MALAT1

Under the terms of the deal, the companies will develop small molecule therapeutics targeting lncRNAs in oncology. PeopleImages.com – Yuri A via Shutterstock. Bayer has teamed up with startup biotech NextRNA Therapeutics to develop small molecules targeting long non-coding RNAs (lncRNAs) in oncology. Under the terms of the deal, NextRNA can get up to $547m if all the milestones are reached, and the deal also included an undisclosed upfront payment. The companies will collaborate on two oncology programmes, the first involving a lncRNA-targeting small molecule in early preclinical development at NextRNA. For the second, NextRNA will pursue lncRNA targets identified by its platform, with Bayer having the option to choose one target for joint development. In 2022, Dana-Farber spinout NextRNA came out of stealth with $9.3m from a seed financing round and $46.8m from a Series A. This is the first high-profile pharma deal for the startup, which focuses on lncRNA-driven diseases. lncRNAs are RNA molecules over 200 nucleotides long that regulate gene expression without coding for proteins. They play key roles in various cellular processes, including those linked to cancer, such as tumour growth, metastasis, drug resistance and angiogenesis. See Also: Shortages improve for Lilly’s GLP-1 weight loss drugs, bumping sales forecast by $3bn Annexon gets grant for anti-c1q antibody fab fragments for inhibiting synapse loss A few companies have hopped on the lncRNA space, with strategies like antisense oligonucleotides, siRNAs, CRISPR/Cas9, small molecules and RNA aptamers being explored to modulate their function. In June 2023, Flamingo Therapeutics secured a €1.7m grant from Flanders Innovation & Entrepreneurship (VLAIO) to advance its lncRNA programme, FTX-001, that targets MALAT-1. The preclinical candidate is being developed in collaboration with Ionis Pharmaceuticals for a Phase I trial in solid tumours. The NextRNA deal comes weeks after Bayer announced that it has cut 3,200 jobs since the beginning of the year, in its Q2 2024 earnings call. At the start of this year, the German pharma giant said that it will roll out a new operating model, one designed to cut bureaucracy and speed up decision-making following which it is aiming to make savings of €2bn a year from 2026. In the announcement accompanying the deal, head of business development and licensing at Bayer’s pharmaceutical division Juergen Eckhardt said: “With NextRNA’s exceptional expertise and lncRNA platform, we aim to advance novel small molecule therapeutics against a new class of targets in oncology. This partnership further adds to our mission to build one of the most transformative and diversified oncology pipelines in the industry.” 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

The blood-brain barrier protects gray matter from unwanted intruders, but its stinginess means it excludes helpful drugs from reaching the brain, too. Antisense oligonucleotides (ASOs), which bind to RNA and prevent them from being translated into proteins, have gained popularity in recent years as a way to treat neurodegenerative diseases. However, getting these drugs into the brain has been challenging, currently requiring invasive infusion directly into the cerebrospinal fluid.Now, Denali Therapeutics has developed a way to deliver these drugs to the brain more easily—by smuggling them across the blood-brain barrier. In studies with mice and macaques, the California-based biotech combined ASOs with their transferrin-targeting transport vehicle platform and successfully knocks down certain gene activity across the brain.“Not only could we get brain uptake, but we could get it into the cell, we could get knock down of the genes that we're interested in,” Denali Chief Scientific Officer Joe Lewcock, Ph.D., told Fierce Biotech in an interview. “Really demonstrating that this platform can be effective for this class of drugs as well.” The results appeared in Science Translational Medicine on Aug. 14. The blood-brain barrier protects precious gray matter from unwanted intruders, but its stinginess means it excludes helpful drugs from reaching the brain too. Denali’s transport vehicle platform is an engineered antibody that targets transferrin receptor 1, which normally shuttles iron—essential for brain function—across the barrier.This technology is the basis for the biotech’s lead drug candidate, DNL310, where iduronate 2-sulfatase enzyme is bound to the transport vehicle and shepherded into cells to treat Hunter syndrome. Individuals with the disease have mutations in the gene that codes for the iduronate 2-sulfatase enzyme, making it not work properly. DNL310 is currently in phase 3 trials.To test the approach with ASOs, Denali scientists chose to focus on a gene called malat1. “It's a commonly used target in the field for proof-of-concept,” according to Lewcock, and is expressed in all cell types of the central nervous system. Binding an ASO targeting malat1 to Denali's transport vehicle forms an oligonucleotide transport vehicle (OTV), which allows the ASO to be shuttled into diverse cells and can successfully reduce expression of the gene in both mice and cynomolgus macaques.Lewcock sees three advantages to OTVs. First is the intravenous delivery, which is less invasive than intrathecal infusion directly into the central nervous system. Another benefit is the even distribution of the drug throughout the brain, hitting all cell types, which could mean greater efficacy and—the third advantage—an improved safety profile.With intrathecal delivery, “to get up to the brain, you have to have very high concentrations in the lumbar spinal cord, and that could cause safety issues,” Lewcock explained. “Even biodistribution allows you to get adequate [amounts of] drug to the right places and avoid that.” With OTVs having proven their mettle in animal studies, Lewcock said Denali is now pursuing two lead OTV candidates in neurodegenerative disease. “One's targeting the MAPT gene, or tau, in the context of Alzheimer's disease, and the second is targeting the alpha-synuclein gene in the context of Parkinson's disease,” he explained. “We've done a lot of work on those targets and optimizing molecules for each of those targets.”The plan is for OTVs to join the broader transport vehicle family, which in addition to enzyme carriers also includes antibody transporters. “We're really building a foundation with the enzyme transport vehicle franchise,” Denali's vice president of investor relations Laura Hansen, Ph.D., said in a joint interview with Fierce Biotech. “Those near- to mid-term revenues expected from those indications will enable us to really continue to expand the transport vehicle platform opportunities into the antibodies and oligonucleotides.”Denali intends to seek accelerated approval for DNL310, the company's enzyme-based lead candidate for Hunter syndrome, Hansen added.

LEUVEN, Belgium and STRASBOURG, France and PHILADELPHIA , June 10, 2024 /PRNewswire/ -- Flamingo Therapeutics ("Flamingo") today announced a poster presentation on FLM-7523 (also referred to as FTX-001) at the Annual Congress of the European Association for Cancer Research (EACR) 2024 Congress, being held in Rotterdam, Netherlands from June 10-13, 2024. Flamingo will present preclinical results highlighting the candidate selection and characterization of FLM-7523, a novel oligonucleotide targeting MALAT1 for the treatment of cancer. Flamingo has advanced FLM-7523 through Phase 1 enabling preclinical activities and is planning for a First-in-Human trial in solid tumors. EACR poster details are as follows: Abstract#: EACR2024-0240 Title: "Preclinical development of FTX-001: First-in-class inhibitor of the long non-coding RNA MALAT1" Session Title: Posters: Experimental/Molecular Therapeutics, Pharmacogenomics Session Date and Time: June 11, 2024, from 11:00 to 20:15 Presenting Author: Dr. Marie-Aline Neveu Abstracts related to the EACR meeting will be published online in a supplement to the FEBS journal, Molecular Oncology, the Congress App and the Congress Website. For more information, please visit the EACR 2024 website. About Flamingo Therapeutics Flamingo is pioneering RNA-targeted therapies for oncology with a clinical-stage pipeline targeting undruggable transcription factors and long non-coding RNAs. Flamingo has an alliance with Ionis Pharmaceuticals and is supported by well-known biotechnology investors including Abrdn (formerly funds managed by Tekla Capital Management LLC), Andera Partners, Bpifrance Large Venture, Bpifrance through its FABS and Fonds Biothérapies Innovantes et Maladies Rares funds, Eurazeo - Kurma Partners, Perceptive Advisors, PMV, Pontifax, Sphera, and VIB. Flamingo has initiated a Phase II trial 'PEMDA-HN' evaluating the STAT3 targeting agent danvatirsen, in combination with pembrolizumab, in patients with head and neck squamous cell carcinoma (HNSCC). A Phase I investigator-initiated trial study has also been initiated evaluating danvatirsen as a monotherapy and in combination with venetoclax in AML/MDS patients. For more information on Flamingo, please visit: PEMDA-HN (head and neck cancer) on clinicaltrials.gov: Danvatirsen monotherapy followed by combination with venetoclax in relapsed/ refractory AML and MDS on clincaltrials.gov: Please engage with us on LinkedIn: . Flamingo Media and Investor Contact: Amy Conrad Juniper Point (858) 366-3243 [email protected] SOURCE Flamingo Therapeutics