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Rapport Therapeutics Presents Data Demonstrating Consistent Association Between Decreases in RNS Measured Long Episodes and Meaningful Reductions in Clinical Seizures

Rapport Therapeutics Presents Data Demonstrating Consistent Association Between Decreases in RNS Measured Long Episodes and Meaningful Reductions in Clinical Seizures

Rapport Therapeutics 提供的數據表明,持續減少測量的 RNS 長時間發作與臨床癲癇發作的顯著減少之間存在一致的關聯。
GlobeNewswire ·  12/07 01:01

A 30% reduction in long episodes was shown to be associated with a 50% or greater reduction in clinical seizures in a post-hoc analysis, validating the biomarker for proof-of-concept studies

在事後分析中,30%的長時間發作減少與臨床癲癇發作降低50%或更多相關,驗證了用於概念板塊研究的生物標誌物。

Change in long episode frequency is the primary endpoint for Rapport's ongoing Phase 2a proof-of-concept trial in focal epilepsy, with topline data expected in mid-2025

長時間發作頻率的變化是Rapport目前進行的2a期概念板塊試驗在局竈性癲癇中的主要終點,預計在2025年中期公佈頂線數據。

Data from additional studies, including preclinical seizure data and Phase 1 pharmacokinetic and safety trial results, support the potential of RAP-219 as a transformational treatment for patients with focal epilepsy

來自額外研究的數據,包括臨床前癲癇發作數據和1期藥代動力學與安全性試驗結果,支持RAP-219作爲局竈性癲癇患者的變革性治療的潛力。

BOSTON and LOS ANGELES, Dec. 06, 2024 (GLOBE NEWSWIRE) -- Rapport Therapeutics, Inc. (Nasdaq: RAPP), a clinical-stage biotechnology company dedicated to the discovery and development of small molecule precision medicines for patients suffering from central nervous system (CNS) disorders, presents novel findings on the association between a seizure biomarker used in the Company's proof-of-concept trial for RAP-219 and clinical seizures. The analysis demonstrated a linear relationship between changes in long episode (LE) frequency and clinical seizure frequency and identified the benchmark to predict clinically meaningful seizure reduction. Rapport is presenting the data at the American Epilepsy Society (AES) Annual Meeting in Los Angeles, December 6-10.

波士頓和洛杉磯,2024年12月06日(環球Newswire)-- Rapport Therapeutics, Inc.(納斯達克:RAPP),一家致力於爲中樞神經系統(CNS)疾病患者發現和開發小分子精準藥物的臨床階段生物技術公司,公佈了關於該公司RAP-219概念板塊試驗中使用的癲癇發作生物標誌物與臨床癲癇發作之間關聯的新發現。分析表明,長時間發作(LE)頻率變化與臨床癲癇發作頻率之間存在線性關係,並確定了預測臨床意義上的癲癇發作減少的基準。Rapport將在2024年12月6-10日在洛杉磯舉行的美國癲癇學會(AES)年會上展示該數據。

Patients with refractory focal epilepsy who met the enrollment criteria for the ongoing RAP-219 proof-of-concept trial were selected from NeuroPace's long-term study database for this post-hoc analysis. LEs, recorded through intracranial electroencephalography (iEEG) data captured by the RNS System, are often referred to as subclinical seizures and we believe function as a more efficient and objective biomarker-based efficacy endpoint for seizures. The biomarker analysis sought to define the percent reduction in LE frequency that correlated with a clinically meaningful change in clinical seizure frequency (≥50% reduction).

在進行中的RAP-219概念驗證試驗中,符合入組標準的難治性局竈性癲癇患者從NeuroPace的長期研究數據庫中選出,進行這一事後分析。通過RNS系統捕獲的顱內腦電圖(iEEG)數據記錄的LE通常被稱爲亞臨床癲癇發作,我們認爲這是一種更有效和客觀的基於生物標誌物的癲癇效果終點。生物標誌物分析旨在定義LE頻率的百分比減少與臨床癲癇發作頻率(≥50%減少)之間的臨床顯著變化的相關性。

Using a receiver operator characteristic (ROC) analysis, the data confirmed that a 30% reduction in LE frequency was the optimal cut point associated with a clinically meaningful (≥50%) reduction in clinical seizures, regardless of the antiseizure medication initiated. We believe these findings establish a new benchmark for evaluating the potential efficacy of RAP-219 and other anti-seizure medications, providing a consistent metric to help inform the development of future treatments.

使用接收器操作特徵(ROC)分析,數據證實LE頻率減少30%是與臨床上顯著(≥50%)減少臨床癲癇發作相關的最佳切點,無論開始的抗癲癇藥物是什麼。我們認爲這些發現爲評估RAP-219和其他抗癲癇藥物的潛在療效建立了一個新的基準,提供了一個一致的指標,以幫助指導未來治療的發展。

"The long episode seizure biomarker provides a potentially transformative approach to evaluating the efficacy of anti-seizure medications," said Dr. Brad Galer, chief medical officer of Rapport Therapeutics. "These new data reveal a clear, linear relationship between long episode and clinical seizure frequencies. We look forward to advancing our research of RAP-219 using this novel biomarker in our proof-of-concept trial, enabling a more precise and expedited development path to hopefully deliver a new potential antiseizure medication for refractory focal epilepsy patients."

"長髮作癲癇生物標誌物提供了一種可能變革的評估抗癲癇藥物療效的方法," Rapport Therapeutics首席醫療官Brad Galer博士說。"這些新數據揭示了長髮作和臨床癲癇發作頻率之間清晰的線性關係。我們期待在概念驗證試驗中利用這一新生物標誌物推進RAP-219的研究,使得開發路徑更加精確和迅速,旨在爲難治性局竈性癲癇患者提供一種潛在的新型抗癲癇藥物。"

Separately, additional data being presented by Rapport at the AES Annual Meeting, include:

此外,Rapport在AES年會上發佈的其他數據包括:

  • Safety, Tolerability, and Pharmacokinetics of RAP-219 in Healthy Volunteers (Poster #372), which showed that RAP-219 was generally well tolerated at target therapeutic exposures. In addition, the projected target receptor occupancy (RO) was achieved following multiple dosing of RAP-219.
  • Impact of Food on the PK and Tolerability of RAP-219 in Healthy Volunteers (Poster #409), which suggested food will not have a clinically meaningful impact on RAP-219, allowing for dosing to disregard mealtime in the planned Phase 2 trials.
  • Antiseizure Effects with Selective TARPγ8 Negative Allosteric Modulators in Preclinical Seizure Models (Poster #390), which revealed RAP-219 provided potent, dose-dependent antiseizure effects in both preclinical seizure models tested, pentylenetretrazol (PTZ) and corneal kindling, with maximal protection observed with 70% RO and RAP-219 mean plasma concentration of 7 ng/mL.
  • 健康志願者中RAP-219的安全性、耐受性和藥代動力學(海報#372)顯示,RAP-219在目標治療暴露水平下通常耐受良好。此外,在進行了多次RAP-219給藥後,預計的目標受體佔用率(RO)得以實現。
  • 食物對健康志願者中RAP-219的藥代動力學和耐受性的影響(海報#409)表明,食物對RAP-219不會產生臨床意義上的影響,從而使得在計劃的第二階段試驗中可以不考慮進餐時間進行給藥。
  • 選擇性TARPγ8負調節劑在臨床前癲癇模型中的抗癲癇作用(海報#390)揭示,RAP-219在測試的兩種臨床前癲癇模型中均提供了強效、劑量依賴的抗癲癇效果,pentylenetetrazol (PTZ)和角膜點燃模型,在70% RO和RAP-219平均血漿濃度爲7 ng/mL時觀察到了最大保護。

To learn more and view the posters, please visit our website here.

要了解更多信息並查看海報,請訪問我們的網站。

About RAP-219
RAP-219 is a clinical-stage AMPAR (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor) negative allosteric modulator (NAM) designed to achieve neuroanatomical specificity through its selective targeting of a RAP known as TARPγ8, which is associated with the neuronal AMPAR. Whereas AMPARs are distributed widely in the central nervous system (CNS), TARPγ8 is expressed only in discrete regions, including the hippocampus and cortex. Because of this restricted expression of TARPγ8 in forebrain regions, the Company believes RAP-219 has the potential to provide a differentiated clinical profile, including improved activity and tolerability along with a higher therapeutic index, potentially providing more patients with sustained therapeutic benefit without intolerable side effects, as compared to traditional neuroscience medications. Due to the role of AMPA biology in various neurological disorders and the precision approach of selective targeting of TARPγ8, the Company believes RAP-219 has significant pipeline-in-a-product potential and is currently evaluating the compound as a transformational treatment for patients with focal epilepsy, peripheral neuropathic pain, and bipolar disorder.

關於RAP-219
RAP-219是處於臨床階段的AMPAR(α-氨基-3-羥基-5-甲基-4-異惡唑丙酸受體)負向變構調節劑(NAM),旨在通過其對名爲TARPγ8的已知RAP的選擇性靶向,實現神經解剖學的特異性。TARPγ8僅在離散地區表達,包括海馬和皮層,而AMPAR廣泛分佈在中樞神經系統(CNS)中。由於TARPγ8在前腦區域的受限表達,公司認爲RAP-219具有提供不同臨床概況的潛力,包括改善活性和耐受性,以及更高的治療指數,有可能爲更多患者提供持續治療益處而不會引起無法忍受的副作用,相比傳統的神經科學藥物。由於AMPA生物學在各種神經系統疾病中的作用,以及選擇性靶向TARPγ8的精確方法,公司認爲RAP-219具有重要的管道產品潛力,並目前正在評估該化合物作爲治療局竈性癲癇、外周神經痛和躁鬱症患者的轉型治療方案。

About Rapport Therapeutics
Rapport Therapeutics is a clinical-stage biotechnology company dedicated to discovering and developing small molecule precision medicines for patients suffering from central nervous system (CNS) disorders. The Company's founders have made pioneering discoveries related to the function of receptor associated proteins (RAPs) in the brain. Their findings form the basis of Rapport's RAP technology platform, which enables a differentiated approach to generate precision small molecule product candidates with the potential to overcome many limitations of conventional neurology drug discovery. Rapport's precision neuroscience pipeline includes the Company's lead clinical program, RAP-219, designed to achieve neuroanatomical specificity through its selective targeting of a RAP expressed in only discrete regions of the brain. The Company is currently advancing RAP-219 in clinical trials in focal epilepsy, peripheral neuropathic pain, and bipolar disorder. Additional preclinical and late-stage discovery stage programs are also underway, targeting CNS disorders including chronic pain and hearing disorders.

關於Rapport Therapeutics
Rapport Therapeutics是一家臨床階段的生物技術公司,致力於爲中樞神經系統(CNS)紊亂患者發現和開發小分子精準藥物。該公司的創始人在與大腦中受體相關蛋白(RAPs)功能相關的開拓性發現方面取得了突破性進展。他們的發現構成了Rapport的RAP技術平台的基礎,該平台通過差異化方法生成精準小分子藥物候選品,具有克服傳統神經病學藥物發現許多限制的潛力。Rapport的精準神經科學產品管線包括公司的主導臨床項目RAP-219,旨在通過選擇性靶向僅在大腦離散區域中表達的一種RAP,實現神經解剖學特異性。公司目前正在推進RAP-219在侷限性癲癇、周圍神經病性疼痛和躁鬱症臨床試驗中的進展。另外,針對包括慢性疼痛和聽力障礙在內的CNS障礙的其他臨床前和晚期發現階段項目也在進行中。

Forward-Looking Statements
This press release contains "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, each as amended. The words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements include, but are not limited to, express or implied statements regarding: the impact of reductions in long episode frequency as measured by the RNS System, including but not limited to Rapport's ability to predict clinically meaningful seizure reduction; the clinical development of RAP-219 for the treatment of drug-resistant focal epilepsy, peripheral neuropathic pain and bipolar disorder; the activity and tolerability of RAP-219; and Rapport's RAP technology platform.

前瞻性聲明
本新聞稿包含《1933年證券法》第27A節和《1934年證券交易法》第21E節(均經修訂)所定義的「前瞻性聲明」。「預期」、「相信」、「繼續」、「可能」、「估計」、「期待」、「打算」、「或許」、「計劃」、「潛在」、「預測」、「項目」、「應該」、「目標」、「會」和類似的表達旨在識別前瞻性聲明,儘管並非所有前瞻性聲明都包含這些識別詞。這些前瞻性聲明包括但不限於關於以下內容的明示或暗示聲明:通過RNS系統測量的長時間 episode 頻率減少的影響,包括但不限於 Rapport 預測臨床上顯著減少癲癇發作的能力;RAP-219用於治療耐藥性局竈性癲癇、外周神經病理性疼痛和雙相情感障礙的臨床開發;RAP-219的活性和耐受性;以及 Rapport 的 RAP 技術平台。

Forward looking statements are based on management's current expectations and are subject to risks and uncertainties that could negatively affect Rapport's business, operating results, financial condition and stock value. Factors that could cause actual results to differ materially from those currently anticipated include: risks relating to the company's research and development activities; Rapport's ability to execute on its strategy including obtaining the requisite regulatory approvals on the expected timeline, if at all; uncertainties relating to preclinical and clinical development activities; the company's dependence on third parties to conduct clinical trials, manufacture its product candidates and develop and commercialize its product candidates, if approved; Rapport's ability to attract, integrate and retain key personnel; risks related to the company's financial condition and need for substantial additional funds in order to complete development activities and commercialize a product candidate, if approved; risks related to regulatory developments and approval processes of the U.S. Food and Drug Administration and comparable foreign regulatory authorities; risks related to establishing and maintaining Rapport's intellectual property protections; and risks related to the competitive landscape for Rapport's product candidates; as well as other risks described in "Risk Factors," in the company's Registration Statement on Form S-1, and most recent Quarterly Report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in Rapport's subsequent filings with the Securities and Exchange Commission. Rapport expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in its expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by law, and claims the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995.

前瞻性聲明基於管理層當前的期望,並受到可能對Rapport的業務、運營成果、財務狀況和股票價值產生負面影響的風險和不確定性的制約。導致實際結果與當前預期大相徑庭的因素包括:與公司研究和開發活動相關的風險;Rapport在期望時間線內(如有)獲得必要的監管批准的戰略執行能力的不確定性;與臨床前和臨床開發活動相關的不確定性;公司依賴第三方進行臨床試驗、製造其產品候選者以及開發和商業化其產品候選者(如獲得批准);Rapport吸引、整合和保留關鍵人員的能力;與公司財務狀況及其需要大量額外資金以完成開發活動和商業化產品候選者(如獲得批准)相關的風險;與美國食品藥品管理局及其他外國監管機構的監管動態和批准程序相關的風險;與建立和維護Rapport的知識產權保護相關的風險;以及與Rapport的產品候選者競爭環境相關的風險;以及在公司的S-1登記聲明和最近的10-Q季報中描述的其他風險,以及Rapport隨後向證券交易委員會(SEC)提交的文件中關於潛在風險、不確定性和其他重要因素的討論。Rapport明確聲明,對在法律要求的情況下,公開發布任何前瞻性聲明的更新或修訂以反映其期望的任何變化或基於任何此類聲明的事件、條件或情況的變化,沒有任何義務或承諾,並主張根據1995年私營證券訴訟改革法案所包含的前瞻性聲明的安全港保護。

CONTACT: Contact
Julie DiCarlo
Head of Communications & IR
Rapport Therapeutics
jdicarlo@rapportrx.com
聯繫人:聯繫
朱莉•迪卡洛
傳播與投資關係負責人
Rapport Therapeutics
jdicarlo@rapportrx.com

譯文內容由第三人軟體翻譯。


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