Sickle Cell Disease: the Challenge of Healthcare Disparity April 2018

Sickle Cell Disease: The Challenge of Healthcare Disparity April 2018

Global Blood Therapeutics, Inc. SICKLE CELL DISEASE (SCD): DISABLING INHERITED BLOOD DISORDER • SCD is an uncommon (or orphan) disease in the U.S., affecting approximately 100,000 people.1

• It disproportionately impacts African American and Hispanic Americans, occurring in 1 out of every 365 African American births and 1 out of every 16,300 Hispanic American births.

• Every system in the body is impacted due to a lack of oxygen

• Symptoms vary from childhood (e.g., stroke, acute chest syndrome) to adulthood (e.g., osteonecrosis of bone)

• Clinical manifestations get worse over time in terms both of the severity of particular episodes (e.g., pain) and the presence or absence of a particular problem (e.g., leg ulcers)

Sickle cell disease decreases median lifespan by decades

Sources: Piel FB et al. N Engl J Med 2017;376:1561-1573 1. Centers f or Disease Control and Prevention. Sickle Cell Disease (SCD) Data & Statistics. https://www.cdc.gov/ncbddd/sicklecell/data.html ©Global Blood Therapeutics 2 SCD SPURRED ADVANCES IN MOLECULAR BIOLOGY AND GENETICS FOR A CENTURY

James Herrick and Ernest E. Irons at Harvey Itano and Linus Pauling used Vernon Ingram at MRC in London Cook County Hospital in Chicago first the newly invented technique of used protein sequencing to described sickle cell disease in a protein electrophoresis to demonstrate demonstrate that HbS derived from a student from Grenada, Walter Clement that sickle hemoglobin (HbS) differed glutamic acid to valine amino acid Noël. He had an anemia marked by from normal hemoglobin (HbA). change at position β-6. The recently red cells that looked like “crescents or elucidated genetic code allowed sickles”. Noël returned to Grenada deduction of the nucleotide change after training in dentistry. (GAG → GTG).

1949 1956  1910 First demonstration of disease due to  First demonstration of disease due to an abnormal protein a specific DNA mutation

3 CLINICAL CARE CONTINUES TO LAG SCIENCE

50 90% of Children reach Hydroxyurea 45 18 years of age Preventive 40 penicillin Median life expectancy:

) 35 Males- 42 years yr Females- 48 years 30 Transfusion for stroke prevention

25 National Sickle Cell Control Act 20

Life Expectancy ( Expectancy Life 15

0 1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000

Increases in Life Expectancy in Persons w ith Sickle Cell Disease, 1910–2000.

4 CONCENTRATED POPULATION, MOSTLY INSURED BY MEDICAID & MEDICARE

Age Distribution Geographical Distribution

West >30, 10% 40% Older Adults ~100K Americans are SCD is fairly concentrated in the US. living with SCD Northeast + 80% of the population resides in 17 states 18 to 20% + ~90% of SCD are African South 30, Transitioning Adults 55% + Most of the rural population lives in the American 27% Midwest south <18, + ~10% are Hispanic American 15% Pediatric Patients 33%

% of patients % of patients

Payer Mix

Medicaid: ~50% of the population Medicaid dominates payer mix These individuals tend to be younger due to Medicaid eligibility criteria

A significant share of Medicare Medicare: 30% of the population are dual eligible ~15% of the population Commercial: ~

Uninsured: More likely to be adult patients <10% of the Most of the southern states did not participate in Medicaid expansion population

Sources: Piel et al NEJM 2017. November 2017 Analysis of Administrative Claims Data For 72,573 patients sourced from Symphony Healthcare Solutions. On File at GBT ©Global Blood Therapeutics 5 CURRENT THERAPIES FOR SCD ARE SUBOPTIMAL…

Consensus Evidence Treatment Use Duration Recommendation Quality

Daily until at least 5 years of Penicillin V • Prevention of Infections • Strong • Moderate age

Pneumococcal • Prevention of Infections Every 5 years for life • Strong • Moderate vaccination

Acute Blood • Treatment of Anemia • Strong • Low Limited Transfusion • Pre-operative transfusion • Strong • Moderate

Analgesics (Opioid • Treatment of Acute Pain • Strong • High Limited and Nonopioid) • Treatment of Chronic Pain • Moderate • Low

• Primary Stroke Prevention • Strong • High Chronic Blood • Secondary Stroke Prevention • Moderate • Low Every 3-6 weeks indefinitely Transfusion • Prevention of additional Silent Cerebral • Moderate • Moderate Infarctions • Universal Use • Moderate • Moderate Hydroxyurea • Prevention of Acute Complications Daily indefinitely • Strong • High • Primary Stroke Prevention • Strong • Moderate

• Not yet Endari • Prevention of Acute Complications Daily indefinitely • Not yet assessed assessed

Sources: Piel FB et al. N Engl J Med 2017;376:1561-1573 Evidence-Based Management of Sickle Cell Disease, Expert Panel Report. National Heart, Lung & Blood Institute. 2014

Average Number of Emergency Department Visits Per Year1 7 6.1 6 5.5 5 • In 2014, SCD was responsible for ~250,000 Commercial Medicaid Emergency Department U.S. visits2 4

3 2.2 2 • About 20% of sickle cell disease patients 1.5 1.4 1.1 receive most of their care in the emergency 1 department setting3 0 < 18 18-30 > 30

Studies in the US indicate that about a third of patients are rehospitalized within 30 days of initial discharge due to SCD-related complications. 3,4

Average Number of Inpatient Stays Per Year1 7 • In 2014, SCD was responsible for ~90,000 6 Inpatient stays in the United States2

5 • Average length of stay was 4-7 days3,4,5

4 Commercial Medicaid

3 2.4 2.3 2 1.2 1 0.7 0.8 0.7

0 < 18 18-30 > 30

Studies in the US indicate that about a third of patients are rehospitalized within 30 days of initial discharge due to SCD-related complications. 3,4

Sources: 1. Dampier et al. Access To Care For Medicaid And Commercially-Insured United States Patients With Sickle Cell Disease. GBT Sponsored ASH 2017 poster 2. Quality A f HRa. HCUPnet Healthcare Cost and Utilization Project. 2017; https://hcupnet.ahrq.gov/#setup. Accessed 02/14/2018 3. Rajpura, J. and J. Thomas Iii, All-cause health care resource utilization in individuals w ith sickle cell disease. Blood, 2015. 126(23): p. 5582 4. Raphael, J.L., et al., Shorter hospitalization trends among children w ith sickle cell disease. Pediatr Blood Cancer., 2012. 59(4): p. 679-84. doi: 10.1002/pbc.24065. Epub 2012 Jan 4 5. Jordan, L., et al., Sickle cell day hospital: A four year review of SCD patient tailored pain management and disease specific comprehensive care in an outpatient setting. American Journal of Hematology, 2012. 87(7): p. E11-E12

©Global Blood Therapeutics 8 SCD DRIVES HIGHEST ALL-CAUSE 30-DAY READMISSION RATES

• Studies in the US indicate that about a third of patients are rehospitalized within 30 days of initial discharge due to SCD-related complications. 2,3

Sources: 1. Elixhauser A and Steiner C, HCUP Strategical Briefs, 201 2. Brousseau, D.C. JAMA., 2010. 303(13): 1288-94 3. Nouraie, M. and V.R. Gordeuk, Transfusion., 2015. 55(10): 2331-8

11 ©Global Blood Therapeutics SCD RESULTS IN ~$10 MM IN LIFETIME HEALTHCARE EXPENSES & LOST PRODUCTIVITY PER INDIVIDUAL

ED Visits, 5% Expected Lifetime

Outpatient Cohort Income Per Visits, 1% Individual Lab Services, 6% SCD (all genotypes) $1.2M Hospital Admissions, 84% Transfusions & Non-SCD (Matched Medications, 5% $1.9M Controls) General US Population $2.1M

+ SCD significantly also limits quality adjusted life % of fees expectancy & costs the US economy over $800M in lifetime productivity • Average annual fee for the care of an adult  This estimate does not include lost with SCD (SS genotype) is $231,000* educational potential, caregiver productivity or patient time spent in the hospital. • Lifetime healthcare fees are ~$9 MILLION per individual*

Sources: 1. Ballas, American Jour of Hematology, 2009. Assumptions based on HbSS patients 2. SCD Societal Cost Model In Development by GBT for Journal Submission. All SCD Patients * in 2009 dollars, cost does not include future inflation rates; fee is defined as the price charged by providers; cost is usually about 60-65% of fee

©Global Blood Therapeutics 10 CURRENT ECONOMICS ARE CHALLENGING FOR SCD CLINICS TO PROVIDE INTEGRATED CARE

Medicaid payments can be significantly lower than …Making it challenging to maintain an other payers… integrated care model

$300 Charges vs Payment Analysis for Commonly Needed Resources Routine Outpatient Visit (Established Adult Patient) for SCD Quality Care Delivery

$250 Benioff Children’s Hospital Oakland (BCHO) • SCD specialist (e.g. Hematologist)

• Nurse Practitioners / Physician Assistants $200 • Primary Care Physician $148 $150 • Community Health Workers (CHW)

• Nurse Educators $100 $92 $89 • Social Workers

$50 62% 60% $28 • Patient Navigators 19% (payment to charges ratio) • Mental Health Professional $0 Charge Commercial Medicare Medicaid

Source: BCHO 2017 Practice Analysis for CPT Code 99214 - 25 minute office visit (most commonly billed code)

Proportion of SCD Population with at Least 1 Hematologist* Visit Per Year

60%

Commercial Medicaid 50% 50%

41% 40% 38%

30%

20%

10% 8% 9% 5%

0% < 18 18-30 > 30

Source: Dampier et al. Access To Care For Medicaid And Commercially-Insured United States Patients With Sickle Cell Disease; ASH 2017 * Includes Board certified Hematologist or Oncologist.

100 Raphael- Pediatr Blood Cancer. 2013 60: 275 90

% o f 50 Patients 40

0 Regular Provider Comprehensive Family-centered Coordinated PCMH

Elements of a Patient-centered Medical Home (PCMH)

• Sickle cell disease is an uncommon debilitating illness affecting primarily African Americans and Hispanic Americans

• Patients lack access to quality chronic care which increases expensive hospital and ED usage and driving up costs to our healthcare system and to our society

• Current treatment options are sub-optimal and therefore limited in use

• Integrated, comprehensive care program with effective and preventative interventions are essential to reverse healthcare disparity in sickle cell disease