Adrenocortical Carcinoma

REM-422, a first-in-class MYB mRNA degrader, induces regression across multiple preclinical models of ACC WATERTOWN, Mass., Oct. 16, 2024 /PRNewswire/ -- Remix Therapeutics (Remix), a clinical-stage biotechnology company developing small molecule therapies to modulate RNA processing and address underlying drivers of disease, will deliver a poster presentation demonstrating the therapeutic potential of REM-422, a potent, selective, oral small molecule MYB mRNA degrader for the treatment of acute myeloid leukemia (AML) and adenoid cystic carcinoma (ACC), at the upcoming 2024 EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics being held on October 23-25, 2024 in Barcelona, Spain. MYB is an oncogenic transcription factor that is dysregulated in human malignancies including ACC, where the majority of tumors contain a hallmark t(6:9) rearrangement resulting in a MYB::NFIB fusion oncogene. The poster presentation will include preclinical data from biophysical and cellular assays that demonstrate the mechanism of action of REM-422 in suppressing MYB mRNA and protein expression by promoting inclusion of a poison exon into the MYB mRNA transcript. In vivo studies in ACC patient-derived xenograft (PDX) mouse models harboring the MYB::NFIB fusion demonstrates that REM-422 induces tumor regressions, including in models that harbor co-occurring mutations in the Notch pathway, a profile that represents especially aggressive clinical cases of ACC. Anti-tumor activity of REM-422 in these models is associated with a reversal of gene transcriptional programs that are associated with ACC, as assessed by genome-wide RNAseq experiments. "We've built an exciting package of preclinical data across various models that reinforces the therapeutic potential of REM-422 for the treatment of ACC and other MYB-dysregulated cancers," said Peter Smith, Ph.D., Co-Founder and Chief Executive Officer of Remix Therapeutics. "The preclinical data demonstrated that REM-422 monotherapy treatment leads to tumor regressions in PDX models of ACC and support clinical development in ACC patients." REM-422 is currently being investigated as a potential treatment for adenoid cystic carcinoma (ACC) and AML/HR-MDS (High-Risk Myelodysplastic Syndromes) in two, phase 1 clinical trials. Details for the poster presentation are as follows: Title: REM-422, a potent, selective, oral small molecule mRNA degrader of the MYB oncogene, induces regressions in mouse patient-derived xenograft models of adenoid cystic carcinoma Authors: M. Cameron1, S. Levin-Furtney1, A. Harney1, M. Thomas1, J. Maag1, B. Dunyak1, M. Shan1, S. Prajapati1, Y.A. Siu1, D. Nguyen1, S. Buonamici1, M. Seiler1, F. Vaillancourt1, P. Smith1, D. Reynolds1, C. Kung1. 1Remix Therapeutics, Research, Watertown, USA. Abstract Number: ENA24-0468 Session Date and Time: Wednesday, October 23, 2024 (11:00 AM – 8:00 PM) Session Location: CCIB Exhibition Hall poster area, Barcelona, Spain About REM-422 REM-422 is a first-in-class, potent, selective, and oral small molecule mRNA degrader that induces the reduction of MYB mRNA and subsequent protein expression. REM-422 functions by facilitating the incorporation of poison exons within the mRNA transcript, leading to nonsense-mediated decay (NMD) of the transcript. REM-422 addresses MYB dysregulation, a driver of oncogenesis, upstream of protein expression. About ACC Adenoid cystic carcinoma (ACC) is a rare cancer that commonly develops in glandular tissues in the head and neck. It is caused by genetic mutations, likely developed over a patient's lifetime, with the majority of ACC cases linked to an overexpression of the MYB protein. Current treatment solutions include surgery, radiation therapy, and chemotherapy. About AML/HR-MDS Acute myeloid leukemia (AML), a rare cancer of the blood and bone marrow, is the most common type of acute leukemia in adults. AML is caused by genetic mutations within bone marrow cells, which in turn causes the production of leukemic white blood cells that crowd out healthy blood cells. This may cause problems with bleeding, infection, and anemia. Myelodysplastic Syndromes (MDS) are disorders of blood-forming units in the bone marrow. High-risk (HR)-MDS patients have a higher percentage of blast cells in the bone marrow and that, in many cases, progresses to AML. There are several approved agents to treat AML, however, many patients relapse after achieving a response, underscoring the need for new therapies. About Remix Therapeutics Remix Therapeutics is a clinical-stage biotechnology company developing novel small molecule therapies designed to reprogram RNA processing and treat disease. The REMaster™ technology platform facilitates RNA processing pattern identification, leveraging these learnings to modulate gene expression. Remix's innovative therapeutic approach has the potential to alter the way genes are read from the genome, to correct, enhance, or eliminate the gene message, thereby addressing disease drivers at their origin. For more information visit . SOURCE Remix Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

CY-101 well tolerated with early signs of clinical activity, especially in tumors with dysregulated Wnt/β-catenin signalling CY-101 granted Orphan Drug Designation in US for the treatment of Adrenocortical Carcinoma, a Wnt/β-catenin driven tumor type September 13, 2024 – Cytovation ASA, a clinical stage oncology company focused on the development of its first-in-class bifunctional immunotherapy CY-101 (CyPep-1) announces that it will deliver a poster presentation at ESMO 2024 entitled “Safety and activity of CY-101 in patients with advanced solid tumors: the Phase I/IIa CICILIA trial.” Data from this study, evaluating intratumoral (IT) administration of CY-101 monotherapy and in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy KEYTRUDA® (pembrolizumab) in patients with heavily pretreated advanced solid tumors, show that CY-101 is well tolerated at the recommended Phase 2 dose (RP2D) of 20 mg. Furthermore, these data demonstrate early signs of antitumor activity, especially in tumors with dysregulated Wnt/β-catenin signaling. CY-101 is a synthetic peptide with a dual mode of action that both inhibits the oncogenic Wnt/β-catenin pathway by activating Axin2 and has a pore-forming membranolytic effect on cancer cells that exposes antigens and triggers a systemic tumor-specific immune response. Interim results from CICILIA were reported in 2023 (link to press release here) confirming that all trial endpoints were met, with CY-101 demonstrating a consistent safety profile across tumor types and strong early signals of efficacy. Data from the ESMO poster show that no dose-limiting toxicities were observed in the dose- escalation part of the study with the RP2D defined at 20 mg. Analyses of paired tumor biopsies demonstrated induction of cancer cell death in >70% across tumor types at the RP2D, translating to a clinical benefit in several different cancer types. Notably, among six patients with adrenocortical carcinoma (ACC) receiving CY-101 monotherapy, a disease control rate of 50% (n = 3/6) was observed, with durable responses (> 6 months) in two patients. Both patients expressed β-catenin and had somatic mutations in the Wnt/β-catenin pathway. Separately, the US Food and Drug Administration (FDA) has granted Orphan Drug Designation to CY-101 monotherapy for the treatment of ACC. Orphan Drug Designation is granted to investigational therapies that are intended for the treatment, diagnosis or prevention of rare diseases or conditions that affect fewer than 200,000 people in the US. Orphan Drug Designation provides several benefits to drug developers, including certain development cost benefits in the US, increased FDA interaction and eligibility for seven-year market exclusivity following approval. “We believe CY-101 is a potentially important new treatment option that offers a truly differentiated approach to targeting Wnt/β-catenin driven cancers, an oncogenic pathway dysregulated in more than 20% of cancers,” said Lars Prestergarden, CEO of Cytovation. “Our early data clearly confirm that CY-101 warrants further investigation in larger studies, and we are very pleased to receive Orphan Drug Designation for CY-101 in ACC. We look forward to advancing towards our planned Phase 2 trial in ACC with registrational intent.” ACC, also known as adrenal cancer, is a rare cancer with a very poor prognosis and few treatment options. In the metastatic setting there is no approved treatment option after first line. Cytovation ASA is a clinical stage immune-oncology company focused on the development of CY-101, a first-in-class bifunctional immunotherapy. CY-101 has a unique dual mechanism of action, specifically eliminating cancer cells by targeting the cell membrane and releasing neo-antigens, and by inhibiting the Wnt/β-catenin oncogenic pathway to restrict tumor growth and reverse immune exclusion associated with β-catenin expression. Dysregulation of this pathway has been associated with several different cancer types including colon, liver, uterine, lung and ovarian cancer, among others. This dual mode of action induces a systemic, tumor-specific immune response. The content above comes from the network. if any infringement, please contact us to modify.

Several big pharmas have made plays into the fast-growing radiopharma space. Image credit: Shutterstock/ Ezume Images. Eli Lilly has partnered with Radionetics Oncology in a $140m deal, as the drugmaker aims to get a leg up in the burgeoning radiopharmaceuticals arena. In addition to the upfront payment, the agreement also gives Eli Lilly the exclusive option to buy the radiopharmaceutical specialist for $1bn once the exercise period finishes, as per a 1 July press release. Radionetics, which spun off from Crinetics in 2021, focuses on developing small molecule G protein-coupled receptor (GPCR)-targeted drugs. The biotech said it will continue to advance its pipeline of radioligands during the exercise period using its platform which consists of small molecules tethered to radioisotopes. The resulting candidates are designed to bind to receptors overexpressed in certain cancers. Radionetics, which has raised a total of $82.5m in venture financing, has a single candidate in clinical trials, Ga-R8760. The radioligand is being evaluated in a  Phase I trial (NCT05999292) in patients diagnosed with adrenocortical carcinoma. However, in a statement announcing the first patient being dosed in the trial, the biotech said it plans to have three clinical programmes underway by 2024. The deal marks the latest push by Eli Lilly into the radiopharmaceuticals space. The company spent $1.4bn to buy POINT Biopharma in October 2023, gaining two late-stage clinical programmes and an 180,000 ft 2 radiopharmaceutical manufacturing plant in the US. See Also: Embracing digital solutions for enhanced patient care From data to action: Igniting the healthcare revolution This was then consolidated by Eli Lilly’s partnership with Aktis in May this year. The deal included a $60m upfront payment and $1.1bn in milestone payments and royalties. Radionetics CEO Paul Grayson said: “We are fortunate to have entered into an agreement with Lilly given its global development capability, oncology expertise, and the radiopharmaceutical experience and capabilities Lilly is building following the acquisition of POINT Biopharma.” Bristol Myers Squibb (BMS) also made a big sign of its intent in this arena when it dropped $4.2bn to acquire RayzeBio in February this year. Novartis also ventured into the radioactive drug landscape when it bought Mariana Oncology in a $1.75bn transaction. Venture financing for US-based companies with radiopharmaceutical drugs saw a rise of 550% between 2017 and 2023, according to GlobalData. GlobalData is the parent company of Pharmaceutical Technology .