Impact Report“25-year Review of Alpha-1 Research”

Mark Brantly, M.D.Scientific Director

Since its inception, the Alpha-1 Foundation has invested more than $81 million to support Alpha-1 Antitrypsin Deficiency

research and programs at 119 institutions in North America, Europe, the Middle East, and

Australia.

Research toward the Cure

Building the Scientific Infrastructure

Government

Alpha-1 Foundation Patient Centered Model

A1F Research investment includes:Research Grants (peer-reviewed)

• Investigator-initiated in-cycle research grants• Out-of-cycle solicited research grants (RFAs)• Matching grants (NIH, ATS, AASLD, ALA, ACCP, AARC, Alpha

One Foundation Ireland)

Scientific Infrastructure• Scientific Meetings and Conferences• DNA & Tissue Bank• Biomaterials Exchange• Research Registry• Foundation-sponsored Detection Programs• Clinical Resource Centers (CRCs)• Therapeutic Development Network (TDN)

Alpha-1 Research for a Cure

Alpha-1 Foundation-sponsoredScientific Conferences and Publications

33 Conferences19 GLS Critical Issues Workshops4 International Research Conferences6 Clinical Resource Center Forums1 International Investigator & Physician Forum6 Investigators’ Meetings

• Academia• Industry• NIH• FDA• Patients• Proceedings are published Publications in Peer-reviewed

journals

Publishing About Alpha-1 Antitrypsin Deficiency

AATD Related Publications by Year. Number of Publications about AATD published by yearbetween 1964 and 2020. Orange indicates publications including an Alpha-1 Foundation grantrecipient in the author list. All other publications about AATD are highlighted in blue.

Resources for Investigators

DNA & Tissue Bank:Over 2,300 donors

Alpha-1 Biomaterials Exchange:Open resource for both academia and industry that matches an investigator in need of biomaterial with an investigator willing to supply it

Alpha-1 Foundation Research RegistryWhat is the Alpha-1 Research Registry?

• Confidential database made up of individuals diagnosed with Alpha-1 Antitrypsin Deficiency (Alpha-1) and individuals identified as Alpha-1 carriers.

• Established to facilitate research initiatives and promote the development of improved treatments and a cure for Alpha-1.

• Located at the Alpha-1 Foundation, Miami, FL, the Registry employs procedures that ensure the most stringent confidentiality of participants.

• Operates under the direction of the Alpha-1 Foundation Board of Directors and is guided by an Advisory Committee comprised of leaders in the medical, ethical, scientific and Alpha communities.

• Registry enrollees have the ongoing opportunity to participate directly in clinical trials of new therapeutic approaches in addition to other research opportunities.

Alpha-1 Foundation Research Registry

• Result = Augmentation TherapyNIH

• University of MiamiA1F

• Medical University of South CarolinaA1F

• Miami office-Alpha-1 FoundationA1F

Research comes back to

the patients

Alpha-1 Foundation Research Registry

How do I enroll in the Registry? Simply sign an informed consent and fill out the questionnaire! To obtain a copy of the informed consent and questionnaire:• Ask an Alpha-1 Research Registry member at the Alpha-1 Research Registry booth• Download the Alpha-1 Research Registry informed consent and questionnaire at:

www.alpha1.org/Newly-Diagnosed/More-Alpha-1-Resources/Research-Registry• Call 1-877-228-7321 ext 327 • Email alpha1registry@alpha1.org

Who is eligible to enroll in the Registry? Individuals of all ages who are diagnosed with Alpha-1 Antitrypsin Deficiency and individuals identified as carriers of Alpha-1 Antitrypsin Deficiency are encouraged to enroll in the Research Registry.

http://www.alpha1.org/Newly-Diagnosed/More-Alpha-1-Resources/Research-Registrymailto:alpha1registry@alpha1.org

Alpha-1 Foundation Research Registry

Alpha-1 Foundation Research Registry

• Facilitates Clinical TrialsContact

• Establishes Natural HistoryClinical

• Capable of expediting Clinical DevelopmentPRO

• Enhances Regulatory Grade Data Linked

Informed Consent

Staff Training

Confidentiality

Alpha-1 Foundation Research Registry

Alpha-1 NIH Grant

• The National Institutes of Health awarded a large rare disease grant entitled Alpha-1 Antitrypsin Disease Cohort: Longitudinal Biomarker Study of Disease that will establish a longitudinal cohort of Alpha-1 patients. The grant was awarded to Jeanine D’Armiento, MD, PhD at Columbia University in New York City as the Principal Investigator along with Co-Principal Investigator, Charlie Strange, MD at the Medical University of South Carolina. The University of Alabama at Birmingham, under the guidance of Dr. J. Michael Wells and Dr. Surya Bhatt, will serve as the imaging core for this study. Dr. Mark Brantly at the University of Florida will serve as a consultant on the proposal. Dr. Gerry McElvaney at the Royal College of Surgeons in Ireland will serve as an international Co-Investigator.

•• The Alpha-1 Foundation will be directly working with the Investigators throughout the

duration of this six-year study. Although the Foundation does not receive direct funding from this NIH grant, the benefit to the Foundation and the patient community will be tremendous. The Alpha-1 Foundation Research Registry will be significantly enhanced through the efforts of the Investigators during the first phase of the study.

•• In addition, the interaction with Alpha-1 community aligns directly with the FDA’s Patient

Focused Drug Development Program. This grant aids in identification of unaddressed research questions in Alpha-1 and clinically relevant outcomes of importance to patients and also facilitates engagement and recruitment of patients and families.

Clinical Resource Centers

Clinical Resource Centers (CRCs) are located throughout North America and specialize in patient care, education and research for those with Alpha-1. Some centers treat lung disease and others liver disease. Many have other resources for Alphas, such as support groups, pulmonary rehabilitation and organ transplant programs.

Currently, there are 72 CRCs. 41 out of the 72 CRCs have a Clinical and Translational Science Award (CTSA).

TDN Oversight Committee

Therapeutic Development Network

TDN Operations Committee

Patient Detection & Testing

A1FPatientRegistry

U3/UH GrantPI: D’Armiento

EndpointAssessmentValidation

BiopharmaIndustry Partners

ContractResearch

Orgs

AcademiaKOLs

Translational Research

Structure and Organization of the Therapeutic Development Network (TDN)

Alpha-1 Research Support: Lung vs. Liver

0%

25%

50%

75%

100%

Fiscal Year

Peer-Reviewed Grants since inceptionLung vs. Liver

% Lung % Liver**combined FY total can exceed 100% as some grants are both liver and lung related**

Alpha-1 Foundation FundedResearch Contributions to

Translational Therapies

25-year Review of Alpha-1 Research

• Augmentation Therapy

• Small Molecule Therapies

• Gene Therapy

• Adeno-Associated Virus Vectors

• RNAi

• Hyaluronic Acid Based Therapy

Contributions to Translational Therapies

Over the last 25 years, the Alpha-1 Foundation has established a synergistic infrastructure serving people with AATD, fostering innovations, and translating discoveries into clinical trials.

In realization of its mission, the foundation has made its website a one-stop source for all the information new Alphas could need regarding genetic screening, connecting with specialists, and becoming involved in the community.

Looking Forward

Investment into basic science has led to the creation of an extensive library of publications.

Supporting such research has also fostered collaborations and the generation of experts committed to discovering improved treatments.

The abundance of research has produced actionable pathways and opportunities for intervention.

Looking Forward

Focused investments enables the Foundation to streamline the availability of resources needed to bring treatments to the FDA and into clinical trials.

Recruitment of patients with AATD is simplified thanks to the Alpha-1 Research Registry.

The abundance of ongoing clinical trials investigating a diverse array of potential treatments for AATD is a credit to the efficacy of the Alpha-1 Foundations’ pipeline in bringing discoveries from benchtop to bedside.

Looking Forward

How to get involved in Alpha-1 Research:Resources for Patients and Caregivers

Contact us:Alpha-1 Foundation

www.alpha1.orgCall: 877-228-7321

Email: alpha1registry@alpha1.org

Current Alpha-1 Clinical Trials are listed in every edition of our Alpha-1-to-One Magazine

www.clinicaltrials.gov and search for “antitrypsin”https://www.fda.gov/science-researchhttps://rarediseases.org/for-patients-and-families/

http://www.alpha1.org/mailto:alpha1registry@alpha1.orghttp://www.clinicaltrials.gov/https://www.fda.gov/science-researchhttps://rarediseases.org/for-patients-and-families/

Thank you to our generous meeting sponsors:

AlphaNetCSL Behring

GrifolsTakeda Vertex

Impact Report�“25-year Review of Alpha-1 Research” Research toward the CureBuilding the Scientific InfrastructureAlpha-1 Foundation Patient Centered ModelAlpha-1 Research for a CureAlpha-1 Foundation-sponsored� Scientific Conferences and Publications�Publishing About �Alpha-1 Antitrypsin DeficiencyResources for InvestigatorsAlpha-1 Foundation Research RegistryAlpha-1 Foundation Research RegistryAlpha-1 Foundation Research RegistryAlpha-1 Foundation Research RegistryAlpha-1 Foundation Research RegistryAlpha-1 Foundation Research RegistryAlpha-1 NIH GrantClinical Resource CentersSlide Number 17Alpha-1 Research Support: Lung vs. Liver25-year Review of Alpha-1 ResearchSlide Number 20Looking ForwardLooking ForwardLooking ForwardHow to get involved in Alpha-1 Research:�Resources for Patients and CaregiversSlide Number 25Slide Number 26