Therapeutic Focus

Human biology provides emerging evidence of the powerful potential of modulating SLC transporters to treat disease.

Human biology provides the critical roadmap for target selection at Jnana. Human genetics and patient data, particularly single cell expression and metabolomics, brought together via innovative bioinformatics approaches, offer critical clues to pathways where SLC modulation can have a profound impact on disease progression. Jnana’s current internal focus is on immune-mediated diseases and metabolite-dependent diseases where metabolites, as biomarkers, provide a clear translational path from preclinical studies to clinical development. With our biopharma partners, we are also working to provide first and best-in-class treatments for immune-mediated and neurological diseases. Jnana is dedicated to diseases with high unmet patient needs where SLC modulation can result in a novel or differentiated approach to current therapies.

Immune-mediated diseases

Immune-mediated diseases are a key therapeutic focus for Jnana given the growing body of data implicating multiple metabolite pathways in controlling immune cell fate and function. Immune cell activation in the disease environment requires rapid and prominent metabolic adaptations. Through targeting specific SLC transporters, we are aiming to activate or suppress cellular differentiation of specific cell populations to control and govern the desired immune response.

Aberrant immune cell activity is involved in numerous diseases ranging from autoimmune (e.g. rheumatoid arthritis, lupus, and psoriasis), neurological (e.g. Parkinson’s), acute and chronic kidney diseases, and inflammatory bowel disease where Jnana is evaluating targets that can address gut barrier integrity as well as inflammation, central factors in both ulcerative colitis and Crohn’s diseases.

Metabolite-dependent diseases

At Jnana, we are interested in diseases characterized by metabolite excess or deficiency, whether systemically or within a specific organ, where SLC modulators provide an effective means to rebalance metabolite levels. In these diseases, the metabolite concentration provides a clear translational path to the clinic, serving as a critical biomarker for patient selection and efficacy. Our focus is on inborn errors of metabolism in addition to complex diseases.

Jnana’s lead program is focused on phenylketonuria (PKU), in many ways the quintessential metabolite-dependent disease.  PKU is a genetic disease where loss of function mutations in the liver enzyme phenylalanine hydroxylase (PAH) result in a high systemic excess of phenylalanine (Phe) which drives all neurocognitive and neuropsychiatric pathologies in these patients.  Systemic levels of Phe are regulated by SLC6A19 (B0AT1), a transporter responsible for Phe reabsorption in the kidney proximal tubule.  In analogy to SGLT2 (SLC5A2) inhibitors that work by blocking glucose reabsorption in the kidney proximal tubule and which have had substantial clinical impact, blocking reabsorption of Phe via inhibition of SLC6A19 will significantly lower levels of plasma Phe.1  The translational path for an SLC6A19 inhibitor in PKU patients is clear where plasma Phe is the primary registrational endpoint.  This differentiated approach will lead to an oral small molecule that can be used in any PKU patient, notwithstanding age or PAH mutation, where unmet need remains high.

Chronic kidney disease (CKD) is among the leading causes of death in the United States, and current therapeutics do not effectively treat the underlying causes of disease.2 At its core, kidney physiology is driven by SLC transporters, which are responsible for excretion, reabsorption and systemic homeostasis of many important metabolites. Recent advances in the fields of genomics, metabolomics, and single cell RNA sequencing have identified many critical SLC transporters and their metabolites that are linked to kidney disease. Dysregulation of SLC transporters in the kidney can result in either build-up of toxic metabolites, or depletion of essential ones. Jnana is developing inhibitors of SLC transporters as therapeutics to regulate their associated metabolites and protect kidney function.

Reference

1 Inhibiting Neutral Amino Acid Tranport for the Treatment of Phenylketonuria, Belanger et al., JCI Insight. 2018, 3(14).

2 The Next Generation of Therapeutics for Chronic Kidney Disease, Matthew D. Breyer, Katalin Susztak, Nature Reviews Drug Discovery. 2016, 15, 568–588

Pipeline

We are committed to developing best-in-class therapeutics for patients with high unmet need across a wide range of diseases.

We aim to discover and develop innovative therapeutics across a broad range of diseases in order to realize the transformative potential of SLC therapeutics. We are advancing an internal pipeline of programs that target SLC transporters in metabolite-dependent and immune-mediated diseases. Collaborations with biopharma partners are a critical part of our strategy, giving us additional opportunities to leverage the RAPID platform and address patient needs, including in therapeutic areas outside of our current internal focus.

Jnana pipeline

 

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