Lars J.S. Knutsen, MA, PhD, FRSC leads Discovery Pharma Consulting LLC, a R&D Consulting group based both in West Chester, PA, USA and Cambridge UK, that provides Drug Discovery and I.P. Expert Witness services.

Lars began his Pharma R&D career at Glaxo in Herts., UK after completing an M.A. in Chemistry at Christ Church, Oxford. At Glaxo, he gained a Ph.D. in C-Nucleoside Medicinal Chemistry (antivirals), joining Novo Nordisk, Copenhagen in 1986. In the Novo CNS R&D Group he led projects that identified GABA uptake inhibitor Tiagabine, an anticonvulsant approved by FDA in 1997 and initiated a project providing adenosine agonist drug candidates for stroke. Lars was appointed Associate Director, Med. Chem. at Vernalis PLC (UK), where he drove several projects forward, specifically the adenosine A_2A antagonist program that led to V2006/BIIB014, exhibiting PoC in Phase IIA trial in Parkinson’s Disease. He was appointed Director of Chemistry at Ionix Pharma in Cambridge in 2001, the UK’s first pain-focused biotech, moving to Cephalon R&D in West Chester, PA, US in 2005 as Distinguished Scientist, inventing the histamine H₃ antagonist Irdabisant, clinically investigated for cognitive disorders at Teva (US). Currently Lars is VP, Med. Chem. at NMD Pharma, Denmark, that raised a $47 M Series A, devising/ designing NMD670: http://www.nmdpharma.com/news/2020/7/15/nmd-pharma

He served as an Adjunct Professor at Drexel University College of Medicine from 2009-19, and lectures widely on Drug Discovery. Discovery Pharma Consulting, founded in 2009, guides Pharma/Biotech firms as well as academic R&D teams in drug design but also provides Expert Input to Law Firms involved in IP litigation. Lars has completed 17 Pharma cases since 2011; he is available to consult worldwide as he holds UK & US passports.

Research Interests:

Drug Discovery, medicinal chemistry relating to treatment of CNS and neuromuscular disorders, specifically epilepsy, neurodegeneration, cognition as well as rare neuromuscular disease such as myasthenia gravis and various myopathies. Lars has experience in adenosine drug design, ion channel drug discovery, antivirals and knows the stroke, Alzheimer’s Disease and sleep disorder fields well. He is an expert in formulating Drug Discovery/ Development/ IP strategies, drug design studies as well as carbohydrate, nucleoside and heterocyclic synthesis.

Pharma R&D/Research Achievements

• On joining new companies, 3 times provided drug candidates in under 6 months: Novo, DK (1986, Gabitril^®), Cephalon, US (2006, Irdabisant) and NMD Pharma DK (NMD670, 2017); NMD has filed 10 patent series since 2016. NMD recently announced NMD670 clinical trials: https://apnews.com/1e0cef259f9ae4747ff59b27b0101da1
• Inventor on 46 issued/ published pharmaceutical patents and applications, involving discovery of new drugs
• Closely involved in design and invention of 14 NCEs; 6 selected for clinical trials in CNS/ neuromuscular disease
• Became a sought-after IP Expert Witness, involved in 17 cases in the past 9 years, some very high-profile
• Chaired the Patent Committees at both Vernalis PLC and Ionix Pharmaceuticals, managing a portfolio of around 85 patents/ patent applications at Vernalis and ~15 at Ionix; liaising extensively with outside IP Counsel   
• At Novo Nordisk, led team that synthesized and identified Gabitril™ a unique anticonvulsant for treatment of partial seizures acting via inhibition of GABA uptake. Drove forward Pharma R & D in demanding environments
• Also at Novo designed & selected NNC 21-0136 a novel breakthrough neuroprotectant for stroke treatment 
• Initiated project: adenosine A_2A antagonists for Parkinson’s Disease at Vernalis 1999; Vipadenant (BIIB014) was  investigated in Phase II clinical trials with BiogenIDEC: http://www.ncbi.nlm.nih.gov/pubmed/20375654
• Headed Pre-Project group at Vernalis, initiated project targeting novel CB₁ antagonists in 2001; lead compound, V24343, entered trials for obesity in 2006, see http://clinicaltrials.gov/show/NCT00734201
• Appointed as Director of Chemistry at the UK’s first pain-focused Biotech, Ionix Pharmaceuticals, Cambridge in 2001
• At Cephalon, invented Irdabisant (CEP-26401) in 2006, Lars’ 5th clinically investigated career NCE and Teva’s most recent CNS drug trial, see: http://adisinsight.springer.com/drugs/800031631
• Recognized by peers as a high-level heterocyclic and nucleoside chemist and expert in IP and Project Management
• Appointed to SAB of the non-profit Charcot Marie Tooth Association in 2013; inventive input to use of proteasome inhibitors in neuropathies (US 2014/0080787). See http://www.cmtausa.org/research/star-advisory-board/

Pharma Industry Appointments:

2017-present      VP, Medicinal Chemistry at NMD Pharma, Aarhus, Denmark: www.nmdpharma.com

2009-present      President, Discovery Pharma Consulting LLC, West Chester, PA www.discoverypharm.com

2013-present      SAB member at US Charcot Marie Tooth Association, appointed to Therapy Expert Board  

2012-present      Founder/ CSO of Requis Pharmaceuticals Inc., West Chester, PA

2005-2008          Distinguished Scientist and Project Leader, Cephalon, Inc., West Chester, PA, USA

2001-2005          Director of Chemistry, Ionix Pharmaceuticals, Cambridge, UK

1997-2001          Associate Director, Medicinal Chemistry, Vernalis, Wokingham, UK

1993-1997          Principal Scientist, Medicinal Chemistry, Novo Nordisk, Måløv, Denmark

1986-1993          Project Leader, Senior Chemist, Novo Industri CNS Division, Copenhagen, Denmark

1978-1986          S2 Research Chemist, Glaxo Group Research, Ware, Herts., UK

Scientific Contributions

• Inventor of NMD670, a novel clinical first in class ClC-1 blocker for treatment of Myasthenia Gravis 
• Inventor of Requisom, a new drug combination to treat OSA, snoring and other sleep disorders 2011 & 2013
• Published 46 articles in peer-reviewed publications; inventor on 46 PCT applications and 25 issued US patents
• NIH/NIMH Review Panel member for major grant applications PA-08-238: NCDDDG for Treatment of Mental Disorders, Drug or Alcohol Addiction, 2010 and 2011.  External reviewer for faculty at NIH, October 2016.
• Published pivotal J. Med. Chem. articles on the rational design of novel anticonvulsant GABA Uptake Inhibitors (1993, 1999) and the design of CNS-selective adenosine agonists (1998, 1999)
• Led 8 major projects in CNS Drug Discovery in Denmark, the UK and US to clinical candidate selection
• Invited speaker at over 30 International Conferences and University Dept. Seminars, 1992 – 2020
• Honored as a Fellow of the Royal Society of Chemistry in 1998; attained US Citizenship in 2015
• Served for over a decade on the Editorial Board of the journal Drug Development Research
• Active member of Society for Neuroscience and American Chemical Society, Treasurer of UK CGZ Award
• Regular Reviewer for the prestigious journals J. Med. Chem. & Bioorg. Med. Chem. Lett. and other scientific journals; won a 2013 award for one of the top 10 reviews for Bioorg. Med. Chem. Lett. 

Academic Appointment: Adjunct Professor, Drexel University College of Medicine, Philadelphia, 2009-2020

Selected Publications: (from a total of 46 peer-reviewed papers)

1. Knutsen, L.J.S. Drug discovery management, small is still beautiful: Why a number of companies get it wrong. Drug Discovery Today, 2011, 16, 476-484 (this article became one of DDT’s top 10 downloads).
2. Marino, M.J.: Knutsen, L.J.S and Williams M. Perspective: Emerging Opportunities for Antipsychotic Drug Discovery in the Postgenomic Era J. Med. Chem., 2008, 51, 1077 – 1107.
3. Marino, M.J.: Davis, R.E.; Meltzer, H.E.; Knutsen, L.J.S and Williams M. Schizophrenia. In Comprehensive Medicinal Chemistry II (Taylor, J.B; Triggle, D. J., Editors-in-Chief) Vol. 6; Therapeutic Areas I (M. Williams, Volume Editor), 2006, pp. 17 – 44.
4. Knutsen, L.J.S and Williams M. Epilepsy. In Comprehensive Medicinal Chemistry II (Taylor, J.B; Triggle, D. J., Editors-in-Chief) Vol. 6; Therapeutic Areas I (M. Williams, Volume Editor), 2006, pp 279 – 296.
5. Knutsen, L.J.S., Lau, J., Petersen, H., Thomsen, C., Weis, J.U., Shalmi, M., Judge, M.E., Hansen, A.J. and Sheardown, M.J.; N-Substituted Adenosines as Novel Neuroprotective A₁ Agonists with Diminished Hypotensive Effects. J. Med. Chem., 1999, 42, 3463 – 3477.
6. Knutsen, L.J.S., Andersen, K.E., Lau, J., Lundt, B.F., Henry, R.F., Morton, H.E., Nærum, L., Petersen, H. et al. The Synthesis of Novel GABA Uptake Inhibitors. 3. Diaryloxime and Diarylvinylether Derivatives of Nipecotic acid and Guvacine as Anticonvulsant Agents.  J. Med. Chem., 1999, 42, 3447 – 3462.
7. Mogensen,J.P., Roberts, S.M., Bowler, A.N., Thomsen, C. and Knutsen, L.J.S.; The Synthesis of New Adenosine A₃ Selective Ligands Containing Bioisosteric Isoxazoles. Bioorg. Med. Chem. Lett. 1998, 8, 1767 – 1770.
8. Knutsen, L.J.S. and Murray, T.F. Adenosine and ATP in Epilepsy. Purinergic Approaches Exp. Ther. (1997), 423 – 447.  Editors: Jacobson, Ken A.; Jarvis, Michael F.  Publisher: Wiley-Liss, New York, N. Y.
9. Andersen, K.E., Braestrup, C., Grønwald, F.C., Jørgensen, A.S., Nielsen, E.B., Sonnewald, U. Sørensen P.O., Suzdak, P.D. and Knutsen, L.J.S.; The Synthesis of Novel GABA uptake inhibitors. 1. Elucidation of the structure activity studies leading to the choice of R‑1‑[4,4‑bis (3‑methyl‑2‑thienyl)‑3‑but­enyl]‑3‑piper­idine carboxylic acid (Tiagabine) as an anticonvulsant drug candidate; J. Med. Chem., 1993, 36, 1716 ‑ 1725.

Discovery Pharma Consulting LLC has a correspondence address of P.O. Box 535, West Chester, PA 19381, USA, E-mail: lars@discoverypharm.com; tel. +1 (484) 319-0117