Lars J. S. Knutsen, Ph.D., FRSC

PROFILE

Results-driven Pharma R&D Leader, Drug Discovery Consultant and Senior Medicinal Chemist. Expert in design and selection of Drug Candidates; broad medicinal chemistry capability focused on treatments for neuromuscular disease, epilepsy, sleep disorders, cognition, neurodegeneration and pain. Motivated teams of scientists to achieve goals in 6 companies over a 30+ year Pharma/Biotech career. Superb analytical skills and deep pharma strategic and IP knowledge. Involved in invention of 8 NCEs, of which 6 progressed to clinical trials, including Vipadenant (Parkinson’s Disease) and Irdabisant (Cognition); anticonvulsant Gabitril™ marketed worldwide. Peer recognized high-level heterocyclic, nucleoside/ carbohydrate chemist.

Adjunct Professor at Drexel University School of Medicine since 2009; regular major conference speaker with 45 peer-reviewed publications, 34 published PCT patents; 24 issued in US. Chaired Patent Committees at Ionix Pharma and Vernalis PLC; strong knowledge of patenting process in US/EU with its manifold issues. Member of NIMH/NCDDDG Grant Review Panel, 2010-11; NIDDK Intramural Staff Review 2016. Articulate and creative scientific leader with excellent interpersonal skills; methodical and focused; deep knowledge of drug design. Biology and PK/ADME knowledge from leading successful clinical drug discovery efforts. Fellow, Royal Society of Chemistry, ACS/SfN member; gained US Citizenship 2015.

PROFESSIONAL EXPERIENCE

NMD Pharma ApS Aarhus, Denmark                                                                               Feb. 2017 – present

Director of Chemistry

Driving forward the design and synthesis of new ClC-1 ion channel ligands via 2 major Med. Chem. CROs as part of the management team in this new VC-funded Biotech focusing on treatments for neuromuscular disorders

Discovery Pharma Consulting LLC West Chester, PA USA                                             Feb. 2009 – present

President

Founded as Lars’ 4th start-up in response to clients requesting Pharma R&D Consulting services. Specializing in IP Expert Witness work, Preclinical Drug Discovery; including Hit-to-Lead, Lead Optimization and Preclinical Development phases. Med. Chem. input provided along with Strategic R&D advice and portfolio reviews, see www.discoverypharm.com. Some assets are now in a product-focused Biotech developing drugs for sleep – Requis Pharma Inc., where I am Acting CEO.

Drexel University College of Medicine Philadelphia, PA, USA        November 2009 – present

Adjunct Professor

Appointed by Prof. James Barrett, Dept. of Pharmacology and Physiology, to advise and collaborate with faculty on drug R&D strategy, to teach Drug Discovery, and to drive entrepreneurism in the wider Drexel community.

Charcot-Marie Tooth Association                                                                                   May 2013 – present

SAB & Therapy Expert Board; driving forward new treatments for CMT Disease in this non-profit; inventive input to use of proteasome inhibitors (US 2014/0080787): http://www.cmtausa.org/research/star-advisory-board/

Cephalon, Inc. West Chester, PA USA                                                                  2005 – 2008

Distinguished Scientist/ Project Leader

Hired into this newly-created role, built new team; drove initiation of and managed new Schizophrenia project. Key input to strategic course of Cephalon R&D in Oncology and CNS in Project Management Group. Major contributor to Cognition program – invented Irdabisant (CEP-26401), my 5th career NCE and Cephalon’s most recent clinical drug: https://www.clinicaltrials.gov/ct2/show/NCT01903824?term=irdabisant&rank=1 As Cephalon’s first Distinguished Scientist; consulted internally on the anticonvulsant Gabitril™, a Cephalon product

Ionix Pharmaceuticals Cambridge, UK                                                                2001 – 2005

Director of Chemistry

Responsible for R & D Chemistry, including strategy/ budgeting, in this pain and ion-channel focused start-up company. Built outstanding team of 15+ medicinal chemists and computational chemist. Key member of Ionix Management Team, Product Management Group and Chair of Intellectual Property Strategy Meeting.  Drove creative medicinal chemistry/parallel synthesis in calcium and sodium channel blocker projects. Project Leader of key Cav2 (N-type channel) program.  Completed major drug design and synthesis projects with CROs such as Tripos and Evotec. Networked into European and worldwide CROs such as Penn, Onyx and SigmaAldrich, planning Preclinical and CMC phases.

Vernalis (formerly Cerebrus), Wokingham, UK                                                  1997 – 2001

Associate Director, Medicinal Chemistry

Initiated Discovery project for new adenosine A2A antagonists for Parkinson’s Disease; Vipadenant (VR 2006) showed PoC, made it to clinical Phase II in Biogen Idec, see: http://production.investis.com/ver/rdc/v2006/?t=print

Leader of Sodium Channel program; Head of Pre-Project group; involved in obesity research via novel 5HT2c agonist.  Started pre-project targeting novel CB1 antagonists in 2001; lead compound, V24343, entered clinical trials for obesity late in 2006, see: http://www.vernalis.com/media-centre/archive-releases/2006-releases/407

Chaired Patent Committee, managing a portfolio of ~85 patent applications; liaised extensively with outside Counsel.  Member of Chemistry Management Team, devised company strategies for I.P. and Parallel Synthesis.  Part of Integration Team following Vanguard merger with Cerebrus in late 1999.

Novo Nordisk, Pharmaceuticals Division, Måløv, Denmark                                 1993 – 1997

Principal Scientist and Department Leader, Medicinal Chemistry

Project Manager, Purine project group; initiated project on adenosine A1 receptor agonists; led high-performing team of chemists. Promoted to Department Head in 1995.  Worked on drug design on 2 new targets for diabetes.   A1 agonist drug candidate NNC 21-0136, selected as pre-clinical compound 2¼ years from project start; back-up NNC 21-0149 also identified. Completed Novo management/ project manager training modules.

Gabitril launched as novel anticonvulsant in 1997; Invented back-up series to Gabitril, NNC-711 – authored 1999 Med. Chem. article. NNC-711 reviewed in CNS Drug Reviews, 1999, 5, 317-330.               

Novo Industri CNS Division, Copenhagen, Denmark                                            1986 – 1993

Project Leader/ Senior Chemist

Project Manager, GABA Uptake III project group. Promoted to Principal Scientist in 1993. Led project team driving discovery & selection of the marketed anticonvulsant Tiagabine (Gabitril).  Principal author of 1993 Med. Chem. describing synthesis, SAR of Gabitril, as well as back-ups in 1999.

Glaxo Group Research, Ware, Herts. UK                                                             1978 – 1986

Research Chemist in Medicinal Chemistry

Drove forward design and synthesis of novel nucleoside antiviral agents, acyclovir analogues and adenosine receptor ligands in this entry-level role; promoted to S2 chemist after 1 year.  Completed Ph.D. studies, yielding 7 publications, externally through King’s College, London while at Glaxo.

AWARDS AND HONORS

Appointed to the Science Advisory Board of the Charcot Marie Tooth Association (2013)

Awarded prize as top 10 reviewer for Bioorganic and Medicinal Chemistry Letters (2012)

Appointed as an Adjunct Professor at Drexel University College of Medicine (2009)

Honored at dinner for the 2 Cephalon Distinguished Scientists; portrait placed in foyer of R&D HQ (2007)

Awarded O-1 Outstanding Expert (“Rock Star”) Visa to the US (2005), became US Citizen (2015)

Appointed as a Fellow of the Royal Society of Chemistry (1999)

EDUCATION

Ph.D. in Medicinal Chemistry (while employed at Glaxo, Ware, Herts, UK) in collaboration with Prof. C.B. Reese, Kings College, London & CNAA).  Ph.D. thesis: “The Synthesis of Bridgehead Nitrogen C-Nucleosides” yielded 7 major peer-reviewed publications.  Advisors: Prof. Roger F. Newton & Dr. David I.C. Scopes.

B.A. (Hons.)/ M.A. in Chemistry 1978, Christ Church, University of Oxford

Journal Involvement & Collaborations

Served on Editorial Advisory Board of Drug Development Research (1994 – 2010) and a regular reviewer for Med. Chem. and Bioorg. Med. Chem. Lett.

 

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