1. Geert Jan Groeneveld, MD, PhD
The Reef Biotech Ltd case – An introduction
Geert Jan Groeneveld, MD, PhD
June 7, 2018
Castle Oud Poelgeest, Oegstgeest
The Netherlands

2. Reef Biotech Ltd. RB3285: 1400 Da stable 13-amino acid peptide
Originally derived from cone snail venom
χ(chi)-conopeptides
The peptide Mr1A, identified in the venom of Conus marmoreus,
causes inhibition of norepinephrine (NE) uptake by the
NE transporter (NET) in a selective, noncompetitive manner

3. Cone snail hunting
Siphon
Harpoon
100 toxins

4. Reef Biotech Ltd. RB3285: 1400 Da stable 13-amino acid peptide
Originally derived from cone snail venom
Non-competitive inhibitor (NAM) of the NET

5. Descending pain pathways

6. Reef Biotech Ltd. RB3285: 1400 Da stable 13-amino acid peptide
Originally derived from cone snail venom
Non-competitive inhibitor (NAM) of the NET
Administered via intrathecal delivery
Excellent potential for intractable pain

7. ? Reef Biotech Ltd. Paul Blackwater, one of the founders, scientist
Both CEO & head drug development
leave Reef Biotech
$ 3.75 m new share issue
$ 1.25 m
investment
$ 2.5 m
new funding
Two board members (investors)
$ 6 m
US patent
EU patent
$ 10 m
equity finance
Ziconotide licensed by FDA for US market
Ziconotide licensed by EMA/EC for EU market
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
Reef Biotech Ltd. Is founded
FDA puts
Phase II trial
on hold
FDA/CDER
IND approval
for RB3285
Pre-clinical studies
on RB3582
(in vitro, rat and dog)
Phase I/II trial
oncology patients
IT admin.
Additional
dog studies
(required by FDA)
Phase I trial HV
IV admin.
bunion surgery ?
Paul Blackwater, one of the founders, scientist
Paul Bevan, experienced drug developer
FIH study in 20 HV, safety, tolerability, IV
2004: JAMA paper on ziconotide
Sever chronic pain and compete with ziconotide?
Bevan in favor of alternative: severe acute pain
Blackwater: sever chronic pain because different mechanism of action than ziconotide and ziconotide very small therapeutic window due to severe AE’s after ziconotide
Fight, Bevan leaves
Blackwater acting CEO