- the completion of patient enrollment in two Phase 2 clinical studies of MGL-3196, a liver-directed thyroid hormone receptor (THR) β-selective agonist, in patients with non-alcoholic steatohepatitis (NASH) and heterozygous familial hypercholesterolemia (HeFH), respectively;
- a second recommendation from the Drug Safety Monitoring Board (DSMB) that included a review of the data from both the NASH and HeFH Phase 2 clinical studies; and,
- the presentation of preclinical results at The Liver Meeting® 2017,
American Association for the Study of Liver Diseases(AASLD) demonstrating that MGL-3196 provides metabolic, anti-inflammatory and anti-fibrotic benefits in a long-term, high fat diet, mouse NASH model.
“With patient enrollment completed for the Phase 2 NASH and HeFH clinical studies we are on track to report top-line results for NASH late this year and HeFH early in 2018,” said
Clinical Program Summaries for MGL-3196
Non-alcoholic Steatohepatitis (NASH) is a common liver disease in
In this trial, patients were randomized 2:1 to receive either MGL-3196 or placebo. The primary endpoint of the trial is the reduction of liver fat, assessed by MRI-PDFF at 12 weeks. Recent published data show a high correlation of reduction of liver fat measured by MRI-PDFF to NASH scoring on liver biopsy.
Efficacy will be confirmed at the end of the trial (36 weeks) by repeat MRI-PDFF and conventional liver biopsy to examine histological evidence for the resolution of NASH. Additional secondary endpoints include changes in clinically relevant biomarkers at 12 and 36 weeks, improvement in fibrosis by at least one stage, improvement of NASH, and safety and tolerability.
Heterozygous familial hypercholesterolemia (HeFH), and a much rarer form called homozygous familial hypercholesterolemia (HoFH), are severe genetic dyslipidemias typically caused by inactivating mutations in the LDL receptor. Both forms of FH lead to early onset cardiovascular disease. HeFH, the most common dominantly inherited disease, is present in up to 1 in 200 people; the disease is found in higher frequencies in certain more genetically homogenous populations. Treatments exist for both HeFH and HoFH but many patients (as many as 40 percent of HeFH patients) are not able to reach their cholesterol (LDL-C) reduction goals on these therapies, reflecting the lifetime burden of cholesterol buildup in their bodies. Based on evidence of impressive LDL cholesterol lowering in Phase 1, and data suggesting that MGL-3196 has a mechanism of action that is different from and complementary to statins, Madrigal initiated a Phase 2 proof-of-concept trial in HeFH in
The 12-week, randomized, double-blind, placebo-controlled, multi-center study was expected to enroll up to 105 patients with HeFH randomized in a 2:1 ratio to receive either MGL-3196 or placebo, in addition to their current drug regimen (including high dose statins and ezetimibe). The primary endpoint of the study is reduction of LDL cholesterol, with secondary endpoints including reductions in triglycerides, Lp(a), and ApoB, as well as safety. Lp(a) is a severely atherogenic lipid particle, commonly elevated in familial hypercholesterolemia patients and poorly controlled by existing lipid lowering therapies. THR-β agonism is one of the few therapeutic approaches that can substantially lower Lp(a).
Financial Results for the Three Months and Nine Months Ended
Operating expenses were
Research and development expenses for the three month and nine month periods ended
General and administrative expenses for the three month and nine month periods ended
Interest income (expense), net, for the three month and nine month periods ended
This communication contains “forward-looking statements” made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.Such statements contain words such as “expect,” “could,” “may,” “will,” “believe,” “estimate,” "continue," "future,” or the negative thereof or comparable terminology and the use of future dates. Forward-looking statements reflect management's current knowledge, assumptions, judgment and expectations regarding future performance or events. Although management believes that the expectations reflected in such statements are reasonable, they give no assurance that such expectations will prove to be correct and you should be aware that actual results could differ materially from those contained in the forward-looking statements. Forward-looking statements are subject to a number of risks and uncertainties including, but not limited to, the company's clinical development of MGL-3196, the timing and outcomes of clinical studies of MGL-3196, and the uncertainties inherent in clinical testing. Undue reliance should not be placed on forward-looking statements, which speak only as of the date they are made. Madrigal undertakes no obligation to update any forward-looking statements to reflect new information, events or circumstances after the date they are made, or to reflect the occurrence of unanticipated events. Please refer to Madrigal's filings with the
|Madrigal Pharmaceuticals, Inc.|
|Condensed Consolidated Statements of Operations|
|(in thousands, except share and per share amounts)|
|Three Months Ended||Nine Months Ended|
|September 30,||September 30,|
|Research and development||6,682||7,806||17,878||10,410|
|General and administrative||1,955||6,285||5,273||7,058|
|Total operating expenses||8,637||14,091||23,151||17,468|
|Loss from operations||(8,637||)||(14,091||)||(23,151||)||(17,468||)|
|Interest income (expense), net||174||42||342||(1,171||)|
|Basic and diluted net loss per common share||$||(0.68||)||$||(1.59||)||$||(1.87||)||$||(6.04||)|
|Basic and diluted weighted average number of common shares outstanding||12,378,622||8,847,155||12,126,008||3,087,588|
|Madrigal Pharmaceuticals, Inc.|
|Condensed Consolidated Balance Sheets|
|September 30,||December 31,|
|Cash, cash equivalents and marketable securities||$||62,137||$||40,500|
|Other current assets||583||707|
|Other non-current assets||111||3|
|Liabilities and Equity|
|Total liabilities and stockholders’ equity||$||62,831||$||41,210|
Source: Madrigal Pharmaceuticals, Inc.