Tumor Virus Infections

RP1 monotherapy showed clear anti-tumor activity with an overall response rate of nearly 35 percent and complete response rate of nearly 22 percent in evaluable patientsSAN DIEGO, April 07, 2024 (GLOBE NEWSWIRE) -- Replimune Group, Inc. (NASDAQ: REPL), a clinical stage biotechnology company pioneering the development of a novel portfolio of oncolytic immunotherapies, today announced the presentation of interim results from ARTACUS, a Phase 1/2 clinical trial evaluating RP1 monotherapy for the treatment of skin cancers in patients who have had solid organ or hematopoietic cell transplants, by Michael R. Midgen, M.D., of the University of Texas MD Anderson Cancer Center during an oral session at the AACR 2024 Annual Meeting in San Diego. The results were initially presented late last year at the 38th Annual Meeting of the Society for Immunotherapy of Cancer (SITC). In the study, treatment with RP1 as monotherapy, for up to 25 doses, resulted in an overall response rate (ORR) of 34.8 percent (8 of 23 evaluable patients, including 5 complete responses and 3 partial responses) with most responses ongoing as of the data cutoff date of September 18, 2023. In the evaluable patient population (n=23), 20 had cutaneous squamous cell carcinoma (CSCC) and three had merkel cell carcinoma. Of note, a patient treated with RP1 for CSCC also had a complete response of a new primary basal cell carcinoma which appeared post baseline. There was no evidence of allograft rejection including of hepatic and lung allografts. RP1 monotherapy was well tolerated, and the safety profile was similar to the profile in non-immunocompromised patients with advanced skin cancers. Additional biomarker data collected showed an increase in CD+8 T, a type of immune cell, and an increase in the expression of PD-L1, after treatment suggesting immune activation. The slides are available on the Replimune website under presentations. “Organ transplant recipients are at a higher risk for skin cancer when compared to the broader population and have access to a limited number of treatment options given that systemic immunotherapy is typically contra-indicated,” said Sushil Patel, Ph.D., CEO of Replimune. “These data show RP1 as monotherapy has clear anti-tumor activity and may be a safe and effective treatment option for these patients with an overall response rate of nearly 35 percent with good durability of benefit to date.” About ARTACUSARTACUS is a multicenter, open-label, two-part Phase 1b/2 study evaluating RP1 as monotherapy for the treatment of locally advanced or metastatic cutaneous malignancies in patients who underwent a kidney, liver, heart, lung, or other solid organ transplant, or hematopoietic cell transplantation, who are on chronic immunosuppressive treatment, in whom systemic immunotherapy is typically contra-indicated. Researchers will assess the safety of RP1 and also evaluate its ability to shrink tumors. ARTACUS is currently recruiting patients. To learn more, contact clinicaltrials@replimune.com or +1-781-222-9570. About RP1RP1 is Replimune’s lead product candidate and is based on a proprietary new strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP R-) and GM-CSF to maximize tumor killing potency, the immunogenicity of tumor cell death and the activation of a systemic anti-tumor immune response. About Replimune Replimune Group, Inc., headquartered in Woburn, MA, was founded in 2015 with the mission to transform cancer treatment by pioneering the development of a novel portfolio of oncolytic immunotherapies. Replimune’s proprietary RPx platform is based on a potent HSV-1 backbone intended to maximize immunogenic cell death and the induction of a systemic anti-tumor immune response. The RPx platform is designed to have a unique dual local and systemic activity consisting of direct selective virus-mediated killing of the tumor resulting in the release of tumor derived antigens and altering of the tumor microenvironment to ignite a strong and durable systemic response. The RPx product candidates are expected to be synergistic with most established and experimental cancer treatment modalities, leading to the versatility to be developed alone or combined with a variety of other treatment options. For more information, please visit www.replimune.com. Forward-Looking StatementsThis press release contains forward looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, including statements regarding the design and advancement of our clinical trials, the timing and sufficiency of our clinical trial outcomes to support potential approval of any of our product candidates, our goals to develop and commercialize our product candidates, patient enrollments in our existing and planned clinical trials and the timing thereof, and other statements identified by words such as “could,” “expects,” “intends,” “may,” “plans,” “potential,” “should,” “will,” “would,” or similar expressions and the negatives of those terms. Forward-looking statements are not promises or guarantees of future performance and are subject to a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in such forward-looking statements. These factors include risks related to our limited operating history, our ability to generate positive clinical trial results for our product candidates, the costs and timing of operating our in-house manufacturing facility, the timing and scope of regulatory approvals, changes in laws and regulations to which we are subject, competitive pressures, our ability to identify additional product candidates, political and global macro factors including the impact of the coronavirus as a global pandemic and related public health issues, and other risks as may be detailed from time to time in our Annual Reports on Form 10-K and Quarterly Reports on Form 10-Q and other reports we file with the Securities and Exchange Commission. Our actual results could differ materially from the results described in or implied by such forward-looking statements. Forward-looking statements speak only as of the date hereof, and, except as required by law, we undertake no obligation to update or revise these forward-looking statements. Investor InquiriesChris BrinzeyICR Westwicke339.970.2843chris.brinzey@westwicke.com Media InquiriesArleen GoldenbergReplimune917.548.1582media@replimune.com

诱导肿瘤细胞凋亡，一直以来是各类肿瘤免疫治疗的根本目标。但这一定是对的吗？如果不对，我们是否需要改变药物研发和临床治疗的策略？肿瘤细胞主动死亡近年来，科学家们发现一些预后不良的高级别癌症往往包含相对高水平凋亡细胞。有人提出死亡的肿瘤细胞有助于肿瘤种群整体的净生存、扩张和进化，可能是肿瘤的一个主动行为。Cancer Cell上，阿拉巴马大学伯明翰分校的一些研究者就发现，凋亡的胶质母细胞瘤会释放胞外囊泡，含有恶性促肿瘤的剪切碎片，它再转入存活的胶质母细胞瘤细胞，促进他们发生恶性表型改变，并对治疗产生抗性。作者发现胶质母细胞瘤中超过70%的肿瘤细胞会发生凋亡。Cancer Cell. 2018英国爱丁堡大学Catriona A. Ford等则认为凋亡的淋巴瘤细胞和肿瘤相关巨噬细胞会促进肿瘤细胞生长，血管生成，对抗肿瘤免疫产生抑制。凋亡的淋巴瘤细胞会激活肿瘤相关巨噬细胞，释放基质金属蛋白酶（MMP2和MMP12等）促进组织重构和转移。伯基特淋巴瘤是增长最快的人类癌症之一，但是其通过凋亡丢失的细胞约占总增量细胞的70%。Curr. Biol. 2015促进肿瘤细胞凋亡和抗肿瘤作用在某些条件下是一个悖论（Apoptosis Paradox）。目前至少发现在10种肿瘤存在这种悖论，包括膀胱癌、乳腺癌、结肠直肠癌、胃癌、胶质母细胞瘤、恶性间皮瘤、NHL、非小细胞肺癌、胰腺管癌、舌鳞状癌。 Int. J. Mol. Sci. 2022凋亡创造促肿瘤生态位根据Paget’s的种子和土壤概念，原发性和转移性癌症的发展从根本上依赖于肿瘤的“生态位”，即肿瘤微环境。凋亡是肿瘤微环境的一个共同特征，其次，在多个较高凋亡水平的肿瘤更具侵袭性。虽然恶性疾病的侵袭性和肿瘤细胞凋亡水平之间的因果关系仍然很大程度上是理论上的，即促凋亡分子的高表达可能与疾病的低侵袭性不相关，反之亦然。比如，促凋亡的Bax表达或Caspase激活与侵袭性疾病相关，而抗凋亡的Bcl-2与较低的侵袭性状态相关。细胞死亡可能促进基因组的不稳定性和创建新的生态位(Onco-Regenerative Niche ,ORN)，导致更具有侵袭性的肿瘤细胞增殖，形成新克隆重新聚集。分泌的凋亡囊泡可以促进血管新生，激活肿瘤相关巨噬细胞，诱导肿瘤微环境重构，转移。 Int. J. Mol. Sci. 2022简评：诱导凋亡是我们抗肿瘤治疗一直以来的目标和策略。但是肿瘤细胞也通过主动诱导凋亡形成促进其生长转移的新生态位。所以，单纯的凋亡可能无法给我抗肿瘤治疗成或败的信息。那么，诱导凋亡的细胞毒性药物（小分子或者大分子）还会是研究和开发的重点吗？参考文献Pavlyukov, M.S.; Yu, H.; Bastola, S.; Minata, M.; Shender, V.O.; Lee, Y.; Zhang, S.; Wang, J.; Komarova, S.; Wang, J.; et al. Apoptotic Cell-Derived Extracellular Vesicles Promote Malignancy of Glioblastoma Via Intercellular Transfer of Splicing Factors. Cancer Cell. 2018, 34, 119–135.e10Ford, C.A.; Petrova, S.; Pound, J.D.; Voss, J.J.; Melville, L.; Paterson, M.; Farnworth, S.L.; Gallimore, A.M.; Cuff, S.; Wheadon, H.; et al. Oncogenic properties of apoptotic tumor cells in aggressive B cell lymphoma. Curr. Biol. 2015, 25, 577–588Morana, O.; Wood, W.; Gregory, C.D. The Apoptosis Paradox in Cancer. Int. J. Mol. Sci. 2022, 23, 1328. https://doi.org/10.3390/ ijms23031328本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处···

BERLIN, April 4, 2024 /PRNewswire/ -- Ariceum Therapeutics (Ariceum), a private biotech company developing radiopharmaceutical products for the diagnosis and treatment of certain hard-to-treat cancers, today announces that it will be presenting a poster, demonstrating its new findings on the discovery of novel macrocyclic peptide radioligands for tumor therapy by mRNA display in collaboration with research partner, UCB, a global pharmaceutical company, at this year's American Association for Cancer Research (AACR) Annual Meeting, held 5-10 April 2024 in San Diego, California. The findings describe the selection and initial characterization of macrocyclic peptides against an undisclosed target discovered using UCB's mRNA-display technology platform, ExtremeDiversity™. Macrocyclic peptides are potent ligands for radioligand therapeutics (RLT) that aim to selectively deliver radioisotopes to cancer tissues to eradicate tumor cells while limiting the damage to surrounding tissues. This new data highlights the potential of UCB's mRNA display platform for fast and efficient discovery of highly specific macrocyclic peptides with optimal binding properties suitable for RLT. Manfred Rüdiger, Chief Executive Officer at Ariceum Therapeutics, said: "Following our exclusive, strategic research collaboration with UCB, we look forward to presenting new findings related to the identification of highly specific macrocyclic peptides for use in radioligand therapeutics at this year's AACR Annual Meeting. These data have positive implications for the future development of RLT and are a potential game-changer in precision cancer therapy. AACR's Annual Meeting is the perfect industry forum at the forefront of cancer research at which to present our findings." Details of the poster presentation are as follow: Title: Discovery of novel macrocyclic peptide radioligands for tumor therapy by mRNA display Presenting Author: Anika Jaekel, Senior Director, Head of Translational Biology and Non-Clinical Pharmacology at Ariceum Therapeutics Session Category: Experimental and Molecular Therapeutics Session Title: Radiation, Theranostics, Radiotheranostics, Normal Tissue, and Cellular Stress Session Date and Time: Tuesday 9 April 2024, 1:30 PM - 5:00 PM PDT Location: Poster Section 29 Poster Board Number: 7 Abstract Number: 6025 Abstracts are available in an online itinerary planner here and will be available in on online only supplement to the AACR journal Cancer Research one month after the conference. Notes to Editors About Ariceum Therapeutics Ariceum Therapeutics (Ariceum) is a private, clinical stage radiopharmaceutical company focused on the diagnosis and precision treatment of certain neuroendocrine and other aggressive, hard-to-treat cancers. The name Ariceum is an anagram of 'Marie Curie' whose discovery of radium and polonium have been huge contributions to finding treatments for cancer. Ariceum's lead targeted systemic radiopharmaceutical product, 177Lu-satoreotide tetraxetan ("Satoreotide"), is an antagonist of the somatostatin type 2 (SSTR2) receptor which is overexpressed in neuroendocrine tumours (NETs) and some aggressive cancers such as small cell lung cancer (SCLC), or Merkel Cell Carcinoma, all of which have few treatment options and poor prognosis. Satoreotide is being developed as a 'theranostic' pair for the combined diagnosis and targeted radionuclide treatment of these tumours. Ariceum is also developing a radiolabelled PARP-inhibitor (ATT001), which is slated to enter clinical development in 2024. ATT001 was part of the acquisition of Theragnostics Ltd which was closed in June 2023. Ariceum Therapeutics, launched in 2021, acquired all rights to Satoreotide from Ipsen. Ipsen remains a shareholder in the Company. Ariceum is headquartered in Berlin, with operations in Germany, Switzerland, Australia, United Kingdom and United States of America and with activities currently across the globe. Ariceum is led by a highly experienced management team and supported by specialist investors including EQT Life Sciences (formerly LSP), HealthCap, Pureos Bioventures, Andera Partners and Earlybird Venture Capital. For further information, please visit . About AACR Founded in 1907, the American Association for Cancer Research (AACR) is the world's first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 54,000 laboratory, translational, and clinical researchers; population scientists; other health care professionals; and patient advocates residing in 130 countries and territories around the world. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, diagnosis, and treatment of cancer by annually convening more than 30 conferences and educational workshops, the largest of which is the AACR Annual Meeting. For more information about the AACR, visit AACR.org. SOURCE Ariceum Therapeutics