Inhibikase Therapeutics Inc (IKT) 2024 Q2 法說會逐字稿

Greetings and welcome to the Inhibikase Therapeutics second-quarter 2024 financial results conference call.

歡迎參加 Inhibikase Therapeutics 2024 年第二季財務業績電話會議。

(Operator Instructions) As a reminder, this conference is being recorded.

（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, Alex Lobo, Precision AQ, Investor Relations.

現在我很高興向您介紹主持人 Alex Lobo，Precision AQ 投資者關係部門的負責人。

Thank you, sir.

謝謝您，先生。

You may begin.

你可以開始了。

Good morning, and welcome to Inhibikase Therapeutics' second-quarter 2024 financial results conference call and audio webcast.

早安，歡迎收看 Inhibikase Therapeutics 的 2024 年第二季財務業績電話會議和音訊網路廣播。

With me today is Dr. Milton Werner, Chief Executive Officer; and Garth Lees-Rolfe, Chief Financial Officer.

今天與我在一起的是執行長 Milton Werner 博士；和財務長 Garth Lees-Rolfe。

On August 14, Inhibikase issued a press release announcing financial results for the second quarter ended June 30, 2024.

8 月 14 日，Inhibikase 發布新聞稿，宣布截至 2024 年 6 月 30 日的第二季財務業績。

We encourage everyone to read yesterday's press release as well as in Inhibikase quarterly report on Form 10-Q, which has been filed with the SEC.

我們鼓勵大家閱讀昨天的新聞稿以及已向 SEC 提交的 10-Q 表中的 Inhibikase 季度報告。

The company's press release and Form 10-Q are also available on Inhibikase's website and Inhibikase.com. In addition, this conference call is being webcast with the Investor Relations section of the company's website and will be archived there for future reference.

該公司的新聞稿和表格 10-Q 也可在 Inhibikase 網站和 Inhibikase.com 上取得。此外，本次電話會議正在公司網站的投資者關係部分進行網路直播，並將存檔以供日後參考。

Please note that certain information on today's call is covered under the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995.

請注意，今天電話會議中的某些資訊受 1995 年《私人證券訴訟改革法案》的安全港條款管轄。

Participants are cautioned that this conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, August 15, 2024.

請與會者註意，本次電話會議包含時間敏感訊息，僅截至本次直播之日（2024 年 8 月 15 日）準確。

Actual results could differ materially from those stated or implied by these forward-looking statements due to risks and uncertainties associated with the company's business.

由於與公司業務相關的風險和不確定性，實際結果可能與這些前瞻性陳述中明示或暗示的結果有重大差異。

Information on potential risks and uncertainties are set forth in our most recent public filings with the SEC at sec.gov. The company undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this webcast, except as may be required by applicable securities law.

有關潛在風險和不確定性的資訊已在我們最近向 SEC 提交的 sec.gov 公開文件中列出。本公司不承擔修改或更新任何前瞻性聲明以反映本網路廣播日期之後發生的事件或情況的義務，除非適用的證券法可能要求。

With that said, I would like to turn the call over to Dr. Milton Werner.

話雖如此，我想將電話轉給米爾頓·維爾納博士。

Milton, you may begin.

米爾頓，你可以開始了。

Thank you, Alex.

謝謝你，亞歷克斯。

Thank you, everybody, for joining us today to review our second-quarter 2024 financial results and recent clinical and business updates.

感謝大家今天加入我們，回顧我們 2024 年第二季的財務表現以及最近的臨床和業務更新。

We've been very pleased with the strength of our clinical progress of the first half of 2024.

我們對 2024 年上半年的臨床進展感到非常滿意。

The speed at which we executed on key clinical and regulatory milestones has underscored what has been a very successful quarter, marked by the accomplishment of many exciting achievements.

我們在關鍵臨床和監管里程碑上執行的速度突顯了這個季度非常成功，並取得了許多令人興奮的成就。

We recently completed enrollment for our Phase 2 ‘201’ trial for risk adaptive or often referred to as risvo in Parkinson's disease, which is a significant milestone that we have been working carefully towards in an effort to bring results to patients suffering from untreated Parkinson's disease, and we expect to report top line data from the trial in November.

我們最近完成了 201 年風險適應性試驗（通常稱為 risvo）帕金森氏症 2 期試驗的註冊，這是一個重要的里程碑，我們一直在認真努力，努力為患有帕金森氏症的患者帶來結果。未經治療的帕金森氏症，我們預計在11 月報告該試驗的主要數據。

Additionally, we have had a productive engaged with the US FDA over the past few months regarding IkT-001Pros opportunity in pulmonary arterial hypertension or PAH imatinib, the active ingredient that won't grow as previously been shown to be disease modifying PAH and we believe that Pro has the potential to further demonstrate safe and efficacious treatment of PAH patients using our novel prodrug technology.

此外，在過去的幾個月裡，我們與美國FDA 就IkT-001Pros 在肺動脈高壓或PAH 中的機會進行了富有成效的合作，伊馬替尼是一種活性成分，不會像之前被證明具有改變疾病的PAH 那樣生長，我們相信Pro 有潛力進一步證明使用我們的新型前藥技術對 PAH 患者進行安全有效的治療。

We filed the IND for PAH and plan to open clinical development with a derisking Phase IIb study as soon as practicable.

我們提交了 PAH 的 IND 申請，並計劃盡快透過消除風險的 IIb 期研究開啟臨床開發。

Let me take we'll take a deeper dive into each of these programs as we expect the back half of 2024 will be a catalyst-rich period.

我假設我們將更深入地研究每個項目，因為我們預計 2024 年下半年將是一個充滿催化劑的時期。

Let me first start with regard to the result is a potent selective inhibitor of (inaudible) that is administered once daily that we believe may slow or halt the progression of Parkinson's disease.

讓我先談談結果是一種有效的選擇性抑制劑（聽不清楚），每天服用一次，我們相信它可以減緩或阻止帕金森氏症的進展。

Our 201 trial was a two phased trial with a 12 week double-blind study across three doses plus placebo for which enrollment has been completed.

我們的 201 試驗是一項兩階段試驗，為期 12 週的雙盲研究，涉及三種劑量加安慰劑，已完成入組。

As of July 29, 41, mild and moderate adverse events have been observed that may be related to (inaudible) We've had six people withdraw from the trial without completing 12 weeks of dosing.

截至 2041 年 7 月 29 日，已觀察到可能與（聽不清楚）有關的輕度和中度不良事件。

Looking ahead, we expect to report top line growth results evaluating the safety and tolerability results in untreated Parkinson's disease in November of this year, following completion of the 12-week double-blind period, we anticipate meeting with the FDA by year's end to discuss our plans for Phase 3 and intend to launch a 12-month open-label extension study as soon as possible.

展望未來，我們預計在今年 11 月報告頂線成長結果，評估未經治療的帕金森氏症的安全性和耐受性結果，在完成 12 週雙盲期後，我們預計在年底前與 FDA 會面討論我們的第三階段計畫並打算盡快啟動為期12 個月的開放標籤擴展研究。

Moving now to IkT-001Pro, our pro-drug formulation of imatinib of late that has been designed to potentially improve the safety and tolerability profile of demanded.

現在轉向 IkT-001Pro，這是我們最近的伊馬替尼前藥製劑，旨在潛在地提高所需的安全性和耐受性。

We continue to make significant strides in the advancement of the prodrug through our ongoing discussions with the FDA to receive final meeting minutes for our pre-IND meeting for pulmonary arterial hypertension in May and file the IND on August 9 to open clinical development later this year, subject to the receipt of the study may proceed letter from the agency.

透過與FDA 的持續討論，我們繼續在前藥的進展方面取得重大進展，以獲得5 月份肺動脈高壓IND 前會議的最終會議紀要，並於8 月9 日提交IND，以便在今年晚些時候啟動臨床開發，以收到該機構的研究信函為前提。

PAH is a rare disease of pulmonary microvasculature.

PAH是一種罕見的肺微血管疾病。

PAH can arise spontaneously or can be caused by genetic mutations by drugs or environmental toxins.

PAH 可以自發性產生，也可以由藥物或環境毒素引起的基因突變引起。

PAH is also associated with connective tissue disease, congenital heart disease, HIV infection and other insults that could affect the right side of the heart.

PAH 也與結締組織疾病、先天性心臟病、愛滋病毒感染和其他可能影響右心的損傷有關。

Most treatments for PAH attempt to address symptoms of this progressive disorder.

大多數 PAH 治療都試圖解決這種進行性疾病的症狀。

With the recent approval of [sotatercep] highlights that disease modification is possible.

最近 [sotatercep] 的批准凸顯了疾病改變是可能的。

We see tremendous opportunity in PAH, which has a global market valued at [7.7 billion] annually worldwide imatinib, the active ingredient Pro has already been shown to be disease-modifying more than 10 years ago, but the side effect profile observed at that time precluded approval.

我們在 PAH 領域看到了巨大的機遇，全球市場每年價值 77 億伊馬替尼，其活性成分 Pro 在 10 多年前就已被證明具有緩解疾病的作用，但當時觀察到的副作用排除批准。

We believe that Pro has the potential to achieve similar potency to imatinib investment without the side effect profile that disqualify imatinib from approval studies reported in 2010.

我們相信，Pro 有潛力實現與伊馬替尼投資類似的功效，且不會出現導致伊馬替尼無法獲得 2010 年批准研究報告資格的副作用。

Based on our constructive discussions with the FDA, we believe that we have alignment on our proposed Phase IIb trial design and at the [pre-NDA] meeting the FDA confirmed that 001Pro would be viewed as a new molecular entity for PAH and that the appropriate path for approval appears to be (inaudible) to the public diabetes status.

基於我們與 FDA 的建設性討論，我們相信我們與提議的 IIb 期試驗設計保持一致，並且在 [NDA 前]會議上 FDA 確認 001Pro 將被視為 PAH 的新分子實體，並且適當的批准的途徑似乎是（聽不清楚）公眾糖尿病狀況。

Further following the advice provided in our pre NDA meeting with the FDA in January, we have scaled our manufacturing and process development efforts for Pro to support late-stage clinical development and NDA batch requirements activities include development of new dosage forms to differentiate 001Pro tablets from generic demand domestically in alignment with the FDA feedback.

進一步遵循我們在一月份與FDA 舉行的NDA 前會議上提供的建議，我們擴大了Pro 的製造和製程開發工作，以支援後期臨床開發和NDA 批次要求活動，包括開發新劑型以區分001Pro 片劑和國內的一般需求與 FDA 的回饋一致。

Finally, turning to reasonable multiple system atrophy or MSA.

最後，轉向合理的多系統萎縮或 MSA。

We are currently exploring alternative financing opportunities, including potential grant funding through a new funding mechanism of clinical development in neuroscience from the National Institute of neurological diseases and stroke or NINDS.

我們目前正在探索替代融資機會，包括透過國家神經疾病和中風研究所或 NINDS 神經科學臨床開發新資助機制提供潛在的資助。

We look forward to advancing this program forward and providing further updates as on the program as appropriate.

我們期待著推進該計劃並酌情提供有關該計劃的進一步更新。

Separately, we are also developing new antibody diagnostic and clinical biomarker tools that we believe will further differentiate the company's efforts in Parkinson's disease and enable analysis of both target engagement and potentially disease modification.

另外，我們也正在開發新的抗體診斷和臨床生物標記工具，我們相信這些工具將進一步使公司在帕金森氏症方面的努力與眾不同，並能夠對目標參與和潛在的疾病修飾進行分析。

Both of these efforts are being pursued through to grant applications that are under review by the NINDS.

這兩項努力正在透過 NINDS 審查的撥款申請進行。

I'd like to now turn the call over to our Chief Financial Officer, Garth Lees-Rolfe, to review our financial results for the quarter.

我現在想將電話轉給我們的財務長 Garth Lees-Rolfe，以審查我們本季的財務表現。

Garth?

加斯？

Thank you, Milton, and Inhibikase, we remain committed to being good stewards of capital as we advance multiple high-value programs in both neurodegenerative and cardiopulmonary disease.

謝謝 Milton 和 Inhibikase，在我們推進神經退化性疾病和心肺疾病領域的多個高價值項目的同時，我們仍然致力於成為良好的資本管理者。

As we approach multiple inflection points this year, we are pleased to bolster our balance sheet in May, raising $4 million in aggregate gross proceeds from our registered direct offering and concurrent private placement.

隨著今年我們接近多個拐點，我們很高興在 5 月加強了我們的資產負債表，透過我們的註冊直接發行和同步私募籌集了 400 萬美元的總收益。

These funds extend our cash runway into December 2024 and are sufficient to see us through top line data for our 201 trial in Parkinson's disease.

這些資金將我們的現金跑道延長至 2024 年 12 月，足以讓我們了解 201 項帕金森氏症試驗的頂線數據。

Now I'd like to take a moment to review highlights from our financial results for the quarter ended June 30, 2024.

現在我想花點時間回顧一下我們截至 2024 年 6 月 30 日的季度財務表現的要點。

Net loss for the quarter ended June 30, 2024 was $5.0 million or $0.66 per share compared to a net loss of $5.8 million or $0.94 per share for the quarter ended June 30, 2023.

截至 2024 年 6 月 30 日的季度淨虧損為 500 萬美元，即每股 0.66 美元，而截至 2023 年 6 月 30 日的季度淨虧損為 580 萬美元，即每股 0.94 美元。

Research and development expenses for the quarter ended June 30, 2024 were $3.1 million compared to $4.5 million for the same period in 2023.

截至 2024 年 6 月 30 日的季度研發費用為 310 萬美元，而 2023 年同期為 450 萬美元。

For $1.5 million decrease in research and development expenses, it was due to a decrease of $1.4 million in IkT-001Pro expenses due to the completion of a three-part dose finding dose equivalent study in 2023 and a net decrease of $0.1 million in other research and development expenses.

研發費用減少 150 萬美元，原因是 IkT-001Pro 費用因 2023 年完成的三部分劑量尋找劑量當量研究而減少 140 萬美元，以及其他研究淨減少 10 萬美元和開發費用。

Selling, general and administrative expenses for the quarter ended June 30, 2024 were $2.0 million compared to $1.8 million for the same period in 2023.

截至 2024 年 6 月 30 日的季度的銷售、一般和管理費用為 200 萬美元，而 2023 年同期為 180 萬美元。

The $0.2 million increase was primarily driven by a $0.4 million increase in legal and consulting fees, partially offset by $0.1 million decrease in D&O insurance and a $0.1 million net decrease in all other normal selling, general and administrative expenses.

增加 20 萬美元主要是由於法律和諮詢費用增加 40 萬美元，部分被 D&O 保險減少 10 萬美元以及所有其他正常銷售、一般和管理費用淨減少 10 萬美元所抵消。

As of June 30, 2024, we had $7.9 million in cash, cash equivalents and marketable securities.

截至 2024 年 6 月 30 日，我們擁有 790 萬美元的現金、現金等價物和有價證券。

We expect that existing cash and cash equivalents will be sufficient to fund operations into December 2024.

我們預計現有現金和現金等價物將足以為 2024 年 12 月之前的營運提供資金。

That concludes our review of the -- of our financial statements.

我們對財務報表的審查到此結束。

I'd like to hand the call back over to Milton for closing remarks.

我想將電話轉回米爾頓做總結發言。

Thank you Garth.

謝謝你加斯。

We expect the back half of the year will accelerate the momentum that we've seen through the first half.

我們預計今年下半年將加速上半年的動能。

We're proud of the hard work put in by our clinical investigators across multiple trial sites, and we appreciate the continued support we receive from our dedicated shareholders.

我們為我們的臨床研究人員在多個試驗地點所做的辛勤工作感到自豪，我們感謝我們熱心股東的持續支持。

We have multiple exciting near-term milestones we expect to achieve, including top line data from our Tier 1 trial in Brazil, occupancies anticipate the opening of clinical development of IkT-001Pro in PAH that will further differentiate a pipeline of neurological and cardio pulmonary assets.

我們預計將實現多個令人興奮的近期里程碑，包括來自巴西一級試驗的頂線數據，預計 IkT-001Pro 在 PAH 中的臨床開發將進一步開展，這將進一步區分神經和心肺資產的管道。

I'd like to now open the call to questions.

我現在想開始提問。

Operator?

操作員？

Thank you.

謝謝。

We will now be conducting a question-and-answer session.

我們現在將進行問答環節。

(Operator Instructions)

（操作員說明）

Jason McCarthy, Maxim Group.

傑森麥卡錫，馬克西姆集團。

Good morning Milton, thank you for taking the question.

早上好，米爾頓，謝謝你提出問題。

As far as the risvo Phase 2 study in the last update back in June, around 70 people had completed the 12 weeks.

根據 risvo 2 期研究在 6 月的最後一次更新，大約 70 人完成了 12 週的研究。

You completed enrollment?

你完成報名了嗎？

Obviously the data is coming in November and you had mentioned starting up the 12 month OLE, is there going to be some lag time between when patients complete this trial and when they have the option to move to the OLE and is there the potential that they might opt for symptomatic treatment during that time?

顯然，數據將於 11 月發布，您提到啟動 12 個月的 OLE，患者完成這項試驗與他們可以選擇轉移到 OLE 之間是否會有一些滯後時間，他們是否有可能在此期間可能會選擇症狀治療？

Well, so the answer is that's already been occurring.

嗯，答案是這種情況已經發生了。

I believe currently 89 people are completed in the trial that leaves 31 total who are still on medication.

我相信目前已有 89 人完成了試驗，剩下 31 人仍在接受藥物治療。

And the last person elected the trial in late September.

最後一個人選擇在9月下旬進行審判。

Because it's an ongoing trial, we've had people that have completed treatment or 12 weeks as long as 12, 9 months ago.

因為這是一項正在進行的試驗，我們已經有人在 12、9 個月前就完成了治療或 12 週的治療。

I believe it's the oldest patients we have in the trial.

我相信這是我們試驗中年紀最大的患者。

And while we have been trying to get the early study running in full force.

儘管我們一直在努力讓早期研究全面展開。

We've done all of the preparative work, we've completed now all the regulatory steps as well as the ethics review board steps.

我們已經完成了所有準備工作，現在已經完成了所有監管步驟以及道德審查委員會步驟。

We've had some financial constraints, but I think those are mostly been worked out now.

我們遇到了一些財務限制，但我認為這些問題現在已經解決了。

And I hope (inaudible) will be formally launched in the coming couple of months.

我希望（聽不清楚）將在未來幾個月內正式推出。

At least that's our current thinking.

至少這是我們目前的想法。

And so yes, it has a potential impact on patients, some of whom because of the progression of their disease following 12 weeks of this reduction of treatment, we may go onto symptomatic meds and we are tracking the number of people who have done that.

所以，是的，它對患者有潛在的影響，其中一些患者在減少治療 12 週後病情進展，我們可能會繼續使用對症藥物，我們正在追蹤這樣做的人數。

So far, it's been a small group, the patient experience, at least what we hear anecdotally from the sites has been extremely positive on the drug.

到目前為止，這只是一個小群體，患者的體驗，至少我們從網站上聽到的軼事，對該藥物非常積極。

That doesn't necessarily mean anything.

這並不一定意味著什麼。

It just means the drug would make them feel badly.

這只是意味著藥物會讓他們感覺很糟。

So that's a good sign.

所以這是一個好兆頭。

But we don't draw any conclusions from that kind of anecdotal commentary, and we'll be communicating this month with all of the sites about the time lines we anticipate for launching the 12-month study with full force.

但我們不會從這種軼事評論中得出任何結論，本月我們將與所有網站溝通我們預計全力啟動為期 12 個月的研究的時間表。

And some of the people who trial may actually be on symptomatic meds.

一些接受試驗的人實際上可能正在服用對症藥物。

As Jason, most of these extension studies are there to develop and begin to collect a safety database.

作為傑森，大多數擴展研究都是為了開發並開始收集安全資料庫。

And so in our view, we also wanted to have as much measurement in the absence of some domestic men's as we can at least at the last measurement point we have about a week-and-a-half ago, very few people have gone through dramatic, meds, given the number of people in the trial.

因此，在我們看來，我們也希望在沒有一些國內男性的情況下進行盡可能多的測量，至少在大約一個半星期前的最後一次測量點上，很少有人經歷過考慮到參與試驗的人數，藥物的作用是戲劇性的。

And so if this thing launches in the time frame we're now thinking -- we should get most of the people who have not started symptomatic beds and some who have, which will help us learn whether people on symptomatic medications tolerate the addition of risk reduction as well.

因此，如果這件事在我們現在考慮的時間範圍內啟動——我們應該讓大多數尚未開始使用症狀床的人和一些已經開始使用症狀床的人，這將幫助我們了解接受對症藥物治療的人是否能夠忍受增加的風險減少也。

And what additional benefit that it might have can't be clean because there's no control group.

它可能有什麼額外的好處，因為沒有對照組，所以無法明確。

But nonetheless, we'll be able to see if there's any effect one way or another on the benefit of symptomatic therapy itself.

但儘管如此，我們將能夠看看對症治療本身的益處是否會以某種方式產生任何影響。

So it could be ultimately informative.

所以它最終可能會提供豐富的資訊。

Thank you.

謝謝。

And so when you think about the Phase 3 program, would that entail two studies?

那麼，當您考慮第三階段計劃時，這是否需要兩項研究？

And would you be looking to go out beyond 3 months to 12 to 18 months targeting avoidance of use of symptomatic treatments is that the goal?

您是否希望外出 3 個月至 12 至 18 個月以上，以避免使用症狀治療為目標？

Right.

正確的。

So Parkinson's disease.

所以帕金森氏症。

So even though we are evaluating on treating Parkinson's disease, that's not a subgroup of patients.

因此，儘管我們正在評估帕金森氏症的治療，但這並不是患者亞群。

We're evaluating untreated Parkinson's disease because we believe risvodetinib is model therapy and disease modifying.

我們正在評估未經治療的帕金森氏症，因為我們相信 risvodetinib 是模型療法和疾病修飾療法。

Although we have not proven yet that it's disease modifying of the disease, that's what all of our preclinical and (inaudible) model data informs us about.

儘管我們尚未證明它可以改變疾病，但這就是我們所有的臨床前和（聽不清楚）模型數據告訴我們的資訊。

So we want to evaluate risvodetinib even in Parkinson's without any confounding components of other symptomatic therapy.

因此，我們希望即使在帕金森氏症中也能評估 risvodetinib，而不需要與其他對症治療產生任何混雜成分。

We've developed patient recruitment tools that are just in our view spectacular, we don't think we'll have any trouble recruiting.

我們開發了在我們看來非常出色的患者招募工具，我們認為我們在招募方面不會遇到任何困難。

The patient population will need 300 or so patients, rough guess for a pair of Phase 3 studies.

根據兩項 3 期研究的粗略猜測，患者群體將需要 300 名左右的患者。

And it would have to be a pair of studies unless some miracle happens, because you must do that for such a large market opportunity there's just too many patients out there.

除非出現奇蹟，否則這必須是兩項研究，因為你必須這樣做才能獲得如此大的市場機會，因為那裡有太多的患者。

It's about a rare disease where occupancies.

這是關於一種罕見的疾病。

So there will be two Phase 3 trials.

因此將有兩個第三階段試驗。

They will be dosed for up to 12 months.

他們的用藥時間長達 12 個月。

Historically, people -- in every other trial that has been run in the space of medications that were intended to alter the course of disease have failed with virtually no exceptions.

從歷史上看，在旨在改變病程的藥物領域進行的所有其他試驗中，人們幾乎無一例外地失敗了。

The one possible exception was a GLP-1 a related molecule last year from that was reported earlier this year or early part of this year.

一個可能的例外是去年早些時候或今年早些時候報導的 GLP-1 相關分子。

That seemed to slow motor dysfunction in the absence of anything else, but people were on motor on symptomatic therapy even in that trial.

在沒有任何其他措施的情況下，這似乎可以減緩運動功能障礙，但即使在那次試驗中，人們仍然在接受症狀治療。

So in our case, we're going to be rolling a significant number of people that will be a 12-month dosing trial.

因此，在我們的案例中，我們將對大量人員進行為期 12 個月的劑量試驗。

They'll be two trials running at the same time, it will be global.

他們將同時進行兩項試驗，這將是全球性的。

Got it.

知道了。

And you said you had or we are near alignment with FDA on the Phase IIb for PAH, can you provide us any details on the size and scope of that study or is that forthcoming still?

您說您已經或我們接近與 FDA 就 PAH 的 IIb 期臨床試驗達成一致，您能否向我們提供有關該研究的規模和範圍的任何詳細信息，或者該研究是否仍在進行中？

No, I think it's probably okay to give you just a rough idea.

不，我想給你一個粗略的想法可能沒問題。

So we initially imagined this to have an initial safety run-in, so that we could confirm that with pro drug at the appropriate doses in a properly enrolled trial where we're really looking carefully at the patient enrollment and the degree of visibility of the individual patients have that we could have people to trial that have a real unmet medical need and could actually do all the tasks that the trial would require and run a Phase 3 read in the Back end.

因此，我們最初設想這是一個初步的安全磨合，這樣我們就可以在一項正確入組的試驗中確認使用適當劑量的前體藥物，在該試驗中，我們確實仔細研究了患者入組情況以及藥物的可見度。

But as we thought through the process, it makes more sense to have a de-risking trial first.

但當我們仔細思考整個過程時，先進行去風險試驗更有意義。

So that's formally a Phase IIb.

這就是正式的 IIb 期。

It's roughly 100 patients in two doses in a placebo, placebo control.

大約 100 名患者服用了兩劑安慰劑，即安慰劑對照。

We're going to do a 12 week probably we plan to do a 12 week safety review when half the patients have been enrolled and completed 12 weeks of dosing.

我們將進行為期 12 週的安全審查，可能我們計劃在一半患者已入組並完成 12 週的給藥後進行為期 12 週的安全性審查。

And then we'll do a futility analysis, what happens people have completed 24 weeks, which is the length of measurement duration.

然後我們會做一個無用性分析，人們完成24週後會發生什麼，這是測量持續時間的長度。

So the trial itself will be is designed to look carefully at safety to make sure that in with a fresh view and a fresh approach and a pro-drug that has the potential to really change the tolerability and safety profile of imatinib itself.

因此，試驗本身的設計將仔細考慮安全性，以確保採用新的觀點、新的方法和前藥，有可能真正改變伊馬替尼本身​​的耐受性和安全性。

That we'll be able to overcome the very unfortunate side effect profile that disqualify demanded from approval 15 years.

我們將能夠克服非常不幸的副作用，該副作用要求 15 年內取消批准資格。

And at that point, it's a rare disease.

從那時起，這是一種罕見的疾病。

If we see the efficacy that was previously proven (inaudible) combined with safety that could be adequate in principle to seek approval on a conditional basis to support going into Phase 3, if approval cannot be sought on a basis depending on the overall benefit and safety profile we observed, et cetera.

如果我們看到先前已證明的功效（聽不清楚）與安全性相結合，則原則上足以尋求有條件批准以支持進入第 3 階段，如果無法根據總體效益和安全性尋求批准我們觀察到的輪廓等等。

So the IND has been filed, of course, this trial design has already been reviewed by the FDA.

那麼IND已經備案了，當然這個試驗設計已經經過FDA的審查了。

And that wasn't part of their concerns in terms of designing a trial and bringing this drug forward again.

這並不是他們在設計試驗和再次推出這種藥物時所關心的部分。

And so we're pretty confident that the IND is going to clear naturally, of course, pro-drug has been in people.

因此，我們非常有信心 IND 會自然清除，當然，前驅藥物已經存在於人體內。

It was reviewed by a cancer division.

它由癌症部門進行了審查。

We've already had pre-NDA discussion with the cancer -- in one of the cancer divisions.

我們已經在癌症部門之一進行了 NDA 前與癌症的討論。

So this little, it seems unlikely that there would be any issues that arise from the review by the cardiology division about leading the study go-forward.

因此，心臟病學部門對領導研究進展的審查似乎不太可能出現任何問題。

Great.

偉大的。

Thank you, Milton.

謝謝你，米爾頓。

Ed White, H.C. Wainwright.

懷特，H.C.溫賴特。

Good morning.

早安.

Thanks for taking my questions, but just wanted to get a little bit more clarification on risvo at Milton.

感謝您提出我的問題，但我只是想進一步了解 Milton 的 risvo。

What do you want to see from the top line data that you're going to get in November to proceed to the Phase 3?

您希望從 11 月獲得的主要數據中看到什麼以進入第三階段？

And then just can you clarify this 300 patients for both trials, so 150 each?

那麼能否澄清一下這兩項試驗都有 300 名患者，即每項 150 名患者？

Or is it 300 patients per trial that you're thinking of for the Phase 3?

還是您考慮的第 3 階段試驗是每次試驗 300 名患者？

(inaudible) with the second question first.

（聽不清楚）先回答第二個問題。

It's somewhere between -- I believe I'm just taking this off the top of my head because we're still refining the trial design.

它介於兩者之間——我相信我只是把這個問題拋在腦後，因為我們仍在完善試驗設計。

It's about 300 to 300 -- between 300 and 400 patients to cover both trials.

這兩項試驗大約需要 300 到 300 名（300 到 400 名）患者。

It depends on the effect size that will ultimately shoot for the trial.

這取決於最終進行試驗的效果大小。

We need to see the unblinded data in November to finalize our view of project size.

我們需要看到 11 月的非盲數據才能最終確定我們對專案規模的看法。

But we believe between 300 and 400 should cover the needs for both trials, at least at current thinking.

但我們認為 300 到 400 之間應該可以滿足這兩項試驗的需求，至少目前認為是這樣。

In terms of what we might expect to see in November, you know, the -- when the trial was originally established, no one would have thought that 12 weeks of treatment would be adequate to see a very substantial impact on the course of the patient's disease.

In terms of what we might expect to see in November, you know, the -- when the trial was originally established, no one would have thought that 12 weeks of treatment would be adequate to see a very substantial impact on the course of the patient's疾病.

We worked very hard with the design of the Tier 1 trial to make sure that we have a fairly uniform population of people enrolled who have not taken symptomatic medications who have very significant disability measured by a set of Parkinson's disease assessments.

我們非常努力地設計一級試驗，以確保我們的入組人群相當一致，這些人沒有服用對症藥物，並且透過一系列帕金森氏症評估來衡量患有非常嚴重的殘疾。

The same type we're using in our secondary endpoints and tried to have that group to be roughly the same level of disability across most people.

我們在次要終點中使用了相同的類型，並試圖讓該群體與大多數人的殘疾程度大致相同。

We've previously presented at Parkinson's disease related meetings that our baseline scores were very substantial part threes were in the 30s -- excuse me, mid 20s.

我們之前在帕金森氏症相關會議上曾表示，我們的基線分數非常可觀，三分之二是 30 多歲——對不起，是 20 多歲。

Part two scores of the UPDRS were in the mid tens.

UPDRS 的第二部分得分在 10 左右。

That's a very substantial disability and that would allow us to see whether 12 weeks of treatment could show any effect on motor or non-motor features of disease by a variety of measures, including measures in the gastrointestinal tract one of the primary organs of disease.

這是一個非常嚴重的缺陷，這將使我們能夠透過多種措施（包括對疾病的主要器官之一胃腸道的測量）來了解12 週的治療是否可以對疾病的運動或非運動特徵產生任何影響。

As the data has evolved, we've remained very encouraged as we see what the measurements in patients have been like.

隨著數據的不斷發展，當我們看到患者的測量結果時，我們仍然感到非常鼓舞。

Of course, it's blinded data we don't know what that means.

當然，這是盲數據，我們不知道這意味著什麼。

We've done the same with biomarker measurements, which have further made us feel encouraged by what could be coming.

我們對生物標記測量也做了同樣的事情，這進一步讓我們對即將發生的事情感到鼓舞。

Again, that's just hypothetical stuff.

再說一遍，這只是假設的東西。

You don't know what you're going to see until it's unblinded, but that combination of seeing trends across one or more assessments, coupled with the potential of seeing an effect on the underlying protein pathology itself through our biomarker studies inside and outside of the central nervous system.

在揭盲之前，你不知道自己會看到什麼，但透過一項或多項評估的趨勢觀察，再加上透過我們內外的生物標記研究，有可能看到對潛在蛋白質病理學本身的影響。

I think will give us a very robust support, even though it's only 12 weeks has the potential of giving us very robust support to go directly into Phase 3 without further studies.

我認為這將為我們提供非常強有力的支持，儘管只有 12 週，但有潛力為我們提供非常強有力的支持，無需進一步研究即可直接進入第 3 階段。

The followed the open-label extension study, which we hope to we will be fully launched, perhaps in a couple of months more time because of both aspects of getting the whole thing, fully functional across 32 sites in the US will remain an important aspect of this as we continue to gain safety and patient safety, tolerability experience at different doses now using our tablet dosage form, which we made public about a year ago, which has a better delivery profile compared to the current profile uses to one trial.

接下來是開放標籤擴展研究，我們希望我們能夠全面啟動該研究，也許需要幾個月的時間，因為在美國 32 個站點上獲得完整功能的兩個方面仍然是一個重要方面隨著我們繼續獲得安全性和患者安全性，現在使用我們的片劑劑型在不同劑量下的耐受性經驗，我們大約一年前公開了該劑型，與一次試驗中使用的當前配置文件相比，它具有更好的交付設定檔。

And so we'll be very well positioned for Phase 3, hoping that between the FDA meeting and our other efforts sometime in the latter half of next year that those trials could launch, which would just be with the assumption that you do something by the fourth quarter of next year.

因此，我們將為第三階段做好準備，希望在 FDA 會議和我們的其他努力之間，在明年下半年的某個時候，這些試驗能夠啟動，這只是假設你按照明年第四季度。

Just hypothetically speaking, it's roughly four years from ground zero, it's a pretty fast development program and a very large market opportunity.

只是假設地說，從零開始大約需要四年時間，這是一個相當快的開發計劃和一個非常大的市場機會。

I think that this reflects the smoothness with which we estimate has continued to show a good patient safety and tolerability profile.

我認為這反映了我們估計的平穩性繼續顯示出良好的患者安全性和耐受性。

And in November, we'll learn whether we also see the indications that it's having an impact on disease, even if the plan impact is small as one might expect for a 12 week dosing study, seeing anything at all in 12 weeks would be very surprising.

11 月，我們將了解是否也看到了它對疾病產生影響的跡象，即使計劃影響很小，正如人們對12 週劑量研究所預期的那樣，在12 週內看到任何東西都將是非常大的。

So but we're encouraged by what we're seeing emerging in the trial overall.

因此，我們對整個試驗中出現的情況感到鼓舞。

Okay.

好的。

Thanks, Milton.

謝謝，米爾頓。

And then just on, 001Pro, what are your expectations for IND clearance?

那麼，001Pro，您對 IND 審批有何期望？

Are there are there any gating factors to start this trial or for locating sites, manufacturing of drug and gating factors at all that could delay the start of that trial?

是否有任何啟動該試驗的門控因素，或者是否有任何可能延遲該試驗開始的場地定位、藥物生產和門控因素？

And when do you expect to see it start.

您預計什麼時候開始？

So from the patient population for pulmonary hypertension is a really delicate patient population.

所以從肺動脈高壓的患者族群來看，是一個非常脆弱的患者族群。

They're literally dying as they're being enrolled.

當他們被錄取時，他們真的快要死了。

It's a rapidly fatal disease and as a consequence, you really have to be mindful of all of those factors.

這是一種迅速致命的疾病，因此，您確實必須注意所有這些因素。

In addition, because these patients are dying and we're working with a medication that's already proven to be effective.

此外，因為這些患者即將死亡，而我們正在研究一種已被證明有效的藥物。

Once you start dosing them every patient, you have to be able to roll every patient into an extension study for as long as it takes to get to approval.

一旦開始對每位患者進行給藥，您就必須能夠將每位患者納入擴展研究，直到獲得批准為止。

So you're never losing the patient along that path.

所以沿著這條路你永遠不會失去病人。

That creates a lot of infrastructure challenges to build up.

這給基礎設施建設帶來了許多挑戰。

We think it's going to take approximately 9 to 12 months to gear up the whole trial, rough guess as we start to think through this process and put in the elements of the execution of that trial in place and we know all the sites fortunately, they're recent study of the approved drug (inaudible) , which was developed by [Acceleron] and then approved by Merck following their acquisition of Acceleron in 2021.

我們認為準備整個試驗大約需要 9 到 12 個月，粗略猜測，因為我們開始思考這個過程並將執行該試驗的要素落實到位，幸運的是我們知道所有站點，它們這是對已批准藥物（聽不見清）的最新研究，該藥物由[Acceleron] 開發，並在2021 年收購Acceleron 後獲得默克公司的批准。

Gives us a lot of insight into sites worldwide that should be used for the study that have a good flow of patients, the right patient characteristics.

讓我們深入了解全球範圍內應該用於研究的站點，這些站點具有良好的患者流量和正確的患者特徵。

And one of the big advantages we have is that just as we've done in Parkinson's disease, where rather than have an internal medical team that has some experience in the disease area, we build the relationship with the leading clinical and scientific investigators worldwide, and they work into the main company in Parkinson's disease.

我們擁有的一大優勢是，就像我們在帕金森氏症方面所做的那樣，我們不是擁有在該疾病領域有一定經驗的內部醫療團隊，而是與全球領先的臨床和科學研究人員建立了關係，他們在帕金森氏症的主要公司工作。

We've now done the same thing in pulmonary hypertension with the two leading investigators worldwide, very close the session with the company now preclinical studies that allows us to also pick sites that are well understood led by proper clinical investigators who both can do trial work and understand the patient population well, and there are a whole bunch of other features that in the future will we'll have an opportunity to discuss that we think will also make the trial run efficiently.

我們現在與世界各地的兩位主要研究人員在肺動脈高壓方面做了同樣的事情，與該公司現在的臨床前研究非常接近，這使我們還可以選擇由適當的臨床研究人員領導的充分理解的地點，他們都可以進行試驗工作並充分了解患者群體，還有一大堆其他功能，將來我們將有機會討論這些功能，我們認為這些功能也將使試驗有效運作。

Of course, the biggest factor is capital.

當然，最大的因素還是資本。

We have reported yesterday, we have about 9 -- $8 million in cash at the moment, not adequate to do trials at this time obviously, and that's another aspect that we'll have to improve on if we're going to execute this trial at all.

我們昨天報道過，我們目前有大約 9 - 800 萬美元的現金，顯然不足以在此時進行試驗，如果我們要執行此試驗，這是我們必須改進的另一個方面根本不。

And but we believe that as we work towards building up the trial aspects though, we'll see opportunities to have the trial properly funded and support that work because one of the real advantages what's gotten us excited about this opportunity, having created a pro-drug.

And but we believe that as we work towards building up the trial aspects though, we'll see opportunities to have the trial properly funded and support that work because one of the real advantages what's gotten us excited about this opportunity, having created a pro-藥物.

This imatinib has already been shown to work.

這種伊馬替尼已經被證明有效。

We have a number of data points, both in the preclinical toxicology setting as well as some information from the clinical studies we've done with Pro that supports our belief that pro drug may be better tolerated form of imatinib.

我們有許多數據點，包括臨床前毒理學環境以及我們使用 Pro 進行的臨床研究的一些信息，這些信息支持我們的信念，即前體藥物可能是伊馬替尼的更好耐受形式。

We understand the dosing from the bioequivalence study as we've previously discussed, in settings like this and in our press releases, et cetera.

正如我們之前在這樣的環境和我們的新聞稿等中討論過的，我們從生物等效性研究中了解了劑量。

And that combination gives you a high chance a high probability.

這種組合給你很大的機會。

You're going to be successful overall and overcome the safety concerns that existed with imatinib therapy 15 years ago.

您將取得整體成功，並克服 15 年前伊馬替尼療法存在的安全問題。

And so when all those pieces come together, the trial will find its natural home and a natural source of capital

因此，當所有這些部分組合在一起時，試驗就會找到它的自然歸宿和自然的資本來源

(inaudible)

（聽不清楚）

Okay.

好的。

Milton.

米爾頓.

Thank you for taking my questions.

感謝您回答我的問題。

(inaudible)

（聽不清楚）

We have reached the end of the question-and-answer session.

我們的問答環節已經結束。

This concludes today's teleconference.

今天的電話會議到此結束。

You may disconnect your lines at this time.

此時您可以斷開線路。

Thank you for your participation.

感謝您的參與。