Marine Technology Summit
November 16, 2010
Nereus Pharmaceuticals
Discovering and Developing
New Medicines from Marine Microbes
Ken Lloyd, Ph.D.
Chief Scientific Officer
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Marine Technology Summit
November 16, 2010
Marine Microbiology: Paths to Success
Natural Product
•Mother Nature best
chemist
Marizomib (NPI-0052)
•Better characteristics than
>60 analogs
•Late Phase 1
•Multiple Myeloma
•Lymphomas
Derivative of Natural
Product
•Analogue Chemistry
•Precursor Manipulation
•Gene Strategies
Plinabulin (NPI-2358)
•Better profile than >200
analogs
•Late Phase 2
•Non small cell lung cancer
•Other solid tumors
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Marizomib: Second Generation Proteasome
Inhibitor with Best-in-Class Properties
Marizomib (NPI-0052)
Key Points
 Unique structure as compared to synthetic
H
H
OH
H
N
O
O
O
H
CH3
Cl
•5 chiral centers
•17-step
chemical
synthesis
•1-step
fermentation
competitors
 Potent, broad spectrum proteasome inhibitor
 Highly selective for proteasome activities as
compared to other proteases
 Marizomib has commercially relevant benefits
secondary to unique structure

Superior safety profile

Superior efficacy (Velcade resistant tumors)

Potential for oral, sc, or sublingual
 Significant market opportunity in validated
indications with considerable upside in other
large market indications
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Marizomib: Clinical Summation
 Excellent clinical safety profile with high levels of
proteasome inhibition
 Excellent pharmacodynamic results translating
from bench to clinic
 Proof of mechanism milestone achieved
 Anti-tumor activity seen in clinical trials
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Cutaneous Marginal Zone Lymphoma Patient
Treated with Marizomib Weekly at 0.7 mg/m2
Baseline
Prior Treatments (2006-2009):
 Hyper-CVAD
 ASCT (Bu-MEL)
 XRT (TSEB & IF)
 Rituximab
Cycle 4 Day 22
Complete Response – Biopsy Confirmed
Continued Complete Response Cycle 4 through Cycle 15
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Plinabulin: A Novel, Potent and Highly Selective
VDA with First-in-Class Potential
Plinabulin; NPI-2358
Themes
 On track to be the next major advance in
the treatment of multiple cancers after
success of angiogenesis inhibitors
O
N
HN
H
N
NH
O
•one of >250 analogues of
the natural product
•Potency >40 fold natural
product
•Straightforward
synthesis
 Major improvements over:

Anti-angiogenesis agents

Anti-microtubule cytotoxic agents
 Unique safety and efficacy profiles,
synergy and utility in unmet need
populations
 Novel plinabulin structure likely
responsible for advantages

Significantly improved safety profile

Potent and selective vascular disruption +
direct apoptotic effect to improve efficacy
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Plinabulin: Clinical Summation
 Excellent clinical safety profile vs other VDAs and
other approved oncology drugs
 CNS/Neurological
 Cardiac
 Decreases docetaxel induced neutropenia
 Major adverse effect of docetaxel, a major chemotherapeutic
in the treatment of NSCLC
 Exceptional pharmacodynamic results (decrease in
tumor blood flow)
 Single agent clinical benefit rate of 30% in solid
tumors
 Durable;
up to 2 years
 Impressive early signal in 2nd line NSCLC study
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Marine Technology Summit
November 16, 2010
Other low-hanging fruit for drug discovery from
marine microbiology
 Antiinfectives
 Major
antibiotic discovery effort ongoing at
SIO/UCSD
 Antifungals
 Antivirals
 Metabolic diseases, cardiovascular diseases
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Thank you!
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