Gastrinoma

Maria Duca speaking at the ELRIG Drug Discovery conference in London, UK. Credit: Frankie Fattorini/ GlobalData As interest mounts in using RNA as a therapeutic target, a group at the Institute of Chemistry in Nice is overcoming the need for lengthy, expensive screening of candidate compounds with a rational design approach. Dr. Maria Duca, head of the Targeting of Nucleic Acids team, outlined her team’s novel approach to RNA-targeting drug discovery, in a presentation today (3 October) at the ELRIG Drug Discovery 2024 conference in London, UK. Duca pointed out, “If we look at currently marketed drugs, these mainly target proteins, but these proteins represent a very small percentage of what the human genome encodes. If we take into account non-coding RNAs as potential targets for drugs, we could really widen the landscape of current medicinal chemistry.” However, according to Duca, “The problem is that you don’t have many rational design methodologies in order to design your compound specific for a particular RNA target. So, everything is mostly based on screenings.” Instead of mass screenings, Duca and her team assemble and test novel molecular conjugates to be target-specific and therapeutically effective. Duca said some of the more promising candidates created using this approach have potential in oncological and infectious disease indications. See Also: Advancing Pharmaceutical Security: The Role of SECURtracers in On-Dose Authentication Healthcare Payers for the Pharmaceutical Industry Duca outlined the discovery process behind her team’s conjugate against microRNA-327 (miRNA-327), an oncogenic RNA implicated in gastric cancer. The team conjugated the aminoglycoside neomycin with different artificial nuclear bases. The conjugates produced were screened in vitro for their selectivity and inhibitive activity towards miRNA-327. Promising candidates from these screens could then be studied in vivo. In gastrinoma cancer cells, which are characterised by miRNA-327 overexpression, the team found the chosen candidates inhibited cell proliferation in a dose-dependent manner. Imaging the conjugate-RNA interactions allowed them to further refine these neomycin conjugates for their miRNA-327 affinity and inhibition. Through this same process of design, in vitro screening, in vivo testing, and further structural refinement of conjugates, Duca and her team have produced therapeutic candidates targeting other RNAs. For example, they built another library of candidates targeted against miRNA-21 which is overexpressed in glioblastoma, a type of brain cancer. Applying the same rational design process, researchers produced candidates that inhibited glioblastoma cell proliferation, in a way that was comparable with the efficacy of temozolomide, one of the few palliative treatments for glioblastoma, marketed as Kimozo / Kizfizo by Orphelia Pharma. mRNA vaccine coverage on Pharmaceutical Technology (Or Clinical Trials Arena) is supported by Trilink . Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content. Free Whitepaper mRNA capping: low cost, high reward Are you aware of the latest mRNA capping techniques? The success of mRNA-based Covid vaccines has seen the technology boom in popularity – but capping is an essential part of the manufacturing process, and pharmaceutical firms face a range of choices on how to do it. This free whitepaper assesses differences in price, time, complexity and availability for the methods on offer – and provides essential insights on TriLink’s trailblazing CleanCap® approach. Fill in your details to find out more. Thank you. You will receive an email shortly. Please check your inbox to download the Whitepaper. By Trilink Thematic By downloading this Whitepaper, you acknowledge that GlobalData may share your information with Trilink Thematic and that your personal data will be used as described in their Privacy Policy

DURHAM, N.C., Feb. 28, 2023 (GLOBE NEWSWIRE) -- Cancer Advances, Inc., a clinical stage biopharmaceutical company developing therapeutics for gastrointestinal (GI) cancers, announced that the U.S. Patent and Trademark Office has issued new patent No. 11,583,576, enhancing the Company’s intellectual property position for lead asset Polyclonal Antibody Stimulator (PAS) vaccine. The new patent titled “Compositions and Methods for Inducing Humoral and Cellular Immunities against Tumors and Cancer” covers a method for treating and/or preventing and/or inhibiting development of a tumor and/or a cancer associated with gastrin signaling in a subject. Gastrin mediated tumors include, but are not limited to, gastrointestinal cancers. The novel IP further covers methods for treatment of GI cancer by administering PAS followed by an immune checkpoint inhibitor. A related claim covers reduction in fibrosis associated with pancreatic cancer via the administration of this combination. “After more than six years of research, we are excited to have this patent issued. We have known that PAS can induce the development of antibodies to Gastrin, bringing Gastrin levels down and increasing survival times by 50% in GI clinical trials. With our research now demonstrating that PAS is able to alter the tumor microenvironment, it opens the door to many new opportunities to improve current treatment for GI cancer patients,” commented Lynda Sutton, President of Cancer Advances. The issued patent adds to the over one hundred granted global patents for PAS. Cancer Advances plans to seek approval for PAS in the treatment of gastric and pancreatic cancers. About Cancer Advances, Inc. Cancer Advances Inc. (Durham, NC) is a biotechnology company focused on impacting human health and preventing the progression of gastrointestinal cancers by enhancing the adaptive immune system. The company is led by an experienced management team with over one hundred and twenty years of combined experience in drug development and commercialization experience. About Polyclonal Antibody Stimulator (PAS) Polyclonal Antibody Stimulator (PAS) vaccine is an immunomodulator potentially applicable in multiple cancer types including gastric, pancreatic, and colorectal. The vaccine is a peptide-conjugate that includes an N-terminal epitope of human gastrin-17 (G17) linked to carrier diphtheria toxoid. PAS has been studied in multiple clinical trials, in over 1,500 human subjects, and has demonstrated an excellent safety and tolerability profile. Cancer Advances exclusively owns PAS and is funding and managing all aspects of the PAS gastrin vaccine program. Contact Cancer Advances, Inc. E-mail: jwingen@canceradvances.com

HOBOKEN, N.J. and PHILADELPHIA, Sept. 20, 2011 /PRNewswire/ -- Niiki Pharma Inc. announced interim results from the ongoing Phase I clinical trial of its lead product, NKP-1339. NKP-1339 is a first-in-class transferrin targeted small molecule that down-regulates GRP78, a key regulator of mis-folded protein processing and a tumor survival factor. NKP-1339 Phase I Interim Data The Phase I trial is conducted in patients with metastatic solid tumors resistant to standard therapies. Previous to enrollment in the trial, all patients had received multiple standard therapies and exhibited disease progression on their last treatment. Of the first 24 patients enrolled, six patients (25%) exhibited anti-tumor activity, demonstrated by disease stability and/or tumor regression for at least 12 weeks. Of the responding six patients, one patient with carcinoid tumor, a non-pancreatic neuroendocrine tumor (non-pNET), has tumor regression and continues on NKP-1339 therapy for more than 70 weeks. The five other patients have experienced stable disease of up to 24 weeks with NKP-1339 treatment. These patients have the following tumor types: one gastrinoma non-pNET, one colorectal cancer, two non-small cell lung cancers and one cancer of unknown primary. NKP-1339 treatment has been well tolerated to date with mild manageable side effects. The most common drug-related side effects are grade 1-2 fever and mild flu-like symptoms, which can be prevented with standard medications. The maximum tolerated dose has not been reached and NKP-1339 dose escalation continues. The trial is being led by Dr. Daniel Von Hoff, Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare in partnership with Translational Genomics Institute (TGen), and Dr. Howard Burris, Director of Drug Development at the Sarah Cannon Research Institute (SCRI). "We need new treatments for patients with non-pNET. The NKP-1339 anti-tumor activity observed in these two non-pNET patients is significant. This activity, together with mild-side effect profile, makes NKP-1339 a potentially promising new treatment for this disease," said Dr. Daniel Von Hoff. "It is gratifying to see someone whose tumor has been resistant to other therapies do well with this promising investigational therapy. The patient has received NKP-1339 for more than a year and continues to benefit," added Dr. Howard Burris. "We are pleased by these interim results demonstrating the single agent anti-tumor activity of NKP-1339 in patients with advanced cancers refractory to standard treatments," said Dr. Angela Ogden, Chief Medical Officer for Niiki Pharma Inc. "The preliminary results of this ongoing trial, showing the anti-tumor activity and the safety pro NKP-1339, support our preclinical studies that the drug targets tumors selectively and is active against different tumors. We are delighted to see years of research come to fruition in collaboration with Niiki Pharma's team," said Professor Keppler, University of Vienna, inventor of NKP-1339. About NKP-1339 NKP-1339 is a first-in-class transferrin targeted ruthenium-based anti-cancer compound. Transferrin receptor is significantly over-expressed in many tumor types. The intracellular target pathways of NKP-1339 include down-regulation of GRP78, a key regulator of mis-folded protein processing and a tumor survival factor. GRP78 is the cause of resistance in many tumor types. In preclinical studies, NKP-1339 has demonstrated activity against multiple tumor types, including those resistant to other anti-cancer agents, including platinum-containing agents, anthracyclines and anti-tubulins. NKP-1339 was invented by Professor Bernard K. Keppler, currently the Dean of the Faculty of Chemistry at University of Vienna, Austria, and Head of the Research Platform "Translational Cancer Therapy Research", a multi-disciplinary collaboration between University of Vienna and the Medical University of Vienna. Professor Keppler is a member of the Vienna Board of Trustees for Innovative and Interdisciplinary Cancer Research, the current President of the Austrian Association of University Professors, and a founding member of the Central European Society of Anticancer-Drug Research. He is on the Editorial Boards of several scientific journals, including: Anticancer Research, Chemical Monthly, Bioinorganic Chemistry and Applications, Journal of Inorganic Biochemistry (2005-2009) and Current Chemical Biology. About NKP-1339 Phase I Trial Principal Investigators Dr. Daniel Von Hoff, M.D., F.A.C.P., is the Physician-in-Chief and Distinguished Professor at Virginia G. Piper Cancer Center Clinical Trials, at Scottsdale Healthcare in partnership with TGen in Phoenix, Arizona, and the Chief Scientific Officer for US Oncology. He was appointed to and served six years on President Bush's National Cancer Advisory Board and was past President of the American Association for Cancer Research (AACR) a former Board member of the American Society of Clinical Oncology (ASCO), and the 2010 recipient of the David A. Karnofsky Memorial Award by ASCO for his outstanding achievements in cancer research. Dr. Howard Burris, M.D., F.A.C.P., is the Director of Drug Development for SCRI, a Nashville, Tennessee, global clinical research organization focusing on advancing therapies and accelerating drug development in areas such as oncology, cardiology and gastroenterology and a member of Tennessee Oncology. He is also a member of the ASCO Ethics, Clinical Practice and Program Committees, Board member of Gilda's Club, Past-President and Trustee for the Southern Association of Oncology, and Editor of the Oncology Report. About Niiki Pharma Inc. Niiki Pharma Inc. is an oncology therapeutics development company, which is focused on development of targeted first-in-class treatments for cancer. LinksNiiki Pharma Inc. Dr. Daniel Von Hoff, TGen Dr. Howard Burris, SCRI Professor Bernard K. Keppler, University of Vienna SOURCE Niiki Pharma Inc.