NEOMORPH
Advancing the science of targeted protein degradation to destroy ‘undruggable’ proteins and cure disease
About
Neomorph is a venture backed biotechnology company based in San Diego, California. The team at Neomorph is building a leading protein degradation company, focusing on ‘molecular glue’ degraders. Our mission at Neomorph is to use this technology to solve critical problems in human health by the discovery and development of innovative new medicines against ‘undruggable targets’. The Neomorph team is composed of leaders from the academic and industrial worlds who have demonstrated years of commitment and success in the field, and who remain dedicated to advancing the technology and delivering highly impactful drugs. The Neomorph team is advancing the science and technology of molecular glue drug discovery, while prosecuting a pipeline of projects through clinical development. Neomorph has a key collaboration with the Center for Protein Degradation at the Dana Farber Cancer Institute.
Science
Targeted Protein Degradation Therapeutic Discovery
Targeted protein degradation drugs work by repurposing the cellular machinery to destroy proteins linked to disease. Some degraders work by redirecting cellular machines known as E3 ubiquitin ligases to disease-causing proteins, causing them to be marked for degradation. These degraders can be classified as heterobifunctional (e.g. PROTACs) or ‘molecular glue’ (e.g. indisulam or thalidomide). There has been an explosion of interest in targeted protein degradation in recent years due to the convergence of two advances: heterobifunctional molecules were optimized to be suitable for in vivo use, and clinically approved drugs were found to function via the ‘molecular glue’ degradation mechanism. Together, these scientific advances offer an opportunity to tackle targets and diseases that had been considered intractable to conventional drug discovery.
Molecular Glue As A Solution to ‘Undruggable’ Targets
Historically, conventional therapeutics fell into the categories of large and small molecule drugs, with large molecules such as antibodies able to target extracellular targets, and small molecules able to target extracellular or intracellular targets. Small molecule campaigns are typically limited to targets shown to be ‘druggable’. Druggable targets have a binding pocket that can support high-affinity binding to a drug molecule with appropriate properties for clinical use. Binding alone is often insufficient to achieve a biological effect, so drug binding in the pocket must also perturb cellular biology in a way that is clinically beneficial. However, many disease-causing proteins lack druggable binding pockets, or drug binding alone does not cause the desired biological effect, and these targets have been considered ‘undruggable’. Targeted protein degradation offers a path to solving this problem by triggering the destruction of the target protein by the 26S proteasome, thereby removing all of the associated biological activities. While heterobifunctional drugs still require a druggable binding pocket on the target protein, molecular glue drugs are able to bypass this requirement, and as such offer a differentiated approach to drug discovery with different rules and the potential to target a broad section of the proteome. Molecular glue drugs have been described relatively recently, but the science is now well-established and the therapeutic mechanism has been clinically validated through an understanding of the recruitment of neomorphic substrates to CRL4CRBN by thalidomide analogs, as well as the recruitment of RBM39 to CRL4DCAF15 by indisulam.
Further Reading
News
Neomorph, Inc. Announces $109 Million Series A Financing to Advance Proprietary Protein Degradation Platform and Programs
Neomorph, Inc. Announces $109 Million Series A Financing to Advance Proprietary Protein Degradation Platform and Programs
(San Diego, CA, Dec. 22nd, 2020)—Neomorph, Inc. announced a $109 million Series A financing to advance a proprietary targeted protein degradation platform and specific programs. Deerfield Management Company established Neomorph earlier this year with scientific founders Phil Chamberlain, DPhil, Eric Fischer, PhD, Benjamin Ebert, MD, PhD, and Scott Armstrong, MD, PhD.
The founding management team comprises pharmaceutical veterans with deep industry knowledge in targeted protein degradation drug discovery. Led by Dr. Chamberlain as President and Chief Scientific Officer, Neomorph has recruited top industry talent who have made major contributions to the field, including: Rohan Beckwith, PhD; Gang Lu, PhD; Mary Matyskiela, PhD; Ben Wen, PhD, and Samer Chmait.
Targeted protein degradation offers opportunities to develop novel therapeutics across a broad range of disease areas, including oncology. Strategies for protein degradation have been shown to solve critical problems in drug discovery by enabling researchers to target previously ‘undruggable’ proteins that lack suitable binding pockets required for conventional drug activity.
Of particular note, Neomorph’s founders are responsible for several fundamental scientific developments in the “molecular glue” field. Molecular glues are types of molecules that encourage proteins to come together that normally wouldn't interact. Neomorph plans to build on the collective pivotal research findings of the team to advance the technology of targeted protein degradation and solve critical problems in human health.
“Having the ability to achieve this milestone during these unprecedented times is a testament to Neomorph’s capabilities in the protein degradation and molecular glue space,” said Dr. Fischer, who is also an Associate Professor in the Department of Biological Chemistry and Molecular Pharmacology at Harvard Medical School and an Independent Investigator at the Dana-Farber Cancer Institute. “I am humbled to be a part of a team poised to make real strides in advancing the science. We believe we are in an excellent position to take our technology to the next level with the ultimate goal of delivering transformative treatments to patients in need.”
“The Neomorph team has deep expertise in pharmacological approaches to targeted protein degradation and we are excited to be developing new therapeutics for patients with diseases that are currently difficult to treat,” said Dr. Armstrong, who is also David G. Nathan, MD, Professor of Pediatrics at Harvard Medical School and the Dana-Farber Cancer Institute.
Utilizing Deerfield seed funding and operational support since the first quarter of 2020, Neomorph has established a research site in San Diego at the Genesis Science Center in Sorrento Mesa, California. This Series A financing will position Neomorph to further develop its platform, advance lead programs, and expand the research team.
“As a drug strategy, protein degradation has enormous potential as it leverages the cell’s natural system for clearing unwanted or damaged proteins,” said Deerfield Partner Cameron Wheeler, PhD. “We believe there continues to be a significant opportunity in protein degradation, in particular as it relates to the glue space. Neomorph is in an exceptional position and couldn’t have a more seasoned and knowledgeable team in place to interrogate and advance drug targets. The Company’s success could potentially lead to life-altering therapies.”
Neomorph will benefit from a close collaboration with the Center for Protein Degradation at Dana Farber Cancer Institute. With its investment, this expands Deerfield’s commitment in the space given the firm’s longstanding partnership and collaboration with Dana Farber Cancer Institute.
About Neomorph, Inc.
A venture-backed biotechnology company based in San Diego, California, Neomorph is building a leading protein degradation entity, focused on ‘molecular glue’ degraders. Neomorph’s mission is to use this technology to solve critical problems in human health with the discovery and development of innovative new medicines against ‘undruggable targets’.
Neomorph comprises scientific leaders from academia and industry who have demonstrated years of commitment and success in the field, and who remain dedicated to advancing the science and technology and delivering highly impactful drugs. The Neomorph team intends to concentrate their efforts on accelerating molecular glue drug discovery, while shepherding a pipeline of projects through clinical development. The Company maintains an important close affiliation with the Center for Protein Degradation at the Dana Farber Cancer Institute.
Media Contact:
Phil Chamberlain
858-428-9877
Neomorph, Inc.
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Phil obtained his BA and D.Phil. degrees from the University of Oxford before traveling to the U.S. to work at the Genomics Institute of the Novartis Research Foundation (GNF). At GNF Phil supported and led projects in serious respiratory and inflammatory disease and solved multiple novel structures. Phil joined Celgene, San Diego in 2007 and built and led the Structural and Chemical Biology department, most recently as Executive Director, Protein Homeostasis and Structural Biology. Phil was responsible for several fundamental scientific breakthroughs on the mechanism of action of thalidomide analogs, including the structural basis for cereblon binding and neosubstrate recruitment, the definition of the neosubstrate ‘structural degron’, and a plausible molecular explanation for the thalidomide teratogenicity disaster of the twentieth century. Based on these discoveries, Phil led the construction of the cereblon modulator platform at Celgene, the pioneering drug discovery effort in the ‘molecular glue’ field generating a portfolio of projects. Phil has published work on targeted protein degradation in journals including Nature, Nature Structural and Molecular Biology and Nature Chemical Biology. Phil was the recipient of the John W. Jackson leadership award, the most prestigious achievement award at Celgene.
Rohan Beckwith, Ph.D. is VP of Chemistry at Neomorph bringing over 15 years of experience in Drug Discovery, 7 in the field of targeted protein degradation. He most recently served as a Director in the Chemical Biology and Therapeutics group at the Novartis Institutes for BioMedical Research, where he was a key contributor in building a molecular glue degrader platform, from which he led efforts to establish drug discovery programs and delivered a clinical candidate. He has developed molecular glue degraders for CRBN, VHL and DCAF15 E3 ligases. In addition, Rohan has worked on over 20 research projects across various therapeutic areas, such as HECT E3 ligase inhibitors, modulators of RNA processing, Wnt pathway modulators, IAP, spinal muscular atrophy, synthetic RNA delivery, cytokine receptors, chemokine receptors, kinases). He has led multi-disciplinary teams in chemical biology and target identification efforts, as well as hit-to-lead and lead optimization. Prior to joining Novartis, Rohan conducted postdoctoral training with Prof. Huw Davies in the field of rhodium carbenoid-mediated C-H activation. He received his Ph.D. in synthetic organic chemistry from University of Nottingham, U.K. and before that his MSci. Chem from Bristol University, U.K.
Mary Matyskiela, Ph.D. is Executive Director of Molecular Sciences at Neomorph and brings more than 20 years of experience in the ubiquitin-proteasome field. Mary received her B.S. in Chemistry from Yale University, where she performed undergraduate research in the lab of Dr. Craig Crews. She then moved to the University of California San Francisco for graduate work on ubiquitin ligase mechanism in the lab of Dr. David Morgan. She went on to perform postdoctoral research at the University of California Berkeley, studying the structure and function of the 26S proteasome with Dr. Andreas Martin, HHMI. Following her academic training, she moved to Celgene and Bristol Myers Squibb, where she spent 6 years working in targeted protein degradation drug discovery, most recently as Associate Director of Structural Biology and Proteomics, Oncology West. Mary is known for her work in elucidating the molecular mechanisms and expanding the horizons of molecular glue targeting through cereblon-CRL4, and is an author of foundational publications in the molecular glue field.
Samer Chmait is the Director of Research Operations at Neomorph. Prior to Neomorph, Samer was heading Strateos Inc’s Research Operations group to enable the access of a remote-controlled lab to other drug discovery companies and research scientists through Strateos’ secure cloud-based platform. Samer’s early research was focused on the purification, crystallization, and structure elucidation of novel proteins in support of Amgen Inc’s small molecule drug discovery programs. Samer later joined Celgene, San Diego and led the Biology Operations team to drive scientific functions forward during growth and expansion. Samer has over 15 years of biotechnology industry experience and has contributed to 17 publications within prestigious journals.
Ben Wen, Ph.D. is VP of Pharmacology at Neomorph with over 15 years of experience in drug discovery pharmacology. Prior to Neomorph, Ben was at the Genomics Institute of the Novartis Research Foundation (GNF) where he conducted his postdoc in T cell development and continued on into varying roles of increasing responsibility in the departments of pharmacology and cancer therapeutics. He has experience in progressing projects from inception to clinical investigation in the areas of autoimmunity, inflammation, allergy, cancer, infectious disease, and transplant conditioning. He received his BA in Molecular and Cellular Biology from UC Berkeley and his Ph.D. in Biology with a focus in immunology from UC San Diego.
Phil obtained his BA and D.Phil. degrees from the University of Oxford before traveling to the U.S. to work at the Genomics Institute of the Novartis Research Foundation (GNF). At GNF Phil supported and led projects in serious respiratory and inflammatory disease and solved multiple novel structures. Phil joined Celgene, San Diego in 2007 and built and led the Structural and Chemical Biology department, most recently as Executive Director, Protein Homeostasis and Structural Biology. Phil was responsible for several fundamental scientific breakthroughs on the mechanism of action of thalidomide analogs, including the structural basis for cereblon binding and neosubstrate recruitment, the definition of the neosubstrate ‘structural degron’, and a plausible molecular explanation for the thalidomide teratogenicity disaster of the twentieth century. Based on these discoveries, Phil led the construction of the cereblon modulator platform at Celgene, the pioneering drug discovery effort in the ‘molecular glue’ field generating a portfolio of projects. Phil has published work on targeted protein degradation in journals including Nature, Nature Structural and Molecular Biology and Nature Chemical Biology. Phil was the recipient of the John W. Jackson leadership award, the most prestigious achievement award at Celgene.
Eric Fischer, PhD, is Independent Investigator at Dana-Farber Cancer Institute and Associate Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School. He is Co-Director of the Center for Protein Degradation at Dana-Farber Cancer Institute.
Dr. Fischer’s research focuses on understanding the molecular architecture, function, and regulation of complex cellular signaling machines and their involvement in cellular processes, as well as leveraging this knowledge to develop new strategies for small-molecule-mediated modulation. Using biochemistry, chemical biology, and cell biology methods, his lab has contributed to the understanding of the efficacy and adverse activity of thalidomide and analogs. Beyond defining the mechanism of action for this transformative cancer drug and solving a decade-old mystery of pharmaceutical sciences, this work inspired numerous projects that intend to utilize similar principles to redirect ligase activity to new targets. This represents a new therapeutic modality often referred to as targeted protein degradation. Dr. Fischer’s lab helped to establish this approach and has defined many of the underlying principles for small molecules degraders. Dr. Fischer’s work has been recognized with awards including, the Damon Runyon Cancer Research Foundation’s 2017 Damon Runyon-Rachleff Innovation Award, and the Mark Foundation’s 2018 Emerging Leaders Award.
Dr. Fischer completed his undergraduate training at the Universities of Hamburg (Germany) and Basel (Switzerland) and completed doctoral training at the Friedrich Miescher Institute for Biomedical Research, also in Basel. Dr. Fischer joined the Dana-Farber faculty in 2015.
Dr. Benjamin Ebert is the George P. Canellos, MD, and Jean S. Canellos Professor of Medicine at Harvard Medical School, Chair of Medical Oncology at the Dana-Farber Cancer Institute, a Howard Hughes Medical Institute Investigator, and an Institute Member of the Broad Institute.
The Ebert laboratory focuses on the molecular basis and treatment of hematologic malignancies and its non-malignant precursor conditions, with a particular focus on myelodysplastic syndromes (MDS) and clonal hematopoiesis. The Ebert laboratory demonstrated that lenalidomide, a derivative of thalidomide, binds the CRL4-CRBN E3 ubiquitin ligase and induces degradation of specific substrates. Subsequent research from the Ebert laboratory has examined the potential of thalidomide analogs to induce degradation of a broad array of zinc finger transcription factors and other proteins, and to identify novel mechanisms of drug-induced protein degradation.
Dr. Ebert is an elected member of the National Academy of Medicine, the American Society for Clinical Investigation and the Association of American Physicians. He served as President of the American Society for Clinical Investigation. His awards include the Till and McCollough Award from the International Society of Experimental Hematopoiesis, the William Dameshek Prize from the American Society of Hematology, the Meyenburg Prize, and mentoring and teaching awards from Harvard Medical School.
Dr. Ebert received a bachelor's degree from Williams College and a doctorate from Oxford University as a Rhodes Scholar where he worked with Peter Ratcliffe, who was subsequently awarded the Nobel Prize in Medicine. He completed an M.D. from Harvard Medical School, a residency in internal medicine at Massachusetts General Hospital, and a fellowship in hematology/oncology at the Dana-Farber Cancer Institute. He was on the faculty of Brigham and Women’s Hospital for 10 years before returning to the Dana-Farber.
Dr. Scott Armstrong is the David G. Nathan Professor of Pediatrics at Harvard Medical School, Chair of Pediatric Oncology at the Dana-Farber Cancer Institute and President of the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center.
The Armstrong laboratory is interested in the relationship between leukemia and normal hematopoietic stem cells, and the mechanisms by which chromatin modifications control gene expression during normal and cancer development. The laboratory has defined developmental gene expression programs that are aberrantly expressed in cancer and identified the chromatin regulatory complexes that are critical for maintenance of cancer-causing gene expression. This work prompted development of small molecules that target chromatin-based mechanisms, a number of which are currently being assessed in adults and children with cancer.
Dr. Armstrong is a member of the National Academy of Medicine and his work has been recognized multiple awards including the Till and McCulloch Award from the International Society of Experimental Hematology, the Wilson S. Stone Award from MD Anderson Cancer Center, the Paul Marks Prize for Cancer Research from Memorial Sloan Kettering Cancer Center, the E. Mead Johnson Award from the Society for Pediatric Research and the Dameshek Prize from the American Society of Hematology.
Dr. Armstrong received his MD and PhD from the University of Texas Southwestern Medical School in Dallas, Texas where he performed his PhD under the mentorship of Nobel laureates Michael Brown and Joseph Goldstein. He performed his residency and fellowship in pediatric hematology/oncology at Children’s Hospital Boston, the Dana Farber Cancer Institute, and Harvard Medical School.
Cameron Wheeler, Ph.D., is a Partner on the Biotherapeutics group at Deerfield and joined the Firm in 2014. Prior to Deerfield, Dr. Wheeler worked for and on behalf of Eleven Biotherapeutics, Inc. as a director since 2009. Previous to that, he was Manager of the Business Development and Operations team at Constellation Pharmaceuticals, Inc. and a Senior Associate at Third Rock Ventures, LLC. Dr. Wheeler holds a Ph.D. and S.M. in Biological Engineering and an S.B. in Mechanical Engineering from the Massachusetts Institute of Technology
Joseph Pearlberg, M.D., Ph.D., is the Vice President of Scientific Affairs on the Biotherapeutics group at Deerfield and joined the Firm in 2017. Prior to Deerfield, Dr. Pearlberg was the Vice President of Clinical Development at Infinity Pharmaceuticals. Before Infinity Pharmaceuticals, Dr. Pearlberg worked as a Medical Director in the oncology unit of Sanofi. Dr. Pearlberg received his M.D. at the University of California, San Francisco, and completed his clinical training at the Massachusetts General Hospital and Dana Farber Cancer Institute. He earned his Ph.D. in Molecular Biology from Harvard University and was a Lecturer in the Department of Biological Chemistry and Molecular Pharmacology at Harvard Medical School. He holds a B.A. in Biochemistry from the University of Pennsylvania.
Phil obtained his BA and D.Phil. degrees from the University of Oxford before traveling to the U.S. to work at the Genomics Institute of the Novartis Research Foundation (GNF). At GNF Phil supported and led projects in serious respiratory and inflammatory disease and solved multiple novel structures. Phil joined Celgene, San Diego in 2007 and built and led the Structural and Chemical Biology department, most recently as Executive Director, Protein Homeostasis and Structural Biology. Phil was responsible for several fundamental scientific breakthroughs on the mechanism of action of thalidomide analogs, including the structural basis for cereblon binding and neosubstrate recruitment, the definition of the neosubstrate ‘structural degron’, and a plausible molecular explanation for the thalidomide teratogenicity disaster of the twentieth century. Based on these discoveries, Phil led the construction of the cereblon modulator platform at Celgene, the pioneering drug discovery effort in the ‘molecular glue’ field generating a portfolio of projects. Phil has published work on targeted protein degradation in journals including Nature, Nature Structural and Molecular Biology and Nature Chemical Biology. Phil was the recipient of the John W. Jackson leadership award, the most prestigious achievement award at Celgene.
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