Lumos Pharma Inc (LUMO) 2022 Q3 法說會逐字稿

Good morning, and welcome to Lumos Pharma's interim data update conference call. (Operator Instructions) As a reminder, this conference call is being recorded. I will now turn the call over to Lisa Miller, Senior Director of Investor Relations. Please go ahead, ma'am.

早上好，歡迎來到 Lumos Pharma 的中期數據更新電話會議。 （操作員說明）作為提醒，正在錄製此電話會議。我現在將把電話轉給投資者關係高級總監 Lisa Miller。請繼續，女士。

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 U.S. 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. Additional information concerning factors that could cause actual results to differ is contained in our periodic reports filed with the 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 the forward-looking statements. Information presented on this call is contained in the press release we issued this morning and in our Form 8-K, which may be accessed from the Investors page of the company's website.

謝謝你，運營商。在我們繼續通話之前，我想提醒大家，根據美國聯邦證券法，本次通話中做出的某些聲明屬於前瞻性聲明。這些陳述受風險和不確定因素的影響，這些風險和不確定因素可能導致實際結果與歷史經驗或當前預期存在重大差異。有關可能導致實際結果不同的因素的更多信息包含在我們向美國證券交易委員會提交的定期報告中。本次電話會議期間作出的前瞻性陳述僅在本新聞稿發布之日有效，公司不承擔更新或修改前瞻性陳述的義務。本次電話會議中提供的信息包含在我們今天上午發布的新聞稿和我們的 8-K 表格中，可以從公司網站的投資者頁面訪問。

Speaking on today's call will be Rick Hawkins, CEO and Chairman; John McKew, our President and Chief Science Officer; and Lori Lawley, our CFO. David B. Karpf, our Chief Medical Officer, will join for the question-and-answer session. I will now turn the call over to Rick.

首席執行官兼董事長 Rick Hawkins 將在今天的電話會議上發言；我們的總裁兼首席科學官 John McKew；和我們的首席財務官 Lori Lawley。我們的首席醫療官 David B. Karpf 將參加問答環節。我現在將把電話轉給里克。

Thank you, Lisa, and good morning, everyone. Thank you for joining the Lumo Pharma team for our announcement of encouraging interim results from our OraGrowtH210 and OraGrowtH212 trials. Earlier this morning, we issued a press release announcing interim data.

謝謝你，麗莎，大家早上好。感謝您加入 Lumo Pharma 團隊，感謝我們宣布 OraGrowtH210 和 OraGrowtH212 試驗令人鼓舞的中期結果。今天上午早些時候，我們發布了一份新聞稿，公佈了中期數據。

On this call, we will go through the results in additional detail and discuss how they inform the next development steps for LUM-201 and for the treatment of PGHD. In a moment, I'll turn the call over to John McKew to walk through the data. For those of you who are new to our story, I'll begin with a brief overview of Lumos and the indications we focused on. We're targeting the growth hormone market with our novel oral therapeutic called LUM-201, and our initial indication is in pediatric growth hormone deficiency, or PGHD. Injectable growth hormone has dominated this market for almost 40 years, but the LUM-201 is the first once-a-day oral therapeutic targeting this indication. LUM-201 is differentiated in a number of ways with a mechanism of action that works within a natural endocrine pathway. The global market opportunity for growth hormone disorder is quite large at approximately $3.4 billion, [$1.2] billion for PGHD alone with additional upside in China of about $1.5 billion.

在這次電話會議上，我們將更詳細地研究結果，並討論它們如何為 LUM-201 的下一步開發步驟和 PGHD 的治療提供信息。稍後，我會將電話轉給 John McKew 來瀏覽數據。對於那些不熟悉我們故事的人，我將首先簡要概述 Lumos 和我們關注的適應症。我們通過名為 LUM-201 的新型口服治療藥物瞄準生長激素市場，我們的初步適應症是兒科生長激素缺乏症或 PGHD。可注射生長激素主導該市場近 40 年，但 LUM-201 是第一個針對該適應症的每日一次口服治療藥物。 LUM-201 以多種方式區分，其作用機制在自然內分泌途徑中發揮作用。生長激素紊亂的全球市場機會相當大，約為 34 億美元，僅 PGHD 就有 [12 億美元]，中國的額外增長空間約為 15 億美元。

The interim results we are reporting today are from 2 Phase II trials: OraGrowtH210, a study in moderate naive to treatment PGHD that's ongoing worldwide at about 45 sites; and the OraGrowtH212, a single site PK/PD trial. A moderate or idiopathic PGHD makes up approximately 2/3 of the total treated PGHD patient population.

我們今天報告的中期結果來自 2 項 II 期試驗：OraGrowtH210，一項針對中度初治 PGHD 的研究，目前在全球約 45 個地點進行；和 OraGrowtH212，單站點 PK/PD 試驗。中度或特發性 PGHD 約佔所有接受治療的 PGHD 患者的 2/3。

As of the end of October 1, I'm pleased to report there were approximately 80% enrolled in both trials and continue to be encouraged by the pace of enrollment. We have $74 million as a cash balance at the end of the third quarter of 2022, and this is enough cash to get us through a full readout of these 2 studies in the second half of 2023, with the cash runway into Q2 2024.

截至 10 月 1 日年底，我很高興地報告，大約有 80% 的人參加了這兩項試驗，並且繼續對參加的速度感到鼓舞。到 2022 年第三季度末，我們有 7400 萬美元的現金餘額，這些現金足以讓我們在 2023 年下半年完成對這兩項研究的全面解讀，並在 2024 年第二季度實現現金跑道。

Now to discuss the interim data. We are very pleased to announce this morning encouraging interim results from these 2 trials. Growth on LUM-201 met expectations. It demonstrated a durable response and showed a favorable safety and tolerability profile. As previously guided, we expect an annualized growth velocity target of 8.3 centimeters a year based on several large historical databases of moderate naive-to-treatment PGHD subjects treated with growth hormone.

現在討論中期數據。我們很高興今天早上宣布這兩項試驗取得了令人鼓舞的中期結果。 LUM-201 的增長符合預期。它表現出持久的反應，並顯示出良好的安全性和耐受性。正如之前的指導，我們預計年化生長速度目標為每年 8.3 厘米，這是基於幾個大型歷史數據庫，這些數據庫包含使用生長激素治療的中度初治 PGHD 受試者。

In fact, the 1.6 mg per kg per day LUM-201 dose at 6 months on therapy achieved a mean annualized height velocity of 8.6 centimeters a year, meeting these expectations. Now recall, this is for the enriched population we identified due to our predictive enrichment marker or PEM -- PEM strategy reflecting those moderate PGHD patients with the potential to respond to LUM-201.

事實上，在治療 6 個月時，每天 1.6 毫克/公斤的 LUM-201 劑量實現了每年 8.6 厘米的平均年化身高增長速度，達到了這些預期。現在回想一下，這是針對我們通過預測性富集標記物或 PEM 確定的富集人群——PEM 策略反映了那些有可能對 LUM-201 做出反應的中度 PGHD 患者。

Importantly, a durable response to LUM-201 was observed at 9 and 12 months.

重要的是，在 9 個月和 12 個月時觀察到對 LUM-201 的持久反應。

We're also very pleased to say that the interim look, we have not observed any treatment-related SAE dropouts due to AEs and no meaningful safety signal across the entire dose range evaluated. In addition to that, we believe these data support the selection of 1.6 mgs per kg a day for a pivotal Phase III trial. Identifying this dose will now help with advanced planning of that pivotal trial.

我們也很高興地說，從中期來看，我們沒有觀察到任何因 AE 導致的與治療相關的 SAE 脫落，並且在評估的整個劑量範圍內沒有有意義的安全信號。除此之外，我們相信這些數據支持選擇每天每公斤 1.6 毫克用於關鍵的 III 期試驗。確定該劑量現在將有助於對該關鍵試驗進行高級規劃。

And finally, I'll mention again that our molecule's unique mechanisms of action and oral administration, we believe these data support the potential for LUM-201 to disrupt the injectable growth hormone therapeutic market worldwide.

最後，我要再次提到我們分子獨特的作用機制和口服給藥，我們相信這些數據支持 LUM-201 破壞全球可注射生長激素治療市場的潛力。

Now I'll turn the call over to our President and Chief Scientific Officer, John McKew, to walk through the data in greater detail. John?

現在，我將把電話轉給我們的總裁兼首席科學官 John McKew，讓他更詳細地瀏覽數據。約翰？

Thank you, Rick. We'd like to start with a quick summary of the mechanism of action. LUM-201 is a small molecule that's specifically designed to interact with the growth hormone secretagogue receptor 1a, when that receptor is expressed in the hypothalamus and the pituitary, our molecule binds and agonizes that receptor. The net result of that action across the 2 organs is to increase the natural pulsatile release of growth hormone, increasing the amplitude of the natural peak sequence.

謝謝你，里克。我們想從對作用機制的快速總結開始。 LUM-201 是一種小分子，專門設計用於與生長激素促分泌素受體 1a 相互作用，當該受體在下丘腦和垂體中表達時，我們的分子會結合併激動該受體。這兩個器官作用的最終結果是增加生長激素的自然脈動釋放，增加自然峰值序列的振幅。

By increasing the amplitude of those peaks, we increase the amount of circulating IGF-1. This circulating growth hormone and the IGF-1 then act on the open growth place of these children with growth hormone deficiency and help them grow. We don't expect to achieve super physiological levels of growth hormone and IGF-1 because of the naturally evolved feedback mechanisms.

通過增加這些峰的振幅，我們增加了循環 IGF-1 的量。這種循環的生長激素和 IGF-1 然後作用於這些生長激素缺乏症兒童的開放生長場所，幫助他們成長。由於自然進化的反饋機制，我們不期望達到超生理水平的生長激素和 IGF-1。

Another important factor to remember is that not every child with growth hormone deficiency has the ability or the physiology to respond to our molecule. The subset of patients who are severely growth hormone deficient and can't make, store or release growth hormone upon stimulation with our molecule won't respond to treatment with LUM-201. We developed a strategy to enrich our trials and subjects with the potential to be responsive. We call that strategy, the Predictive Enrichment Marker strategy or PEM, which selects for the more moderate end of the growth hormone deficiency spectrum.

另一個需要記住的重要因素是，並非每個患有生長激素缺乏症的孩子都有能力或生理機能對我們的分子做出反應。嚴重缺乏生長激素並且在用我們的分子刺激後不能製造、儲存或釋放生長激素的患者子集不會對 LUM-201 治療產生反應。我們制定了一項策略來豐富我們的試驗和具有反應潛力的受試者。我們稱該策略為預測性富集標記策略或 PEM，它選擇生長激素缺乏譜中較溫和的一端。

Our Phase II trial applies that PEM strategy prospectively and evaluates 3 dose cohorts for LUM-201: 0.8, 1.6 and 3.2 mgs per kgs per day. Full enrollment will consist of 20 subjects in each LUM-201 cohort with a fourth cohort of 20 subjects on daily injectable growth hormone. The interim analysis for read today is based on approximately 10 subjects in each cohort at 6 months on therapy. We will also look at 9- and 12-month data for a smaller number of these subjects.

我們的 II 期試驗前瞻性地應用了 PEM 策略，並評估了 LUM-201 的 3 個劑量組：每天每公斤 0.8、1.6 和 3.2 毫克。全部註冊將包括每個 LUM-201 隊列中的 20 名受試者，以及第四組 20 名每日註射生長激素的受試者。 read today 的中期分析基於每個隊列中大約 10 名接受治療 6 個月的受試者。我們還將查看其中少數受試者的 9 個月和 12 個月數據。

The fully enrolled dataset of 80 patients at 6 months on therapy is expected to be available in the second half of next year. At that point, we will have data from a significant number of subjects on therapy for 9 to 12 months and a smaller number beyond 12 months.

預計將於明年下半年提供 80 名接受治療 6 個月的患者的完整數據集。屆時，我們將獲得來自接受治療 9 至 12 個月的大量受試者和超過 12 個月的少數受試者的數據。

As Rick mentioned, the 1.6 mg per kg per day LUM-201 cohort met our expectations for growth. I thought it would be helpful to review where that expected value for growth came from. We utilized Eli Lilly's large historical database called GeNeSIS, representing 20 years of treatment with their daily injectable growth hormone, Humatrope. We applied our PEM cutoffs to this data set of naive-to-treat subjects to understand their first-year growth response to growth hormone. This analysis showed a mean annualized height velocity of 8.3 centimeters per year in the first year of treatment in this moderate PGHD population. This growth rate is consistent with values from other published data sets in the first year of growth hormone treatment in moderate PGHD.

正如 Rick 提到的，每天每公斤 1.6 毫克的 LUM-201 隊列符合我們對增長的預期。我認為回顧一下增長預期值的來源會很有幫助。我們利用了 Eli Lilly 的名為 GeNeSIS 的大型歷史數據庫，代表了 20 年的每日註射生長激素 Humatrope 治療。我們將我們的 PEM 截止值應用到這個未經治療的受試者的數據集，以了解他們對生長激素的第一年生長反應。該分析顯示，在這個中度 PGHD 人群中，在治療的第一年，年均身高增長速度為 8.3 厘米。該增長率與中度 PGHD 生長激素治療第一年的其他已發表數據集的值一致。

The previous Merck 020 recombinant human growth hormone arm when filtered for PEM positive subjects provided growth rates consistent with these other data sets. Expectations from these data are that PEM-positive subjects in our trial, should grow about 8.3 centimeters per year regardless of whether they're treated with LUM-201 or with the daily injectable growth hormone. As Rick mentioned, the 1.6 mg per kg per day cohort grew at 8.6 centimeters per year mean annualized height velocity and met our expectations for growth. These interim data demonstrated a dose response between the 0.8 and the 1.6 dose cohorts, while a growth rate at 1 point -- growth rates at 1.6 and 3.2 mgs per kg per day are similar.

之前的 Merck 020 重組人生長激素組在針對 PEM 陽性受試者進行過濾時提供了與這些其他數據集一致的增長率。這些數據的預期是，在我們的試驗中，PEM 陽性受試者每年應該長約 8.3 厘米，無論他們接受 LUM-201 治療還是每天注射生長激素。正如 Rick 提到的，每天攝入 1.6 mg/kg 的人群平均每年增長 8.6 厘米，符合我們的增長預期。這些中期數據顯示了 0.8 和 1.6 劑量組之間的劑量反應，而 1 點的增長率——每天每千克 1.6 和 3.2 毫克的增長率相似。

Based on the pharmacodynamic response that Merck generated early in their clinical development of this molecule, we expect a smaller dose response between 1.6 and 3.2 mgs per kg per day doses since this 3.2 dose lies above the pharmacodynamic plateau. The annualized height velocity observed in the growth hormone arm of 11.1 centimeters was above what historical data would have predicted in that group. In order to understand the surprising level of growth in this arm, we examined base line characteristics and looked for growth outliers in the cohorts. In the recombinant human growth hormone arm, there were 2 children under the age of 5, with 15.6 and 12.7 centimeters per year growth, among other imbalances and baseline characteristics predictive of greater growth on treatment. A key predictor of growth is age at the start of treatment. Younger PGHD subjects are known to grow faster on treatment. Other factors, including baseline height, standard deviation score or SDS, baseline IGF-1 SDS; the delta or distance from mid-parental height and weight or BMI are all measures of how growth hormone deficient a child is.

根據默克公司在該分子臨床開發早期產生的藥效學反應，我們預計每天每公斤 1.6 至 3.2 毫克的劑量反應較小，因為該 3.2 劑量高於藥效學平台。在 11.1 厘米的生長激素組中觀察到的年化身高速度高於歷史數據對該組的預測。為了了解這支隊伍驚人的增長水平，我們檢查了基線特徵並尋找隊列中的增長異常值。在重組人生長激素組中，有 2 名 5 歲以下的兒童，每年生長 15.6 和 12.7 厘米，其他不平衡和基線特徵預測治療後生長更快。生長的一個關鍵預測指標是治療開始時的年齡。眾所周知，較年輕的 PGHD 受試者在治療中生長得更快。其他因素，包括基線身高、標準差評分或SDS、基線IGF-1 SDS；與父母身高和體重中位數或 BMI 的差值或距離都是衡量兒童生長激素缺乏程度的指標。

As these values lie further from the mean, faster first-year growth would be predicted. The power of these baseline characteristics to predict first-year growth is well-known to pediatric endocrinologists. The baseline characteristics for the LUM-201 treatment cohort at 50% enrollment are well-balanced for the key variables just mentioned. However, the growth hormone arm shows a different story. There are significant differences in age of BMI and more subtle differences between cohorts and the delta from mid-parental height and IGF-1 SDS. The baseline characteristics in the rhGH arm predict that these subjects will have a greater response to treatment. At only 50% enrollment, it is not uncommon for cohorts to show imbalances, which should normalize as the trial approaches full enrollment.

由於這些值遠離平均值，因此預計第一年增長更快。這些基線特徵預測第一年生長的能力為兒科內分泌學家所熟知。 LUM-201 治療組在 50% 入組時的基線特徵對於剛剛提到的關鍵變量是均衡的。然而，生長激素臂顯示出不同的故事。 BMI 的年齡存在顯著差異，隊列與父母身高中值和 IGF-1 SDS 的增量之間存在更細微的差異。 rhGH 組的基線特徵預測這些受試者將對治療有更大的反應。在只有 50% 的入組率下，隊列表現出不平衡的情況並不少見，隨著試驗接近完全入組率，這種情況應該會正常化。

As I mentioned earlier, we identified 2 outliers in the growth hormone arm who grew significantly more than expected in this moderate PGHD population at 15.6 and 12.7 centimeters per year, respectively. Two of the 3 subjects under 5, including these subjects are randomized to the growth hormone arm. Remember that age is one of the most important variables to predict faster growth on the start of treatment. These outliers are represented by red stars on the graph of expected first-year growth and less severe growth hormone deficiency as predicted by Ranke's analysis of Pfizer's KIGS data set. Our trial is stratified by age, so as enrollment progresses, we would expect these baseline ages to be more evenly distributed across all cohorts, diminishing the impact of these early outliers.

正如我之前提到的，我們在生長激素組中發現了 2 個異常值，他們在這個中度 PGHD 人群中的增長顯著超過預期，分別為每年 15.6 和 12.7 厘米。 3 名 5 歲以下受試者中的兩名，包括這些受試者，被隨機分配到生長激素組。請記住，年齡是預測治療開始時更快生長的最重要變量之一。正如 Ranke 對輝瑞公司 KIGS 數據集的分析所預測的那樣，這些異常值在第一年的預期增長和較不嚴重的生長激素缺乏症圖表上由紅色星星表示。我們的試驗按年齡分層，因此隨著招募的進行，我們預計這些基線年齡將更均勻地分佈在所有隊列中，從而減少這些早期異常值的影響。

As Rick mentioned, we are now at approximately 80% enrollment that we can examine baseline characteristics where all subjects currently randomized. As we have predicted, age differences and BMI differences have become much less pronounced between the growth hormone and LUM-201 treatment cohorts. While we don't have annualized height velocity on these new subjects, we know that older subjects have been enrolled in the growth hormone arm, which will likely offset the effect of the youngest subjects enrolled early in that cohort. First examine durability of response to LUM-201 next, particularly for the 1.6 mg per kg per day arm growth rates are similar at 6, 9 and 12 months. On the other hand, the well-known propensity for injectable were common human growth hormone catch-up growth to decline over the 6- to 12-month time frame is observed in our comparator arm.

正如 Rick 提到的，我們現在大約有 80% 的入學率，我們可以檢查所有受試者當前隨機分配的基線特徵。正如我們預測的那樣，年齡差異和 BMI 差異在生長激素和 LUM-201 治療組之間變得不那麼明顯。雖然我們沒有這些新受試者的年化身高增長速度，但我們知道年齡較大的受試者已被納入生長激素組，這可能會抵消較早納入該隊列的最年輕受試者的影響。接下來首先檢查對 LUM-201 反應的持久性，特別是每天每公斤 1.6 毫克的手臂生長率在 6、9 和 12 個月時相似。另一方面，在我們的比較組中觀察到眾所周知的注射傾向是常見的人類生長激素追趕生長在 6 至 12 個月的時間範圍內下降。

The LUM-201 1.6 mg per kg per day cohort achieved a mean annualized height velocity of 8.1 centimeters per year at 12 months. The recombinant growth hormone arm showed a mean annualized height velocity of 9.9 centimeters per year. A pivotal non-inferiority trial is 12 months in duration. So we were pleased by the durability of LUM-201 growth with the difference in growth between these 2 arms of 12 months aligned within the non-inferiority margin used in recent PGHD registrational studies. Also as cohorts continue to enroll and more subjects achieve 12 months on treatment, we would expect a better balance characteristics to be reflected in the convergence of these 12-month growth rates.

LUM-201 1.6 毫克/千克/天隊列在 12 個月時實現了每年 8.1 厘米的平均年化身高增長速度。重組生長激素組的平均年身高增長速度為每年 9.9 厘米。一項關鍵的非劣效性試驗持續 12 個月。因此，我們對 LUM-201 增長的持久性感到滿意，這兩個 12 個月的分支之間的增長差異在最近的 PGHD 註冊研究中使用的非劣效性邊界內對齊。此外，隨著隊列繼續招募和更多受試者達到 12 個月的治療時間，我們預計這些 12 個月增長率的趨同將反映出更好的平衡特徵。

We will now discuss our OraGrowtH212 trial. This trial is a single-site open-label trial evaluating the pharmacokinetic and pharmacodynamic effects of oral LUM-201 in up to 24 treatment-naive PGHD subjects at 2 dose levels, 1.6 and 3.2 mg per kg per day. These data will supplement the PK/PD data at 0.8 mg per kg per day from an earlier study in PGHD demonstrating the unique mechanism of action of LUM-201 to stimulate pulsatile release of growth hormone. Annualized height velocity is also being evaluated at these 2 higher LUM-201 doses. This trial will continue until the subjects reach near adult height.

我們現在將討論我們的 OraGrowtH212 試驗。該試驗是一項單點開放標籤試驗，評估口服 LUM-201 在多達 24 名未接受過治療的 PGHD 受試者中的藥代動力學和藥效學作用，劑量水平為 1.6 和 3.2 mg/kg/天。這些數據將補充 PGHD 早期研究中每天 0.8 mg/kg 的 PK/PD 數據，該研究證明了 LUM-201 刺激生長激素脈衝釋放的獨特作用機制。還在這 2 種更高劑量的 LUM-201 下評估年化身高增長速度。該試驗將一直持續到受試者達到接近成人身高為止。

Today, we are announcing interim data on 10 subjects in this trial and expect to provide top line data on up to 24 subjects in these 2 dose cohorts in the second half of next year. We will review the annualized height velocity for 5 subjects on 1.6 and 5 subjects on 3.2 mg per kg per day at 6 months on therapy. We expect to release the PK/PD data once it has been fully analyzed. All subjects in the OraGrowtH212 study are PEM positive.

今天，我們將公佈該試驗中 10 名受試者的中期數據，並預計在明年下半年提供這 2 個劑量組中多達 24 名受試者的主要數據。我們將在治療 6 個月時審查 5 名受試者的年化身高增長速度為 1.6 和 5 名受試者的劑量為 3.2 mg/kg/天。我們希望在完全分析後發布 PK/PD 數據。 OraGrowtH212 研究中的所有受試者均為 PEM 陽性。

The interim OraGrowtH212 data showed a mean 6-month annualized height velocity of 7.1 centimeters per year on 1.6 mg per kg per day, and 8.6 centimeters per year on 3.2 mg per kg per day, demonstrating a similar growth rate seen on these 2 higher LUM-201 doses in the OraGrowtH210 trial. Again, the number of subjects in each cohort is small, but we believe these OraGrowtH212 data represent a secondary validation of the results that we observed in the Phase II OraGrowtH210 trial.

中期 OraGrowtH212 數據顯示，每天 1.6 毫克/公斤的平均 6 個月年化身高速度為 7.1 厘米，每天 3.2 毫克/公斤的平均年身高增長速度為 8.6 厘米，表明在這兩個更高的 LUM 上看到的生長速度相似OraGrowtH210 試驗中的 -201 劑量。同樣，每個隊列中的受試者數量很少，但我們相信這些 OraGrowtH212 數據代表了我們在 II 期 OraGrowtH210 試驗中觀察到的結果的二次驗證。

When we evaluate growth at 6, 9 and 12 months on LUM-201, durability of effect is evident. The 1.6 mg per kg per day arm produce mean AHVs of 7.1 centimeters per year at 6 months and 7.2 centimeters per year at 12 months on therapy. The 3.2 mg per kg arm produced 8.6 and 7.8 centimeters per year, respectively, at 6 and 12 months on therapy. The error bars are tight for both cohorts at all time points, suggesting a rather homogeneous population.

當我們評估 LUM-201 在 6、9 和 12 個月時的生長時，效果的持久性是顯而易見的。每天每公斤 1.6 毫克的手臂在治療後 6 個月產生平均每年 7.1 厘米的 AHV，在治療 12 個月時產生每年 7.2 厘米的平均 AHV。在治療第 6 個月和第 12 個月時，每公斤 3.2 毫克的手臂每年分別長出 8.6 和 7.8 厘米。在所有時間點，兩個隊列的誤差線都很緊，表明人口相當均勻。

Again, both of these cohorts showed durability of growth out to 12 months at interim data, confirming a similar trend observed in the OraGrowtH210 trial. From the comparability data, from these 2 independent trials, we feel confident that we should see similar growth patterns for our selected LUM-201 dose in a pivotal Phase III trial. In a further effort to determine an optimal dose for our Phase III trial, we combined the growth velocity data for both cohorts from each OraGrowtH210 and 212 trial in a post-hoc analysis to find the mean growth rates for each dose. In that analysis, we observed comparable mean growth rates for the top 2 LUM-201 doses at 6, 9 and 12 months. Our analysis of the separate and combined data support the selection of 1.6 mg per kg per day as the optimal dose for a pivotal Phase III trial in PGHD.

同樣，這兩個隊列在中期數據中都顯示出長達 12 個月的增長持久性，證實了在 OraGrowtH210 試驗中觀察到的類似趨勢。從這兩項獨立試驗的可比性數據來看，我們有信心在關鍵的 III 期試驗中看到我們選擇的 LUM-201 劑量具有相似的生長模式。為了進一步確定我們 III 期試驗的最佳劑量，我們在事後分析中結合了每個 OraGrowtH210 和 212 試驗的兩個隊列的生長速度數據，以找到每個劑量的平均增長率。在該分析中，我們觀察到前 2 個 LUM-201 劑量在 6、9 和 12 個月時的平均增長率相當。我們對單獨和合併數據的分析支持選擇 1.6 mg/kg/天作為 PGHD 關鍵 III 期試驗的最佳劑量。

In addition to efficacy data, we also reviewed the safety data for our molecule for all subjects enrolled in the OraGrowtH trials to date. We believe LUM-201 will demonstrate a favorable safety profile as our interim data from both OraGrowtH trial shows comparable safety and tolerability to the recombinant human growth hormone subjects in the trial. There were no treatment-related serious adverse events, no dropouts due to SAEs and no meaningful safety signals observed in either laboratory values, adverse event data or in ECG values. The safety AE for the OraGrowtH212 is consistent with the data in the OraGrowtH210 trial. A summary of some of these adverse event tables may be found in the supplementary slides available on our website. I will now turn the call over to Lori to run through financial highlights for the third quarter 2022.

除了療效數據外，我們還審查了迄今為止參加 OraGrowtH 試驗的所有受試者的分子安全性數據。我們相信 LUM-201 將展示良好的安全性，因為我們來自 OraGrowtH 試驗的中期數據顯示與試驗中的重組人生長激素受試者相當的安全性和耐受性。沒有與治療相關的嚴重不良事件，沒有因 SAE 導致的退出，也沒有在實驗室值、不良事件數據或 ECG 值中觀察到有意義的安全信號。 OraGrowtH212 的安全性 AE 與 OraGrowtH210 試驗中的數據一致。在我們網站上提供的補充幻燈片中可以找到其中一些不良事件表的摘要。我現在將把電話轉給 Lori，讓她了解 2022 年第三季度的財務亮點。

Thank you, John. Lumos Pharma ended the third quarter on September 30, 2022, with cash and cash equivalent totaling $73.7 million compared to $94.8 million on December 31, 2021. The company expects a cash use of approximately $8.5 million to $9.5 million in Q4 2022. Cash on the end as of September 30, 2022, is expected to support operations into the second quarter of 2024, inclusive of the primary outcome data readout from OraGrowtH210 and OraGrowtH212 trials anticipated in the second half of 2023. Research and development expenses were $4.1 million for the quarter ended September 30, 2022, flat compared to the same period in 2021. General and administrative expenses were $3.9 million for the quarter ended September 30, 2022, as compared to $3.4 million for the same period in 2021, primarily due to royalties paid to the Public Health Agency of Canada for revenues received from Merck for the sale of the Ebola vaccine. The net loss for the third quarter was $7.3 million compared to a net loss of $7.5 million for the same period in 2021. Lumos Pharma ended the third quarter of 2022 with 8,375,271 shares outstanding.

謝謝你，約翰。 Lumos Pharma 截至 2022 年 9 月 30 日的第三季度末，現金和現金等價物總額為 7370 萬美元，而 2021 年 12 月 31 日為 9480 萬美元。公司預計 2022 年第四季度的現金使用量約為 850 萬至 950 萬美元。截至 2022 年 9 月 30 日結束，預計將支持 2024 年第二季度的運營，包括預計在 2023 年下半年從 OraGrowtH210 和 OraGrowtH212 試驗中讀取的主要結果數據。本季度的研發費用為 410 萬美元截至 2022 年 9 月 30 日，與 2021 年同期持平。截至 2022 年 9 月 30 日的季度，一般和行政費用為 390 萬美元，而 2021 年同期為 340 萬美元，這主要是由於支付給加拿大公共衛生署從默克公司獲得的埃博拉疫苗銷售收入。第三季度的淨虧損為 730 萬美元，而 2021 年同期的淨虧損為 750 萬美元。Lumos Pharma 截至 2022 年第三季度末的流通股為 8,375,271 股。

Additional information may be found in our quarterly press release and 10-Q filed this morning. And with that, I will turn the call back to Rick to conclude for us.

更多信息可以在我們的季度新聞稿和今天早上提交的 10-Q 中找到。有了這個，我會把電話轉回給里克來為我們總結。

Thank you, Lori. We're very pleased to report that we've meaningfully derisked our entire program in not just 1 study, but across 2 separate studies. In the OraGrowtH210 trial to date, subjects on 1.6 mg per kg per day of LUM-201 grew at a mean annualized height velocity of 8.6 centimeters per year at 6 months as expected. Our patient population that are PEM positive, in other words, those with moderate idiopathic growth hormone deficiency, were predicted to grow about 8.3 centimeters in the first year on treatment.

謝謝你，洛瑞。我們很高興地報告，我們不僅在一項研究中，而且在 2 項獨立研究中有意義地降低了我們整個計劃的風險。在迄今為止的 OraGrowtH210 試驗中，每天服用 1.6 毫克/千克 LUM-201 的受試者在 6 個月時的平均年身高增長速度為 8.6 厘米/年，符合預期。我們的 PEM 陽性患者群體，換句話說，那些患有中度特發性生長激素缺乏症的患者，預計在治療的第一年會增長約 8.3 厘米。

We also are very pleased to report a durability out to 12 months with the margin between treatment and control arms within the non-inferiority range used in recent growth hormone registrational trials. Also, as John just reported, interim data has not identified any safety and tolerability concerns to date for LUM-201 across all doses.

我們也非常高興地報告了長達 12 個月的耐久性，治療組和對照組之間的差距在最近的生長激素註冊試驗中使用的非劣效性範圍內。此外，正如 John 剛剛報導的那樣，迄今為止，中期數據尚未發現所有劑量的 LUM-201 存在任何安全性和耐受性問題。

These interim data support the identification of 1.6 mg per kg per day dose of LUM-201 for our Phase III trial, enabling us to initiate advanced planning for this important pivotal study. Also, these interim data reported today corroborate prior data suggesting LUM-201 has the potential to disrupt the growth hormone market that's been dominated for almost 40 years by injectable products. LUM-201 is once again a small molecule given orally once a day, and we believe as our preliminary market research demonstrates that the majority of pediatric growth hormone-deficient children with moderate PGHD would prefer an oral alternative.

這些中期數據支持為我們的 III 期試驗確定 1.6 毫克/公斤/天的 LUM-201 劑量，使我們能夠為這項重要的關鍵研究啟動高級計劃。此外，今天報告的這些中期數據證實了先前的數據，表明 LUM-201 有可能破壞近 40 年來被注射產品主導的生長激素市場。 LUM-201 再次成為每天口服一次的小分子，我們相信，我們的初步市場研究表明，大多數患有中度 PGHD 的兒童生長激素缺乏兒童更喜歡口服替代品。

We should thank all of our investigators and the PGHD patients and their families involved in our trials. And to say the least, we're excited to continue to advance our programs and look forward to disclosing top line data in the second half of 2023. Thank you very much.

我們應該感謝參與我們試驗的所有研究人員和 PGHD 患者及其家屬。至少可以說，我們很高興繼續推進我們的計劃，並期待在 2023 年下半年披露頂線數據。非常感謝。

(Operator Instructions) The first question we have is from Charles Duncan from Cantor Fitzgerald.

（操作員說明）我們的第一個問題來自 Cantor Fitzgerald 的 Charles Duncan。

Yes. I had a question regarding the interest of the investigators and patients and the screen failure rate. How is that going? It seems like this can even further help enrollment? And then second question is related to the dose response, at least numerically forgetting about the error bars, it looks like there's a little bit of a U-shaped dose response. Do you have a mechanistic rationale for them?

是的。我有一個關於研究者和患者的興趣以及篩查失敗率的問題。進展如何？好像這樣還能進一步幫助招生？然後第二個問題與劑量反應有關，至少在數字上忘記了誤差條，看起來有點 U 形劑量反應。你有他們的機械原理嗎？

Yes. So John -- or actually, David, why don't you answer that first question about screen failure rate. And then, John, why don't you answer the second question.

是的。所以約翰 - 或者實際上，大衛，你為什麼不回答關於屏幕故障率的第一個問題。然後，約翰，你為什麼不回答第二個問題。

Sure. Our screen failure rate remains really quite low, which is why our enrollment is going so well for both trials. So I don't see that improving -- I mean the sites remain very engaged and our kids are happy with the growth in the trial. So it's helping a lot. Second question was...

當然。我們的篩選失敗率仍然非常低，這就是為什麼我們的註冊在這兩個試驗中都進行得如此順利。所以我看不到這種改善——我的意思是網站仍然非常活躍，我們的孩子對試驗的增長感到滿意。所以它有很大幫助。第二個問題是...

Dose response, and I think John is going to answer that question.

劑量反應，我想約翰會回答這個問題。

Yes. So Chaz, if you remember, we've showed you the pharmacodynamic dose response curve that Merck generated in their early trial. And we've kind of -- our lowest dose was 0.8 mg per kg. And on that PD dose response curve, that was about 1/3 of the way up the dose response curve. When we go to 1.6, our mid-dose, it's about 75% of the way up the curve, and then when we go from 1.6 to 3.2, you're kind of above the plateau. So we knew the dose response curve would be -- or the dose response change between 0.8 and 1.6 would be larger than 1.6 and 3.2 based on that data. So it's not too surprising for us that the 1.6 and 3.2 -- we expected a little bit of a dose response, but they're essentially the same by the time we look at them across both studies and combine the cohorts.

是的。 Chaz，如果你還記得的話，我們已經向你展示了默克公司在他們早期試驗中生成的藥效劑量反應曲線。我們有點——我們的最低劑量是每公斤 0.8 毫克。在那個 PD 劑量反應曲線上，這大約是劑量反應曲線的 1/3。當我們達到 1.6 時，我們的中間劑量，它大約是曲線上升的 75%，然後當我們從 1.6 到 3.2 時，你有點高於平台。所以我們知道劑量反應曲線將是——或者根據該數據，0.8 和 1.6 之間的劑量反應變化將大於 1.6 和 3.2。因此，1.6 和 3.2 對我們來說並不奇怪——我們預計會有一點劑量反應，但當我們在兩項研究中查看它們並結合隊列時，它們基本上是相同的。

And then if I could ask a follow-up, Rick, John or David. It looks like the error bars are actually quite reasonable despite the sample size. And I guess I'm wondering how might this impact the sample size calculus that you're doing and/or design of a pivotal study. And then could this fast forward, you being able to really operationalize a pivotal program with LUM-201.

然後，如果我可以請 Rick、John 或 David 跟進。儘管樣本量很大，但看起來誤差線實際上是相當合理的。我想我想知道這會如何影響您正在進行的樣本量計算和/或關鍵研究的設計。然後可以快速前進，您能夠真正實施具有 LUM-201 的關鍵程序。

John, go ahead.

約翰，繼續。

So I think the first part is we got the key -- one of the key answers that we wanted out of this, which is the dose for Phase III, right? So now that we have the dose, we can actually start to plan a lot of the -- make sure the CMC activities are going to align with having that dose ready and all the other pieces so protocol writing, we can start with I think we would like to wait a little bit longer and see the full data set and the variability in an [n of 20]. The error bars are very tight actually for the 212 study, they're a little bit larger for 210, and I think we'd like to know where we're going to be in between those 2 standard deviations as we start to plan for what our variability will be in the larger study. So I think our estimates for Phase III remained about the same that we've been projecting. And I think once we have a broader data set, we'll be able to essentially calculate better and then go negotiate with the FDA and agree on what our margin will be.

所以我認為第一部分是我們得到了關鍵 - 我們想要從中得到的關鍵答案之一，即 III 期的劑量，對嗎？所以現在我們有了劑量，我們實際上可以開始計劃很多 - 確保 CMC 活動將與準備好劑量和所有其他部分保持一致，以便協議編寫，我們可以從我認為我們開始想再等一會兒，看看完整的數據集和 [n of 20] 中的可變性。對於 212 研究，誤差線實際上非常緊湊，對於 210 研究，它們稍微大一點，我想我們想知道在我們開始計劃時我們將處於這兩個標準偏差之間的哪個位置在更大的研究中我們的可變性是什麼。所以我認為我們對第三階段的估計與我們一直預測的大致相同。而且我認為一旦我們擁有更廣泛的數據集，我們將能夠從本質上更好地計算，然後與 FDA 談判並就我們的利潤率達成一致。

Okay. Last question for Rick. You mentioned China. I was intrigued with that specific call out in terms of incidence or prevalence pediatric growth hormone deficiency. I guess I'm wondering, is there a specific strategy that you're contemplating with regard to ex U.S. And can you provide any color on that and when you would like to maybe pursue a partnership?

好的。瑞克的最後一個問題。你提到了中國。就兒童生長激素缺乏症的發病率或患病率而言，我對那個具體的呼籲很感興趣。我想我想知道，您是否正在考慮針對前美國的具體戰略？您能否提供任何顏色以及您希望何時尋求合作夥伴關係？

Sure, Chaz. Look, there's no question about it. The China market is probably going to be approaching the second largest market in the world. It's already about $1.5 billion in sales per year, and it's growing 20%, 25% a year. So we certainly have to pay attention to it. I think there is a number of Asian partners who certainly would be interested in talking to us. It's a little too early right now, but I think that in the coming months and year, I think that we're probably step-up activity in terms of the outreach. But it is no question, it's a very important market. And when we do a global clinical trial we'll include Asian patients, of course.

當然，查茲。看，這毫無疑問。中國市場可能正在接近世界第二大市場。它每年的銷售額已經達到 15 億美元左右，並且還在以每年 20%、25% 的速度增長。所以我們當然要注意它。我認為有許多亞洲合作夥伴肯定有興趣與我們交談。現在有點太早了，但我認為在接下來的幾個月和一年裡，我認為我們可能會加強外展活動。但毫無疑問，這是一個非常重要的市場。當然，當我們進行全球臨床試驗時，我們會包括亞洲患者。

The next question we have is from Yasmeen Rahimi from Piper Sandler.

我們的下一個問題來自 Piper Sandler 的 Yasmeen Rahimi。

Congrats on the data. It would be really great if you could maybe comment a little bit more on the baseline characteristics of 210. I appreciate you sharing the baselines on the 75% of the population that's complete. But when we look -- in terms of the mid-parental height and the variability in the BMI, it still seems to be slightly as an outlier. So just kind of help us comment a little bit more why those would be balanced. And then b, is there a reason to -- as you're screening the additional patients for full enrollment? Is there a way to maybe homogenize that population so that, that 25% that's coming in is also doesn't account for any variability? And then maybe like one more follow-up question for you, team.

恭喜數據。如果您能對 210 的基線特徵多加評論，那就太好了。感謝您分享 75% 的已完成人口的基線。但是當我們看——就父母身高中值和 BMI 的變異性而言，它似乎仍然有點異常。所以只是幫助我們多評論一下為什麼這些會被平衡。然後 b，是否有理由——因為您正在篩選額外的患者以進行全面登記？有沒有一種方法可以使該人口同質化，以便進入的 25% 也不會考慮任何可變性？團隊，也許還有一個跟進問題要問你。

All right. Go ahead, David. Why don't you answer the question.

好的。去吧，大衛。你為什麼不回答問題。

Yes. So we only have 2 factors for stratification, high SDS and age and it becomes problematic to stratify it for more than 2 factors in a trial. But we are getting a more homogeneous population in the latter half of the trial than the first half of the trial simply because we're closely scrutinizing all the factors at a prescreening form before we allow them to screen. So we're making sure that they're all reasonably similarly GHD. So that should help. And I do expect the full population to be much more homogeneous than the interim analysis. You did highlight some of the key features that I think in addition to the outliers, provenly provided the imbalance in this current interim analysis because the BMI in particular, was a significant factor after age, I think in driving that group's response.

是的。所以我們只有 2 個分層因素，高 SDS 和年齡，並且在試驗中將其分層為超過 2 個因素會變得有問題。但是我們在試驗的後半部分比試驗的前半部分獲得了更均勻的人群，這僅僅是因為我們在允許他們進行篩選之前仔細檢查了預篩選表格中的所有因素。所以我們要確保它們都是相當相似的 GHD。所以這應該有所幫助。而且我確實希望整個人口比中期分析更加同質。你確實強調了一些我認為除了異常值之外的關鍵特徵，證明了當前中期分析中的不平衡，因為 BMI 特別是年齡之後的一個重要因素，我認為它推動了該群體的反應。

And John, why don't you...

約翰，你為什麼不...

Yes. Yes. If I may add, I mean, I think one of the biggest issues for the interim was age, right? There was about a 9.5 month difference between 1.6 and the growth hormone arm, and we are stratifying by age. And so when we added 5 more kids to the growth hormone cohort, we've cut that differential in half, right? So I think that is probably -- we're down to about 4 months difference between growth hormone and the 1.6 arm. So I think that's going to have a big effect and things will gradually -- to be honest, the youngest kid in the growth hormone arm was also the kid with the largest BMI, right? So I think we will add kids as older kids come in. These will balance out even more, right? The next 5 kids will continue that trend.

是的。是的。如果我可以補充一點，我的意思是，我認為過渡期間最大的問題之一是年齡，對嗎？ 1.6 和生長激素組之間大約有 9.5 個月的差異，我們按年齡分層。所以當我們在生長激素隊列中增加了 5 個孩子時，我們就把這個差異減半了，對吧？所以我認為這可能是——我們將生長激素和 1.6 臂之間的差異縮小到大約 4 個月。所以我認為這會產生很大的影響，事情會逐漸發生——老實說，生長激素組中最小的孩子也是 BMI 最高的孩子，對吧？所以我認為我們會隨著大孩子的加入而增加孩子。這些會平衡得更多，對吧？接下來的 5 個孩子將延續這一趨勢。

Great. And then, team, I know that there was going to be additional analyses in 2012 in terms of the pulsatility, the PK/PD, like, when should we be expecting that data to be shared with us?

偉大的。然後，團隊，我知道 2012 年將在脈動性、PK/PD 方面進行額外的分析，比如，我們應該期望什麼時候與我們共享數據？

Go ahead, John.

去吧，約翰。

So I think that data will be shared before the end of the year.

所以我認為數據將在年底前共享。

Yes.

是的。

The next question we have is from Ed White from H.C. Wainright.

我們的下一個問題來自 H.C. 的 Ed White。溫賴特。

The first question is just on those 2 patients that were seen as outliers in the growth hormone cohort. How many months have they been on treatment?

第一個問題只是關於那些在生長激素隊列中被視為異常值的 2 名患者。他們接受治療幾個月了？

John, do you want to answer that question?

約翰，你想回答這個問題嗎？

Yes. So the fastest-growing child is 15.6, we have data through 9 months, so 6 and 9 months; and 12.8, I think we have 6, 9 and 12 months on.

是的。所以增長最快的孩子是 15.6，我們有 9 個月的數據，所以 6 和 9 個月；和 12.8，我認為我們還有 6、9 和 12 個月。

Okay. And then just looking at the dosing and you had mentioned about why we shouldn't have seen a dose response, are you giving any consideration to doing a dose perhaps between 1.6 and 3.2 perhaps 2.4 to sort of 0 in more on that. And you did mention the Phase III dose is probably going to be the 1.6. But is it really too early to tell that right now? And shouldn't you wait for more data?

好的。然後只看劑量，你提到了為什麼我們不應該看到劑量反應，你是否考慮過劑量可能在 1.6 到 3.2 之間，或者 2.4 到更多的 0。你確實提到了 III 期劑量可能是 1.6。但現在說這個真的太早了嗎？你不應該等待更多數據嗎？

John, go ahead.

約翰，繼續。

So I think we feel pretty confident with the selection of 1.6, right? So we have 2 separate trials. They are slightly different populations, but they both point to very similar growth rates between the 2 doses. We know from earlier work that the plateau for growth hormone release is somewhere in between those 2 doses. And I don't think we're going to gain much by trying to split the difference between those 2 doses and come up with like a 2.4 mg per kg per day arm. I think the 1.6 should be sufficient. And the FDA is always going to want us to use the minimum drug to get a good effect, right? And I think looking at this data, that looks to be the 1.6 arm.

所以我認為我們對選擇 1.6 很有信心，對吧？所以我們有 2 個單獨的試驗。它們是略有不同的種群，但它們都表明兩種劑量之間的增長率非常相似。我們從早期的研究中知道，生長激素釋放的穩定期介於這兩種劑量之間。而且我認為我們不會通過嘗試拆分這 2 種劑量之間的差異並得出每天每公斤 2.4 毫克的劑量來獲得太多收益。我認為1.6應該足夠了。而且FDA總是要我們用最少的藥才能有好的效果，對吧？而且我認為查看這些數據，看起來是 1.6 臂。

Okay. And perhaps my last question is just when you see the data from the outliers being the youngest patients, how are you thinking about your Phase III protocol? And would you accept those patients under 5 years? Do you think that perhaps you look at older patients? I just wanted to answer that question.

好的。也許我的最後一個問題是，當您看到來自異常值的數據是最年輕的患者時，您如何看待您的 III 期方案？您會接受那些 5 歲以下的患者嗎？你認為也許你會看老年患者嗎？我只是想回答那個問題。

David, do you want to answer that?

大衛，你想回答這個問題嗎？

Yes. I'll say 2 things. One is that the much larger patient population in a Phase III trial usually results in very good balance for all of these factors. And secondly, we could focus on that and do a 3-part stratification per age just to make sure that we get the same number of the youngest mid and old subjects in each group. There's different ways to handle that. But I think the sample size itself takes care of most of those issues.

是的。我會說兩件事。一是 III 期試驗中的患者人數要多得多，通常會在所有這些因素之間取得很好的平衡。其次，我們可以專注於此，並按年齡進行 3 部分分層，以確保我們在每組中獲得相同數量的最年輕的中年和老年受試者。有不同的方法來處理它。但我認為樣本量本身可以解決大部分問題。

(Operator Instructions) The next question we have is from Catherine Novack from Jones Research.

（操作員說明）我們的下一個問題來自 Jones Research 的 Catherine Novack。

Congrats on the data. Just going back to some of the baseline characteristics. I'm curious about trying to understand how to think about remaining imbalances in characteristics that we might be seeing at 75% enrollment. Which of these characteristics -- few characteristics would have had the greatest impact in difference on AHV. And I have a follow-up.

恭喜數據。回到一些基線特徵。我很好奇試圖了解如何考慮我們在 75% 的入學率下可能會看到的剩餘特徵不平衡。這些特徵中的哪一個 - 少數特徵會對 AHV 的差異產生最大影響。我有一個後續行動。

David, go ahead.

大衛，繼續。

Yes. In most of the models, including Ranke, the #1 and 2 are basically the growth hormone dose and age. In the trial, the growth hormone dose is fixed. So that's taken out of the equation. So age is probably the single most important factor and that's followed then by basically BMI, higher BMI being faster growth than lower BMI or higher weight versus lower weight. And then the other factors are also meaningful. So if you have big differences in IGF-1 SDS or in higher mid-parental height or Delta mid-parental height all of the -- so the short you are compared to what you should be, will give you better growth. And the greater -- farther away you are from that the better growth and lower IGF-1. So they are all factors, but the 2 -- the ones that we -- that are effective in our trial probably age is the single most important because the growth hormone dose is fixed. Does that answer your question?

是的。在大多數模型中，包括 Ranke，#1 和 2 基本上是生長激素劑量和年齡。在試驗中，生長激素的劑量是固定的。因此，這已被排除在外。所以年齡可能是最重要的因素，其次是 BMI，較高的 BMI 比較低的 BMI 增長更快，或者較高的體重與較低的體重相比。然後其他因素也很有意義。因此，如果您在 IGF-1 SDS 或更高的父母身高中值或 Delta 父母身高中值方面存在很大差異，那麼與您應有的身高相比，您的矮個子會給您帶來更好的成長。你離那個越大——越遠，生長越好，IGF-1 越低。所以它們都是因素，但在我們的試驗中有效的 2 個因素可能是年齡是最重要的因素，因為生長激素的劑量是固定的。這是否回答你的問題？

Yes. That's very helpful. And then the second one, just thinking about expansion of indications now that you've selected an effective what you expect to be an effective dose. Are you planning to disclose additional LUM-201 indications?

是的。這很有幫助。然後是第二個，現在你已經選擇了一個有效的你期望的有效劑量，只是考慮擴大適應症。您是否計劃披露其他 LUM-201 適應症？

We haven't given any guidance yet, but we've had some ongoing plans for quite some time. And I think some time in the near future, we'll make it an appropriate announcement.

我們還沒有給出任何指導，但我們已經制定了一些正在進行的計劃很長一段時間了。我想在不久的將來，我們會發布一個適當的公告。

The next question we have is from Eun Yang from Jefferies.

我們的下一個問題來自 Jefferies 的 Eun Yang。

So it sounds like for upcoming Phase III trial based on the data today, you don't feel that you have to modify the enrollment criteria. Am I understanding it correctly?

因此，根據今天的數據，聽起來對於即將進行的 III 期試驗，您並不覺得必須修改入組標準。我理解正確嗎？

David?

大衛？

I think that there will be some tweaks to the enrolling criteria for Phase III. But just getting more to what kind of a standard entry criteria?

我認為第三階段的招生標準會有一些調整。但只是越來越多地以什麼樣的標准進入標準呢？

But there will still be the PEM positive entry criteria, right? That is -- and we'll validate...

但仍然會有 PEM 正面准入標準，對嗎？那就是——我們將驗證……

Yes, for sure. Yes. And the screening rate, would you still stand by PEM positive kids would be about 50%, 60% of or growth hormone deficient kids?

是肯定的。是的。而篩查率，您是否仍然支持 PEM 陽性兒童大約為 50%、60% 或生長激素缺乏兒童？

Yes. I think that it's 2 questions. One is what percentage of kids are PEM positive, idiopathic PGHD. And based upon all the available data, that's about 2/3 of the population. In terms of screening for the study, what we found in this trial as long as we educate the investigators to identify kids with idiopathic GHD, then the vast majority of them are PEM-positive. So the PEM itself does not factor really meaningfully into the screening or enrollment process. As long as you identify the right subjects to screen, it works very, very well.

是的。我認為這是2個問題。一是 PEM 陽性、特發性 PGHD 兒童的百分比。根據所有可用數據，這大約佔人口的 2/3。在這項研究的篩選方面，我們在這項試驗中發現，只要我們教育研究人員識別患有特發性 GHD 的孩子，那麼他們中的絕大多數都是 PEM 陽性的。因此 PEM 本身在篩選或註冊過程中並沒有真正有意義的因素。只要您確定要篩選的正確主題，它就會非常非常有效。

Right. And then if you mentioned this, I apologize. So in the daily growth hormone injection on the 2 youngest kids showing the highest growth of velocity. If you actually exclude those 2 kids, what would have been the growth of velocity in that population in that cohort?

正確的。然後，如果您提到了這一點，我深表歉意。因此，在每天注射生長激素時，最小的 2 個孩子表現出最高的生長速度。如果你真的排除了那兩個孩子，那麼那個群體中那個人口的速度增長會是多少？

John, do you want to answer that?

約翰，你想回答這個問題嗎？

I didn't get the question -- so 1 way to do that is to instead of using the mean annualized height velocity, if you look at the median annualized height velocity, right? So that gets you -- because that minimizes the impact of outliers -- so you get down to about, I think, 10.8 centimeters 8-month growth -- or I'm sorry, 6-month growth in that growth hormone cohort. So it does go down pretty significantly.

我沒聽明白這個問題——所以一種方法是不使用平均年化身高增長速度，如果你看中值年化身高增長速度，對嗎？所以這會讓你 - 因為這最大限度地減少了異常值的影響 - 所以你可以降低到大約 10.8 厘米 8 個月的增長 - 或者我很抱歉，那個生長激素隊列的 6 個月增長。所以它確實下降了很多。

Okay. And the last question is on the patent. So the competition (inaudible) patent has expired but you have orphan exclusivity and you have a use of patent -- but what are you -- how do you think about the strength of your other patents for 201?

好的。最後一個問題是關於專利的。所以競爭（聽不清）專利已經過期，但你有孤兒排他性，你有專利的使用——但你是什麼——你如何看待 201 的其他專利的實力？

Good question. And we do have a U.S. patent and it's the diagnosis and treatment of not just PGHD, but across the board with all of these growth hormone disorders. And it's the application of our predictive enrichment marker strategy is where that lies. That patent has been issued in the U.S. It goes out to 2036 and were executed in other parts of the world right now. But of course, we have orphan status in the U.S., Europe, and we'll get it in Japan and other parts of the world when it's appropriate.

好問題。我們確實擁有一項美國專利，它不僅可以診斷和治療 PGHD，還可以診斷和治療所有這些生長激素紊亂。這就是我們預測性富集標記策略的應用所在。該專利已在美國頒發，有效期至 2036 年，目前已在世界其他地區實施。但當然，我們在美國、歐洲有孤兒身份，我們會在適當的時候在日本和世界其他地方獲得它。

Our final question comes from Elemer Piros from ROTH.

我們的最後一個問題來自 ROTH 的 Elemer Piros。

Yes. What I'd like to ask is, were there any other groups in which there were children that were under the age of 5 that have been enrolled in this study.

是的。我想問的是，是否有任何其他組中有 5 歲以下的兒童參加了這項研究。

Yes. John?

是的。約翰？

I'm sorry?

對不起？

Yes, there was 1 other subject to is -- so there were 3 subjects under the 5, 2 are in the growth hormone arm and 1 within the 0.8 mg per kg per day arm.

是的，還有 1 個其他主題 - 所以有 3 個主題低於 5，2 個在生長激素組，1 個在每天每公斤 0.8 毫克的組。

Okay. And maybe a follow-up to that. And after taking out those 2 outliers, and I know that the sample size is still very small. But you -- I think you mentioned that there is a 10.8 centimeter annualized height velocity that would seem to be congruent with if you were to look at the Ascendis pivotal trial, both the daily injection and the once weekly. Have you been able to look at the baseline characteristics of your study versus that pivotal trial?

好的。也許是後續行動。在去掉那兩個異常值之後，我知道樣本量仍然很小。但是你——我想你提到過有一個 10.8 厘米的年化身高速度，如果你要看 Ascendis 關鍵試驗，每天注射一次和每週注射一次，這似乎是一致的。您是否能夠查看您的研究與該關鍵試驗的基線特徵？

Yes. David, why don't you go ahead. John, you go first and then David...

是的。大衛，你為什麼不繼續。約翰，你先走，然後戴維……

So I gave the wrong number, Elemer, the first time. The median for the growth hormone arm is 10.5. So I just wanted to clarify that. I remember the -- it's 10.5. And then, David, you could talk about the baseline for Ascendis.

所以我第一次給了錯誤的號碼，Elemer。生長激素組的中位數為 10.5。所以我只想澄清一下。我記得 - 它是 10.5。然後，大衛，你可以談談 Ascendis 的基線。

Right. Yes. There is no question that the Ascendis Phase II trial that we're comparing against a 6-month trial enrolled a much more severely GHD population than we did. It wasn't as deficient as the Opko Phase II trial. But significantly -- so the (inaudible) trials and the [Ascendis] trials were pretty comparable than enrolling by 50-50 organic and idiopathic GHD. So their baseline height SDS, it was at least an SD lower than in our trial. IGF1-SDS was lower, Delta mid-parental height is lower. So all in all, in a much more severe population. So we wouldn't expect to see the same growth hormone response in our trial as in either the TransCon trial or the (inaudible) trial that, in fact, it behaved like it was in those populations. That's what's so unusual. And that's why we really feel it's built driven by baseline differences and in a couple of outliers in the trial.

正確的。是的。毫無疑問，我們正在與為期 6 個月的試驗進行比較的 Ascendis II 期試驗招募了比我們嚴重得多的 GHD 人群。它不像 Opko II 期試驗那樣有缺陷。但重要的是 - 所以（聽不清）試驗和 [Ascendis] 試驗與通過 50-50 有機和特發性 GHD 註冊相當可比。所以他們的基線身高 SDS，至少比我們的試驗低一個 SD。 IGF1-SDS 較低，Delta 父母身高中值較低。所以總而言之，在一個更嚴重的人群中。因此，我們不希望在我們的試驗中看到與 TransCon 試驗或（聽不清）試驗相同的生長激素反應，事實上，它的表現就像在那些人群中一樣。這就是不尋常的地方。這就是為什麼我們真的覺得它是由基線差異和試驗中的幾個異常值驅動的。

But baseline height standard deviation -- the baseline height standard deviation score, Elemer for the Ascendis trial was about minus 3.3. Ours is about minus 2. So it's a full standard deviation kind of closer to the mean. So much less growth on a deficient population.

但是基線身高標準差——Ascendis 試驗的 Elemer 基線身高標準差得分約為負 3.3。我們的大約是負 2。所以這是一個更接近平均值的完整標準差。人口不足的增長要少得多。

Thank you. So ladies and gentlemen, at this stage, there are no further questions in the queue. Thank you for joining us and enjoy your day.

謝謝。女士們，先生們，在這個階段，隊列中沒有其他問題了。感謝您加入我們並享受您的一天。