Science & Pipeline
Lophora has built a drug discovery platform leveraging decades of structure-activity relationship studies around the most inherently selective class of 5-HT2A agonists.
Early read-outs from clinical trials of lead candidate LPH-5 indicate unrivalled safety and tolerability in humans, lending itself to diverse dosing paradigms in depression, mood and anxiety disorders. Fast-follower LPH-48 is designed as a short duration of action therapeutic, with similar primary pharmacology to parent compound LPH-5. Several additional candidates are in development for neurodegenerative disorders and longevity.
Lophora’s rich and easily expandable pipeline can address multiple psychiatric disorders. Like other agonists of the 5 HT2A receptor, LPH-5 is believed to be a potent psychoplastogen and has shown anti-depressant effect in an animal model of depression at doses that do not induce hallucinogenic effects, indicating that this compound is well suited for subperceptual-dosing paradigms to address a breadth of CNS-related indications, which do or do not require induction of the psychedelic state.
Scientific Publications
Representative scientific publications from the Lophora-research team:
- The Selective Serotonin 5-HT2A Receptor Agonist (S)-3-(2,5-Dimethoxy-4-(trifluoromethyl)phenyl)piperidine (LPH-5) Induces Persistent and Robust Antidepressant-Like Effects in Rodents. Jensen, A.A.; Cecchi, C.R.; Hibicke, M.; Bach, A.H.; Kaadt, E.; Märcher-Rørsted, E.; Nichols, C.D.; Elfving, B.; Kristensen, J.L. ACS Pharmacol. Transl. Sci. 2025, 8 (6), 1791-1803.
- Discovery and Structure–Activity Relationships of 2,5-Dimethoxyphenylpiperidines as Selective Serotonin 5-HT2A Receptor Agonists. Marcher-Rørsted, E.; Jensen, A.A; Smits, G.; Frydenvang, K. Kristensen, J.L. J. Med. Chem. 2024, 67 (9), 7224-7244.
- Animal Behavior in Psychedelic Research. Odland, A.U.; Kristensen, J.L.; Andreasen, J.T. Pharm. Rev. 2022, 74, 1176.
- 25CN‐NBOH: A Selective Agonist for in vitro and in vivo Investigations of the Serotonin 2A Receptor. Marcher-Rørsted, E.; Jensen, A.A.; Kristensen, J.L. ChemMedChem 2021, 16, 3263.
- Investigation of the 2,5-dimethoxy motif in phenethylamine Serotonin 2A receptor agonists. Marcher-Rørsted, E.; Halberstadt, A.L.; Klein, A.; Chatha, M.; Jademyr, S.; Jensen, A.A.; Kristensen, J.L. ACS Chem. Neurosci. 2020, 11, 1238.
- Dark classics in chemical neuroscience: NBOMes. Poulie, C.B.M.; Jensen, A.A.; Halberstadt, A.L.; Kristensen, J.L. ACS Chem. Neurosci. 2020, 23, 3860.
- Human biodistribution and radiation dosimetry of the 5-HT2A receptor agonist Cimbi-36 labeled with carbon-11 in two positions. Johansen, A.; Holm, S.; Dall, B.; Keller, S.; Kristensen, J.L.; Knudsen, G.M.; Hansen, H.D. EJNMMI Research 2019, 9, 71.
- Detailed characterization of the in vitro pharmacological and pharmacokinetic properties of N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine (25CN-NBOH), a highly selective and brain-penetrant 5-HT2A receptor agonist. Jensen, A.A.; McCorvy, J.D.; Leth-Petersen, S.; Bundgaard, C.; Liebscher, G.;
- 5-HT2A/5-HT2C Receptor Pharmacology and Intrinsic Clearance of N-Benzylphenethylamines Modified at the Primary Site of Metabolism. Leth-Petersen, S.; Petersen, I.N.; Jensen, A.A.; Bundgaard, C.; Bæk, M.; Kehler, J.; Kristensen, J.L. ACS Chem. Neurosci. 2016, 7, 1614-1619.
- Metabolic fate of hallucinogenic NBOMes. Leth-Petersen, S.; Gabel-Jensen, C.; Gillings, Nic.; Lehel, S.; Hansen, H.D.; Knudsen, G.M.; Kristensen, J.L. Chem Res. Toxicol. 2016, 29, 96-100.
- Hallucinogen-like effects of 2-([2-(4-cyano-2,5-dimethoxyphenyl) ethylamino]methyl)phenol (25CN-NBOH), a novel N-benzylphenethylamine with 100-fold selectivity for 5-HT2A receptors, in mice. Fantegrossi, W.; Gray, B.; Bailey, J.; Smith, D.; Hansen, M.; Kristensen, J. Psycopharmacology, 2015 232(6), 1039-47.
- Serotonin 2A receptor agonist binding in the human brain with [11C]Cimbi-36. Ettrup, S. Cunha-Bang, B. McMahon, S. Lehel, A. Dyssegaard, A.W. Skibsted, L.M. Jørgensen, M. Hansen, A.O. Baandrup, S. Bache, C. Svarer, J.L. Kristensen, N. Gillings, J. Madsen, G.M. Knudsen. JCBFM, 2014, 34, 1188.
- Synthesis and Structure-Activity Relationships of N-Benzyl Phenethylamines as 5-HT2A/2C Agonists. M. Hansen, K. Phonekeo, J.S. Paine, S. Leth-Petersen, M. Begtrup, H. Bräuner-Osborne, J.L. Kristensen. ACS Chem. Neurosci. 2014, 5, 243.
- Structure-Activity Relationships of Constrained Phenylethylamine Ligands for the Serotonin 5-HT2 Receptors. V. Isberg, J. Paine, S. Leth-Petersen, J.L. Kristensen, D.E. Gloriam. PLoS ONE, 2013, 8(11): e78515.
- Radiosynthesis and in vivo evaluation of a series of substituted 11C-phenethylamines as 5-HT2A agonist PET tracers. Ettrup, A.; Hansen, M.; Santini, M.A.; Paine, J.; Gillings, N. Palner, M.; Lehel, S.; Herth, M.M.; Madsen, J.; Kristensen, J.; Begtrup, M.; Knudsen, G.M. Eur. J. Nucl. Med. Mol. Imaging, 2011, 38, 681.
Patents
Lophoras IP portfolio includes a composition of matter patent covering a wide area of chemical space encompassing millions of novel compounds within a novel compound class of phenethylamine derived psychedelics- granted in the US, Europe and elsewhere.
Furthermore, Lophora controls the rights to the proprietary manufacture of lead candidate LPH-5 and fast follower LPH-48, including protection of the novel salt and polymorphic form of both compounds.
- Australia (Granted 9 July 2026)
- Brazil
- Canada
- China (Granted 13 February 2024)
- Europe (Granted 31 May 2023) In force in Albania, Austria, Bosnia & Herzegovina, Belgium, Bulgaria, Switzerland, Cyprus, Czech Republic, Germany, Denmark, Spain, Finland, France, United Kingdom, Greece, Croatia, Hungary, Ireland, Iceland, Italy, Cambodia, Lithuania, Luxembourg, Latvia, Morocco, Monaco, Republic of Moldova, Montenegro, The Former Yugoslav Republic of Macedonia, Malta, Netherlands, Norway, Poland, Portugal, Romania, Sweden, Slovenia, Slovakia, Tunisia & Turkey
- Hong Kong (Granted 19 April 2024)
- India
- Israel (Granted 3 July 2023)
- Japan (Granted 3 October 2024)
- New Zealand
- South Africa (Granted 30 November 2022)
- US (Granted 15 February 2022)
- US divisional 1 (Granted 25 April 2023)
- US divisional 2 (Granted May 2023)
- Australia
- Brazil (Granted 23 December 2025)
- Canada
- China
- Europe
- Hong Kong
- India
- Japan (Granted 18 June 2026)
- US