Pipeline - Amarna Therapeutics

Amarna has developed a broad product pipeline based on the fundamental features of its proprietary SVec gene delivery vector platform: Safe, non-immunogenic and tolerance inducing delivery and long term expression of transgenes in humans.

The pipeline is focused on 3 different therapeutic modalities

Classical Gene replacement therapy for monogenic indications, where SVec is used to deliver an active copy of a missing or dysfunctional gene. This is currently in development for a number of rare diseases, where SVec overcomes the limitations encountered by other vectors, mainly caused by immune reactions in humans.

Induction of tolerance towards specific self-proteins that are primary self-antigens in autoimmune diseases. SVec-mediated delivery of primary self-antigens to a tolerizing setting, induces tolerance to the self-antigens to reestablish immune homeostasis and resolve the autoimmune condition.

Down-regulation of inflammation in chronic inflammatory diseases, by localized delivery of anti-inflammatory and regeneration promoting transgenes. Our current project is targeting a generic mechanism which will be applicable for a range of inflammatory indications.

Hemophilia B

AMA005 is a gene replacement therapy product for the treatment of patients with HEMB. HEMA and HEMB are rare X-linked genetic disorders where mutations in the genes encoding FVIII and FIX, respectively, lead to impaired blood clotting. In hemophilia patients even a minor injury can result in severe and life-threatening blood loss. Currently, there is no cure for hemophilia and patients need regular infusions of the missing clotting factor. Gene replacement therapy using AAV vectors to deliver a functional copy of the gene encoding the clotting factor to the liver of patients has been shown to be a highly promising alternative to protein replacement therapy. In AMA005 we intend to restore the blood clotting process in HEMB patients using an SVec vector encoding human FIX.

Hemophilia A

AMA006 is a gene replacement therapy product for the treatment of patients with hemophilia A (HEMA). HEMA and hemophilia B (HEMB) are rare X-linked genetic disorders where mutations in the genes encoding blood clotting factor VIII (FVIII) and IX (FIX), respectively, lead to impaired blood clotting. In hemophilia patients even a minor injury can result in severe and life-threatening blood loss. Currently, there is no cure for hemophilia and patients need regular infusions of the missing clotting factor. Gene replacement therapy using AAV vectors to deliver a functional copy of the gene encoding the clotting factor to the liver of hemophilia patients has been shown to be a highly promising alternative to protein replacement therapy. In AMA006 we intend to restore the blood clotting process in HEMA patients using an SVec vector encoding human FVIII.

Age-related Macular Degeneration

AMA004 is a gene therapy product for the treatment of patients with the dry form of Age-related Macular Degeneration (AMD). AMD is the main cause of irreversible impaired vision and blindness in elderly living in industrialized countries. The dry form of the disease is characterized by inflammation and destruction of the macula. The wet form is a later stage of the disease characterized by choroidal neovascularization (CNV) resulting from the growth of abnormal leaky blood vessels from the choroid into the retina. Using AMA004 we intend to stop the macular degeneration in patients by administration of an SVec vector encoding anti-inflammatory proteins.

Multiple Sclerosis

AMA003 is a aim to develop a novel treatment of Multiple Sclerosis (MS). MS is an autoimmune disease where self-reactive T lymphocytes selectively attack and destroy oligodendrocytes leading to demyelination of axons in the brain and spinal cord that finally results in functional disability and premature death. Myelin components such as myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP) are considered to represent the primary self-antigens involved in the chronic autoimmune destruction of oligodendrocytes. To date, MS cannot be cured. The current treatment options include the use of immune-suppressing antibodies to prevent the recurrence of acute attacks and to delay disease progression. However, long-term use of general immuno-suppressing drugs coincides with severe adverse side effects. Using AMA003 we intent to restore the immune tolerance to MOG and MBP and potentially cure the patients from the disease.

Diabetes Mellitus type 1

AMA002 is a tolerance inducing gene therapy for the treatment of Diabetes Mellitus type 1 (DM1). DM1 is an autoimmune disease where self-reactive T lymphocytes selectively attack and destroy insulin-producing β cells lodged within the pancreas, leaving the patient unable to maintain glucose homeostasis. Proinsulin (PI) is considered to be the primary self-antigen involved in the autoimmune β cell destruction. To date, DM1 cannot be cured and the glucose homeostasis can be more or less maintained in patients by daily insulin injections. Although DM1 is seen as a manageable disease nowadays, secondary complications of the current therapy are considerable and lead to significant morbidity and mortality. Using AMA002 we intend to restore the immune tolerance to proinsulin and potentially cure the patients.

Primary Hyperoxaluria type 1

AMA001 is a gene replacement therapy product for the treatment of primary hyperoxaluria type 1 (PH1), a rare genetic liver disease with high unmet clinical need. PH1 is caused by mutations in the AGXT gene that encodes alanine-glyoxylate aminotransferase (AGT) that converts glyoxylate to glycine in the liver. As a result of the impaired AGXT function oxalate is overproduced resulting in excessive excretion of oxalate in the urine, in the deposition of calcium oxalate crystals in organs and joints and in the accumulation of kidney and bladder stones, eventually leading to premature death of the patients. Using AMA001 we intend to restore the AGT activity in the liver of PH1 patients, thereby potentially curing patients from the disease.

Amyotrophic Lateral Sclerosis

AMA007 is a Eurostar grant project in collaboration with our Swedish partner Redoxis. It is a discovery project, aiming to identify targets that can be used for the development a gene therapy for Amyotrophic lateral sclerosis (ALS).

ALS is a devastating and fatal neurodegenerative disease, which causes muscle weakness and paralysis, which can ultimately result in respiratory failure. In most cases, patients die within five years after diagnosis. ALS is a neurodegenerative disease, resulting from T-cell mediated destruction of the motor neurons. Effective treatments for ALS have not become available, and research to study and develop new therapies for ALS is hampered by a lack of therapeutic targets as well as animal models. The AMA007 project aims to validate self-antigen(s) for ALS by creating an inducible mouse model, reproducing the symptoms observed in ALS patients. Based on the identified self-antigen of ALS, Amarna aims to develop a new gene therapy modality for ALS patients.