Advances in molecular genetics and biology have led to the development of new classes of targeted therapies for the treatment of hematologic cancers. However, many of these therapies, while selective for a particular drug target, often interact with other related proteins which can limit their efficacy and lead to unwanted side effects. At Ajax, we are targeting myeloproliferative neoplasms (MPNs) with greater precision by applying state-of-the-art computational chemistry and structural biology throughout the drug discovery and development process to create best-in-class therapies for significant unmet medical needs.
Myeloproliferative neoplasms (MPNs), including myelofibrosis, are neoplastic myeloid diseases driven by aberrant JAK/STAT signaling due to mutations in JAK2, MPL and CALR genes. This has led to the development and approval of JAK2 inhibitors for the treatment of MPNs. All approved JAK2 inhibitors, including ruxolitinib, bind the Type I conformation of the JAK2 kinase and, while providing symptomatic relief, continue to allow JAK/STAT signaling which leads to disease persistence.
JAK2 inhibitors that bind the Type II conformation of the JAK2 kinase offer a next-generation approach to JAK inhibitor therapy for MPNs. Type II JAK2 inhibitors have been shown to improve therapeutic efficacy, overcome disease persistence to Type I JAK2 inhibitors, including ruxolitinib, and, most importantly, reduce mutant JAK2 allele burden that drives MPNs. At Ajax, we are applying our unique drug discovery capabilities, including state-of-the-art computational methods, to develop a new generation of selective and potent Type II JAK2 inhibitors.
Learn more about data on Ajax’s Type II JAK2 inhibitors in our ASH press release and poster presentation, showing superior selectivity and efficacy, as well as significant reductions in mutant allele fraction in bone marrow and spleen not observed with Type I JAK2 inhibitors.
Ajax has a unique partnership with Schrödinger, Inc. (NASDAQ: SDGR), the industry leader in molecular simulation software for drug discovery, to develop a pipeline of selectively targeted small molecules. Through this ongoing collaboration, Schrödinger and Ajax scientists work as an integrated team to precisely design and optimize compounds with the desired functional activity, selectivity and drug-like properties.
Martin Vogelbaum is a co-founder of Ajax and also serves on the company’s board of directors. He has more than 27 years of investment experience in the life sciences having been involved with companies at all stages of development, including co-founding several biotech start-ups. He is Managing Partner of Inning One Ventures, an early-stage life sciences venture capital firm, and a founding investor of Ajax. Previously, Mr. Vogelbaum served as Corporate Vice President, Business Development at Celgene Corporation. Prior to joining Celgene, Mr. Vogelbaum served as a partner of Rho Ventures where he focused on investments in biopharmaceuticals and medical devices. He serves or has served on the Board of Directors of multiple private and public life sciences companies including Cara Therapeutics (NASDAQ: CARA), Gloucester Pharmaceuticals (acquired by Celgene), Mersana (NASDAQ: MRSN), SARcode (acquired by Shire) and AqueSys (acquired by Allergan). Prior to his venture capital career, he was a research associate in the bone marrow transplantation unit at Memorial Sloan Kettering Cancer Center. He currently serves on the Healthcare Advisory Board for the Partnership Fund for New York City as well as the External Advisory Board for the Office of Therapeutic Alliances at NYU Langone Health. Mr. Vogelbaum received his A.B. in biology and history from Columbia University.
Dr. David Steensma has a more than 25-year distinguished career as a clinician, investigator and researcher in hematology-oncology. He was formerly the Global Head of Hematology at Novartis Institutes for Biomedical Research, where he led early clinical development in malignant and non-malignant hematology conditions. Previously, Dr. Steensma was a faculty member at Harvard Medical School and Institute Physician in the Adult Leukemia Program in the Division of Hematological Malignancies at the Dana-Farber Cancer Institute, where he cared for patients with hematological malignancies and bone marrow failure and served as the Edward P. Evans Chair in Myelodysplastic Syndromes (MDS). Earlier in his career, Dr. Steensma was a fellow and then faculty member in the Division of Hematology, Department of Medicine, at the Mayo Clinic. Since 2000, he has been on numerous committees and held several editorial roles for the American Society of Hematology and served as consultant editor for the Journal of Clinical Oncology. He was also a voting member of the Oncology Drug Advisory Committee (ODAC) for the U.S. Food and Drug Administration (FDA), and member of the Board of Directors of the MDS Foundation. Dr. Steensma has published over 200 original research papers as well as numerous reviews, editorials and book chapters. Dr. Steensma received his medical degree from the University of Chicago’s Pritzker School of Medicine.
Alan Collis, PhD, has over 25 years of drug development experience including previous preclinical development roles at Novartis, Forma Therapeutics and Nimbus Therapeutics. At Nimbus, he managed the preclinical development of the company’s drug discovery program targeting tyrosine kinase 2 (TYK2), a member of the JAK kinase family. Prior to joining Ajax Therapeutics, Dr. Collis was Vice President of Integrated Drug Discovery at Syngene International where he led a portfolio of 20 drug discovery programs. Prior to Syngene, he served as Senior Vice President of Preclinical Development at Nimbus Therapeutics where led the preclinical and IND activities for the company’s TYK2 and HPK-1 inhibitor programs. Previously, Dr. Collis was Executive Director, DMPK and Safety for Forma Therapeutics where he supported the company’s IDH1 and BET inhibitor programs. He has also worked in various director level positions at Novartis Institute for Biomedical Research, Sanofi-Aventis and Rhone Poulenc Rorer. Dr. Collis received a PhD in chemistry from the University of Manchester, UK.
Craig E. Masse, PhD, has over 18 years of discovery and development experience in the biotechnology industry with a strong track record of delivering high value drug development candidates. Prior to joining Ajax Therapeutics, Dr. Masse was Executive Director and Head of Medicinal Chemistry at Nimbus where he led multiple immunology and immuno-oncology programs, all of which were prosecuted within a capitally efficient, virtually integrated, globally distributed operating model that involved a first-of-its-kind partnership with Schrödinger, Inc. (NASDAQ: SDGR). At Nimbus, he led the advancement of the company’s allosteric Tyk2 inhibitor program to a Development Candidate and helped secure an alliance with Celgene Corporation. Prior to joining Nimbus, Dr. Masse served as Head of Medicinal Chemistry at Concert Pharmaceuticals (NASDAQ: CNCE) where he oversaw the creation of three Development Candidates all of which entered the clinic within 18 months. While at Concert, he led multidisciplinary drug-discovery projects teams, supported strategic assessment of programs for portfolio management; and provided scientific support for Business Development that resulted in a $1 billion multi-product transaction with GlaxoSmithKline. Prior to Concert, Dr. Masse started his career as a Research Scientist at Amgen-Cambridge where he worked in the oncology, inflammation, and neuroscience therapeutic areas. He is an inventor on over 60 patents and has co-authored more than 65 scientific publications including several book chapters. He earned his Ph.D. in synthetic organic chemistry from Boston University and conducted post-doctoral research at Harvard University with Professor David A. Evans.
Maria Kleppe, PhD has more than 15 years of research experience in hematology oncology and helped elucidate several new therapeutic approaches in the treatment of myeloproliferative neoplasms (MPNs) including the use of novel therapies to improve efficacy in MPN patients who do not achieve sufficient benefit from type I JAK inhibitors such as ruxolitinib. Prior to joining Ajax, Dr. Kleppe was Senior Director, Discovery Biology at Imago Biosciences until its acquisition by Merck & Co. in January 2023. At Imago, she coordinated all internal and external research activities for the company’s lead LSD-1 inhibitor, Bomedemstat, for the treatment of MPNs including myelofibrosis and essential thrombocythemia. Dr. Kleppe began her career as a postdoctoral fellow and then as a research associate in the laboratory of Dr. Ross Levine at Memorial Sloan Kettering Cancer Center (MSKCC). While at MSKCC, she was not only involved in validating the role of type II JAK2 inhibition in reversing MPN cell persistence to type I JAK inhibitors but also helped identify LSD-1 and BET inhibition as novel therapeutics approaches for the treatment of MPNs. Dr. Kleppe is the author or co-author of over two dozen research publications in hematology oncology. She received her PhD in human genetics from KU in Leuven, Belgium.
Christine Richardson, PhD, PMP, brings over 25 years of successful drug development experience to Ajax having served in Project and Operations Management roles in both large pharmaceutical companies and small biotechnology companies. Dr. Richardson joins Ajax from ContraFect Corporation where she was Director, Program Management and responsible for early discovery programs, including oversight of all line functions, as well as serving as a liaison with external partners. She began her career at Novartis Pharmaceutical Corporation where she spent 19 years working initially in Pharmaceutical Operations and Chemical Development and then in the Primary Care Development Franchise in Program Management. Dr. Richardson received her Ph.D. in organic chemistry from New York University and holds a PMP Certification.
Ming Cheah, PhD, is a Vice President in Life Sciences Investing at Goldman Sachs Alternatives with close to 20 years’ experience in venture investing, biopharma, and academic research within the life sciences. Prior to joining Goldman Sachs, Dr. Cheah was a Principal at Pivotal bioVenture Partners, where he led investments in and was on the boards of private biotechnology companies. Previously, he worked in business development, search and evaluation, and competitive intelligence at Roche and Genentech and served as a consultant at McKinsey & Company advising life sciences companies on M&A. Dr. Cheah currently serves as a board observer of TORL BioTherapeutics, Septerna and Attovia Therapeutics. He earned his PhD in Immunology from Stanford University and his MS and BS in Biology from Yale University.
Dr. Ramy Farid is President, Chief Executive Officer and a member of the board of directors of Schrödinger, Inc (NASDAQ: SDGR). He joined Schrödinger in 2002 and helped advance the company’s computational platform and drug discovery portfolio while assuming positions of increasing responsibility before becoming CEO in 2017. Dr. Farid has played a key role in implementing major strategic initiatives, including more than 40 research collaborations and joint ventures, and led the company through its IPO in 2020. Dr. Farid currently serves on the board of directors of ShouTi. Previously, he served on the board of Nimbus Therapeutics, a biotechnology company he helped found in 2009. He also served on the board of directors of Morphic Therapeutic (NASDAQ: MORF) and currently serves on the company’s scientific advisory board. Dr. Farid began his career in academia and was an assistant professor in the chemistry department at Rutgers University. He was a National Institutes of Health postdoctoral fellow in the Department of Biochemistry and Biophysics at the University of Pennsylvania and received his doctorate degree in chemistry from Caltech. He is an author on 70 peer reviewed publications.
Dr. Ross Levine is Senior Vice President for Translational Research at Memorial Hospital, a Member of the Human Oncology and Pathogenesis Program (HOPP) and an Attending Physician on the Leukemia Service, Department of Medicine at Memorial Sloan Kettering Cancer Center (MSK). He is the Laurence Joseph Dineen Chair in Leukemia Research and a Professor of Medicine at Weill Cornell Medical College. Dr. Levine earned his A.B. from Harvard College and M.D. from Johns Hopkins University School of Medicine. Dr. Levine served as a Resident in Internal Medicine at Massachusetts General Hospital and as a Hematology-Oncology Fellow at Dana-Farber Cancer Institute. His laboratory has identified myeloproliferative neoplasm (MPN) predisposition alleles and characterized somatic genetic and epigenetic alterations in MPN and acute myeloid leukemia (AML) patients, which has led to new mechanism-based therapies. In 2011, he was elected to the American Society of Clinical Investigation and in 2018 to the Association.
Scott Platshon is a Partner at EcoR1 Capital, a fundamental biotechnology-focused investment firm in San Francisco. Prior to joining EcoR1 in 2015, he was an analyst for Aquilo Partners, a boutique life-science investment bank. Scott holds a Bachelor of Science in Bioengineering from Stanford University.
Amit Sinha is head of Life Sciences Investing within Goldman Sachs Asset Management. Previously, he was global head of Biotechnology within the Investment Banking Division of Goldman Sachs and was also a member of the Mergers and Acquisitions Group. Mr. Sinha joined Goldman Sachs in 2004 as an associate and was named managing director in 2012 and partner in 2018. Previously, he worked at The Boston Consulting Group as a management consultant. Mr. Sinha currently serves as a member of the Board of Trustees of Stanford University. He is also on the Board of Directors of Stanford Health Care, Stanford Medicine Children’s Health and Lucile Packard Children’s Hospital at Stanford. Mr. Sinha earned a BS, with honors, in Biological Sciences from Stanford University and an MBA from Harvard Business School.
Martin Vogelbaum is a co-founder of Ajax and also serves on the company’s board of directors. He has more than 27 years of investment experience in the life sciences having been involved with companies at all stages of development, including co-founding several biotech start-ups. He is Managing Partner of Inning One Ventures, an early-stage life sciences venture capital firm, and a founding investor of Ajax. Previously, Mr. Vogelbaum served as Corporate Vice President, Business Development at Celgene Corporation. Prior to joining Celgene, Mr. Vogelbaum served as a partner of Rho Ventures where he focused on investments in biopharmaceuticals and medical devices. He serves or has served on the Board of Directors of multiple private and public life sciences companies including Cara Therapeutics (NASDAQ: CARA), Gloucester Pharmaceuticals (acquired by Celgene), Mersana (NASDAQ: MRSN), SARcode (acquired by Shire) and AqueSys (acquired by Allergan). Prior to his venture capital career, he was a research associate in the bone marrow transplantation unit at Memorial Sloan Kettering Cancer Center. He currently serves on the Healthcare Advisory Board for the Partnership Fund for New York City as well as the External Advisory Board for the Office of Therapeutic Alliances at NYU Langone Health. Mr. Vogelbaum received his A.B. in biology and history from Columbia University.
Dr. Eric Fischer is an Independent Investigator and Director of the Chemical Biology Program at Dana Farber Cancer Institute and Associate Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School. Dr. Fischer’s research focuses on understanding the molecular architecture, function, and regulation of complex cellular signaling machines and their involvement in cellular processes. His work helping to understand the mechanism of action of Thalidomide and related drugs was critical to establishing the novel therapeutic modality known as targeted protein degradation. Dr. Fischer’s research has been recognized by awards including the Damon Runyon-Rachleff Innovation Award and the Mark Foundation’s Emerging Leaders Award. He is a co-founder of Civetta Therapeutics, Neomorph, Inc. and Proximity Therapeutics. Dr. Fischer completed his undergraduate training at the Universities of Hamburg and Basel and his doctoral training at the Friedrich Miescher Institute for Biomedical Research.
Dr. Stevan Hubbard is Professor of Biochemistry and Molecular Pharmacology at the New York University (NYU) Grossman School of Medicine and a member of the Skirball Institute of Biomolecular Medicine at NYU. His longstanding research interests are the structural/molecular mechanisms governing the regulation of protein tyrosine kinases. Among his major contributions in this field are: the determination of the first crystal structure of a tyrosine kinase domain (insulin receptor); the first crystal structures of small-molecule inhibitors bound to a tyrosine kinase domain (fibroblast growth factor receptor); and, with Ajax co-founder Dr. Olli Silvennoinen, the crystal structure of the JAK2 pseudokinase domain. Dr. Hubbard holds a B.Sc. with distinction from Cornell University (Engineering Physics) and a Ph.D. from Stanford University (Applied Physics). He received postdoctoral training at Columbia University in the Department of Biochemistry and Molecular Biophysics.
Dr. Ross Levine is Senior Vice President for Translational Research at Memorial Hospital, a Member of the Human Oncology and Pathogenesis Program (HOPP) and an Attending Physician on the Leukemia Service, Department of Medicine at Memorial Sloan Kettering Cancer Center (MSK). He is the Laurence Joseph Dineen Chair in Leukemia Research and a Professor of Medicine at Weill Cornell Medical College. Dr. Levine earned his A.B. from Harvard College and M.D. from Johns Hopkins University School of Medicine. Dr. Levine served as a Resident in Internal Medicine at Massachusetts General Hospital and as a Hematology-Oncology Fellow at Dana-Farber Cancer Institute. His laboratory has identified myeloproliferative neoplasm (MPN) predisposition alleles and characterized somatic genetic and epigenetic alterations in MPN and acute myeloid leukemia (AML) patients, which has led to new mechanism-based therapies. In 2011, he was elected to the American Society of Clinical Investigation and in 2018 to the Association.
Dr. Olli Silvennoinen is Director of Biocenter Finland. He is also professor of Microbiology and Immunology at Tampere University, Chief Physician at Fimlab Laboratories and Research Director at the Institute of Biotechnology, Helsinki Institute of Life Science (HiLIFE) at the University of Helsinki. Prior to his current position, he served as Director of HiLIFE, Director of the Institute of Biotechnology in Helsinki and Director of the Institute of Medical Technology in Tampere. Dr. Silvennoinen received his M.D. and Ph.D. degrees at the University of Helsinki and clinical microbiology specialization at the University of Tampere. During his postdoctoral training at St Jude Children´s Research Hospital and New York University Medical School, Dr. Silvennoinen was centrally involved in the original characterization of the JAK-STAT pathway and his laboratory has continued to elucidate the regulatory mechanisms of JAK kinases in malignancies and autoimmune diseases. He has been active in facilitating research innovations in both academic settings and start-up companies.
Dr. Radek Skoda is a Professor of Molecular Medicine and research group leader at the Department of Biomedicine at the University of Basel and the University Hospital Basel. His research interests are focused on the molecular pathogenesis of myeloproliferative neoplasms (MPNs). His major contributions to the field include describing the JAK2-V617F mutation in patients with MPNs, dissecting the factors that contribute to the clonal evolution of MPNs and discovering mutations in the TPO gene in familial thrombocythemia and EPO gene in familial erythrocytosis. Dr. Skoda obtained his M.D. from the University of Zürich and trained in internal medicine and hematology at the University Hospital Basel. He began his research career as a postdoctoral fellow at the Biozentrum of the University of Basel and later moved to the Department of Genetics at Harvard Medical School. In 2000, he returned to the Biozentrum as a research group leader with a SCORE career development award from the Swiss National Science Foundation and became head of the Molecular Hematology-Oncology unit at the German Cancer Research Center in Heidelberg. In 2002, Dr. Skoda was appointed to his current professorship in Basel and served as chair of the Department of Biomedicine until May 2021. In 2013, he was elected to the Swiss Academy of Medical Sciences. Since 2016, he has served as Chair of the Personalized Health Basel Initiative of the University and University Hospital Basel. Dr. Skoda has also served on the advisory board for the Ludwig Boltzman Institute in Vienna and consulted on MPN-related projects for Novartis, Baxalta, Shire and Celgene.
Dr. Srdan “Serge” Verstovsek is the Chief Medical Officer of Kartos Therapeutics. Previously, he was United Energy Resources, Inc. Professor of Medicine, Department of Leukemia, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center. He was also Director of the Hanns A. Pielenz Clinical Research Center for Myeloproliferative Neoplasms and Chief, Section for Myeloproliferative Neoplasms. Dr. Verstovsek has achieved international acclaim for his leadership in developing landmark MPN therapeutics and has led more than 60 early/advanced phase clinical trials of novel MPN drugs, including ruxolitinib. He has published 24 book chapters, more than 600 peer-reviewed original articles/reviews in leading medical journals and has received numerous clinical research awards. He was elected member of the American Society for Clinical Investigation in 2015 and is co-founder/Executive Committee Member of the International Working Group for MF Treatment and Research. Dr. Verstovsek received his MD and PhD from the University of Zagreb, Croatia.
Dr. David Weinstock is Vice President of Discovery Oncology at Merck & Co. Previously, he was a Professor of Medicine and Pediatrics at Dana-Farber Cancer Institute and Harvard Medical School where he was involved in translational research focused on novel therapeutics for lymphoid malignancies. He completed fellowship training in Medical Oncology and Infectious Diseases at Memorial Sloan-Kettering Cancer Center. He joined the staff of Dana-Farber Cancer Institute and Brigham and Women’s Hospital in 2008.
At Ajax, we see ourselves as warriors operating at the intersection of computational chemistry and cancer biology. We are committed to creating medicines that will have a transformative impact on the lives of cancer patients. And we’re always on the hunt for talented people to join us in our quest.
We are based in Cambridge, MA and New York, NY.
Contact us at info@ajaxtherapeutics.com.