Alethiomics, a drug discovery company developing targeted therapies to treat a family of blood cancers called myeloproliferative neoplasms (MPNs - see explanation at the base of this story), has launched backed by £6 million in seed financing from Oxford Science Enterprises.
A spin-out from the University of Oxford, the company is based on world-leading discoveries in clinical haematology and single-cell multi-omics by its founders, Professor Adam Mead and Professor Beth Psaila. Mark Throsby Ph.D. has been appointed as Chairman and Edward Ainscow Ph.D. has joined as Chief Scientific Officer (CSO).
Adam and Beth will act as consultants to Alethiomics and serve on the Scientific Advisory Board, whilst continuing to lead their research groups at the MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford alongside their clinical practices in the Department of Haematology at Oxford University Hospitals NHS Trust.
MPNs are a group of chronic blood cancers that begin with mutations occurring in cancer stem cells in the bone marrow. Currently available treatments provide some symptomatic benefit, but do not tackle the underlying disease drivers meaning that many patients have a persistent burden of disease and remain at risk of disease progression.
Alethiomics foundational research has been supported by academic and charitable grants including the support of Cancer Research UK, which becomes a minority shareholder in the company.
Identifying new drug targets within these mutant cells is critical to developing targeted and curative therapies. The Alethiomics founders have pioneered the use of single-cell multi-omics approaches to better understand the biology of mutant-positive stem cells in MPNs and to discover novel molecular targets as the basis for drug discovery. They have also developed bespoke platforms for target validation to accelerate successful translation to the clinic.
Professor Mead said: “Despite tremendous advances in oncology, the quality of life and outcome for patients with many aggressive cancers remains poor. It is now clear that precision treatments targeted at specific driver mutations in cancer-initiating cells are required. Current approaches to single-cell tumour analysis are unable to resolve both cellular and mutational heterogeneity. The Alethiomics TARGET-seq platform simultaneously detects DNA mutations, the RNA transcriptome and cell surface proteins from individual cells to provide a holistic understanding of pathologies and more intelligent target identification.
Professor Psaila added: “Our initial focus is on the most sinister MPNs, for which current treatments are really inadequate and many of our patients still suffer very poor outcomes. We are really excited to have founded Alethiomics, which will enable us to translate our discoveries in novel target identification into precision medicines to improve the lifespan and quality of life for the patients we care for in the clinic.”
The breakthrough potential of the founders’ research is underlined by the fact that work using TARGET-seq, led byProfessor Mead, has been selected for the Plenary Session at one of most prestigious scientific presentations in haematology; the American Society of Hematology (ASH) annual meeting.
The seed financing will be used to establish Alethiomics’ research operations at the Oxford BioEscalator, to advance its pipeline of programmes in MPNs, and to industrialise the company’s proprietary TARGET-seq drug discovery platform. I
Claire Brown, PhD, MBA, Life Sciences Partner at Oxford Science Enterprises said: “We are tremendously impressed by the unparalleled expertise in haematological cancer of Professors Mead and Psaila, and their passion for bringing new therapies to the clinic to benefit patients. We look forward to building on their foundational discoveries and to developing clinical programmes and new therapies that deliver on the early promise of the technology.”
Co-founders, Adam and Beth, will serve on the Scientific Advisory Board, whilst continuing to lead their research groups at the MRC Weatherall Institute of Molecular Medicine, University of Oxford alongside their clinical practices in the Department of Haematology at Oxford University Hospitals NHS Trust.
Chairman Dr Mark Throsby is a biopharmaceutical executive with extensive research experience and a track record of innovation and execution. He is an expert in antibody engineering and immunology with over two decades of commercial experience gained in pharma and biotech at Crucell NV and Merus NV. Alongside his role at Alethiomics he acts as COO/CSO of Gadeta BV and serves on the Board of Ona Therapeutics.
CSO Dr Ed Ainscow brings two decades of experience working on innovative approaches to early drug discovery in both pharma and biotech. He joins from Carrick Therapeutics Ltd where he has been Chief Technology Officer for the past five years.
Myeloproliferative neoplasms (MPN)
Myeloproliferative neoplasms (MPN) are cancers that start in the bone marrow, where blood cells are made.
In MPN, the bone marrow makes too many of one or more types of blood cells (red blood cells, white blood cells and/or platelets). These cells change the thickness of the blood. Sometimes they don’t work properly. They also crowd the bone marrow and then it can’t make enough healthy blood cells.
There are seven types of MPN, diagnosed using blood tests and a bone marrow biopsy. Some forms can transform into other types of MPN or into acute myeloid leukaemia.
Symptoms depend on which type of MPN you have. Symptoms common to the types are: fatigue, weakness, weight loss, enlarged spleen (splenomegaly), bruising and bleeding, night sweats, pain in bones or joints.
In most cases we don’t know what causes MPN. There is usually a mutation in (change to) the genetic material of growing blood cells. There’s no way to prevent MPN and you can’t catch it or pass it on.
Myeloproliferative neoplasms are a rare group of blood cancers. Polycythaemia vera is diagnosed in an estimated 250 Australians each year, essential thrombocythaemia around 200 and myelofibrosis an estimated 150. The rarer sub types of MPN, as a group, are diagnosed in less than 50 Australians per year.
Most people with an MPN have no family history. MPN is more commonly diagnosed in people over the age of 50 although it can rarely occur in younger people, even very rarely in children.
The exact cause of MPNs remain unknown but there are likely to be a number of factors involved. That’s why MPNs, like most leukaemias and other cancers, become more common as we get older. A mutation of a particular gene (a segment of DNA that makes proteins) known as Janus kinase 2 (JAK2) is found in a large proportion of people with MPNs. The exact meaning of this mutation remains unclear but it appears to play a role in the overproduction of blood cells seen in these disorders. The discovery of a mutation in the JAK2 gene is important because it is likely to have a significant impact on the way MPNs are diagnosed and treated.
Long-term exposure to high levels of benzene or very high doses of ionising radiation may increase the risk of myelofibrosis in a small number of cases. Around one third of people with myelofibrosis have been previously diagnosed with polycythaemia or essential thrombocythaemia.
Many people have no symptoms when they are first diagnosed with an MPN and the disease is picked up accidentally during a routine blood test or physical examination. In other cases, people go to see their GP because they have some troubling symptoms of their disease. When symptoms do occur, they develop gradually over time. Common symptoms include:
- blurred vision
- itchiness (pruritus)
- night sweats
- raised blood pressure (hypertension).
Other symptoms experienced in MPN are a result of the affected cell involved with the MPN.