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Development of a New Treatment for Anthraxin Partnership with DoD and HHS

Jeremy MiddletonVP Corporate Development

1

Anthim®(obiltoxaximab)

• STARTING IN 2002, Elusys developed Anthim® (obiltoxaximab), a monoclonal anthrax antibody antitoxin in partnership with the US government

• $240M in funding from HHS, DoD and NIAID contracts to support Anthimdevelopment over 13 years

• $45M procurement contract in November 2015 to manufacture Anthimfor the US Strategic National Stockpile

• FDA licensure March 18, 2016

2

2001 Anthrax Attacks

3

Bioterrorism Threats

Category A Priority Pathogens:

• Bacillus anthracis (anthrax)• Clostridium botulinum toxin (botulism)• Yersinia pestis (plague)• Variola major (smallpox) and other related pox viruses• Francisella tularensis (tularemia)• Viral hemorrhagic fevers

• Arenaviruses • Junin, Machupo, Guanarito, Chapare, Lassa, Lujo

• Bunyaviruses• Hantaviruses causing Hanta Pulmonary syndrome, Rift Valley Fever, Crimean Congo Hemorrhagic

Fever

• Flaviviruses• Dengue

• Filoviruses• Ebola• Marburg

NIAID

Early-stage researchPre-clinical work on

novel drugs & vaccines

$1.35B

BARDA

Advanced developmentPhase II-III studies of

promising MCMs

$511M

BioShield

SRF

Stockpile procurementProcurement of MCMs not

approved by FDA

$510M

SNS

Stockpile maintenanceProcurement of FDA-approved

MCM products

$575M

HHS Medical Countermeasure Development Pathway

DOD also works with industry to develop MCMs for some of these same threats, with a focus on the needs of the warfighter

*Funding figures reflect FY16 Omnibus level

DHS

Threat determinationGov’t determines threat, asks industry

to develop MCMs to protect public

ASPR

FDA

Industry

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Elusys Contract Awards

2009 2010 2011 2012 2013 2014 20152008 201620072006200520042003

R&D$7.8 MDoD

R&D$1.4 MDoD

R&D$1 MDoD

R&D$1 MDoD

R&D$1 MDoD

R&D$1.3 MNIAID

R&D$5 MNIAID

R&D$4.4 MNIAID

R&D$14 MNIAID/BARDA

Advanced Development$143 MBARDA

Advanced Development$69 MBARDA

$45 MDeliveryOrderDepartment of Defense

NIAID

BARDA

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Anthim Development Timeline

2009 2010 2011 2012 2013 2014 20152008 201620072006200520042003

PEP animal studies

Cell linedevelopment

NIAIDcontract

1st ARDcontract

2nd ARDcontract

Begin BLAwriting

Pivotalsafetystudy

BLAsubmitted

FDA licensure

Manufacturingvalidation

Pivotalanimal studies

Assayvalidation

1st primate study

1st treatment rabbit study

1st human safety

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SNS Inventory ShortfallD

ose

s

Stockpiling Target

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BioShield SRF Funding Shortfall $2.8B Authorized by Congress over FY14-FY18

Only $1.02B (36%) appropriated

Slide courtesy of The Alliance for Biosecurity

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Development Considerations

Targeted – “One Drug – One Bug”e.g. • Vaccines• Monoclonal Antibodies

Broad Spectrum – “One Drug – Many Bugs” e.g.• Antibiotics• Antivirals

• Incremental R&D• Predictable Development Path• Lower Risk• Dependent on Single Purchaser

(usually US Government)

• Radical R&D• Unpredictable Development Path• Higher Risk• Commercial Potential (beyond USG)

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“Animal Rule” Challenges

• Understanding disease pathophysiology

• Demonstrating efficacy in well-characterized animal models

– FDA requires randomized double blind placebo controlled studies

• Pharmacokinetics and pharmacodynamics of the countermeasure

– Measuring drug and target antigen in:

• Infected animals

• Uninfected animals

• Uninfected humans

Predictive dose in infected humans

Interspecies Comparison on Inhalational Anthrax Disease Progression

0 1 42 53 6 7 108 119 12 13 14 15

Incubation Period Prodromal Stage Fulminant Stage

Anthrax

in Humans

TtT: Trigger to Treat; MTD: Median Time to Death1Based on BARDA sponsored Updated Statistical Meta-Analysis of Anthrax Therapeutic Studies dated February 22, 2013 (SN0120, April 10, 2013).

2Based on Holty et al. Ann Intern Med. 2006;144:270; 3Based on Inglesby et al. JAMA. 2002; 287: 2236; 4Based on Vasconcelos et al. Lab Invest. 2003; 83:1201;

5Based on Zaucha et al. Arch Pathol Lab Med. 1998; 122

Anthrax

in Primates94%1 mortality

if untreated

Anthrax

in Rabbits99.5%1 mortality

if untreated

MTD*TtT*SIBT

or PA-ECL

MTD*TtT*PA-ECL

days

97%2 mortality at

fulminant stage

200 LD501.2x107

spores4

LD50 est.

2.0x103 - 5.5x104

spores3

200 LD502.1x107

spores5

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Summary Thoughts

• Anthim licensure demonstrates value & success of industry and the USG working together to develop needed MCMs

– NIAID, DOD and BARDA Advanced Research and Development (ARD) awards have sustained the development of several important MCMs

• Procurement of Medical Countermeasures is not guaranteed!

• Development and FDA approval of Medical Countermeasures under the animal rule is complex time consuming but possible