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RESEARCH HIGHLIGHT
Aug. 11, 2022

Creyon Bio, Inc., a drug development company engineering Oligonucleotide-Based Medicines (OBMs) with predictable safety and efficacy profiles, published new research advancing their efforts to predict the chemical and biological properties of OBMs. The research shows proof-of-concept for a novel approach to predicting the electronic structure of large molecules, such as oligonucleotides: machine learning the electron-electron correlations on short polymers and then stitching these together to obtain highly accurate electronic structure of large polymers. The paper, titled “Machine Learning 1- and 2-electron reduced density matrices of polymeric molecules” is available in arXiv.

Identifying chemical features of molecules is a key step in drug discovery. At the most fundamental level, these chemical features are related to the quantum state of the electrons in the molecule, or the electronic structure. Computational chemistry tools for finding electronic structure of small molecules have been available for a long time, but these tools are too slow for larger molecules like oligonucleotides. This research describes proof-of-concept calculations to demonstrate that machine learning can be used to predict electronic structure of large molecules. We envision that this novel approach will be used to predict the electronic properties of OBMs. Efficient prediction of electronic properties in turn will allow us to connect the chemical design of OBMs to their chemical and biological properties, including toxicity and activity.

With advances propelled by machine learning and AI tools such as predicting the electronic structure of OBMs, the Creyon™ Platform creates unprecedented efficiency and will change how precision medicines are created for patients. Traditional trial-and-error approaches to screening gene-based medicines cannot scale up to meet the increasingly rapid pace of genomic discoveries. Creyon Bio develops and uses advanced machine learning and artificial intelligence along with optimal purpose-built datasets to connect foundational biophysical properties of OBM chemistry and sequence with accurate predictive models of safety and efficacy. Creyon Bio’s purpose-built datasets are orders-of-magnitude more efficient than using retrospective or ad-hoc screening data for building predictive models. This allows Creyon Bio to develop models to engineer optimal OBMs across a broad range of molecular modalities from single-stranded antisense oligonucleotides (ASOs) that reduce gene expression levels or change splicing events, to small interfering RNA (siRNA), to DNA and RNA editing systems, to even targeting aptamers.

In this research on predicting electronic structure of large molecules, the Creyon team’s work relies on a concept that Walter Kohn (a theoretical physicist and chemist who won the 1998 Nobel Prize in Chemistry for developing Density Functional Theory) called quantum nearsightedness, which states that electron-electron correlations in molecules are short-ranged. The Creyon team leveraged quantum nearsightedness, by first machine learning the electron-electron correlations on small polymeric molecules from training data generated using high-level quantum chemistry calculations, and then “stitching” these units together to obtain highly accurate electronic structure of bigger molecules.

In addition, the Creyon team’s work also addresses a fundamental problem in quantum chemistry. Since 1955 chemists have appreciated that electronic structure of molecules can be encoded using 2-electron reduced density matrices (2RDMs). 2RDMs store the electron-electron correlations and only require polynomial amount of storage while the conventional many-electron wave functions require exponential amount of storage. However, the adoption of 2RDMs for quantum chemistry calculations has been stymied by the n-representability problem: our inability to distinguish valid and invalid 2RDMs (using a polynomially complex algorithm). Creyon’s machine learning models provide a route around the n-representability problem by teaching the computer what valid 2RDMs look like.

David Pekker, Ph.D., Director of Theory at Creyon Bio, is lead author of the paper. Additional authors are Chungwen Liang, Ph.D., Principal Scientist, Computation Science, Sankha Pattanayak, Ph.D., Director of Chemistry, and Swagatam Mukhopadhyay, Ph.D., Co-founder and Chief Scientific Officer.

About Creyon Bio, Inc.

Creyon Bio is a pre-clinical stage company reimagining drug development as it should be, using a data-first approach for generating uniquely powerful datasets and developing machine learning models to uncover the engineering principles that make precision oligonucleotide-based medicines possible for patient populations of all sizes. To learn more, visit creyonbio.com.

SAN DIEGO, RESEARCH TRIANGLE PARK, NC – May 17, 2022 — Creyon Bio, Inc. (“Creyon Bio”), a drug development company engineering RNA-based medicines and their components (oligonucleotide-based medicines or OBMs) with predictable safety and efficacy profiles, today announced that David Fajgenbaum, MD, MBA, MSc, will serve as a Company Advisor and Board Observer. Dr. Fajgenbaum is a recognized thought leader in innovative biomedical research and drug development, particularly for rare disease, and will help Creyon Bio’s work to align and connect with regulatory, patient, and clinical communities.

“There are so many diseases and patients that do not have any effective treatment options even though medical technologies and tools exist that could help them. Creyon is helping to advance those technologies to help patients as quickly as possible,” said Dr. Fajgenbaum. “I am thrilled to support the Creyon team and excited by the platform they are building and their commitment to improving outcomes for patients.”

Dr. Fajgenbaum is an Assistant Professor of Translational Medicine and Human Genetics at the Perelman School of Medicine at the University of Pennsylvania and Associate Director of Patient Impact at the Penn Orphan Disease Center. An NIH-funded physician-scientist, he has dedicated his life to discovering new treatments and cures for deadly disorders including idiopathic multicentric Castleman disease (iMCD), which he was diagnosed with during medical school. He is currently in remission because of a precision treatment that he identified and that has been repurposed for iMCD. He described his journey to a precision treatment for his disease in his 2019 national bestselling memoir Chasing My Cure: A Doctor’s Race to Turn Hope Into Action. As the Co-Founder and President of the Castleman Disease Collaborative Network (CDCN), Dr. Fajgenbaum is a champion for the application of business-inspired solutions to advance iMCD research and works to apply this innovative model for accelerating rare disease research and drug repurposing. Dr. Fajenbaum is also Co-director of the advisory committee for the CURE Drug Repurposing Collaboratory, which is a FDA/NIH/C-Path public-private partnership, and a Board Member of the Reagan-Udall Foundation for the FDA.

“David’s focus on patients and their needs is unwavering, and his passion for creating a better world is compelling. We are excited to have David join our team as a company advisor and official board observer,” said Christopher Hart, Ph.D., Co-Founder, Chief Executive Officer, and President of Creyon Bio. “As we advance the Creyon Platform, David’s deep understanding of the rare community at a personal, medical, scientific and regulatory level will help shape our efforts and strategies.”

About Creyon Bio, Inc.

Creyon Bio is a pre-clinical stage company reimagining drug development as it should be, using a data-first approach for generating uniquely powerful datasets and developing machine learning models to uncover the engineering principles that make precision oligonucleotide-based medicines possible for patient populations of all sizes. To learn more, visit creyonbio.com.

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Media Contact:

Lissette Steele
Verge Scientific Communications
lsteele@vergescientific.com

SAN DIEGO and RESEARCH TRIANGLE PARK, NC, March 24, 2022 – Creyon Bio, Inc. (“Creyon Bio”), a drug development company engineering RNA-based medicines and their components (oligonucleotide-based medicines or OBMs) with predictable safety and efficacy profiles, announced today that David Dimmock, M.D., has joined the company as Chief Medical Officer. Dr. Dimmock is a preeminent expert in clinical genomic medicine and a practicing clinician. His medical practice has focused on the long-term care of patients with mitochondrial and metabolic disorders and the identification of rare disorders through newborn screening and advanced genomic techniques.

“It is difficult to find someone today who is more passionate or experienced than David in translating genomic diagnosis to precision medical care. David complements our exceptional multidisciplinary team, and together we will change how precision medicines are created for patients,” said Chris Hart, Ph.D., Co-Founder, Chief Executive Officer, and President of Creyon Bio. “We are committed to improving the outcome for patients, and David is the CMO who can help us achieve our mission.”

For the past six years, Dr. Dimmock has been a leader in the implementation of rapid precision medicine based on whole genome sequencing at Rady Children’s Institute for Genomic Medicine in San Diego (RCIGM). At RCIGM, he designed and led studies demonstrating that genomic sequencing of critically ill children provides dramatic change in medical management and health care cost savings. In addition to his genomics research, Dr. Dimmock has been the principal investigator on more than twenty industry sponsored clinical trials for novel therapeutics in orphan metabolic disease. 

“Creyon Bio’s vision is to lead a shift in oligonucleotide-based medicine development and over time deliver a regulatory agency-approved platform that connects definitive diagnosis to precision, personalized therapy,” said Dr. Dimmock. “I am excited to join Creyon Bio in building a faster, more cost-effective path to safely and predictably engineer novel OBM therapeutics for patients in need in time to make a difference.”

Dr. Dimmock will play a key role in developing the pre-clinical and clinical data that will support Creyon Bio’s first-of-a-kind platform to deliver on-demand OBMs. Creyon Bio’s interdisciplinary team of scientists and engineers develop proprietary, purpose-built datasets to inform powerful machine learning models, rapidly identifying the design rules and engineering principles for safe and effective OBMs, ideal for treating patients with rare or common diseases.

About Creyon Bio, Inc.

Creyon Bio is a pre-clinical stage company reimagining drug development as it should be, using a data-first approach for generating uniquely powerful datasets and developing machine learning models to uncover the engineering principles that make precision oligonucleotide-based medicines possible for patient populations of all sizes. To learn more, visit creyonbio.com.

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Media Contact:

Tabatha Thompson
Verge Scientific Communications
tthompson@vergescientific.com

Creyon Bio secures $40M in financing led by DCVC Bio and Lux Capital

Creyon’s drug development platform creates purpose-built data sets orders of magnitude more efficient than current approaches

Proprietary machine learning models reveal design rules and engineering principles for optimal oligonucleotide-based medicines, ideal for treating rare or common diseases

SAN DIEGO and RESEARCH TRIANGLE PARK, NC, March 8, 2022 – Creyon Bio, Inc. (“Creyon Bio”), a drug development company engineering RNA-based medicines and their components (oligonucleotide-based medicines or OBMs) with predictable safety and efficacy profiles, launched today with the goal of making precision medicines on demand a real possibility for populations ranging from one patient to millions. Creyon Bio creates proprietary, purpose-built datasets that inform powerful machine learning models, rapidly identifying the design rules and engineering principles for safe and effective OBMs.

Knowledge and understanding of the genetic and molecular causes of disease are rapidly expanding. OBMs are potentially ideal for precision medicine because they directly target these genetic and molecular causes. Creating new OBM therapeutics has been slow and expensive. The full potential of this class of drugs has yet to be realized, both for rare and common diseases. As the diagnostic odyssey ends for more and more patients, Creyon Bio is working to ensure novel OBM therapeutics are rapidly available.

“At Creyon Bio, we have built the company from the ground up to engineer OBMs, rejecting the idea that they need to be discovered through trial-and-error screening. Our mission is to design and offer predictably safe and effective options for patients with any disease amenable to OBM therapies,” said Chris Hart, Ph.D., Co-Founder, Chief Executive Officer and President of Creyon Bio. “No matter how rare or common their condition, no matter the size of the patient population, we believe that the Creyon Platform is creating a fast, efficient, and equitable path to engineering new medicines for patients.”

Creyon Bio uses advanced machine learning and artificial intelligence along with optimal purpose-built datasets to connect foundational biophysical properties of OBM chemistry and sequence with accurate predictive models of safety and efficacy. Creyon Bio’s purpose-built datasets are orders-of-magnitude more efficient than using retrospective or ad-hoc screening data for building predictive models. This allows Creyon Bio to develop models to engineer optimal OBMs across a broad range of molecular modalities from single-stranded antisense oligonucleotides (ASOs) that reduce gene expression levels or change splicing events, to small interfering RNA (siRNA), to DNA and RNA editing systems, to even targeting aptamers. The Creyon Platform creates unprecedented efficiency and will change how precision medicines are created for patients.

“At Creyon Bio, we believe it is time to use modern technologies and methods to engineer safe and effective therapies,” said Swagatam Mukhopadhyay, Ph.D., Co-Founder and Chief Scientific Officer at Creyon Bio. “Our unique datasets are optimized for efficiently building generalizable machine learning models, and we constantly refine our models through active learning. The Creyon Platform ultimately allows us to create safe and effective OBMs with exceptional efficiency, building a world where there is no gap between diagnosis and treatment.”

Creyon Bio has secured more than $40 million in seed and Series A financing led by DCVC Bio and Lux Capital. Other investors include Casdin Capital, Alexandria Venture Investments, and BioBrit. The funding supports continued optimization of the Creyon Platform, expanding the team, and laying the foundations for a diverse internal pipeline.

The Creyon Bio team is led by an interdisciplinary group of scientists and engineers with deep expertise in OBM development and machine learning:

Chris Hart, Ph.D., Co-founder, Chief Executive Officer & President

Swagatam Mukhopadhyay, Ph.D., Co-founder, Chief Scientific Officer

Nathan Billings, Ph.D., Chief Strategy Officer

Monica McArthur, Ph.D., Chief Technology Officer

In addition to Hart and Mukhopadhyay, Creyon’s Board of Directors includes Kiersten Stead, Ph.D., DCVC Bio; Zavain Dar, Lux Capital; and Dennis Langer, M.D., J.D., an independent board member.

“With a team that includes chemists, biologists, and computational scientists, Creyon Bio’s cross-disciplinary approach breaks down silos to tackle the drug design problem from all angles and create an efficient path to patient impact,” said Zavain Dar, Lux Capital.

“Creyon Bio’s groundbreaking approach and long-term planning, including partnerships with advocates and policymakers, is poised to revolutionize treatments for patients of rare disease and likely many common diseases as well,” said Kiersten Stead, Ph.D., DCVC Bio. “We are excited to work with the team to realize the full potential of engineering OBMs.”

About Creyon Bio, Inc.

Creyon Bio is a pre-clinical stage company reimagining drug development as it should be, using a data-first approach for generating uniquely powerful datasets and developing machine learning models to uncover the engineering principles that make precision oligonucleotide-based medicines possible for patient populations of all sizes. To learn more, visit creyonbio.com.

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Media Contact:

Tabatha Thompson
Verge Scientific Communications
tthompson@vergescientific.com