AI-informed drug design enabled approval to dose within one year of project initiation
Data highlight use of AI to engineer investigative allele selective antisense oligonucleotide treatment for baby with ultra-rare neurological disease
Study provides initial clinical proof-of-concept for Creyon’s platform
SAN DIEGO, RESEARCH TRIANGLE PARK, N.C., May 7, 2024 — Creyon Bio, Inc. (“Creyon”), a clinical stage drug development company that engineers Oligonucleotide-Based Medicines (OBMs) with industry-leading efficiency creating novel, best-in-class gene-centric medicines to treat rare and common diseases, today announced encouraging clinical data highlighting the use of its custom designed data set paired with artificial intelligence (AI) to rapidly engineer an investigational antisense oligonucleotide (ASO) therapy. Within one year of project initiation in partnership with The TNPO2 Foundation, Creyon developed a novel allele-selective Locked Nucleic Acid (LNA) treatment candidate for an ultra-rare and severe neurological disease caused by a single nucleotide variant in the Transportin-2 (TNPO2) receptor, and an investigator-initiated clinical trial received approval to dose a patient. Initial data from this trial demonstrate that the investigational treatment successfully reduced seizures, restored developmental milestones, and was well-tolerated over nine months. Creyon will share these results during an oral presentation at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting in Baltimore on Friday, May 10, 2024, between 5:15-5:30 p.m. EDT in Room 307-308 of the Baltimore Convention Center.
“These results illustrate a key pillar of our approach – to engineer drugs for safety for rare and common diseases faster and more efficiently compared to traditional drug discovery techniques,” said Chris Hart, Ph.D., Co-Founder, Chief Executive Officer, and President of Creyon Bio. “We developed predictive models that guide our molecular engineering from the outset and help mitigate potential safety concerns. This approach allowed us to rapidly identify a drug candidate to target a specific genetic variant and have a clinical study initiated within a year. This proof-of-concept underscores the transformative potential of AI in OBM drug engineering to rapidly create new OBMs for common and rare diseases and target the genetic underpinning of disease anywhere in the body.”
“Our mission in pursuing a research program with Creyon Bio was to help our son develop to his fullest potential,” said Yiwei She, founder of The TNPO2 Foundation. “Faced with an ultra-rare diagnosis and a patient population ‘too small’ for academic labs and traditional industry, developing a personalized treatment was our only path forward. We have been encouraged by the measurable improvements in his behavior, health, and developmental progress, especially his reduced seizure burden. Through The TNPO2 Foundation, we will work collaboratively to create opportunities for other rare disease families to give this same opportunity to other children and families with rare diseases.”
Creyon has built the first and only platform capable of engineering for safety first, creating novel OBMs with optimal pharmacological properties engineered to minimize side effects. Utilizing proprietary tools, AI, and custom datasets, Creyon created 96 ASO candidates. Of those, 88 of the candidates were demonstrated to be safe utilizing in vivo and in vitro model systems, and several allele selective ASOs against the disease-causing TNPO2 variant were identified that demonstrated both safety and target selectivity in a cell model. The safest and most effective molecule was scaled up for GMP manufacturing, quality assessment and compounding.
Following toxicology studies and U.S. FDA permission to initiate the clinical study granted to the clinical investigator, Dr. Nicole Coufal, M.D., Ph.D., Associate Professor of Pediatrics at University of California San Diego and an attending physician at Rady Children’s Hospital San Diego, the patient received four increasing doses up to 40mg. This treatment has been well-tolerated with no increase in inflammatory markers in the cerebrospinal fluid (CSF) or adverse changes on brain MRI scans. Notably, the patient experienced reduced seizure frequency after the second dose and regained developmental milestones including rolling, sustained attention and gaining novel skills such as tripod sitting and responsive babbling after the third dose.
“It has been so rewarding to care for this patient and to see the hope and joy that this investigational treatment has brought his family,” said Dr. Coufal.
“Seeing the patient regain several key developmental milestones and that the investigational treatment was well-tolerated over nine months is beyond what we dared hope for,” commented David Dimmock, M.D., Chief Medical Officer of Creyon Bio. “Inflammatory reactions to oligonucleotide therapies have caused serious adverse reactions in other early clinical-stage therapies delivered directly to the central nervous system. Our platform is designed to mitigate these risks by leveraging AI-driven predictive models to identify and engineer solutions that reduce the potential for such adverse reactions.”
The oral presentation is titled “AI enabled ASO design can lead to rapid initiation of treatment for an ultra-rare disorder leading to allele selective knockdown of a toxic protein and consequent clinical improvement” (Abstract 309), and the full abstract can be viewed here.
About Creyon Bio, Inc.
Creyon Bio is a clinical stage biotechnology company developing best-in-class precision medicines with industry-leading efficiency through molecular engineering of Oligonucleotide-Based Medicines (OBMs). This includes ASOs, siRNAs, and aptamers. The company is changing how we create novel OBMs, transforming the process from drug discovery to drug engineering. Creyon has built the first and only platform capable of engineering for safety first, translating new target discoveries to OBMs with optimal pharmacological properties. Coupled with our aptamer-based delivery technologies, Creyon Bio is unlocking the full potential of OBMs for common and rare diseases alike. To learn more, visit creyonbio.com.
About The TNPO2 Foundation
The TNPO2 Foundation was created to provide hope and action for families with children facing rare diseases. Grounded in the belief that even the most devastating diagnoses can be treatable with modern science, medicine, and technology, the organization is dedicated to expanding access to cutting-edge precision medicine and therapies. The TNPO2 Foundation strives to support the challenges of those with the greatest unmet needs, by raising and strategically deploying funds to accelerate the research, development, and administration of personalized treatments for children with TNPO2 mutations and other ultra-rare conditions. To learn more, visit www.TNPO2.org.
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