Epstein-Barr virus associated gastric carcinoma

SINGAPORE, July 16, 2024 /PRNewswire/ -- Biosyngen, a leading biotechnology company focused on the development of innovative cell therapies, recently announced that the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) in China has approved the initiation of a pivotal Phase ll clinical trial evaluating BRG01, the company's autologous Epstein-Barr virus (EBV) specific chimeric antigen receptor T-cell (CAR-T) therapy, for the treatment of patients with recurrent or metastatic EBV-positive nasopharyngeal carcinoma. BRG01 is the world's first CAR-T therapy for solid tumor to obtain clinical trial approvals from China and the U.S. and to advance to a pivotal Phase ll clinical trial, representing a significant milestone in the field of cell-based immuno-therapies for solid cancers. Continue Reading Professor Zhang Li "The approval of the Phase ll clinical trial for BRG01 is a testament to the robust preclinical data and strong early clinical results observed with this innovative therapy" said Professor Zhang Li, Director of the Phase l Ward at the Sun Yat-Sen University Cancer Center and Deputy Director of the Lung Cancer Research Institute at Sun Yat-sen University, who is serving as the principal investigator for the BRG01 clinical trial. "BRG01 has the potential to be a first-in-class T-cell therapy for EBV-positive tumors, and we are confident in its ability to deliver meaningful clinical benefits to patients with this difficult-to-treat malignancy." The Phase l clinical trial of BRG01 in China and the U.S. has completed patient enrollment in January this year. All participants have received BRG01 infusion as part of this registered clinical trial. The Phase l study has successfully completed assessments of dose-limiting toxicity (DLT) and preliminary efficacy in nine patients with advanced nasopharyngeal carcinoma who had previously been treated with at least one immune checkpoint inhibitor, such as a PD-1antibody. Initial data from the study have demonstrated excellent safety and encouraging signs of clinical activity, with 75% of high-dose patients experiencing local tumor shrinkage and reduced metabolic activity on PET-CT scans, and some patients achieving complete remission of their tumor lesions . Additionally, BRG01 has shown potent anti-EBV activity, with significant reductions in peripheral blood EBV viral load observed following treatment . These findings underscore BRG01's potential in tumor therapy and highlight its dual benefits in antiviral treatment, establishing a robust foundation for future clinical applications. These results are likely pivotal in the CDE's decision to advance BRG01 to phase II clinical trials. BRG01 is an autologous T cell immunotherapy product that has been engineered to express chimeric receptors targeting the Epstein-Barr virus (EBV) antigen on the surface of T cells. This innovative therapy represents a new generation of CAR-T cell treatment specifically designed to target EBV. BRG01 received phase I clinical trial approval from the CDE in China in December 2022 and from the FDA in the United States in February 2023. Subsequently, it was granted orphan drug designation (ODD) and fast track designation (FTD) by the FDA in June and July 2023, respectively. At the annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) in May, Biosyngen presented preclinical research on the therapy, and the data was published as an original study in Frontiers in lmmunology. In addition, at the Gordon Research Conference (GRC) on Nasopharyngeal Carcinoma held in Switzerland in early June this year, Biosyngen's scientist and pipeline inventor, Chair of Translational Immuno-Oncology at the University of Cologne, Professor Renata Stripecke also presented the results of preclinical research and the latest clinical data of this therapy. The development of cell therapy drugs for hematological malignancies has seen substantial progress, yet advancements in solid tumor treatments have lagged behind. The FDA's accelerated approval of lovance's tumor-infiltrating lymphocyte (TlL) therapy, lifileucel, for the treatment of advanced melanoma in February represents a significant milestone in the commercialization of solid tumor cell therapies. This milestone has bolstered confidence among companies engaged in the development of cell therapies for solid tumors. However, overcoming the challenges posed by solid tumors requires a unique and comprehensive approach from the outset. This approach must encompass considerations regarding technology, target selection, and indication, ensuring satisfaction of clinical needs and druggability of the therapeutic interventions. As one of the most common head and neck tumors, nasopharyngeal carcinoma - an epithelial carcinoma arising from the nasopharyngeal mucosal lining, is closely related to EBV infection. According to WHO, an estimated number of 133,000 new cases of nasopharyngeal carcinoma worldwide was reported in 2020; 50% of which was diagnosed in China. South China provinces such as Guangdong and Guangxi provinces make up for more than 60% of nasopharyngeal carcinoma patient population in China. Though existing practice such as immune checkpoint inhibitor has been applied in second-line treatment of nasopharyngeal carcinoma, overall response rates were generally below 30%. In another words, more than 70% patients did not benefit from existing therapy. Therefore, it is imperative to explore new approaches to improve efficacy and satisfy unmet medical needs. The emergence and progression of nasopharyngeal carcinoma are closely associated with Epstein-Barr virus (EBV) infection. EBV has infected about 95% of population worldwide. It has been listed as Group 1 carcinogen ("Carcinogenic to humans") by World Health Organization (WHO) and proved to be associated with a range of diseases including nasopharyngeal carcinoma, EBV-positive gastric cancers, lymphoma and lymphoproliferative diseases. Research indicates that tumor cells in nasopharyngeal carcinoma frequently exhibit EBV antigen expression, and EBV-positive tumor cells display target proteins for CD4+T cells and CD8+T cells, facilitating the infiltration of EBV-targeting CAR T cells into tumor tissue to exert a cytotoxic effect. Leveraging this specific EBV target, CAR T-cell therapy developed by Biosyngen is also being explored for treating EBV-positive lymphoma. In April 2023, BRG01 obtained approval from the Drug Evaluation Center (CDE) and the Food and Drug Administration (FDA) for clinical trials in this new indication, with Phase I clinical studies currently ongoing. Biosyngen has evolved into a biotechnology company specializing in three major cell therapies for solid tumors and hematologic malignancies, including CAR-T, TCR-T, and TIL. The company's therapies utilizing these strategies have all been granted approvals for clinical trials, with its TCR-T and TIL therapies targeting various solid tumors such as lung and liver cancer. "The approval of BRG01 for a pivotal Phase ll clinical trial is a major milestone for Biosyngen and underscores our commitment to developing innovative cell therapies to address significant unmet needs in solid tumors," said Dr. Michelle Chen, Co-Founder and CEO of Biosyngen. "We plan to continue investing in research and development to expedite the clinical progress and market availability of BRG01, offering more effective treatment options for patients worldwide." With Biosyngen's efficient operations and rapid research outcomes, there is optimism for significant advancements in solid tumor cell therapies within a shorter timeframe, potentially bringing new treatment possibilities and hope to patients. SOURCE Biosyngen

Evaluation of the Safety and Efficacy of Eflornithine (Difluoromethylornithine, DFMO) in Patients with Gastric Premalignant Conditions in the High Incidence Areas of Latin AmericanMINNEAPOLIS, June 10, 2024 (GLOBE NEWSWIRE) -- Panbela Therapeutics, Inc. (OTCQB: PBLA), a clinical stage biopharmaceutical company developing disruptive therapeutics for the treatment of patients with cancer, today announces an oral presentation at the Digestive Disease Week (DDW) conference, which was held May 18-21, 2024. The work reflects the Company’s on-going collaboration with Vanderbilt University Medical Center. “Gastric adenocarcinoma is the fifth leading global cause of cancer mortality and leading infection-associated cancer. In the U.S., gastric adenocarcinoma represents a major cancer disparity, with incidence rates 2-3 times or more greater in all non-white populations. Patients with gastric premalignant conditions, intestinal metaplasia and atrophic gastritis, represent a high unmet need for chemopreventative approaches,” said Dr. Douglas R. Morgan, UAB Division of Gastroenterology and Hepatology, The University of Alabama at Birmingham, AL and Dr. Keith T. Wilson, Division of Gastroenterology and Hepatology, Vanderbilt University Medical Center, Nashville, TN. A National Cancer Institute funded, Phase IIa placebo-controlled Randomized Clinical Trial of eflornithine in patients with gastric premalignant conditions was conducted between September 2016 and December 2022 in rural Honduras and Puerto Rico and was an oral presentation at DDW by Dr. Wilson on May 21, 2024. H. pylori (Hp) positive and negative subjects ages 30-60 were treated with eflornithine or placebo for 18 months, with endoscopy at baseline, and 6, 18, and 24 months. At baseline, 80% of subjects were Hp positive, and 46% and 54% had global histology of atrophy and intestinal metaplasia, respectively. A total of 78, 69, and 55 patients reached the 6-month primary outcome, the end-of-treatment 18 month (EoT), and the end-of-study (EoS) 24 month time points, respectively. Eflornithine treatment was safe and well-tolerated. Overall grade 1-2 adverse events (AEs) were greater in the placebo group (108 vs 81) and grade 3 AEs were also higher in the placebo (3 vs 1). The results of the study demonstrated that eflornithine reduced DNA damage long-term in patients after completing treatment, as measured by pH2AX immunostaining, a DNA damage marker was significantly lower at the 24 month vs. 18 month time point in the eflornithine group and unchanged in the placebo group. “Panbela’s focus on the polyamine pathway has implications for both the prevention and treatment of cancer. It is established that pro-tumorigenic and cancer cells are highly dependent on polyamines for survival and the ability of eflornithine to reduce gastric epithelial cell DNA damage may have implications for prevention in those patients at high risk for developing infection-associated gastric cancer,” said Jennifer K. Simpson, PhD, MSN, CRNP, President & Chief Executive Officer of Panbela. Details of the presentation are as follows: Oral Presentation Title: Evaluation of the Safety and Efficacy of Eflornithine (Difluoromethylornithine, DFMO) in Patients with Gastric Premalignant Conditions in the High Incidence Areas of Latin America Session Type: Research Forum Session Title: Chemoprevention for GI Cancers: Drugs and/or Bugs Session Date and Time: May 21, 2024 from 2:00 PM to 3:30 PM EDT (UTC –4) Additional meeting information can be found on the DDW website: https://eppro02.ativ.me/src/EventPilot/php/express/web/planner.php?id=DDWLITE24 The abstract will also be available on the Company's website at https://panbela.com/events-presentations/ once the information has been released by DDW. About Panbela’s PipelineThe pipeline consists of assets currently in clinical trials with an initial focus on familial adenomatous polyposis (FAP), first-line metastatic pancreatic cancer, neoadjuvant pancreatic cancer, colorectal cancer prevention and ovarian cancer. The combined development programs have a steady cadence of anticipated catalysts with programs ranging from pre-clinical to registration studies. Ivospemin (SBP-101)Ivospemin is a proprietary polyamine analogue designed to induce polyamine metabolic inhibition (PMI) by exploiting an observed high affinity of the compound for pancreatic ductal adenocarcinoma and other tumors. It has shown signals of tumor growth inhibition in clinical studies of metastatic pancreatic cancer patients, demonstrating a median overall survival (OS) of 14.6 months and an objective response rate (ORR) of 48%, both exceeding what is typical for the standard of care of gemcitabine + nab-paclitaxel suggesting potential complementary activity with the existing FDA-approved standard chemotherapy regimen. In data evaluated from clinical studies to date, ivospemin has not shown exacerbation of bone marrow suppression and peripheral neuropathy, which can be chemotherapy-related adverse events. Serious visual adverse events have been evaluated and patients with a history of retinopathy or at risk of retinal detachment will be excluded from future SBP-101 studies. The safety data and PMI profile observed in the previous Panbela-sponsored clinical trials provide support for continued evaluation of ivospemin in the ASPIRE trial. Flynpovi ™Flynpovi is a combination of CPP-1X (eflornithine) and sulindac with a dual mechanism inhibiting polyamine synthesis and increasing polyamine export and catabolism. In a Phase III clinical trial in patients with sporadic large bowel polyps, the combination prevented > 90% subsequent pre-cancerous sporadic adenomas versus placebo. Focusing on FAP patients with lower gastrointestinal tract anatomy in the recent Phase III trial comparing Flynpovi to single agent eflornithine and single agent sulindac, FAP patients with lower GI anatomy (patients with an intact colon, retained rectum or surgical pouch), showed statistically significant benefit compared to both single agents (p≤0.02) in delaying surgical events in the lower GI for up to four years. The safety profile for Flynpovi did not significantly differ from the single agents and supports the continued evaluation of Flynpovi for FAP. CPP-1XCPP-1X (eflornithine) is being developed as a single agent tablet or high dose powder sachet for several indications including prevention of gastric cancer, treatment of neuroblastoma and recent onset Type 1 diabetes. Preclinical studies as well as Phase I or Phase II investigator-initiated trials suggest that CPP-1X treatment may be well-tolerated and has potential activity. About PanbelaPanbela Therapeutics, Inc. is a clinical-stage biopharmaceutical company developing disruptive therapeutics for patients with urgent unmet medical needs. Panbela’s lead assets are Ivospemin (SBP-101) and Flynpovi. Further information can be found at www.panbela.com. Panbela’s common stock is eligible for quotation on the OTCQB under the symbol “PBLA”. Cautionary Statement Regarding Forward-Looking StatementsThis press release contains “forward-looking statements,” including within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by words such as: “anticipate,” “believe,” “can,” “design,” “expect,” “focus,” “intend,” “looking forward,” “may,” “plan,” “positioned,” “potential,” and “will.” All statements other than statements of historical fact are statements that should be deemed forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based only on our current beliefs, expectations, and assumptions regarding the future of our business, future plans and strategies, projections, anticipated events and trends, the economy and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict and many of which are outside of our control. Our actual results and financial condition may differ materially and adversely from the forward-looking statements. Therefore, you should not rely on any of these forward-looking statements. Important factors that could cause our actual results and financial condition to differ materially from those indicated in the forward-looking statements include, among others, the following: (i) our ability to obtain additional funding to execute our business and clinical development plans; (ii) progress and success of our clinical development program; (iii) the impact of the current COVID-19 pandemic on our ability to conduct our clinical trials; (iv) our ability to demonstrate the safety and effectiveness of our product candidates: ivospemin (SBP-101) and eflornithine (CPP-1X); (v) our reliance on a third party for the execution of the registration trial for our product candidate Flynpovi ; (vi) our ability to obtain regulatory approvals for our product candidates, SBP-101 and CPP-1X in the United States, the European Union or other international markets; (vii) the market acceptance and level of future sales of our product candidates, SBP-101 and CPP-1X; (viii) the cost and delays in product development that may result from changes in regulatory oversight applicable to our product candidates, SBP-101 and CPP-1X; (ix) the rate of progress in establishing reimbursement arrangements with third-party payors; (x) the effect of competing technological and market developments; (xi) the costs involved in filing and prosecuting patent applications and enforcing or defending patent claims; (xii) our ability to obtain a listing of our common stock on a national securities exchange; and (xii) such other factors as discussed in Part I, Item 1A under the caption “Risk Factors” in our most recent Annual Report on Form 10-K, any additional risks presented in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Any forward-looking statement made by us in this press release is based on information currently available to us and speaks only as of the date on which it is made. We undertake no obligation to publicly update any forward-looking statement or reasons why actual results would differ from those anticipated in any such forward-looking statement, whether written or oral, whether as a result of new information, future developments or otherwise.

- Confirmed objective response rate (ORR) of 40% in PD-L1 positive (TPS ≥1%)patients with no prior checkpoint inhibitor therapy (CPI) - Median progression-free survival (PFS) of 6.3 months in PD-L1 positive patients at time of data cut off - Confirmed ORR of 50% in patients with PD-L1 high expression (TPS ≥50%) and 38% in patients with PD-L1 low expression (TPS 1-49%) - RAPT to host webcast conference call today at 10:00 am PT SOUTH SAN FRANCISCO, Calif., Nov. 03, 2023 (GLOBE NEWSWIRE) -- RAPT Therapeutics, Inc. (Nasdaq: RAPT), a clinical-stage, immunology-based therapeutics company focused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in inflammatory diseases and oncology, today announced safety and efficacy data from its Phase 2 trial of FLX475 (tivumecirnon) in patients with advanced non-small cell lung cancer (NSCLC) who had no prior checkpoint inhibitor therapy. The trial evaluated FLX475, an oral small molecule CCR4 antagonist designed to block the migration of regulatory T cells, in combination with the checkpoint inhibitor pembrolizumab. In this cohort of NSCLC patients, 36 patients were evaluable for efficacy, of which 20 were PD-L1 positive. In these PD-L1 positive patients, the combination of FLX475 and pembrolizumab showed a 40% (8/20) confirmed ORR and a median PFS of 6.3 months as of the data cut off date, with seven patients continuing on study. For comparison, historical pembrolizumab monotherapy activity in checkpoint inhibitor-naïve and previously-treated NSCLC patients showed a confirmed ORR of 18% and a median PFS of 4.0 months. The confirmed ORR for the combination of FLX475 and pembrolizumab in PD-L1 low and high subsets were 38% (6/16) and 50% (2/4), respectively. For comparison, the ORR for pembrolizumab monotherapy in the PD-L1 low and high subsets has been previously reported as 10% and 30%, respectively. The data were presented today in a poster at the Society for Immunotherapy of Cancer (SITC) 38th Annual Meeting being held in San Diego. The presenting author was Julie Brahmer, M.D., Co-director of the Upper Aerodigestive Department and Professor of Oncology, Johns Hopkins University. “We are excited by the response rates and PFS data for FLX475 in combination with a checkpoint inhibitor in this cohort of NSCLC patients. The data from this cohort, which will continue to mature and potentially improve, met our criteria to advance development of FLX475,” said Brian Wong, M.D., Ph.D., President and Chief Executive Officer of RAPT. “We are particularly intrigued to see differentiating efficacy in patients with cool (PD-L1 low) tumors, which are typically poorly responsive to checkpoint inhibitors and checkpoint inhibitor combinations, such as those with anti-TIGIT antibodies. Along with RPT193, we now have two internally discovered compounds that have demonstrated clinical proof of concept in large, commercially attractive indications.” Phase 2 Data Summary in CPI-naïve NSCLC Patients (n=20) PD-L1 Status Confirmed Responses (n) Confirmed ORR Positive (TPS ≥1%) 8/20 40% Low (TPS 1-49%) 6/16 38% High (TPS ≥50%) 2/4 50% At the time of data cut off, there was one additional response among the PD-L1 low patients awaiting confirmation. The combination of FLX475 and pembrolizumab was well tolerated in this Phase 2 NSCLC cohort. The most common treatment-emergent adverse event deemed related to study treatment was QT prolongation that was asymptomatic and reversible. FLX475 has now been dosed in more than 300 patients with various advanced cancers and has been generally well tolerated, and the combination with pembrolizumab has not increased immune-related toxicity beyond that expected with pembrolizumab alone. In previous disclosures, FLX475 showed durable objective responses as monotherapy in an EBV+ lymphoma, as well as in combination with pembrolizumab in EBV+ gastric cancer. Webcast Conference Call Information RAPT will host a webcast conference call today, November 3, 2023 at 10:00 a.m. PT. To join the conference call via phone and participate in the live Q&A session, please pre-register online here to receive a telephone number and unique passcode required to enter the call. The live webcast and audio archive of the presentation may be accessed on the RAPT Therapeutics website at . About FLX475 FLX475 (tivumecirnon) is a small molecule CCR4 antagonist designed to block the migration of regulatory T cells (Treg) specifically into tumors, but not healthy tissues. Treg represent a dominant pathway for downregulating the immune response, generally correlate with poor clinical outcomes, and may limit the effectiveness of currently available therapies such as checkpoint inhibitors. FLX475 may restore naturally occurring antitumor immunity alone and may synergize with a variety of both conventional and immune-based therapies, such as radiation, chemotherapy, checkpoint inhibitors, immune stimulators, cancer vaccines, and adoptive T cell therapy. About RAPT Therapeutics, Inc. RAPT Therapeutics is a clinical stage immunology-based therapeutics company focused on discovering, developing and commercializing oral small molecule therapies for patients with significant unmet needs in inflammatory diseases and oncology. Utilizing its proprietary discovery and development engine, the company is developing highly selective small molecules designed to modulate the critical immune drivers underlying these diseases. RAPT has discovered and advanced two unique drug candidates, RPT193 (zelnecirnon) and FLX475 (tivumecirnon), each targeting C-C motif chemokine receptor 4 (CCR4), for the treatment of inflammation and cancer, respectively. The company is also pursuing a range of targets that are in the discovery stage of development. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “anticipate,” “could,” “expect,” “look forward,” “plan,” “target,” “will” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These statements relate to future events and involve known and unknown risks, uncertainties and other factors that may cause our actual results, performance or achievements to be materially different from any future performances or achievements expressed or implied by the forward-looking statements. Each of these statements is based only on current information, assumptions and expectations that are inherently subject to change and involve a number of risks and uncertainties. Forward-looking statements include, but are not limited to, statements about the therapeutic potential of FLX475, plans to advance clinical development of FLX475 and RPT193, plans to seek a partner to accelerate development of FLX475 and other statements that are not historical fact. Many factors may cause differences between current expectations and actual results, including unexpected safety or efficacy data observed during clinical studies, preliminary data and trends may not be predictive of future data or results, may not demonstrate safety or efficacy or lead to regulatory approval by the FDA or other regulatory agencies, clinical trial site activation or enrollment rates that are lower than expected, changes in expected or existing competition, changes in the regulatory environment, the uncertainties and timing of the regulatory approval process, the timing and results of unexpected litigation or other disputes, and the sufficiency of RAPT’s cash resources. Detailed information regarding risk factors that may cause actual results to differ materially from the results expressed or implied by statements in this press release may be found in RAPT’s Form 10-Q for the quarter ended June 30, 2023 and subsequent filings made by RAPT with the Securities and Exchange Commission. These forward-looking statements speak only as of the date hereof. RAPT disclaims any obligation to update these forward-looking statements. Investor Contact: Sylvia Wheeler swheeler@wheelhouselsa.com Media Contact: Aljanae Reynolds areynolds@wheelhouselsa.com