Marker Therapeutics Announces Clinical Program Updates and Pipeline Prioritization
Marker Therapeutics Announces Clinical Program Updates and Pipeline Prioritization
Strategic prioritization of clinical programs with focus on MT-601 in patients with lymphoma
對臨床項目進行戰略優先排序，重點關注淋巴瘤患者的 MT-601
MultiTAA-specific T cell therapies demonstrate clinical safety and positive clinical data across multiple indications
MultiTAA 特異性 T 細胞療法在多種適應症中顯示出臨床安全性和陽性臨床數據
Marker provides updates supporting the clinical benefits of MT-401 in patients with measurable residual disease (MRD)
Marker 提供最新信息，支持 MT-401 對可測量殘留疾病 (MRD) 患者的臨床益處
HOUSTON, Jan. 08, 2024 (GLOBE NEWSWIRE) -- Marker Therapeutics, Inc. (Nasdaq: MRKR), a clinical-stage immuno-oncology company focusing on developing next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumors, today announced a restructuring of its clinical programs and a strategic prioritization of its multi-tumor associated antigen (multiTAA)-specific T cell product pipeline. In addition, the Company reported a clinical update on the Phase 2 ARTEMIS study investigating MT-401, a multiTAA-specific T cell product, for the treatment of patients with acute myeloid leukemia (AML).
休斯頓，2024年1月8日（環球新聞專線）——Marker Therapeutics, Inc.（納斯達克股票代碼：MRKR）是一家臨床階段的免疫腫瘤學公司，專注於開發用於治療血液系統惡性腫瘤和實體瘤的下一代基於T細胞的免疫療法，今天宣佈重組其臨床項目，並確定其多腫瘤相關抗原（MultiTAA）特異性T細胞產品管線的戰略優先事項。此外，該公司報告了研究用於治療急性髓系白血病（AML）患者的Multaa特異性T細胞產品 MT-401 的2期研究的最新臨床情況。
Following the non-dilutive transaction with Cell Ready (Press Release, May 1, 2023), Marker has made significant progress on clinical and corporate restructuring with the objective of accelerating the commercial development of our unique multiTAA technology. The Company today announced the prioritization of MT-601 in chimeric antigen receptor (CAR) relapse patients with lymphoma (APOLLO; clinicaltrials.gov identifier: NCT05798897). This strategic decision was made based on 1) the Company's promising non-clinical and clinical data using the multiTAA technology in lymphoma, and 2) the lack of an approved treatment for patients who experience relapse after treatment with CD19 CAR T (up to 60% within a year; Chong EA et al, N Engl J Med, 2021), which is a clear unmet medical need and provides an opportunity for accelerated product development.
繼與Cell Ready進行非稀釋性交易（新聞稿，2023年5月1日）之後，Marker在臨床和公司重組方面取得了重大進展，目標是加快我們獨特的MultiTAA技術的商業開發。該公司今天宣佈，在嵌合抗原受體（CAR）復發淋巴瘤患者（APOLLO；clinicaltrials.gov 標識符：NCT05798897）中優先使用 MT-601。該戰略決策的依據是：1) 該公司使用MultiTAA技術治療淋巴瘤的非臨床和臨床數據，以及2) CD19 CAR T治療後復發的患者缺乏經批准的治療方法（一年內高達60％；Chong EA等人，N Engl J Med，2021年），這顯然是一種未得到滿足的醫療需求，爲加快產品開發提供了機會。
Highlights from the Lymphoma Study
Clinical Efficacy in Patients with Lymphoma in Previous Clinical Trial
淋巴瘤研究的要點
先前臨床試驗中淋巴瘤患者的臨床療效
The multiTAA-specific T cell product targeting 5 TAAs was investigated in the TACTAL study, a Phase 1 trial conducted at Baylor College of Medicine.
The TACTAL study enrolled patients with Hodgkin's and non-Hodgkin's lymphoma and demonstrated clinical safety and efficacy with durable clinical responses for 6 years (Vasileiou et al, J Clin Oncol, 2021).
TACTAL研究是貝勒醫學院進行的一項1期試驗，對靶向5種TAA的Multaa特異性T細胞產品進行了研究。
TACTAL研究招收了霍奇金淋巴瘤和非霍奇金淋巴瘤患者，證明了臨床安全性和有效性，持續了6年的臨床反應（Vasileiou等人，J Clin Oncol，2021年）。
Non-Clinical Proof-of-Concept Data
非臨床概念驗證數據
Marker developed a long-term in vitro killing assay 1) to better understand resistance mechanisms following CAR T cell treatment and 2) to determine if a product that is capable of targeting 6 TAAs (MT-601) will be able to kill CAR-resistant lymphoma cells (Press Release, May 31, 2023).
After CD19-targeting CAR T cell treatment, 98% of lymphoma cells were eliminated in vitro. Long-term follow-up (three weeks) demonstrated outgrowth of CD19-negative tumor cells. Additional anti-CD19 CAR T cell treatment failed to inhibit tumor growth due to the lack of target antigen (CD19) expression on the tumor.
Treating CAR-resistant lymphoma cells with MT-601 resulted in complete long-term growth inhibition (over three weeks) highlighting that MT-601 has the potential to effectively treat CD19 CAR-resistant tumors (Pre-Clinical Data in Lymphoma, May 31, 2023).
Marker 開發了一種長期體外殺傷試驗 1) 以更好地了解 CAR T 細胞治療後的耐藥機制，2) 確定能夠靶向 6 個 TAA (MT-601) 的產品是否能夠殺死 CAR 耐藥淋巴瘤細胞（新聞稿，2023 年 5 月 31 日）。
靶向CD19的CAR T細胞治療後，體外消滅了98％的淋巴瘤細胞。長期隨訪（三週）顯示CD19陰性腫瘤細胞會生長。由於腫瘤上缺乏靶抗原（CD19）表達，額外的抗CD19 CAR T細胞治療未能抑制腫瘤的生長。
使用 MT-601 治療 CAR-耐藥淋巴瘤細胞可完全抑制長期生長（超過三週），這突出表明 MT-601 有可能有效治療 CD19 CAR耐藥腫瘤（淋巴瘤臨床前數據，2023 年 5 月 31 日）。
Durable Response in CAR Relapsed Patient with Lymphoma
CAR復發淋巴瘤患者的持久反應
The Company-sponsored Phase 1 APOLLO study investigates the safety and efficacy of MT-601 in patients with lymphoma who have failed or are ineligible to receive anti-CD19 CAR T cell therapy.
The first study participant, a 57-year-old female with diffuse large B cell lymphoma (DLBCL), was enrolled in the Phase 1 dose escalation stage of the trial after failing 4 prior lines of therapy, including anti-CD19 CAR T cell therapy (Press Release, June 12, 2023). The participant relapsed within 90 days of CAR T cell therapy, and was treated with MT-601 without prior lymphodepletion.
The patient tolerated MT-601 well without treatment-related adverse events and achieved a complete response eight weeks after the second infusion of MT-601 (Press Release, Sep 11, 2023).
Six months following treatment with MT-601 the study participant has maintained a complete response to treatment suggesting that MT-601 is more durable compared to CAR T cells in this study participant (Press Release, Dec 11, 2023).
公司贊助的阿波羅第一期研究調查了 MT-601 對失敗或沒有資格接受抗 CD19 CAR T 細胞療法的淋巴瘤患者的安全性和有效性。
第一位研究參與者是一名患有瀰漫性大B細胞淋巴瘤（DLBCL）的57歲女性，在包括抗CD19 CAR T細胞療法在內的4種先前療法失敗後，被納入該試驗的1期劑量遞增階段（新聞稿，2023年6月12日）。該參與者在 CAR T 細胞治療後 90 天內復發，並接受了 MT-601 治療，事先沒有淋巴消耗。
該患者對 MT-601 的耐受性良好，沒有出現與治療相關的不良事件，並在第二次輸注 MT-601 八週後取得了完全的緩解（新聞稿，2023 年 9 月 11 日）。
在使用 MT-601 治療六個月後，研究參與者對治療保持了完全的反應，這表明該研究參與者的 MT-601 比 CAR T 細胞更耐用（新聞稿，2023 年 12 月 11 日）。
CD19-targeting CAR T cell therapies are associated with severe side effects and toxicities, and up to 60% of patients with DLBCL relapse within a year (Chong EA et al, N Engl J Med, 2021). Additionally, the FDA is investigating CAR T therapies for the potential risk of inducing secondary cancers (U.S. Food and Drug Administration, Nov 28, 2023). To date, multiTAA-specific T cell therapies have been well-tolerated in over 200 patients in clinical trials, and Marker believes that, unlike CAR T cells, multiTAA-specific T cells could represent a safer therapeutic option due to their non-genetically engineered approach that selectively expands tumor-specific T cells from a patient's/donor's blood without the risk of mutagenesis.
靶向CD19的CAR T細胞療法與嚴重的副作用和毒性有關，多達60％的DLBCL患者在一年內復發（Chong EA等人，N Engl J Med，2021年）。此外，美國食品和藥物管理局正在調查CAR T療法是否存在誘發繼發癌症的潛在風險（美國食品藥品監督管理局，2023年11月28日）。迄今爲止，在臨床試驗中，已有超過200名患者對MultiTAA特異性T細胞療法具有良好的耐受性，Marker認爲，與CAR T細胞不同，MultiTAA特異性T細胞可能是一種更安全的治療選擇，因爲其非基因工程方法可以選擇性地從患者/捐贈者的血液中擴增腫瘤特異性T細胞，而不會產生誘變的風險。
Promising Clinical Observations and New Directions with MT-401 in Patients with MRD in AML
Today, Marker is providing a clinical update on the Phase 2 ARTEMIS clinical study (clinicaltrials.gov identifier: NCT04511130), and the direction it will pursue. This multicenter study is evaluating the safety and efficacy of MT-401 in patients with AML after allogeneic hematopoietic stem cell transplantation (HSCT).
MT-401 對急性髓細胞白血病患者有前景的臨床觀察和新方向
今天，Marker正在提供ARTEMIS二期臨床研究（clinicaltrials.gov標識符：NCT04511130）的臨床最新情況及其前進方向。這項多中心研究正在評估 MT-401 對異基因造血幹細胞移植 (HSCT) 後急性髓細胞白血病患者的安全性和有效性。
A total of 8 patients with MRD+ AML after HSCT were enrolled and treated with MT-401. None of the 8 treated patients experienced a drug related adverse event. Of the 8 treated patients, 4 experienced a clinical benefit, with 3 showing a conversion to MRD-negative, and one patient showing a partial response with a logarithmic reduction of MRD levels by PCR. One patient has not yet had the first assessment post treatment. Of the 8 treated patients in the study, only 1 patient had documented disease progression and was taken to a second transplant. The other 3 patients were taken off the study for reasons unrelated to the clinical outcome.
共有 8 名 HSCT 後 MRD+ 急性髓細胞白血病患者入組並使用 MT-401 進行治療。8名接受治療的患者均未出現與藥物相關的不良事件。在8名接受治療的患者中，有4名患者獲得了臨床益處，其中3例顯示轉化爲MRD陰性，一名患者表現出部分反應，通過聚合酶鏈反應以對數方式降低了MRD水平。一名患者尚未接受治療後的首次評估。在研究的8名接受治療的患者中，只有1名患者記錄了疾病進展並接受了第二次移植。其他3名患者因與臨床結果無關的原因被排除在研究之外。
Obtaining timely consent and re-accessing HSCT donors for apheresis for the manufacture of MT-401 caused delayed patient accrual and patient eligibility issues. Consequently, the rapid progression of disease contributed to some patients to withdraw from the study prior to administration of study product. Therefore, to streamline resources and to reduce time to treatment, Marker intends to focus on a ready for use product from commercially available leukapheresis material and will discontinue the patient-specific part (ARTEMIS) of the AML program.
及時獲得同意並重新接觸 HSCT 捐贈者進行血液分離以製造 MT-401 會導致患者累積延遲和患者資格問題。因此，疾病的快速進展導致一些患者在給藥研究產品之前退出研究。因此，爲了精簡資源和縮短治療時間，Marker打算將重點放在使用市售白細胞分離材料製成的即用型產品上，並將終止反洗錢計劃的患者特定部分（ARTEMIS）。
"We are encouraged by the clinical observations in patients with MRD in our AML study," said Juan Vera, M.D., President and CEO of Marker Therapeutics. "The data demonstrate the safety of MT-401 and provide evidence that MT-401 could benefit patients with MRD+ AML."
Marker Therapeutics總裁兼首席執行官胡安·維拉醫學博士說：“我們的反洗錢研究中對MRD患者的臨床觀察令我們感到鼓舞。”“這些數據證明了 MT-401 的安全性，並提供了證據，表明 MT-401 可以使 MRD+ 急性髓細胞白血病患者受益。”
Dr. Vera continued: "Decreasing the time to treatment is critical when it comes to the treatment of patients that suffer from rapidly progressing cancers, such as patients with MRD in AML, which typically advances rapidly into frank relapse with poor outcomes. We believe using commercial leukapheresis material from healthy donors can bypass the bottleneck associated with donor identification and facilitate large-scale manufacturing. This approach is expected to not only reduce manufacturing costs, but also expedite time to treatment to as little as 72 hours. We are currently working to initiate the clinical study and anticipate that the first patient with AML will be treated with MT-401 manufactured from healthy donors in the second half of 2024."
維拉博士繼續說：“對於那些患有快速進展的癌症患者，例如急性髓細胞白血病的MRD患者，縮短治療時間至關重要，這種患者通常會迅速發展爲明顯的復發，但預後不佳。我們認爲，使用來自健康捐贈者的商用白血球置換材料可以繞過與捐贈者識別相關的瓶頸，促進大規模生產。預計這種方法不僅可以降低製造成本，還可以將治療時間縮短至72小時。我們目前正在努力啓動臨床研究，並預計第一位急性髓細胞白血病患者將在2024年下半年接受由健康捐贈者製造的 MT-401 的治療。”
The Company previously announced that the FDA has cleared the clinical protocol to investigate a ready for use MT-401 product manufactured from healthy donors in patients with AML, and a cellular inventory has been established with continuous efforts to expand this inventory (Press Release, Aug 7, 2023).
該公司此前宣佈，美國食品和藥物管理局已批准臨床協議，以研究一種由急性髓細胞白血病患者健康捐贈者生產的即用型 MT-401 產品，並且已經建立了細胞清單，以不斷努力擴大該庫存（新聞稿，2023 年 8 月 7 日）。
Marker has secured non-dilutive funding to support the clinical investigation of a ready for use MT-401 product in patients with AML. Using these allocated funds will allow the Company to proceed with the ready for use program without affecting the ongoing Phase 1 APOLLO study and the capital runway of the Company into the fourth quarter of 2025.
Marker 已獲得非稀釋資金，以支持對急性髓細胞白血病患者即用型 MT-401 產品的臨床研究。使用這些分配的資金將使公司能夠在不影響正在進行的阿波羅第一階段研究和公司2025年第四季度資本跑道的情況下繼續進行即用型計劃。
In addition, the Company has an Investigational New Drug (IND) application cleared by the U.S. FDA for a Phase 1 trial to investigate MT-601 in patients with pancreatic cancer in combination with first-line chemotherapy. The clinical advancement of this multicenter study will be pending additional funding from non-dilutive sources, including grant activities.
此外，該公司還有一項已獲得美國食品藥品管理局批准的研究性新藥（IND）申請，用於研究胰腺癌患者中與一線化療聯合使用的 MT-601 進行的 1 期試驗。這項多中心研究的臨床進展將取決於非稀釋性來源的額外資金，包括撥款活動。
"The strategic restructure of our multiTAA pipeline reflects our ongoing commitment to innovate and deliver groundbreaking treatments," said Dr. Vera. "The decision to shift our focus on MT-601 in patients with lymphoma is based on our promising non-clinical and clinical observations. Lymphoma is a highly competitive landscape with numerous companies striving to compete with CAR T cell therapies. However, our approach differs by targeting multiple antigens and focusing on a unique niche: patients who have experienced CAR T cell relapse or are ineligible for CAR T therapy."
維拉博士說：“我們的MultiTAA管道的戰略重組反映了我們對創新和提供開創性治療的持續承諾。”“決定將重點轉移到淋巴瘤患者的 MT-601 上，是基於我們充滿希望的非臨床和臨床觀察。淋巴瘤是一個競爭激烈的格局，許多公司都在努力與CAR T細胞療法競爭。但是，我們的方法不同之處在於靶向多種抗原並專注於一個獨特的利基市場：經歷過CAR T細胞復發或沒有資格接受CAR T治療的患者。”
Dr. Vera continued: "We believe that MT-601 could address the unmet medical need in this patient population. Developing a product in this patient population is commercially attractive due to the well understood natural history, the unmet medical need, and the lower number of competing trials. Assuming we continue to see promising results in our APOLLO study, this would allow us to accelerate the development of MT-601 in CAR relapse patients with lymphoma."
維拉博士繼續說：“我們相信 MT-601 可以解決這些患者群體中未得到滿足的醫療需求。由於自然病史衆所周知，醫療需求未得到滿足，競爭試驗數量較少，因此在這些患者群體中開發產品具有商業吸引力。假設我們在 APOLLO 研究中繼續看到令人鼓舞的結果，這將使我們能夠加快 MT-601 在 CAR 復發淋巴瘤患者中的開發。”
About multiTAA-specific T cells
The multi-tumor associated antigen (multiTAA)-specific T cell platform is a novel, non-genetically modified cell therapy approach that selectively expands tumor-specific T cells from a patient's/donor's blood capable of recognizing a broad range of tumor antigens. Clinical trials that enrolled more than 200 patients with various hematological malignancies and solid tumors showed that autologous and allogeneic multiTAA-specific T cell products were well tolerated and demonstrated durable clinical responses, and consistent epitope spreading. The latter is typically not observed with other T cell therapies and enables the potential contribution to a lasting anti-tumor effect.
關於 multiTAA 特異性 T 細胞
多腫瘤相關抗原（MultiTAA）特異性T細胞平台是一種新型的非轉基因細胞療法方法，可選擇性地從患者/捐贈者的血液中擴展腫瘤特異性T細胞，能夠識別多種腫瘤抗原。招收了200多名患有各種血液學惡性腫瘤和實體瘤的患者的臨床試驗表明，自體和異體MultiTAA特異性T細胞產品的耐受性良好，表現出持久的臨床反應和持續的表位擴散。後者通常不會在其他 T 細胞療法中觀察到，因此可能有助於產生持久的抗腫瘤作用。
About Marker Therapeutics, Inc.
Marker Therapeutics, Inc. is a clinical-stage immuno-oncology company specializing in the development of next-generation T cell-based immunotherapies for the treatment of hematological malignancies and solid tumor indications. The T cell therapy technology developed by Marker is based on the selective expansion of non-engineered, tumor-specific T cells that recognize tumor associated antigens (i.e., tumor targets) and kill tumor cells expressing those targets. This population of T cells is designed to attack multiple tumor targets following infusion into patients and to activate the patient's immune system to produce broad spectrum anti-tumor activity. Because Marker does not genetically engineer the T cells, Marker believes that its product candidates will be easier and less expensive to manufacture, with reduced toxicities, compared to current engineered CAR-T and TCR-based approaches, and may provide patients with meaningful clinical benefit. As a result, Marker believes its portfolio of T cell therapies has a compelling product profile, as compared to current gene-modified CAR-T and TCR-based therapies.
關於 Marker Therapeutics,
Marker Therapeutics, Inc. 是一家臨床階段的免疫腫瘤學公司，專門開發用於治療血液系統惡性腫瘤和實體瘤適應症的下一代基於T細胞的免疫療法。Marker 開發的 T 細胞療法技術基於選擇性擴增非工程化腫瘤特異性 T 細胞，這些細胞可識別腫瘤相關抗原（即腫瘤靶標）並殺死表達這些靶標的腫瘤細胞。這組 T 細胞旨在在輸液給患者後攻擊多個腫瘤靶標，並激活患者的免疫系統以產生廣譜抗腫瘤活性。由於Marker不對T細胞進行基因工程，因此Marker認爲，與目前工程化的基於CAR-T和TCR的方法相比，其候選產品的製造將更容易、更便宜，毒性更低，並且可能爲患者提供有意義的臨床益處。因此，Marker認爲，與目前的基因修飾CAR-T和基於TCR的療法相比，其T細胞療法產品組合具有引人注目的產品概況。
譯文內容由第三人軟體翻譯。