Science & Pipeline
Lophora’s drug design platform is built on rational engineering of 5-HT2A agonists with optimized drug-like properties and reduced off-target activity. LPH-5 is now in first-in-human evaluation, with LPH-48 and additional NCE candidates in expansion.
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 could be used for micro or macro-dosing paradigms to address a breadth of CNS-related indications, which do or do not require induction of the psychedelic state.
Drug Design
Embracing the future of psychedelic medicine, rational drug-design, building on decades of scientific research into psychedelic drug scaffolds, has led the Lophora R&D team to the discovery of a novel compound class in which the problematic off-target effects of classic psychedelics have been systematically engineered out.
Having spent the past decades developing selective tool compounds to investigate the Serotonin 2A receptor and its pharmacology in clinical and pre-clinical research, the Lophora R&D team have directed their efforts towards the challenge of developing a selective therapeutic for the Serotonin 2A receptor. The Lophora compound class has been fully characterized, thus arriving at a candidate for psychedelic drug-therapy which not only shows very desirable drug-like properties and potent activity, but also has been rigorously investigated with regards to preclinical toxicology. Furthermore, CMC development has resulted in a scalable and robust procedure for the manufacture of LPH-5 on Kg-scale under GMP conditions.
LPH-5 (Phase I)
LPH-48 (Pre-clinical)
LPH-48 is a shorter acting direct analog of LPH-5 with similar optimized characteristics and safety profile, but with a shorter duration of action.
Designed as a fast-follower to LPH-5, LPH-48shows significantly faster metabolism, indicating a much shorter activity profile in man. LPH-48 is a representative of the same proprietary compound class as LPH-5 and is therefore endowed with the same optimized characteristics including drug-like properties and safety pharmacological profile.
Scientific Publications
Representative scientific publications from the Lophora-research team:
- 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.
Patent family “Selective 5-HT2A agonists”
International filing date: 6 November 2020.
Composition of matter patent covering a new class of small molecules with selective 5-HT2A agonism. Compound claims encompass chemical space of >1B compounds. Medical use claims on a wide range of indications applicable to psychedelics.
- Australia
- 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)
Patent family “Specific salts and polymorphs of 5-HT2A agonists”
International filing date: 5 May 2022.
Composition of matter patent covering specific salts and polymorphs of lead compounds. Positive International Preliminary Report on Patentability received (IPRP)
- Australia
- Brazil
- Canada
- China
- Europe
- Hong Kong
- India
- Japan
- US
Our patents have been developed in close collaboration with COPA Copenhagen Patents K/S.
Alliances & Partners
Lophora’s R&D work is conducted in collaboration with a range of academic and industrial partners: University of Copenhagen, University of Aarhus, Louisiana State University, WuXi AppTec, STA, Eurofins, Sygnature, Biotrial, Ardena and LIOS
