WNT5A

SHANGHAI, Feb. 10, 2025 /PRNewswire/ -- On December 19, 2024, BioRay Pharmaceutical Co., Ltd. ("BioRay") announced that the National Medical Products Administration (NMPA) has accepted the clinical trial application for its self-developed Class 1 innovative therapeutic biological product, BR111 for injection. BR111 is an antibody-drug conjugate (ADC) targeting dual epitopes of ROR1, intended for the treatment of ROR1-positive hematological malignancies and solid tumors. ROR1 is a transmembrane receptor tyrosine kinase protein that is either not expressed or expressed at low levels in normal tissues, but is highly expressed in various hematological malignancies and solid tumors, such as lymphoma, breast cancer, ovarian cancer, and lung cancer. ROR1 is involved in the non-canonical Wnt signaling pathway mediated by Wnt5a, regulating the growth and invasion of tumor cells. It is closely associated with tumorigenesis and drug resistance, making it a potential target for oncology drug development. To date, no ROR1-targeting drugs have been marketed. BR111 utilizes BioRay's next-generation CysX™ irreversible site-specific conjugation technology platform to conjugate an antibody targeting dual epitopes of ROR1 with the small-molecule toxin eribulin. It is the world's first anti-ROR1 Bi-paratopic ADC to enter clinical trials. BR111 can recognize two non-overlapping epitopes of ROR1 on the surface of tumor cells, and dual-epitope recognition brings stronger affinity and endocytosis. Once endocytosed into ROR1-positive tumor cells, BR111 releases the small-molecule toxin in the lysosome, effectively killing tumor cells. Developed using the CysX™ platform, BR111 has higher homogeneity and circulating stability, significantly reducing toxin release in circulation, which enhances safety and optimizes the therapeutic window. In preclinical studies, BR111 demonstrated superior in vivo anti-tumor efficacy compared to its clinical counterparts in multiple animal models and exhibited better safety. Additionally, BR111 can induce a bystander effect and activate immune response in the tumor microenvironment, showing potential for combination therapy with various drugs, including targeted therapies and immunotherapies. The acceptance of this project application is a testament to BioRay's R&D capabilities and a validation of the CysX™ platform technology. Moving forward, BioRay will continue to focus on clinical needs, drive innovative research, and advance biopharmaceutical technology, with the goal of delivering more effective and safer treatment options to patients through innovative drugs. SOURCE BioRay Pharmaceutical Co., Ltd WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Image credit: Shutterstock/Smart Calendar BioAtla has received a fast track designation from the US Food and Drug Administration (FDA) for its antibody drug conjugate (ADC) ozuriftamab vedotin (BA3021) to treat a certain type of head and neck cancer. Ozuriftamab vedotin is a conditionally and reversibly active ADC targeted against ROR2, a receptor tyrosine kinase present in many solid tumours. ROR2 is a non-canonical wnt5A signalling receptor, the overexpression of which is associated with poor prognosis and resistance to standard therapies. This fast track designation concerns the use of ozuriftamab vedotin in treating patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) for whom the disease has progressed despite platinum-based chemotherapy and anti-PD-1/PD-L1 antibody treatment. The ADC is the subject of an ongoing multi-centre, open label Phase II trial (NCT05271604) investigating the therapy’s efficacy and safety for this indication. Though a full readout is still pending, interim data from the trial suggests the treatment is generally well-tolerated. In the US alone, over 400,000 people live with cancer of the head and neck as per the American Cancer Society. Over 70,000 new cases are estimated to arise in 2024, according to American Association for Cancer Research. Around half of those cases with locally advanced disease develop recurrent or refractory disease for which treatment options are limited. See Also: EC conditionally approves Pfizer’s haemophilia B gene therapy MHRA approves Pfizer-BioNTech’s Comirnaty JN.1 vaccine Announcing the FDA designation in a 23 July press release, BioAtla CEO and cofounder Jay Short, PhD, said, “To date, ozuriftamab vedotin has shown promising clinical activity in treatment-refractory SCCHN patients who had a median of three prior lines of therapy. In addition, ozuriftamab vedotin continues to have a manageable safety profile with no new safety signals.” BioAtla is developing a cohort of novel, reversibly active monoclonal and bispecific antibodies and other therapeutic products, with operations both in the US and China. Ozuriftamab vedotin is one of several antibody therapies being developed through the company’s patented conditionally active biologics (CAB) technology. According to GlobalData’s projections , the revenue from ozuriftamab vedotin is estimated to reach $59m annually in the US by 2038. GlobalData is the parent company of Pharmaceutical Technology .

Investigators have provided new understanding of how diabetes delays wound healing in the eye, identifying for the first time two related disease-associated changes to the cornea. Investigators from Cedars-Sinai have provided new understanding of how diabetes delays wound healing in the eye, identifying for the first time two related disease-associated changes to the cornea. The findings, published today in the peer-reviewed journal Diabetologia, also identified three therapeutic pathways that reversed these changes and partially restored wound-healing function to the cornea -- a discovery that could ultimately inform new treatments for diabetes. "We have found that diabetes induces more cellular changes than we were aware of previously," said Alexander Ljubimov, PhD, director of the Eye Program at Cedars-Sinai's Board of Governors Regenerative Medicine Institute and senior author of the paper. "The discovery does not affect gene sequence but entails specific DNA modifications altering gene expression -- what are known as epigenetic alterations." More than 37 million people in the United States -- 11% of the population -- have diabetes, a systemic disorder that can result in kidney disease, heart disease, amputation, stroke and nerve damage. Most diabetes drugs are designed to increase glucose tolerance or supply depleted insulin, but do not address molecular and cellular changes or their associated complications. The new research also identifies for the first time an important role of Wnt-5a, a secreted signaling protein investigators found responsible for corneal wound healing and the function of stem cells -- cells capable of differentiating into many cell types. "Current treatments only address symptoms, so there is an urgent need to understand the molecular mechanisms of diabetes-related wound-healing problems," said Ruchi Shah, PhD, a scientist in Ljubimov's lab and the study's first author. "Understanding of this novel epigenetically regulated wound-healing mechanism could lead to therapeutic treatments that could help patients avoid further long-term ocular health issues." Though much focus of diabetic eye disease is on the retina, up to 70% of diabetes patients suffer from problems of the cornea, the transparent, protective exterior surface of the eye. In advanced diabetes, corneal stem cells become dysfunctional, and the cornea heals more slowly and less completely following an injury or procedures such as cataract surgery and laser treatment for diabetic retinopathy. To identify the epigenetic changes discovered in this study -- changes not hard-wired into the genome from birth, but introduced later -- Ljubimov and his team compared cells from the corneas from six diabetic patients with those of five healthy donors. They found that in diabetic corneas, the protein product of the WNT5A gene was repressed. Additionally, in diabetic samples, they found an increase in the microRNA that inhibits WNT5A. The team of scientists then induced wounds to corneal cells in culture and corneal organ cultures, and tested three interventions designed to normalize Wnt-5a protein expression. They added the Wnt-5a protein directly; they introduced a DNA methylation inhibitor, originally approved to treat cancer; and they targeted microRNA levels with a novel gene therapy approach using a nanoscale compound. The team developed the compound, which uses synthetic molecules to block the microRNA, as a substitute for a viral gene therapy they found to be toxic to stem cells. All three therapeutic methods, in the diabetic samples, stimulated stem cell marker production and improved tissue regeneration, accelerating wound healing. "Novel therapies to reverse epigenetic effects could improve corneal function, and may also prove significant in other diabetic complications," said Clive Svendsen, PhD, director of the Board of Governors Regenerative Medicine Institute and study co-author. "This work certainly helps move the field forward." Investigators will continue to analyze their data to better understand the mechanisms of WNT5A and other genes related to wound healing. They are also studying a combination therapy to target both microRNA and DNA methylation in hopes that it will more thoroughly normalize wound healing by increasing Wnt-5a protein. "Our goal is to develop topical, sustained-release drugs for corneal wound healing," said Ljubimov. "Drugs that are FDA [Food and Drug Administration] approved and could be easily applied may be one of the most promising approaches for effective future therapies." Funding: This work was funded by National Institutes of Health grant numbers R01EY013431482, R01EY031377, R01EY025377, and R01CA206220; and the Cedars-Sinai Board of Governors Regenerative Medicine Institute.