Alpha-1 Antitrypsin Deficiency: New Hope for Diagnosis and Treatment Final Live Outcome ReportPrepared For CSL Behring

February 14, 2019

Persistent Educational Gapsv Though improvements were observed, learners demonstrated score slippage on the PCA indicating persistent gaps in the several

areas including:

v Mechanism of action of alpha-1 antitrypsin and the impact of its deficiency on lung tissue

v Laboratory testing in AATD

v Treatment strategies for patients with AATD and COPD

v Comorbid conditions associated with AATDThe post-test scores, and self reported confidence regarding the management of patients with PAH, signifies a clear gap in knowledge

and an unmet need among clinicians. It continues to be an important area for future educational programs.

Executive Summary

*These numbers represent the total number of attendees, irrespective of assessment participation

495* total attendees

on site: 113 attendees

National online simulcast: 382 attendees

v This curriculum focused on discussing the pathophysiology and diagnosis of AATD, recognizing its impact on risk of COPD and other comorbidities, treatment options according to the latest GOLD guidelines and strategies to increase detection in practice.

v 495 attendees in multiple professional specialties were reached via both live onsite and online formats.

v Improvement across all learning domains was noted ranging from 43% to 138%.

v Overall, the program improved the ability of learners to recognize the impact of AATD on the risk for COPD, understand the pathophysiology of disease, incorporate laboratory testing and treat patients with AATD and COPD.

Learning Objectives

4

3

2

1 Discuss the pathophysiology of AAT deficiency (AATD) and its impact on chronic obstructive pulmonary disease (COPD) risk.

Interpret the clinical significance of laboratory test results for AATD.

Discuss treatment options for AATD and latest GOLD guideline recommendations.

Discuss strategies to enhance detection and treatment of AATD in clinical practice.

Course DirectorFranck Rahaghi, MD, MHS, FCCPDirector of Advanced Lung Disease ClinicDirector, Pulmonary Hypertension ClinicChairman, Dept. of Pulmonary and Critical CareCleveland Clinic FloridaWeston, FL

Gregg Sherman, MD

Michelle Frisch, MPH, CCMEP

Sandy Bihlmeyer M.Ed

Franck Rahaghi, MD, MHS, FCCP

Sheila Lucas, CWEP

Kevin Flaherty, MD, MSProfessor in Pulmonary and Critical Care MedicineUniversity of MichiganAnn Arbor, MI

Mehdi Mirsaeidi MD, MPHDirector of UM and VA Sarcoidosis ProgramsIRB Vice-Chairman, Miami VA Healthcare SystemDivision of Pulmonary, Critical Care,Sleep and AllergyDepartment of MedicineUniversity of MiamiMiller School of MedicineMiami, FL

Franck Rahaghi, MD, MHS, FCCPDirector of Advanced Lung Disease ClinicDirector, Pulmonary Hypertension ClinicChairman, Dept. of Pulmonary and Critical CareCleveland Clinic FloridaWeston, FL

Dennis K. Ledford, MD, FAAAAIEllsworth and Mabel Simmons Professor of Allergy/ImmunologyPast-President of Medical FacultyMorsani COM, University of South FloridaTampa, FL

Adam Wanner, MD*Joseph Weintraub Professor of MedicineDivision of Pulmonary & Critical Care MedicineUniversity of Miami Miller School of MedicineScientific DirectorAlpha-1 FoundationMiami, FL

Victor Test, MDChief, Division of Pulmonary & Critical Care MedicineDirector, Pulmonary Vascular Disease ProgramTexas Tech University School of MedicineLubbock, TX

Robert A. Sandhaus, MD, PhD, FCCPProfessor of MedicineDirector, Alpha-1 ProgramNational Jewish HealthClinical Director, Alpha-1 FoundationExecutive VP and Medical Director, AlphaNetMedical Director, AlphaNet Canada Coral Gables, FL

Faculty

Activity Planning Committee

*Presented the AATD Lecture

Commercial Support

The Challenges in Pulmonary and Critical Care: 2018 CME activity was supported through educational grants or donations from the following companies:

vBayer HealthCare Pharmaceuticals, Inc.

vActelion Pharmaceuticals US, Inc.

vBoehringer Ingelheim Pharmaceuticals, Inc.

vCSL Behring, LLC.

vGrifols

vInsmed

vMallinckrodt Pharmaceuticals, LLC

Levels of EvaluationConsistent with the policies of the ACCME, NACE evaluates the effectiveness of all CME activities using a systematic process based on Moore’s model. This outcome study reaches Level 5.

Level 1: Participation

Level 2: Satisfaction

Level 3: Declarative and Procedural Knowledge

Level 4: Competence

Level 5: Performance

Level 6: Patient Health

Level 7: Community Health

Moore DE Jr, Green JS, Gallis HA. Achievingdesired results and improved outcomes: integratingplanning and assessment throughout learningactivities. J Contin. Educ. Health Prof. 2009 Winter;29(1):1-15

Level 1:Participation and Demographics

495 total attendees

On site: 113 attendees

90%Provide direct patient care

National online simulcast : 382 attendees

Level 1:Participation

December 1, 2018 Fort Lauderdale, FL

Profession Years in Practice

Patient Care Focus: 90%

Level 1: Demographics and Patient Reach

Patients seen each week, in any clinical setting:Specialty

31%

7%

20%

43%

<5 5-10 11-20 >20

36%

0%

50%

5%0%

9%

MD DO NP PA RN Other

27%

17%

29%

27%

0% 20% 40% 60% 80% 100%

<25

25-50

51-75

>75

31%

57%

6% 6%0%

Pulmonology PrimaryCare/Internal

Medicine

Hospitalist EmergencyMedicine/ Critical

Care

Endocrinology

Level 2-5:Outcomes Metrics

99% rated the activity as excellent

99% indicated the activity improved their knowledge

97% stated that they learned new and useful strategies for patient care

91% said they would implement new strategies that they learned

100% said the program was fair-balanced and unbiased

Level 2: Satisfaction

Please rate your confidence in your ability to integrate the detection and treatment of AATD into your practice:(Learning Objective 4)

Confidence Assessment

Pre: Post: PCA:N= 175 162 117

59%

22%

10% 8%2%

5%

33% 33%

10%

19%

11%

35%

45%

8%

1%0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Not at all confident Slightly confident Moderately confident Pretty much confident Very confident

3%

49%

12%

34%

67%

1%

82%

4%9%

3%2%

53%

8%

32%

5%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

0% 25% 33% 50% 100%

Two carriers of the alpha-antitrypsin gene have children. The statistical chance they will have a child with severe alpha-1 antitrypsin deficiency disease is:(Learning Objective 2)

Pre: Post: PCA:

Knowledge Assessment

N= 175 162 117

P<=05

Pre to Post Change 67%Pre to PCA Change 8%

18% 17%

3%

37%

25%

5%0%

3%

88%

5%

20%22%

9%

22%27%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

COPD Interstitial Lung Disease Bronchiectasis COPD and Bronchiectasis COPD and Interstitial LungDisease

What lung conditions are clearly associated with alpha-1 antitrypsin deficiency?(Learning Objective 1)

Pre: Post: PCA:

Knowledge Assessment

N= 175 162 117

Pre to Post Change 138%

Pre to PCA Change -40%

P<=05

0%5%

47% 46%

2%2% 3%

87%

8%

0%1% 3%

70%

25%

1%0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Prevent sexual interactionbetween cells

Supervise cellular socialactivities

Promote the intracellulartrafficking of misfolded

proteins and their transportout of the cell

Block reverse transcriptase Discard alcohols createdduring chemical reactions

What are chemical chaperones thought to do in alpha-1 antitrypsin deficiency?(Learning Objective 1)

Pre: Post: PCA:

Knowledge Assessment

N= 175 162 117

P<=.05

Pre to Post Change 85%Pre to PCA Change 49%

Are there other treatments for lung disease due to alpha-1 antitrypsin deficiency, in addition to augmentation therapy?(Learning Objective 3)

Pre: Post: PCA:

Knowledge Assessment

N= 175 162 117

P=>.05

11%

35%

4%

44%

7%7%

33%

2%

58%

0%

8%

50%

8%

29%

6%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

No Yes, all the treatments one wouldoffer to any patient with COPD

Yes, although alpha-1 antitrypsinpatients should always avoid

pulmonary rehabilitation

Yes, but their effectiveness is lessthan in common COPD

No, but some homeopathicremedies have been shown to behighly effective in the treatment of

emphysema

Pre to Post Change -6%

Pre to PCA Change 43%

Timely referralPatient education Disease state awareness

Diagnostic evaluation Pharmacotherapy

Please select the specific areas of skills, or practice behaviors, you have improved regarding the screening, diagnosis and treatment of Alpha-1 Antitrypsin Deficiency since this CME activity. (Select all that apply.)N=117

(4-week Post Assessment)

64% 62% 61%

59% 58%

Insurance/Financial issues

Lack of knowledge System constraints

Medication costs Formulary constrictions

What specific barriers have you encountered that may have prevented you from successfully implementing screening, diagnosis and treatment of Alpha-1 Antitrypsin Deficiency since this CME activity? (Select all that apply) N=117

(4-week Post Assessment)

64%

60%61%

62%63%

67% improvement in awareness of the laboratory testing and the genetic heritability of AATD

138% increased awareness of the impact of AATD on risk of COPD and other associated conditions

85% increase in recognition of the underlying pathophysiology of alpha-1 antitrypsin deficiency

43% increased recognition that in addition to AATD replacement therapy, incorporating all treatments for any patient with COPD is appropriate

Participant Educational Gains

Persistent Educational Gaps After 4 Weeks

Mechanism of action of alpha-1 antitrypsin and the impact of its deficiency on lung tissue

Laboratory testing in AATD

Treatment strategies for patients with AATD and COPD

Comorbid conditions associated with AATD

Key Take-home Points

Significant increases in ability to integrate the detection and treatment of AATD into practice that persisted after 4 weeks

90% of participants provide direct patient care

After 4 weeks, the following improved skills were reported regarding the screening, diagnosis and treatment of AATD : 64% timely referral pharmacotherapy, 62% patient education and 61% disease state awareness

Despite gains seen in 4 out of 5 questions, score slippage after 4 weeks reinforces the need for continued education on the management of AATD.