PARP inhibitor(Satyarx Pharma)

225Ac-Satoreotide is a first-in-class somatostatin receptor 2 antagonist targeting extensive stage small cell lung cancer and is the first antagonist labelled with 225Ac to enter clinical development Satoreotide expressed a superior pharmacokinetic profile relative to DOTA-TATE with a higher pre-clinical anti-tumour efficacy, irrespective of radionuclide used 100% survival with a single dose of 30 kBq 225Ac-satoreotide but not with 225Ac-DOTA-TATE BERLIN, Oct. 22, 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 presented data on its proprietary radiolabelled peptide SS0110 (satoreotide), a first-in-class antagonist of the somatostatin receptor 2 (SSTR2), at this year's European Association of Nuclear Medicine (EANM) Annual Conference, held in Hamburg, Germany from 19-23 October 2024. The Top-Rated Oral Presentation (TROP) entitled '225Ac-SSO110 induces long-lasting anti-tumour responses in contrast to 225Ac-DOTA-TATE and 161Tb-DOTA-TATE in the treatment of SSTR2-positive tumour xenografts', details the anti-tumour efficacy of different radiolabelled satoreotide antagonists (225Ac, 161Tb, 177Lu-labelled SSO110) versus respective DOTA-TATE agonists (225Ac- and 161Tb-labelled DOTA-TATE) in mice engrafted with SSTR2 positive xenografts of small cell lung cancer (SCLC) and pancreatic cancer using clinically relevant associated dose ranges. Results demonstrate that 225Ac-satoreotide shows the strongest anti-tumoural effect in vivo at a low single dose when evaluating satoreotide and DOTA-TATE radiolabelled with different radionuclides. Irrespective of the radionuclides used, satoreotide demonstrated a higher pre-clinical anti-tumour efficacy when compared to DOTA-TATE which was less potent and required increased dose levels. Satoreotide was well tolerated across all dose levels and with all used radionuclides. These comparisons between satoreotide and DOTA-TATE will facilitate and guide further clinical development of satoreotide across multiple indications expressing SSTR2, such as SCLC, pancreatic cancers and Merkel Cell Carcinoma (MCC). Previous comparisons between satoreotide and DOTA-TATE demonstrated that antagonist, 225Ac-satoreotide, is multiple times more potent than SSTR2 agonist, 225Ac-DOTA-TATE, signifying a durable complete response in standard murine xenograft models of SCLC in animal models, versus tumour growth delay. Ariceum had previously shown at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting 2024 that 212Pb was not seen to be more potent than Lutetium or Terbium but caused more side effects and hence was not further pursued. Manfred Rüdiger, Chief Executive Officer at Ariceum Therapeutics, said: "These results provide strong evidence for satoreotide and its potential to clinically outperform SSTR2 targeting agonists, by demonstrating significantly better efficacy in tumour growth control, up to complete tumour eradication depending on isotope used. In addition, when a single dose of 30 kBq 225Ac-satoreotide was administered, we observed high frequency of complete durable responses and 100% survival which strongly supports further clinical development for the treatment of SCLC, MCC and other cancers." Details of the oral presentation are as follow: Title: 225Ac-SSO110 induces long-lasting anti-tumour responses in contrast to 225Ac-DOTA-TATE and 161Tb-DOTA-TATE in the treatment of SSTR2-positive tumour xenografts Presenting Author: Prachi Desai, Scientist at Ariceum Therapeutics Session Number: 1204 Session Title: M2M Track - TROP Session: Radiopharmaceutical Sciences + Translational Molecular Imaging & Therapy Committee: From Radionuclide to Clinical Translation Oral Presentation Date & Time: Tuesday 22 October 2024, 09:00 AM – 09:10 AM CEST Abstract Authors: Prachi Desai, Manuel Sturzbecher-Hoehne, Dennis Mewis, Manfred Ruediger & Anika Jaekel of Ariceum Therapeutics Session Date & Time: Tuesday 22 October 2024, 08:00 AM – 09:30 AM CEST Location: Session Hall X1-X4 Abstracts are available in the September edition of Springer's European Journal of Nuclear Medicine and Molecular Imaging (EJNMMI) abstract book here and on the Ariceum website here. 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 (MCC), 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), currently in Phase 1 clinical development under the trial name CITADEL-123. 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 European Association of Nuclear Medicine (EANM) The European Association of Nuclear Medicine (EANM) is a non-profit organization that promotes nuclear medicine and aims to improve public health. The EANM's mission is to advance nuclear medicine through personalized healthcare, innovation in diagnosis and treatment, and raising awareness of nuclear medicine SOURCE Ariceum Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

– New data show istisociclib (KB-0742) triggered cell death in preclinical ovarian cancer models of platinum and PARP-inhibitor (PARPi) resistance – – New PK/PD results demonstrate that istisociclib given at 80mg on a 4 days on/3 days off schedule resulted in sustained downregulation of CDK9-dependent genes in peripheral blood mononuclear cells (PBMCs) – SAN MATEO, Calif. and CAMBRIDGE, Mass., Sept. 23, 2024 (GLOBE NEWSWIRE) -- Kronos Bio, Inc. (Nasdaq: KRON), a company dedicated to developing small molecule therapeutics that address cancers and other diseases driven by deregulated transcription, today highlighted new preclinical data from a study of istisociclib (KB-0742). The poster presentation took place over the weekend at the American Association for Cancer Research (AACR) 15th Biennial Ovarian Cancer Research Symposium. Kronos Bio is currently evaluating istisociclib, a CDK9 inhibitor, in an expansion cohort of a Phase 1/2 clinical trial to explore single agent activity in platinum-resistant high-grade serous ovarian cancer (HGSOC). "We’ve demonstrated preclinical evidence that istisociclib induced DNA damage and subsequent cell death, which further supports our clinical program focused on platinum-resistant high-grade serous ovarian cancer," said Luis A. Carvajal, Ph.D., Director of Translational Development at Kronos Bio, the lead author on the poster. "Importantly, platinum or PARPi insensitive cell lines showed greater sensitivity to istisociclib in cell viability assays. Moreover, ovarian cancer cells with PARPi resistance were sensitized to PARP inhibition in the presence of istisociclib.” Dr. Carvajal added, “Based on new PK data from our ongoing clinical trial, we conclude that plasma levels were consistent with efficacious exposures observed in preclinical models of ovarian cancer, and we are excited to be enrolling patients into an expansion cohort of patients with platinum-resistant high-grade serous ovarian cancer.” From the presentation, “Preclinical and clinical data support clinical expansion of istisociclib (KB-0742), an oral CDK9 inhibitor, into platinum-resistant ovarian cancer,” a summary of results is outlined below. In vitro data demonstrate that istisociclib induced apoptosis/cell deathIstisociclib resulted in the accumulation of γH2AX, a sensitive molecular marker of DNA damageIstisociclib disrupted homologous recombination (HR) DNA damage repair by downregulating BRCA1 and RAD51 creating a “BRCAness” phenotype in platinum and PARP resistant HR-proficient ovarian cancer cells From the dose escalation portion of the Company's ongoing Phase 1/2 trial of istisociclib in relapsed or refractory transcriptionally addicted advanced solid tumors, new pharmacokinetic/pharmacodynamic (PK/PD) results were presented. From the dose and schedule optimization portion of the trial evaluating 60mg and 80mg of istisociclib administered once daily on a 4 days on/3 days off schedule: Clinical exposures resulted in a long half-life of approximately 24 hours, and increased and prolonged weekly exposures consistent with efficacious levels observed in preclinical modelsConcurrent with increased and prolonged istisociclib exposure, deeper and more sustained downregulation of CDK9-dependent genes was observed in peripheral blood mononuclear cells (PBMCs) The poster from the presentation is available under the Science & Pipeline section of the Kronos Bio website. About Kronos BioKronos Bio, Inc. (Nasdaq: KRON) is a clinical-stage company dedicated to developing small molecule therapeutics that address deregulated transcription, a hallmark of cancer and other diseases. Our proprietary discovery engine decodes complex transcription factor regulatory networks to identify druggable cofactors. We screen for and optimize small molecules that target these cofactors in a tumor-specific context. These efforts have yielded a preclinical pipeline along with two internally developed drug candidates. Istisociclib (KB-0742) targets CDK9 to address MYC deregulation in solid tumors and KB-9558 targets p300 to address IRF4 dependence in multiple myeloma. Kronos Bio is based in San Mateo, Calif., and has a research facility in Cambridge, Mass.For more information, visit https://www.kronosbio.com or follow the Company on LinkedIn.