Ciraparantag

Analyst Day May 22, 2019

2 Forward-Looking Statements

This presentation contains forward‐looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 (PSLRA) and other federal securities laws. Any statements contained herein which do not describe historical facts, including, among others, statements regarding the anticipated regulatory timeline for AMAG’s products and product candidates and expectations for AMAG’s product portfolio; AMAG’s 2017-2022 strategic plan and progress on such plan; the potential for AMAG’s commercial platforms; expectations for AMAG’s product development timeline, including the timing for commercial launches, clinical trial enrollment and results and regulatory submissions; beliefs about the commercial opportunities, and the assumptions underlying such beliefs, for Vyleesi, ciraparantag and AMAG-423, including as to pricing, volume, patient population, including demographics and trends, and the prevalence of indications; beliefs about the data, science and addressable market for AMAG’s product candidates; anticipated safety profiles; anticipated reimbursement availability; expectations for patient sentiments and behaviors and the manner in which the proposed indications for AMAG’s product candidates present; beliefs about and expectations for clinical trial results; beliefs that new products will drive future growth and that commercial product opportunities can be maximized; AMAG’s expectations for its commercial product portfolio from 2019 through 2022, including the timing for key events; beliefs about revenue and adjusted EBITA opportunities and trajectories; AMAG’s business development goals and initiatives, including potential partnering opportunities and the availability of non-dilutive capital; beliefs that the EBITDA negative phase in 2019 is short-lived and that AMAG will return to EBITDA neutral in 2020 and AMAG’s 2019 development goals are forward‐looking statements which involve risks and uncertainties that could cause actual results to differ materially from those discussed in such forward‐looking statements.

Such risks and uncertainties include, among others, the risk that sales of Makena will continue to be negatively impacted by the supply disruption and recent and future generic entries in the market; the risk that AMAG may be unable to gain approval of its product candidates, including Vyleesi, AMAG-423 and ciraparantag, on a timely basis, or at all, including as a result of delays or set-backs in clinical trial enrollment, design or results; the potential for such approvals, if obtained, to include unanticipated restrictions or warnings and the risk that the costs and time investments for AMAG’s development efforts will be higher than anticipated, or that AMAG has over-estimated the market and potential revenues for its products and product candidates, if approved, including AMAG’s beliefs about the market opportunity for Vyleesi, AMAG-423 and ciraparantag; and those risks identified in AMAG’s filings with the U.S. Securities and Exchange Commission (the “SEC”), including its Annual Report on Form 10‐K for the year ended December 31, 2018, its Quarterly Report on Form 10-Q for the quarter ended March 31, 2019 and subsequent filings with the SEC, which are available at the SEC’s website at www.sec.gov. Any such risks and uncertainties could materially and adversely affect AMAG’s results of operations, its profitability and its cash flows, which would, in turn, have a significant and adverse impact on AMAG’s stock price. AMAG cautions you not to place undue reliance on any forward‐looking statements, which speak only as of the date they are made.

AMAG disclaims any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward‐looking statements.

AMAG Pharmaceuticals® and Feraheme® and the logo and designs are registered trademarks of AMAG Pharmaceuticals, Inc. VyleesiTM is a trademark of AMAG Pharmaceuticals, Inc. Makena® is a registered trademark of AMAG Pharma USA, Inc. Intrarosa® is a registered trademark of Endoceutics, Inc. Other trademarks referred in these materials are the property of their respective owners.

Slides 7, 9, 18, 177, 181-184, 187, 188 and 190 contain forward-looking estimates of AMAG’s growth trajectory in revenue and adjusted EBITDA on a multi-year timeframe based on a strategy of maximizing commercial product opportunities to fund investments in new products, with various assumptions, including certain assumptions about the progression and approval of AMAG’s product candidates. In addition to the risk factors and forward-looking statements disclosed above, these estimates involve risks and uncertainties related to: (i) the success of AMAG’s development pipeline; (ii) an increased focus on durable assets; (iii) ongoing efforts to leverage clinical development capabilities against later-stage, lower-risk development opportunities which are themselves subject to considerable risk; (iv) the cash-flows required to the fund AMAG’s evolving business model, including its development efforts; (v) the uncertain and highly speculative commercial potential of therapeutic areas of interest; and (vi) external pricing / reimbursement. The purpose of these long-term revenue and adjusted EBITDA estimates is not to provide financial guidance or forecasts, but rather to illustrate AMAG’s current growth model based on current plans for the advancement of Vyleesi, ciraparantag and AMAG-423 and potential future portfolio expansion. These estimates include assumptions based on current circumstances with respect to, among other things, (A) design, enrollment, timing and successful execution of clinical trials, (B) anticipated timetables for regulatory filings and related reviews and potential approvals of products, and approved indications, (C) cost and timing for development efforts and commercial launches, (D) forecasted volumes and pricing and (E) the performance of AMAG’s commercialized products. Additional risk factors include, among others, (i) the risk that AMAG’s commercial products will not achieve the level of revenues needed to support AMAG’s research and development efforts, including because such efforts require greater costs than anticipated or because such revenues fall short of expectations, (ii) the speculative nature of the addressable market for the indications being pursued for AMAG’s product candidates, (iii) the risk that the FDA will not approve AMAG’s product candidates for commercial use on the expected timeframe, for the anticipated indications, uses and label, or at all, and (iv) the risk that AMAG will not be able to continue to execute on its business plan. There can be no assurance that all or any of the assumptions and estimates built into our long-term models will prove correct, and we caution you not to place undue reliance on such statements and the overall progression of revenue or adjusted EBITDA for our products, as the timing of regulatory approvals, clinical study results, commercial launch, supply availability, competition, volume and pricing may turn out to be significantly different from our current estimates. You are strongly encouraged to read those risks and uncertainties identified above and in AMAG’s filings with the SEC.

Welcome Linda Lennox, AMAG Vice President, Investor Relations Strategic overview and outlook Bill Heiden, AMAG President and Chief Executive Officer AMAG-423 • Disease overview John Barton, MD, OB/GYN, MFM Specialist, Baptist Health, KY* • MOA, Phase 2a data, current Phase 2b/3a trial Baha Sibai, MD, Professor, Department of OB/GYN and Reproductive Sciences, McGovern Medical School, University of Texas Health Sciences, TX* • AMAG market opportunity Tony Casciano, AMAG Chief Commercial Officer • Q&A with panel Moderated by Julie Krop, MD, AMAG Chief Medical Officer Vyleesi™ • Condition, unmet medical need Sheryl Kingsberg, PhD, Chief, Division of Behavioral Medicine, University Hospitals Cleveland Medical Center, OH* • Role of Vyleesi in clinical practice David Portman, MD, Director Emeritus, Columbus Center for Women’s Health Research, Adjunct Instructor, Ohio State University* • Doctor/patient fireside chat Sheryl Kingsberg, PhD; HSDD patient • Vyleesi commercial launch overview Meghan Rivera, AMAG Vice President, Head of Women’s Health Sales & Marketing • Q&A with panel Moderated by Julie Krop, MD Ciraparantag • Unmet need, MOA, Phase 2 data, coagulometer Jack Ansell, MD, Professor of Medicine, Hofstra Northwell School of Medicine, NY* • Role of/need for reversal agent in ER setting Joseph Bledsoe, MD, Department of Emergency Medicine, Intermountain Healthcare, UT* • Role of reversal agent in cardiology practice C. Michael Gibson, MD, Interventional Cardiologist, Beth Israel Deaconess Medical Center, MA* • AMAG market opportunity Tony Casciano • Q&A with panel Moderated by Julie Krop, MD Financial evolution and business development Ted Myles, AMAG Chief Financial Officer Closing remarks / Q&A Bill Heiden

* Key opinion leaders were compensated for their time and participation in this event. © 2019 AMAG Pharmaceuticals, Inc. All rights reserved 5 Strategic Overview and Outlook Bill Heiden AMAG President and CEO

6 Key Take-Aways for Today

View to 2022 is bright Valuable product • Current commercial products portfolio today will continue to perform well • Development-stage products Significant progress • Commercial products growing represent new & durable from 2017 to today • Development-stage products revenue opportunities address significant unmet • Return to cash flow positive • Expanded product portfolio medical needs and represent from 2 products to 6 products substantial commercial • Strong and proven commercial opportunities track record • Successful drug development capabilities

2 6

Strategic Overview

Progress to Date

Portfolio Value

Delivering Innovative Therapies Investing Innovation Expanding Creating new, durable revenue streams and capabilities and Acquiring/licensing profitable growth investing in the development-stage development products to address and launch of new unmet medical products needs Acquiring/Licensing

Specialty Pharma: Acquiring/licensing cash generating products 2018 2019 2020 2021 2022

Strategic Overview

Progress to Date

Portfolio Value

© 2019 AMAG Pharmaceuticals, Inc. All rights reserved 10 Strong Progress To Date On Strategic Evolution 2017-2022 Maximizing Commercial Product Opportunities and Adding New Products to the Portfolio 2017 Regulatory Approved/ Phase 1 Phase 2 Phase 3 Review Marketed

Treatment of iron deficiency anemia CKD

Broad label all iron deficiency anemia HEMATOLOGY

Treatment to reduce recurrent preterm birth in certain at-risk women Subcutaneous auto-injector

Treatment for moderate to severe dyspareunia (pain during sex) in postmenopausal women

TM Treatment of low desire or libido with associated distress (HSDD*) in premenopausal women

WOMEN’S HEALTHCARE Neonatal cord blood storage business

* HSDD: Hypoactive Sexual Desire Disorder

© 2019 AMAG Pharmaceuticals, Inc. All rights reserved 11 Strong Progress on Strategic Evolution 2017-2022 Maximizing Commercial Product Opportunities and Adding New Products to the Portfolio 2018 Regulatory Approved/ Phase 1 Phase 2 Phase 3 Review Marketed

Treatment of iron deficiency anemia CKD

Broad label all iron deficiency anemia HEMATOLOGY

Treatment to reduce recurrent preterm birth in certain at-risk women Subcutaneous auto-injector

Treatment for moderate to severe dyspareunia (pain during sex) in postmenopausal women

TM Treatment of low desire or libido with associated distress (HSDD*) in

premenopausal women WOMEN’S HEALTHCARE

* HSDD: Hypoactive Sexual Desire Disorder

© 2019 AMAG Pharmaceuticals, Inc. All rights reserved 12 Strong Progress on Strategic Evolution 2017-2022 Maximizing Commercial Product Opportunities and Adding New Products to the Portfolio 2018 Regulatory Approved/ Phase 1 Phase 2 Phase 3 Review Marketed

Treatment of iron deficiency anemia CKD

Broad label all iron deficiency anemia

Anticoagulant reversal agent

Ciraparantag (potential for orphan drug designation) HEMATOLOGY

Treatment to reduce recurrent preterm birth in certain at-risk women Subcutaneous auto-injector

Treatment for moderate to severe dyspareunia (pain during sex) in postmenopausal women

TM Treatment of low desire or libido with associated distress (HSDD*) in premenopausal women

AMAG-423 Treatment of severe preeclampsia

WOMEN’S HEALTHCAREDigoxin Immune (orphan drug designation) Fab (ovine)

* HSDD: Hypoactive Sexual Desire Disorder

Fundingfunding

HISTORICAL Value of AMAG FUTURE Value of AMAG

Coming Soon ciraparantag AMAG-423

Commercial

Hematology Women’s Health Maternal Health

48 Sales Representatives => 124 Sales Representatives => OB/GYNS Heme Clinics & Hospitals

STRONG COMMERCIAL PLATFORM

1H-2019 2H-2019 1H-2020 2H-2020 1H-2021 2H-2021

June 23 Potential PDUFA date commercial

Vyleesi launch

423 -

Target complete enrollment in Phase 2b/3a trial Topline data NDA submission Potential FDA approval AMAG

Closed End of Phase 2 Complete NDA Potential Perosphere meeting with Phase 3a trials; submission1 FDA approval acquisition FDA; Initiate announce Phase 3a trials topline data Apply for orphan Initiate

Ciraparantag and breakthrough Phase 3b/4 trial designation

1 Ciraparantag NDA submission expected to include only the first 50-100 patients in the Phase 3b clinical trial, based on precedent.

Strategic Overview

Progress to Date

Portfolio Value

Net Revenues Per Year For Every 1% of Market Penetration? AMAG-423 ciraparantag

Affects 5.8 million U.S. premenopausal women1 ~6 million patients on NOAC / LMWH therapy1 Annual U.S. incidence of preeclampsia: (1 in 10 premenopausal women)2,3 Xarelto®, Eliquis®, Savaysa®, Pradaxa®, Lovenox® ~140,000 pregnant women1 98% (5.7M) of affected ~150,0002 estimated NOAC / LMWH Annual U.S. incidence of severe premenopausal women patients per year requiring a preeclampsia: not on therapy1 reversal agent ~50,000 pregnant women1,2 Every 1%Every 1%of equals affected Every Every1% 1% of equals patients Every Every1% 1%of equals patients $35M4 / year $36M3 / year $70M3 / Year patients treated = requiring reversal treated = with severe preeclampsia = 4 3 $70M3 / Year $35M / year $36M / year

1 Patient & Economic Flow Study sponsored by Palatin Technologies, Inc. and 1 Perosphere sponsored commercial assessment report conducted by a third 1 Ananth, C. V., Keyes, K. M., & Wapner, R. J. (2013). Pre-eclampsia rates conducted by Burke Inc., April 2016. party in May 2016. in the United States, 1980-2010: age-period-cohort analysis. The 2 Shifren JL, Monz BU, Russo PA, Segreti A, Johannes CB. Sexual problems and 2 AMAG estimate based on the following: (i) Zhu J., Alexander GC, et al. BMJ, 347, f6564. http://doi.org/10.1136/bmj.f6564. distress in United States women: prevalence and correlates. Obstet Pharmacotherapy 2018 September; 38(9): 907-920. (ii) Sindet-Pedersen C, et 2 AMAG Phase 2b/3a clinical trial population is a subset of the severe Gynecol. 2008;112(5):970–978. al. European Heart Journal - Cardiovascular Pharmacotherapy (2018) 4, 220– preeclampsia population. 3 Goldstein I, Kim NN, Clayton AH, et al. Hypoactive sexual desire disorder: 227. (iii) Garcia D, Alexander JH, et al. Blood 2014 124: 3692-3698. (iv) 3 Price reference: $140,000/patient average annual cost for orphan drug, International Society for the Study of Women’s Sexual Health (ISSWSH) expert www.aha-org/statistics/fast-facts-us-hospitals. (v) Balakrishna, P, et al. Blood EvaluatePharma®, Orphan Drug Report 2017. consensus panel review. Mayo Clin Proc. 2017;92(1):114‐128. 2017 130:5585. (vi) 4 Price reference: The currently approved product for treatment of HSDD www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_atrial_fibrillation.hem. (flibanserin) WAC (assume 50% gross to net discount) x 3 months of therapy. 3 Price reference: The currently approved reversal agent (coagulation factor Xa recombinant, inactivated-zhzo) price of ~$24,000.

AMAG-423 John Barton, MD, OB/GYN, MFM specialist at Baptist Health, Lexington, KY (in development for the Baha Sibai, MD, Professor, Department of OB/GYN and Reproductive Sciences, UT Physicians treatment of severe preeclampsia) Maternal-Fetal Medicine Center, Texas Medical Center

Sheryl Kingsberg, PhD, Chief, Division of Behavioral Medicine, University Hospitals Cleveland Medical Center, MacDonald Women’s Hospital, Professor, Depts of Reproductive Biology and Psychiatry, Case Vyleesi™ Western Reserve University School of Medicine (hypoactive sexual desire disorder (HSDD); David Portman, MD, Director Emeritus, Principal Investigator, Columbus Center for Women’s Health PDUFA date: June 23) Research, Adjunct Instructor, Ohio State University, Columbus, OH HSDD patient – fireside chat with patient and Dr. Kingsberg

Jack Ansell, MD, Professor of Medicine, Hofstra Northwell School of Medicine Ciraparantag Joseph Bledsoe, MD, Dept. of Emergency Medicine, Intermountain Healthcare, Salt Lake City, UT; (in development as an Stanford University medical faculty: Intermountain-Stanford collaborative anticoagulant reversal agent) C. Michael Gibson, MD, Interventional cardiologist, cardiovascular researcher, Beth Israel Deaconess Medical Center, Boston, MA

20 Preeclampsia A Disease Overview

John R. Barton, M.D. Baptist Health Lexington Lexington, KY Disclosures

• Dr. Barton has received research grant support and Present Research/Grant Funding consulting fees in the past from Matria and Alere. Kyowa Kirin, Incs

• This is an educational lecture and is not intended to be an inducement to use any drug or drug in a Data Monitoring Committees fashion that is inconsistent with the drug or device rEVO Biologics label. Momenta Pharmaceuticals GestVision • The slides were prepared by John Barton, M.D. and/or were under the editorial control of John Barton, M.D.

22 Agenda

• Disease overview

• Health consequences for mother and infant

• Current management unsatisfactory

23 Preeclampsia

• Disease unique to human pregnancy • New hypertension usually beginning after 20 weeks of pregnancy • Untreated, preeclampsia can lead to serious — even fatal — complications

24 Preeclampsia is NOT just hypertension

25 Severe Preeclampsia is a Multi-System Maternal Disorder

Mild Proteinuria Severe Blood Pulmonary edema Pressure Capillary Leak Ascites

Epigastric pain Symptoms Renal failure Headache Fibrinolysis Hemolysis Nausea/vomiting Low platelets  Liver enzymes

26 Severe Preeclampsia Diagnosis

• Hypertension or preeclampsia Plus new onset any of the following: • SBP > 160 or DBP > 110 mmHg • 4 hr apart while on bed rest • Once if anti-hypertensives are used

• Persistent headaches and visual disturbances • Pulmonary edema • Persistent upper abdominal pain • Elevated liver enzymes ( >2x upper limits of normal) • Low platelets <100,000/mm • Serum creatinine >1.1 mg/dl

27 Severe Preeclampsia is Increasing

Temporal changes in rates of preeclampsia 1980 to 2010 in the U.S. for 120 million hospital discharges

Causes of trend: 1. Increased obesity 2. Older mothers

3. Decrease in smoking Preeclampsia (%) Preeclampsia

Year

Ananth CV, Ke2009 Natality Statistics, CDC Adverse Fetal / Neonatal Effects of Preeclampsia

Stillbirth Neonatal death

Reduced amniotic fluid Long-term Abruption consequences

Growth restriction Preterm birth

29 Balancing Act Between Health of Mother and Baby

Fetal / Newborn Maternal Risk Benefit

30 Agenda

• Disease overview

• Health consequences for mother and infant

• Current management unsatisfactory

31 Current Management of Early Onset Preeclampsia is Associated with Severe Neonatal and Maternal Morbidity

Expectant treatment of preeclampsia <28 weeks, UT - Houston

100% Composite Neonatal Morbidity (CNM) 90% Composite Maternal Morbidity (CMM) 80%

70%

60%

50%

40%

30%

20% <23.0 23-23.6 24-24.6 25-25.6 26-26.6 27-27.6 Gestational age at diagnosis (weeks) CMM; defined as HELLP, eclampsia, placenta abruption, pulmonary edema, or renal failure CNM; defined as BPD, NEC, IVH 3 or 4, proven sepsis, or death

Balogun OA, et al. Am J Perinatol 2018 32 Delivery is Not Good for the Extremely Preterm Infant

33 Increasing Gestational Age at Delivery Decreases Neonatal Mortality and Morbidity

Mortality Survived without Significant Morbidity

% % 50 50

40 40

30 30

20 20

10 10

0 0 24 25 26 27 28 24 25 26 27 28 Gestational Age (wks)

Stoll et al, Pediatrics, 2010 Morbidity: BPD, IVH, PVL, NEC, ROP, late sepsis 34 Babies Born at 24-28 Weeks Suffer Severe Neonatal Complications

65%

24%

8% 10% 5%

RDS BPD NEC PVL IVH Respiratory Distress Bronchopulmonary Necrotizing Periventricular Intraventricular Syndrome Dysplasia Enterocolitis Leukomalacia Hemorrhage

Stoll et al, Pediatrics, 2010 35 Babies Born at 24-28 Weeks have Significant Risk of Complications

Chronic Lung Disease

Chronic Heart Disease

Hearing/vision Disorders

Cerebral Palsy

Other Neurological disabled

36 Women with Severe Preeclampsia Have a High Rate of Pulmonary Edema

37 Women with Severe Preeclampsia are at Risk of Kidney Injury

38 Women with Severe Preeclampsia are at Risk for Seizures and Stroke

Resolved 2 wk PP

39 Severe Preeclampsia is a Major Burden to the Healthcare System

• Severe preeclampsia < 32 weeks gestation − Incidence: 0.2- 0.3%1 • Significant cost of preeclampsia within first 12 months of delivery − Greater than $2 billion per year in the U.S.

1 Sibai BM, Barton JR. Am J Obstet Gynecol 2007; Stevens W, et al. Am J Obstet Gynecol 2017 40 Agenda

• Disease overview

• Health consequences for mother and infant

• Current management unsatisfactory

41 Current Management of Severe Preeclampsia ACOG / SMFM Guidelines

< 23 or ≥ 34 wk. 23 - 33 5/7 wk.

• Corticosteroids • Magnesium sulfate • Anti-hypertensives

• Magnesium sulfate • Expectant management • Stabilize mother Delivery for • Delivery • Maternal reasons • Fetal reasons • GA of 34 wks ACOG: American College of Obstetricians and Gynecologists SMFM: Society for Maternal-Fetal Medicine 42 Current Management of Severe Preeclampsia < 340/7 wks

• Admit to L&D: 24-48 hrs. • Magnesium sulfate prophylaxis • Corticosteroids • Anti-hypertensives • Ultrasound: EFW, BPP. Doppler • Frequent FHR monitoring • Daily monitoring of VS and symptoms • Daily laboratory tests • Delivery for maternal or fetal indications

43 In Summary

• The incidence of severe preeclampsia is increasing

• Severe preeclampsia is associated with a high risk for maternal and neonatal complications

• Currently the only cure for preeclampsia is delivery, which may not be in the best interest of the newborn

• There is an urgent need for a new therapy to prevent complications of severe preeclampsia in order to improve maternal and newborn outcomes

44 AMAG-423 for the Treatment of Severe Preeclampsia An Opportunity to Improve Maternal and Neonatal Outcomes Worldwide Baha M. Sibai, MD Professor, MFM Division Director, MFM Fellowship Program Department of Obstetrics, Gynecology and Reproductive Sciences McGovern Medical School-The University of Texas Health Sciences at Houston Disclosures

• Dr. Sibai has received research grant support and Present Research/Grant Funding consulting fees in the past from Alere, Progenity, and • NICHD rEVO Biologics . • NIHHLB • Progenity Inc. • This is an educational lecture and is not intended to be • AMAG Pharmaceuticals, Inc. (principal investigator) an inducement to use any drug or drug in a fashion that is inconsistent with the drug or device label. Adjudication Committee • The slides were prepared by Baha Sibai, M.D. and/or • GestVision were under the editorial control of Dr. Sibai

46 Take-Away Messages

1. Severe preeclampsia is associated with high maternal and neonatal morbidity and mortality and economic burden

2. EDLFs play a key role in the pathogenesis of preeclampsia, and its levels correlate with abnormal renal function, pulmonary edema, and neonatal NEC

3. Novel therapy that targets EDLFs has potential for significant improvement in maternal and neonatal outcomes worldwide

4. AMAG-423 has the potential to reduce costs associated with severe preeclampsia

47 Agenda

• Etiology of preeclampsia and role of Endogenous Digitalis-Like Factors (EDLFs)

• Potential role of AMAG-423 for the treatment of severe preeclampsia

• DEEP trial

• Phase 2b/3a study

48 Role of EDLFs in Pathogenesis of Preeclampsia / Clinical Manifestations

Maternal effects Fetal / neonatal effects • Hypertension • Intraventricular hemorrhage • Proteinuria Increased EDLFs • Necrotizing enterocolitis • Reduced kidney function • Placenta • NICU admission • Pulmonary edema • Respiratory distress • Fetus • Brain edema syndrome • Liver dysfunction • Mother • Death • Death • Long-term disease • Long-term disease 49 Rationale to Study AMAG-423 in Severe Preeclampsia

• EDLFs are circulating inhibitors of the Na+ K+ ATPase pump (“sodium pump”)1 − Vasoconstriction − Elevated blood pressure − Decreased blood flow to tissues

• EDLFs are implicated in a number of diseases including hypertension and preeclampsia1

• AMAG-423 originally developed and currently commercialized (outside of AMAG) as treatment for digoxin overdose − Binds to EDLFs, removing from the circulation2 − Reverses sodium pump inhibition1 − Potential to improve maternal/ neonatal outcome3

1 Lam GK et al. Digoxin antibody fragment, antigen binding (Fab), treatment of preeclampsia in women with EDLF: a secondary analysis of the DEEP Trial. American Journal of Obstetrics & Gynecology. August 2013, pp119.e1- 119.e6. 2 DigiFab® Prescribing Information, 12.1 Mechanism of Action. 3 Wang Y et al, Digoxin Immune Fab Protects Endothelial Cells from Ouabain-Induced barrier Injury. Am J Reprod Immunol. Author manuscript; available in PMC 2016 December 07. 50 Binding to EDLFs Restores Sodium Pump Activity

Ginsenosides Ca2+ B AMAG-423 K+ K+ K+ K+

A C EDLFs K+ K+ K+ K+ K+ Na+ - K+ Inhibits ATPase potassium 2 pumps Ca + Na+ Na+ current Intracellular cAMP calcium compartments Ca2+ Glucose metabolism ATP Ca2+ Ca2+ Cell

Microtubule D Insulin myosin granule filament

51 Results of Phase 2 DEEP Study Published in Major Obstetric Journals

2010

52 DEEP Trial Demonstrated Potential of AMAG-423 to Improve Maternal and Neonatal Outcomes1

Entry Criteria Treatment Primary Maternal Endpoints

• Severe preeclampsia E AMAG-423 (n= 24) Z • Change in creatinine • 23w5d - 34w clearance at 24-48 hours • Expected delivery < 72 h DOMI • Change in use of

Dosing every 6 h (1.6mg/kg) N Placebo (n= 27) antihypertensive drugs

for 2 days RA

Results Secondary analysis of DEEP Trial2 • No decline in creatinine clearance in AMAG-423 arm, • Included patients who were EDLF positive at baseline compared to decrease in placebo arm (p=0.02) • 78% of DEEP patients were EDLF positive • Antihypertensive use similar between DIF and placebo (p=0.7) Safety • Two infant deaths in placebo arm (GA 24 and 27 weeks); no deaths in AMAG-423 arm

1 Adair CD, Buckalew VM, Graves SW, et al. Digoxin immune fab treatment for severe preeclampsia. Am J Perinatol. 2010;27:655-62. 2 Lam GK et al. Digoxin antibody fragment, antigen binding (Fab), treatment of preeclampsia in women with EDLF: a secondary analysis of the DEEP Trial. American Journal of Obstetrics & Gynecology. August 2013, pp119.e1- 119.e6. 53 Change in Creatinine Clearance and Relationship with EDLF Levels

AMAG-423 Preserved Renal Function as Compared to Placebo

Statistically Significant Preservation of Creatinine Clearance Decline in Placebo Group Renal Function in DIF Treated Women1 Correlated to EDLF Levels2 (measured by sodium pump activity)

0 0 n=15 -10 -10 -20

-30 -20 n=20 -40 -30 -50 p=0.02 -60 -40

-70

-50 from baseline (mL/min) baseline from

Change in creatinine clearance creatinine in Change -60

24-48h (LOCF) No EDLF Lo EDLF Hi EDLF Change in creatinine clearance (mL/min) clearance creatinine in Change ‒ AMAG-423 ‒ Placebo Plasma EDLF Levels

1 Adair CD, Buckalew VM, Graves SW, et al. Digoxin immune fab treatment for severe preeclampsia. Am J Perinatol. 2010;27:655-62. 2 Lam GK et al. Digoxin antibody fragment, antigen binding (Fab), treatment of preeclampsia in women with EDLF: a secondary analysis of the DEEP Trial. American Journal of Obstetrics & Gynecology. August 2013, pp119.e1- 119.e6. 54 Maternal Outcomes in Patients Who Were EDLF Positive at Baseline1

Trends in Improvements in Maternal Outcomes in AMAG-423 Treated Patients Compared to Placebo

Blurred Vision Use of Antihypertensives Pulmonary Edema

p=0.136 p=0.117 p=0.035* 70% 70% n=12 70% 60% 60% 60%

50% 50% 50% n=7 40% n=7 40% 40% n=6 30% 30% 30%

20% n=3 20% 20%

10% 10% 10% n=1

% of use of antihypertensives of use of % % of patients with blurred vision blurred with patients of %

0% 0% 0% % of patients with pulmonary edema pulmonary with patients of % AMAG-423 n=17 Placebo n=19 AMAG-423 n=17 Placebo n=19 AMAG-423 n=17 Placebo n=19

*Statistically significant

DEEP Trial: Selected Neonatal Outcome Measures1

Intraventricular Hemorrhage (IVH) Necrotizing Enterocolitis (NEC) Neonatal Deaths Severe (grades 3 and 4)

p=0.24 p=0.61 15% p=0.49 15% 15%

n=3 n=3 10% 10% 10% n=2

5% 5% n=1 5%

% of neonatal Deaths neonatal of %

% of neonates with IVH with neonates of % % of neonates with NEC with neonates of % n=0 n=0 0% 0% 0% DIF n=24 Placebo n=27 DIF n=24 Placebo n=27 DIF n=24 Placebo n=27

1 Adair CD, Buckalew VM, Graves SW, et al. Digoxin immune fab treatment for severe preeclampsia. Am J Perinatal. 2010;27:655-62 56 Clinical and Mechanistic Evidence Supporting Role of EDLFs in Preeclampsia

• EDLFs elevated in 78% of patients in DEEP trial1

• Increased EDLF levels in mother correlated with decline in creatinine clearance

• Increased EDLF levels in cord blood correlated with necrotizing enterocolitis in infant2

• Subjects who were EDLF positive showed better responses to AMAG-423, implying potential for drug benefit

• Proof of principle established in DEEP trial demonstrating consistent and positive trends in both maternal and fetal outcomes with favorable safety profile

1 Lam GK et al. Digoxin antibody fragment, antigen binding (Fab), treatment of preeclampsia in women with EDLF: a secondary analysis of the DEEP Trial. American Journal of Obstetrics & Gynecology. August 2013, pp119.e1- 119.e6. 2 Graves SW et al. Association of cord blood digitalis like factor and necrotizing enterocolitis. Am J Obstet Gynecol 2014;210:328.e1-e5. 57 AMAG-423 Phase 2b/3a Study Design Efficacy and Safety of AMAG-423 in Antepartum Severe Preeclampsia Composite Neonatal Entry Criteria Treatment Primary Endpoint

• Severe preeclampsia • Severe intraventricular AMAG-423 (n= 100) E hemorrhage • 23w - 31w6d Z • Singleton gestation Dosing IV (3.2 mg/kg) every • Necrotizing enterocolitis

• Candidate for expectant DOMI 6 h for 4 days (16 total doses) • Death management N RA Placebo (n= 100)

Secondary Maternal Outcomes:

• Pulmonary edema • Use of anti-hypertensive medications • Delivery latency • Modified early obstetric warning score • Change in serum creatinine ≥3 at 24 hours post final dose

58 Contraindications to Continuing Expectant Management

• Eclampsia • < 230/7 weeks (individualize) • Pulmonary edema • Acute renal failure • HELLP syndrome • Abruptio placentae • Abnormal fetal testing • Achievement of 34 weeks

59 Challenges to Enrollment

• Low incidence of severe preeclampsia • Patient eligibility: new guidelines added strict criteria for expectant management • Need for frequent blood draws • Labor intensive study: requires unique infrastructure • Fear of participation in research: not FDA-approved drug in pregnancy

60 SUMMARY Take-Away Messages

1. Severe preeclampsia is associated with high maternal and neonatal morbidity and mortality and economic burden

2. EDLFs play a key role in the pathogenesis of preeclampsia, and its levels correlate with abnormal renal function, pulmonary edema, and neonatal NEC

3. Novel therapy that targets EDLFs has potential for significant improvement in maternal and neonatal outcomes worldwide

4. AMAG-423 has the potential to reduce costs associated with severe preeclampsia

61 Tony Casciano AMAG Chief Commercial Officer

62 AMAG-423 Has the Potential to Address a Serious Unmet Need Significant burden to the healthcare system

 Unmet medical need Annual U.S. incidence of Annual U.S. incidence of preeclampsia SEVERE preeclampsia  Strong target product profile ~140,000 ~50,000  Space for innovation pregnant women pregnant women  AMAG strategic fit

Significant $2.2 billion annual burden to U.S. healthcare system1

1 Stevens W et al, Short-term costs of preeclampsia to the U.S. health care system. American Journal of Obstetrics & Gynecology. September 2017, Volume 217, Issue 3, pp237- 248.e16.

66 Hypoactive Sexual Desire Disorder (HSDD)

Sheryl Kingsberg, PhD Chief, Division of Behavioral Medicine University Hospitals Cleveland Medical Center MacDonald Women’s Hospital Professor, Departments of Reproductive Biology and Psychiatry Case Western Reserve University School of Medicine Cleveland OH, USA

67 Disclosures

• Paid consultant or on a scientific advisory board: AMAG Pharmaceuticals, Daré, Duchesney, Emotional Brain, Endoceutics, GTx, IVIX, Lupin, Materna, MTNA, Palatin Technologies, Pfizer, Sprout, Strategic Science Technologies, TherapeuticsMD

• Institutional Grant Support (Clinical Trial Investigator): Endoceutics, Palatin

• Stock options: Viveve

68 Agenda

• Condition overview and unmet need

• Adverse impact

• Diagnostic tools and efficacy endpoints

• Current treatment options

69 Biopsychosocial Factors that Contribute to Sexual Function

(e.g., physical health, (e.g., performance neurobiology, Biology Psychology anxiety, depression) endocrine function)

(e.g., upbringing, (e.g., quality of current cultural norms and Sociocultural Interpersonal and past relationships, expectations) intervals of abstinence, life stressors, finances)

Rosen RC, Barsky JL. Obstet Gynecol Clin North Am. 2006;334:515-526. 70 HSDD is a Medical Condition Characterized by Low Sexual Desire and Associated Distress1-4

• Women with HSDD experience absence or marked reduction in desire or motivation to engage in sexual activity • Associated with clinically significant distress • Onset for at least several months

1. ICD-11: HA00 Hypoactive sexual desire dysfunction. WHO website. https://icd.who.int/browse11/l-m/en. Accessed February 20, 2019. 2. ACOG Committee on Practice Bulletins-Gynecology. Obstet Gynecol. 2011;117(4):996-1007. 3. Goldstein I, et al. Mayo Clin Proc. 2017;92(1):114-128. 4. APA. In: APA, ed. Diagnostic and Statistical Manual of Mental Disorders: DSM-IV-TR; 2000:539-541. 71 HSDD in 2019 is Akin to Depression in 1989

72 Etiology of HSDD: Imbalance Between Excitation/Inhibition

• Dopamine • Oxytocin Physiological/ • Serotonin • Melanocortin • Opioids • Vasopressin Organic • Endocannabinoids • Norepinephrine

• Intimacy • Relationship conflict • Shared values Psychosocial/ • Negative stress • Romance Interpersonal • Negative beliefs about sex • Experience/behavior • Experience/behavior

EXCITATION INHIBITION

1. Bancroft J, et al. J Sex Res. 2009;46:121-142. 2. Perelman MA. J Sex Med. 2009;6:629-32. 73 PET Scan Differences Between Women With and Without HSDD

• Women with HSDD have weaker activation in cerebral cortex in right hemisphere . Muted response to sexual cues • Women with HSDD have less deactivation in left hemisphere . Inability to deactivate higher order processing perpetuates inhibitory neural pathways

Holstege G. Sex Med Rev. DOI: http://dx.doi.org/10.1016/j.sxmr.2016.04.002 74 High Prevalence of Female Sexual Dysfunction (FSD) PRESIDE1 Approximately 6 million premenopausal women in the United States have HSDD2

Prevalence of Female Sexual Problems OBJECTIVES Associated with Distress Estimate the prevalence of self-reported sexual problems (any, desire, arousal, and Sexual Problems Distressing Sexual Problems orgasm), the prevalence of problems accompanied by personal distress, and 43.1% describe related correlates 37.7% NOT DETERMINED Whether low desire with sexually related personal distress was primary or secondary 25.3% to another illness; pain was not assessed 21.1%

POPULATION 11.5% 31,581 US female respondents 9.5% ≥18 years of age from 50,002 households 5.1% 4.6%

Desire Arousal Orgasm Any

1. Shifren JL, Monz BU, Russo PA, Segreti A, Johannes CB. Obstet Gynecol. 2008;112(5):970-978. 2. Johannes CB, Clayton, AH, Odom AM, Rosen, RC, Russo PA, Shifren JL, Monz, BU. J Clin Psychiatry. 2009;70(12): 1698-706. 75 Agenda

• Condition overview and unmet need

• Adverse impact

• Diagnostic tools and efficacy endpoints

• Current treatment options

76 Impact of HSDD on a Relationship

When sex is good… When sex is bad or non-existent… It adds additional value to a It plays an inordinately powerful relationship role draining the relationship of positive value!

77 HSDD is NOT

• Lack of desire due to a bad relationship • Lack of desire due to time pressures • Lack of desire due to fatigue • Lack of desire due to no privacy

78 Agenda

• Condition overview and unmet need

• Adverse impact

• Diagnostic tools and efficacy endpoints

• Current treatment options

79 Diagnostic Tools for Clinicians

Diagnostic Tool • Decreased Sexual Desire Screener (DSDS)

80 Easy-to-Administer Screening Tool

Clayton AH, Goldfischer ER, Goldstein I, et al. J Sex Med. 2009;6(3):730-738. 81 Easy-to-Administer Screening Tool

If yes to all four questions, evaluate for potential contributing factors:

Clayton AH, Goldfischer ER, Goldstein I, et al. J Sex Med. 2009;6(3):730-738. 82 Validated Scales for Trial Endpoints

Efficacy Endpoints • Female Sexual Function Index-Desire Domain (FSFI-D) • Female Sexual Distress Scale (FSDS-R) Item 13 • Satisfying Sexual Events (SSEs)

83 Female Sexual Function Index – Desire Domain (FSFI-D)1

Sexual desire or interest is a feeling that includes wanting to have a sexual experience, feeling receptive to a partner’s sexual initiation, and thinking or fantasizing about having sex FSFI-D ≤3 may indicate the presence of HSDD

1. Over the past 4 weeks, how often did you feel sexual desire or interest? A few times Most times Almost never Sometimes Almost always or (less than half (more than half or never (about half the time) always the time) the time) 1 2 3 4 5

2. Over the past 4 weeks, how would you rate your level (degree) of sexual desire or interest?

Very low or Low Moderate High Very high none at all 1 2 3 4 5

1. Gerstenberger EP, et al. J Sex Med. 2010;7(9):3096-3103. 84 Female Sexual Distress Scale-Revised (item 13)

0 = Never Q13: 1 = Rarely How often did you feel 2 = Occasionally bothered by low desire? 3 = Frequently 4 = Always

85 Agenda

• Condition overview and unmet need

• Adverse impact

• Diagnostic tools and efficacy endpoints

• Current treatment options

86 Few HSDD Treatment Options

• Psychotherapy: Safe but often won’t address neurobiologic etiology • Only one approved medication (Addyi) • >50% of women with HSDD have sought treatment options on the Internet − An estimated $39B by 2024 will be spent on sexual wellness, including unregulated, suspiciously marketed products with no proven safety or efficacy1

1. Arizton Research Sexual Wellness Market - Global Outlook and Forecast 2019-2024 3rd Ed March 2019 87 In Summary

• Approximately 6 million premenopausal women suffer from Hypoactive Sexual Desire Disorder (HSDD) • HSDD similar to Depression in biopsychosocial etiology and response to treatment • Currently only 1 FDA approved pharmacologic option • Screening and diagnosis can be managed by non-specialist HCPs

88 VyleesiTM (bremelanotide) Overview

David J Portman, MD Director Emeritus, Columbus Center for Women’s Health Research, Adjunct Instructor, Ohio State University Columbus, Ohio

89 • Paid consultant, scientific advisory board, or speaker’s bureau: AMAG Pharmaceuticals, Palatin Technologies, TherapeuticsMD, Agile, Duchesney, Endoceutics, ITF Pharma Disclosures • Employee: Sermonix Pharmaceuticals

• Shareholder: Sermonix Pharmaceuticals

90 • Neurobiologic basis of HSDD and Vyleesi—mechanism of action • Phase 3 clinical overview • Co-primary endpoints Agenda • Practice considerations / patient implications • Summary

91 Neurotransmitter and Central Regulation of Desire / Arousal: Melanocortin a Key Component

Serotonin

Melanocortins

(+)

Estrogen (-) Progesterone Serotonin

Adapted from Clayton A et al. Obstet Gynecol Clin North Am. 2009;36(4):861-876.

92 MOA: Potential to Modulate Brain Pathways Involved in Sexual Desire

HSDD-related Dopamine Release Treatment of HSDD With Vyleesi Vyleesi (bremelanotide): an investigational, novel cyclic 7-amino acid melanocortin- receptor-4-agonist (MC4R)1 BMT Vyleesi acts on the physiological and neurobiological components of female sexual function Increased release • Potential to modulate brain pathways of dopamine involved in sexual desire and arousal in women with HSDD2

1. Molinoff PB, et al. Ann N Y Acad Sci. 2003;994:96-102. 2. Pfaus J. J Sex Med. 2007;4(suppl 4):269-279.

93 Phase 3 Outcome Measures: Clinical Overview

• Co-primary Efficacy Endpoints – Change in Female Sexual Function Index (FSFI): Desire Domain – Change in Female Sexual Distress Scale (FSDS): Item 13 Score • Responder Analysis—basis for determining clinical meaningfulness – Patient self-reporting “To what degree do you think you benefited from taking the study drug?” – The proportion of participants meeting or exceeding predefined minimal clinically important differences (MCIDs)

94 Key Entry Criteria and Demographics

• Healthy premenopausal, non-pregnant women • >18 years of age, currently in a stable (>6 months) relationship • Diagnosed with HSDD (with/without decreased arousal) for >6 months • Experience ‘normal’ sexual function in the past for >2 years • Willing to engage in sexual activities >1x/month during the study

95 Vyleesi Improves Co-primary Desire Endpoint

0.9 Study 301 – Placebo (n=316) Study 302 – Placebo (n=290) Study 301 – BMT 1.75 mg (n=314) Study 302 – BMT 1.75 mg (n=282) 0.8

0.7

D Score (SD) Score D -

0.6 Improvement

0.5

0.4

0.3 Placebos 0.2

0.1 P <0.001 for all evaluable time points

0.0 Change from Baseline FSFI from Baseline Change 0 1 2 3 4 5 6

Months AMAG data on file

96 Vyleesi Improves Co-primary Distress Endpoint Female Sexual Distress Scale FSDS-DAO item 13

Study 301 – Placebo (n=316) Study 302 – Placebo (n=290) Study 301 – BMT 1.75 mg (n=314) Study 302 – BMT 1.75 mg (n=282) 0.0 -0.1 -0.2

-0.3 Placebos Improvement DAO Score 13 ItemDAO

- -0.4 -0.5 -0.6 -0.7 -0.8 -0.9 P <0.001 for all evaluable time points -1.0

0 1 2 3 4 5 6 Change from Baseline FSDS Baseline from Change AMAG data on file Months

97 Higher Meaningful Response Rate with Vyleesi than Placebo

Global Assessment Questionnaire Q3 Percent Responders Defined by a Score for Co-Primary Endpoints at EOS of ≥5 on GAQ Question #3

“Compared with the start of the study (prior to 70.0 p<0.0001 taking the study drug), to what degree do you 60.0 58.2 think you benefited from taking the study drug?” 50.0

Very No Very 40.0 35.6 Much Change Much BMT Worse Better 30.0 1.75mg 1 2 3 4 5 6 7 20.0 Placebo

Percent Responders in GAQ #3 GAQ in Responders Percent 10.0

Responder defined as score of ≥5 0.0 N = 606 596 Integrated Phase 3 AMAG data on file

98 • Favorable safety profile . Adverse events (AEs) were primarily tolerability related - nausea, flushing, injection site reactions, headache were most common AEs • Data demonstrates positive benefit risk Practice • Meaningful data for the clinician and patients Considerations • Self-administered subcutaneous injection was well-tolerated and not a barrier to use in Phase 3 program • Significant unmet need and large addressable patient population

99 • Vyleesi is a novel, as-needed treatment for HSDD with a near-term PDUFA date • Robust efficacy data with co-primary Summary endpoints met • Clinicians and patients are eager for an on-demand product with no alcohol warning and few prescribing hurdles

100 Fireside chat with 1 in 10 premenopausal women in the Dr. Kingsberg U.S. have HSDD and HSDD patient (approximately 6 million women)

101 TM TMaa Vyleesi (bremelanotide) Commercial Overview

Meghan Rivera Vice President, Head of Women’s Health Sales and Marketing

Vyleesi is an investigational product currently under review by FD. Safety and efficacy has not been established 102 Situation

When it comes to female sexual health–and more specifically hypoactive sexual desire disorder (HSDD)–there’s a huge gap in the market.

103 The HSDD Market Provides Substantial Untapped Opportunity —

1/101,2 — Number of premenopausal women who have low desire with associated distress

1. Shifren JL, Monz BU, Russo PA, Segreti A, Johannes CB. Sexual problems and distress in United States women: prevalence and correlates. Obstet Gynecol. 2008;112(5):970–978. 2. Goldstein I, Kim NN, Clayton AH, et al. Hypoactive sexual desire disorder: International 104 Society for the Study of Women’s Sexual Health (ISSWSH) expert consensus panel review. Mayo Clin Proc. 2017;92(1):114‐128. The HSDD Market Provides Substantial Untapped Opportunity —

95%1 — Percentage of women who are not yet aware of HSDD and that their distressing lack of desire is a medical condition

1. Palatin supported research that was performed by Burke, Inc., an ISO 20252–certified company, in compliance with the established standard 105 for market, opinion, and social research. The HSDD Market Provides Substantial Untapped Opportunity —

91%1 — Percentage of HCPs not satisfied with current treatment options

1. Palatin supported research that was performed by Burke, Inc., an ISO 20252–certified company, in compliance with the established standard 106 for market, opinion, and social research. Question How can women seek treatment for a condition that they don’t even know about?

Answer

AMAG will make HSDD part of the larger cultural conversation and connect with mass audiences.

107 Can it be Done??

Following the launch of a novel solution for depression, the rate of diagnosis, dialogue and understanging about the condition dramatically shifted.

Similarly, with the introduction of Vyleesi, the landscape for the treatment of female sexual dysfunction will change fundamentally.

108 The “How”

109 An Approach with Proven Results

Several health and wellness brands have embraced consumer branding principles and prioritized digital channels as growth engines, showing tremendous success.

110 A Focus on Digital Channels

Focus paid media on social and digital channels where women already are.

111 Destigmatizing the Conversation

Create an online community where women with HSDD can get a wealth of accurate resources, check their symptoms, and get support.

112 Accelerating Path to Treatment

Create a line-up experience program to allow early adopters to get an advanced prescription through telemedicine.

113 Ensuring Provider Readiness

Activate a sales force and HCP campaign that will ensure our grant rate allows us to capitalize on consumer interest.

114 The Initial Metrics Speak for Themselves

Leading indicators of campaign performance continue to instill our confidence in our approach… - Close to 50% open rate on email to providers, more than double industry benchmark - In just week one, 2.82M impressions, 80k clicks to our community, and over 700 engagements with only one promoted post - 485% increase in daily click-through’s from HSDD search terms YoY

115 Experience, Experience, Experience

Vyleesi is all about experience. From the experience of engaging with our brand to the meaningful impact we believe Vyleesi will have on women’s lives. And this gives us reason to believe that the experience will reverberate via word of mouth and earned media

116 In Summary

• There is a significant market opportunity and unmet need

• The Vyleesi experience will allow for reverberation and growth

• A disruptive go-to-market strategy is critical to drive awareness and rapid uptake

117 VYLEESI

C. Michael Gibson, MD, Interventional cardiologist, cardiovascular researcher, Beth Israel Deaconess Medical Center, Boston, MA Ciraparantag (in development as an Joseph Bledsoe, MD, Dept. of Emergency Medicine, Intermountain Healthcare, Salt Lake City, UT; anticoagulant reversal agent) Stanford University medical faculty: Intermountain-Stanford collaborative Jack Ansell, MD, Professor of Medicine, Hofstra Northwell School of Medicine

120 The Need For Anticoagulant Reversal Agents: A Physician’s Perspective

Harvard C. Michael Gibson, M.S., M.D. Medical School Interventional Cardiologist Chief, Clinical Research, Beth Israel Deaconess CV Division Professor of Medicine Harvard Medical School President & CEO of Non-Profit Baim Institute & PERFUSE Study Group Founder, Editor-In-Chief www.wikidoc.org Disclosure

• Dr. Gibson has received research grant support and consulting fees in the past from all major manufacturers of antiplatelets and antithrombins and the manufacturers of andexanet (Portola) and PCC (CSL)

• This is an educational lecture and is not intended to be an inducement to use any drug or drug in a fashion that is inconsistent with the drug or device label. Rivaroxaban is not approved for use in acute coronary syndromes in the US, but is so in many other countries

• The slides were prepared by C. Michael Gibson, M.S., M.D. and / or were under the editorial control of C. Michael Gibson, M.S., M.D.

Slide by C. Michael Gibson, M.S., M.D. 122 Disclosures

Present Research/Grant Funding Spouse: Employee of Boston Clinical Research Institute, she has equity position Angel Medical Corporation Amarin Medtelligence Bayer Corp. / Janssen CSL Behring Amgen MedImmune Portola Pharmaceuticals Bayer/Janssen/ J&J The Medicine’s Co. Baim Institute (no salary) Boehringer Ingelheim Merck & Co. Inc. Patents and Stocks: None Boston Scientific Microport Cardiovascular Research Novo Nordisk Equity: nference, Inc. Foundation PERT Consortium Consultant CSL Behring PharmaMar AMAG Pharmaceuticals Chiesi Portola Boston Clinical Research Institute DCRI Sanofi Cardiovascular Research Foundation CSL Eli Lilly Somahlution Eli Lilly Impact Bio, LTD Verseon Corporation Medtelligence Gilead Sciences, Inc. Novo Nordisk PharmaMar The Medicines Company Portola Bayer / Janssen/ J&J WedMD

Slide by C. Michael Gibson, M.S., M.D. 123 Agenda

Growing use of NOACs

Large current unmet need

Role of cardiology clinical practice in reversal agents

Slide by C. Michael Gibson, M.S., M.D. 124 The Growing Number of Indications for Factor Xa Inhibitors Means We Need Reversal Agents

• Atrial fibrillation

• Surgical venous thromboembolism (VTE) prophylaxis (knee and hip surgery)

• Medically ill VTE prophylaxis

• VTE treatment (Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE))

• Acute coronary syndrome (Ex U.S.)

Slide by C. Michael Gibson, M.S., M.D. 125 NOACs Are Now More Widely Prescribed Than Warfarin

Treatment Share – All Specialties Current 6 Months

Warfarin 40% NOACs 60%

NOACs include XARELTO, Eliquis, Pradaxa, Savaysa, Bevyxxa Slide by C. Michael Gibson, M.S., M.D. Source: IQVIA NPA Weekly TRx, Data to: Apr 19, 2019 126 NOAC Market Share Now Greater than Warfarin and Growing

TRx Share – All Specialties Share - TRx 70% 62.3% 60% NOACs 50%

40% Warfarin 37.7% 30%

20%

10%

NOACs include XARELTO, Eliquis, Pradaxa, Savaysa, Bevyxxa Slide by C. Michael Gibson, M.S., M.D. Source: IQVIA NPA Weekly TRx, Data to: Apr 19, 2019 127 Agenda

Growing use of NOACs

Large current unmet need

Role of cardiology clinical practice in reversal agents

Slide by C. Michael Gibson, M.S., M.D. 128 Major Bleeding (e.g. GI Bleeding) Complication of Factor Xa Inhibitors

Heterogeneity ICH, p=0.22 GI Bleeding, p=0.009 Risk Ratio (95% CI)

ICH 0.48 (0.39 - 0.59) p<0.0001

GI Bleeding 1.25 (1.01 - 1.55) p=0.043

0.2 0.5 1 2 Favors NOAC Favors Warfarin

Slide by C. Michael Gibson, M.S., M.D. Ruff CT, et al. Lancet 2014;383:955-962 129 Anticoagulants Are a Major Contributor to Emergency Department Visits for Adverse Drug Effects (2005-2014)

ED Visits National Estimate, % (95% CI)

Drug Class 2005-2006 2007-2008 2009-2010 2011-2012 2013-2014

Antibiotics 19.2 (17.7-20.7) 18.6 (16.8-20.4) 18.6 (16.7-20.6) 17.9 (16.6-19.3) 16.1 (14.4-17.8)

Anticoagulants 7.3 (4.6-9.9) 9.9 (7.6-12.2) 11.2 (8.2-14.1) 13.3 (11.1-15.4) 17.6 (14.2-21.0)

Antineoplastic agents 1.8 (0.8-2.8) 1.6 (0.8-2.4) 2.5 (1.2-3.9) 2.4 (1.3-3.4) 3.0 (1.6-4.3)

Antiplatelets 3.7 (2.1-5.2) 4.6 (2.7-6.5) 4.6 (2.9-6.2) 4.8 (3.2-6.4) 6.6 (4.7-8.5)

Antipsychotics 2.8 (2.2-3.4) 3.0 (2.5-3.5) 3.0 (2.6-3.4) 3.1 (2.5-3.7) 2.7 (2.1-3.2)

Diabetes agents 10.9 (7.3-14.5) 12.8 (9.1-16.6) 12.0 (9.1-14.9) 12.0 (9.1-14.8) 13.3 (10.8-15.8)

NSAIDs 4.1 (3.4-4.8) 3.5 (3.0-3.9) 3.2 (2.8-3.6) 3.2 (2.7-3.7) 2.8 (2.4-3.2)

Opioid analgesics 7.7 (6.9-8.6) 7.9 (7.1-8.8) 7.2 (6.6-7.8) 7.9 (7.2-8.5) 6.8 (6.3-7.4)

RAS inhibitors 2.4 (1.9-2.9) 2.5 (1.9-3.0) 2.9 (2.2-3.7) 3.2 (2.4-4.0) 3.5 (2.6-4.4)

Sedative/hypnotic agents 3.2 (2.7-3.7) 3.2 (2.8-3.6) 3.6 (3.1-4.2) 3.4 (2.8-3.9) 3.0 (2.4-3.5)

Slide by C. Michael Gibson, M.S., M.D. JAMA 316.20 (2016): 2115-2125 130 NOACS Are A Growing Contributor to Emergency Department Visits for Adverse Drug Effects (2005-2014)

ED Visits ED Visits Resulting in Hospitalizations

Drug Class Cases National Estimates, % Cases National Estimates, %

Anticoagulants 7211 17.6 (14.1-21.0) 3691 48.8 (42.0-55.5)

Vitamin K antagonists (warfarin) 6179 15.1 (12.3-17.9) 3156 48.5 (41.8-55.1)

Factor Xa inhibitors 580 1.4 (0.9-2.0) 300 50.4 (43.0-57.8)

UFH & LMWH 450 0.8 (0.6-1.1) 224 46.5 (38.7-54.4)

Direct thrombin inhibitors 173 0.5 (0.2-0.7) 107 63.8 (49.8-77.8)

Slide by C. Michael Gibson, M.S., M.D. JAMA 316.20 (2016): 2115-2125 131 PIONEER Results: It is Difficult to Predict Patients at Risk for Bleeding

Major Bleeding

Univariate* Multivariate* OR (95% CI) p-value OR (95% CI) p-value BMI 0.94 (0.89-1.00) 0.06 # Stents 1.39 (1.01-1.90) 0.043 Hemoglobin 0.98 (0.96-1.00) 0.023

Age ≥ 75 Years (Y vs. N) 2.84 (1.55-5.22) <0.001 2.84 (1.55-5.22) <0.001

Prior MI (Y vs. N) 0.40 (0.16-1.03) 0.06

Hypercholesterolemia (Y vs. N) 0.49 (0.25-0.94) 0.032

*Models were adjusted for treatment and baseline HASBLED score

HAS-BLED c-statistic: 0.537 Final Logistic Regression c-statistic: 0.658 Slide by C. Michael Gibson, M.S., M.D. AHA 2017 132 Reducing the Dose of NOACs to Reduce Bleeding May Increase the Risk of Ischemic Stroke/Systemic Embolization by Nearly 5 Fold

Patients Initiating NOACs Without A Renal Indication For Dose Adjustment – US Insurance Claims Database (1 Oct 2010 - 30 Sep 2015)

Event rate per 100 person-years Hazard ratio (95% CI) p-value

Reduced dose Standard dose Reduced dose vs standard dose Apixaban N=550 N=550 S/SE 2.57 0.54 4.87 (1.30–18.26) 0.02 Major bleeding 6.01 4.64 1.29 (0.48–3.42) 0.61 Dabigatran N=412 N=412 S/SE 1.64 1.75 0.92 (0.30–2.87) 0.89 Major bleeding 4.99 5.54 0.91 (0.45–1.85) 0.80 Rivaroxaban N=815 N=815 S/SE 1.23 1.65 0.71 (0.24–2.09) 0.54 Major bleeding 5.42 4.90 1.09 (0.63–1.87) 0.76

Propensity-score matched based on 50 socio-demographic characteristics, co-morbidities and baseline medication use

Favours Favours reduced dose standard dose

Slide by C. Michael Gibson, M.S., M.D. Yao et al. JACC 2017:2779–2790. 133 Two Broad Categories Of Need For Reversal Agents

Patient who needs Patient who is actively 1 surgery, but patient is on 2 bleeding (fewer cases) an anticoagulant (more – Intracranial Hemorrhage (ICH) – GI Bleeding cases)

Slide by C. Michael Gibson, M.S., M.D. 134 Unmet Needs With Current Agents: Thrombotic Events Occur Following Andexanet

Patients in Safety Analysis (n=352) <6 days after 6-14 days 15-30 days Total bolus after bolus after bolus Patients with at least one thrombotic 34 (9.7%) 11 11 12 event in 30 days Myocardial Infarction 7 6 1 0

Ischemic Stroke (or uncertain etiology) 14 5 6 3

Transient Ischemic Attack 1 0 0 1

Deep Vein Thrombosis 13 1 5 7

Pulmonary Embolism 5 1 0 4

Slide by C. Michael Gibson, M.S., M.D. N Engl J Med. 2019 Apr 4;380(14):1326-1335. doi: 10.1056/NEJMoa1814051. Epub 2019 Feb 7. 135 Agenda

Growing use of NOACs

Large current unmet need

Role of cardiology clinical practice in reversal agents

Slide by C. Michael Gibson, M.S., M.D. 136 Cardiologists Often Consulted For NOAC Bleeding Reversal

• Cardiologists are the biggest prescribers of NOACs

• Cardiologists may poke holes in arteries and hearts

• Cardiologists are often consulted to manage bleeding in patients on NOACs

Slide by C. Michael Gibson, M.S., M.D. 137 In Summary

• NOAC use is increasing and has overtaken warfarin (Vitamin K antagonists)

• Anticoagulants, and in particular NOACs, are a major cause of bleeding including bleeding requiring emergency room evaluation and treatment

• There remains a large unmet need for anticoagulation reversal agents

Reversal Agent

Slide by C. Michael Gibson, M.S., M.D. 138 Anticoagulation Reversal in the Joseph Bledsoe MD Emergency Department Disclosures

• Dr. Bledsoe has received research grant support Present Research/Grant Funding paid to Intermountain Healthcare on his behalf by BMS/Pfizer BMS/Pfizer Consultant • Dr. Bledsoe serves on the Advisory Board for Health Catalyst VendRX VendRx

• The slides were prepared by Joseph Bledsoe, MD Owner JAJ LLC consulting

140 Patient case presentation

ED clinician perspective

AGENDA Current direct oral anticoagulant reversal options

Ideal Reversal Agent

Summary Grandma Helen • 82yoF on chronic anticoagulation for atrial fibrillation • Fall at home while vacuuming, on “new blood thinner, but can’t remember which one”. • Presents to the emergency department due to headache 8 hours later • Exam: Unequal pupils, mild left arm and leg weakness. • CT imaging: Acute subdural hematoma with midline shift • ED management…

https://www3.rbwm.gov.uk/publichealth/info/4/ageing_well Patient case presentation

ED clinician perspective

AGENDA Current direct oral anticoagulant reversal options

Ideal Reversal Agent

Summary Immediate Clinical Need:

• Surgical intervention? Emergency • What blood thinning agent is the patient taking? Physician − Lab testing: • INR- unreliable Perspective • Factor Xa assays- limited availability, slow turn around times • Whole blood clotting time − Reversal agent • Depends on NOAC • Time to administer

144 Patient case presentation

ED clinician perspective

Current direct oral anticoagulant AGENDA reversal options

Ideal Reversal Agent

Summary • One FDA off label agent- (PCC) • Only two FDA approved- (Andexanet Current alpha, Praxbind) • Prolonged administration time Reversal Agent • Storage issues Limitations • NOAC - limited effectiveness • EXPENSIVE • Thrombotic complications • Black Box ANDEXXA Has a Black Box Warning

Black Box Warning

147 https://www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM606687.pdf Patient case presentation

ED clinician perspective

AGENDA Current direct oral anticoagulant reversal options

Ideal Reversal Agent

Summary STORED AT THE READY TO SAFE (NO POINT OF CARE ADMINISTER THROMBOTIC Ideal Reversal COMPLICATIONS Agent

UNIVERSALLY DURATION OF COST EFFECTIVE ACTION > NOAC DURATION EFFECTIVE Patient case presentation

ED clinician perspective

AGENDA Current direct oral anticoagulant reversal options

Ideal Reversal Agent

Summary  Must be quickly available

Reversal  Single dose Agents: Emergency  Safe (“First - do no harm”) Physician Priorities  Universally effective

 Low-Cost Ciraparantag in Development as an Anticoagulant Reversal Agent

Jack E. Ansell, MD, MACP Professor of Medicine, Hofstra Northwell School of Medicine

152 Disclosures

• Dr. Ansell has received research support and consulting fees in the past from all major manufacturers of anticoagulants and the developer of ciraparantag (Perosphere Pharma). Present Consulting relationships • Dr. Ansell was a consultant and equity holder in Perosphere Technologies Perosphere Pharma, the developer of ciraparantag, AMAG Pharmaceuticals acquired by AMAG Pharmaceuticals in 2019 Alere Home Monitoring • This is an educational lecture and is not intended to be Roche Diagnostics an inducement to use any drug or drug in a fashion that is inconsistent with the drug or device label. Rivaroxaban is not approved for use in acute coronary syndromes in the US, but is so in many other countries

• The slides were prepared by Jack Ansell, MD and / or were under the editorial control of Jack Ansell, MD

153 Agenda

• Overview of anticoagulant therapies

• Ciraparantag mechanism of action (MOA) and measure of efficacy

• Phase 2b data

• Phase 3 development program

154 Need for Anticoagulants

Anticoagulants (referred to as blood thinners) reduce the ability of the blood to form clots – Approved to prevent stroke and pulmonary emboli in patients with atrial fibrillation or a history of clots in the legs or lungs

~2% of population of U.S., EU5 and Japan are on an anticoagulant or low molecular weight heparin (LMWH) therapy1

Use of anticoagulants increases the risk of bleeding, especially major, life-threatening bleeding Warfarin was the first and only oral anticoagulant for over 60 years – Bleeding of any type on long-term warfarin therapy occurs in approximately 10%-17% of patients per year for all events2 – Most common drug bringing patients to the emergency room because of an adverse event due to the drug (e.g. bleeding)3 Novel Oral Anticoagulants (NOACs) were developed and introduced starting in 2010 – Xarelto® (rivaroxaban) − Savaysa® (edoxaban) – Eliquis® (apixaban) − Pradaxa® (dibigatran) NOACs are easier to manage, but are still associated with major bleeding in approximately 1.5%-2.0% of patients on drug per year4

1 2017 population data, www.data.un.org, accessed 12/11/18; Perosphere sponsored commercial assessment report conducted by a third party in May 2016. 2 Rubboli A et al. World J Cardiol 2011 November 26; 3(11): 351-358. 3 JAMA. 2016;316(20):2115-2125. doi:10.1001/jama.2016.16201. 4 Tepper, Ping G et al. (2018 ) Real-world comparison of bleeding risks among non-valvular atrial fibrillation patients prescribed apixaban, dabigatran, or rivaroxaban” PLOS ONE 13(11): e0205989. https://doi.org/10.1371/journal.pone.0205989. 155 NOACs Work by Binding and Neutralizing Specific Coagulation Factors

XII XI New Oral Xa IX Inhibitors VII Rivaroxaban Unfractionated VIII Apixaban Heparin Edoxaban X Betrixaban

Low Warfarin Molecular Weight V Heparin II New Oral IIa I Inhibitors Dabigatran etexilate

Fibrin Clot 156 Gaps Exist in Current Anticoagulation Reversal Therapies

• Anticoagulants are associated with a high risk of major and life-threatening bleeds in the ER setting – Severe bleeds (GI, trauma, intracranial) – Need for emergent procedure/surgery

• NOACs were developed without a reversal agent, which has been a barrier to broader use – Anticipate broader future use of NOACs • October 2018 approval of expanded label for Xarelto® (rivaroxaban) to reduce the risk of major cardiovascular events in patients with chronic coronary artery disease or peripheral artery disease

• Reversal agents approved by FDA – Praxbind® for Pradaxa® (dabigatran) - initially approved October 2015; full approval April 2018 • Only reverses dabigatran; no effect on other NOACs – AndexXa® for Xarelto® (rivaroxaban) and Eliquis® (apixaban) – approved May 2018 • Reverses Xa inhibitors, but has drawbacks

• Both FDA approved reversal agents have limitations

157 Agenda

• Overview of anticoagulant therapies

• Ciraparantag mechanism of action (MOA) and measure of efficacy

• Phase 2b data

• Phase 3 development program

158 Ciraparantag binds to the heparins and NOACs and neutralize their activity “Is this the antidote we need?” Molecular Structure Allows Ciraparantag To Reverse Multiple Anticoagulants Already On The Market Ciraparantag H-Bonding Sites

Generic Name Brand Name Manufacturer H-Bond #1 H-Bond #2 H-Bond #3 H-Bond #2

Edoxaban Savaysa Daiichi Sankyo ü ü Dabigatran Pradaxa Boehringer Ingelheim ü ü ü Rivaroxaban Xarelto Bayer and J&J ü ü ü Apixaban Eliquis Bristol Meyer and Pfizer ü ü Enoxaparin Lovenox Sanofi ü ü ü

159 Ciraparantag Binds Directly to NOACs

XII XI

IX Ciraparantag VII BINDS to and Unfractionated VIII INACTIVATES Ciraparantag Heparin Factor Xa Inhibitors Xarelto® (rivaroxaban) X Eliquis® (apixaban) Savaysa® (edoxaban) Low Molecular Weight V Heparin II I

Fibrin Clot 160 Ciraparantag Reduces Bleeding in Animal Models

Visual demonstration of reduced blood loss in rat tail bleeding time model

Ansell J. Reversing the effect of oral anticoagulant drugs: Established and newer options. Am J CVD 2016;16:163-170 161 Ciraparantag First in Human Trial

Ciraparantag (PER977) 50% or Placebo Administered 60 mg edoxaban

d Placebo reversal

l 40% 100 mg PER977 reversal

b 200 mg PER977 reversal

o N=8/cohort 300 mg PER977 reversal

h 30%

n 20%

(2014) 371:2141-2142

o 10%

a 0%

C 0 3 6 9 12 15 18 21 24 27

-10% Hours post edoxaban administration Agenda

• Overview of anticoagulant therapies

• Ciraparantag mechanism of action (MOA) and measure of efficacy

• Phase 2b data

• Phase 3 development program

163 Phase 2b Clinical Trial Design

• Placebo-controlled study in age matched cohorts of healthy subjects (50-75 years of age)

• 16 subjects per dosing cohort; 12 active:4 placebo

• Subjects received a NOAC (rivaroxaban, apixaban, edoxaban) or LMWH (enoxaparin) until they reached steady state drug levels (3-4 days)

• Ciraparantag acetate 50, 100, 200, 300 mg1 or placebo administered by IV injection after individual NOAC/LMWH at maximal activity

• Pharmacodynamic assessments of WBCT performed every 15 minutes for the first hour post study drug dose, and then periodic sampling thereafter out to 24 hours post administration of study drug

• Primary outcome: proportion of subjects who return to within 10% of their baseline WBCT

1 Doses previously presented as ciraparantag acetate doses: 300 mg acetate = 180 mg; 200 mg acetate = 120 mg; 100 mg acetate = 60 mg; 50 mg acetate = 30 mg. 164 Phase 2b Study: Reversal of Xarelto®

Ongoing study in healthy subjects; high dose group demonstrates 100% response rate*

Mean WBCT by Timepoint Individual Responder Analysis (n=12 per dose) 40% 100.0% 100% 30%

80% 20% 66.7% 58.3% 60% 10%

40% % of % Subjects of

WBCT% NormalofBaseline 0% 0.25 0.5 0.75 1 2 4 6 8 24 20% Ciraparantag -10% or placebo dose Hours Post Dose 0.0% 0% Baseline & Xarelto® dose *WBCT reversed to within 10% of baseline 1 n Placebo n Ciraparantag 60 mg n Ciraparantag 120 mg n Ciraparantag 180 mg within 30 minutes and sustained for 24 hours

1 Doses previously presented as ciraparantag acetate doses: 300 mg acetate = 180 mg; 200 mg acetate = 120 mg; 100 mg acetate = 60 mg. 165 Favorable Safety Profile To Date1

Favorable safety profile in over 250 treated healthy volunteers

Most common adverse events were mild sensations of coolness, warmth or tingling, skin flushing, and alterations in taste No serious adverse events

No procoagulant signal observed: no significant difference between placebo and ciraparantag treatment groups based on markers of hypercoagulability: D-dimer,

PTF1.2 (prothrombin fragment 1.2)

1 Data on file. 166 Agenda

• Overview of anticoagulant therapies

• Ciraparantag mechanism of action (MOA) and measure of efficacy

• Phase 2b data

• Phase 3 development program

167 Whole Blood Clotting Time (WBCT) is a Good Measure of Anticoagulation

• Traditional assays such as the PT or aPTT cannot measure Perosphere Technologies’ ciraparantag’s reversal effect because ciraparantag binds to the Broad-Spectrum reagents in the test tubes used to anticoagulate blood for these assays Point-of-Care (PoC) 1 • Ciraparantag reversal of anticoagulant activity is best measured Coagulometer by the WBCT

• WBCT is a holistic measure of the blood’s ability to form a clot

• Traditional WBCT was done manually, was labor intensive and not suitable for routine use in today’s hospital

• A Point-of-Care coagulation instrument has been developed to provide an automated WBCT measurement that can be done at the bedside and provide results in minutes − Progressing through validation for IDE approval by FDA

1 AMAG plans to utilize a coagulometer, currently being developed by Perosphere Technologies Inc., as part of the Phase 3 ciraparantag clinical program. 168 WBCT Directly Correlates with NOAC Drug Exposure

• Perosphere Technologies’ P0C 310 coagulometer tracks the PK (anti-FXa) y = 0.295x + 178.073 rise and return to baseline following i.v. R² = 0.994

edoxaban (0.5 mg/kg) administration 260 in rats (n=5)

• Clotting time as measured by Perosphere 210

Technologies coagulometer correlates PoC Clotting Time PoC (s) Clotting Time 2 strongly with anti-FXa assay, with an R 160 value of 0.99 0 100 200 300 400 500 ng edoxaban/mL plasma

Ansell, J., et al. “A Novel Whole Blood Point-of-Care Coagulometer to Measure the Effect of Direct Oral Anticoagulants and Heparins.“ Semin. Thromb. Hemost. 2019 Apr;45(3):259-263. 169 Ciraparantag Phase 3 Clinical Development Program Overview1

Phase 3a Clinical Trials (Laboratory Endpoint) Study Objective: • Establish lowest effective dose after reaching peak steady state blood concentrations of: – Xarelto® (rivaroxaban) -- Eliquis® (apixaban) – Savaysa® (edoxaban) -- Lovenox® (enoxaparin) Study Design: • Placebo-controlled dose finding study in 60-90 healthy subjects per study Endpoints: • Proportion of subjects who return to within 10% of their baseline WBCT, using an automated coagulometer, within 30-60 minutes and sustained for at least 5 hours • Safety

Phase 3b Clinical Trial • Final design to be determined based on end of Phase 2 meeting with FDA • Based on precedent, anticipate 50-100 patients to be completed for NDA submission, with remainder submitted post approval

1 AMAG plans to utilize a coagulometer, currently being developed by Perosphere Technologies Inc., as part of the Phase 3 ciraparantag clinical program. 170 What You Need to Remember

1. Large unmet need • Medical community desires a more optimal antidote or reversal agent to NOACs

2. Ciraparantag has a number of characteristics that suggest it may be the ideal reversal agent • Ready to use with longer shelf-life than current therapies • Potential for a fixed dose for all Xa inhibitors • Demonstrates a sustained effect over 24 hours after one IV dose • No prothrombotic signal to date

3. Ciraparantag has the potential to be an effective reversal agent of anticoagulant activity for NOACs and LMWH

4. Phase 3 studies in patients with bleeding or needing emergent surgery are being planned

171 Tony Casciano AMAG Chief Commercial Officer

172 Ciraparantag Has the Potential to Addresses a Serious Unmet Medical Need Significant cost associated with life-threatening bleeds

Estimated NOAC/LMWH Patients on patients per year  Unmet medical need requiring a reversal agent NOAC/LMWH  Strong target product profile ~6 million ~150,000 Xarelto®, Eliquis®,  Space for innovation Savaysa®, Pradaxa®, Lovenox®  AMAG strategic fit

Intracranial hemorrhage and major gastrointestinal bleeding with oral anticoagulants: 1-year costs ranged from $7,584 to $193,8041

1 www.amcp.org Vol. 19, No. 9 November/December 2013 JMCP Journal of Managed Care Pharmacy.

Financial Evolution

Business Development

Specialty Pharma: Acquiring/licensing cash generating products 2018 2019 2020 2021 2022

© 2019 AMAG Pharmaceuticals, Inc. All rights reserved 177 2016 | Prior to the Business Evolution AMAG was Heavily Leveraged More than $1B in Debt, Near-Term Maturities and Restrictive Covenants Capital Structure Key Items 12/31/16 Cash: $578M Outstanding debt balance: $1,028M Total annual interest cost: $60M

Debt Payments $M $500

$218 $258

$18 $18 $18 2017 2018 2019 2020 2021 2022 2023

© 2019 AMAG Pharmaceuticals, Inc. All rights reserved 178 2017 | Debt Reduction and Maturity Extensions Removed Term Loan and Extended Time to Maturity to Support New Product Launches Capital Structure Key Items 12/31/16 6/30/17 Cash: $578M $399M Outstanding debt balance: $1,028M $861M Total annual interest cost: $60M $51M

Debt Payments $M $500

$320

$41

2017 2018 2019 2020 2021 2022 2023

© 2019 AMAG Pharmaceuticals, Inc. All rights reserved 179 2019 | Balance Sheet Evolved, Significantly De-levered and Extended Maturity Current capital structure supports development of innovative products Capital Structure Key Items 12/31/16 6/30/17 3/31/19 Cash: $578M $399M $267M Outstanding debt balance: $1,028M $861M $320M Total annual interest cost: $60M $51M $10M

Debt Payments $M

$320

2017 2018 2019 2020 2021 2022 2023

Revenues $1,000 (Millions)

$500

$0 2018 2019 2020 2021 2022

Current Commercial Portfolio

• Continued growth through market expansion and increasing market share − Brand on track to achieve >$200M annual revenues

• Continue to promote benefits of Makena subcutaneous auto-injector − 1Q19: SC auto-injector 54% market share of HPC market • PROLONG study results expected to be published 2H-2019

• Continue to grow and gain market share • Leverage 124 person sales force calling on OB/GYNs • Optimize efficiency and effectiveness of consumer campaign • Positive margin contributor by end of 2019

© 2019 AMAG Pharmaceuticals, Inc. All rights reserved 182 Strategic Evolution: New Products Drive Future Growth Current Commercial Products Provide Stable Cash Flows and Growth Potential Revenues $1,000 (Millions)

$500

$0 2018 2019 2020 2021 2022

Current Commercial Portfolio

© 2019 AMAG Pharmaceuticals, Inc. All rights reserved 183 Strategic Evolution: New Products Drive Future Growth Current Commercial Products Provide Stable Cash Flows Projected U.S. Revenues $1,000 (Millions) Potential

AMAG-423 ciraparantag $500

$0 2018 2019 2020 2021 2022

Current Commercial Portfolio Current Development Portfolio Adjusted EBITDA

AMAG Evolution

Business Development

. Core therapeutic areas (TAs) (maternal health, Therapeutic hem/onc & select hospital) Criteria . Adjacent TAs (women’s health, nephrology)

. Differentiated & durable Financial . Criteria Stage of development . Cash payback period and IRR

Leverage . Physician relationships Core . Commercial execution skills Capabilities . Consumer / digital platform

• Acquisition of ciraparantag and AMAG-423 provide AMAG with global opportunities • Opportunity for ex-U.S. out-licensing . Potential source of non-dilutive capital . Initiation of ex-U.S. development

• Transformation of balance sheet to support evolution of business plan • Short lived EBITDA-negative phase in 2019, return to EBITDA neutral in 2020 as pipeline matures and newer products begin to contribute cash flows • Recent pipeline additions provide global opportunities

189 Key Take-Aways for Today

2 6

Regulatory Approved/ Phase 1 Phase 2 Phase 3 Review Marketed

Treatment of iron deficiency anemia CKD

Broad label all iron deficiency anemia

Anticoagulant reversal agent

Ciraparantag (potential for orphan drug designation) HEMATOLOGY

Treatment to reduce recurrent preterm birth in certain at-risk women Subcutaneous auto-injector

Treatment for moderate to severe dyspareunia (pain during sex) in postmenopausal women

TM Treatment of low desire or libido with associated distress (HSDD*) in premenopausal women

AMAG-423 Treatment of severe preeclampsia

WOMEN’S HEALTHCAREDigoxin Immune (orphan drug designation) Fab (ovine)

* HSDD: Hypoactive Sexual Desire Disorder