click to edit master title style leader in antiviral drug development stifel 2015 healthcare...
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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)
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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
100 mg vapendavir bid
25 mg vapendavir bid
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
400 mg vapendavir bid
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
264 mg vapendavir bid
528 mg vapendavir bid
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.
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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
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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
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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
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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
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