transferrin

Caris Life Sciences to present 14 abstracts, inclusive of 2 oral presentations and 12 posters IRVING, Texas, April 17, 2025 /PRNewswire/ -- Caris Life Sciences® (Caris), a leading next-generation AI TechBio company and precision medicine pioneer, today announced that the company and collaborators within the Caris Precision Oncology Alliance™ (Caris POA) will collectively present 14 abstracts across 9 tumor types at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2025, from April 25-30, in Chicago, IL. "We are thrilled about the abstracts accepted for presentation at AACR this year, highlighting the importance of Caris' comprehensive molecular profiling and our Caris POA collaboration," said Caris EVP and Chief Medical Officer George W. Sledge, Jr., MD. "The findings represent a broad spectrum of cancer research by tumor type including gastro-esophageal, lung and pancreatic all utilizing Caris' comprehensive clinic-genomic datasets." "The variety of cancer research presenting at AACR this year demonstrates how Caris empowers clinicians by facilitating research, ultimately paving the way for advancements," said James Hamrick, MD, MPH, Chairman of the Caris Precision Oncology Alliance. "The findings illustrate how our collaborators in the Caris POA leverage real-world evidence to deepen our understanding of the mechanisms of cancer pathogenesis and improve outcomes of all patients affected by cancer." Minisymposium presentations include: Pre-operative abemaciclib in localized cisplatin-ineligible MIBC with tissue and ctDNA molecular response validation (CLONEVO) (Abstract Number CT127) April 28, 2:50-3 PM CT Kinase fusion landscape of pancreatic cancer (Abstract Number 3781) April 28, 3:40-3:55 PM CT Poster presentations include: Clinical, biologic, and immunogenic characteristics of gastro-esophageal cancers (GEC) harboring CLDN18::ARHGAP fusions (Poster Number 496/8) April 27, 2-5 PM CT Functional characterization of SMARCA4 genomic variants (Poster Number 674/7) April 27, 2-5 PM CT Targeting ATM modulates oncogenic pathways and amplifies chemotherapy efficacy in small cell lung cancer (Poster Number LB016/16) April 27, 2-5 PM CT Recurrent PRKCI gene fusions represent a drug target in gastric cancer and esophageal junction cancer (Poster Number 1474/10) April 28, 9 AM -12 PM CT Improving capability for biomarker discovery of glioblastoma-enriched poly-ligand profiling library using Aptamer Capture Microarrays (Poster Number 1895/25) April 28, 9 AM -12 PM CT Comprehensive molecular and immunological characterization of CLDN18.2 in pancreatic cancer (Poster Number 2026/28) April 28, 9 AM -12 PM CT FXIIIa-mediated transferrin sequestration drives cancer stem cell phenotype in colorectal cancer (Poster Number 2688/5) April 28, 2-5 PM CT Association of cyclin E1 expression with genomic instability in ovarian cancer (Poster Number 2846/13) April 28, 2-5 PM CT The ERBB4 exon skipping isoform JMA-CYT2 is the dominant isoform of ERBB4 gene fusions (Poster Number 4761/28) April 29, 9 AM -12 PM CT GPR171, a prognostic marker of improved survival in cervix cancer: A Deep South Consortium in Oncology (DSCO) Project (Poster Number LB261/10) April 29, 9 AM -12 PM CT Non-synonymous mutations in the IFN-γ pathway are predictive of response to immune checkpoint inhibition in NSCLC (Poster Number 7140/4) April 30, 9 AM – 12 PM CT The effects of socioeconomic deprivation on the tumor microenvironment of bladder cancer (Poster Number 7392/20) April 30, 9 AM -12 PM CT Poster and abstract summaries highlighting this research will be available onsite at Caris' booth #400. The full abstracts will be available on the Caris website following the presentation. The Caris POA includes 96 cancer centers, academic institutions, research consortia and healthcare systems, including 47 NCI-designated cancer centers, collaborating to advance precision oncology and biomarker-driven research. Caris and POA members work together to establish and optimize standards of care for molecular testing through innovative research to improve clinical outcomes for cancer patients. About Caris Life Sciences Caris Life Sciences® (Caris) is a leading next-generation AI TechBio company and precision medicine pioneer that is actively developing and delivering innovative solutions to revolutionize healthcare and improve the human condition. Through comprehensive molecular profiling (Whole Exome and Whole Transcriptome Sequencing) and the application of advanced AI and machine learning algorithms, Caris has created the large-scale, multimodal database and computing capability needed to analyze and further unravel the molecular complexity of disease. This convergence of sequencing power, big data and AI technologies provides a differentiated platform to deliver the next generation of precision medicine tools for early detection, diagnosis, monitoring, therapy selection and drug development. Caris was founded with a vision to realize the potential of precision medicine in order to improve the human condition. Headquartered in Irving, Texas, Caris has offices in Phoenix, New York, Cambridge (MA), Tokyo, Japan and Basel, Switzerland. Caris or its distributor partners provide services in the U.S. and other international markets. To learn more, please visit CarisLifeSciences.com. Caris Life Sciences Media: Corporate Communications [email protected] 214.294.5606 SOURCE Caris Life Sciences WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

The properties of the blood-brain barrier serve a vital protective role, but they also keep drugs from reaching the organ. Big pharmaceutical companies have been making deals for technologies that could help them get their molecules through this protective membrane and now GSK is joining in, striking up an alliance that gives it a new way to shuttle drugs into the brain to treat neurodegeneration. The agreement announced Monday gives GSK access to a platform technology developed by ABL Bio. Specific diseases covered by the pact were not disclosed. The deal kicks off with GSK paying South Korea-based ABL £38.5 million (about $49.1 million) up front. The drug delivery approach of ABL is based on Grabody, a platform technology that develops bispecific antibodies, proteins engineered to bind to two targets. For treating brain diseases, the bispecific antibodies from Grabody contain a domain designed to bind to insulin-like growth factor 1 receptor (IGF1R), a receptor that transports proteins across the blood-brain barrier. The other binding domain is designed to go after the desired target for treating a brain disorder. Sponsored Post Changes in Nurse Staffing Answer Clinician Demands The ongoing nursing shortage facilitates high turnover rates since nurses know they won’t have difficulties finding new jobs. In order to retain and attract staff, it’s in a facility’s best interest to understand what nurses want. By Tomasz Rezik GSK and ABL aren’t disclosing the brain targets they’re pursuing. But the agreement covers multiple programs for novel targets that could be treated with various therapeutic modalities. For example, they say an ABL brain drug could be used to deliver genetic medicines to the brain, such as a small-interfering RNA drugs or antisense oligonucleotides. ABL’s most advanced brain program is a Parkinson’s disease drug candidate in development under a partnership with Sanofi. The brain target of this preclinical drug, ABL301, is alpha-synuclein. While that protein is also the target of other Parkinson’s drug candidates, ABL contends the bispecific approach of its drug could more efficiently target alpha-synuclein compared to traditional monoclonal antibodies. Under GSK’s deal, ABL will transfer to the pharma giant technology and know-how related to the Grabody-B platform. GSK will take on responsibility for preclinical and clinical development, along with manufacturing and potential commercialization. Depending on the progress of the research, ABL could receive up to £2.075 billion (about $2.6 billion) in milestone payments, plus royalties if any drugs resulting from collaboration reach the market. “Many of the most promising new therapies are antibodies, which cannot efficiently reach the brain without a shuttle to get them across the [blood-brain barrier],” Christopher Austin, senior vice president of research technologies, GSK, said in a prepared statement. “This agreement reflects our commitment to innovative platform technologies to overcome the BBB and thus open entirely new opportunities for treating these devastating diseases, an important component of our emerging pipeline.” presented by Sponsored Post What Are the Best Medical Coding Outsourcing Companies? Outsourcing your medical coding can help ensure a healthy revenue cycle. Discover the best medical coding outsourcing companies and find the right one for you. By Global Healthcare Resources GSK already has clinical-stage Alzheimer’s programs from a partnership with Alector that began 2021. Latozinemab (formerly AL001) is in Phase 3 testing; Alector has said it expects preliminary data by the end of 2025. AL101 (also known as GSK4527226) is in Phase 2. Both drugs are monoclonal antibodies intended to reduce degradation of progranulin, a protein that regulates immune activity in the brain. The targeting of a receptor to deliver a therapy across the blood-brain barrier gives GSK another way to potentially treat neurodegeneration, but it’s not alone in this approach, called receptor-mediated transcytosis. The platform technology of Aliada Therapeutics engineers antibodies to target the transferrin and CD98 receptors to transport molecules across the blood-brain barrier. Similar to ABL, Aliada said its technology can be applied to multiple types of therapeutic cargos, such as enzymes, proteins, and oligonucleotides. With the biotech’s lead program in early clinical development for Alzheimer’s disease, AbbVie last year agreed to pay $1.4 billion to acquire Aliada. ABL’s research also spans Grabody drugs in development for cancer. A partnership with I-Mab is developing PD-L1- and claudin 18.2-targeting drugs; both programs are in Phase 1 for solid tumors. The most advanced ABL program is ABL001 (also known as tovecimig), a VEGF-targeting drug in late-stage clinical development for biliary tract cancer among other cancer indications under a partnership with Compass Therapeutics.

iStock, Jorm Sangsorn After some high-pro the one-time biotech darling is inching toward success with its Hunter syndrome treatment, which today began a rolling BLA for accelerated approval. Denali Therapeutics has its wheels on the fast track. The company initiated a biologics license application Wednesday for accelerated approval for Hunter syndrome treatment tividenofusp alfa (DNL310). It’s been a long time coming for Denali, which launched in 2015 with what was then the largest first-round venture financing in biotech history, a whopping $215 million. But a decade later, Denali doesn’t yet have an approved product, and its stock has dipped from its 2020 peak of more than $85 to just over $12 today. “When we came out of stealth in 2015, we raised a significant amount of money,” Carole Ho, Denali’s chief medical officer and head of development, told BioSpace . “And there was a question: What were we doing differently?” The brand-new company trumpeted a lofty goal of deploying new approaches to tackle neurodegenerative diseases—by targeting newly discovered genes tied to degenerative brain diseases. A year after launching, Denali scored another $130 million in a series B round led by Genentech veterans and maintained all of its founding investors. The company signed a bevy of research agreements, including deals with Blaze Bioscience and the Fred Hutchinson Cancer Research Center, to work on one of neurology’s toughest problems: getting drugs across the blood-brain barrier (BBB). Now, Denali is eyeing the culmination of these approaches with DNL310, an enzyme-replacement therapy that rides a specialized transport vehicle across the blood-brain barrier. The therapy secured FDA Breakthrough Therapy Designation in January, adding to a list of honors already held by the drug, including Fast Track Designation, Orphan Drug Designation and Rare Pediatric Disease Designation. “All of this suggests the agency’s enthusiasm for the molecule,” Ho said. Stifel analysts responded to the BLA submission Wednesday morning, saying, “We’re potentially nearing the end of an up-and-down regulatory path for [DNL310], where DNLI was finally able to align with FDA’s CDER on leveraging CSF heparan-sulfate (HS) as a surrogate biomarker for the basis of accelerated approval.” Stifel also noted the turbulent times in which this application has been submitted. “Notably, this announcement comes amidst significant turnover at FDA, where several senior directors across both CBER/CDER have departed,” the analysts wrote. From Small to Large Molecules In tackling Hunter syndrome, Denali has tried to set itself up for success. The company wanted to pursue a disease that was relatively derisked, where the underlying biology was very clear, Ho said. Hunter syndrome, a rare, X-linked condition resulting from a loss in the iduronate 2-sulfatase (IDS) enzyme, primarily affects boys and causes damage affecting both physical and mental development. There is one missing gene, the cause is monogenic and the mechanics of how a drug might treat the condition are very clear, even if practically achieving a treatment is still difficult, Ho explained. “If you could just replace that enzyme, you should see benefit.” DNL310 does just that. It is currently being tested in Phase I/II and II/III trials for the disease. Denali recently reported primary results from the earlier-stage study, touting improvements in hearing, cognition and adaptive behavior and a “generally well-tolerated” safety pro to four years. Denali’s getting to the one-yard line on Hunter syndrome may be partly due to a little bit of good timing—piggybacking off of technical advancements in gene sequencing that occurred in the mid-2010s—and changing tactics when other clinical trials failed. “Our early years were focused on small molecules,” Ho said. That includes parts of Denali’s pipeline still in development today, like DNL151, a Biogen-partnered LRRK2-targetting small molecule being developed for Parkinson’s disease. Denali’s pipeline also includes small molecules for Alzheimer’s and amyotrophic lateral sclerosis (ALS), developed as part of a partnership with Sanofi that began in 2018, netting Denali $125 million up front. Those molecules—DNL747 and DNL758—flopped on multiple occasions in early- and mid-stage trials. In a Phase Ib trial testing the drug in Alzheimer’s and ALS, DNL747 had dangerous and difficult-to-manage side effects, and in a Phase II study, DNL788 simply “did not meet the primary endpoint of change” on the ALS Functional Rating Scale-Revised, according to a company statement. In response, Denali laid off staff and dropped not only the Sanofi partnership and molecules but the entire molecular class: no more new small molecules. Going forward, the focus would be almost entirely on large molecules, such as biologics and engineered enzymes. For now, though, the focus is on Hunter and Parkinson’s, Ho said, with ALS and Alzheimer’s having been moved to the back burner. Denali currently has no candidate molecules in the pipeline targeting either disease, according to Ho. “We have a wealth of data there, and we are still interested in ALS in general,” she said, adding that the company is still analyzing data from past trials. Crossing the Blood-Brain Barrier With DNL310 leading the way, Denali is going all-in on drugs that cross the blood-brain barrier. “In terms of therapeutic development, crossing the BBB has been the greatest challenge in neurology,” Ho said. Indeed, it’s a hurdle that has tripped up generations of scientists and pharma companies. To overcome this challenge, the company has a suite of what it calls transport vehicles—molecules engineered to bind to transferrin, a cell surface receptor enriched on the BBB. In the case of DNL310, this is a so-called enzyme transport vehicle, or ETV. “Denali was built on the ability to build a next-gen platform to enable molecules to cross the blood brain barrier,” Ho said. Other biomolecules in Denali’s pipeline have different types of transport vehicles. An oligo transport vehicle (OTV) targets alpha synuclein in Parkinson’s disease, for example, while a progranulin transport vehicle (PTV) delivers a key neuroprotective molecule to patients with frontotemporal dementia. For its now-canned Alzheimer’s program, Denali had developed an antibody transport vehicle (ATV) in partnership with Biogen to deliver anti-amyloid antibodies to the brain (a partnership Biogen walked away from last summer ). Ho emphasized the nuanced nature of this transferrin-based drug delivery system. “In the past, you would always hear that you want high specificity,” she said. “But you don’t want it to stick too much. With transferrin, you want the opposite. You want it to bind but then come off. . . . We’ve fine-tuned this affinity.” This, Ho said, is key to the success of DNL310, which according to Wednesday’s announcement, Denali hopes to launch in late 2025 or early 2026.