Trevena Inc
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Trevena Inc is a clinical stage biopharmaceutical company, headquartered in Chesterbrook, Pennsylvania, USA, and is involved in the discovery and development of G-protein coupled receptors (GPCR) biased ligands. Trevena was founded in 2007 with technology licensed from
Duke University Duke University is a private research university in Durham, North Carolina. Founded by Methodists and Quakers in the present-day city of Trinity in 1838, the school moved to Durham in 1892. In 1924, tobacco and electric power industrialist James ...
, which originated in the labs of company founders
Robert Lefkowitz Robert Joseph Lefkowitz (born April 15, 1943) is an American physician (internist and cardiologist) and biochemist. He is best known for his groundbreaking discoveries that reveal the inner workings of an important family G protein-coupled recep ...
winner of the 2012
Nobel Prize The Nobel Prizes ( ; sv, Nobelpriset ; no, Nobelprisen ) are five separate prizes that, according to Alfred Nobel's will of 1895, are awarded to "those who, during the preceding year, have conferred the greatest benefit to humankind." Alfr ...
in Chemistry and Howard Rockman. Trevena's approach to drug discovery is based on utilizing ligand bias, or
functional selectivity Functional selectivity (or “agonist trafficking”, “biased agonism”, “biased signaling”, "ligand bias" and “differential engagement”) is the ligand-dependent selectivity for certain signal transduction pathways relative to a referen ...
, at GPCR targets to produce drugs with improved efficacy and reduced side effect profiles. Trevena was named one of the top 15 US startups of 2008 by Business Week. Trevena's expertise lies in engineering "biased ligands" that activate only the beneficial signaling pathways downstream of a GPCR to unlock new biology and avoid drug adverse effects. Trevena's pipeline currently includes a clinical stage mu-opioid biased ligand for post-operative pain, and discovery-stage programs for chronic pain, migraine, and Parkinson's disease.


History

In 2008, the company raised $25 Million in a Series A financing round led by
Alta Partners Alta Partners is a venture capital firm based in San Francisco which invests primarily in biotechnology and life science companies. History The company was founded in 1996 by Dr. Jean Deleage, Ph.D., who was also a founder of the venture capi ...
,
Polaris Ventures Polaris Partners is a venture capital firm active in the field of healthcare and biotechnology companies. The company has offices in Boston, Massachusetts, New York, NY and San Francisco, California. History Polaris Partners was founded in 1996 ...
, New Enterprise Associates, Healthcare Ventures, and Yasuda Economic Development Corporation. In early 2009, Trevena entered into a collaborative agreement with
Ligand Pharmaceuticals Ligand Pharmaceuticals is a biopharmaceutical company located in San Diego, California. Founded in 1987 as Progenix Inc., the company went public in 1992. Initially focused on developing its own drugs, a period of turbulence in the early 2000s cul ...
to identify biased ligands at numerous GPCRs from a large, diverse chemical library. Later that year, Trevena received a competitively awarded American Recovery and Reinvestment Act Grand Opportunities Grant, spanning two years and funding US$7.65 million of research. The company has disclosed specific interests in the mu Opioid receptor and kappa Opioid receptor. The company raised an additional US$35 million in a B round of venture financing in the summer of 2010. In 2011, Treveva received another NIH grant as part of the NIH Blueprint Neurotherapeutics Network, potentially worth up to $10M USD, to support preclinical development of a
delta opioid receptor Delta commonly refers to: * Delta (letter) (Δ or δ), a letter of the Greek alphabet * River delta, at a river mouth * D (NATO phonetic alphabet: "Delta") * Delta Air Lines, US * Delta variant of SARS-CoV-2 that causes COVID-19 Delta may also r ...
biased ligand for
major depressive disorder Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Introdu ...
. Trevena has received funding from the
Michael J. Fox Foundation The Michael J. Fox Foundation for Parkinson's Research is dedicated to finding a cure for Parkinson's disease (PD) established in 2000 by Michael J. Fox. It concentrates on funding research and ensuring the development of improved therapies for ...
to explore the potential for delta opioid receptor biased ligands to treat
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
. Trevena's initial public offering was on January 30, 2014.


Pipeline


Oliceridine

Trevena's leading drug candidate is Oliceridine (TRV130), a G protein-biased ligand binding to the mu opioid receptor for the intravenous treatment of acute moderate-to-severe post-operative pain. Phase I and II clinical trials of TRV130 for postoperative pain are complete. Phase II trials showed effectiveness is analgesia and a wider therapeutic window than
morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...
. In February 2016, the FDA granted Breakthrough Therapy status to olicerdine. In January 2017, Trevena announced that enrollment for its phase III trials, APOLLO-1 and APOLLO-2 are complete. In November 2018, Trevena received a Complete Response Letter (CRL) from FDA regarding Oliceridine and the need for additional safety data. As of late December 2018, the company has yet to release the meeting minutes from FDA on how to move forward with Oliceridine approval in 2019. Trevena announced FDA approval of oliceridine on August 7, 2020. Trevena announced DEA scheduling, Schedule II controlled substance, of oliceridine on October 30, 2020 https://finance.yahoo.com/news/trevena-announces-publication-comprehensive-review-110010409.html


TRV027

Trevena's developed TRV027 for acute
heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...
, targets the angiotensin receptor utilizing beta-arrestin bias, an approach that has shown numerous beneficial cardiovascular and renal actions in preclinical species. Trevena completed Phase I clinical trials in 2010. Phase 2 clinical trials on TRV027 began in the spring of 2011. In May 2016, Trevena announced that the TRV027 phase II trial failed to meet its primary endpoints and they were no longer developing the drug. Trevena announced it has entered into a collaboration with Imperial College London to evaluate the potential of TRV027, a novel AT1 receptor selective agonist, to treat acute lung injury contributing to acute respiratory distress syndrome (ARDS) in COVID-19 patients. ARDS is a major complication leading to mortality associated with COVID-19. Imperial College London will be sponsoring and funding this study, with additional support through the British Heart Foundation Centre for Research Excellence Award. https://www.biospace.com/article/releases/trevena-announces-collaboration-with-imperial-college-london-to-evaluate-trv027-in-covid-19-patients/


TRV250

TRV250 is a pre-clinical drug candidate for migraine binding to the delta opioid receptor. This avoids the addiction potential of drugs that activate the mu opioid receptor. Other delta opioid-targeting drugs are known to cause seizures, but Trevena hopes to avoid this with TRV250 by bypassing the
β-arrestin Arrestins (abbreviated Arr) are a small family of proteins important for regulating signal transduction at G protein-coupled receptors. Arrestins were first discovered as a part of a conserved two-step mechanism for regulating the activity of ...
pathway.


TRV734

TRV734 TRV734 is a drug developed by Trevena Inc which acts as a biased agonist at the μ-opioid receptor, selective for activation of the G-protein signalling pathway over β-arrestin 2 recruitment. It is closely related to oliceridine Oliceridine ...
is an oral follow-up to the injected TRV130 mu-opioid biased ligand program. While it binds to the same receptors as opioid analgesics, TRV734 has very weak β-arrestin recruitment, unlike other available opioids, and produced fewer off-target effects. Phase I clinical trials were completed in 2014.


References


External links


Official Trevena site
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