Amendment 5 Preproposal Presentation 5 Aug.pdf

AMENDMENT TO BARDA BROAD AGENCY ANNOUNCEMENT

ADVANCED DEVELOPMENT OF CHEMICAL, BIOLOGICAL,

RADIOLOGICAL, AND NUCLEAR MEDICAL COUNTERMEASURES

Broad Agency Announcement Number: BAA-BARDA-09-34

Amendment Number: Five (5)

Amendment Posting Date: August 20, 2009

Issued By: Biomedical Advanced Research and

Development Authority (BARDA) 330 Independence Ave., SW, Room G640 Washington, D.C. 20201

Point of Contact: Primary: Glynis Fisher, Contract Officer glynis.fisher@hhs.gov

Alternate: Jeannett Jackman, Contract Specialist jeannett.jackman@hhs.gov

SUMMARY OF CHANGES

A. PURPOSE: The purpose of this amendment is to post the Pre-Proposal Conference Presentation held August 5, 2009 at BARDA.

(1) The date for receipt of white papers under these special instructions remains August 31, 2009.

(2) The Broad Agency Announcement (BAA) date specified for receipt of proposals remains unchanged. Except as provided herein, all terms and conditions of the BAA remain unchanged.

mailto:glynis.fisher@hhs.gov mailto:jeannett.jackman@hhs.gov

CBRN MCM Development “Rolling” BAA BARDA-09-34

Amendment #4 Special Instructions - Cutaneous and

Pulmonary Injury from Ionizing Radiation

Pre-Proposal Conference August 5, 2009

John Esker, Ph.D.

Project Officer, Branch of CRN Countermeasures

Presenter� Presentation Notes� Amendment #4 Posted Date June 30, 2009 Questions were due July 15 White Papers Due Aug 31.

ASPR

Agenda

1. 9:00 Welcome and Introductions

2. 9:15 Overview of BAA Process

3. 9:45 Answers to Questions submitted

4. 10:00 Break (5-10 minutes)

5. 10:15 Open discussion

6. 11:00 Adjourn

HHS Organization (Role in BioDefense)

Office of the Secretary

ATSDR

FDA

HRSA

IHS

NIH

SAMHSA

ACF

AoA

CMS

AHRQ

CDC

ASAM

PSC

ASBTF

ASPE

ASPR

ASL

ASPA

ASH GC

OMHA

OCR

CFCI

IG

DAB

OGHA

ONCHIT

Presenter� Presentation Notes� Mary – the official acronym for our department is HHS. They dropped the “D” when the Dept of Homeland Security stood up.

ASH – Assistant Secretary for Health ASAM – Assistant Secretary for Admin and Management PSC – Program Support Center ASBTF – Assist Sec for Budget Technology and Finance

ASPE –

ASPR – Assist Sec for Preparedness and Response ASL – Assist Sec for Legislation ASPA – Assist Sec for Public Affairs

ACF

AHRQ –

CDC – Center for Disease Control FDA – Food and Drug Administration HRSA – Health Resources and Services Administration NIH – National Institutes of Health

ASPR Organization

ASPR

Biomedical Advanced Research

& Development Authority

Office of Medicine, Science, & Public Health

Office of Preparedness &

Emergency Operations

Immediate Office of the ASPR

Chem/Bio Rad/Nuc

(CBRN)

Pandemic Influenza

(PI)

OS

Anthrax Vaccines

Anthrax Therapeutics

Smallpox MCMs

Botulinum Antitoxins

Rad/Nuc and Chem Programs

BARDA manages advanced development and procurement programs for vaccines, drugs, therapeutics and diagnostics for CBRN threats and pandemic influenza

Programs are supported by:

Advanced Research and Development Appropriations Project BioShield Special Reserve Fund Pandemic Influenza appropriations

Biomedical Advanced Research and Development Authority (BARDA)

The Pandemic and All-Hazards Preparedness Act

P.L. 109-417, Sec. 401 Establishes the Biomedical Advanced Research and Development Authority (BARDA)

Facilitate collaboration among USG, industry, and academia Support the advanced research and development of MCMs Promote innovation to reduce time and cost of MCM

Establishes the Biodefense MCM Development Fund Fund development of products across so-called “Valley of Death” Authorizes (not appropriated) $1.07 billion for FY2006-2008

Reflects existing commitments in biodefense and pandemic flu initiatives Separate from the preexisting BioShield Special Reserve Fund

FDA to provide technical assistance to developers on manufacturing and regulatory processes if the Secretary determines that a shortage or potential shortage may occur of such a critical countermeasure Makes reforms to BioShield procurement program

Allows for milestone-based performance payments

IND NDA/BLA

PHASESPHASES

PR

O

D U

C T

PI

PE

LI

N

E

PR

O D

U C

T

PI

PE

LI

N E

Licensed Product

1 2 3 4 5 6A- B 6C 7 8 9

Advanced Research and Development Zone

TRLsTRLs

Discovery Phase I Phase II LicensurePhase IIIPreclinical Development

Production & Delivery

Sources: DiMasi, et al, 2007; PRTM Reports; Lehman Bros. & McKinsey 2001

PROBABILITY OF SUCCESS TO LICENSURE

1-3% 5 - 17% 10 - 25% 18 - 35% 45 – 70% 90%

3-7 yr 0.5-2 yr 1-2 yr 2-3.5 yr 2.5 -4 yr 1-2 yrs TIMETIME

$100M -130M $60-70M $70M-100M $130M-160M $190M-220M $18M-20MPIPELINEPIPELINE

PHASE COST*PHASE COST*

Presenter� Presentation Notes� Advanced Development of Medical Countermeasures entails many technical challenges- not only clinical trials in humans, but also the development of animal models and demonstration of efficacy using the Animal Rule, as well as process development and scale-up Industry benchmarks illustrate that MCM development takes time, is expensive, and incorporates significant technical risks.

For instance:

Of a group of five candidate products in Phase I at the start of Advanced Development, only one of them would be expected to successfully complete the development process and achieve licensure.

That successful product will have cost $570 to $700M in out of pocket costs to a company, including investments in unsuccessful candidates (attrition) Project BioShield funding is structured for procuring products Without adequate funding to also develop products, BARDA has been left having to pick winners early in hopes that they will achieve licensure.�

Early/Advanced Product formulation Pilot lot production Animal rule correlates IND enabling studies Phase I/II clinical trials Animal efficacy models

End-Stage Commercial scale process development

Facility validation EUA-enabling studies Large scale safety trials Animal rule efficacy studies BLA/NDA filing activities

Applied Target ID/validation Assay development In vitro screening Medicinal chemistry Animal model development

Basic Applied Product Development Acquisition

USG Funded Product Development Activities

NIH Activities BARDA Activities

ARD BioShield

Early Advanced End-StageBasic Microbiology Immunology Pathogenesis

Presenter� Presentation Notes� ARD - Advanced Research and Development Bio Shield - Project BioShield Special Reserve Fund

Need careful attention that Development is sufficiently developed before it enters under BARDA activities NIH can funds early research in Technical Readiness levels 1-4 Acquisitions under BioShield Special Reserve Fund Advanced Research and Development appropriations carries studies inbetween.�

CBRN BAA Team

Project Officers Mary Homer John Esker Ron Manning

Contracting Officers Glynis Fisher Jeannett Jackman

Presenter� Presentation Notes� Points of contact in BARDA�

CBRN Broad Agency Announcement Process Overview

The BARDA CBRN BAA – a two stage process

Stage I:

Adds the white paper/quad chart stage and means that offerors only have to submit a brief technical paper (5 – 15 pages) rather than the full proposal

The white paper/quad chart will be reviewed for scientific and technical viability and BARDA will provide feedback on your white paper within 90 days of submission

Reduced initial investment of resources

More opportunity for interaction with BARDA prior to submission of proposals

The BARDA CBRN BAA –

Stage II:

BARDA will invite offerors to submit a full proposal provided their white paper/quad chart are scientifically and technically sound

The primary basis for selecting proposals for acceptance shall be:

Program Relevance to the BARDA mission Scientific and Technical Merit Capabilities and Related Experience Funding availability

Open continuously through 12/31/2009

Purpose of the BAA

Identify innovative and promising technologies for advanced development across CBRN Research Areas of Interest, focusing on Technology Readiness Levels 6 to 7 (Pre-IND to Phase 2) #1 Vaccines #2 Antitoxins and Therapeutics #3 Antimicrobial Drugs #4 Radiological/Nuclear Threat Countermeasures #5 Chemical Threat Countermeasures #6 Clinical Diagnostic Tools

Presenter� Presentation Notes� Accelerate and Improve Solicitations

Reduce up-front planning and document review by creating unified advanced development solicitation Standardize common deliverables across research areas of interest, and internal review processes Provide flexibility to accommodate range of contract awards (type, scope, number) in one vehicle

Purpose of the BAA

Accelerate contract awards with a flexible solicitation

Build a sustainable advanced development program to meet PHEMCE implementation plan goals and generate a pipeline of mature MCM candidates for Project BioShield acquisition

Presenter� Presentation Notes� Accelerate and Improve Solicitations

Reduce up-front planning and document review by creating unified advanced development solicitation Standardize common deliverables across research areas of interest, and internal review processes Provide flexibility to accommodate range of contract awards (type, scope, number) in one vehicle

BAA Process Flow Chart

Cat II Scientifically & technically sound proposals that may require further development. May be recommended for acceptance subject to funds availability.

Cat III Proposals not technically sound or do not meet agency needs.

Not acceptable for funding.

Cat I Well conceived scientifically & technically sound proposals important to program objectives. Recommended for approval subject to funds availability.

Within 90 days

Within 270 days

Presenter� Presentation Notes� Quad Chart and White Paper should describe the effort in sufficient detail to allow evaluation of the concept's technical merit and its potential contribution to the BARDA mission. Offerors whose Quad Chart and White Paper receive a favorable evaluation will be invited to submit a Full Proposal. Offerors whose Quad Chart and White Paper did not receive a favorable evaluation will be notified by email.

Special Instructions

May be issued periodically under the rolling BAA Published as an Amendment to the BAA (Amendment #4 to BARDA-09-34)

Posting Date (June 30, 2009) Pre-Proposal Date (August 5, 2009) White Paper and Quad

Chart submission Date (August, 31, 2009 Closing Date (December 31, 2009)

Purpose: To specifically solicit solutions in a particular area of interest

Special Instructions in Amendment #4

Objective: - to focused on development of Medical Countermeasures to Mitigate and Treat Cutaneous and/or Pulmonary Injury Resulting from Exposure to Ionizing Radiation

Presenter� Presentation Notes� Ionizing Radiation only – Not thermal, Microwave, UV and other Non-ionizing sources of radiation�

Cutaneous Injury - Overview

Prodromal stage (within hours of exposure) — This stage is characterized by early erythema (first wave of erythema), heat sensations, and itching that define the exposure area. The duration of this stage is from 1 to 2 days.

Latent stage (1–2 days post-exposure) — No injury is evident.

Depending on the body part, the larger the dose, the shorter this period will last. The skin of the face, chest, and neck will have a shorter latent stage than will the skin of the palms of the hands or the soles of the feet.

Presenter� Presentation Notes� stages Pro-drōm-al er-uh-thee-muh

Cutaneous Injury - Overview

Manifest illness stage (days to weeks post-exposure) — The basal layer is repopulated through proliferation of surviving clonogenic cells. This stage begins with main erythema (second wave), a sense of heat, and slight edema, which are often accompanied by increased pigmentation.

Third wave of erythema (10–16 weeks post-exposure, esp. post beta-IR) — The exposed person experiences late erythema, injury to blood vessels, edema, and increasing pain.

Presenter� Presentation Notes� 4 stages Pro-drōm-al er-uh-thee-muh

Cutaneous Injury - Overview

Late effects Stage (months to years post-exposure; threshold dose ~10 Gy) — Symptoms can vary from slight dermal atrophy (or thinning of dermis layer) to constant ulcer recurrence, dermal necrosis, and deformity.

Possible effects include:

• Occlusion of small blood vessels with subsequent disturbances in the blood supply (telangiectasia)

• Destruction of the lymphatic network

• Regional lymphostasis; and increasing invasive fibrosis, keratosis, vasculitis, and subcutaneous sclerosis of the connective tissue

• Pigmentary changes and pain are often present

• Skin cancer is possible in subsequent years

Recovery (months to years)

Pulmonary Injury from IR:

Timeline for Pneumonitis and Fibrosis

Early events (2 - 4 months) Pneumonitis/alveolitis Inflammation, reduced lung capacity

Late events (6+ months) Fibrosis Scarring, reduced lung capacity

From: Hopewell et al, 2000From: Hopewell et al, 2000 mice – >20%↑ b.r.

mice - death 40-196 days

Lung IR Sensitivity Pneumonitis ED50

Pulmonary Injury:

IR Sensitivity

ED50 (single dose):

MouseMouse 1111--15 Gy15 Gy RatRat 1010--15 Gy15 Gy PigPig 88--10 Gy10 Gy HumanHuman ~10 Gy ~10 Gy (estimated)(estimated) DogDog 1010--11 Gy 11 Gy (estimated)(estimated) human - pneumonitis pig - pneumonitis

Note the steepness of these curves!

rats – death @40-196 days

CBRN Broad Agency Announcement

Questions and Answers

Please hold new questions until the open discussion section

Open discussion

CBRN BAA Pre-Proposal Conference