Odiparcil

Odiparcil

We are developing odiparcil for the treatment of several subtypes of MPS, a group of rare, progressive genetic disorders which manifest early in life.

Odiparcil, an orally-available small molecule, can potentially decrease the lysosomal accumulation of chondroitin sulfates (CS) and dermatan sulfates (DS) in patients with certain MPS subtypes.

Odiparcil acts to modify how DS and CS are synthesized, thereby facilitating the production of soluble DS and CS glycosaminoglycans (GAGs), which can be excreted in the urine, rather than accumulating in cells.

We believe odiparcil’s mechanism of action is relevant to a number of tissues in which GAGs accumulate and which are addressed with limited efficacy by the current standard of care, which is enzyme replacement therapy (ERT). Unlike ERT, odiparcil is a small molecule that we have observed to be well distributed in the body, even in tissues that are poorly vascularized or protected by a barrier. We believe odiparcil’s mechanism of action could be effective in patients with MPS I, II, IVa, VI and VII.

We are currently investigating odiparcil in the iMProveS Phase IIa clinical trial for the treatment of adult patients with MPS VI. We expect to report data in the second half of 2019,

Odiparcil
in Mucopolysaccharidosis Type VI (MPS VI)

In arylsulfatase B mutant mice, a relevant model for mucopolysaccharidosis type VI (MPS VI), administration of odiparcil was associated with reductions in GAG levels in tissues and organs relevant to the human disease.

In this same MPS VI mouse model, we also observed that odiparcil was active in cartilage tissues. As shown in the figures below, we observed that treatment of MPS VI mice with odiparcil was associated with a decrease in thickness in trachea and knee cartilage. In addition, we observed statistically significant improvements in mobility in the MPS VI mice treated with odiparcil. In this same MPS VI mouse model, we also observed that odiparcil was active in tissues of the eyes.

As shown in the figures below, we observed that corneal thickness and the number of cell layers in the corneal epithelium were decreased in MPS VI mice treated with odiparcil. We also tested the accumulation of GAGs in the corneal stroma, which is a layer of the cornea in which GAGs are known to accumulate in MPS patients and observed decreases in GAG accumulation in MPS VI mice treated with odiparcil in comparison to untreated MPS VI mice.

Source: Inventiva S.A. proprietary data

Source: Inventiva S.A. proprietary data

We observed that administration of odiparcil was associated with a decrease in CS intracellular content, while increasing the extra cellular level of GAGs.

Source: Inventiva S.A. proprietary data

Odiparcil has received orphan drug designation for MPS VI in the USA and the EU and is currently being tested in the iMProveS trial in adult MPS VI patients. Headline results are expected for the second half of 2019.

Odiparcil
preclinical in vivo safety data

In clinical trials conducted in other indications prior to our founding, odiparcil was administered to over 1,800 subjects.

In these trials, odiparcil displayed a favorable safety and tolerability profile at daily doses in excess of the therapeutic range. Low toxicity was also observed in in vivo toxicology studies of up to 36 weeks.