元，而截至2021 年12月31 日為1.175 億美元。如果沒有額外的融資，我們預計當前的現金、現金等價物和有價證券足以為我們的運營提供充足的資金到 2024 年中期。

Research and development expenses for the fourth quarter and full year 2022 were $10.4 million and $36.6 million, respectively, compared to $7.4 million and $26.5 million for the same periods in 2021 respectively. General and administrative expenses for the 3 months and 12 months ended December 31, 2022 were $7.1 million and $26.8 million respectively, compared to $5.9 million and $27.8 million for the same periods in 2021 respectively.

2022 年第四季度和全年的研發費用分別為 1040 萬美元和 3660 萬美元，而 2021 年同期分別為 740 萬美元和 2650 萬美元。截至2022年12月31日的3個月和12個月的一般和行政費用分別為710萬美元和2680萬美元，而2021年同期分別為590萬美元和2780萬美元。

Lastly, our net loss for the fourth quarter and full year 2022 was $17.3 million and $63.3 million respectively, compared to $13.3 million and $53.1 million for the same periods in 2021 respectively. Excluding noncash charges, primarily equity-based compensation expense, the non-GAAP net loss was $13.3 million for the fourth quarter and $47.8 million for the full year 2022, compared to $10 million and $28.8 million for the same period in 2021 respectively.

最後，我們 2022 年第四季度和全年的淨虧損分別為 1730 萬美元和 6330 萬美元，而 2021 年同期分別為 1330 萬美元和 5310 萬美元。不包括非現金費用（主要是基於股權的薪酬費用），2022 年第四季度的非公認會計原則淨虧損為1,330 萬美元，2022 年全年淨虧損為4,780 萬美元，而2021 年同期分別為1,000萬美元和2,880 萬美元。

This concludes my remarks on the financial results, and I will now turn the call back over to Talat for closing comments. Talat?

我對財務業績的評論到此結束，現在我將把電話轉回塔拉特以徵求結束意見。塔拉特？

Thank you, Svai. In closing, we are very pleased with our progress so far and look forward to maintaining our momentum in 2023. From a clinical perspective, 2023 is really going to be a year of execution for Rani, and we believe that the potential milestones I've laid out could be transformative for our company. We look forward to the initiation of our Phase 2 clinical trial in RT-102 in the second half of 2023, our first Phase 2 trial, as well as the initiation of three additional Phase 1 studies with pipeline molecules, Rt-105, RT-110, and RT-111.

謝謝你，斯瓦伊。最後，我們對迄今為止的進展感到非常滿意，並期待在 2023 年保持我們的勢頭。從臨床角度來看，2023 年確實將是 Rani 的執行年，我們相信我已經實現的潛在里程碑制定的計劃可能會給我們公司帶來變革。我們期待在 2023 年下半年啟動 RT-102 的 2 期臨床試驗，這是我們的第一個 2 期試驗，並啟動另外三項關於管道分子 Rt-105、RT-1 的 1 期研究。 110 和RT-111。

We have built a world-class leadership team at Rani, and I would like to thank everyone at the company for their efforts this past year and so far in 2023. I'd also like to thank all of our stakeholders for your continued support of Rani and for helping us move closer to our vision of making oral biologics a reality. With that, I will now open the call up for questions. Operator?

我們在 Rani 建立了一支世界一流的領導團隊，我要感謝公司每個人在過去一年和 2023 年迄今為止所付出的努力。我還要感謝我們所有利益相關者對 Rani 的持續支持Rani 幫助我們更接近使口服生物製劑成為現實的願景。現在，我將開始提問。操作員？

Thank you. (Operator Instructions)

謝謝。 （操作員說明）

Brandon Folkes, Cantor.

布蘭登·福克斯，坎托。

Hi, thanks taking my questions and congratulations on all the progress in 2022. Maybe just firstly from me, when you sat down with the FDA, did they provide any color in terms of the safety base -- safety database they may require for the RaniPill device in light of the 505(b)(2) pathway. I'll stop here and then ask a follow-up.

您好，感謝您提出我的問題，並祝賀 2022 年取得的所有進展。也許首先，當您與 FDA 坐下來時，他們是否提供了安全基礎方面的任何信息——他們可能需要 RaniPill 的安全數據庫根據505(b)(2) 途徑的設備。我會在這裡停下來，然後詢問後續情況。

Sure. And Brandon, good to hear from you. Thank you for your question. They did not in the context of the RT-102 program. But we have had prior interactions with the FDA where the database size was about 2000 deployments, 40 subjects over eight weeks. It turns out that in this Phase 2, we will reach thereabouts or maybe a little bit higher. So I think we're hopefully going to be answering that question for them as well. But we've decided to do it essentially concurrent with the data that we're generating around the efficacy and biomarkers with the RT-102 products.

當然。布蘭登，很高興收到你的來信。謝謝你的問題。他們沒有在 RT-102 計劃的背景下這樣做。但我們之前曾與 FDA 進行過互動，數據庫規模約為 2000 個部署，八週內有 40 個受試者。事實證明，在第二階段，我們將達到這個水平，或者可能更高一點。所以我認為我們也有希望為他們回答這個問題。但我們決定基本上與我們圍繞 RT-102 產品的功效和生物標誌物生成的數據同時進行。

Great. Thanks. And then maybe just a follow-up to that. How should we think about the size of the Phase 1 trials that you're running into 2023? And then similarly on RT.-102 Phase 2 trial. And then maybe just focusing on in on that RT-111. Is that just going to be a normal Phase 1 trial or any nuances we should pay attention to there just given the (inaudible)? Thank you.

偉大的。謝謝。然後也許只是後續行動。我們應該如何考慮 2023 年進行的第一階段試驗的規模？ RT.-102 第 2 期試驗也類似。然後也許只是專注於 RT-111。這只是正常的第一階段試驗還是我們應該注意的任何細微差別（聽不清）？謝謝。

Sure. So they will look very similar to the single dose portion of the RT-102 Phase 1. So it'll be on the order of 15 to 20, maybe a little bit more in terms of the number of subjects. These are healthy volunteers, single dose. We may test with RT-111 a couple of different doses, just to see what the dose response curves look like, similar to what we did with RT-102. But I think you framed it well. It's going to look very, very similar. It's become -- I don't want to say cookie-cutter. Whenever you go into the clinic, its work and you have to take it very seriously. But I think we've gotten relatively good at it, putting these together and conducting them.

當然。因此，它們看起來與 RT-102 第一階段的單劑量部分非常相似。因此，其數量約為 15 至 20 人，就受試者數量而言可能會多一點。這些是健康志願者，單劑量。我們可以用 RT-111 測試幾個不同的劑量，只是為了看看劑量反應曲線是什麼樣的，類似於我們用 RT-102 所做的。但我認為你把它構想得很好。它看起來會非常非常相似。它已經變得——我不想說千篇一律。每當你進入診所時，它都是工作，你必須非常認真地對待它。但我認為我們已經比較擅長將這些整合在一起並進行實施。

And I think one last point you had around the Celltrion relationship. I think the expectation is similar data to what we generated with RT-102 should be sufficient to get us completed with the Phase 1 and into the [option] period.

我認為您關於 Celltrion 關係的最後一點是。我認為預期與我們使用 RT-102 生成的數據類似的數據應該足以讓我們完成第一階段並進入[選項]階段。

Great. I look forward to seeing that data. Again, congrats on all the progress over the last 12 to 18 months.

偉大的。我期待看到這些數據。再次祝賀過去 12 至 18 個月取得的所有進展。

Thank you so much.

太感謝了。

Geoff Meacham with Bank of America.

美國銀行的傑夫·米查姆 (Geoff Meacham)。

Good afternoon. This is (inaudible) calling in for Geoff Meacham. Thank you for the question.

下午好。這是（聽不清）呼叫傑夫·米查姆的電話。感謝你的提問。

So I think maybe I'll go back to the RT-102 multiple dose trial. I think you have on the shelf delivery for most of patients happened in day one and day two. So just wanted to double check if there any interventions happens once a patient missed -- had a failed delivery and joined that setup.

所以我想也許我會回到 RT-102 多劑量試驗。我認為大多數患者的上架交付發生在第一天和第二天。因此，我只是想仔細檢查一下，一旦患者錯過了分娩，並加入了該設置，是否會發生任何干預措施。

Hi, (inaudible). And to answer your question, no, there was no intervention and we don't expect there to be any. There will be some missed doses, but we manage that through -- in the case of RT-102 having significantly higher bioavailability, and if you recall from our PD preclinical study showing faster bone growth than we saw with the subcutaneous, and when you get to monoclonal antibodies, a missed dose here, there will be a wash because of the long half-life of the drug.

你好，（聽不清）。回答你的問題，不，沒有任何干預，我們也不認為會有任何干預。會有一些錯過的劑量，但我們通過這一點來解決——RT-102 具有顯著更高的生物利用度，並且如果您還記得我們的PD 臨床前研究顯示骨骼生長比我們在皮下注射時看到的更快，並且當您獲得對於單克隆抗體，由於藥物的半衰期較長，因此漏服劑量後會被清洗。

And in terms of when they happened, it was completely random. I think the point is there were so few failures in that study that you can kind of look at it and say that maybe there were more at the beginning. But we don't think it was anything it more than just random chance.

就它們發生的時間而言，完全是隨機的。我認為關鍵在於該研究中的失敗案例太少了，以至於你可以看一下它並說也許一開始就有更多失敗案例。但我們認為這不僅僅是隨機的機會。

Great. And just a quick follow-up. So for the Phase 2 expected by second half, what exactly needs to happen before the Phase 2 can be initiated?

偉大的。只是快速跟進。那麼對於下半年預計的第二階段來說，在第二階段啟動之前到底需要發生什麼？

Sure. So the guidance we got from the FDA was to run a repeat-dose GLP study of 28 days. We're going to be doing that here in the first half of the year and completing it and then submitting and hopefully getting that Phase 2 started as you said in the second half of '23.

當然。因此，我們從 FDA 獲得的指導是進行為期 28 天的重複劑量 GLP 研究。我們將在今年上半年這樣做並完成它，然後提交並希望像您在 23 年下半年所說的那樣開始第二階段。

Okay, makes sense. Thank you.

好吧，有道理。謝謝。

Yes, absolutely.

是的，一點沒錯。

(inaudible)

（聽不清）

All right. Hey guys. Thanks for taking our questions here. So just to (inaudible) here. So how does the Celltrion deal in the right of first negotiation indicate what the strategy would be for the company and the pipeline of biosimilars going forward?

好的。大家好。感謝您在這裡提出我們的問題。所以就到這裡（聽不清）。那麼，Celltrion 的首次談判權交易如何表明該公司的戰略以及未來的生物仿製藥產品線？

And then secondly, is the Celltrion deal indication-specific? Could you still partner out RT-111 for a different indication? Thanks.

其次，Celltrion 交易是否針對具體情況？您還能與 RT-111 合作用於不同的適應症嗎？謝謝。

Sure. I'll take the second first. It's a short answer. No, it is not indication-specific. It's for ustekinumab biosimilar or ustekinumab in general. So it's that entire drug, if you will, and any indications you could pursue with it. So CD, ulcerative colitis, or psoriasis.

當然。我先拿第二個。這是一個簡短的答案。不，它不是特定於適應症的。它適用於優特克單抗生物仿製藥或一般優特克單抗。所以，如果你願意的話，這就是整個藥物，以及你可以用它尋求的任何適應症。所以 CD、潰瘍性結腸炎或牛皮癬。

In terms of what the relationship with Celltrion implies, I think from our perspective implies that what we're doing is valuable and there's an interest in supporting us both in the clinical and commercial development from Celltrion, but also potentially taking over commercial rights as well.

就與Celltrion 的關係意味著什麼而言，我認為從我們的角度來看，這意味著我們正在做的事情是有價值的，並且有興趣支持我們從Celltrion 進行臨床和商業開發，但也有可能接管商業權利。

I think as we look ahead to additional deals, this could be the flavor of how things are done. And as we generate more data, I think there is a potential that the pharma companies will be less inclined to enable us to compete against them as opposed to working with us.

我認為，當我們展望更多交易時，這可能就是做事的方式。隨著我們生成更多數據，我認為製藥公司可能不太願意讓我們與他們競爭，而不是與我們合作。

Great. Thanks and congrats on progress.

偉大的。感謝並祝賀取得的進展。

Thank you.

謝謝。

Annabel Samimy, Stifel.

安娜貝爾·薩米米，斯蒂菲爾。

Hi. Thanks for taking my questions, and good progress. So on the Celltrion partnership again, are there any key requirements or metrics that Celltrion is looking for as far as the Phase 1 is concerned? Like they're saying bioavailability tech and stuff, and you need repeat dosing for that trial before you offer it up for an option or right of first negotiation?

你好。感謝您提出問題，並取得了良好的進展。那麼，關於 Celltrion 的合作夥伴關係，就第一階段而言，Celltrion 是否正在尋找任何關鍵要求或指標？就像他們說的生物利用度技術和其他東西一樣，您需要在該試驗中重複給藥，然後才能提供選擇權或首次談判權？

And then secondly, any further discussion with FDA regarding the design of the safety trail for 102. I think you are contemplating three different doses to have a sense of the dosing range, the timeframe, how large it could be, et cetera. Or is it primarily about a 505(b)(2) pathway?

其次，與 FDA 關於 102 安全試驗設計的任何進一步討論。我認為您正在考慮三種不同的劑量，以了解劑量範圍、時間範圍、劑量大小等。或者主要是關於 505(b)(2) 途徑？

Sure. So we should not need to do a repeat dosing to complete the Phase 1. It's a single dose study with probably half a meg and three quarters of a meg is the doses that we used for the RT-111 program for the Phase 1. There is nothing in particular beyond showing the bioavailability is similar to a subcutaneous injection of their CT-P43 ustekinumab biosimilar. I think that's what everyone's been looking for, what we would like to demonstrate as well.

當然。因此，我們不需要重複給藥來完成第一階段。這是一項單劑量研究，可能是半兆兆和四分之三兆兆，這是我們用於第一階段 RT-111 項目的劑量。除了顯示其生物利用度與CT-P43 ustekinumab 生物仿製藥的皮下注射相似之外，沒有什麼特別的。我認為這就是每個人都在尋找的東西，也是我們想要展示的東西。

And just to remind everyone, this will be the first time us or really anyone has been able to demonstrate systemic bioavailability of an orally administered monoclonal antibody. So this is a big milestone for the company. And I think hopefully that's sufficient to garner interest from Celltrion as we get into the option period.

只是提醒大家，這將是我們或任何人第一次能夠證明口服單克隆抗體的全身生物利用度。所以這對公司來說是一個重要的里程碑。我認為，當我們進入期權期時，這足以引起 Celltrion 的興趣。

As far as the RT-102 Phase 2 design is concerned, we did ask the FDA what they would want to see in terms of endpoints. And we're going to be looking at biomarkers. So P1NP, NCTX. And the duration is likely going to be eight weeks. You can see separation on those biomarkers fairly rapidly. And then from there, we would start planning for a Phase 3 where we would likely be looking at BMD as the endpoint.

就 RT-102 第 2 期設計而言，我們確實詢問了 FDA 他們希望在終點方面看到什麼。我們將研究生物標誌物。所以P1NP，NCTX。持續時間可能是八週。您可以相當快地看到這些生物標記物的分離。然後從那裡開始，我們將開始規劃第三階段，我們可能會將 BMD 作為終點。

Great. Thank you so much.

偉大的。太感謝了。

Thank you, Annabel.

謝謝你，安娜貝爾。

Ash Verma, UBS.

阿什·維爾瑪，瑞銀集團。

Hi, thanks for taking my questions. Congrats on the progress so far. I have two. So one was just, just on these Phase 1 studies that you're planning right in 2023. So single dose study. These should be relatively quick I would imagine. What kind of timeline do you think we can expect for the completion of these studies? And then second, anything that you can comment on kind of the cadence of OpEx given that you plan to initiate the Phase 2 for RT-102 in the second half year? How would OpEx compare in '23 versus 2022? Thanks.

您好，感謝您回答我的問題。祝賀迄今為止取得的進展。我有兩個。因此，其中之一就是您計劃在 2023 年進行的第一階段研究。單劑量研究。我想這些應該相對較快。您認為我們預計完成這些研究的時間表是怎樣的？其次，考慮到您計劃在下半年啟動 RT-102 的第 2 階段，您對 OpEx 的節奏有何評論？ 23 年與 2022 年的運營支出如何比較？謝謝。

Thank you, Ash. Appreciate the question. You are correct. The timeline for these Phase 1 is relatively short. It's a matter of months to get them done. I will say the RT-111 one will take a bit longer than RT-102 single dose just because the half-life of that drug is significantly longer. So in order to get the full curve, you have to track the patients for a bit longer. But we're also hoping and hope is not a plan. But with COVID not being as much of an issue as it was early last year, that if recruitment is fairly straightforward. This is a healthy volunteer study that we should be able to enroll fairly quickly. And that will help with getting it done quickly as well. And we all are incentivized.

謝謝你，阿什。感謝這個問題。你是對的。第一階段的時間表相對較短。完成它們只需幾個月的時間。我想說 RT-111 比 RT-102 單劑量需要更長的時間，因為該藥物的半衰期明顯更長。因此，為了獲得完整的曲線，您必須跟踪患者更長時間。但我們也希望，希望不是一個計劃。但由於新冠疫情不像去年初那麼嚴重，因此招聘相當簡單。這是一項健康的志願者研究，我們應該能夠相當快地註冊。這也將有助於快速完成任務。我們都受到激勵。

With your second question, I'm going to turn that over to Svai, our CFO, to answer.

關於你的第二個問題，我將把這個問題交給我們的首席財務官 Svai 來回答。

Thank you, Talat. Hopefully everyone can hear me. Ash, thank you for the question. As you can see in our filing, we ended the 2022 with the non -- with the cash portion of the OpEx just under $50 million. I expect that our operating expenses will increase for 2023 in the range of 20% to 30% from last year.

謝謝你，塔拉特。希望每個人都能聽到我的聲音。阿什，謝謝你的提問。正如您在我們的文件中看到的，我們在 2022 年結束時運營支出的現金部分略低於 5000 萬美元。我預計 2023 年我們的運營費用將比去年增加 20% 至 30%。

Great. Thanks, guys.

偉大的。多謝你們。

Thank you, Ash.

謝謝你，阿什。

Bert Hazlett, BTIG.

伯特·哈茲利特，BTIG。

Yes, thank you. Thank you for taking the question and congratulations on all the progress. Two topics in general. One is Celltrion. And as you think about the development of RT-111 CT-P43, is there a prioritization with regard to indication with the development of that program? Or how are you thinking about kind of steps beyond Phase 1? And then second question is kind of a similar question with regard to prioritization of the monoclones that you've mentioned, whether that's pembrolizumab, trastuzumab or others. How are you thinking about maybe prioritization of those types of molecules? Just general thoughts there would be helpful. Thank you.

是的，謝謝。感謝您提出問題並祝賀所有進展。總體來說有兩個話題。其中之一是 Celltrion。當您考慮 RT-111 CT-P43 的開發時，該程序的開發是否有適應症的優先順序？或者您如何考慮第一階段之後的步驟？第二個問題是關於您提到的單克隆抗體的優先順序的類似問題，無論是派姆單抗、曲妥珠單抗還是其他藥物。您如何考慮這些類型分子的優先順序？只是一般性的想法會有幫助。謝謝。

Sure. So it's a great question, Bert. First of all, thank you for the questions. In terms of our RT-111 CT-P43, we are in discussions with Celltrion right now to figure out how to prioritize. It would either be psoriasis or Crohn's disease I would imagine. And part of it will be determining the cost, the time to proof of concept, and also the regulatory plan, and if there's PK read on from what we're doing to whichever trial we decide to run to other indications. So can't provide guidance around that at this moment in time. But we have time. The Phase 1 is a healthy volunteer study. So we'll take this year to kind of coalesce around the plan, and we'll share that early next year.

當然。所以這是一個很好的問題，伯特。首先，感謝您提出的問題。就 RT-111 CT-P43 而言，我們現在正在與 Celltrion 進行討論，以確定如何確定優先級。我想這要么是牛皮癬，要么是克羅恩病。其中一部分將是確定成本、概念驗證的時間以及監管計劃，以及我們正在做的事情與我們決定進行其他適應症的任何試驗是否存在 PK。因此，目前無法及時提供相關指導。但我們有時間。第一階段是一項健康的志願者研究。因此，我們將在今年圍繞該計劃進行整合，並於明年初分享該計劃。

In terms of what we're planning to do with the RaniPIll HC, immunology I think as a general area is right in the sweet spot for what we're doing. Chronic diseases, crowded categories where differentiation to oral with a monoclonal antibody could be tremendous. And after that, we are looking at the delivery of antisense oligonucleotides and SRRNA. We're exploring that in discovery this year. And I would like to look in the future, I think, Bert, we've talked about this in the past. If daily administration and increasing [serum C] .trough levels, if you will, improves the efficacy of a monoclonal antibody, there's some evidence of that with certain drugs in the past. So we would want to look at that with oncology, whether it's as a standalone or as a maintenance to one of the popular oncology drugs like pembro and nivo. So that's for maybe next year. We have plenty on our plate as it is now, but that's kind of how we're thinking about utilizing the RaniPill HC.

就我們計劃用 RaniPIll HC 做的事情而言，我認為免疫學作為一個一般領域正是我們正在做的事情的最佳位置。慢性疾病是一個擁擠的類別，與口服單克隆抗體的區別可能是巨大的。之後，我們正在研究反義寡核苷酸和 SRRNA 的遞送。我們今年將在探索中探索這一點。我想展望未來，伯特，我們過去已經討論過這個問題。如果每天給藥並增加[血清C]谷水平（如果願意的話）可以提高單克隆抗體的功效，那麼過去有一些證據表明某些藥物可以達到這一點。因此，我們希望通過腫瘤學來看待這一點，無論是將其作為獨立的藥物還是作為流行的腫瘤藥物（如 pembro 和 nivo）的維持藥物。所以這可能是明年的事情。我們現在有很多事情要做，但這就是我們考慮使用 RaniPill HC 的方式。

Thanks for the color. Appreciate it.

謝謝你的顏色。欣賞它。

Yes, absolutely. Thank you.

是的，一點沒錯。謝謝。

Mitchell Kapoor, H.C. Wainwright.

米切爾·卡普爾，H.C.溫賴特。

Hi team. I hope everyone's well and thanks for taking the questions. I wanted to start out with RT-102. I wanted to understand more about the PK profile in terms of have you -- do you think you've established a margin of safety at this point for moving forward in a way that if efficacy follows PK, which we would expect that it probably should, could PK look slightly different in the next trials and still be considered positive?

大家好。我希望大家都好，感謝您提出問題。我想從 RT-102 開始。我想更多地了解 PK 概況，您是否認為您現在已經建立了安全邊際，以便以某種方式前進，如果功效遵循 PK，我們預計它可能應該，在接下來的試驗中PK 是否會略有不同，但仍然被認為是積極的？

Sure. So thank you for the question, Mitchell. And I realize in you asking that, that I failed to answer one of Annabell's questions. So I'll do both in the same shot. We're looking at doses between 10 micrograms and 40 micrograms. So 10, 20 and 40 specifically to address the question you just had, which is if we're getting better or significantly better bone growth, I would caution that we had a lower AE incidence in our single dose and even in our multi-dose. Well, we didn't compare in the multi-dose. But compared to the -- even the 80 microgram Rani oral versus a 20 microgram Forteo and the single dose, it looked the cleaner from an AE perspective. We need to conduct that study in the Phase 2 or look at the AE rates, I should say. But through the dose selection, I think we can find a sweet spot where we have the efficacy we need for noninferiority, and a safety profile that is commensurate with what you see with Forteo currently.

當然。謝謝你的提問，米切爾。我意識到你問這個問題時我沒能回答安娜貝爾的問題之一。所以我會在同一個鏡頭中完成這兩個動作。我們正在研究 10 微克到 40 微克之間的劑量。因此，10、20 和40 特別是為了解決您剛才提出的問題，即我們的骨骼生長情況是否有所改善或顯著改善，我要提醒您的是，我們的單劑量甚至多劑量中的AE 發生率較低。好吧，我們沒有比較多劑量。但與 80 微克 Rani 口服液與 20 微克 Forteo 和單劑量相比，從 AE 角度來看，它看起來更乾淨。我應該說，我們需要在第二階段進行這項研究，或者看看 AE 率。但通過劑量選擇，我認為我們可以找到一個最佳點，使我們具有非劣效性所需的功效，以及與您目前所看到的 Forteo 相稱的安全性。

Okay. That's very helpful. And then on the RT-101 program, could you just provide an update there and when we might be able to see more developments from that program, or what the plan going forward for?

好的。這非常有幫助。然後，關於 RT-101 計劃，您能否提供最新情況，以及我們何時能夠看到該計劃的更多進展，或者未來的計劃是什麼？

Sure. So as I mentioned in the past, we're working on a sustained release formulation. This is the technology that's going into our RT-110 PTH for hypoparathyroidism program. We have made considerable progress, which is why it's in our roadmap for Phase 1. And that same approach is what we're going to be working on this year with our RT-101 formulation to reformulate it into a long acting so that it's more competitive with the (inaudible). So nothing to report at this moment in time, but I think that's something that we'll revisit later this year.

當然。正如我過去提到的，我們正在研究緩釋製劑。這是我們用於治療甲狀旁腺功能減退症的 RT-110 PTH 項目中採用的技術。我們已經取得了相當大的進展，這就是為什麼它被列入我們第一階段路線圖的原因。今年我們將採用同樣的方法，將 RT-101 製劑重新配製為長效製劑，使其更有效。與（聽不清）競爭。因此，目前沒有什麼可報告的，但我認為我們將在今年晚些時候重新討論這一問題。

Okay, great. Thank you very much.

好的，太好了。非常感謝。

Thank you.

謝謝。

Thank you. I'm showing no further questions in the queue. I would now like to turn the call back to Talat for closing remarks.

謝謝。我在隊列中沒有顯示任何其他問題。現在我想將電話轉回塔拉特，讓其致閉幕詞。

Thank you, operator. This concludes our fourth quarter and full year 2022 financial results and corporate update conference call. Thank you again, everyone, for joining us this afternoon.

謝謝你，接線員。我們的 2022 年第四季度和全年財務業績和公司更新電話會議到此結束。再次感謝大家今天下午加入我們。

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.

女士們、先生們，今天的電話會議到此結束。感謝您的參與。您現在可以斷開連接。