William Marsh Rice University

iStock, Mary Long Changing how biopharmas package their products, how regulators review new drugs and how mutated genes are fixed could make ultrarare disease treatments possible. In early May, a nine-month-old baby named KJ became the first patient to ever receive a custom-made gene therapy , a single-use CRISPR treatment for an ultrarare disease called CPS1 deficiency. That therapy, created a collaboration of a series of companies and administered at the Children’s Hospital of Philadelphia, immediately begat a question: Can we do it again? Almost by definition, treatments for ultrarare diseases cannot be developed in the same way as treatments for more common conditions. With so few patients, traditional clinical research is impossible and economies of scale do not exist. The promise of gene therapies in the imagination is one of simplicity, where a gene editor can simply snip out a problematic sequence and replace it with a healthy one. But genetic conditions are often extraordinarily complex, even if they’re monogenic. Take hemophilia, for instance, which is often caused by a damaged copy of the gene for factor VII, a critical blood clotting component. “But there’s a wide range of errors in factor VII [that cause hemophilia]. How do you serve a wide population with a single product?” Tom Madden, president and CEO of the biotechnology company Acuitas Therapeutics, told BioSpace . “Realistically, you cannot do that.” Acuitas has experience here: it manufactured the lipid nanoparticle (LNP) delivery system for baby KJ. Meanwhile, Aldevron made the base editor and Inegrated DNA Technologies (IDT) constructed the guide nucleic acid. All contributions were provided free of charge. “It’s not surprising to me that we haven’t been able to do this before,” said John Evans, CEO of genetic medicines company Beam Therapeutics. “We need certain capabilities and we’re just now getting to the point where [treating ultrarare diseases] is plausible.” Platform Technologies Streamline Development Ultrarare genetic diseases are defined as those that affect one of every 50,000 or more people. But there are ways to facilitate treatment even if cheap, large-scale trials and manufacturing are out of the question. Madden recalled hearing former Center for Biologics Evaluation and Research (CBER) chief Peter Marks speak about platform technologies where the structural components of a therapy—like the delivery system—could be approved, while allowing for one part to be switched out. A genetic medicine approach could have a vector like an AAV or LNP, a guide molecule and a therapeutic payload approved as a platform. To treat a patient with a unique, so-called “n of 1” disease, a custom guide could be created and plugged into an-already approved platform technology. Marks was “quite fulsome” about the possibilities of facilitating treatments for rare and genetic conditions, according to Madden. At the time BioSpace spoke with Madden, May 23, it was not clear whether Marks’ successor, Vinay Prasad, would deviate from this vision. So far, he hasn’t: two weeks later, the FDA granted the first ever Platform Technology Designation to Sarepta Therapeutics for a viral vector called rAAVrh74 that the company uses with a variety of the treatments it is developing. The designation, developed under the Biden administration, is seemingly the first step toward fulfilling recent promises bynew CBER Director Vinay Prasad, FDA Commissioner Marty Makary and HHS Secretary Robert F. Kennedy Jr. to make treatments for genetic and rare diseases easier to develop. Acuitas is one company trying to take advantage of this type of streamlining. Madden envisions something along the lines of an at-home (or at-hospital) kit. A manufacturer would make a batch of vectors (LNPs in Acuitas’ case), and a regional facility would create a guide and editor in small quantities, taking advantage of the ease of producing the nucleic acids needed. This is similar to how KJ’s treatment came together. Acuitas prepared the LNPs in Vancouver while Aldevron worked on the base editor in North Dakota and IDT manufactured the guide in Iowa, with all three components finally being shipped to Philadelphia for assembly by KJ’s medical team. Precision Editors Lead the Way Perhaps the biggest breakthrough that made a treatment like KJ’s possible, Evans told BioSpace , was leaving behind the limitations of traditional CRISPR technologies. “Older tools could go anywhere, but all they could do is make a cut, including in CPS1 ,” he said. “In CPS1, just cutting it isn’t going to help; the gene is broken.” Traditional CRISPR-Cas9 cuts across both strands of a DNA molecule in an act that quite literally damages the DNA. The idea, or hope, was that the gene-editing machinery could remove the cut, mutated section and, using the cell’s difficult-to-control DNA damage repair pathways, write in the replacement part. In a medical setting this was a scattershot, almost luck-based approach that simply didn’t cut muster, Evans said. “The original Cas9 wasn’t versatile.” The treatment that KJ received instead relied on base editing, which directly changes a base in a gene sequence without making cuts or replacing whole sections. A CRISPR enzyme known as a nickase only cuts one strand, and a guide RNA tethered to a second protein converts a C/G base pair to a T/A, or vice versa. This system, developed by a number of labs but particularly David Liu’s at Harvard, can make targeted and specific changes to the genome. “It’s like a pencil and eraser,” Evans said. “It’s known as gene editing 2.0 for a reason.” With that tech in hand, other diseases are in sight, including for more common conditions than CPS1 deficiency. Beam is trialing its base editors in sickle cell disease and has preclinical work ongoing in a number of other conditions, such as in mouse models with ALS while its competitor Verve recently showed strong results in a Phase Ib trial for its cholesterol-lowering base editor. Some hurdles remain for treating ultrarare diseases, according to Isaac Hilton, a bioengineer at Rice University. The most prominent of these is that despite recent advances, there’s no good way to specifically target most of the body’s organs with a gene therapy. The exception is the liver, since that organ is easily targeted with LNPs and other vehicles. CPS1 deficiency specifically affects the liver, meaning KJ was a good candidate for a gene therapy. “Liver-based conditions are advantageous in these kinds of rare diseases,” Hilton said. If a rare disease is not routed through the liver, delivery becomes more difficult. Another issue is inherent to CRISPR based editors, even nickases. “Cas9 is a large protein,” Evans said. “It’s not trivial to get it to the right place.” Viral vectors, for years the most common method for packaging and delivering therapies, can have tremendous variability from batch to batch, which is difficult to control since they are not-quite-living organisms. LNPs, like the ones Acuitas manufacture and used for KJ’s treatment, have an ease of production advantage and simply have a larger cargo capacity than AAVs, without also running the risk of inducing an immune response. “I’m not surprised [KJ’s treatment] used LNPs, they’re much more straightforward and easier to manufacture,” Evans said. Finally, there are regulations to consider. KJ’s treatment got fast-tracked through the FDA, with organizations like the Innovative Genomics Institute and Danaher (IDT’s parent company) intervening on his behalf. The FDA approved his treatment within a week—a process that likely cannot be replicated for every patient needing a custom therapy. Still, Evans is hopeful for the future of treating ultrarare diseases, as regulators catch up and companies find solutions to manufacturing hurdles. While gene editing companies are scaled to produce enough materials to run clinical trials, testing therapies for ultrarare diseases involves learning how to produce therapies on smaller scales—something Evans said companies including Beam and even Moderna are actively working on. “We are thinking about getting involved in these n of 1 cases,” Evans said of Beam. “It should absolutely be achievable to get people in a clinic, as long as it’s in an organ we can target. Start in the liver, maybe go to the blood. It’s not that hard to do anymore.”

HOUSTON, TX, USA and CHICAGO, IL, USA I May 29, 2025 I RBL LLC, a pioneering biotech venture creation studio dedicated to rapidly building companies based on breakthrough medical technologies from Rice University, today announced the launch of Sentinel BioTherapeutics at the 2025 ASCO Annual Meeting. Sentinel’s launch marks RBL’s first company spin-out since its formation in October 2024 and positions Sentinel to begin preparations ahead of the next phase of clinical development for its lead cancer immunotherapy program. Developed in the laboratory of bioengineering expert, Omid Veiseh Ph.D., at Rice, Sentinel’s platform enables sustained and local delivery of the cytokine interleukin-2 (IL-2) to activate the immune system and enhance the potency and effectiveness of checkpoint inhibitors against solid tumors. The allogeneic encapsulated cell-based system enables constitutive expression of human IL-2. This approach can offer a new paradigm for treating cancers that typically respond poorly to checkpoint inhibitors, such as ovarian cancer and mesothelioma. “We believe this is a powerful, new approach that can increase the sensitivity of solid tumors to immunotherapy” said Rima Chakrabarti, M.D., the company’s Chief Executive Officer and managing partner at RBL. “Data from a Phase 1 study show the significant potential of our IL-2-producing cell-based platform to specifically stimulate immune checkpoint expression, supporting the rationale for using our agent in combination with immunotherapy. With the backing of RBL, we are moving forward with GMP manufacturing and clinical trial preparation plans in high unmet need solid tumor indications. We are proud to be part of the growing Houston biotech ecosystem that is supported by the Rice Biotech Launch Pad and RBL.” Sentinel’s Phase 1 data will be presented in a poster at the 2025 ASCO Annual Meeting in Chicago. The presentation will highlight clinical biomarker data showing the ability of the company’s IL-2 immune priming therapy to induce dose-dependent increases in CTLA-4 expression on both CD8+ and CD4+ T cells, supporting its use as a priming agent for effective checkpoint inhibition. Full details of the abstract (#5562) can be viewed here . Session Title: Gynecologic Cancer Poster Title: Phase I Study of Sustained and Local Delivery of Intraperitoneal IL-2 using Encapsulated Cells in Patients with Platinum-Resistant High-Grade Serous Carcinoma Date & Time: June 1, 2025, 9 – 12 p.m. CT Location: Poster Bd #460 “The launch of Sentinel represents a major milestone in RBL’s mission to support companies that are transforming bold scientific ideas into therapeutic products with the potential for rapid patient impact,” said Paul Wotton, Chief Executive Officer and Managing Partner of RBL and Chairman of Sentinel. “Sentinel’s cytokine factory platform is the breakthrough technology that we believe has the potential to define the next era of cancer treatment.” About RBL LLC: RBL LLC is a pioneering biotech venture creation studio based in Houston that is dedicated to accelerating the development of breakthrough medical technologies and therapies through company formation. RBL provides entrepreneurs, researchers and innovators with infrastructure, financial support and strategic guidance as well as access to laboratory space and shared resources in the Texas Medical Center Helix Park. For more information, please visit https://www.rbl-llc.com/ . About Sentinel BioTherapeutics: Sentinel BioTherapeutics is a Houston-based clinical stage biotech company developing localized cytokine immunotherapies that safely activate the immune system against solid tumors. The company’s lead program SENT001, formerly known as AVB-001, stimulates effector T cell activity and immune checkpoint expression which can enhance the efficacy of checkpoint inhibitors in patients with primary or secondary peritoneal and pleural cancer. The company holds a fast-track designation for PROC and orphan disease designation for mesothelioma. The company has plans to initiate “immune priming” clinical trials for peritoneal solid tumors. For more information visit www.sentinelbiotx.com . SOURCE: Sentinel BioTherapeutics

HOUSTON and WALTHAM, Mass., April 17, 2025 /PRNewswire/ -- Biostate AI, a leading innovator in artificial intelligence for RNA sequencing, today announced a strategic partnership with the Accelerated Cure Project (ACP), a nonprofit organization dedicated to accelerating research and improving outcomes for people with multiple sclerosis (MS). The partnership aims to develop next-generation AI models capable of predicting disease progression and treatment response in MS, leveraging transcriptomic data from ACP's extensive biorepository. Continue Reading Under the collaboration, Biostate AI will sequence patient samples from the ACP Repository, one of the world's largest and most comprehensive MS-related collections of biospecimens and clinical data. Utilizing its proprietary barcode-integrated reverse transcription (BIRT) technology, Biostate AI will generate high-resolution RNA expression profiles at scale and train transformer-based AI models to personalize treatment strategies for MS patients. "By partnering with Biostate AI, we're turning data into actionable insights that could revolutionize patient care." Post this "Biostate's RNA sequencing and AI technologies offer a unique opportunity to transform our understanding of MS progression and treatment response," said Sara Loud, CEO of the Accelerated Cure Project. "We are thrilled to collaborate with Biostate AI to unlock the full potential of our biorepository and accelerate innovations leading to better outcomes for people with MS." The ACP Repository includes thousands of blood samples from individuals with MS and controls, including valuable longitudinal samples linked to extensive clinical and demographic data. This rich dataset facilitates the creation of AI systems to detect molecular patterns associated with disease onset, relapse, remission, and treatment responses. "At ACP, we've dedicated years to building a resource designed to advance breakthroughs in MS research," said Dr. Stephanie Buxhoeveden, Chief Scientific Officer at ACP. "By partnering with Biostate AI, we're turning data into actionable insights that could revolutionize patient care." Biostate will sequence the entire ACP Repository and develop a series of AI models addressing a range of clinical and research questions. These models will be designed to improve the prediction of disease progression and identify patients most likely to benefit from therapies across the MS disease spectrum. "Current MS management relies heavily on trial and error due to limited predictive tools," said David Zhang, co-founder and CEO of Biostate AI, and former Associate Professor at Rice University. "By combining high-throughput RNA sequencing with AI, we aim to equip clinicians with precise, data-driven guidance, ensuring patients receive appropriate therapy promptly." This partnership marks Biostate's entry into neuroimmunology and extends its portfolio of disease-specific AI models. Leveraging transcriptomic data, Biostate's platform aims to support personalized medicine at unprecedented scale. "Our goal is creating adaptable disease models tailored to individual patient biology, surpassing existing diagnostics," said Ashwin Gopinath, co-founder and CTO of Biostate AI, and former Assistant Professor at MIT. "MS's complexity and variability make it an ideal candidate for our approach, and we're eager to collaborate with ACP to develop clinically actionable tools." This initiative strengthens ACP's commitment to accelerating cures via collaboration, data sharing, and innovative science, while allowing Biostate to extend its AI capabilities into therapeutic areas with significant unmet needs. About Biostate AI. Biostate AI is a startup building generative AI that predicts the evolution of human disease and drug response based on RNA sequencing data. Its patented wetlab technologies, including BIRT, allow affordable and scalable collection of massive amounts of transcriptomic and genomic data. With sites in Houston, TX, Palo Alto, CA, Bangalore, India, and Shanghai, China, Biostate AI is an international company with collaborations with top hospitals, academic researchers, and biotech/biopharma companies. Biostate AI was founded by serial entrepreneurs and former professors David Zhang (Rice U.) and Ashwin Gopinath (MIT) and is backed by top investors and experts including Accel, Dario Amodei (Anthropic), Emily Leproust (Twist Biosciences), and Mike Schnall-Levin (10X Genomics). About the Accelerated Cure Project for Multiple Sclerosis. The Accelerated Cure Project is a patient-centered nonprofit organization dedicated to accelerating research and improving the well-being of people affected by MS. Through its biorepository, research network, and collaborative initiatives, ACP connects people with MS, researchers, and clinicians to advance understanding and drive innovation in MS care. For more information, please contact: Jessie Yang Finance and Business Associate [email protected] SOURCE Biostate AI WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED