Lumos Pharma Inc (LUMO) 2024 Q1 法說會逐字稿

Greetings and welcome to Lumos Pharma first quarter 2024 financial results and clinical programs update call. (Operator Instructions) As a reminder, this conference is being recorded.

您好，歡迎參加 Lumos Pharma 2024 年第一季財務業績及臨床專案更新電話會議。 （操作員指示）謹此提醒，本次會議正在錄製中。

It is now my pleasure to introduce your host, Ms. Lisa Miller, Vice President, Investor Relations. Thank you, Ms. Miller. You may begin.

現在我很高興向您介紹主持人，投資者關係副總裁麗莎·米勒女士。謝謝你，米勒女士。你可以開始了。

Thank you, operator. Before we proceed with the call, I would like to remind everyone that certain statements made during this call are forward-looking statements under US federal securities laws. These statements are subject to risks and uncertainties that could cause actual results to differ materially from historical experience or present expectations.

謝謝你，接線生。在我們進行電話會議之前，我想提醒大家，根據美國聯邦證券法，本次電話會議中所做的某些陳述屬於前瞻性陳述。這些陳述存在風險和不確定性，可能導致實際結果與歷史經驗或當前預期有重大差異。

Additional information concerning factors that could cause actual results to differ is contained in our periodic reports filed with SEC. The forward-looking statements made during this call speak only as of the date hereof, and the company undertakes no obligation to update or revise these forward-looking statements. Information presented on this call is contained in the press release we issued yesterday afternoon and in our Form 8-K , which may be accessed from the investor's page of the Lumos Pharma website.

有關可能導致實際結果不同的因素的更多資​​訊包含在我們向 SEC 提交的定期報告中。本次電話會議期間所做的前瞻性陳述僅代表截至本新聞稿發布之日的情況，本公司不承擔更新或修改這些前瞻性陳述的義務。本次電話會議提供的資訊包含在我們昨天下午發布的新聞稿和 8-K 表格中，您可以從 Lumos Pharma 網站的投資者頁面存取該表格。

Speaking on today's call will be Rick Hawkins, CEO and Chairman; John McKew, President and Chief Scientific Officer; and Lori Lawley, Chief Financial Officer. Dr. Duke Pitukcheewanont, Chief Medical Officer; will also join the call for the question and answer session. It's now my pleasure to turn the call over to Rick for our opening remarks.

執行長兼董事長 Rick Hawkins 將在今天的電話會議上發言。 John McKew，總裁兼首席科學官；和財務長洛里·勞利 (Lori Lawley)。 Duke Pitukcheewanont 博士，首席醫療官；也將參加問答環節的徵集。現在我很高興將電話轉給里克，讓他致開幕詞。

Thank you, Lisa, and good morning, everyone. I'm pleased to be speaking with you today to provide an update on our progress advancing LUM-201 as the first oral therapeutic for moderate pediatric growth hormone deficiency, or PGHD. Our recent months have been incredibly productive at Lumos, marked by significant milestones.

謝謝你，麗莎，大家早安。我很高興今天與您交談，介紹我們將 LUM-201 作為第一個口服治療中度兒科生長激素缺乏症 (PGHD) 的藥物的最新進展。最近幾個月，Lumos 取得了令人難以置信的成果，取得了重大里程碑。

We've had a constructive end-to-Phase 2 meeting with the FDA and conducted fresh analyses on updated data from our OraGrowtH212 and 210 trials. I'll keep my opening remarks concise before handing over to my colleagues to review in greater detail the strides we've made so far this year. So, let's begin.

我們與 FDA 舉行了建設性的第 2 階段結束會議，並對 OraGrowtH212 和 210 試驗的最新數據進行了新的分析。在讓我的同事們更詳細地回顧我們今年迄今為止所取得的進展之前，我將保持簡潔的開場白。那麼，讓我們開始吧。

As detailed in our press release, we recently held a collaborative end-to-Phase 2 meeting with the FDA, where we reviewed the promising data from our Phase 2 OraGrowtH210 and 212 trials and discussed an optimal Phase 3 design for a successful regulatory path forward. Both Phase 2 OraGrowtH trials, as you may recall, successfully met their primary and secondary endpoints, providing robust evidence supporting the potential of Ora LUM-201 in treating moderate PGHD.

正如我們的新聞稿中所詳述的，我們最近與FDA 舉行了一次2 期最終合作會議，會上我們審查了OraGrowtH210 和212 2 期試驗的有希望的數據，並討論了成功的監管路徑的最佳3 期設計。您可能還記得，兩項 OraGrowtH 2 期試驗均成功達到了主要和次要終點，為支持 Ora LUM-201 治療中度 PGHD 的潛力提供了強有力的證據。

Additionally, the trials demonstrated the effectiveness of our predictive enrichment marker test in identifying patients likely to respond to LUM-201. During our dialogue with the FDA, it was acknowledged that LUM-201 operates distinctly from growth hormone or its mimetics. The FDA recognized LUM-201 as a novel growth hormone promoter with a unique mechanism of action and consequently proposed that we consider a placebo-controlled Phase 3 trial design.

此外，這些試驗證明了我們的預測富集標記物測試在識別可能對 LUM-201 產生反應的患者方面的有效性。在我們與 FDA 的對話中，我們承認 LUM-201 的作用與生長激素或其模擬物不同。 FDA 認可 LUM-201 是一種具有獨特作用機制的新型生長激素促進劑，因此建議我們考慮安慰劑對照的 3 期試驗設計。

This trial design would not require an active comparator arm with a non-inferiority margin but would necessitate demonstrating clinically significant improvements in growth compared to placebo.

此試驗設計不需要具有非劣效性裕度的主動比較組，但需要證明與安慰劑相比，臨床上生長顯著改善。

Now, we are delighted by these developments as we see them greatly enhancing the prospects for a successful Phase 3 Trial of LUM-201. Pending final FDA approval of this trial design, we plan to initiate this trial by year-end 2024. We firmly believe that this refined design significantly bolsters our chances of advancing LUM-201 toward approval as the first oral therapeutic for moderate PGHD.

現在，我們對這些進展感到高興，因為我們看到它們極大地提高了 LUM-201 第三階段試驗成功的前景。在等待FDA 最終批准該試驗設計時，我們計劃在2024 年底之前啟動該試驗。的機會。

Our confidence in LUM-201 was further strengthened through our examination of additional data from our Phase 2 OraGrowtH Trials. As detailed in our press release, we unveiled updated 12-month and 24-month data from these trials, which consistently demonstrate a durable effect and substantial improvement over baseline annualized height velocity.

透過檢查 2 期 OraGrowtH 試驗的額外數據，我們對 LUM-201 的信心進一步增強。正如我們的新聞稿中所詳述的，我們公佈了這些試驗的最新 12 個月和 24 個月數據，這些數據一致證明了其持久效果，並且比基線年化身高速度有顯著改善。

We are confident that the advancements made positioned Lumos Pharma as a late-stage biopharmaceutical company with substantial growth prospects and continue to support the potential of oral LUM-201 to disrupt the $4.7 billion global market for injectable growth hormone deficiency.

我們相信，所取得的進步使 Lumos Pharma 成為一家具有巨大成長前景的後期生物製藥公司，並繼續支持口服 LUM-201 的潛力，顛覆價值 47 億美元的全球注射生長激素缺乏症市場。

Now, I'll hand the call over to John McKew for further insights and to our interaction with the FDA and our strategic planning for this pivotal Phase 3 Trial. John?

現在，我將把電話轉給 John McKew，以獲取更多見解、我們與 FDA 的互動以及我們對這項關鍵 3 期試驗的策略規劃。約翰？

Thanks, Rick, and good morning, everyone. As Rick mentioned, we recently concluded our end of Phase 2 meeting with the FDA to evaluate data from our OraGrowtH Trials and explore potential strategies for a Phase 3 pivotal trial. A key highlight from the meeting was its overwhelmingly positive and constructive nature. With approximately 30 FDA staff members present, including senior representatives from pertinent departments, the adversary remained collegial and centered on determining the optimal approach for the pivotal trial design of LUM-201 in treating moderate PGHD.

謝謝瑞克，大家早安。正如 Rick 所提到的，我們最近結束了與 FDA 的第二階段會議，以評估 OraGrowtH 試驗的數據並探索第三階段關鍵試驗的潛在策略。會議的一個主要亮點是其極其積極和建設性的性質。大約有 30 名 FDA 工作人員在場，其中包括相關部門的高級代表，對手仍然保持合議，並集中精力確定 LUM-201 治療中度 PGHD 關鍵試驗設計的最佳方法。

The data package we presented to the FDA underscored the outcomes of our Phase 2 OraGrowtH Trials. As you may recall, these trials successfully met their primary and secondary endpoints, demonstrating that LUM-201 achieved annualized height velocity consistent with predetermined targets derived from historical benchmarks in a moderate PGHD patient population.

我們向 FDA 提交的資料包強調了我們 2 期 OraGrowtH 試驗的結果。您可能還記得，這些試驗成功地達到了主要和次要終點，證明 LUM-201 實現的年化身高速度與中度 PGHD 患者群體的歷史基準得出的預定目標一致。

Additionally, the growth rates observed at both 6 and 12 months on treatment with LUM-201 at the 1.6 mg per kg per day dose aligned with historical recombinant human growth hormone growth rates in similar patient cohorts with sustained efficacy observed at both 12 and 24 months. Notably, LUM-201 also exhibited the ability to normalize IGF-1 standard deviation scores within six months of treatment initiation.

此外，每天每公斤體重1.6 毫克的LUM-201 治療在第6 個月和第12 個月觀察到的生長率與相似患者群組中的歷史重組人生長激素生長率一致，並且在第12 個月和第24 個月觀察到持續療效。值得注意的是，LUM-201 也表現出在治療開始後六個月內使 IGF-1 標準差評分正常化的能力。

Furthermore, the trial data provided preliminary confirmation that our predictive emergent marker, or PEM, strategy accurately identified potential LUM-201 responders and showcased the PEM classification as 100% reproducible, surpassing the predefined statistical margin.

此外，試驗數據初步證實我們的預測緊急標記（PEM）策略準確地識別了潛在的 LUM-201 反應者，並顯示 PEM 分類具有 100% 可重複性，超過了預先定義的統計裕度。

Additionally, safety profile of an investigational LUM-201 was further validated. Upon reviewing these data, FDA representatives indicated a shift in their perspective regarding LUM-201s distinct mechanism. They acknowledged that LUM-201 is not merely a growth hormone mimetic, but rather a distinct growth promoter. The FDA's understanding of these data prompted them to suggest that LUM-201 should not necessarily be directly compared to traditional growth hormone products.

此外，研究中的 LUM-201 的安全性也得到了進一步驗證。在審查這些數據後，FDA 代表表示他們對 LUM-201 獨特機制的看法發生了轉變。他們承認 LUM-201 不僅僅是一種生長激素模擬物，而是一種獨特的生長促進劑。 FDA 對這些數據的理解促使他們建議 LUM-201 不一定應該與傳統的生長激素產品直接進行比較。

As a reminder, LUM-201 is a small molecule that binds to the growth hormone's receptor 1A in both the pituitary and the hypothalamus. LUM-201 agonizes the receptor, and that signals the release of stored growth hormone in the Somatrogon. By also modulating Somatrogon and growth hormone releasing hormone in the hypothalamus, LUM-201 restores the natural pulsatile release of growth hormone.

提醒一下，LUM-201 是一種小分子，可與腦下垂體和下丘腦中的生長激素受體 1A 結合。 LUM-201 會激動受體，從而發出 Somatrogon 中儲存的生長激素釋放的信號。 LUM-201 也透過調節下丘腦中的 Somatrogon 和生長激素釋放激素，恢復生長激素的自然脈動釋放。

The increase in the amplitude, or peak, of each growth hormone pulse boosts the circulating levels of growth hormone, subsequently elevating the levels of circulating IGF-1. Both growth hormone and IGF-1 then act on the open growth plates in the long bones of children with growth hormone deficiency, stimulating growth.

每個生長激素脈衝的幅度或峰值的增加會提高生長激素的循環水平，從而提高循環 IGF-1 的水平。然後，生長激素和 IGF-1 都會作用於生長激素缺乏症兒童長骨中開放的生長板，刺激生長。

The FDA's acknowledgement that LUM-201 operates as a novel growth promoter, rather than a mimetic of injectable exogenous recombinant human growth hormone, enables a more expansive view in considering design approaches for a Phase 3 Trial. A significant portion of the meeting was dedicated to exploring different options, culminating in the suggestion by the FDA that we contemplate a placebo-controlled design.

FDA 承認 LUM-201 是一種新型生長促進劑，而不是可注射的外源重組人生長激素的模擬物，這使得在考慮 3 期試驗的設計方法時能夠有更廣闊的視野。會議的很大一部分時間致力於探索不同的選擇，最終 FDA 建議我們考慮安慰劑對照設計。

Heading into the FDA meeting, we examined historical pivotal trial designs with growth promoting agents and proposed to the FDA a standard non-inferiority design consisting of-- in this case, a 12-month study evaluating LUM-201 against the lower-approved dose of growth hormone.

在FDA 會議之前，我們審查了使用生長促進劑的歷史關鍵試驗設計，並向FDA 提出了一個標準的非劣效性設計，其中包括一項為期12 個月的研究，針對較低批准劑量評估LUM -201生長激素。

We chose this comparator dose because it more closely mirrors the physiological levels of growth hormone and IGF-1 that LUM-201 restores. We engaged in productive discussions with the FDA regarding this non-inferiority approach, but during these conversations, the FDA suggested we could explore a placebo-controlled trial.

我們選擇這個比較劑劑量是因為它更接近地反映了 LUM-201 恢復的生長激素和 IGF-1 的生理水平。我們與 FDA 就這種非劣效性方法進行了富有成效的討論，但在這些對話中，FDA 建議我們可以探索一項安慰劑對照試驗。

A placebo-controlled trial would be required to demonstrate clinically significant growth compared to the placebo with 12 months of treatment. Following the FDA's recommendation and drawing from insights provided by our regulatory consultants, clinical and scientific advisory board, statisticians, we have designed a placebo-controlled trial featuring a two-to-one randomization of LUM-201 to placebo.

需要進行安慰劑對照試驗來證明在 12 個月的治療中與安慰劑相比有臨床顯著的增長。根據 FDA 的建議並借鑒我們的監管顧問、臨床和科學顧問委員會、統計學家提供的見解，我們設計了一項安慰劑對照試驗，其中 LUM-201 與安慰劑進行二比一隨機化。

One arm will receive LUM-201 for 12 months, while the other arm will initially receive placebo and then transition to LUM-201 after six months, remaining on treatment for the next six months. All subjects enrolled in the trial will be PEM positive.

一隻手臂將接受 LUM-201 治療 12 個月，而另一隻手臂將首先接受安慰劑，然後在六個月後過渡到 LUM-201，並在接下來的六個月內繼續接受治療。所有參加試驗的受試者將呈現 PEM 陽性。

This Phase 3 Trial design serves two strategic objectives. The first, providing the FDA with ample data to evaluate LUM-201 for approval and ensuring that all subjects receive treatment with LUM-201, the active agent. For this trial, we envisage two co-primary endpoints. First, the 12-month treatment arm must demonstrate clinically significant growth. Second, there will be a pairwise comparison within subject assessing growth on placebo versus growth on LUM-201, which must also exhibit clinically meaningful growth.

第三階段試驗設計有兩個策略目標。首先，為 FDA 提供充足的數據來評估 LUM-201 的批准，並確保所有受試者都接受活性藥物 LUM-201 的治療。對於這項試驗，我們設想了兩個共同主要終點。首先，12 個月的治療組必須表現出臨床上顯著的成長。其次，將在受試者中進行配對比較，評估安慰劑的生長與 LUM-201 的生長，LUM-201 也必須表現出有臨床意義的生長。

Following the 12-month trial period, all participants will have the option to transition into a long-term safety extension, which will provide LUM-201 treatment for up to three years. We are confident that the trial size is more than adequate to meet the described co-primary endpoints. We anticipate finalizing this design over the next couple of months and pending approval from the agency, we aim to initiate the Phase 3 Trial before the end of 2024.

12 個月的試用期結束後，所有參與者都可以選擇過渡到長期安全延期，這將提供長達三年的 LUM-201 治療。我們相信試驗規模足以滿足所描述的共同主要終點。我們預計在未來幾個月內完成該設計，並等待該機構的批准，我們的目標是在 2024 年底之前啟動第 3 階段試驗。

Our potential for success in a pivotal trial is bolstered by the evolving data and deeper analysis from our OraGrowtH Trials. In yesterday's press release, we unveiled preliminary updated 12- and 24-month growth data from our OraGrowtH210 Trial.

OraGrowtH 試驗中不斷變化的數據和更深入的分析增強了我們在關鍵試驗中取得成功的潛力。在昨天的新聞稿中，我們公佈了 OraGrowtH210 試驗的初步更新的 12 個月和 24 個月增長數據。

A data snapshot from our trials, specifically the six and updated 12-month data on LUM-201, when measured against similar populations from Phase 4 studies, indicate comparable growth rates. Like these historical databases, we are focusing on treating the moderate PGHD population while excluding the more severe growth hormone deficient cases. Our updated data consistently demonstrate that we are achieving growth rates similar to those observed in historical data for the moderate PGHD patient cohort.

我們試驗的數據快照，特別是 LUM-201 的 6 個月和更新的 12 個月數據，與第 4 期研究的類似人群進行測量時，表明增長率相當。與這些歷史資料庫一樣，我們專注於治療中度 PGHD 族群，同時排除更嚴重的生長激素缺乏病例。我們的更新數據一致表明，我們正在實現與中度 PGHD 患者群組歷史數據中觀察到的成長率相似的成長率。

Further analyses compare the six- and 12-month growth rates on LUM-201 and baseline growth rates. These findings highlight a noteworthy increase in AHV or annualized site velocity from baseline upon treatment of LUM-201. The baseline growth rate of 4.7 centimeters per year documented in our Phase 2 Trial should serve as an indicator of the placebo arms annualized growth rate in our Phase 3 Trial. The full 12-month data for all cohorts in the OraGrowtH210 Trial reinforces our choice to advance the 1.6 mg per kg, LUM-201 dose into Phase 3.

進一步的分析比較了 LUM-201 的 6 個月和 12 個月增長率與基線增長率。這些發現強調了 LUM-201 治療後 AHV 或年化站點速度較基線顯著增加。我們的第 2 階段試驗中記錄的每年 4.7 公分的基線成長率應作為我們第 3 階段試驗中安慰劑組年化成長率的指標。 OraGrowtH210 試驗中所有隊列的完整 12 個月數據強化了我們將 1.6 mg/kg LUM-201 劑量推進到第 3 期的選擇。

Finally, we combined the 1.6 and 3.2 mg per kg per day cohorts from our two Phase 2 Trials, since their growth rates were not statistically different. These data include all subjects who were treated to 24 months, excluding those who transitioned from [tender 1 to tender 2] to enable a comparison to historical Pfizer’s KIGS database. These updated data continue to underscore the enduring efficacy of LUM-201. When comparing year one AHV to year two AHV for LUM-201, only a modest drop-off of approximately 10% is observed.

最後，我們將兩個 2 期試驗中每天每公斤 1.6 毫克和 3.2 毫克的隊列合併起來，因為它們的生長率沒有統計學差異。這些數據包括接受治療至 24 個月的所有受試者，不包括從[招標 1 到招標 2] 過渡的受試者，以便與歷史輝瑞的 KIGS 資料庫進行比較。這些更新的數據繼續強調了 LUM-201 的持久性。當比較 LUM-201 的第一年 AHV 和第二年 AHV 時，僅觀察到約 10% 的適度下降。

This stands in contrast to the published data from the less severe GHD population in the KIGS database treated with recombinant hemoglobin where the drop-off is closer to 20%. These findings from our Phase 2 studies highlighted how LUM-201 could normalize growth hormone secretion and IGF-1 levels, thus restoring normal physiological growth with sustained benefits over time.

這與 KIGS 資料庫中接受重組血紅蛋白治療的較不嚴重的 GHD 族群公佈的數據形成鮮明對比，後者的下降接近 20%。我們的 2 期研究結果強調了 LUM-201 如何使生長激素分泌和 IGF-1 水平正常化，從而恢復正常的生理生長，並隨著時間的推移帶來持續的益處。

These data were presented at the FDA end of Phase 2 meeting and were compelling enough to convince the agency of LUM-201's novel mechanism of action, granting them the freedom to suggest innovative Phase 3 study designs.

這些數據在 FDA 2 期會議結束時公佈，足以說服 FDA 相信 LUM-201 的新穎作用機制，使他們能夠自由地提出創新的 3 期研究設計。

We believe that this placebo-controlled design significantly mitigates our regulatory risk and enhances our potential to introduce the first oral therapeutic for growth hormone deficiency to the market. This innovative oral therapeutic is anticipated to be a welcome treatment option for pediatric endocrinologists seeking to address pediatric growth hormone deficiency in their patients.

我們相信，這種安慰劑對照設計顯著降低了我們的監管風險，並增強了我們向市場推出第一種治療生長激素缺乏症的口服療法的潛力。對於尋求解決患者兒童生長激素缺乏症的兒科內分泌學家來說，這種創新的口服療法預計將成為受歡迎的治療選擇。

Earlier this month, analyses of top-line OraGrowtH Trial results were presented at three major endocrinology conferences at the Pediatric Endocrine Society meeting in Chicago by Dr. [Andrew Dauber], highlighting data showing LUM-201 achieved comparable annualized height velocity to daily recombinant hemoglobin and PGHD at the 1.6 mg per day dose with a promising safety profile.

本月早些時候，[Andrew Dauber] 博士在芝加哥兒科內分泌學會會議上的三個主要內分泌學會議上介紹了OraGrowtH 試驗的主要結果分析，其中強調的數據顯示LUM-201 實現了與每日重組血紅蛋白相當的年化身高速度每日 1.6 毫克劑量的 PGHD 具有良好的安全性。

And at two subsequent conferences in Stockholm, the Growth Hormone Research Society and European Congress of Endocrinology, Dr. [Peter Clayton] presented a comprehensive analysis of LUM-201 restoration of growth hormone secretion and the increase in AHV-induced and moderate PGHD patient.

隨後在斯德哥爾摩舉行的兩場會議上，生長激素研究學會和歐洲內分泌學大會上，[Peter Clayton] 博士對 LUM-201 恢復生長激素分泌以及 AHV 誘發和中度 PGHD 患者增加的情況進行了全面分析。

We are pleased to announce that we have had two abstracts accepted for presentation at the upcoming Endocrine Society meeting, or ENDO, next month, where we also plan to release the full 12 month data from our OraGrowtH212 trial with additional analyses from the OraGrowtH210 trial.

我們很高興地宣布，我們已經接受了兩份摘要，以便在下個月即將召開的內分泌學會會議(ENDO) 上發表，我們還計劃在會上發布OraGrowtH212 試驗的完整12 個月數據以及OraGrowtH210 試驗的其他分析。

The maturing data from our OraGrowtH Trials continue to resonate with the global endocrinology community, and we are encouraged by the growing interest among experts as we finalize our plans for a pivotal trial.

我們的 OraGrowtH 試驗的成熟數據繼續引起全球內分泌學界的共鳴，隨著我們最終確定關鍵試驗的計劃，專家們越來越感興趣，這讓我們感到鼓舞。

With that, I would like to turn it over to Lori for a review of our financial results for Q1.

至此，我想將其交給 Lori 來審查我們第一季的財務表現。

Thanks, John. We ended the quarter on March 31, 2024, with cash, cash equivalents, and short-term investments totaling $23.2 million, as compared to $36 million on December 31, 2023. Cash on hand is expected to support operations through the third quarter of this year, inclusive of Phase 3 planning and preparatory activities.

謝謝，約翰。截至 2024 年 3 月 31 日的季度，我們的現金、現金等價物和短期投資總額為 2,320 萬美元，而 2023 年 12 月 31 日為 3,600 萬美元。 ，包括第三階段的規劃和準備活動。

With the recent developments from the FDA, we are confident that we will be able to finance our Phase 3 trial for patients with pediatric growth hormone deficiency in the near term. Research and development expenses were $7.2 million, an increase of $2.9 million for the quarter ended March 31, 2024, compared to the same period in 2023, primarily due to increases of $2 million in licensing expense, $0.8 million in clinical trial expenses, and $0.2 million in consulting expenses, offset by a decrease of $0.1 million in personnel-related expenses.

隨著 FDA 的最新進展，我們有信心在短期內能夠為兒童生長激素缺乏症患者的 3 期試驗提供資金。截至 2024 年 3 月 31 日的季度，研發費用為 720 萬美元，較 2023 年同期增加 290 萬美元，主要是由於許可證費用增加 200 萬美元、臨床試驗費用增加 80 萬美元、以及 0.2 美元增加。費用減少10 萬美元，但被人事相關費用減少10 萬美元所抵銷。

General and administrative expenses were $3.8 million, a decrease of $0.6 million, compared to the same period in 2023, primarily due to decreases of $0.4 million in licensing expenses, $0.1 million in travel expenses, $0.1 million in consulting expenses, and $0.1 million in other expenses, offset by an increase of $0.1 million in personnel-related expenses.

一般及管理費用為 380 萬美元，與 2023 年同期相比減少 60 萬美元，主要是因為許可證費用減少 40 萬美元、差旅費減少 10 萬美元、諮詢費用減少 10 萬美元，其他費用減少 10 萬美元。費用，被人事相關費用增加10 萬美元所抵銷。

The net loss for the quarter ended March 31, 2024, with $10.4 million, compared to a net loss of $7.3 million for the same period in 2023. Lumos Pharma ended Q1, 2024, with $8,107,121 shares outstanding.

截至 2024 年 3 月 31 日的季度淨虧損為 1,040 萬美元，而 2023 年同期淨虧損為 730 萬美元。

And now I will turn it over to Rick for his closing remarks.

現在我將把它交給里克做總結發言。

Thank you, Lori, and John. As mentioned earlier in the call, it's been an exciting and fruitful time for Lumos, and we are steadily progressing towards our objective of unlocking the potential of LUM-201 as a pioneering oral therapeutic poised to revolutionize the global growth hormone market, which has been dominated by injectable products for nearly four decades.

謝謝洛瑞和約翰。正如前面在電話會議中提到的，這對Lumos 來說是一個激動人心且富有成效的時刻，我們正在穩步推進我們的目標，即釋放LUM-201 作為開創性口服治療藥物的潛力，有望徹底改變全球生長激素市場，該市場已近四十年來一直以注射產品為主。

Before opening the call to your questions, I'd like to take a moment to discuss the commercial potential we envision for oral LUM-201. If approved, we believe LUM-201 presents several potential advantages over current injectable recombinant growth hormone products, including sustained growth benefits and the restoration of physiological pulsatile release of growth hormone within the natural endocrine feedback loop.

在開始回答大家的問題之前，我想花點時間討論一下我們對口服 LUM-201 的商業潛力的設想。如果獲得批准，我們相信 LUM-201 比目前的注射重組生長激素產品具有幾個潛在優勢，包括持續的生長效益和恢復自然內分泌反饋迴路內生長激素的生理脈衝釋放。

As an oral therapy, LUM-201 represents an appealing alternative to daily and weekly injections and has the potential to broaden the pediatric growth hormone deficient treatment market, particularly among moderately growth hormone deficient patients.

作為一種口服療法，LUM-201 是每日和每週注射的一種有吸引力的替代方案，並有潛力擴大兒科生長激素缺乏治療市場，特別是在中度生長激素缺乏患者中。

Additionally, it's worth noting that as a small molecule, the cost of goods for commercial scale production of LUM-201 would be significantly lower than for recombinant growth hormone. And as we've consistently emphasized, we view LUM-201 not only as a singular product, but also as a robust pipeline.

此外，值得注意的是，作為一種小分子，LUM-201商業規模生產的商品成本將明顯低於重組生長激素。正如我們一直強調的那樣，我們不僅將 LUM-201 視為單一產品，而且將其視為強大的產品線。

We see the potential for LUM-201 to address 10 additional indications currently treated with recombinant growth hormone, including Prader-Willi syndrome and idiopathic short stature.

我們看到 LUM-201 有潛力解決目前使用重組生長激素治療的 10 種其他適應症，包括普瑞德威利症候群和特發性身材矮小。

With the FDA acknowledging LUM-201 as a novel growth promoter, we believe this paves the way for a streamlined clinical trial design for these other indications, as well as for attractive commercial positioning.

隨著 FDA 承認 LUM-201 是一種新型生長促進劑，我們相信這為這些其他適應症的簡化臨床試驗設計以及有吸引力的商業定位鋪平了道路。

Now, this is truly a pivotal moment in a company's trajectory. With the positive guidance from the FDA, we're propelling our late-stage program for oral LUM-201 towards a regulatory pathway with a high likelihood of success. Additionally, we anticipate some very exciting developments in the coming year and eagerly anticipate sharing updates on our progress with you.

現在，這確實是公司發展軌跡的關鍵時刻。在 FDA 的積極指導下，我們正在推動口服 LUM-201 的後期專案走向監管途徑，成功的可能性很高。此外，我們預計來年會出現一些非常令人興奮的發展，並熱切期待與您分享我們的最新進展。

Thank you all very much for listening today. And operator, we're ready to take questions. Will, please.

非常感謝大家今天的收聽。接線員，我們準備好回答問題。威爾，請。

Thank you. (Operator Instructions) The first question comes from the line of Liam Hiester, Piper Sandler. Please go ahead.

謝謝。 （操作員說明）第一個問題來自 Liam Hiester、Piper Sandler 的線。請繼續。

Hi, team. This is Liam Hiester on for Yas. Thanks so much for the update this morning. Just to start, in regard to the upcoming Phase 3 study, I was wondering if you could provide some update on your expected bar for success in connection to growth. And then also any clarity on why you chose a specific dose to move forward with.

大家好。我是亞斯隊的利亞姆·希斯特。非常感謝今天早上的更新。首先，關於即將進行的第三階段研究，我想知道您是否可以提供一些有關成長成功預期標準的最新資訊。然後也要澄清為什麼您選擇特定劑量繼續進行。

Further, what is the overall safety database requirement for approval, and have you had any chance to engage with the EMA in regard to the Phase 3 design as well? And then also, if you could comment at all on how long you expect it to take to enroll the Phase 3 trial, as well as if there's any overlap between the Phase 2 and Phase 3 sites. That's for now.

此外，核准的整體安全資料庫要求是什麼？另外，您是否可以評論一下您預計註冊第 3 階段試驗需要多長時間，以及第 2 階段和第 3 階段試驗地點之間是否有重疊。目前就這樣。

All excellent questions. I think the bar to success question probably should be answered by John. Go ahead, John.

所有的問題都很好。我認為成功的障礙問題可能應該由約翰來回答。繼續吧，約翰。

As we mentioned, we have to show clinically meaningful growth. What we have agreed to in the past with the FDA to define clinically meaningful growth is that an agreement with the FDA at the end of 12 months in our Phase 2 trial subjects have to achieve 6.7 centimeters per year growth. That was what we defined as the minimal clinically meaningful growth to continue on treatment with LUM-201. So one of the options that we have is to present that as an option for clinically meaningful growth in this Phase 3 study.

正如我們所提到的，我們必須表現出具有臨床意義的成長。我們過去與 FDA 就定義具有臨床意義的生長達成的協議是，在 12 個月結束時，我們的 2 期試驗受試者必須實現每年 6.7 公分的生長。這就是我們定義的繼續 LUM-201 治療的最小臨床有意義的增長。因此，我們擁有的選擇之一就是將其作為這項 3 期研究中具有臨床意義的成長的選擇。

I think just to tackle some of your other questions, the 1.6 Mg per kg per day dose we've shown throughout the study to be both numerically the highest AHV across the three doses. We don't really see a difference between the 1.6 and 3.2 Mg per kg per day doses. So I think there's no point to go to that higher dose. We do believe that there's a pharmacodynamic plateau, so we're not getting increased growth hormone secretion at the higher dose. So it would make sense that we wouldn't see an increase in AHV.

我想只是為了解決您的其他一些問題，我們在整個研究中顯示的每天每公斤 1.6 毫克的劑量在數字上是三個劑量中最高的 AHV。我們實際上並沒有看到每天每公斤 1.6 毫克和 3.2 毫克劑量之間的差異。所以我認為沒有必要服用更高的劑量。我們確實相信存在藥效學平台，因此在較高劑量下我們不會增加生長激素的分泌。因此，我們不會看到 AHV 增加是有道理的。

Yeah, the interaction with EMA. So the interaction with EMA, we will start that interaction after we have finalized our protocol with the FDA.

是的，與 EMA 的互動。因此，與 EMA 的互動，我們將在與 FDA 敲定協議後開始互動。

Yeah, and Duke, why don't you talk about the enrollment, number of patients, enrollment, and so on.

是的，杜克大學，你為什麼不談談入組情況、患者數量、入組情況等等。

Yeah, so thank you. So I think answer the first question, do we have overlap of a Phase 2 site and a Phase 3? Yes, there will have some, Phase 2 sites to continue to pass it in Phase 3. And also, we plan to initiate a new site for Phase 3 as well. As you know, the number of subjects that enroll in Phase 2 is much smaller than Phase 3, which is nearly double. We want to increase the number of countries and number of sites around the world.

是的，所以謝謝你。所以我想回答第一個問題，第二階段和第三階段的地點是否有重疊？是的，會有一些第二階段站點在第三階段繼續通過它。如您所知，第二階段報名的受試者數量比第三階段少得多，幾乎是第三階段的兩倍。我們希望增加世界各地的國家數量和站點數量。

At this point, we have significant, kind of like increased awareness of Phase 2 trials at the global scale. We do get significant increase in interest of the KOL around the world as well. So we do believe that with enrollment timeline as we planned, initially 15 to 18 months should stay intact if we start their enrollment towards the end of this year.

目前，我們對全球範圍內的第二階段試驗的認識有了顯著的提高。我們確實也得到了世界各地 KOL 的興趣的顯著增加。因此，我們確實相信，按照我們計劃的招生時間表，如果我們在今年年底開始招生，最初的 15 至 18 個月應該保持不變。

So again, pretty much everything on track. And we do believe that we'll be able to enroll all those patients with the new placebo-controlled trial at the timely manner. And especially, when we increase the number of sites and the number of countries to participate in this trial.

再說一次，幾乎一切都步入正軌。我們確實相信，我們將能夠及時招募所有這些患者參加新的安慰劑對照試驗。尤其是當我們增加參與試驗的站點數量和國家數量時。

Okay. Awesome. Oh, and then just one more question. Sorry. Just how do you plan on funding the Phase 3 beyond yearend 3Q '2024? Are there any details on that?

好的。驚人的。哦，還有一個問題。對不起。您計劃如何為 2024 年第三季末之後的第三階段提供資金？有這方面的詳細資訊嗎？

Yeah. Lori, go ahead.

是的。洛瑞，繼續吧。

Yeah. You know, we've been really busy since we've had our FDA meeting and planning for the upcoming Phase 3 trial design. Now that we have some of the details finalized, we are confident that we can go out to the investment community and finance the Phase 3 trial as is planned.

是的。你知道，自從我們召開 FDA 會議並規劃即將到來的 3 期試驗設計以來，我們一直非常忙碌。現在我們已經敲定了一些細節，我們有信心能夠向投資界伸出援手，並按計劃為第三階段試驗提供資金。

Also, as we've said previously, we believe that there is opportunity to bring in potential strategic or --potential partners for regional licensing deals, which would also allow for non-dilutive financing in some of those territories that we would not necessarily go out and commercialize on our own.

此外，正如我們之前所說，我們相信有機會引入潛在的戰略或潛在合作夥伴進行區域許可交易，這也將允許在我們不一定會去的一些地區進行非稀釋性融資我們自己出去並商業化。

Great. Thank you so much.

偉大的。太感謝了。

Thank you. Charles Duncan, Cantor Fitzgerald.

謝謝。查爾斯鄧肯，坎托菲茨杰拉德。

Yeah. Good morning, Rick, and team. Congrats on the progress and recent constructive interaction with the FDA. Also, really appreciate all the color you provided. I did have a couple of questions on the Phase 3 trial design and then one on your perspective regarding FDA engagement. So, with regard to the Phase 3 trial design, I'm wondering if you could affirm that the enrollment criteria in Phase 3 will be the same or, if not, how different from the Phase 2?

是的。早上好，瑞克和團隊。祝賀取得的進展以及最近與 FDA 的建設性互動。另外，非常感謝您提供的所有顏色。我確實有幾個關於 3 期試驗設計的問題，還有一個關於您對 FDA 參與的看法。那麼，關於第三階段的試驗設計，我想知道您是否可以確認第三階段的入組標準將相同，或者如果不是，與第二階段有何不同？

And then the second question I had with regard to that is if you could provide a little more color on the co-primaries. Is it a true co-primary or is there-- call it a step down from the first 12-month AHV to the second? Thanks.

然後我提出的第二個問題是，你是否可以在聯合初選上提供更多的色彩。這是真正的聯合初選，還是——稱之為從第一個 12 個月 AHV 到第二個的降級？謝謝。

Yeah. Duke, why don't you answer the first part of the Phase 3 design question in terms of enrollment criteria?

是的。杜克大學，為什麼不回答第三階段設計問題的第一部分的招生標準呢？

And then, John, if you'll talk about the co-primary.

然後，約翰，請談談聯合初選。

Thank you. That's a very good question. So, the majority of inclusion-- exclusion criteria are pretty much similar compared to Phase 3 and Phase 2. The only small changes that we want to implement is, number one, the upper limit of the age enrollment we're going to lower one year. The reason behind that, because we want to make sure, since we compare to placebo, we want to make very clear that, no single subject would get into the tender stage 2 during the 12-month trial period.

謝謝。這是一個非常好的問題。因此，與第三階段和第二階段相比，大多數納入-排除標準非常相似。背後的原因是，因為我們想確保，由於我們與安慰劑進行比較，我們想非常明確地表明，在 12 個月的試驗期內，沒有任何一個受試者會進入招標第二階段。

And we have a bonus criteria that, initially the bonus delay was greater or equal to 6 months, but now we can have it greater than 12 months. And other than that, pretty much the same. And again-- part of this inclusion exclusion criteria for the moderate PGHD. We do believe that majority of physicians who actually will participate in this trial will see significant-- when we have a placebo-controlled trial.

我們有一個獎金標準，最初獎金延遲大於或等於 6 個月，但現在我們可以大於 12 個月。除此之外，幾乎相同。再次強調，這是中度 PGHD 納入排除標準的一部分。我們確實相信，當我們進行安慰劑對照試驗時，大多數實際參與這項試驗的醫生都會看到顯著的結果。

The different primary endpoints will be very clear. As you know, I think in majority of those patients, as you see the data John presented earlier, the baseline high velocity coming into this trial was 4.7, and our trial achieved 7.6 centimeters at 12 months.

不同的主要終點將非常明確。如您所知，我認為在大多數患者中，正如您看到 John 之前提供的數據，該試驗的基線高速為 4.7，而我們的試驗在 12 個月時達到了 7.6 公分。

So, basically, we see very clearly that, we can achieve the clinical significance based on the FDA requirement at the end of this Phase 3 trial.

所以，基本上，我們非常清楚地看到，在這個3期試驗結束時，我們可以根據FDA的要求來達到臨床意義。

Helpful. And John, the co-primary.

有幫助。還有約翰，副校長。

Yes. So, Charles, we do see these as co-primary endpoints, the 12-month growth endpoint and the 6-month comparison to placebo, both showing clinically meaningful growth. So, that's the plan going in. Obviously, we'll release more details once we have a final sign-off from the FDA on the full Phase 3 protocol.

是的。所以，Charles，我們確實將這些視為共同主要終點，即 12 個月的增長終點和與安慰劑的 6 個月的比較，兩者都顯示出具有臨床意義的增長。所以，這就是計劃。

And that will include powering, John? Which of the [two D] you power to? Or does it not matter?

這將包括供電，約翰？您對 [2 D] 中的哪一個有權力？還是沒關係？

No, we'll pair to both. They'll both be powered. And we do believe right now that we have, -- but the end that we have is more than sufficient to power both of those endpoints.

不，我們將兩者配對。他們都會通電。我們現在確實相信我們已經做到了，但我們所擁有的目標足以為這兩個端點提供動力。

Okay. Neat design. Is the agency asking for bone mineral density imaging or any bone health monitoring?

好的。簡潔的設計。該機構是否要求進行骨礦物質密度成像或任何骨骼健康監測？

Duke?

公爵？

No, they did not. And actually, most of the trials to get approved, the focus on the efficacy in terms of growth velocity. And the bone density trial in general, you may not see significant change in the first 12 months. So, that would not require for this 12-month study.

不他們沒有。事實上，大多數獲得批准的試驗都專注於生長速度方面的功效。而骨密度試驗一般而言，在前 12 個月內您可能看不到明顯的變化。因此，這不需要進行為期 12 個月的研究。

Okay. And last question regarding the agency perspective. And always hazard for that, speculating on that. But what do you think was the key shift or driver to the shift in the view of this, of LUM-201 being a stimulator, not a simple mimetic? And did you get a sense that they appreciated compliance challenges with the current standard of care with the growth hormone injectables?

好的。最後一個問題是關於機構的視角。並且總是為此冒險，對此進行推測。但您認為 LUM-201 是一種刺激器而不是簡單的模仿物這一觀點的關鍵轉變或驅動力是什麼？您是否感覺到他們重視目前生長激素注射劑護理標準的合規性挑戰？

Yes, go ahead, John.

是的，繼續吧，約翰。

So, I think the turning point, Chasles, just in their viewing of our mechanism was around the extensive data that we've shared publicly and with the FDA about restoration of pulsatile, Ultragenyx rhythm of growth hormone release. And I think that data package was pretty substantial. And as we've shown that we can restore normal pulses and levels of growth hormone across a 24-hour period in growth hormone deficient subjects, which amounts to about 20% of the growth hormone that you need from an exogenous bolus dose.

所以，我認為，Chasles，他們對我們機制的看法的轉折點在於我們公開分享並與 FDA 分享的大量有關恢復生長激素釋放的脈衝式 Ultragenyx 節律的數據。我認為該數據包相當可觀。正如我們所證明的，我們可以在生長激素缺乏的受試者中在 24 小時內恢復正常的脈搏和生長激素水平，這相當於外源性推注劑量所需生長激素的 20% 左右。

And we're achieving almost the same amount of AHV. And I think that level of understanding and realizing that our growth hormone delivery is significantly more efficient because we're doing it in a pulsatile 24-hour period, I think that was really the key to differentiate us away from-- differentiate us away from exogenous growth hormone and really open up this whole discussion about kind of creative ways to evaluate the growth potential of LUM-201 in Phase 3.

我們實現了幾乎相同數量的 AHV。我認為，理解和認識到我們的生長激素輸送效率明顯更高，因為我們是在 24 小時的脈動時間內進行的，我認為這確實是使我們與其他國家區分開來的關鍵。 ，並真正開啟了關於評估LUM-201 在第3 階段生長潛力的創造性方法的整個討論。

Good deal. Great to hear. Appreciation of pulsatile mechanism, always a key point of our thesis. Thanks for taking the questions.

好交易。很高興聽到。對脈動機制的認識，始終是我們論文的重點。感謝您提出問題。

Thank you, Charles.

謝謝你，查爾斯。

Thank you. Leland Gershell Oppenheimer & Co. I

謝謝。利蘭·格謝爾·奧本海默公司 I

Hi, good morning. Thanks for taking our questions. I also wanted to comment on a positive surprise to hear the agency's view on the Phase 3 requirements. A couple questions from us. Just sort of playing devil's advocate at the same time that we're trying to hear about the placebo control versus inferiority versus serious growth hormone injections.

早安.感謝您回答我們的問題。我還想評論一下聽到該機構對第三階段要求的看法時所感到的積極驚喜。我們提出幾個問題。在我們試圖聽到安慰劑對照與自卑與嚴重生長激素注射的同時，有點唱反調。

It may be early days, but I wanted to hear to what extent could those data or the lack thereof of comparability data to growth hormone impact endocrinologists view on LUM-201 as they go to potentially use it in their patients?

現在可能還為時過早，但我想知道這些數據或缺乏與生長激素的可比性數據會在多大程度上影響內分泌學家對LUM-201 的看法，因為他們可能會將LUM-201 用於患者？

And two, I want to ask, given the ancillary but important metabolic benefits of (inaudible) , will you be looking for those potential benefits apart from growth itself in the Phase 3? Thank you.

第二，我想問，考慮到（聽不清楚）的輔助但重要的代謝益處，除了第三階段的增長本身之外，您還會尋找那些潛在的益處嗎？謝謝。

Yeah. Duke, I only heard part of the question, but I think that was really for you. So, why don't you start?

是的。杜克，我只聽到了問題的一部分，但我認為這確實適合你。那麼，為什麼不開始呢？

You know what? Honestly, I cannot hear the question quite well. So, if anybody can read.

你知道嗎？老實說，我聽不太清楚這個問題。所以，如果有人能讀的話。

So, go ahead, John.

所以，繼續吧，約翰。

So, I think Leland was asking about the impact of not having, comparative treatment data in Phase 3 for pediatric endocrinologists as they think about how to prescribe this once we're on the market.

因此，我認為 Leland 是在詢問兒科內分泌學家在第三階段沒有比較治療數據的影響，因為他們正在考慮一旦我們上市後如何開處方。

So, Leland, that's a very good question, right? I think this is very important, right. As you know, first of all, FDA fully understood that mechanism of action of LUM-201 is totally different than growth hormone, and they make it clear to us that you are not growth hormone. And as a pediatric endocrinologist, that if you participate in the trial, if the patient with growth hormone deficiency, such as in moderate PGHD, the only impact with no treatment is only height.

所以，利蘭，這是一個很好的問題，對嗎？我覺得這個非常重要，對吧。大家知道，首先FDA充分了解LUM-201的作用機轉與生長激素完全不同，他們向我們明確表示你不是生長激素。作為兒科內分泌學家，如果參加試驗，如果患者患有生長激素缺乏症，例如中度 PGHD，不治療的唯一影響只是身高。

No other significant detrimental outcome that could, implicate the patient without treatment for six months or one year. So, we do believe that most patients are fully aware of that, -- especially the patient who enrolls in this study is prepubertal.

沒有其他重大的有害結果可能導致患者六個月或一年不接受治療。因此，我們確實相信大多數患者都充分意識到這一點，尤其是參與這項研究的患者處於青春期前。

So, again, pubertal impact with no treatment six months to one month is not going to have significant impact in the final adult height. With that said, we do believe that, when we conduct this trial, they will have no issue to enroll the subject. And not to mention that all the patients participate in this trial potentially will be able to enroll into long-term extension study, which is we already have that in place, and FDA approved that long-term extension study for three years. So, I do believe that we incentive to really help for physician to enroll their patient, knowing that in the long-term will be beneficial to their patient, especially when the drug is approved.

因此，同樣，六個月到一個月不接受治療的青春期影響不會對最終成年身高產生重大影響。話雖如此，我們確實相信，當我們進行這項試驗時，他們不會有任何問題來招募該受試者。更不用說所有參與這項試驗的患者都可能能夠參加長期擴展研究，這是我們已經準備好的，FDA 批准了這項為期三年的長期擴展研究。因此，我確實相信我們會激勵真正幫助醫生招募患者，因為我們知道這對患者有利，尤其是在藥物獲得批准後。

(inaudible)

（聽不清楚）

John, do you want to answer that question?

約翰，你想回答這個問題嗎？

So, I think we won't be examining that question specifically in this Phase 3 study. We do have an investigator-initiated study going on in NAFLD where some of that data is being collected in the context of examining the impact on liver fat. So, it's being run at MGH.

因此，我認為我們不會在第三階段研究中專門研究這個問題。我們確實正在進行一項由研究者發起的針對 NAFLD 的研究，其中一些數據是在檢查對肝臟脂肪的影響的背景下收集的。所以，它正在 MGH 運行。

But for our Phase 3 trial, we're going to focus on the approvable endpoints and the path forward in PGHD to get an approval.

但對於我們的第 3 階段試驗，我們將重點放在可批准的終點以及 PGHD 的前進道路以獲得批准。

Yes, thank you.

是的，謝謝。

Thank you. But, Leland, I think you were also referring to okay, go ahead.

謝謝。但是，利蘭，我想你也指的是，好吧，繼續吧。

Thank you. Edward White H.C. Wainwright & Co, LLC.

謝謝。愛德華懷特 H.C.溫賴特有限公司

Good morning. Thanks for the update this morning. So, just a couple of questions from me. Can you comment on your manufacturing readiness for the Phase 3 Trial and regulatory filings?

早安.感謝您今天早上的更新。那麼，我只問幾個問題。您能否評論一下您對第三階段試驗和監管備案的生產準備？

John, go ahead. Manufacturing readiness.

約翰，繼續吧。製造準備。

Yeah. So, thanks for the question, Ed. So, yeah, we-- as you know, we recently filed a patent on a new drug product form. For Phase 3, which will give us very tight dose variance across the large weight range for children with pediatric growth hormone deficiency and also provide easier routes of administration.

是的。所以，謝謝艾德的提問。所以，是的，正如你所知，我們最近申請了一種新藥品形式的專利。對於第三階段，這將為患有小兒生長激素缺乏症的兒童提供在大體重範圍內非常嚴格的劑量差異，並且還提供更簡單的給藥途徑。

So, we have a mini tablet in a capsule. So, larger kids can take the capsule with the mini tablet. Smaller kids can open the capsule and take the mini tablets by themselves or in soft food. So, that design is in place. The bridging studies are complete and we're moving forward to get our Phase 3 material ready to go.

所以，我們有一個裝在膠囊裡的迷你片劑。因此，較大的孩子可以將膠囊與迷你藥片一起服用。較小的孩子可以打開膠囊並自行服用迷你藥片或透過軟食物服用。所以，這個設計已經就位了。橋接研究已經完成，我們正在繼續準備第三階段的材料。

So, there are no, -- there are no hiccups in the road there. We're well prepared to provide that Phase 3 slash commercial material to get us through Phase 3.

所以，那裡的道路上沒有任何問題。我們已做好充分準備，提供第三階段削減商業材料，以幫助我們完成第三階段。

Okay. Okay. Thanks, John. And just a question on the study, as you mentioned, it's going to have some overlap with the Phase 2. Can you just let us know what you're thinking of as far as a geographical breakdown for the US versus outside the US for sites and the number of patients enrolled?

好的。好的。謝謝，約翰。正如您所提到的，關於該研究的一個問題，它將與第二階段有一些重疊。 ？

Duke, why don't you answer that question?

杜克，你為什麼不回答這個問題？

Yeah. So, for this, as we plan right now, is that-- we plan to enroll about 150 subjects. So, two to one randomization will be 100 subjects in LUM-201 and 50 subjects in placebo. We plan to include more countries outside the US. We're in the process of sending out a site survey to multiple regions around the world.

是的。因此，為此，正如我們現在的計劃，我們計劃招募大約 150 名受試者。因此，二比一隨機化將是 LUM-201 中的 100 名受試者和安慰劑的 50 名受試者。我們計劃將美國以外的更多國家納入其中。我們正在向世界多個地區發送現場調查。

We're waiting to receive those sites survey back before we make a decision which country we go to. So, around the site that we plan, it's about 90 sites ish. So, again, so potentially about 14 countries. However, the final number and number of sites in the country will be finalized when we receive the survey back.

在我們決定去哪個國家之前，我們正在等待收到這些網站調查回來的資訊。因此，圍繞著我們規劃的站點，大約有 90 個站點左右。再次強調，可能有 14 個國家。不過，最終的數量和全國站點數量將在我們收到調查回饋後才最終確定。

Okay. Thank you. Leland, if you recall, you were in? -- (technical difficulty)

好的。謝謝。利蘭，如果你記得的話，你在嗎？ ——（技術難度）

I'm sorry, Rick. I'm sorry for interrupting you, Rick. My last question. Can I ask another question?

對不起，瑞克。很抱歉打擾你，瑞克。我的最後一個問題。我可以再問一個問題嗎？

Sure, absolutely.

當然，絕對。

So, the, you know, we've talked about this before, but out of the 60% to 62% of the patient population that's eligible, I just want to get your thoughts on why children who are eligible wouldn't want to be on the oral solution versus the injectable. Especially since, as you mentioned, the cost will be lower, but the ease of use is apparent. And so, I'm just taking the other side of that and why wouldn't patients and children want to take your product?

所以，你知道，我們之前已經討論過這個問題，但是在 60% 到 62% 的符合條件的患者群體中，我只是想了解您對為什麼符合條件的兒童不想成為這樣的想法。比較。尤其是，正如您所提到的，成本會更低，但易用性是顯而易見的。所以，我只是站在另一面，為什麼病人和兒童不想服用你的產品呢？

Well, we did some preliminary research, Leland, and, no-- this is Ed, excuse me, Ed, and it's pretty clear. When we asked both the families, but also the repeat dose, if they had a choice between a weekly injection or a once a day oral, they overwhelmingly said that they would prefer to take a daily oral. That's sort of a given.

好吧，我們做了一些初步研究，利蘭，不，這是艾德，對不起，艾德，這很清楚。當我們詢問兩個家庭以及重複劑量時，他們是否可以選擇每週注射或每天口服一次，他們絕大多數表示他們更願意每天口服。這是既定的。

So, and, of course, we have a way to identify the patients who our drug will most likely be effective in, and that is our predictive enrichment or PEM strategy, and that further enhances our ability to not only be successful in this trial, but also to easily identify those patients at will be effective.

因此，當然，我們有一種方法來確定我們的藥物最有可能有效的患者，這就是我們的預測豐富或 PEM 策略，這進一步增強了我們不僅在這項試驗中取得成功的能力，還可以輕鬆識別那些患者將有效。

Yeah, Ed, I would like to add on top of what Rick just said. As a pediatric endocrinologist, majority of patients with PGHD fall into PEM positive category. As you know, over 40 years, we don't have option but just give injection to those children, right-- just until about four, five years, And we get long-acting approved, but just not get rid of injection, which is some of the children do not want it, especially not only treatment for a month or so, not a year or so, but much longer period of time.

是的，艾德，我想在瑞克剛才所說的基礎上補充一點。作為兒科內分泌科醫生，大多數 PGHD 患者屬於 PEM 陽性類別。如你所知，40多年來，我們別無選擇，只能給這些孩子注射，對吧——直到大約四五年，我們獲得了長效藥物的批准，但只是沒有擺脫注射，這是有些孩子不願意，尤其是不只治療一個月左右，不是一年左右，而是更長的時間。

So physician in general, I do believe that their perception was if this drug get approved, they will offer this LUM-201 to mature those patients by using PEM positive category. The PEM positive, they potentially can be on the treatment. So I do believe that-- this is extremely important, right, to have this option for the treatment for patient moving forward. We never really have this option until LUM-201, you know, at this point.

因此，總的來說，我確實相信醫生的看法是，如果這種藥物獲得批准，他們將提供這種 LUM-201，透過使用 PEM 陽性類別來使這些患者成熟。 PEM 呈陽性，他們有可能接受治療。所以我確實相信——這是非常重要的，對的，為患者的治療提供這種選擇是非常重要的。在 LUM-201 之前，我們從來沒有真正擁有過這個選項，你知道，在這一點上。

Okay. Thanks for taking my questions.

好的。感謝您回答我的問題。

Thank you. Catherine Novack JonesTrading Institutional Services, LLC.

謝謝。凱瑟琳·諾瓦克·瓊斯貿易機構服務有限責任公司。

Hi, guys. Morning. I just wanted to drill down on the cash position. You know, you need to bring in additional funding before you start the Phase 3. Do you see any inflection points between now and the start that might be where--you might be able to use to bring in new investors? And then just throwing out the possibility of pursuing strategic partnership, for example, what do you think they'd want to see before stepping in? You know, are there more analyses that you think partners or investors would be interested in? Or at this point, are most of the relevant data in hand?

嗨，大家好。早晨。我只是想深入了解現金狀況。你知道，在開始第三階段之前，你需要引入額外的資金。然後就拋出尋求策略夥伴關係的可能性，例如，您認為他們在介入之前希望看到什麼？您認為合作夥伴或投資者是否會對更多分析感興趣？或者說現在大部分相關數據都掌握在手了嗎？

Yes. Catherine, that's a good question. And I don't think there's any question that investors have enough information at this stage to make a decision. I think we're, as Lori said, we're very confident since the FDA gave us this trial design with a placebo comparator arm that we are fully confident-- we're going to be able to raise the capital needed to get this drug across the finish line.

是的。凱瑟琳，這是個好問題。我認為投資者在現階段有足夠的資訊來做出決定，這是毫無疑問的。我認為，正如 Lori 所說，我們非常有信心，因為 FDA 給了我們這個帶有安慰劑比較臂的試驗設計，我們完全有信心——我們將能夠籌集實現這一目標所需的資金藥物衝過終點線。

And Lori, I don't know if you want to add any more to that or anyone else on the team.

洛瑞（Lori），我不知道你是否想補充更多內容或團隊中的其他人。

Yeah, I think, Catherine, I think, when we've talked with investors, I think a lot of investors have just been waiting to determine what the Phase 3 Trial design would look like. And now that we have gotten feedback from the FDA, they have proposed the placebo control trial as an option. As we finalize that trial design and move forward with FDA approval of that trial design, we do believe that that will instill confidence in the investors and allow us to complete a financing in this near term.

是的，我想，凱瑟琳，我想，當我們與投資者交談時，我認為很多投資者一直在等待確定第三階段試驗的設計是什麼樣子。現在我們已經收到 FDA 的回饋，他們提議將安慰劑對照試驗作為一種選擇。當我們最終確定試驗設計並獲得 FDA 批准該試驗設計時，我們確實相信這將為投資者註入信心，並使我們能夠在短期內完成融資。

As far as looking for regional partners, we've talked previously about looking for ex-US options for regional partners and retaining US rights, of course. And so that is something that we will continue to pursue. And I think what they also were waiting on and the partners that we've talked with have also been waiting on -- what the phase three trial design will look like.

至於尋找區域合作夥伴，我們之前已經討論過為區域合作夥伴尋找美國以外的選擇，當然還要保留美國的權利。這就是我們將繼續追求的目標。我認為他們也在等待，我們交談過的合作夥伴也一直在等待——第三階段試驗設計會是什麼樣子。

So now that we have that information in hand and we have more of those details, I think that is why we are confident we will be able to move forward and complete a financing in the near term.

現在我們已經掌握了這些信息並且掌握了更多詳細信息，我認為這就是為什麼我們有信心能夠在短期內繼續前進並完成融資。

Got it. And then just, I guess, clarification on the first co-primary endpoint. If you can help me understand the statistical analysis, since placebo is not followed for 12 months, what is the hypothesis testing assumption for the first co-primary endpoint if you could clarify?

知道了。然後，我想，對第一個共同主要終點進行澄清。如果您能幫助我理解統計分析，由於 12 個月內沒有服用安慰劑，您能否澄清一下，第一個共同主要終點的假設檢定假設是什麼？

Yeah. John, go ahead if you had a question.

是的。約翰，如果你有問題，請繼續。

Sure. So as we mentioned, we just have to show clinically meaningful growth. And so we talked a little bit about one approach to show that, which is the agreement we already have with the FDA on 6.7 centimeters per year representing minimal clinically meaningful growth. So we're using that to transition essentially from our Phase 2 study into our long-term safety extension. And that is an agreement we already have with the FDA. So that is the first option that we'll pursue.

當然。正如我們所提到的，我們只需要表現出具有臨床意義的成長。因此，我們討論了一種方法來證明這一點，這就是我們已經與 FDA 達成的協議，每年增長 6.7 厘米，這代表了具有臨床意義的最小增長。因此，我們正在利用它從第二階段研究本質上過渡到我們的長期安全擴展。這是我們已經與 FDA 達成的協議。所以這是我們將追求的第一個選擇。

Okay. And then just one more. Thinking about this down the road-- right now you're focusing on treatment night use patients, but it seems like, does this make sense to use after an initial year or two with growth hormone for people who aren't maybe interested in having daily injections indefinitely?

好的。然後還有一個。考慮一下這一點——現在你的重點是治療夜間使用的患者，但看起來，對於那些可能不感興趣的人來說，在使用生長激素一兩年後使用這是否有意義？

Duke, let's go ahead, if you will.

杜克，如果你願意的話，我們就繼續吧。

Yeah. So I think that that's a very good question. I do believe that most physicians will look into that potentially because we patient LUM-201. At this point, we don't have data to show yet. So what we think that moving forward, when we get this Phase 3 trial done, we put that in registry. So majority of those patients going to get into the long-term extension, especially registry is someone who's not in Phase 2.

是的。所以我認為這是一個非常好的問題。我確實相信大多數醫生會潛在地研究這一點，因為我們的患者是 LUM-201。目前，我們還沒有數據可以顯示。因此，我們認為，當我們完成第三階段試驗時，我們會將其記錄在案。因此，大多數將進入長期延期的患者，尤其是登記的患者都不是處於第二階段的患者。

They can continue to, have the Phase 4 study when the drug get approved, we'll be able to determine some of those, especially when the patient want to discontinue daily and go into LUM-201. We'd be able to evaluate those efficacy in those trials.

當藥物獲得批准後，他們可以繼續進行 4 期研究，我們將能夠確定其中的一些研究，特別是當患者想要每天停藥並使用 LUM-201 時。我們將能夠在這些試驗中評估這些功效。

Okay. Got it. That's helpful. Thanks.

好的。知道了。這很有幫助。謝謝。

Thank you. This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation.

謝謝。今天的電話會議到此結束。此時您可以斷開線路。感謝您的參與。