Nimbus Therapeutics LLC

Takeda Pharmaceutical, Japan's largest drugmaker, reported second-quarter earnings on Thursday that beat market expectations. The company also raised its full-year earnings forecast. Takeda is currently undergoing a restructuring plan aimed at cutting costs and improving efficiency. Takeda posted an operating profit of 184.2 billion yen ($1.21 billion) in the three months through September, compared with a loss of 49.3 billion yen a year earlier, when the company was in the red. According to a survey of four analysts by LSEG, Takeda's results far exceeded the consensus forecast of 93.6 billion yen in earnings. Based on the strong first-half performance and an update to currency assumptions, Takeda raised its full-year operating profit forecast to 265 billion yen from 225 billion yen. In May, Takeda announced it would restructure to improve margins and refocus on drug discovery. The company plans to cut or reposition about 1,200 employees at centers in San Diego and Massachusetts, according to domestic media reports, and last week unveiled an early retirement plan for employees in Japan. While Takeda declined to give details on the specific positions affected, the company told Reuters that the restructuring was aimed at "maximizing the potential of our therapeutic portfolio, product lines and organizational structure for long-term growth." Takeda is trying to rebuild its drug pipeline. Last year, the company suffered failures in clinical trials for lung cancer and Crohn's disease treatments, leading to large impairment losses. However, the company has high hopes for its experimental narcolepsy treatment TAK-861 and psoriasis candidates. The drugs were acquired by Takeda from Us-Based Nimbus Therapeutics in late 2022 for up to $6 billion. While Takeda's shares are up 5.2% this year, that still underperforms the benchmark Nikkei average's 17% gain.

-- New development candidate, NTX-452, a non-covalent WRN inhibitor, demonstrated significant tumor regression and complete responses at low oral doses in MSI-H tumor models refractory to immunotherapy and chemotherapy -- -- Company plans to initiate clinical trial of NTX-452 in first half of 2025 -- BOSTON--(BUSINESS WIRE)-- Nimbus Therapeutics , LLC (“Nimbus Therapeutics” or “Nimbus”), a biotechnology company that designs and develops breakthrough medicines for patients through its powerful computational drug discovery engine, announced that it is presenting preclinical data on its new development candidate, NTX-452, a novel Werner syndrome helicase (WRN) inhibitor, at the 36 th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, taking place October 23-25, 2024 in Barcelona, Spain. WRN is a helicase required for DNA replication and DNA repair and is a validated target for tumors with microsatellite instability (MSI). MSI is a phenotypic consequence of defective mismatch repair (dMMR) and occurs in various tumor types, including colorectal, gastric and endometrial cancers. Inhibition of WRN activity has the potential to induce synthetic lethality in MSI-high (MSI-H) tumors. Using a structure-based drug design approach, Nimbus developed highly potent and selective covalent and non-covalent inhibitors of WRN, and has selected a novel non-covalent inhibitor, NTX-452, as the clinical candidate. In a poster (abstract #356) titled “Preclinical Characterization of NTX-452, a Potent, Selective and Highly Efficacious WRN Inhibitor for the Treatment of MSI-H Tumors,” Nimbus is presenting new data from preclinical assays and several tumor models that support the potential of the company’s non-covalent WRN inhibitor as a treatment for MSI-H tumors. Key findings from the preclinical studies include: NTX-452 demonstrated potent and selective inhibition of WRN activity with favorable drug-like properties. The compound showed synthetic lethality in MSI-H tumor cells, triggering a DNA damage response that suppressed cell viability and promoted cell death. Treatment with NTX-452 at low doses in vivo exhibited a robust pharmacodynamic response, resulting in tumor regression across multiple MSI-H cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) tumor models, including established models for colorectal, gastric and endometrial cancers. Significant tumor regression and complete responses were observed at low oral doses in MSI-H models refractory to immunotherapy and chemotherapy. “These compelling preclinical results for NTX-452 further highlight the significant potential of our WRN inhibitor as a promising therapeutic approach for patients with MSI-H tumors, many of whom fail to respond to or eventually relapse with current standard of care therapies including immune checkpoint inhibitors,” said Peter Tummino, Ph.D., Chief Scientific Officer of Nimbus. “Our novel non-covalent approach to WRN inhibition, coupled with the robust efficacy demonstrated across diverse tumor types and treatment settings, positions our program for potential best-in-class status. We are particularly encouraged by the low doses required to achieve robust anti-tumor activity in preclinical models, which may translate to an improved benefit-risk pro the clinic.” The preclinical pro NTX-452 suggests several potential advantages in the treatment of MSI-H tumors, including: The non-covalent mechanism may offer more durable on-target activity, and a greater safety window compared to covalent inhibitors. High potency and favorable pharmacokinetic properties indicate the potential for target levels of efficacy at lower doses. Broad efficacy across treatment-naïve, chemotherapy-pretreated, and immunotherapy-pretreated models suggests potential utility in both early-stage and advanced disease settings. Activity in multiple MSI-H tumor types, including those with diverse genetic alterations, indicates potential broad applicability across dMMR/MSI-H cancers. Nimbus is advancing NTX-452 with plans to enter the clinic in the first half of 2025. About Nimbus Therapeutics Nimbus Therapeutics is a clinical-stage, structure-based drug discovery company developing novel small molecule medicines designed to act against well-validated but difficult-to-drug targets implicated in multiple human diseases. The company advances promising research based on a unique strategy that combines leading-edge computational technologies with a tailored array of machine learning-based predictive modeling approaches. Nimbus’ pipeline includes a clinical-stage HPK1 inhibitor for the treatment of cancer (NCT05128487), as well as a diverse portfolio of preclinical programs focused on cancer, including the WRN program, autoimmune conditions, and metabolic diseases. The company is headquartered in Boston, Mass. To learn more about Nimbus, please visit . Contacts Media Cindy Fung, PhD Nimbus Therapeutics cindy.fung@nimbustx.com

On Wednesday, Triveni Bio became the latest immunology and inflammation startup this year to announce a $100 million-plus financing round. Money has come thick and fast to I&I companies this year, and Triveni’s Series B comes less than a year after it announced a $92 million Series A. The new round was led by Goldman Sachs and included Fidelity, Deep Track Capital and other previous investors in the company, like Atlas Venture and OrbiMed. With the raise, Triveni will fund its lead experimental eczema antibody drug, TRIV-509, and plans to ask the FDA to let it start clinical trials of its lead program in the first quarter of 2025. That study will be in healthy volunteers, medical chief Bhaskar Srivastava told Endpoints News , and the company is seeking to develop the asset for atopic dermatitis, or eczema. Srivastava joined the company in June, leaving his post as SVP of clinical development at Nimbus Therapeutics. TRIV-509 targets kallikreins 5 and 7, and is involved in what’s called barrier dysfunction — when the skin can’t act as a proper protector from allergens and other irritants in people with atopic dermatitis. Triveni CEO Vishal Patel described barrier dysfunction as a hallmark feature of atopic dermatitis, as well as inflammation. “The barrier part, in particular, is novel because that is a unique part of that atopic dermatitis vicious cycle that really hasn’t been prosecuted in the past,” Patel told Endpoints. The company is also working on a follow-on compound called TRIV-573 that combines kallikrein 5/7 inhibition with IL-13, a well-known target (one of Dupixent’s targets). Triveni’s third program is an antibody treatment for hereditary pancreatitis.