MyFatDog
Preclinical Drugs Under
Development
Development
Pre-Clinical Pipeline Drugs
AAV-miApoB Developed by Amsterdam Molecular Therapeutics. AAV-miApoB is a micro RNA
that is delivered to its target using an adeno-associated virus as a vehicle. The drug targets
apoB, the major protein on LDL, reducing its production by the liver. Mice injected with
AAV-miApoB has a sustained 60-80% reduction of LDL cholesterol levels. The drug is not
currently (January 2012) listed on the company website so future development is uncertain.
AEM-18 Developed by LipimetiX. AEM-18 is a small piece (peptide) of the apoE protein that can
bind to lipoprotein receptors in the liver and promote LDL clearance. The company also has a
second compound, AEM-28, that reportedly has similar effects. The drug is being developed as a
way to reduce LDL levels. There has been no new news regarding these peptides since April
2010 so continued development is uncertain.
aPCSK9s Developed by Nativis. aPCSK9s is a drug that reduces plasma levels of PCSK9 using
RNA interference. PCSK9 prevents LDL from being cleared from blood so lowering PCSK9
enhances LDL clearance from blood resulting in lower LDL levels.
ATI-5261 (Artpep) Being developed by Artery Therapeutics, Inc. and Roche This drug is a
apoA-I mimetic peptide that is designed to increase reverse cholesterol transport.
AHRO-001 Developed by AtheroNova. The treatment appears to contain the bile salts
hyodeoxycholic acid (HDCA) and D-limonene and was shown to reduce artery plaque by 95% in a
preclinical animal model. The company plans to submit an Investigational New Drug (IND)
application with the US FDA in 2012 which will be a step towards conducting human studies.
DGAT1 inhibitors Being developed by Madrigal Pharmaceuticals under license from Roche.
DGAT1 is an enzyme that facilitates triglyceride production in many tissues in the body including
liver and fat tissue. DGAT1 inhibitors are being developed as treatments for obesity, diabetes
and dyslipidemia. The company apparently is still searching for a DGAT1 inhibitor to move
forward into pre-clinical studies.
GRC 9332 Being developed by Glenmark Pharmaceuticals. GRC 9332 is an inhibitor of an
enzyme involved in fatty acid synthesis known as SCD1. Inhibiting SCD1 in animal models has
been shown to reduce triglyceride and LDL levels.
LDL receptor gene therapy Being developed by ReGenX. Gene therapy with the LDL receptor
is designed to insert DNA for the LDL receptor into liver where it will be made normally in people
who have absent or defective receptors. The LDL receptor is responsible for clearing most of
LDL from blood so this treatment has the potential to significantly reduce LDL cholesterol levels
in patients with homozygous familial hypercholesterolemia.
MAHDL01 (Mazal Plant Pharma). This is a formulation that consists of a mixture of herbs that is
designed to alter plasma lipid levels, particularly HDL. Although it earlier appears that the
company ran out of money, in 2010 the company obtained a small amount of funding and would
like to move forward towards phase I/II human studies. The company's current financial
position is unknown.
miR-33 LNA Being developed by Santaris Pharma. Micro RNA-33 (miR-33) is a new target that
has been shown to regulate levels of HDL cholesterol. Santaris specializes in developing
therapies (called locked nucleic acids or LNA's) that can target specific RNA sequences. The
miR-33 LNA is expected to increase levels of HDL cholesterol which have been associated with
reduced risk of cardiovascular disease. The drug isn't currently listed in the pipeline on the
company's website so development is uncertain.
Recombinant apoA-I and apoA-I(Milano) Being developed by SemBioSys Genetics. This
company is using a novel approach of protein production by using genetic engineering of plants
to produce an abundant supply of recombinant apoA-I. This is being developed as a treatment
for low HDL levels.
VRX1243 Being developed by VIRxSYS. VRX1243 is a gene therapy that is designed to
promote production of apoA-I, the major protein on HDL. This is expected to promote reverse
cholesterol transport and reduced atheroscerlotic plaque formation. The initial target population
is anticipated to be patients with a rare disorder where apoA-I is deficient.
AAV-miApoB Developed by Amsterdam Molecular Therapeutics. AAV-miApoB is a micro RNA
that is delivered to its target using an adeno-associated virus as a vehicle. The drug targets
apoB, the major protein on LDL, reducing its production by the liver. Mice injected with
AAV-miApoB has a sustained 60-80% reduction of LDL cholesterol levels. The drug is not
currently (January 2012) listed on the company website so future development is uncertain.
AEM-18 Developed by LipimetiX. AEM-18 is a small piece (peptide) of the apoE protein that can
bind to lipoprotein receptors in the liver and promote LDL clearance. The company also has a
second compound, AEM-28, that reportedly has similar effects. The drug is being developed as a
way to reduce LDL levels. There has been no new news regarding these peptides since April
2010 so continued development is uncertain.
aPCSK9s Developed by Nativis. aPCSK9s is a drug that reduces plasma levels of PCSK9 using
RNA interference. PCSK9 prevents LDL from being cleared from blood so lowering PCSK9
enhances LDL clearance from blood resulting in lower LDL levels.
ATI-5261 (Artpep) Being developed by Artery Therapeutics, Inc. and Roche This drug is a
apoA-I mimetic peptide that is designed to increase reverse cholesterol transport.
AHRO-001 Developed by AtheroNova. The treatment appears to contain the bile salts
hyodeoxycholic acid (HDCA) and D-limonene and was shown to reduce artery plaque by 95% in a
preclinical animal model. The company plans to submit an Investigational New Drug (IND)
application with the US FDA in 2012 which will be a step towards conducting human studies.
DGAT1 inhibitors Being developed by Madrigal Pharmaceuticals under license from Roche.
DGAT1 is an enzyme that facilitates triglyceride production in many tissues in the body including
liver and fat tissue. DGAT1 inhibitors are being developed as treatments for obesity, diabetes
and dyslipidemia. The company apparently is still searching for a DGAT1 inhibitor to move
forward into pre-clinical studies.
GRC 9332 Being developed by Glenmark Pharmaceuticals. GRC 9332 is an inhibitor of an
enzyme involved in fatty acid synthesis known as SCD1. Inhibiting SCD1 in animal models has
been shown to reduce triglyceride and LDL levels.
LDL receptor gene therapy Being developed by ReGenX. Gene therapy with the LDL receptor
is designed to insert DNA for the LDL receptor into liver where it will be made normally in people
who have absent or defective receptors. The LDL receptor is responsible for clearing most of
LDL from blood so this treatment has the potential to significantly reduce LDL cholesterol levels
in patients with homozygous familial hypercholesterolemia.
MAHDL01 (Mazal Plant Pharma). This is a formulation that consists of a mixture of herbs that is
designed to alter plasma lipid levels, particularly HDL. Although it earlier appears that the
company ran out of money, in 2010 the company obtained a small amount of funding and would
like to move forward towards phase I/II human studies. The company's current financial
position is unknown.
miR-33 LNA Being developed by Santaris Pharma. Micro RNA-33 (miR-33) is a new target that
has been shown to regulate levels of HDL cholesterol. Santaris specializes in developing
therapies (called locked nucleic acids or LNA's) that can target specific RNA sequences. The
miR-33 LNA is expected to increase levels of HDL cholesterol which have been associated with
reduced risk of cardiovascular disease. The drug isn't currently listed in the pipeline on the
company's website so development is uncertain.
Recombinant apoA-I and apoA-I(Milano) Being developed by SemBioSys Genetics. This
company is using a novel approach of protein production by using genetic engineering of plants
to produce an abundant supply of recombinant apoA-I. This is being developed as a treatment
for low HDL levels.
VRX1243 Being developed by VIRxSYS. VRX1243 is a gene therapy that is designed to
promote production of apoA-I, the major protein on HDL. This is expected to promote reverse
cholesterol transport and reduced atheroscerlotic plaque formation. The initial target population
is anticipated to be patients with a rare disorder where apoA-I is deficient.
Discovery is the earliest phase of drug development. A company may test
thousands or millions of drug candidates in the test tube to discover one that
has the characteristics they are looking for. Once a drug is found that has the
desired result, the company may have their chemists work on it a bit more to
improve its characteristics.
thousands or millions of drug candidates in the test tube to discover one that
has the characteristics they are looking for. Once a drug is found that has the
desired result, the company may have their chemists work on it a bit more to
improve its characteristics.
Once a drug has passed the Discovery phase, it moves from the test tube to
testing in a whole animal. Usually this is done in a mouse model of the disease
and then move in to larger animals like dogs and monkeys. This is done to
show that the drug is safe and effective in animals.
testing in a whole animal. Usually this is done in a mouse model of the disease
and then move in to larger animals like dogs and monkeys. This is done to
show that the drug is safe and effective in animals.
Copyright © 2008-2012 John Millar. All rights reserved.