Document




UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, DC 20549
FORM 8-K

CURRENT REPORT PURSUANT
TO SECTION 13 OR 15(d) OF THE
SECURITIES EXCHANGE ACT OF 1934

Date of report (Date of earliest event reported): September 26, 2018

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AMAG PHARMACEUTICALS, INC.
(Exact name of registrant as specified in its charter)

Delaware
(State or other jurisdiction of incorporation)
001-10865
 
04-2742593
(Commission File
Number)
 
(IRS Employer Identification
No.)
1100 Winter St.
 
 
Waltham, Massachusetts
 
02451
(Address of principal executive
offices)
 
(Zip Code)

(617) 498-3300
(Registrant’s telephone number, including area code)

(Former name or former address, if changed since last report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

o Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
o Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
o Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
o Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company  ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.  ☐

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Item 7.01. Regulation FD Disclosure.

The following information and Exhibit 99.1 and 99.2 attached hereto shall not be deemed “filed” for purposes of Section 18 of the Exchange Act or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act, except as expressly set forth by specific reference in such filing.

On September 26, 2018, AMAG Pharmaceuticals, Inc. (the "Company") issued a press release announcing that it had acquired the global rights to develop and market digoxin immune Fab (ovine) for the treatment of severe preeclampsia from Velo Bio, LLC, a privately held life sciences company and its intention to hold a conference call to discuss the acquisition.

A copy of the press release is attached hereto as Exhibit 99.1 and a copy of the presentation slides to be used during the conference call is furnished herewith as Exhibit 99.2.

Item 9.01. Financial Statements and Exhibits.
 
(d) Exhibits.
 
AMAG hereby furnishes the following exhibits: 
Exhibit
Number
 
Description
99.1
 
99.2
 

Forward-Looking Statements

This report contains forward-looking information about AMAG Pharmaceuticals, Inc. within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. Any statements contained herein which do not describe historical facts, including, among others, AMAG’s expectation that it will announce topline data from the Phase 2b/3a study in the first half of 2020 and submit a new drug application to the FDA in the second half of 2020; the expected development and regulatory timeline for all product candidates; AMAG’s expectations to accelerate the development timeline for the AMAG-423 program, including the number and location of study sites to be opened; beliefs about preeclampsia, including the potential benefits of DIF and the expected market opportunity; AMAG’s beliefs regarding the target product profile for DIF, including the presumed mechanism of action, indication, and safety profile; AMAG’s beliefs that decreasing EDLFs may improve vascular function and lead to better post-delivery outcomes in affected mothers and babies; beliefs that DIF is a natural fit for AMAG based on its’ significant presence in women's healthcare and the evolution of its current portfolio expansion strategy to include innovative development-stage therapeutics; AMAG’s beliefs that DIF could significantly benefit women and their newborns suffering from severe preeclampsia, potentially improve patient outcomes and reduce health care costs; and AMAG’s expectations that the incremental research and development costs associated with advancing the DIF program in 2018 will not impact the financial guidance issued by AMAG on August 2, 2018; beliefs that the proof of concept study demonstrated consistent and encouraging trends and that its current Phase 2b/3a study has potential to form the basis for accelerated approval 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 DIF will not be approved on the expected timeline or at all, including as a result of the clinical trial design and enrollment, or as a result of any safety issues that may arise as part of such trial; the risk that, even if approved, the market for AMAG-423 may be smaller than expected or AMAG may not be successful in accessing such market or otherwise realize the expected benefits of the acquisition, as well as those risks identified in the Company’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, 2017, its Quarterly Report on Form 10-Q for the quarter ended June 30, 2018 and subsequent filings with the SEC. 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® is a registered trademark of AMAG Pharmaceuticals, Inc.  

2




SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the Registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 
AMAG PHARMACEUTICALS, INC.
 
By:
/s/ Joseph D. Vittiglio
 
 
Joseph D. Vittiglio
Executive Vice President, General Counsel, Quality & Corporate Secretary
 
 
 
Dates: September 26, 2018




3
Exhibit

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AMAG PHARMACEUTICALS ACQUIRES ORPHAN DRUG CANDIDATE FOR TREATMENT OF SEVERE PREECLAMPSIA

Currently no FDA-approved treatment options for severe preeclampsia, a leading cause of maternal and neonatal mortality

Acquisition expands AMAG’s maternal health portfolio and commitment to innovative therapies that address unmet medical needs

Conference call scheduled today at 8:00 a.m. ET

WALTHAM, Mass., September 26, 2018 — AMAG Pharmaceuticals, Inc. (NASDAQ:AMAG) today announced it has acquired global rights to develop and market digoxin immune Fab (ovine) (DIF), a polyclonal antibody in development for the treatment of severe preeclampsia in pregnant women. AMAG and Velo Bio, LLC, a privately held life sciences company located in the Research Triangle Park region of North Carolina, entered into an option agreement in July 2015 to develop DIF. The companies have amended the agreement, enabling AMAG to exercise its option to acquire the program (now referred to as AMAG-423) for an upfront fee of $12.5 million. AMAG will now manage and complete the Phase 2b/3a study that Velo initiated in mid-2017. The company expects to announce topline data in the first half of 2020 and to submit a new drug application to the U.S. Food and Drug Administration (FDA) in the second half of 2020. DIF has been granted both orphan drug and fast-track designations by the FDA for use in the treatment of severe preeclampsia.

Preeclampsia results in adverse neonatal outcomes, and is a leading cause of maternal morbidity and mortality, affecting approximately 140,000 pregnant women in the U.S. annually., The condition typically develops in women after 20 weeks of pregnancy and is characterized by elevated blood pressure, as well as vascular abnormalities, that can lead to end organ damage, intrauterine growth restriction and premature delivery. Premature delivery can lead to a number of serious health consequences for the infant, including intraventricular hemorrhage (bleeding in the brain) or necrotizing enterocolitis (severe inflammation of the infant bowels). Severe preeclampsia, a more serious form of the condition that can be life threatening to both the woman and infant, impacts approximately 50,000 women per year., Currently, there are no FDA-approved treatments for preeclampsia or severe preeclampsia.

“Severe preeclampsia is a global health concern. We are excited about the potential of DIF to significantly benefit mothers and babies around the world who are affected by this serious, and sometimes fatal, medical condition,” said Julie Krop, M.D., chief medical officer and executive



vice president of development at AMAG. “In a recently published review article, data was summarized that strongly support a potential role of EDLFs in the pathogenesis of preeclampsia. DIF is a polyvalent antibody intended to bind to EDLFs and remove them from circulation. We believe that decreasing EDLFs may improve vascular function and lead to better post-delivery outcomes in affected mothers and babies."

Approximately 200 antepartum women with severe preeclampsia between 23 and 32 weeks gestation will be enrolled in the multi-center, randomized, double-blind, placebo-controlled, parallel-group Phase 2b/3a study, including the 26 patients who have enrolled in the study since initiation by Velo. To accelerate enrollment, AMAG intends to increase the number of trial sites, including potentially initiating sites outside of the U.S. Participants in the study will receive DIF or placebo intravenously four times a day over four days. The study’s primary endpoint is to demonstrate a reduction in the percentage of babies who develop severe intraventricular hemorrhage, necrotizing enterocolitis or death by 36 weeks corrected gestational age between the DIF and placebo arms. Secondary endpoints include the maternal incidence of pulmonary edema during treatment and the period of time between treatment and delivery.

“The absence of an approved therapy for preeclampsia represents a significant unmet patient need,” said Eleni Tsigas, chief executive officer of the Preeclampsia Foundation. “Premature delivery to alleviate preeclampsia and severe preeclampsia can be associated with life- threatening complications for the baby, as well as long-term developmental delays. Additionally, preeclampsia places an annual burden of $2.2 billion on the U.S. health care system, including $1 billion in healthcare costs to treat the mother and the remainder for infants born to mothers with preeclampsia.”

In addition to the upfront $12.5 million that AMAG will pay in connection with the option exercise, AMAG will be responsible for a $35 million milestone payment upon FDA approval. AMAG will also pay sales milestone payments of an aggregate of $240 million, triggered at various annual net sales thresholds of $300 million and above, and a $10 million payment to a previous licensor of the AMAG-423 program on the first $100 million of sales. AMAG will also pay mid-single digit royalties based on net sales.  

“Our portfolio expansion strategy is evolving to include innovative development-stage therapeutics, and with our significant presence in women's healthcare, DIF is a natural fit for AMAG,” said Nik Grund, chief commercial officer at AMAG. "We believe that DIF could have a significant impact on women and their newborns suffering from this often life-threatening condition, potentially improving patient outcomes and reducing health care costs. If approved, this product could represent more than a $1 billion annual market opportunity in the U.S.” 

The expected incremental research and development costs associated with advancing AMAG-423 in 2018 does not impact the financial guidance issued on August 2, 2018.




Conference Call and Webcast Access
AMAG Pharmaceuticals, Inc. will host a conference call and webcast today at 8:00 a.m. ET to discuss AMAG-423.
 
Dial-in Number
U.S./Canada dial-in number: (877) 412-6083
International dial-in number: (702) 495-1202
Conference ID: 8488288
 
Replay dial-in number: (855) 859-2056
Replay International dial-in number: (404) 537-3406
Conference ID: 8488288
 
A telephone replay will be available from approximately 11:00 a.m. ET on September 26, 2018 through midnight on October 3, 2018.
 
The webcast with slides will be accessible through the Investors section of AMAG’s website at www.amagpharma.com. A replay of the webcast will be archived on the website for 30 days.    


About AMAG-423 (digoxin immune Fab)
Elevated levels of endogenous digitalis-like factors (EDLFs) have been found in the placental and maternal circulation of the majority of patients with preeclampsia, and the degree of elevation has been correlated with severity of changes in creatinine clearance (a measure of kidney function). DIF is thought to bind to these factors, causing a decrease in available serum EDLFs and inhibition of their activity. The DEEP trial, a smaller, prior placebo-controlled Phase 2 proof-of-concept study in 51 pregnant women with severe preeclampsia, was suggestive of clinical benefit in both mothers and their babies. 

DIF is currently indicated for the treatment of patients with life-threatening or potentially life-threatening digoxin toxicity or overdose.


About AMAG
AMAG is a pharmaceutical company focused on bringing innovative products to patients with unmet medical needs. The company does this by leveraging its development and commercial expertise to invest in and grow its pharmaceutical products across a range of therapeutic areas, including women’s health. For additional company information, please visit www.amagpharma.com.









Forward Looking Statements
This press release contains forward-looking information about AMAG within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws. Any statements contained herein which do not describe historical facts, including, among others, AMAG’s expectation that AMAG will announce topline data from the Phase 2b/3a study in the first half of 2020 and submit a new drug application to the FDA in the second half of 2020, AMAG’s beliefs regarding the mechanism of action of DIF and that decreasing EDLFs may improve vascular function and lead to better post-delivery outcomes in affected mothers and babies; AMAG’s intention to increase the number of trial sites in the study, including by initiating sites outside of the U.S.; beliefs that DIF is a natural fit for AMAG based on its’ significant presence in women's healthcare and the evolution of its current portfolio expansion strategy to include innovative development-stage therapeutics; AMAG’s beliefs that DIF could significantly benefit women and their newborns suffering from severe preeclampsia, potentially improve patient outcomes and reduce health care costs; beliefs regarding the market opportunity for DIF; and AMAG’s expectations that the incremental research and development costs associated with advancing the DIF program in 2018 will not impact the financial guidance issued by AMAG on August 2, 2018 are based on management’s current expectations and beliefs and 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 DIF will not be approved on the expected timeline or at all, including as a result of the clinical trial design and enrollment, or as a result of any safety issues that may arise as part of such trial; the risk that, even if approved, the market for AMAG-423 may be smaller than expected or AMAG may not be successful in accessing such market or otherwise realize the expected benefits of the acquisition, as well as those risks identified in AMAG’s filings with the U.S. Securities and Exchange Commission (SEC), including its Annual Report on Form 10-K for the year ended December 31, 2017, its Quarterly Report on Form 10-Q for the quarter ended June 30, 2018 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® is a registered trademark of AMAG Pharmaceuticals, Inc.






CONTACTS: 
Investors:
Linda Lennox
908-627-3424

Media:
Rushmie Nofsinger
781-530-6838

____________________

1 Task Force Report "Hypertension in Pregnancy", issued by ACOG (November 2013)

2 Ananth, C. V., Keyes, K. M., & Wapner, R. J. (2013). Pre-eclampsia rates in the United States, 1980-2010: age-period-cohort analysis. The BMJ, 347, f6564. http://doi.org/10.1136/bmj.f6564

3 Society for Maternal-Fetal Medicine, Washington, DC (Publications Committee); and Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Clinical Perinatal Research, University of Cincinnati College of Medicine, Cincinnati, OH (Dr. Sibai).

4Premature Birth,” Mayo Clinic (August 2018) https://www.mayoclinic.org/diseases-conditions/premature-birth/symptoms-causes/syc-20376730

5 Ananth, C. V., Keyes, K. M., & Wapner, R. J. (2013). Pre-eclampsia rates in the United States, 1980-2010: age-period-cohort analysis. The BMJ, 347, f6564. http://doi.org/10.1136/bmj.f6564

6 AMAG Phase 2b/3a clinical trial population is a subset of the severe preeclampsia population.

7 Buckalew, V.M. (2018). Role of endogenous digitalis-like factors in the clinical manifestations of severe preeclampsia: a systemic review. Clinical Science, 32(12):1215-1242. http:// doi: 10.1042/CS20171499. Print 2018 Jun 29.

8 Stevens, Warren et al. (2017). Short-term costs of preeclampsia to the United States health care system. American Journal of Obstetrics & Gynecology, Volume 217, Issue 3, 237 - 248.e16. https://doi.org/10.1016/j.ajog.2017.04.032

9 Lam GK et al, a secondary analysis of the DEEP Trial. American Journal of Obstetrics & Gynecology. August 2013, pp119.e1- 119.e6

10 Adair, David C. et al. (2010). Digoxin Immune Fab Treatment for Severe Preeclampsia. American Journal of Perinatology, Volume 27: 655-662. http://dx.doi.org/10.1055/s-0030-1249762


ex992velo
AMAG-423 Digoxin Immune Fab (ovine) (DIF) for the Treatment of Severe Preeclampsia September 26, 2018 © 2018 AMAG Pharmaceuticals, Inc. All rights reserved 1


 
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, the expected development and regulatory timeline for all product candidates; AMAG’s expectations to accelerate the development timeline for the AMAG-423 program, including the number and location of study sites to be opened; AMAG’s belief that its August 2, 2018 financial guidance remains unchanged; beliefs about preeclampsia, including the potential benefits of DIF and the expected market opportunity; AMAG’s beliefs regarding the target product profile for DIF, including the presumed mechanism of action, indication, and safety profile; and AMAG’s beliefs that the proof of concept study demonstrated consistent and encouraging trends and that its current Phase 2b/3a study has potential to form the basis for accelerated approval 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 DIF will not be approved on the expected timeline or at all, including as a result of the clinical trial design and enrollment, or as a result of any safety issues that may arise as part of such trial; the risk that, even if approved, the market for AMAG-423 may be smaller than expected or AMAG may not be successful in accessing such market or otherwise realize the expected benefits of the acquisition, as well as 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, 2017, its Quarterly Report on Form 10-Q for the quarter ended June 30, 2018 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® 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. © 2018 AMAG Pharmaceuticals, Inc. All rights reserved 2


 
Speakers / Agenda • Transaction terms • Severe preeclampsia condition • Commercial opportunity Bill Heiden President and Chief Executive Officer • DEEP study and secondary analysis results • The role of EDLFs in preeclampsia • Phase 2b/3a trial status • Development and regulatory timeline Julie Krop, MD Chief Medical Officer © 2018 AMAG Pharmaceuticals, Inc. All rights reserved 3


 
Growing Innovative Pipeline Approved/ PHASE 1 PHASE 2 PHASE 3 Regulatory Review Marketed AMAG-423 Digoxin Immune Treatment of severe preeclampsia Fab (ovine) (DIF) Treatment of low desire or libido with PDUFA TM AdCom: early Q1-2019 Vyleesi associated distress in postmenopausal 03/23/19 women Treatment for moderate to severe dyspareunia (pain during sex) in postmenopausal women HSDD* Indication Treatment of iron deficiency anemia Treatment to reduce recurrent preterm birth in certain at-risk women * HSDD: Hypoactive Sexual Desire Disorder MATERNAL HEALTH: AMAG-423 © 2018 AMAG Pharmaceuticals, Inc. All rights reserved 4


 
AMAG-423 DIF for the Treatment of Severe Preeclampsia • Financial terms to acquire global rights to DIF for the treatment of severe preeclampsia • Severe preeclampsia: Disease overview • Significant unmet medical need and global commercial opportunity • Endogenous digitalis-like factors (EDLF) in preeclampsia • Proof of concept study: The DEEP trial results • DEEP trial secondary analysis of EDLF positive patients • Current Phase 2b/3a clinical trial design, status and go-forward plan • Development and regulatory timeline MATERNAL HEALTH: AMAG-423 © 2018 AMAG Pharmaceuticals, Inc. All rights reserved 5


 
Transaction Leverages AMAG’s Development & Commercial Capabilities and Resources Accelerate Development Timeline for a Potential Treatment with a Significant Unmet Medical Need July 2015 September 2018 • Entered into exclusive option to acquire DIF • Acquired rights to develop and market DIF for for the treatment of severe preeclampsia the treatment of severe preeclampsia • Option exercisable at completion of 2b/3a • AMAG will manage and complete the Phase trial conducted by Velo Bio 2b/3a study initiated by Velo Bio July 2015 September 2018 Upfront $10M Option exercise $25M $12.5M FDA approval milestone1 $45M $35M Aggregate sales milestones1 Total < $260M Total < $250M at annual net sales $100M-$900M $300M-$900M Royalties1 High single-digit Mid single-digit Global rights   AMAG 2018 financial guidance issued on August 2nd remains unchanged 1 Inclusive of two milestone payments, including $10M on the first $100M of gross sales, and royalties due to a previous licensor of the DIF program. MATERNAL HEALTH: AMAG-423 © 2018 AMAG Pharmaceuticals, Inc. All rights reserved 6


 
Preeclampsia and Severe Preeclampsia No Effective Treatment • Preeclampsia is a multi-system disorder that occurs only during pregnancy and the postpartum period and affects both the mother and unborn baby1 – Increasing at a rate faster than obesity and diabetes2 • Condition is characterized by hypertension, vascular abnormalities and decreased renal function, that can lead to end organ damage, intrauterine growth restriction and premature delivery3 – Leading cause of maternal morbidity and mortality and results in adverse neonatal outcomes4 – Affects approximately 140,000 pregnant women in U.S. annually5 . Severe preeclampsia impacts approximately 50,000 women with preeclampsia5,6 • No effective treatments – Current interventions do not treat underlying pathophysiology – Only “treatment” is delivery of baby (balanced between maternal and fetal risks)7 1 Preeclampsia Foundation, www.preeclampsia.org, accessed 9/21/18. 2 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 3 Society for Maternal Fetal Medicine Clinical Opinion: Evaluation and management of severe preeclampsia before 34 weeks' gestation. SMFM Publications Committee, with the assistance of Baha M. Sibai. AJOG 2011. 4 Task Force Report “Hypertension in Pregnancy,” issued by ACOG (November 2013). 5 Ananth, C. V., Keyes, K. M., & Wapner, R. J. (2013). Pre-eclampsia rates in the United States, 1980-2010: age-period-cohort analysis. The BMJ, 347, f6564. http://doi.org/10.1136/bmj.f6564. 6 AMAG Phase 2b/3a clinical trial population is a subset of the severe preeclampsia population. 7 Agunanne E et al, Marinobufagenin Levels in Preeclamptic Patients: A Preliminary Report. American Journal of Perinatology/Volume 28, Number 7, 2011, p 509. MATERNAL HEALTH: AMAG-423 © 2018 AMAG Pharmaceuticals, Inc. All rights reserved 7


 
Preeclampsia: Unmet Medical Need is Substantial Significant Burden to Healthcare System • Often results in premature births1, leading to serious health consequences for the baby2 – Intraventricular hemorrhage: bleeding in the brain – Necrotizing enterocolitis: severe inflammation of the bowels – Life-long developmental abnormalities – Death • Maternal complications1 – Pulmonary edema – Renal failure – Death • Cost of preeclampsia within the first 12 months of delivery is approximately $2.2B in the U.S.3 – $1.0B for mothers – $1.2B for infants 1 Sibai B et al, Pre-eclampsia, www.thelancet.com, Vol 365, February 26, 2005. 2 “Premature Birth,” Mayo Clinic (August 2018) https://www.mayoclinic.org/diseases-conditions/premature-birth/symptoms-causes/syc-20376730. Accessed 9/24/18. 3 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 . MATERNAL HEALTH: AMAG-423 © 2018 AMAG Pharmaceuticals, Inc. All rights reserved 8


 
Significant Market Opportunity AMAG-423 • FDA granted orphan status (7-years exclusivity expected upon approval) and fast track review Estimated U.S. market • No current treatments for preeclampsia opportunity4 – Only “treatment” is delivery of the baby, often times very preterm1 • Ex-U.S. estimated incidence of severe preeclampsia: ~1.6M pregnant women2 – Europe: 96,000 ~$1B – Developing countries incidence of preeclampsia is 7x higher than in developed countries3 1 Agunanne E et al, Marinobufagenin Levels in Preeclamptic Patients: A Preliminary Report. American Journal of Perinatology/Volume 28, Number 7, 2011, p 509. 2 Society for Maternal Fetal Medicine Clinical Opinion: Evaluation and management of severe preeclampsia before 34 weeks' gestation. SMFM Publications Committee, with the assistance of Baha M. Sibai. AJOG 2011; AMAG internal analytics. 3 Preeclampsia Foundation, www.preeclampsia.org, accessed 9/21/18. 4 AMAG estimate based on market research and internal analytics. MATERNAL HEALTH: AMAG-423 © 2018 AMAG Pharmaceuticals, Inc. All rights reserved 9


 
EDLFs: Contribution to Hypertension and Preeclampsia Rationale to Study DIF • EDLFs are circulating inhibitors of the Na+ K+ ATPase pump (“sodium pump”)1 – Inhibit the sodium potassium ATPase pump, which can lead to vasoconstriction, elevated blood pressure, and decreased blood flow • EDLFs have been implicated in a number of diseases including hypertension and preeclampsia1 • DIF: originally developed and currently commercialized as treatment for digoxin overdose – Binds to EDLFs, removing from the circulation2 – Reverses sodium pump inhibition1 – Potential to improve endothelial dysfunction, vasoconstriction and vascular flow associated with preeclampsia3 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. MATERNAL HEALTH: AMAG-423 © 2018 AMAG Pharmaceuticals, Inc. All rights reserved 10


 
DEEP Trial1: Small Proof of Concept Study Positive Trends across Multiple Endpoints Double-blind, placebo-controlled, randomized trial to evaluate the effect of DIF administration on maternal and fetal outcomes in severe preeclampsia Study population and eligibility criteria Results • DIF (Digibind®) (n=24, placebo n=27 • No decline in creatinine clearance observed in DIF arm, • Met ACOG criteria for severe preeclampsia compared to decrease in placebo arm (p=0.02) • Enrolled between 23 weeks/5 days to 34 weeks • Antihypertensive use similar between DIF and placebo (p=0.7) gestational age Safety • Probable delivery within 72 hours • One maternal SAE in placebo arm; none in DIF arm • Dosing every 6 hours for 2 days (1.6 mg/kg) • Two infant deaths in placebo arm (GA 24 and 27 weeks); no deaths in DIF arm Two primary maternal endpoints • Change in creatinine clearance at 24-48 hours Secondary analysis of DEEP Trial2 • Change in use of antihypertensive drugs • Included patients who were EDLF positive at baseline • 78% of DEEP patients were categorized as EDLF positive 1 Adair CD, Buckalew VM, Graves SW, et al. Digoxin immune fab treatment for severe preeclampsia. Am J Perinatal. 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. MATERNAL HEALTH: AMAG-423 © 2018 AMAG Pharmaceuticals, Inc. All rights reserved 11


 
DEEP Trial1: Sodium Pump Activity (Surrogate for EDLF Activity) DIF Significantly Decreased EDLF Activity (Increased Sodium Pump Function) Sodium Pump Activity 30 25 20 n=19 15 n=15 n=21 n=22 10 5 n=20 n=12 n=21 0 n=19 -5 % Change from baseline from Change % -10 p=0.05 p=0.10 p=0.07 0-12h 12-24h 24-48h 24-48h (LOCF)* ‒ DIF ‒ Placebo 1 Adair CD, Buckalew VM, Graves SW, et al. Digoxin immune fab treatment for severe preeclampsia. Am J Perinatol. 2010;27:655-62. * Last Observation Carried Forward. MATERNAL HEALTH: AMAG-423 © 2018 AMAG Pharmaceuticals, Inc. All rights reserved 12


 
Change in Creatinine Clearance and Relationship with EDLF Levels Statistically Significant Preservation of Creatinine Clearance Decline in Placebo Renal Function in DIF Treated Women1 Group Correlated to EDLF Levels2 (measured by sodium pump activity) (mL/min) 10 0 0 n=15 -10 (mL/min) -10 -20 -30 -20 n=20 -40 -30 -50 p=0.02 -60 -40 -70 in creatinine clearance clearance creatinine in -50 -60 in creatinine clearance from baseline from clearance creatinine in 24-48h (LOCF) Change No EDLF Lo EDLF Hi EDLF Change Change ‒ DIF ‒ 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. MATERNAL HEALTH: AMAG-423 © 2018 AMAG Pharmaceuticals, Inc. All rights reserved 13


 
Secondary Endpoints: Selected Maternal Outcomes in Patients Who Were EDLF Positive at Baseline1 Trends in Improvements in Maternal Outcomes in DIF Treated Patients Compared to Placebo Blurred Vision Use of Antihypertensives Pulmonary Edema p=0.136 p=0.117 p=0.035 70% 70% 70% n=12 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 % % of patients with pulmonary edema pulmonary with patients of % % 0% 0% 0% DIF n=17 Placebo n=19 DIF n=17 Placebo n=19 % DIF n=17 Placebo n=19 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. MATERNAL HEALTH: AMAG-423 © 2018 AMAG Pharmaceuticals, Inc. All rights reserved 14


 
Selected Neonatal Outcomes in Infants Delivered by EDLF Positive Mothers at Baseline 1 78% of women were EDLF Positive1 Nonreassuring Fetal Status* Intraventricular Hemorrhage 50% p=0.136 50% p=0.015 n=8 40% 40% 30% 30% n=4 n=5 20% 20% 10% 10% % of neonates with IVH with neonates of % nonreassuring fetal status fetal nonreassuring % % n=0 0% 0% DIF n=17 Placebo n=19 DIF n=17 Placebo n=19 * Clinical signs of worsening fetal hypoxia documented as abnormal fetal blood flow by doppler imaging and/or worsening biophysical 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. MATERNAL HEALTH: AMAG-423 © 2018 AMAG Pharmaceuticals, Inc. All rights reserved 15


 
Evaluation of Neonatal Outcomes to be Used in Current Phase 2b/3a Study DEEP Trial: Selected Neonatal Outcome Measures1 Intraventricular Hemorrhage (IVH) Necrotizing Enterocolitis (NEC) Deaths Severe (grades 3 and 4) 15% 15% 15% p=0.24 p=0.61 p=0.49 n=3 n=3 10% 10% 10% n=2 5% Deaths neonatal 5% n=1 5% of neonates with IVH with neonates of of neonates with NEC with neonates of % of of % % % % % n=0 0% n=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 MATERNAL HEALTH: AMAG-423 © 2018 AMAG Pharmaceuticals, Inc. All rights reserved 16


 
Significant Clinical and Mechanistic Evidence Supports Further Development Study Conclusions • EDLFs elevated in 78%1 of patients in DEEP trial (similar to a previous trial2) • Increased EDLF levels correlated with decline in creatinine clearance • Subjects who were EDLF positive showed better responses to DIF, implying potential for drug benefit • Proof of principle established in small proof of concept study demonstrating consistent and positive trends in both maternal and fetal outcomes with favorable safety profile (currently marketed drug) 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 Agunanne E et al, Marinobufagenin Levels in Preeclamptic Patients: A Preliminary Report. American Journal of Perinatology/Volume 28, Number 7, 2011,p 512, Figure 2. MATERNAL HEALTH: AMAG-423 © 2018 AMAG Pharmaceuticals, Inc. All rights reserved 17


 
Phase 2b/3a Study Design • Study design: – Multi-center, randomized, double-blind, placebo-controlled, parallel group study with DigiFab® – Dosing every 6 hours for 4 days • Study population: – 200 antepartum subjects with severe preeclampsia between 23 weeks/0 days and 31 weeks/6 days • Endpoints: – Primary outcome: composite endpoint comparing the incidence of babies who develop severe intraventricular hemorrhage, necrotizing enterocolitis or death – Secondary outcomes: change in baseline in serum creatinine, pulmonary edema, delivery latency, anti-hypertensive use, proportion of mothers with modified early obstetric warning score >=3 at 24 hours post final dose • Study update – AMAG will take over study execution and completion – Increasing study sites from 14 to approximately 50 – Considering expansion to include ex-U.S. sites MATERNAL HEALTH: AMAG-423 © 2018 AMAG Pharmaceuticals, Inc. All rights reserved 18


 
Development and Regulatory Timeline Q3-2018 Q4-2018 Q1-2019 Q2-2019 Q3-2019 Q4-2019 Q1-2020 Q2-2020 Q3-2020 Q4-2020 AMAG acquires global Accelerate patient enrollment in Topline data NDA filing rights to develop and Phase 2b/3a trial market DIF for treatment of severe preeclampsia MATERNAL HEALTH: AMAG-423 © 2018 AMAG Pharmaceuticals, Inc. All rights reserved 19


 
SUMMARY AMAG-423 • Addresses a serious unmet medical need with significant global commercial potential • Mechanism of action of DIF has strong scientific rationale • Proof of concept study demonstrated consistent and encouraging trends in improving neonatal and maternal outcomes with no significant safety concerns identified to date • Current Phase 2b/3a study has potential to form the basis for accelerated approval • Aligned with AMAG’s evolution to expand pipeline with innovative development stage compounds • Capitalizes on AMAG’s experience and presence in maternal/women’s healthcare MATERNAL HEALTH: AMAG-423 © 2018 AMAG Pharmaceuticals, Inc. All rights reserved 20


 
AMAG-423 Digoxin Immune Fab (ovine) (DIF) for the Treatment of Severe Preeclampsia September 26, 2018 © 2018 AMAG Pharmaceuticals, Inc. All rights reserved 21