Brain Stem Neoplasms

Topline Results For Progression-Free Survival Expected In Q2 2024 CARDIFF, UK / ACCESSWIRE / March 28, 2024 / Biodexa Pharmaceuticals (NASDAQ:BDRX) ("Biodexa"), an acquisition-focused biopharmaceutical company, is developing MTX110 for the treatment of Diffuse Midline Glioma (DMG) in pediatric patients and for Recurrent Glioblastoma (rGBM) in adults; two aggressive brain cancers with universally poor prognoses. The company says early trials of MTX110 in both cancers show promise in extending survival rates beyond those reported in previously published studies. DMG tumors are highly aggressive grade IV tumors that exhibit a propensity to infiltrate the surrounding tissues. Commonly found throughout the brainstem, these tumors pose significant challenges in treatment. The median overall survival rate for individuals - typically children diagnosed with diffuse midline glioma is less than one year - generally ranges from eight to 11 months. A small percentage, approximately 10%, manage to survive for at least two years following diagnosis. Glioblastoma (GBM) is the most prevalent malignant primary tumor of the central nervous system in adult patients and is known for its aggressive nature and tendency to invade surrounding tissues. Although GBM is rare, it carries a high fatality rate, with an incidence of 3.44 per 100,000 individuals and a median overall survival of only eight months, regardless of treatment. The five-year survival rate stands at a mere 7.2%. Recurrence poses a significant challenge for adult patients with GBM, and the prognosis remains bleak. Tumor recurrence, typically occurring within seven months from the initial diagnosis, is the primary cause of mortality. Both cancers have a high mortality rate and a high unmet need. Biodexa is hoping to meet these needs as it further develops MTX110. The main chemotherapy agent of MTX110, panobinostat, was originally used to treat multiple myeloma and received FDA approval in 2015. The company is currently reworking the chemotherapy agent by changing its delivery method and leveraging Convection Enhanced Delivery (CED) technology. Researchers discovered that the original formulation of panobinostat was capable of blocking enzymes involved in cancer cell growth, exhibiting high potency against brain stem tumor cells in vitro and in vivo. However, the original oral tablet form is both insoluble and incapable of crossing the blood-brain barrier at therapeutic levels - making it an ineffective treatment method for brain cancers. The distinctive feature of MTX110 is that it combines a water-soluble form of panobinostat with a CED device that delivers the drug directly to the brain tumor through a surgically implanted catheter and refillable pump. Biodexa says the drug achieves high drug concentrations within the tumor while limiting systemic exposure. The proof-of-concept phase 1 clinical trial of MTX110 took place at the University of California San Francisco with patients battling DMG. The trial produced promising results with a median overall survival of 26 months, compared to a historical overall survival rate of 10 months. Similarly, a phase 1 trial involving newly diagnosed DMG patients at Columbia University Irving Medical Center also had encouraging outcomes, with MTX110 treatment increasing median overall survival to 16 months from a historical overall survival rate of 10 months. The findings from this study will be presented at the 21st International Symposium on Pediatric Neuro-Oncology (June 28 - July 2, 2024), and the company may potentially continue developing the drug in this indication in a phase 2 study. Biodexa reports that the ongoing MAGIC-G1 phase 1 trial in recurrent GBM patients at Duke Cancer Institute and Baptist MD Anderson Cancer Center is currently showing considerable progress with completion of recruitment for cohort A of the study. The first patient survived for 12 months, and three patients currently remain in the study. The expected topline results for progression-free survival from cohort A will be available in Q2 of 2024. The retrospective analysis of 299 patients with similar recurrent GBM disease showed a median overall survival of only 6.5 months after the recurrence of GBM cancer. Biodexa is hopeful MTX110 could potentially help extend patient life, offering much-needed hope to patients and their families. The company's delivery method may also help prevent full-body exposure, which could minimize negative side effects. For cancers with such high mortality rates, any amount of extra time with a better quality of life is groundbreaking. Click here for more information on Biodexa Pharmaceuticals: Featured photo sourced from Shutterstock Important notice, please read: Certain statements in this material are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as "anticipate," "believe," "forecast," "estimate," "expect," and "intend," among others. These forward-looking statements are based on Biodexa's current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval, and commercialization of new products. Biodexa does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in the Annual Report on Form 10-K for the year ended December 31, 2022, as filed with the Securities and Exchange Commission (the "SEC") in March 2023, and periodic reports filed with the SEC on or after the date thereof. All Biodexa's forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof. This is not a solicitation of any offer to buy or sell. Redington, Inc. is paid by Biodexa Pharmaceuticals PLC to provide investor relations services, and its employees or members of their families may from time to time own an equity interest in companies mentioned herein. Contact: Stephen Stamp, CEO, CFO ir@biodexapharma.com SOURCE: Biodexa Pharmaceuticals Plc View the original press release on accesswire.com

2024年伊始，CAR-T研发领域不断传来好消息，近日世界权威期刊《自然医学（nature medicine）》上，报道了首次使用 双靶点CAR-T细胞（即CART-EGFR-IL13Rα2细胞） 治疗 胶质母细胞瘤（GBM） ， 显示出初步活性和安全性 ， 在治疗短短2天内，MRI就已出现肿瘤缩小表现 ，这意味着CAR-T在治疗实体瘤的有效性、持久性方面再进一层楼，攻克实体瘤指日可待！ ▲截图源自“nature medicine” 双靶点CAR-T具有强大抗肿瘤活性，治疗2天内肿瘤奇迹般缩小 CAR-T细胞疗法已获FDA批准，用于治疗多种血液系统恶性肿瘤。近年来，研究人员一直在努力研发并提升CAR-T细胞，用于对抗各类实体瘤。 本次应用的“双靶点”CAR-T细胞，打破了传统CAR-T只具有单一靶点的局限性，针对脑肿瘤常见的两种相关蛋白，即 表皮生长因子受体 （ EGFR ，存在于约60%的胶质母细胞瘤中）、 白细胞介素13受体α2 （ IL13Rα2 ，存在于约75%的胶质母细胞瘤中），进行研发。 在1期试验（NCT05168423）中，纳入6例复发性胶质母细胞瘤患者，采用鞘内注射的方式，对患者施用这款“EGFR”和“IL13Rα2”双靶点CAR-T细胞（即CART-EGFR-IL13Rα2）后， 24~48小时复查MRI显示，所有6例患者的肿瘤体积均缩小 （详见下图），而且部分患者缩小状态维持数月。此外， 神经毒性也在可控范围内 。 图1 一例胶质母细胞瘤患者治疗前后MRI变化 ▲图源“Penn Medicine News”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 综上，CART-EGFR-IL13Rα2细胞在治疗复发性胶质母细胞瘤方面，具有初步的安全性及生物活性。全球肿瘤医生网小编会持续关注后续研究报道，也期望它能早日上市惠及更多的患者。其实除了这款新型双靶点CAR-T细胞外，还有多款CAR-T细胞在实体瘤治疗领域，获得了不俗的疗效，下面简单盘点一下，以供参考。 国研GPC3 CAR-T细胞，晚期肝细胞癌患者无瘤生存超7年 ▲截图源自“WILEY Online Library” 国际知名期刊《Cancer Communications（癌症通讯）》，介绍了1例晚期肝细胞癌患者，在接受国研创新——CAR-GPC3 T细胞治疗后，完全缓解长达7年的报道，引起了巨大轰动！ 这位54岁的男性肝细胞癌患者，既往接受过手术治疗，但效果不佳，术后3个月后癌症复发，在多次治疗后，出现 下腔静脉癌栓、腹膜后淋巴结转移 等表现。此时对他而言，临床已无更好的治疗方案。抱着最后的希望，他参加了中国进行的CAR-GPC3 T细胞临床试验。这款CAR-T细胞针对的是肝细胞癌中名为“GPC3”的癌胚抗原， GPC3因其在70%~80%的肝细胞癌中高表达，而在正常组织中几乎不表达，因而被认为是精准治疗肝癌细胞的“黄金”靶标！ 该患者在入组接受CAR-T细胞联合局部治疗2周后，达到了完全缓解（详见下图）。幸运的是，截至目前他 已实现7年以上无瘤生存 。值得一提的是，在此期间，该患者除口服抗乙型肝炎病毒（HBV）药物治疗外，并未接受其他抗癌治疗。 CAR-T 疗法招募进行时： 目前有多款CAR-T临床实验正在进行中，主要针对以下癌种： Claudin18.2 ：用于治疗胃癌，胰腺癌等； 间皮素 （mesothelin）：用于治疗间皮瘤、胰腺癌、卵巢癌、肺癌； CEA ：用于治疗肺癌、结肠癌、胃癌、乳腺癌和胰腺癌； MUC-1 ：用于治疗肝癌、肺癌、胰腺癌、结肠癌、胃癌; GPC3： 用于治疗肝癌; GUCY2C ：用于治疗结直肠癌； PSMA ：用于治疗前列腺癌等； EGFＲvII ：用于治疗神经胶质瘤、头颈部肿瘤； B7-H3 ：用于治疗尤文肉瘤、横纹肌肉瘤、肾母细胞瘤、神经母细胞瘤、髓母细胞瘤、特别难以治疗的脑干肿瘤（DIPG）。 上述癌种患者如果想检测相关靶点或寻求CAR-T疗法帮助，可提交资料至 全球肿瘤医生网医学部 进行初步评估。 国研CT041宣战胰腺癌，肿瘤大幅缩小 ▲截图源自“BMC”网站 2023年11月，《血液学与肿瘤学杂志》报道了一例转移性胰腺癌患者，在接受国研CT041治疗后，靶病灶和转移灶明显缩小的的案例。 该患者为58岁女性，既往接受标准治疗失败，肿瘤持续进展，已发生全身转移。万念俱灰下，她入组接受了CT041细胞回输治疗。这是一款针对 CLDN18.2（即Claudin18.2，在胰腺癌中高表达）的新型CAR-T细胞产品 ，既往在治疗消化系统恶性肿瘤中获得了良好的缓解率。该患者在CT041治疗后，幸运的达到 部分缓解（PR），靶病灶显著缩小30%以上，同时肺转移也出现了大幅缩小 （详见下图）！ 图 患者治疗前后肺部影像学评估 ▲图源“BMC”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 注;“★”表示“原发病变”。 CAR-T在其他实体瘤治疗领域大放异彩 PART1 晚期铂耐药卵巢癌，PRGN-3005治疗后疾病控制率高达85.7% PRGN-3005是一种Ultra CAR-T细胞疗法，用于治疗 晚期复发性卵巢癌、输卵管癌、原发性腹膜癌 等。 《临床肿瘤学杂志》发表了“PRGN-3005治疗复发或难治性卵巢癌”的1/1b期临床研究结果，在入组的25例可评估患者中，其中位年龄为64岁(38-76)，既往接受过8种治疗方案的大量预处理。将这些患者分为三组，即环磷酰胺LD治疗组（IVLD，n=7）、经腹膜内(IP)输注组（C1，n=12）、经静脉(IV)输注组（C2，n=6）。 结果显示，IVLD组患者首次再分期时的 疾病控制率(DCR)高达85.7%，CA125平均降低了27.4% ， 靶肿瘤负荷降低57% (4/7)。在接受第二次PRGN-3005回输治疗后，1例患者的 目标肿瘤负荷减少28% 。且未发生与PRGN-3005相关的严重不良反应，如≥3级细胞因子释放综合征(CRS)、神经毒性、剂量限制性毒性等。 综上，PRGN-3005 Ultra CAR-T细胞疗法，在治疗卵巢癌中获得了较为理想的疾病控制率（DCR）率，且耐受性良好、总体肿瘤负荷减少。 PART2 结直肠癌：GCC19CART治疗后，客观缓解率达50% GCC19CART是由上海斯丹赛生物公司研发的一款CAR-T细胞产品，已获得美国食品和药物管理局（FDA）授予的快速通道资格，用于治疗结直肠癌。 根据实体肿瘤疗效评价标准，13例1级剂量组患者的 客观缓解率（ORR）达15.4% (2/13)，8例2级剂量组患者的 ORR达50% (4/8)！ 小编寄语 美国生物学家乔治•戴利曾说过：“如果说20世纪是药物治疗的时代，那么21世纪就是细胞治疗的时代”。随着医学技术的不断发展，以过继性免疫细胞治疗、癌症疫苗等为代表的肿瘤免疫疗法，也成了继手术、放疗、化疗后的第四种肿瘤治疗方法。 其中就不得不提到获得突破性进展的CAR-T细胞疗法，随着多款产品相继获批上市，CAR-T进入井喷式的发展模式。目前国内共有24家企业布局CAR-T疗法，包括 驯鹿医疗、传奇生物、复星凯特科济生物、药明巨诺、信达生物、西比曼生物 等。研究人员也在不断探索新的靶点、甚至开发双靶点，以尝试用于多款实体瘤的治疗。全球肿瘤医生网小编也希望在各国专家的共同努力下，CAR-T细胞可以早日突破价格和实体瘤的瓶颈，让更多晚期癌症患者受益！ 参考资料 [1]Bagley SJ,et al.Intrathecal bivalent CAR T cells targeting EGFR and IL13Rα2 in recurrent glioblastoma: phase 1 trial interim results. Nat Med. 2024 Mar 13. https://www.nature.com/articles/s41591-024-02893-z [2]Qi C,et al.CT041 CAR T cell therapy for Claudin18.2-positive metastatic pancreatic cancer. J Hematol Oncol.2023 Sep 9;16(1):102. https://jhoonline.biomedcentral.com/articles/10.1186/s13045-023-01491-9 [3]https://www.pennmedicine.org/news/news-releases/2024/march/dual-target-cell-therapy-appears-to-shrink-brain-tumors

AGOURA HILLS, Calif., March 25, 2024 (GLOBE NEWSWIRE) -- Oncotelic Therapeutics, Inc (OTCQB:OTLC) announced today the peer reviewed publication of Transforming Growth Factor Beta 2 (TGFB2) mRNA Levels, in Conjunction with Interferon-Gamma Receptor Activation of Interferon Regulatory Factor 5 (IRF5) and Expression of CD276/B7-H3, Are Therapeutically Targetable Negative Prognostic Markers in Low-Grade Gliomas: Past, Present, and Future Strategies in the Treatment and Management of Gliomas. Dr. Vuong Trieu, CEO and Chairman of Oncotelic, stated, ”Our R&D team has discovered crosstalk between the TGF-β and IFN signaling pathways, linking gliomas and Systemic Lupus Erythematosus (SLE). This publication has identified IRF5 as a common target for both diseases, opening up a new avenue for combating cancer,” Our findings place IRF5 at the intersection of inflammation and cancer. Understanding the role of IRF5 in both SLE and cancer opens an avenue for targeting IRF5 or its downstream pathways. This could offer new strategies for treating SLE and various cancers by modulating the immune response. The article can be accessed for free online: https://www.mdpi.com/2072-6694/16/6/1202 Abstract: Gliomas develop in the central nervous system from the glial cells that support it. Low-grade gliomas (LGGs) are characterized by a reduced number of immune cells infiltrating the tumor, requiring immune-boosting therapies to release the immunosuppressive environment of the tumor. We conducted a bioinformatics-led study to evaluate the prognostic impact of cell surface receptor markers for tumor-associated macrophages (TAMs) that produce transforming growth factor beta (TGFB) ligands and interferon-gamma receptor activation to maintain the tumor microenvironment in an immunosuppressed state. Detailed investigation of messenger RNA levels and their impact on OS in LGG patients demonstrated that low mRNA levels of a specific TGFB ligand, TGFB2, and the receptor along with the signaling molecules from interferon-gamma receptor activation (IFNGR2, IRF1, IRF5, and STAT1) result in improved survival of LGG patients. LGG patients expressing high levels of TGFB2 and IFNGR2 are over-represented in IDH wild-type tumor samples, suggesting that TGFB2 and IFNGR2 mRNA can be therapeutically targeted in these high-risk patients. Furthermore, demethylation of TFGB2, IFNGR2, IRF1, IRF5, STAT1, and CD276 genes also results in worse survival outcomes, pointing to a molecular mechanism that increases the negative prognostic effects of increased mRNA levels of these target genes. We observed that significant upregulation of mRNA expression levels for three TAM markers, MSR1/CD204, CD86, and CD68, suggested that TGFB2 is pivotal in establishing a pro-tumorigenic TME in gliomas mediated through TAMs. Interestingly, a tumor-associated antigen CD276/B7-H3 mRNA expression increased in tumor tissue, giving further insights into the roles of macrophages and tumor cells in the immunosuppressive TME. Therefore, to improve OS in LGG patients, combination therapies must target TGFB2 and IFN-γ activation (via IRF5 inhibition) or immune therapies targeted against CD276/B7-H3 About Oncotelic Oncotelic (f/k/a Mateon Therapeutics, Inc.), was formed in the State of New York in 1988 as OXiGENE, Inc., was reincorporated in the State of Delaware in 1992, and changed its name to Mateon Therapeutics, Inc. in 2016, and Oncotelic Therapeutics, Inc. in November 2020. Oncotelic is seeking to leverage its deep expertise in oncology drug development to improve treatment outcomes and survival of cancer patients with a special emphasis on rare pediatric cancers. Oncotelic has rare pediatric designation for Diffuse Intrinsic Pontine Glioma (“DIPG” through OT-101) through its 45% joint venture, GMP Biotechnology Limited, melanoma (through CA4P), and Acute Myeloid Leukemia (through OXi 4503). Oncotelic acquired PointR Data Inc. in November 2019 to build an AI driven biotechnology company. Further, Oncotelic acquired AL-101, during the 4th quarter of 2021, for the intranasal delivery of apomorphine. We intend to develop AL-101 for the treatment of Parkinson Disease, erectile dysfunction, female sexual disorder and hypoactive sexual desire disorder. All these ailments have a very large population suffering from them and there is a need for treatments for each. For more information on AL-101, refer to our Annual Report on Form 10-K/A filed with the SEC on April 19, 2023. Oncotelic's Cautionary Note on Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, included in this communication regarding strategy, future operations, future financial position, prospects, plans and objectives of management are forward-looking statements. Words such as "may", "expect", "anticipate" "hope", "vision", "optimism", "design", "exciting", "promising", "will", "conviction", "estimate," "intend," "believe", "quest for a cure of cancer", "innovation-driven", "paradigm-shift", "high scientific merit", "impact potential" and similar expressions are intended to identify forward-looking statements. Forward looking statements contained in this press release include, but are not limited to, statements about future plans related to the operations of the JV, taking the JV into an initial public offering or the success thereof, the progress, timing of clinical development, scope and success of future clinical trials, the reporting of clinical data for the Company’s product candidates and the potential use of the Company's product candidates to treat various cancer indications as well as obtaining required regulatory approval to conduct clinical trials and upon granting of approval by the regulatory agencies, the successful marketing of the products; building and the success of our nanoparticle platform and the related success of launching the platform, the development of the Company’s AI suite including but not limited to AI Chatbots, the public access to the Company’s AI suite, the success of the development of the AI suite or any other AI technologies and whether if any or portion thereof the Company’s AI suite or technologies will be commercialized and launched for sale. Each of these forward-looking statements involves risks and uncertainties, and actual results may differ materially from these forward-looking statements or may not occur at all. Many factors may cause differences between current expectations and actual results, including unexpected safety or efficacy data observed during preclinical or clinical studies, clinical trial site activation or enrollment rates that are lower than expected, changes in expected or existing competition, changes in the regulatory environment, failure of collaborators to support or advance collaborations or product candidates and unexpected litigation or other disputes, taking the Company or its affiliates through initial public offerings. These risks are not exhaustive, the company faces known and unknown risks, including the risk factors described in the Company's Annual Report on Form 10-K/A filed with the SEC on April 19, 2023 and in the company's other periodic filings. Forward-looking statements are based on expectations and assumptions as of the date of this press release. Except as required by law, the company does not assume any obligation to update forward-looking statements contained herein to reflect any change in expectations, whether because of new information, future events, or otherwise. Contact Information: For Oncotelic Therapeutics, Inc.:Investor Relationsir@oncotelic.com