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MARTIN PHARMACEUTICALS is a repurposed therapeutics company seeking treatment for patients with liver diseases.

Our first drug is LIVANTRA®, a repurposed drug (trimetazidine) for Acute on Chronic Liver Failure (ACLF).

Martin has purchased a global patent portfolio (US, Europe and Japan) covering the drug’s use in treating liver conditions.

The liver plays an important role in many bodily functions, from protein production and blood clotting, to cholesterol, glucose (sugar), and iron metabolism. The factors driving the rapid growth in liver injury include swiftly changing lifestyle patterns such as increasing consumption of alcohol and unhealthy (fatty) diets, and an ever-aging population.

Chronic liver injury leads to liver scarring called fibrosis. cirrhosis occurs when the fibrosis becomes advanced enough that the liver architecture is distorted. Once patients become cirrhotic, they are at risk of developing life-threatening complications including variceal (varicose-type veins in the esophagus and stomach) bleeding, ascites (abdominal fluid accumulation which may get infected) and encephalopathy (mental status changes from confusion to coma).

ACLF refers to those patients who experience one or more organ-system failures. The greater the number of organ systems involved, the higher the mortality rate.

Each year in the U.S. some 50,000 people are rushed to hospital with ACLF. Costs of care can range from $116,000 to $180,000 per episode. Despite current aggressive medical management, mortality at 30 and 90 days remains high, ranging from about 50% in milder cases to 80% in patients with 3 or more organ system failures.

Medical management is often viewed as a bridge to transplantation, but many patients don’t qualify (age, co-morbidities, etc.) and demand greatly exceeds the supply ⏤ 50% die before getting a transplant and only 25% of patients are successfully transplanted

As the liver generates energy to perform its myriad functions, toxic molecules, called reactive oxygen species, are generated. These molecules can damage individual liver cells (hepatocytes) in an already-injured liver, leading to their death.

LIVANTRA shifts the generation of energy in the liver from fatty acid oxidation to glucose oxidation so that fewer of these toxic molecules are produced. As a consequence, there is less damage to individual hepatocytes, leading to less hepatocyte death. Additionally, LIVANTRA is hypothesized to preserve cellular energy, leading to increased ATP (cell fuel) levels in hepatocytes. Being able to maintain a good energy balance is important for hepatocytes under the stress of ACLF.

In a study of 133 ACLF patients (out of a study of 180 liver failure patients) were treated for 30 days. LIVANTRA-treated ACLF patients had less than half the mortality rate of control patients.

This finding was highly statistically significant. Additionally, this benefit in survival was accompanied by significant improvement at 30 and 90 days in the Meld score (prognostic score used when listing patients for transplant).

Significant improvement was seen in markers of the liver’s ability to perform its normal functions (total bilirubin, albumin levels, and clotting factors). LIVANTRA was well tolerated by patients without safety issues being reported.

We are in the middle of a confirmatory open-label study of LIVANTRA in ACLF patients. The study is taking place in several European countries. For more information on the TRUST Trial (Trimetazidine For Acute On Chronic Liver Failure Study) study click here.

We have secured an Orphan Drug Designation for the use of LIVANTRA in ACLF patients. While sold in many countries for several decades for non-liver indications (angina), the original manufacturer of trimetazidine did not seek US FDA approval. Therefore we expect an overlapping New Chemical Entity designation.

We estimate the market size of LIVANTRA to be $1.5 billion in the U.S. alone.

We are developing a liquid formulation of the drug so it will be easy to modify dose based on patient characteristics.

Martin Pharmaceutical’s second drug is CIQUAAX®, a repurposed drug for the indication of ascites.

Ascites is a condition involving the excessive accumulation of a protein-rich fluid in the abdominal cavity. This can be severe enough to cause the abdomen to bulge outwards grotesquely.

Ascites is due to advanced liver cirrhosis resulting from NASH (non-alcoholic steatohepatitis), hepatitis B & C, alcoholism, or other causes. If allowed to advance, the conditions responsible for ascites can also give rise to additional complications.

About 15% of ascites patients die within a year of diagnosis, and 44% die within five years. No drugs are approved for ascites. There is currently no adequate treatment for ascites available beyond diuretics and draining by large bore needle.

There are 325,000+ hospitalizations annually in the U.S. for ascites. We estimate the addressable market at over $500 million. About 100,000 Americans have ascites, and of that number some 20% advance to refractory ascites. We anticipate receiving Orphan Drug Designation for the use of CIQUAAX in ascites. We also anticipate receiving a New Chemical Entity designation, since docarpamine has never been approved for use in the U.S.

Large Volume Paracentesis (LVP) is an effective, albeit temporary, treatment, but it is resource-intensive, often being done in response to a visit to the emergency department, and even when done in a paracentesis clinic, patients typically occupy hospital space and personnel for 3-4 hours per procedure. 

LVP may be required as often as every week or two. Perhaps more importantly, LVP is an invasive procedure exposing patient to a risk of infection. Infection is a common reason for hospitalization and death in cirrhotic patients.

Starting in 2020, Martin intends to conduct a proof of principle Phase 2 study using CIQUAAX in cirrhotic patients with refractory ascites.