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RESEARCH HIGHLIGHT
July 2023

Creyon Bio is excited to be part of the inaugural Decoding Bio Snapshot, sharing our view at the intersection of computation and biology as Creyon, along with the other companies profiled, push the pharma and biotech industry forward. Led by Pablo Lubroth at Hummingbird Ventures and Amee Kapadia at Cantos Ventures, this research project highlights the next generation of bio companies.

At Creyon Bio, we develop better precision medicines faster and at lower cost through molecular engineering of Oligonucleotide-Based Medicines (OBMs) – this includes ASOs, siRNAs, guide RNAs, RNA editing guides, mRNAs, aptamers. Creyon is leveraging the driving forces discussed throughout this report – accessibility of data, AI/ML tools, scale and automation, and a culture shift of multidisciplinary teams – to change how OBM drug development is done.

Creyon has built the most informative dataset that connects biophysical properties of OBMs at a quantum chemistry level with purpose-built datasets of 1000’s of IND-like in vivo studies and hundreds of 1000’s of in vitro and ex vivo experiments, and we have combined this with best-in-class tools for OBM engineering, including AI/ML, data science ops, chemistry, and bioassays.

Our un-siloed team includes biologists, chemists, and physicists with both deep quantitative and data science expertise and management experience in driving inter- and multidisciplinary science and engineering teams; legal, business and financial strategists; and clinical, genomics, and advocacy leaders.

With our data, tools, technologies, and team, Creyon is driving non-clinical costs toward zero and improving the probability of early clinical success by replacing trial-and-error screening with engineering and validation to identify safe and efficacious OBMs.

Creyon is changing the economics, scale and timelines at which new medicines are made to address unmet medical needs for diseases that affect millions, thousands, or even just a few.

RESEARCH HIGHLIGHT
July 2023

DCVC has released their inaugural Deep Tech Opportunities Report. It highlights their “organizing passion and principle” of investing in companies dedicated to disrupting and transforming industries like drug development. Creyon Bio is honored to be included among so many other amazing DCVC portfolio companies and to share about our efforts to quickly develop precision medicines for rare and common diseases, whether for millions of patients or for just one.

This recognition that deep tech has the potential to transform industries was, in part, what helped get Creyon Bio off the ground. Creyon was founded with the goal of solving the fundamental problem in drug development – it takes too long and costs too much to develop too few drugs.  DCVC Bio, one of our lead investors, aligned with our vision that the convergence of advances across many technologies presents an opportunity to disrupt drug development of Oligonucleotide-Based Medicines (OBMs) like antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), guide RNAs (gRNAs), RNA-editing guides, and aptamers.  Creyon Bio’s deep tech solution required the creation of purpose-built pharmacology datasets, a quantum-level understanding of OBM biophysics and the creation of ML/AI tools that tie these pieces together. With this deep tech solution, we can engineer for drug safety, something never before possible – ultimately radically lowering the cost and time required to rapidly develop new Oligonucleotide-Based Medicines. This transformative approach opens up drug development opportunities for any patient population size. And in a way that will make novel therapies accessible and available to people in need within the health care systems of the world today.

Company Announces Chief Operating Officer & General Counsel Jason Ferrone, JD, and Chief Financial Officer Robert Muir

SAN DIEGO and RESEARCH TRIANGLE PARK, NC, July 20, 2023 – Creyon Bio, Inc. (“Creyon Bio”), a drug development company engineering Oligonucleotide-Based Medicines (OBMs) to develop novel gene-centric medicines faster and at lower cost for rare and common diseases, today announced that Jason Ferrone, JD, and Robert Muir have joined the executive leadership team. Mr. Ferrone has been appointed as Chief Operating Officer and General Counsel, and Mr. Muir has been appointed as Chief Financial Officer.

“Creyon is increasing the probability of development success by engineering OBM drugs for safety and efficacy,” said Chris Hart, Ph.D., Co-Founder, Chief Executive Officer, and President of Creyon Bio. “Strategic expansion of the executive leadership of Creyon will support efforts to clinically validate our platform as the first OBMs engineered by Creyon advance toward clinical trials.”

Hart added, “Jason is a seasoned industry leader, with deep and diverse experience across all aspects of drug development, and Robert brings tremendous knowledge and experience in financial and management strategy and investor engagement. This expansion of our uniquely un-siloed team will serve us well as we continue to build out key functions to advance our vision of creating a radical abundance of novel precision medicines, whether for diseases affecting millions of people or for diseases affecting hundreds or even just a few people.”

As COO and General Counsel, Jason will leverage his distinctive combination of leadership and experience across drug discovery and development. Prior to joining Creyon Bio, he co-founded Intrinsic Medicine, serving as its President and Chief Operating Officer, where he continues to hold a position on its board of directors. Prior to Intrinsic, Jason held leadership positions in Regulatory Affairs, Corporate Development and Patents, and provided intellectual property, regulatory and business strategy consulting services to early-stage private and public drug discovery and development companies. Jason earned his JD cum laude from Suffolk University Law School with an Intellectual Property Concentration. He is a registered patent attorney, licensed to practice law in Massachusetts, and is presently pursuing authorization to practice in California. Prior to law school, Jason was a research medicinal chemist, earning an MA in Chemistry from San Diego State University.

As CFO, Robert joins Creyon with more than two decades of deep experience across a variety of areas including corporate management, financial strategy, valuation, and investor engagement. He has served in multiple team leader roles, including his most recent role on the New York management team as Director of Equity Research at Berenberg. Prior to this, Robert served as a successful senior analyst at Berenberg and at Morgan Stanley in London. He began his career as a management consultant with PwC, where he was engaged in corporate strategy and due diligence, the latter for private equity clients. A CFA charter holder, Robert holds an MA and MSci in Natural Sciences from the University of Cambridge.

About Creyon Bio, Inc.

Creyon Bio is a pre-clinical stage drug development company developing better precision medicines faster and at lower cost through molecular engineering of Oligonucleotide-Based Medicines (OBMs). This includes ASOs, siRNAs, guide RNAs, RNA editing guides, mRNAs, and aptamers. Creyon has built the most informative dataset and the best tools ever assembled to learn the engineering rules for OBMs, replacing trial-and-error screening with engineering and validation to identify safe and efficacious OBMs. To learn more, visit creyonbio.com.

Media Contact:

Joan Bosisio
Verge Scientific Communications
jbosisio@vergescientific.com

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