Sarepta Therapeutics, Inc. () is a

medical research Medical research (or biomedical research), also known as experimental medicine, encompasses a wide array of research, extending from "basic research" (also called ''bench science'' or ''bench research''), – involving fundamental scientif ...

and

drug development Drug development is the process of bringing a new pharmaceutical drug to the market once a lead compound has been identified through the process of drug discovery. It includes preclinical research on microorganisms and animals, filing for re ...

company with

corporate A corporation is an organization—usually a group of people or a company—authorized by the state to act as a single entity (a legal entity recognized by private and public law "born out of statute"; a legal person in legal context) and re ...

offices and research facilities in

Cambridge, Massachusetts Cambridge ( ) is a city in Middlesex County, Massachusetts, United States. As part of the Boston metropolitan area, the cities population of the 2020 U.S. census was 118,403, making it the fourth most populous city in the state, behind Boston, ...

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...

. Incorporated in 1980 as AntiVirals, , archiveurl = http://www.gene-tools.com/sites/default/files/Summerton2005_IPT.pdf shortly before going public the company changed its name from AntiVirals to AVI BioPharma soon with stock symbol AVII and in July 2012 changed name from AVI BioPharma to Sarepta Therapeutics and SRPT respectively. As of the end of 2019, the company has two approved drugs (see the Products section below).

History

Sarepta started in Corvallis, Oregon on January 1, 1980 and was originally named Antivirals Inc. After occupying several research laboratory spaces in Corvallis, the company opened a production laboratory in Corvallis in February 2002 and was renamed AVI BioPharma Inc. The company made headlines in 2003 when it announced work on treatments for

severe acute respiratory syndrome Severe acute respiratory syndrome (SARS) is a viral respiratory disease of zoonotic origin caused by the severe acute respiratory syndrome coronavirus (SARS-CoV or SARS-CoV-1), the first identified strain of the SARS coronavirus species, ''seve ...

(SARS) and the

West Nile virus West Nile virus (WNV) is a single-stranded RNA virus that causes West Nile fever. It is a member of the family ''Flaviviridae'', from the genus ''Flavivirus'', which also contains the Zika virus, dengue virus, and yellow fever virus. The virus ...

. In July 2009, the company announced they would move their headquarters from

Portland, Oregon Portland (, ) is a port city in the Pacific Northwest and the largest city in the U.S. state of Oregon. Situated at the confluence of the Willamette and Columbia rivers, Portland is the county seat of Multnomah County, the most populous co ...

, north to

Bothell, Washington Bothell () is a city in King and Snohomish counties in the U.S. state of Washington. It is part of the Seattle metropolitan area, situated near the northeast end of Lake Washington. As of the 2020 census, it had a population of 48,161 resident ...

, near

Seattle Seattle ( ) is a seaport city on the West Coast of the United States. It is the seat of King County, Washington. With a 2020 population of 737,015, it is the largest city in both the state of Washington and the Pacific Northwest regio ...

. At that time, the company led by president and CEO Leslie Hudson had 83 employees and quarterly revenues of $3.2 million. AVI had yet to turn a profit and had not yet developed any commercial products as of July 2009. The company lost $19.7 million in the second quarter of 2009, and then won an $11.5 million contract with the

U.S. Department of Defense The United States Department of Defense (DoD, USDOD or DOD) is an executive branch department of the federal government charged with coordinating and supervising all agencies and functions of the government directly related to national secur ...

Defense Threat Reduction Agency The Defense Threat Reduction Agency (DTRA) is a combat support agency within the United States Department of Defense (DoD) for countering weapons of mass destruction (WMD; chemical, biological, radiological, nuclear, and high explosives). Accor ...

in October 2009. By this time, the company had completed its headquarters move to Bothell. In 2012, the company moved a second time, to Cambridge, Massachusetts. At the time,

CEO A chief executive officer (CEO), also known as a central executive officer (CEO), chief administrator officer (CAO) or just chief executive (CE), is one of a number of corporate executives charged with the management of an organization especially ...

Chris Garabedian indicated the move was motivated by the need to recruit expertise in

rare disease A rare disease is any disease that affects a small percentage of the population. In some parts of the world, an orphan disease is a rare disease whose rarity means there is a lack of a market large enough to gain support and resources for discove ...

s. The Corvallis laboratory facility was closed in 2016. In February 2019, Sarepta acquired five gene therapy candidates for $165 million after one of them, MYO-101, produced results with a new gene therapy candidate for patients with Limb-Girdle muscular dystrophy; two months after receiving a single treatment, muscles from all three patients were producing the protein they couldn't make on their own. As of 2022, there are three FDA-approved

Duchenne muscular dystrophy Duchenne muscular dystrophy (DMD) is a severe type of muscular dystrophy that primarily affects boys. Muscle weakness usually begins around the age of four, and worsens quickly. Muscle loss typically occurs first in the thighs and pelvis fol ...

drugs in Sarepta Therapeutics' portfolio.

Products

Its primary products are based on

Morpholino A Morpholino, also known as a Morpholino oligomer and as a phosphorodiamidate Morpholino oligomer (PMO), is a type of oligomer molecule (colloquially, an oligo) used in molecular biology to modify gene expression. Its molecular structure contains ...

oligomers (PMOs), synthetic nucleic acid analogs that were conceived of by James Summerton and invented by Summerton with Dwight Weller, originally developed under the name NeuGene Antisense. Since morpholino oligomers can form sequence-specific double-stranded complexes with RNA they are suitable use in

antisense therapy Antisense therapy is a form of treatment that uses antisense oligonucleotides (ASOs) to target messenger RNA (mRNA). ASOs are capable of altering mRNA expression through a variety of mechanisms, including ribonuclease H mediated decay of the pre-m ...

. In one application, translation blocking, a morpholino oligomer binds to

messenger RNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein. mRNA is created during the p ...

produced by a known disease-causing gene to prevent it from being

translated Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transla ...

into protein. Morpholinos can also work as splice-switching

oligos Oligonucleotides are short DNA or RNA molecules, oligomers, that have a wide range of applications in genetic testing, research, and forensics. Commonly made in the laboratory by solid-phase chemical synthesis, these small bits of nucleic acids c ...

, targeting pre-mRNA to alter splicing and so causing changes in the structure of the mature mRNA (the mechanism of the approved drug eteplirsen). Morpholinos have been tested for a wide range of applications including prevention of cardiac

restenosis Restenosis is the recurrence of stenosis, a narrowing of a blood vessel, leading to restricted blood flow. Restenosis usually pertains to an artery or other large blood vessel that has become narrowed, received treatment to clear the blockage and s ...

after

angioplasty Angioplasty, is also known as balloon angioplasty and percutaneous transluminal angioplasty (PTA), is a minimally invasive endovascular procedure used to widen narrowed or obstructed arteries or veins, typically to treat arterial atheroscle ...

, treatment of coronary artery bypass grafts, treatment of polycystic kidney disease, redirection of drug metabolism, treatment of some mutations causing Duchenne muscular dystrophy (DMD), and inhibition of infectious diseases. Their greatest clinical and commercial success thus far has been in the treatment of DMD. A new class of Morpholino oligos, the peptide-linked Morpholinos or PPMO, are linked to an arginine-rich cell-penetrating peptide to enhance their delivery into cells and have entered clinical trials The Morpholino drug

eteplirsen Eteplirsen (brand name Exondys 51) is a medication to treat, but not cure, some types of Duchenne muscular dystrophy (DMD), caused by a specific mutation. Eteplirsen only targets specific mutations and can be used to treat about 14% of DMD cases. ...

, targeting exon 51 of the

dystrophin Dystrophin is a rod-shaped cytoplasmic protein, and a vital part of a protein complex that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane. This complex is variously known as the costa ...

mRNA, was approved as a human therapeutic by the FDA in 2016 and antisense oligonucleotides for Morpholinos targeting other exons are also subsequently approved. Morpholinos have been used in preclinical studies to inhibit replication of a broad range of viruses, including

influenza Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptoms ...

SARS Severe acute respiratory syndrome (SARS) is a viral respiratory disease of zoonotic origin caused by the severe acute respiratory syndrome coronavirus (SARS-CoV or SARS-CoV-1), the first identified strain of the SARS coronavirus species, ''sever ...

hepatitis C Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, a ...

dengue fever Dengue fever is a mosquito-borne tropical disease caused by the dengue virus. Symptoms typically begin three to fourteen days after infection. These may include a high fever, headache, vomiting, muscle and joint pains, and a characterist ...

Ebola Ebola, also known as Ebola virus disease (EVD) and Ebola hemorrhagic fever (EHF), is a viral hemorrhagic fever in humans and other primates, caused by ebolaviruses. Symptoms typically start anywhere between two days and three weeks after becom ...

and

Calicivirus The ''Caliciviridae'' are a family of "small round structured" viruses, members of Class IV of the Baltimore scheme. Caliciviridae bear resemblance to enlarged picornavirus and was formerly a separate genus within the picornaviridae. They are p ...

, all of which are single stranded

RNA virus An RNA virus is a virusother than a retrovirusthat has ribonucleic acid (RNA) as its genetic material. The nucleic acid is usually single-stranded RNA ( ssRNA) but it may be double-stranded (dsRNA). Notable human diseases caused by RNA viruses ...

es. They are in advanced development for prevention and treatment of Ebola and

Marburg virus Marburg virus (MARV) is a hemorrhagic fever virus of the ''Filoviridae'' family of viruses and a member of the species '' Marburg marburgvirus'', genus ''Marburgvirus''. It causes Marburg virus disease in primates, a form of viral hemorrhagic f ...

es. In March 2013, the Company announced positive results from a non-human primate study of AVI-7288, the drug candidate for treatment of Marburg virus infection. The results showed that intramuscular administration of AVI-7288 resulted in survival rates up to 100 percent in monkeys exposed to this fatal virus. These results are similar to those in previous studies when the drug was given by intravenous injection. In December 2019,

golodirsen Golodirsen, sold under the brand name Vyondys 53, is a medication used for the treatment of Duchenne muscular dystrophy (DMD). It is an antisense oligonucleotide drug of phosphorodiamidate morpholino oligomer (PMO) chemistry. The most common ...

(Vyondys 53) received FDA approval for the treatment of cases that can benefit from skipping exon 53 of the dystrophin transcript. AMONDYS45 is the other approved PMOs developed by Sarepta which is indicated for the treatment of DMD in patients amendable by exon 45 skipping respectively. In addition to development of Morpholinos as therapeutics, AVI has conducted six human trials for

colorectal The large intestine, also known as the large bowel, is the last part of the gastrointestinal tract and of the digestive system in tetrapods. Water is absorbed here and the remaining waste material is stored in the rectum as feces before being ...

and

pancreatic The pancreas is an Organ (anatomy), organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdominal cavity, abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine ...

cancers using their cancer

vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifie ...

AVICINE Avicine, tested and developed by AVI BioPharma, and also known as CTP-37 was trialled as a possible cancer vaccine to treat a number of different cancers. These included colorectal cancer, pancreatic cancer and prostate cancer. The treatment was tr ...

References

External links

*
AVI BioPharma drops two directors, shareholder group to dissolve
– ''Portland Business Journal'' {{Pharmaceutical companies of the United States Companies based in Cambridge, Massachusetts Pharmaceutical companies of the United States Companies established in 1980 Companies listed on the Nasdaq 1980 establishments in Oregon Orphan drug companies Life sciences industry Health care companies based in Massachusetts Corvallis, Oregon Health care companies based in Oregon

History

Products

See also

References

External links