Trevena Inc

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Trevena Inc
Public
Traded as NASDAQTRVN
Industry Biotechnology / Pharmaceutical
Headquarters Chesterbrook, Pennsylvania, United States
Key people
Maxine Gowen (President and CEO)
Website www.trevena.com

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, which originated in the labs of company founders Robert Lefkowitz winner of the 2012 Nobel Prize in Chemistry [1] and Howard Rockman. Trevena's approach to drug discovery is based on utilizing ligand bias, or functional selectivity, at GPCR targets to produce drugs with improved efficacy and reduced side effect profiles.[2] Trevena was named one of the top 15 US startups of 2008 by Business Week.[3]

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.[4] 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.[5]

History[edit]

In 2008, the company raised $25 Million in a Series A[clarification needed] financing round led by Alta Partners, Polaris Ventures, New Enterprise Associates, Healthcare Ventures, and Yasuda Economic Development Corporation.[6]

In early 2009, Trevena entered into a collaborative agreement with Ligand Pharmaceuticals to identify biased ligands at numerous GPCRs from a large, diverse chemical library.[7] Later that year, Trevena received a competitively awarded American Recovery and Reinvestment Act Grand Opportunities Grant, spanning two years and funding $7.65 million USD of research.[8] The company has disclosed specific interests in the mu Opioid receptor and kappa Opioid receptor.[9] The company raised an additional $35 million USD in a B round of venture financing in the summer of 2010.[10] 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 biased ligand for major depressive disorder.[11] Trevena has received funding from the Michael J. Fox Foundation to explore the potential for delta opioid receptor biased ligands to treat Parkinson's disease.[12]

Trevena's initial public offering was on January 30, 2014.[13]

Pipeline[edit]

Oliceridine[edit]

Trevena's leading drug candidate is Oliceridine (TRV130), a G protein-biased ligand binding to the mu opioid receptor[14] 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.[15] In February 2016, the FDA granted Breakthrough Therapy status to olicerdine.[16] In January 2017, Trevena announced that enrollment for its phase III trials, APOLLO-1 and APOLLO-2 are complete.

TRV027[edit]

Trevena's developed TRV027 for acute heart failure, targets the angiotensin receptor utilizing beta-arrestin bias, an approach that has shown numerous beneficial cardiovascular and renal actions in preclinical species.[17][18] Trevena completed Phase I clinical trials in 2010.[19] Phase 2 clinical trials on TRV027 began in the spring of 2011.[20] 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.[21]

TRV250[edit]

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,[22] but Trevaga hopes to avoid this with TRV250 by bypassing the β-arrestin pathway.[23]

TRV734[edit]

TRV734 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.[24] Phase I clinical trials were completed in 2014.[25]

References[edit]

  1. ^ "The Nobel Prize in Chemistry 2012". Nobelprize.org. 2012-10-10.
  2. ^ Violin, Jonathan D.; Lefkowitz, Robert J. (2007). "Β-Arrestin-biased ligands at seven-transmembrane receptors". Trends in Pharmacological Sciences. 28 (8): 416–22. doi:10.1016/j.tips.2007.06.006. PMID 17644195.
  3. ^ "Most Successful U.S. Startups 2008". Business Week. 2008-12-31.
  4. ^ "Exploring GPCRs as Therapeutic Targets". Genetic Engineering News. 2013-04-15.
  5. ^ "Trevena Inc - Pipeline". Trevena Inc - Company Website. 2010-01-01.
  6. ^ "Trevena Inc Announces $24 Million Series A Financing". BioSpace.com. 2008-03-05.
  7. ^ "Trevena to Use Ligand's Library to Identify GPCR Therapeutics". Genetic Engineering News. 2009-02-06.
  8. ^ "Trevena Awarded $7.65 Million NIH Grant to Accelerate Identification and Selection of Biased GPCR Ligands". Business Wire. 2009-11-03.
  9. ^ "Refining GPCR Discovery Approaches". Genetic Engineering News. 2011-04-15.
  10. ^ "Trevena lands $35M round to fund its first PhII". Fierce Biotech. 2010-07-14.
  11. ^ "Trevena Receives Major New Award from NIH To Develop Delta Opioid Biased Ligand Drug". Business Wire. 2011-08-18.
  12. ^ "Pathway Validation of a Biased Delta Opioid Receptor Ligand for PD Symptoms & Side Effects Relief". Michael J. Fox Foundation. 2011-12-19.
  13. ^ http://investors.trevena.com/faq.cfm
  14. ^ DeWire, SM; Yamashita, D; et al. (2013). "A G Protein-Biased Ligand at the μ-Opioid Receptor Is Potently Analgesic with Reduced Gastrointestinal and Respiratory Dysfunction Compared with Morphine". The Journal of Pharmacology and Experimental Therapeutics. 344 (3): 708–17. doi:10.1124/jpet.112.201616. PMID 23300227.
  15. ^ http://www.trevena.com/news-details.php?id=155
  16. ^ http://www.trevena.com/TRV130.php
  17. ^ Violin, JD; Dewire, SM; Yamashita, D; Rominger, DH; Nguyen, L; Schiller, K; Whalen, EJ; Gowen, M; Lark, MW (2010). "Selectively engaging β-arrestins at the angiotensin II type 1 receptor reduces blood pressure and increases cardiac performance". The Journal of Pharmacology and Experimental Therapeutics. 335 (3): 572–9. doi:10.1124/jpet.110.173005. PMID 20801892.
  18. ^ Boerrigter, G; Lark, MW; Whalen, EJ; Soergel, DG; Violin, JD; Burnett Jr, JC (2011). "Cardiorenal actions of TRV120027, a novel ß-arrestin-biased ligand at the angiotensin II type I receptor, in healthy and heart failure canines: A novel therapeutic strategy for acute heart failure". Circulation: Heart Failure. 4 (6): 770–8. doi:10.1161/CIRCHEARTFAILURE.111.962571. PMID 21835984.
  19. ^ "Trevena Initiates Clinical Development of TRV120027, a First-in-Class Biased Ligand". Pipeline Review. 2010-04-14.
  20. ^ "Trevena Initiates Phase 2 Study of TRV120027 for Acute Heart Failure". Pennsylvania BioWatch. 2011-02-23.
  21. ^ http://www.trevena.com/news-details.php?id=145
  22. ^ http://www.trevena.com/pdf/J_Pharmacol_Exp_Ther-2002-Broom-723-9.pdf
  23. ^ http://www.trevena.com/TRV250.php
  24. ^ http://www.trevena.com/TRV734.php
  25. ^ https://clinicaltrials.gov/ct2/results?term=trv734&Search=Search

External links[edit]