BIOCRYST PHARMACEUTICALS INC - FORM 8-K - EX-99.2 - SLIDE PRESENTATION

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8-K - FORM 8-K - BIOCRYST PHARMACEUTICALS INC	d426793d8k.htm
EX-99.1 - PRESS RELEASE - BIOCRYST PHARMACEUTICALS INC	d426793dex991.htm

BioCryst & Presidio Merger

Overview

October 18, 2012

Exhibit

99.2

Disclaimer

Important Additional Information and Where to Find It

BioCryst Pharmaceuticals, Inc. (“BioCryst”) intends to file with the SEC a registration statement on Form S-4, which will also include a proxy statement and prospectus with respect to

the proposed acquisition of Presidio. The final proxy statement/prospectus will be mailed to the stockholders of BioCryst. Investors and security holders are urged to read the proxy

statement/prospectus regarding the proposed transaction carefully and in its entirety when it becomes available because it will contain important information regarding BioCryst,

Presidio and the proposed merger. Investors will be able to obtain a free copy of the proxy statement/prospectus, as well as other filings containing information about BioCryst,

without charge, at the SEC’s website (http://www.sec.gov/). Investors may also obtain these documents, without charge, from BioCryst’s website at

http://investor.shareholder.com/biocryst/sec.cfm.

This communication shall not constitute an offer to sell or the solicitation of an offer to buy any securities in the equity financing.

Participants in the Merger Solicitation

BioCryst and its directors, executive officers and other members of management and employees may be deemed to be participants in the solicitation of proxies from shareholders

with respect to the transactions contemplated by the merger agreement. Information regarding BioCryst’s directors and executive officers is contained in BioCryst’s 2011 Annual

Report on Form 10-K filed with the SEC on March 6, 2012 and its definitive proxy statement filed with the SEC on April 9, 2012 in connection with its 2012 meeting of stockholders.

Other information regarding the participants in the proxy solicitation and a description of their direct and indirect interests, by security holdings or otherwise, will be contained in the

proxy statement/prospectus and other relevant materials to be filed with the SEC when they become available.

BioCryst Forward-Looking Statements

This press release contains forward-looking statements, including statements regarding future results, performance or achievements. These statements involve known and unknown

risks, uncertainties and other factors which may cause BioCryst’s actual results, performance or achievements to be materially different from any future results, performances or

achievements expressed or implied by the forward-looking statements. These statements reflect our current views with respect to future events and are based on assumptions and

subject to risks and uncertainties. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Some of the factors that could affect the

forward-looking statements contained herein include: that the merger might not be completed for any number of reasons, most of which are outside of the control of BioCryst; that

BioCryst may not be able to obtain the requisite financing on commercially reasonable terms or that or that the financing may be raised at prices below the currently prevailing price

for BioCryst common stock; that integration of BioCryst and Presidio may prove more challenging than anticipated or that anticipated benefits of the merger may not be achieved, or

may be achieved less rapidly than anticipated; the outcome of any legal proceedings that may be instituted against BioCryst or Presidio; risks relating to any unforeseen liabilities,

future capital expenditures, revenues, expenses, earnings, economic performance, indebtedness, financial condition, losses and future prospects, business and management

strategies or the expansion and growth of Presidio’s operations; BioCryst’s ability to integrate Presidio’s business successfully after the closing of the merger agreement; and the risk

that disruptions from the merger agreement will harm BioCryst’s or Presidio’s businesses. There can be no assurance that the proposed merger and financing will in fact be

consummated. Other important factors include: that there can be no assurance that BioCryst’s or Presidio’s compounds will prove effective in clinical trials; that development and

commercialization of BioCryst’s or Presidio’s compounds may not be successful; that BARDA/HHS may further condition, reduce or eliminate future funding of the peramivir program;

that BioCryst, Presidio or licensees may not be able to enroll the required number of subjects in planned clinical trials of its product candidates and that such clinical trials may not be

successfully completed; that the companies or licensees may not commence as expected additional human clinical trials with product candidates; that the FDA may require additional

studies beyond the studies planned for product candidates or may not provide regulatory clearances which may result in delay of planned clinical trials, clinical hold with respect to

such product candidate or the lack of market approval for such product candidate; that ongoing and future preclinical and clinical development may not have positive results; that the

companies or licensees may not be able to continue future development of current and future development programs; that such development programs may never result in future

product, license or royalty payments being received; that the companies may not be able to retain their current pharmaceutical and biotechnology partners for further development

of its product candidates or may not reach favorable agreements with potential pharmaceutical and biotechnology partners for further development of product candidates; that their

actual cash burn rate may not be consistent with its expectations; that BioCryst or Presidio may not have sufficient cash to continue funding the development, manufacturing,

marketing or distribution of products and that additional funding, if necessary, may not be available at all or on terms acceptable to BioCryst or Presidio. Please refer to the

documents BioCryst files periodically with the Securities and Exchange Commission, specifically BioCryst's most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q,

and current reports on Form 8-K, all of which identify important factors that could cause the actual results to differ materially from those contained in BioCryst’s projections and

forward-looking statements.

Experienced

leadership

Near-term

milestones

Two pronged focus: high-value antivirals & orphan indications

Resourced to reach value

creating events

Three oral, pan-genotypic HCV molecules with distinct MOAs

First oral prophylactic would revolutionize HAE treatment

Peramivir & ulodesine programs have potential to contribute non-dilutive capital

Planned $60 million financing to reach potential value creating events for HCV & HAE

HCV

Unique

portfolio

HAE

Revolutionary

treatment

Transaction overview & capitalization plan

•

All Presidio assets

•

$25M cash committed from Presidio

shareholders

•

24.5M BCRX shares valued at $101M

Minimum $60 million equity financing required as a closing condition

Includes $25 million committed by Presidio shareholders

Transaction & financing close expected 1Q13

Headquarters in Durham, NC with sites in San Francisco, CA & Birmingham, AL

NewCo to launch with a new name and ticker at closing

Hepatitis industry leaders joining an established leadership team

Nathaniel

Brown,

MD,

Chief

Medical

Officer,

Presidio

Former EVP Clinical Development & CMO, Idenix Pharmaceuticals;

Head of Hepatitis Section, Infectious Disease, GlaxoWellcome/GSK

23 years of experience in antiviral/antiinfective development U.S. & global

Clinical development leader for globally registered antivirals/antiinfectives:

HCV -

Wellferon (interferon alfa-n1)

Pneumocystis pneumonia -

Mepron (atovaquone)

HBV -

Epivir-HBV (lamivudine)

Varicella -

Zovirax (acyclovir)

HBV -

Tyzeka (telbivudine)

HIV -

Retrovir (zidovudine) for children

HIV -

Reyataz (atazanavir),

protease inhibitor

HBV -

Baraclude (entecavir),

polymerase inhibitor

Richard

Colonno,

PhD,

Chief

Scientific

Officer,

Presidio

Former VP Infectious Diseases Drug Discovery, Bristol-Myers Squibb;

Senior Director, Merck Research Labs

Internationally

recognized

expert

the

areas

antiviral

drug

discovery

viral

resistance, with over 30 years of pharmaceutical industry experience

Key leadership role in advancement & global approval of important antivirals:

Experienced governance & HCV investors: Board nominees

Presidio nominees to Board

Srinivas Akkaraju, MD, PhD

Managing Director, New Leaf Venture Partners

Felix

Baker,

PhD

Managing

Partner,

Baker

Bros.

Advisors

Kenneth

Galbraith

General

Partner,

Ventures

West

Capital

BioCryst nominees to Board

George Abercrombie

Former President & CEO, Hoffmann-La Roche

Fred Cohen, MD, D.Phil

Partner & Managing Director, TPG Biotech

Nancy Hutson, PhD

Former Senior Vice President of Global R&D, Pfizer

Peder

Jensen,

Former

SVP/GM,

R&D

Japan/Asia/Pacific,

Schering-Plough

Kenneth

Lee,

Jr.

General

Partner,

Hatteras

Venture

Partners

Jon

Stonehouse

President

CEO,

BioCryst

Pharmaceuticals

Jon Stonehouse will be CEO & Kenneth Galbraith will be Board Chairman

Hepatitis C Portfolio Overview

Opportunity for unique, all-oral, pan-genotypic combinations

HCV Mechanism of Action

Preclinical

Phase 1

Status

NS5A inhibitor

Ph 2 ready

Nucleoside NS5B inhibitor

Ph 1 ready 4Q12

Non-nucleoside NS5B inhibitor

Ph 1 ready 1H13

PPI-668

BCX5191

PPI-668

PPI-383

PPI-668

BCX5191

PPI-383

PPI-668

PPI-383

BCX5191

Strategy:

Build

HCV

combination

therapies

around

lead

NS5A

compound,

PPI-668

Aggressively pursue external collaborations to identify optimal regimens

Opportunity to address significant HCV market segments:

Pan-genotypic & genotype-specific combination therapies

Regional opportunities

Patient subpopulations

NS5A inhibitor: Potential foundation for curative combinations

BCX5191

and/or

PPI-383

Additional

DAAs from

external

sources

Internal

combinations

Internal/external

combinations

PPI-668

PPI-668 is an “optimized”

NS5A inhibitor

Oral, QD dosing in humans

Pan-genotypic coverage of all

major HCV genotypes

–

Equivalent to daclatasvir (BMS-052)

Additive to synergistic with other

classes of HCV antivirals, no

antagonism noted

Excellent safety profile in 3-month

animal studies & well tolerated in

human trials

PK profile results in strong clinical

potency & coverage of pre-existing

resistant variants

HCV Genotype

0.01

0.1

PPI-668

BMS-052

Completed single & multi-dose

administration (40-320 mg once daily)

All doses generally safe & well

tolerated

PK results support once-daily dosing

Rapid (2 hr) attainment of high plasma

levels (C

max

2-7 µM), with first dose

Excellent trough coverage (60-415 nM),

exceeds the EC for all HCV genotypes

Dose-proportional systemic exposures

No significant food effect

Efficacy implications

Rapid efficacy starting with first dose

against WT & resistant variants harboring

single amino acid substitutions

Hours Post Dosing

Rapid tissue distribution

(liver and other tissues)

Prolonged

-phase half-life,

maintains inhibitory levels

Favorable PPI-668 pharmacokinetic (PK) profile –

Phase 1a results

Micromolar blood levels within 2 hr,

for rapid HCV inhibition

1000

2000

3000

4000

5000

6000

80 mg

160 mg

320 mg

PPI-668: Optimal PK profile with once-daily dosing

Time Post Dosing (hr)

Only C

24 hr

PK time points examined

5-day once-daily oral

dosing @ 320 mg

Intensive PK sampling

after 1st & 5th doses;

trough levels (C

24hr

) on

other days

Steady

state

achieved

Day 2, no subsequent

accumulation or

induced elimination

No need for loading

dose

achieve

maximal

efficacy

100

1000

10000

100

110

120

Steady state

achieved

Dose 1

Dose 2

Dose 3

Dose 4

Dose 5

PPI-668 Phase 1b: POC & antiviral activity demonstrated

Phase 1b design

10 patients per dose cohort, randomized 8:2 (active : placebo)

40, 80, 160 or 240 mg QD x 3 days, with 14 days follow up

3-day dosing consistent with draft FDA HCV guidance

Dose group

Mean maximal HCV RNA

reduction,

3 days of treatment

40 mg/day

3.2 log

IU/mL

80 mg/day

3.5 log

IU/mL

160 mg/day

3.5 log

IU/mL

240 mg/day

3.7 log

IU/mL

Detailed results to be presented at AASLD

meeting November 9-13

Results

Well tolerated at all doses

Unsurpassed viral load reduction in

first 24-30 hr, indicating potent

antiviral activity

HCV RNA reductions typically

exceeded 3 log

during first day of

dosing

Coverage of resistant variants

demonstrated

Four patients with high levels of

pre-existing resistant variants (single

substitutions) responded well

Two complementary inhibitors of HCV NS5B polymerase

NS5B protein serves as the viral polymerase & is essential for HCV replication

•

Nuc Catalytic Site (A)

•

NNuc Binding Sites

–

Palm I (B)

–

Palm II (C)

–

Thumb I (D)

–

Thumb II (E)

•

Opportunity to

develop a superior

NNuc as a 3rd class of

oral, potent, pan-

genotypic agents

•

Opportunity to

develop highly

potent Nuc-based

combinations with a

high barrier to

resistance

Allosteric

non-nucleoside

inhibitor

PPI-383

Adenosine

nucleoside

inhibitor

BCX5191

PPI-383 (NNuc) exhibits pan-genotypic activity in replicon assays

HCV Genotype

NNucs currently in advanced

development are HCV GT-1 specific

PPI-383 distinct feature: near

equivalent coverage of HCV

genotypes tested

Additive to synergistic with other

classes of HCV antivirals

Favorable pharmacological profile:

Metabolic stability

No CYP inhibition

Low protein binding

Animal PK profile predictive of QD-

BID dosing in humans

PPI-383 is undergoing GLP toxicology studies to enable Phase 1 studies to initiate 1H13

10000

1000

100

PPI-383

VX-222

NS5B Enzyme

*Data from Lam et al 2010 AAC 54:3187-3196

BCX5191 (Nuc): Pan-genotypic at sub-micromolar concentrations

Adenosine nucleoside analog

Pan-genotypic coverage

Sub-micromolar potency on NS5B

Compares favorably with GS-7977

Favorable pharmacological profile:

Metabolic stability

No CYP inhibition

Parent drug plasma concentrations

track liver concentrations

Once-daily dosing

Preclinical PK predicts antiviral efficacy

at low daily doses

Initiation of Phase 1 trial program

planned for 4Q12

BCX5191

GS-7977

10000

1000

100

Hereditary Angioedema Overview

BCX4161 could be the first oral

prophylactic HAE therapy

Problems with current parenteral KK inhibitors:

IV infusions create a significant treatment burden

IV access maintenance

Risk of infection

SC injection reactions

Goals of BCX4161 development program:

Oral administration

Highly effective attack prevention

Safe

A safe, effective ORAL kallikrein inhibitor could revolutionize the lives of patients

with hereditary angioedema

Image

obtained

from

www.haeimages.com

used

with

permission

BCX4161 targets kallikrein, which is fully validated clinically in HAE

Factor XIIa

Plasmin

High-Molecular-Weight

Kininogen

Prekallikrein

Kallikrein

Bradykinin

Stop vasodilatation, nonvascular

smooth muscle contraction & edema

Trauma

BK receptor

Inhibit kallikrein activity

Prevent BK from binding receptors

Cinryze —

IV prophylaxis

Berinert —

IV acute therapy

Kalbitor —

SC acute therapy

BCX4161 —

Oral prophylaxis

Firazyr —

SC acute therapy

BCX4161 has demonstrated preclinical POC for oral dosing

Inhibition of kallikrein activity through 24 hours post-dose

PK of BCX4161 in rats –

30, 100 & 300 mg/kg oral dosing

Pharmacodynamics of BCX4161 in rats –

100 mg/kg oral dosing

50%

100000

10000

1000

100

Rat Kl

0.1

100

30 mg/kg

100 mg/kg

300 mg/kg

100

Time, hr

BCX4161 inhibits kallikrein

in human plasma

Median EC

~ 6 nM

BCX4161 at 50-100 nM maximally

inhibits kallikrein

Phase 1 trial will deliver:

Preliminary safety

PK from oral dosing

Degree of kallikrein inhibition

Dose selection for HAE patient trials

BCX4161 inhibits Kallikrein at very low doses

Inhibition of kallikrein in plasma from 51

normal subjects: EC

< 12 nM in all cases

Kallikrein inhibition assay will be used as a

PD biomarker in the clinical program to select effective doses

Biomarker assay developed to support clinical program

First clinical studies will determine pharmacokinetics & pharmacodynamics, as well as

BCX4161 profile for HAE: Entering Phase 1 4Q12

Profile

Results

Attractive preclinical pharmacology

profile

BCX4161 inhibits kallikrein in human plasma

Median EC50 ~ 6 nM

Preclinical POC for oral dosing

Nonclinical safety

IND-enabling program complete

Therapeutic window assessed

Doses selected for first clinical studies

likelihood of success

Pipeline with development focus on HCV & HAE

Disease

Program

Pre-IND

Phase 1

Phase 2

Pivotal

HCV

PPI-668

NS5A inhibitor

BCX5191

Nucleoside NS5B

PPI-383

Non-nucleoside NS5B

HAE

BCX4161

Oral kallikrein inhibitor

Other

Peramivir, i.v.

Outpatient, seasonal influenza

Peramivir, i.v.

Inpatient, influenza

Ulodesine, BCX4208

Gout

1. Peramivir is approved in Japan & Korea

Approved

Important near-term events support value creation

2012

2013

BCX5191 Phase 1 results

AASLD

BCX4161 Phase 1 results

Peramivir Phase 3

interim analysis

Complete merger

PPI-383 Phase 1 results

PPI-668 Phase 2a

combo results

EASL

AASLD

HAE events

Influenza events

HCV events

Business events

A well-capitalized HCV player with numerous value creating events

Experienced

leadership

Near-term

milestones

Attractive assets

Resourced to reach value

creating events

HCV

Unique

portfolio

HAE

Revolutionary

treatment

NewCo

Shareholder value

Attached files

BIOCRYST PHARMACEUTICALS INC Reports

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