click to edit master title style leader in antiviral drug development stifel 2015 healthcare...

Click to edit Master title style

Leader in Antiviral Drug Development

STIFEL 2015 Healthcare Conference

Click to edit Master title styleSafe Harbor

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This presentation contains forward-looking statements about Biota Pharmaceuticals, Inc. and its business, business prospects, strategy and plans, including but not limited to statements regarding anticipated preclinical and clinical drug development activities and timelines and market opportunities. All statements other than statements of historical facts included in this presentation are forward looking statements. The words “anticipates,” “may,” “can,” “plans,” “believes,” “estimates,” “expects,” “projects,” “intends,” “likely,” “will,” “should,” “to be,” and any similar expressions or other words of similar meaning are intended to identify those assertions as forward-looking statements. These forward-looking statements involve substantial risks and uncertainties that could cause actual results to differ materially from those anticipated. Factors that may cause actual results to differ materially from such forward-looking statements include those identified under the caption “Risk Factors” in the documents filed by Biota Pharmaceuticals with the Securities and Exchange Commission from time to time, including its Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this presentation. Except to the extent required by applicable law or regulation, Biota Pharmaceuticals undertakes no obligation to update the forward-looking statements included in this presentation to reflect subsequent events or circumstances.


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Biota Pharmaceuticals Overview

Developing first-in-class direct-acting antivirals that have the potential to the change the treatment paradigm for infections with limited therapeutic options

Four clinical stage antiviral programs Special emphasis on respiratory viral infections Multiple Phase 2 data readouts in the next 12 months

Well-financed and two royalty streams that help facilitate execution of our strategic plan

Clinically-focused, data-driven and proven management team

Click to edit Master title styleAdvanced Antiviral Pipeline and Royalty Stream

Vapendavir (BTA798)Human rhinovirus (HRV)

BTA585 (Fusion protein inhibitor)

Human papillomavirus 6 & 11 (HPV)BTA074 (AP611074)

Respiratory syncytial virus (RSV)

Laninamivir Octanoate (LANI) ex-JapanInfluenza A & B

Zanamivir (Relenza®)1

Influenza A & B

Laninamivir Octanoate (Inavir®) Japan2

Influenza A & B

17-10% royalty on global net sales24% royalty on net sales in Japan

Preclinical Phase 1 Phase 2 Phase 3 MarketedCommercial

Partner

Non-fusion inhibitor programRespiratory syncytial virus (RSV)


Vapendavir

Click to edit Master title style Prevents release of viral RNA from capsid thereby blocking the initiation of a new

viral infectious cycle Broad spectrum picornavirus antiviral EC50 < 100 nM for ≈ 90% of HRV serotypes ≈ 10X more potent than pleconaril

Potential to develop first-in-field oral drug that specifically addresses HRV infections in at-risk populations

Moderate to severe asthmatics, COPD, pediatrics (asthma) and hematopoietic stem cell transplant recipients

HRV mediated respiratory infections are associated with worsening asthma symptoms, decline in lung function, and exacerbations

Multiple studies suggest that HRV infections associated with wheezing in children are strongly associated with the eventual development of asthma

Proof of principle established in Phase 2 HRV challenge study as well as in Phase 2 HRV natural infection study in mild asthma patients

Vapendavir – Potent Capsid Inhibitor

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Phase 2a HRV Challenge Trial Design

Study Population: Healthy male volunteers age 18-45 Design: Double-blind, placebo-controlled, randomized, parallel group

study Primary Efficacy Endpoint: To evaluate the efficacy of vapendavir in

preventing human rhinovirus 39 (HRV39) infection

400 mg vapendavir bid

Placebo bidn = 10 n = 11

Day -2 first dose

Day 6 last dose



Day 0 HRV Challenge

n = 10

n = 10


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Vapendavir - Antiviral Proof-of-Concept

AU

C P

CR

Day

s 1-

6(l

og

10T

CID

50.d

ays/

mL

)

Place

bo

25 m

g

100

mg

400

mg

0

2

4

6

8

Dose-depenent Decrease in HRV39 Viral Load

Vapendavir

P=0.01

Per

cen

t H

RV

39

Cu

ltu

re P

os

itiv

e (D

ays

1-6

)

Place

bo

25 m

g

100

mg

400

mg

0

20

40

60

80

100

Dose-depenent Reduction in HRV39 Positive Subjects

Vapendavir


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Phase 2 Rhino Trial Design

Study Population: Mild adult asthmatics with symptomatic HRV infection

Design: Multi-center, randomized, double-blind, placebo-controlled study

Primary Efficacy Endpoint: Daily change in Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21) severity score over days 2 through 4


Placebo bidn = 42n = 51

HRV(+)Day 1

first doseDay 6

last doseDay 14

Daily WURSS-21 scoring ACQ-5

Total Randomized

Screening -90 days

n = 155

n = 145


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Primary Efficacy Results: Statistically significant reduction in the mean daily change in WURSS-21 severity score over days 2 through 4 for vapendavir treated cohort compared to placebo (ITT-I observed p=0.046; ITT-I imputed p=0.02)

Secondary Efficacy Results: Mean daily change for the vapendavir treated cohort compared to placebo for days 2-5

(ITT-1; p=0.001) and days 2-14 (ITT-I; p=0.001) Daily 2 agonist use (# of puffs) over days 1-14 reduced in the vapendavir treated cohort

vs placebo (ITT-I; p=0.09) Reduction in the least square mean difference in asthma control questionnaire (ACQ-5)

score at day 14; vapendavir (0.94) vs placebo (1.24) (ITT-I; p=0.10) Safety Results: Favorable safety profile among 263 unique subjects. The most

common AE was headache (≤5%). No serious adverse events were reported.

Positive Phase 2 Rhino Results


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Phase 2b SPIRITUS Trial Design - Ongoing Study Population: Moderate-to-severe adult asthmatics with symptomatic HRV infection

and a history of asthma worsening or exacerbation with colds Design: Multi-center, randomized, double-blind, placebo-controlled dose-ranging study Primary Efficacy Endpoint: Least Square mean change from baseline to study day 14 in

ACQ-6 total score (80% power to detect a 0.5 change in ACQ-6) Key Secondary Endpoints: FEV1, forced vital capacity, daily 2-agonist use, and the

incidence of moderate and severe exacerbations Data: 2H 2016



Placebo bid

n ≈ 61

HRV(+)

Day 1 first dose

ACQ-6

Day 7 last dose

ACQ-6

Day 14 ACQ-6

Day 28ACQ-6

last study day

Day 21ACQ-6

dosingPatient screening -120 days

n ≈ 61

n ≈ 61


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Impact on the Loss of Asthma Control

0% 10% 20% 30% 40% 50% 60%

1%

6%

12%

8%

32%

30%

3%

8%

13%

11%

40%

40%

10%

17%

19%

21%

51%

57%

Severe

Moderate

Mild

Hospitalization*

Ever Intubated

Missed ≥1 Day Schoolor Work†

Emergency Department Visit*

Unscheduled OfficeVisit*

Steroid Burst

*In past 3 months†In past 2 weeks

Data from Dolan CM, et al. Ann Allergy Asthma Immunol. 2004;92:32-39.


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Treatment of HRV Infections in High Risk Patients Represents a Significant Revenue Opportunity

20202021

20222023

20242025

20262027

20282029

20302031

20322033

20342035

20360.00

200.00

400.00

600.00

800.00

1,000.00

1,200.00

1,400.00

1,600.00

Adult Moderate - Severe Asthma Pediatric Moderate - Severe AsthmaModerate - Severe COPD

U.S

. Rev

enue

bi

llion

s ($)

Forecast Assumptions1

U.S. only Patients at increased risk:

6.7 M moderate asthmatics

3.8M severe asthmatics 10.9 M COPD patients

Penetration rates 18-30%

1The forecasts and assumptions on this slide are from IMS Consulting Group and are estimates. Historical information is based on IMS’ research of primary and secondary market sources dating between 2008 and 2015. Forecasts are based on clinical/ regulatory timelines and certain other information provided by Biota. IMS expressly reserves all rights, including rights of copying, distribution and republication.


BTA585RSV Fusion Inhibitor


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RSV F Protein and Non-F Protein Inhibitor Program

Najjar, Viruses 2014, 6, 3019-3054

BTA585

Non-F targets


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Opportunity for Therapeutic Intervention

First symptoms

Peak symptoms

Peak viral load

Start of disease resolution &viral load reduction

Symptoms first appear about 2 days before peak RSV viral load

Peak symptoms occur 1 day before peak RSV viral load

RSV viral load drives disease RSV viral load remains high for 2-3

days ≈ 3 day treatment window to

provide therapeutic antiviral

* DeVincenzo et al (2010) Am J Respir Crit Care Med Vol 182. p1305-1314


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Significant U.S. Market Opportunity to Treat Acute RSV Infections

1 https://www.census.gov/population/projections/data/national/2014/summarytables.html; 2 2006 DataMonitor Stakeholders Opinions: RSV Infection3 http://bloodcell.transplant.hrsa.gov/about/general_faqs/index.html#1990 number tx in US

RSV Infected

≈ 9 million patients

Children <5 years of age 1,2

≈ 20M

Adults > 65 years of age 1,2

≈ 48M

Bone marrow & Umbilical transplants 3

≈ 18,000

Adults with underlying pulmonary or cardiac disease 1,2

≈29M


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BTA585 Achieves Antiviral Levels in Non-Human Primates

Plasma

Time (Hr)

BT

A58

5 (n

g/m

L)

Mea

n

S.D

.

0 4 8 12 16 20 241

10

100

1000

10000

100000

25 mg/kg

75 mg/kg

150 mg/kg

Oral DoseBTA585

in vitro EC50

Lung Epithelial Lining Fluid (ELF)

Time (Hr)

BT

A58

5 (n

g/m

L)

Mea

n

S.D

.

0 4 8 12 16 20 241

10

100

1000

10000

100000

1000000

25 mg/kg

75 mg/kg

150 mg/kg

Oral DoseBTA585

in vitro EC50

Click to edit Master title style Cotton rats inoculated intranasally with 104 pfu RSV A/Long Compounds orally dosed @ 25, 50, 100, 200 mg/kg Lungs harvested at peak infection - 4 days

Results 0.7 – 1.7 log reduction of virus titres at 25-200 mg/kg by plaque assay 1.0 – 2.8 log reduction 25-200 mg/kg by qPCR

BTA-C585 Demonstrated Robust Antiviral Activity in Preclinical Model of RSV Infection

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Click to edit Master title style Single oral dose in healthy volunteers (18 to 60 years)

10 subjects per dosing cohort (7 active, 3 placebo) Objectives are safety and pharmacokinetics

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Phase 1 Single Ascending Dose Trial - Ongoing

50 mg BTA585

100 mg BTA585

200 mg BTA585

400 mg BTA585

500 mg BTA585

Fasted dosing

100 mg BTA585Fed dosing Completed

Completed

Completed

Completed

Completed

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRxqFQoTCMn9wp2ug8cCFckcPgodbPABag&url=http://www.hellotrade.com/capella-enterprises/product.html&ei=Wly6VcnoEcm5-AHs4IfQBg&bvm=bv.99028883,d.cWw&psig=AFQjCNEKS7MsdbXU8-PaZr508lc90uQcRw&ust=1438363068884463


BTA074 (AP611074)Human Papillomavirus (HPV)

E1/E2 Protein-Protein Inhibitor


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BTA074 (AP611074) – first-in-class direct-acting antiviral for the treatment of HPV 6 & 11 infections Current topical therapies have suboptimal efficacy and exhibit significant local skin

toxicities Reoccurrence rates with current therapies >20%

Condyloma (anogenital warts) Most common sexually transmitted disease in the United States CDC estimates that there 79 million infected persons and approximately 14 million new

HPV infections occur annually in the U.S. Recurrent respiratory papillomatosis (RRP)

No known cure for this rare orphan disease Incidence of RRP ranges from 1.8 to 4.3 per 100,000 for adults and children, respectively Estimated that 15,000 surgical procedures are performed per year in the U.S., at a total

cost of $150 million, and lifetime costs per individual patient can reach up to $470,000

BTA074 – HPV Direct Acting Antiviral


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Topical Treatment of BTA074 Exceeds Antiviral Levels at Site of Viral Replication

Topically applied BTA074 5% gel penetrates to the basal layer of the epidermis Site of HPV reservoir and infection

Low systemic exposure and no plasma drug accumulation

High local concentration at the target site of viral replication (30 – 60X the IC50)

E2

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRxqFQoTCLaS6b_btccCFUEZPgodJG8CKA&url=http://www.medscape.com/viewarticle/732740_3&ei=tMLUVbboLMGy-AGk3onAAg&bvm=bv.99804247,d.cWw&psig=AFQjCNGr1BvPjQhdy6Jmj3q_FvkRVpD-Yw&ust=1440093184859289


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Phase 2a BTA074 Trial Study Population: Adult condyloma (anogenital warts) patients Design: Multi-center, randomized, double-blind, placebo-controlled Primary Objectives: Safety, tolerability, and partial or total clearance of baseline anogenital

wart lesions at end of treatment (EOT) Dosing: twice daily for 6 weeks

BTA074 5% gel

Placebo gel

n = 16

Week 0 Week 6EOT

n = 8

Dosing period

Assessment at End of Treatment BTA074 5% gel Placebo gel

Complete Clearance 13% (2/16) 25% (2/8)*

Partial Clearance >0 to <100 % 44% (7/16) 13% (1/8)

Overall Response Rate 56% (9/16) 38% (3/8)

Percent Reduction in Total Condyloma Area (mm2) 38% +123%

*Placebo clearance rates of <5% at 6 weeks were observed in Zyclara® and Veregen® Phase 3 pivotal trials in patients with anogenital warts

Efficacy Results:

Week 6EOS



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BTA074 Exhibited a Favorable Local Skin Tolerability

Erosions and Ulcerations

Edema Erythema0

10

20

30

40

50

60

70

80

90

100

Aldara® - 5% imiquimod cream

Zylcara® - 3.75% im-iquimod cream

Veregen® - 15% sinecatechins

BTA074 - 5% gelPerc

ent o

f Pati

ents


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Phase 2 BTA074 Trial - Planned Study Population: Adult condyloma (anogenital warts) patients Design: Multi-center, randomized, double-blind, placebo-controlled Primary Objective: Pharmacokinetics, safety and tolerability with special focus

on local skin reactions Secondary Objective (efficacy): Complete clearance of baseline anogenital warts

at end of treatment (EOT) Dosing: twice daily for up to 16 weeks Timing: Planned start 1Q 2016

BTA074 5% gel

Placebo gel

n ≈ 140

Week 0 Week 16EOT

Week 28End of Study

n ≈ 70

Follow-period for reoccurrenceDosing periodPatient Screening weeks 1-4



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Significant Condyloma Market Opportunity

8 million potential patients in the seven major markets and advanced economies by 2018

Advanced economies include Canada, Denmark, Finland, Netherlands, Norway, Sweden, Switzerland, Australia, Austria, Belgium, Ireland, New Zealand, Portugal, Greece, Israel, Singapore, Slovenia, South Korea

U.S.; 2,472,108

Japan; 1,013,932

Germany; 648,628

France; 502,164

Italy, 478,632

Spain; 365,948

UK, 490,000

Advanced Economies; 1,863,767

Potential patients assumption = 1 new patient and 1 recurrent patient; 0.37% incidence of new condyloma cases


Laninamivir Octanoate

Long-Acting Neuraminidase Inhibitor (LANI)


Click to edit Master title styleLaninamivir Octanoate (LANI) Overview

Potent inhibitor of influenza neuraminidases and associated viruses including highly pathogenic avian influenza “One and done” inhaled antiviral Active against clinically relevant oseltamivir and peramivir resistant viruses (H1N1;

H275Y) Daiichi-Sankyo markets Inavir® (LANI) for the treatment and prevention of

influenza A & B in Japan Favorable profile has resulted in Inavir® becoming the market leading neuraminidase

inhibitor in Japan 2014 sales were 16.6 billion yen (≈$135M USD) Biota receives a 4% royalty on net sales

Biota and Daiichi-Sankyo are jointly exploring third-party partnering opportunities for the development of LANI outside of Japan

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Multiple Value Creating Events in 2015 - 20162015Q3

2015 Q4

2016 Q1

2016 Q2

2016 Q3

2016 Q4

Vapendavir (HRV)

Phase 2b SPIRITUS trial top-line data

Initiate Phase 1 bioavailability trial

BTA074 (HPV)Initiate Phase 2 trial for condyloma

Phase 2 top-line data

BTA585 fusion inhibitor (RSV)Initiate Phase 1 SAD trial

Phase 1 SAD top-line data

Initiate Phase 1 MAD trial

Phase 1 MAD top-line data

Initiate Phase 2 RSV challenge study

Phase 2 challenge study top-line data

Non-fusion inhibitor program (RSV)Initiate IND-enabling studies


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Financial Strength for Effective Execution

NASDAQ Symbol BOTA

Commons Shares Outstanding (primary) 38.6 M

Cash, short and long term investments $66.3 M

September 30, 2015


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Investment Summary Robust clinical stage pipeline of four product candidates addressing

viral infections with substantial unmet need that impact large populations

Three Phase 2 clinical trial data readouts anticipated in 2016 Vapendavir Phase 2b SPIRITUS trial

BTA585 Phase 2a RSV challenge trial

BTA074 Phase 2 HPV condyloma trial

Clinically-focused, data-driven and proven management team Well-financed with two royalty streams that help facilitate execution of

our strategic plan

click to edit master title style leader in antiviral drug development stifel 2015 healthcare...

Documents

forwardlooking statements

statements of historical

royalty streams

hrv infections

quarterly reports

current reports

annual reports

actual results