Nymirum RNA Revealed

Nymirum

Nymirum is a venture-backed, privately held company that has developed a proprietary platform to rapidly solve high-resolution RNA 3D structures and therapeutically target RNA using small molecules.

Drug developers around the world have focused on RNA as one of the most promising drug discovery targets of the 21st century. Utilizing small molecules avoids the drug delivery difficulties inherent in nucleic acid-based approaches and enables orally available treatments for a broad range of diseases.

Nymirum's platform is both complimentary and disruptive. Our platform was specifically built to fit within the industry's existing infrastructure, providing new molecules and scaffolds for newly validated RNA targets which are fed into the traditional med chem and biology pipeline. We enable the industry to attack a new generation of higher-probability targets while leveraging their existing small molecule library.

Management & Founders

Andrew C. Stelzer

Dr. Stelzer heads all internal and external computational programs at Nymirum. He also sets scientific priorities, oversees the scientific team, and leads the company's IP development.

Stelzer is a co-inventor of the Nymirum technology and has authored multiple peer-reviewed publications and patents detailing break-through discoveries in RNA structural biology and small molecule recognition. He also has extensive experience in strategic IP development.

He received his Ph.D. in Chemical Biology from the University of Michigan and his B.S. in Chemistry from the University of Toledo. During his Ph.D., he studied business management at the University of Michigan’s Ross School of Business.

Michael E. Pape

Dr. Pape designs, develops, and manages the internal and external drug discovery programs

Pape is a founding partner of Orchard Venture Partners, a venture capital firm. He is a co-founder of Esperion Therapeutics (sold to Pfizer in 2004 for $1.3 billion), Nymirum and Akebia Therapeutics. He worked as a scientist at Upjohn, Parke-Davis, and Pfizer directing drug discovery and publishing extensively on metabolic diseases.

He received his Ph.D. in Biochemistry from Purdue University, his MBA from the University of Chicago Graduate School of Business, and his bachelor's degree in Microbiology from the University of Michigan.

J. P. Fairbank

Mr. Fairbank manages business finances and is the Chairman of the Board.

Fairbank is a founding partner of Orchard Venture Partners, a venture capital firm founded in 2004, and a co-founder of Akebia Therapeutics. Before escaping to VC/entrepreneurship he survived a decade in investment banking and investment management.

He received his MBA from the University of Chicago Graduate School of Business (Booth) and his bachelor's degree in Economics from Connecticut College.

Hashim M. Al-Hashimi

Prof. Al-Hashimi is a co-inventor of the technology underlying Nymirum's platform. He provides specific direction on the scienific undertakings at Nymirum.

Al-Hashimi is the James B. Duke Professor of Biochemistry at the Duke School of Medicine and is the Director of the Duke Center for RNA Biology.

He received his Ph.D. from Yale University, worked as a Research Scientist at Sloan-Kettering, and is the recepient of the National Science Foundation Career Award. His breakthroughs in RNA research have been repeatedly published in Science and Nature.

RNA-targeted Small Molecule Drug Discovery Platform

The Problem

Small molecules that target RNA comprise one of the most successful drug classes of all time: antibiotics. Even with this precedence and the emergence of RNA being responsible for cellular dysfunction, technologies do not exist to robustly discover RNA-targeting small molecule drugs...until now.

Human genome related research indicates that up to 93% of the genome is transcribed into RNA, yet fewer than 2% of RNA is translated into protein. Drug discovery efforts over the last fifty years have almost exclusively focused on the protein products derived from the 2% and have ignored nearly the entire RNA population. Using the Nymirum Platform, the other 93% can be directly targeted.

With recent discoveries of diseases caused by dysfunctional human RNA, along with the explosion of potential RNA targets emerging from whole genome sequencing of disease causing microorganisms, enabling technologies to identify drugs that alter RNA activity and thereby alleviate disease are desperately needed. Experimental high-throughput screening approaches often fail because most RNA targets lack enzymatic activity while small molecule binding assays do not provide atomic level structural information needed to relate binding affinity to biological activity for robust structure activity relationship (SAR) studies. While computational methods provide the desired structural information and can in principle be implemented in a high throughput manner without experimental limitations, inherent RNA flexibility precludes computational methods from correctly accounting for the large structural changes that occur on RNA-small molecule binding. The Nymirum platform directly solves this problem by using RNA plasticity to its advantage to solve RNA structures with small molecule amenable binding pockets.

The Solution

Nymirum's platform can begin as early as target selection and proceeds through chemical and biological lead optimization.

RNA drug discovery solution
Small molecule binding pockets in the Human microRNA-122 loop

The core of Nymirum's drug discovery platform experimentally determines atomic-level RNA conformers that display pockets amenable to specifically bind small molecules. Using the atomic coordinates of these conformers, Nymirum is able to delineate all possible RNA-small molecule interactions, a critical step in structure-based drug design. In fact, the platforms's virtual screening methodology can rapidly assess the ability of millions of small molecules to favorably interact with the binding pockets. By harnessing inherent RNA plasticity to generate multiple small molecule binding pockets, Nymirum is able to rapidly identify small molecules that modulate RNA cellular function and provide necessary biological specificity.

Employing an iterative feedback process between all experimental and computational modeling phases of the Nymirum Platform, drug discovery projects rapidly progress from hit to lead to drug candidate. During our partnered projects we are able to incorporate our partners' domain expertise and requirements into the process.

RNArchitect

By combining the power of residue-position-specific isotope labeling (SPOTLIGHT) and state of the art NMR data-driven 3D modeling technologies (CONSTRUCTOR), RNArchitect offers academic and non-profit researchers easy-to-use, rapid and economic solutions to solve high-resolution 3D RNA structures. Click here to access RNArchitect

SPOTLIGHT

SPOTLIGHT

A section of superimposed 2D 13C-1H HSQC NMR spectra from the Human microRNA-122 loop sequence using an in vitro transcribed uniformly 13C/15N labeled RNA (in gray) and a SPOTLIGHT (in orange) with two select residues, U11 and A12.

CONSTRUCTOR

CONSTRUCTOR