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Reports Third Quarter Revenue of $133 million; Increases 2020 Pro Forma Revenue Guidance to $540 million to $560 million; Introduces 2021 Revenue Guidance of $750 million to $850 million

Holiday Savings at Dollar General Deliver Continued Focus on Customer Needs

Major Retailer Expands Holiday Savings Events to Help Customers Stretch Budgets in a Safe Shopping Environment

GOODLETTSVILLE, Tenn.–(BUSINESS WIRE)–
Dollar General (NYSE: DG) announced plans today to help customers celebrate and stretch their budgets this holiday season through savings events beginning on Friday, November 13, all while continuing safety measures and giving back to the nearly 17,000 communities the Company calls home. The major retailer also announced an additional 20% military appreciation discount from Friday, November 13 through Sunday, November 15.

“We understand customers may be celebrating the upcoming holidays differently this year, and Dollar General has a number of ways to help,” said Jeff Owen, Dollar General’s chief operating officer. “We remain focused on serving our customers by increasing contactless options with DG Pickup and self-checkout, delivering clean and inviting store environments and offering a series of sales events through an extended holiday season. We are equally excited to celebrate our mission of Serving Others through our ongoing partnerships with St. Jude Children’s Research Hospital and local toy drives including the Marine Toys for Tots Foundation.”

Extended Veteran Discounts

Dollar General has extended its military appreciation discount to provide an additional 20% off qualifying purchases from November 13 through November 15 for veterans, active duty military members, members of the National Guard & Reserve and their families. Additional savings are available in stores or by using the code MILITARY20 at DG.com.

Dollar General has a longstanding history of supporting those who serve through exclusive discounts, outreach in military communities through the Company’s military employee resource group, SERVE, and the founding of the Paychecks for Patriots program that supports service members’ transition to civilian life through meaningful employment opportunities.

DG Deal Days

Kickstarting an extended shopping period and series of savings events, DG first plans to offer a Pre-Holiday Event on November 13 and continue to provide exciting savings during selected periods below. Specific offerings and savings will be available online.

• Three Days of Lower Prices: November 19-21, 2020
• Four Days of Deals: November 22-25, 2020
• Thanksgiving Day Deals: November 26, 2020
• Thanksgiving Deal Days: November 26-28, 2020
• Three Days of Deals: December 3-5, 2020
• Additional Three Days of Deals: December 6-8, 2020

More Ways to Shop This Holiday

DG enhances customer shopping experiences by offering additional ways to save time and money this holiday season.

• DG Pickup: DG Pickup helps to make shopping even more convenient and contactless and is now available for most Dollar General stores. Through the DG app, customers may shop from the convenience of their smart phone and receive a communication when their order is ready. Once at the store, customers can grab their order from the in-store DG Pickup shelves and be on their way. DG Pickup also allows customers to take full advantage of the DG Digital Coupons for instant savings.

• DG Rewards: Customers have a new way to save on their favorite products in the DG app with the launch of DG Rewards, which allows customers to earn discounts on their favorite items over time in addition to DG Digital Coupons. To get started, customers can activate available DG Rewards online at DG.coupons.com/rewards. Once rewards are activated, they may head to the store to shop their favorite items, enter their phone number at check out and redeem their rewards.

• Dollar General Digital Coupons: One of the most popular ways to find additional savings on the DG app is through the DG Digital Coupons Program that provides savings throughout the year on national and private brand items to help customers’ wallets stretch even further. Customers may sign-up today by visiting www.dollargeneral.com/coupons or accessing coupons on the DG mobile app. Customers may digitally add coupons to their account and redeem them at checkout by entering the ten digit telephone number associated with their account on the pin pad.

• Cart Calculator: Also available through the DG app, customers can use the Cart Calculator to scan items as they shop and see a running total of items in their basket (including tax). Additionally, the app’s Coupon Surfacing functionality can alert customers if a digital coupon offer is available. When alerted, customers download the digital offer and see their savings appear after entering their 10-digit Digital Coupon number at register. When scanning products, Cart Calculator can also alert customers if a DG comparable private brand may be available for a lesser cost.

• Shopping List: For customers seeking to pre-plan their shopping trips, DG recently introduced the Shopping List on the DG mobile app. Customers can create their shopping list, find which items have an available digital coupon and calculate an estimated total before they arrive at their local DG store.

Serving Others

In keeping with Dollar General’s mission of Serving Others, the Company plans to continue its annual partnerships with the Marine Toys for Tots Foundation, local toy drives and the St. Jude’s Thanks and Giving® campaign to support the communities it proudly calls home. In total, the Company plans to provide $485,000 to support the meaningful work of nonprofit organizations and schools this holiday season through the following activations:

• St. Jude Children’s Research Hospital’s Thanks and Giving® campaign: In 2020, Dollar General is celebrating its 15^th anniversary in partnering with St. Jude to support its Thanks and Giving® campaign. In addition to providing $125,000 to the Memphis-based global leader in finding cures and saving children with cancer and other deadly diseases, Dollar General will also collect in-store donations from November 20 through December 18. To date, Dollar General and in-store donations have provided more than $26.3 million in support of the Thanks and Giving® campaign.

• Toy Drives: From November 20 through December 4, Dollar General plans to host toy drives to make the holidays brighter for families this season, as well as provide Marine Corps Toys for Tots with a $100,000 donation to support their efforts. Customers may purchase and donate toys to a local recipient organization, which is chosen by each DG store manager. Toys donated in each community are awarded to area residents either through a local toy drive or the Marine Toys for Tots Foundation’s community presence.

• Surprise Donations: Dollar General also plans to spread the holiday cheer and extend excitement through the donation of $260,000 in the communities it calls home! Throughout November and December, Dollar General plans to award 26 surprise grants in the amount of $10,000 each to schools or nonprofits across its hometown communities.

Hiring Opportunities

DG continues to seek candidates to support opportunities across its stores, distribution centers, private fleet and corporate functions. The Company provides employees with competitive wages, world-class and award-winning training and development programs and benefits including day-one telemedicine eligibility and Dollar General’s Employee Assistance Foundation, as well as health insurance coverage options, 401K savings and retirement plans, tuition reimbursement, paid parental leave and adoption assistance to eligible employees. Individuals seeking to begin or grow their career are encouraged to review opportunities and apply online at www.dollargeneral.com/careers.

COVID

DG is proud to be an essential retailer and to have been able to remain open during the COVID-19 pandemic and takes its responsibility to help American households stretch their budgets very seriously.

For the upcoming holiday season, DG remains committed to keeping employee and customer safety a top priority and will continue proactive and preventative actions including a company-wide mask mandate, robust cleaning protocols and social distancing measures, as well as supplying additional hand sanitizer for employees and customers and providing paid sick leave for employees impacted by COVID-19.

DG’s response to the COVID-19 pandemic response has been recognized by Forbes magazine, which identified the Company among its top 25 corporate responders, and is reflected in a Harris Poll that outlines the essential role DG stores are playing.

Holiday Hours of Operation

DG will extend store hours of operations over the holiday shopping season. Localized store operating hours may be found on the store locator here.

• Thanksgiving Day: Open from 7 a.m. to 5 p.m.*

* Massachusetts, Maine and Rhode Island stores will be closed on Thanksgiving Day, November 26, 2020.

• Black Friday: Normal Operating Hours

• Friday, December 18 – Wednesday, December 23: Open at normal hours and close at 11 p.m.

• Thursday, December24: Open at normal hours and close at 10 p.m.

• Friday, December 25: Closed

• Saturday, December 26: Normal Operating Hours

FedEx and Western Union

DG continues to provide customers with added convenience options this holiday from Western Union and FedEx.

• Western Union: DG customers may send and/or receive Western Union wire transfer services at DG locations nationwide. To send funds, customers may initiate international and domestic wire money transfers digitally through the Western Union® mobile app or at westernunion.com, then pay in person at any DG location.

• FedEx: Customers can take advantage of the extensive FedEx retail convenience network at more than 8,000 DG stores to provide a safe and secure location to drop-off and/or pickup packages.

For additional information, photographs or items to supplement a story, please visit the DG Newsroom, contact the Media Relations Department at 1-877-944-DGPR (3477) or via email at [email protected].

About Dollar General Corporation

Dollar General Corporation has been delivering value to shoppers for more than 80 years through its mission of Serving Others. Dollar General helps shoppers Save time. Save money. Every day!® by offering products that are frequently used and replenished, such as food, snacks, health and beauty aids, cleaning supplies, basic apparel, housewares and seasonal items at everyday low prices in convenient neighborhood locations. Dollar General operated 16,720 stores in 46 states as of July 31, 2020. In addition to high-quality private brands, Dollar General sells products from America’s most-trusted manufacturers such as Clorox, Energizer, Procter & Gamble, Hanes, Coca-Cola, Mars, Unilever, Nestle, Kimberly-Clark, Kellogg’s, General Mills, and PepsiCo. Learn more about Dollar General at www.dollargeneral.com.

View source version on businesswire.com: https://www.businesswire.com/news/home/20201113005179/en/

Investor Contacts:

Donny Lau (615) 855-5591

Kevin Walker (615) 855-4954

Media Contact:

Crystal Ghassemi (615) 855-5210

KEYWORDS: United States North America Tennessee

INDUSTRY KEYWORDS: Men Other Retail Family Discount/Variety Department Stores Consumer Food/Beverage Parenting Retail Women Seniors Home Goods

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AECOM awarded TEXRail extension project

Trinity Metro will extend TEXRail commuter rail line south into Fort Worth’s Medical District

LOS ANGELES–(BUSINESS WIRE)–
AECOM (NYSE:ACM), the world’s premier infrastructure consulting firm, has been selected by Trinity Metro to conduct the environmental assessment and preliminary engineering for the TEXRail extension project. Trinity Metro plans to extend the commuter rail line south from downtown Fort Worth, Texas, connecting the Fort Worth T&P Station to the future TEXRail station in the Fort Worth Medical District. The extension will serve the more than 40,000 people who work in the fast-growing Medical District, plus residents and businesses in the surrounding Near Southside neighborhood.

“We’re thrilled to continue supporting Trinity Metro and the city in its efforts to make public transportation more accessible,” said Lara Poloni, AECOM’s president. “AECOM looks forward to leveraging its global transportation expertise on this project and remains committed to advancing key infrastructure during this economic recovery.”

“Trinity Metro’s commuter rail line already has nine stations in Fort Worth, North Richland Hills and Grapevine, and this expansion is intended to improve transit equity by providing access to healthcare services for local residents who may not have a vehicle and will ease the commute for healthcare workers traveling in and out of the district,” said Dev Rastogi, AECOM’s vice president and Dallas executive.

The TEXRail commuter rail line opened in January 2019 and extends northeast for 27 miles between downtown Fort Worth and Dallas Fort Worth International Airport’s Terminal B. Stations are located along the corridor in North Fort Worth, North Richland Hills, Grapevine and DFW Airport. Currently the rail line only goes as far south as the Fort Worth T&P Station, but does not yet serve the city’s medical district or southern neighborhoods. The new project will extend the line 2.1 miles with a proposed station south of Mistletoe Boulevard, near Baylor Scott & White All Saints Medical Center.

Prior to the COVID-19 pandemic, ridership on TEXRail had increased by more than 50% to more than 50,000 per month, providing a more efficient and environmentally conscious transportation method for riders. As project consultant, AECOM’s role will include a study to review the environmental impact of the project. AECOM will prepare the preliminary engineering plans, environmental documentation and support public outreach consistent with all Federal Transit Administration (FTA) and National Environmental Policy Act (NEPA) requirements. In a similar role, AECOM supported Trinity Metro throughout the development of the initial phase of the TEXRail project.

“We are excited about moving forward with this extension to the TEXRail commuter rail line,” said Jon-Erik “AJ” Arjanen, vice president and chief operating officer of Trinity Metro. “Working through the environmental assessment and preliminary engineering are important phases in this project.”

Ranked as ENR’s 2020 Top Environmental Firm, AECOM has extensive experience in the environmental services industry, helping industrial and public sector clients around the world balance growth with resiliency.

AECOM’s previous North Texas projects include the environmental impact statement for the proposed 240-mile Dallas to Houston high speed rail project; environmental permitting, compliance and remediation services for Texas’ largest freight railroad headquartered in North Texas; and remediation and due diligence services for numerous public and private sector clients throughout the region.

About AECOM

AECOM (NYSE:ACM) is the world’s premier infrastructure consulting firm, delivering professional services throughout the project lifecycle – from planning, design and engineering to program and construction management. We partner with our clients in the public and private sectors to solve their most complex challenges and build legacies for generations to come. On projects spanning transportation, buildings, water, governments, energy and the environment, our teams are driven by a common purpose to deliver a better world. AECOM is a Fortune 500 firm and its Professional Services business had revenue of approximately $13.6 billion in fiscal year 2019. See how we deliver what others can only imagine at aecom.com and @AECOM.

Forward-Looking Statements

All statements in this communication other than statements of historical fact are “forward-looking statements” for purposes of federal and state securities laws, including any statements of the plans, strategies and objectives for future operations, profitability, strategic value creation, coronavirus impacts, risk profile and investment strategies, and any statements regarding future economic conditions or performance, and the expected financial and operational results of AECOM. Although we believe that the expectations reflected in our forward-looking statements are reasonable, actual results could differ materially from those projected or assumed in any of our forward-looking statements. Important factors that could cause our actual results, performance and achievements, or industry results to differ materially from estimates or projections contained in our forward-looking statements include, but are not limited to, the following: our business is cyclical and vulnerable to economic downturns and client spending reductions; impacts caused by the coronavirus and the related economic instability and market volatility, including the reaction of governments to the coronavirus, including any prolonged period of travel, commercial or other similar restrictions, the delay in commencement, or temporary or permanent halting of construction, infrastructure or other projects, requirements that we remove our employees or personnel from the field for their protection, and delays or reductions in planned initiatives by our governmental or commercial clients or potential clients; losses under fixed-price contracts; limited control over operations run through our joint venture entities; liability for misconduct by our employees or consultants; failure to comply with laws or regulations applicable to our business; maintaining adequate surety and financial capacity; high leverage and potential inability to service our debt and guarantees; exposure to Brexit; exposure to political and economic risks in different countries; currency exchange rate fluctuations; retaining and recruiting key technical and management personnel; legal claims; inadequate insurance coverage; environmental law compliance and adequate nuclear indemnification; unexpected adjustments and cancellations related to our backlog; partners and third parties who may fail to satisfy their legal obligations; AECOM Capital real estate development projects; managing pension cost; cybersecurity issues, IT outages and data privacy; risks associated with the benefits and costs of the Power transaction and other recent acquisitions and divestitures, including the risk that the expected benefits of such transactions or any contingent purchase price will not be realized within the expected time frame, in full or at all; the risk that costs of restructuring transactions and other costs incurred in connection with recent acquisitions and divestitures will exceed our estimates or otherwise adversely affect our business or operations; as well as other additional risks and factors that could cause actual results to differ materially from our forward-looking statements set forth in our reports filed with the Securities and Exchange Commission. Any forward-looking statements are made as of the date hereof. We do not intend, and undertake no obligation, to update any forward-looking statement.

View source version on businesswire.com: https://www.businesswire.com/news/home/20201113005135/en/

Investor Contact:

Will Gabrielski

Senior Vice President, Investor Relations

213.593.8208

[email protected]

Media Contact:

Brendan Ranson-Walsh

Vice President, Global Communications & Corporate Responsibility

213.996.2367

[email protected]

KEYWORDS: California Texas United States North America Canada

INDUSTRY KEYWORDS: Construction & Property Natural Resources Defense Environment Other Transport Engineering Trucking Urban Planning Rail Maritime Logistics/Supply Chain Management Landscape Air Manufacturing Transport Architecture Other Energy Utilities Oil/Gas Coal Contracts Alternative Energy Energy Public Transport Building Systems Mining/Minerals Nuclear

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Posted on November 13, 2020 6:53 am

Aerie Pharmaceuticals Receives Positive CHMP Opinion for Roclanda® in the European Union

Aerie Pharmaceuticals Receives Positive CHMP Opinion for Roclanda^® in the European Union

-European Commission Decision Anticipated in Approximately Two Months-

DURHAM, N.C.–(BUSINESS WIRE)–
Aerie Pharmaceuticals, Inc. (NASDAQ: AERI), an ophthalmic pharmaceutical company focused on the discovery, development and commercialization of first-in-class therapies for the treatment of patients with open-angle glaucoma, ocular surface diseases and retinal diseases, today announced the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending approval of the marketing authorisation application (MAA) for Roclanda^® (netarsudil and latanoprost ophthalmic solution) 0.02%/0.005%. The recommended indication is the reduction of elevated intraocular pressure in adult patients with primary open-angle glaucoma or ocular hypertension for whom monotherapy with a prostaglandin or netarsudil provides insufficient IOP reduction.

The CHMP positive opinion is a scientific recommendation for marketing authorisation, which is referred to the European Commission for a final decision on the Company’s MAA. The final decision is expected in approximately two months and will be applicable to all European Union member states plus Iceland, Norway and Liechtenstein.

“We are delighted that the CHMP has adopted a positive opinion for Roclanda^®,” said Vicente Anido, Jr., Ph.D., Chairman and Chief Executive Officer at Aerie. “We look forward to the European Commission’s final decision on the MAA for Roclanda^®, which is expected by early next year.”

Roclanda^® is currently marketed as Rocklatan^® in the United States and is indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or hypertension.

About Aerie Pharmaceuticals, Inc.

Aerie is an ophthalmic pharmaceutical company focused on the discovery, development and commercialization of first-in-class therapies for the treatment of patients with open-angle glaucoma, ocular surface diseases and retinal diseases. Aerie’s first product, Rhopressa^® (netarsudil ophthalmic solution) 0.02%, a once-daily eye drop approved by the U.S. Food and Drug Administration (FDA) for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension, was launched in the United States in April 2018. In clinical trials of Rhopressa^®, the most common adverse reactions were conjunctival hyperemia, corneal verticillata, instillation site pain, and conjunctival hemorrhage. More information about Rhopressa^®, including the product label, is available at www.rhopressa.com. Aerie’s second product for the reduction of elevated IOP in patients with open-angle glaucoma or ocular hypertension, Rocklatan^® (netarsudil and latanoprost ophthalmic solution) 0.02%/0.005%, the first and only fixed-dose combination of Rhopressa^® and the widely-prescribed PGA (prostaglandin analog) latanoprost, was launched in the United States in May 2019. In clinical trials of Rocklatan^®, the most common adverse reactions were conjunctival hyperemia, corneal verticillata, instillation site pain, and conjunctival hemorrhage. More information about Rocklatan^®, including the product label, is available at www.rocklatan.com. Aerie continues to focus on global expansion and the development of additional product candidates and technologies in ophthalmology, including for wet age-related macular degeneration and diabetic macular edema. More information is available at www.aeriepharma.com.

Forward-Looking Statements

This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should,” “exploring,” “pursuing” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Forward-looking statements in this release include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the duration and severity of the coronavirus disease (COVID-19) outbreak, including the impact on our clinical and commercial operations, demand for our products and financial results and condition of our global supply chains; our expectations regarding the commercialization and manufacturing of Rhopressa^®, Rocklatan^®, Rhokiinsa^® and Roclanda^® or any current or future product candidates, including the timing, cost or other aspects of their commercial launch; our commercialization, marketing, manufacturing and supply management capabilities and strategies in and outside of the United States; the success, timing and cost of our ongoing and anticipated preclinical studies and clinical trials for Rhopressa^® and Rocklatan^®, with respect to regulatory approval outside of the United States, and any current or future product candidates; our expectations regarding the effectiveness of Rhopressa^®, Rocklatan^®, Rhokiinsa^®, Roclanda^® or any current or future product candidates; the timing of and our ability to request, obtain and maintain FDA or other regulatory authority approval of, or other action with respect to, as applicable, Rhopressa^®, Rocklatan^® or any current or future product candidates, including the expected timing of, and timing of regulatory and/or other review of, filings for, as applicable, Rhopressa^®, Rocklatan^® or any current or future product candidates; the potential advantages of Rhopressa^® and Rocklatan^® or any current or future product candidates; our plans to pursue development of additional product candidates and technologies; our plans to explore possible uses of our existing proprietary compounds beyond glaucoma, including development of our retina program; our ability to protect our proprietary technology and enforce our intellectual property rights; and our expectations regarding strategic operations, including our ability to in-license or acquire additional ophthalmic products, product candidates or technologies. In particular, FDA approval of Rhopressa^® and Rocklatan^® do not constitute FDA approval of any future product candidates, and there can be no assurance that we will receive FDA approval for any future product candidates. In addition, FDA approval of Rhopressa^® and Rocklatan^® and EMA approval of Rhokiinsa^® do not constitute regulatory approval of Rhopressa^® and Rocklatan^® in other jurisdictions, including EMA approval of Roclanda^®, and there can be no assurance that we will receive regulatory approval for Rhopressa^® and Rocklatan^® in such other jurisdictions, including EMA approval of Roclanda^®. Furthermore, EMA acceptance of the MAA for Roclanda^® and the CHMP opinion of Roclanda^® do not constitute EMA approval of Roclanda^®, and there can be no assurance that we will receive EMA approval of Roclanda^®. By their nature, forward-looking statements involve risks and uncertainties because they relate to events, competitive dynamics, industry change and other factors beyond our control, and depend on regulatory approvals and economic and other environmental circumstances that may or may not occur in the future or may occur on longer or shorter timelines than anticipated. We discuss many of these risks in greater detail under the heading “Risk Factors” in the quarterly and annual reports that we file with the Securities and Exchange Commission (SEC). Forward-looking statements are not guarantees of future performance and our actual results of operations, financial condition and liquidity, and the development of the industry in which we operate may differ materially from the forward-looking statements contained in this press release. Any forward-looking statements that we make in this press release speak only as of the date of this press release. We assume no obligation to update our forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.

View source version on businesswire.com: https://www.businesswire.com/news/home/20201113005354/en/

Media: Tad Heitmann 949-526-8747; [email protected]

Investors: Ami Bavishi 908-947-3949; [email protected]

KEYWORDS: North Carolina Europe United States North America

INDUSTRY KEYWORDS: Health Pharmaceutical Optical Clinical Trials Medical Supplies

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Ra Medical Systems to Participate in A.G.P.’s Virtual Healthcare Symposium

CARLSBAD, Calif.–(BUSINESS WIRE)–
Ra Medical Systems, Inc. (NYSE: RMED) , a medical device company focusing on commercializing excimer laser systems to treat vascular and dermatological diseases, announces that management will participate in A.G.P.’s Virtual Healthcare Symposium. This event, which features one-on-one meetings, is being held Thursday, November 19, 2020.

Ra Medical management will be available for one-on-one meetings. Interested investors should contact Ra Medical President Jeffrey Kraws at [email protected] or Jody Cain at [email protected].

About Ra Medical Systems

Ra Medical Systems commercializes excimer lasers and catheters for the treatment of vascular and dermatological diseases. In May 2017 the DABRA excimer laser system received FDA 510(k) clearance in the U.S. for crossing chronic total occlusions, or CTOs, in patients with symptomatic infrainguinal lower extremity vascular disease with an intended use for ablating a channel in occlusive peripheral vascular disease. The Pharos excimer laser system is FDA-cleared and is used as a tool in the treatment of psoriasis, vitiligo, atopic dermatitis and leukoderma. DABRA and Pharos are both based on Ra Medical’s core excimer laser technology platform and deploy similar mechanisms of action. Ra Medical manufactures DABRA and Pharos excimer lasers and catheters in a 32,000-square-foot facility located in Carlsbad, Calif. The vertically integrated facility is ISO 13485 certified and is licensed by the State of California to manufacture sterile, single-use catheters in controlled environments.

View source version on businesswire.com: https://www.businesswire.com/news/home/20201113005006/en/

At the Company:

Jeffrey Kraws

President, Ra Medical Systems

760-496-9008

[email protected]

Investors:

LHA Investor Relations

Jody Cain

310-691-7100

[email protected]

KEYWORDS: United States North America California

INDUSTRY KEYWORDS: General Health Health Medical Devices

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Posted on November 13, 2020 6:53 am

Madrigal Pharmaceuticals Highlights Presentations at The Liver Meeting Digital Experience™, The American Association for the Study of Liver Diseases Meeting November 13, 2020, Including NASH Expert Insights on the Ongoing Open Label Arm of Resmetirom 52-Week Phase 3 MAESTRO-NAFLD-1 Trial

• Dr. Stephen Harrison will present
  Resmetirom for the Treatment of NASH: Early Data from the Phase 3 MAESTRO Clinical Trials | The Liver Meeting Digital Experience™
  , AASLD
  Product Theater
  on Friday
  ,
  November 13
  , 2020
  ,
  at 4:30 PM ET.

• In the 100 mg open label arm of MAESTRO-NAFLD
  :
  • At
    week
    16
    ,
    MRI-PDFF
    (magnetic resonance imaging-proton density fat fraction)
    reduction
    compared to baseline
    was 53% overall
    (p<0.0001)
    and
    up to 62% in key subgroups
  • At weeks 12-24, statistically significant
    lowering of
    liver enzymes, inflammatory biomarkers and
    atherogenic lipids and lipoproteins
    were observed
  • At week 16
    ,
    compared to baseline
    ,
    a meaningful reduction
    (p=0.003)
    in
    magnetic resonance elastography (MRE)
    , a measure of liver of fibrosis and inflammation
    was
    seen

CONSHOHOCKEN, Pa., Nov. 13, 2020 (GLOBE NEWSWIRE) — Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL), announced that Dr. Stephen Harrison, M.D., Medical Director for Pinnacle Clinical Research, San Antonio, Texas, and Visiting Professor of Hepatology, Oxford University, and Principal Investigator of the MAESTRO studies, will make an oral presentation today at 4:30 PM ET at The Liver Meeting Digital Experience™, The American Association for the Study of Liver Diseases Meeting, November 2020 accessible via the Product Theaters and Satellite Symposium page. Dr. Harrison’s presentation, based on data from studies with MGL-3196 (resmetirom), will also highlight key insights from three posters, which are available to registered attendees on The Liver Meeting Digital Experience™ website throughout the four-day meeting. Resmetirom is the first orally administered, small-molecule, liver-directed, truly β-selective thyroid hormone receptor (THR) agonist and is currently in Phase 3 development for the treatment of NASH patients both with biopsy-confirmed fibrosis stage 2-3 (ClinicalTrials.gov NCT03900429) and in presumed NASH subjects diagnosed non-invasively (ClinicalTrials.gov/NCT04197479).

Dr. Harrison commented, “In the MAESTRO-NASH study, using a series of readily available tests such as FibroScan, MRI-PDFF and PRO-C3 in patients with metabolic risk factors (diabetes, obesity, dyslipidemia and hypertension) we have demonstrated that, in recruiting a clinical trial, NASH with advanced fibrosis (F2-F3) may be confirmed on liver biopsy with an increasing level of confidence. The MAESTRO-NAFLD-1 study in patients with presumed NASH diagnosed non-invasively, now with 1,200 enrolled patients, is helping to build a robust safety and efficacy data set in NASH patients treated with resmetirom.”

Becky Taub, M.D., Chief Medical Officer and President of Research & Development of Madrigal, stated, “Interim data from the ongoing open label arm of MAESTRO-NAFLD-1 confirm the safety and efficacy at a 100 mg dose of resmetirom, with 80% of patients achieving at least a 30% reduction from baseline in liver fat measured on MRI-PDFF, and more than half achieving a 50% or greater reduction in liver fat at Week 16, both of which percentage fat reductions have been associated with increased NASH resolution and reduction in liver fibrosis on subsequent liver biopsy in resmetirom treated patients. The reduction in MRE at Week 16 is novel, and consistent with potential fibrosis and inflammation reductions in patients with baseline F1-F3 fibrosis. MRE is potentially a more accurate measurement of liver fibrosis than other non-invasive measures such as FibroScan because MRE measures a larger area of the liver, and may demonstrate correlations with Week 52 liver biopsy in MAESTRO-NASH. Of note, no safety flags have been observed at the 100 mg dose in the open-label arm, consistent with earlier Phase 1 and Phase 2 data.”

Paul Friedman, M.D., Madrigal’s Chief Executive Officer, added, “The open label arm of MAESTRO-NAFLD-1 provides opportunities to observe safety and the potential benefits of resmetirom treatment on an ongoing basis in non-cirrhotic NASH and compensated NASH cirrhotic patients, with completion of the double-blind arms of the study in the next 12 months. We believe that these data will inform the results of the blinded 80 and 100 mg arms of the MAESTRO-NAFLD-1 and MAESTRO-NASH studies.”  

POSTER PRESENTATIONS

• #1657
  ALGORITHM FOR PREDICTING ADVANCED NASH FIBROSIS ON SCREENING BIOPSY IN RESMETIROM PHASE 3 MAESTRO-NASH CLINICAL TRIAL
  
  Dr. Stephen A Harrison
  ¹, Dr. Rebecca A. Taub², Prof. Morten Asser Karsdal³, John Franc², Dr. Mustafa R Bashir⁴, Mr. Jordan Mark Barbone², Dr. Guy Neff⁵, Dr. Nadege T Gunn¹ and Dr. Sam Moussa⁶, (1) Pinnacle Clinical Research, (2) Madrigal Pharmaceuticals, (3) Biomarkers & Research, Nordic Bioscience, (4) Department of Radiology, Duke University Medical Center, (5) Covenant Research, LLC, (6) Medical, Adobe Gastroenterology

  MAESTRO-NASH is a Phase 3 double-blind placebo-controlled serial liver biopsy study to evaluate resmetirom for the treatment of NASH with F2 or F3 fibrosis and an exploratory F1 arm. Data was assessed for the power of the screening paradigm to predict eligible NASH with fibrosis on liver biopsy. These data suggest that PRO-C3 is a marker not only of fibrosis stage in NASH but also of the level of NASH activity (inflammation and ballooning) in the NASH liver. In the absence of a liver biopsy, elevated PRO-C3 in the setting of metabolic syndrome (or FIBC3 (PRO-C3 [age, BMI, platelets, T2D]), fibroscan and MRI-PDFF may predict advanced NASH.

• #1707
  TREATMENT WITH RESMETIROM IN PHASE 3 MAESTRO-NAFLD-1 NASH STUDY OPEN LABEL ARM: EFFECTS ON BIOMARKERS AND IMAGING
  Dr. Stephen A Harrison, Pinnacle Clinical Research, Dr. Naim Alkhouri, Arizona Liver Health, Dr. Rebecca A. Taub, Madrigal Pharmaceuticals, Dr. Guy Neff, Covenant Research, LLC, Dr. Seth J Baum, Excel Medical Clinical Trials and Dr. Mustafa R Bashir, Department of Radiology, Duke University Medical Center Data from the ongoing Open Label Arm of Madrigal’s MAESTRO-NAFLD-1 trial will be presented.

  In this 52-week Phase 3 open label study, NASH patients identified using non-invasive imaging and biomarkers were treated with resmetirom 100 mg and demonstrated rapid reduction in hepatic fat, biomarkers and atherogenic lipids after 12-16 weeks of treatment, potentially supporting use of non-invasive tests to monitor individual NASH patient response to resmetirom treatment.

	All	SHBG (high)
MRI-PDFF (%)
Baseline (%)	17.6	17.9
Relative % Change	-53%	-62%
p-value	<0.0001	<0.0001
MRE (kPa)
Baseline (>2.9, F1-F3)	3.5	3.5
Absolute Change	-0.34	-0.46
p-value	0.003	0.003

• #1675
  IMPROVEMENT OF HEALTH-RELATED QUALITY OF LIFE IS ASSOCIATED WITH
  IMPROVEMENT OF FAT FRACTION BY MRI-PDFF IN PATIENTS WITH NONALCOHOLIC
  STEATOHEPATITIS TREATED WITH RESMETIROM 
  Dr. Zobair M. Younossi, MD, MPH, FAASLD¹, Maria Stepanova², Dr. Rebecca A. Taub³, Mr. Jordan Mark Barbone³, Dr. Sam Moussa⁴and Dr. Stephen A Harrison⁵, (1) Center for Liver Disease, Department of Medicine, Inova Health System, (2) Center for Outcomes Research in Liver Diseases, Washington, DC, United States, (3) Madrigal Pharmaceuticals, (4) Medical, Adobe Gastroenterology, (5) Pinnacle Clinical Research

  A review of patient reported outcome data from resmetirom’s Phase 2 NASH study demonstrates that NASH patients treated with resmetirom who had liver fat reduction also improved some quality of life measures, particularly physical components such as bodily pain. Ongoing Phase 3 studies will assess long-term sustainability of quality of life improvements with resmetirom treatment.

About
R
esmetirom (MGL-3196)

Thyroid hormone, through activation of its β-receptor in hepatocytes, plays a central role in liver function impacting a range of health parameters from levels of serum cholesterol and triglycerides to the pathological buildup of fat in the liver. Thyroid hormone receptor (THR)-β action in the liver is key to proper function of the liver, including regulation of mitochondrial activity such as breakdown of liver fat and control of the level of normal, healthy mitochondria. Patients with NASH have reduced levels of thyroid hormone activity in the liver with resultant impaired hepatic function, in part due to the inflamed state of the liver that causes degradation of thyroid hormone.

To exploit the thyroid hormone receptor (THR)-β pathway for therapeutic purposes in cardio-metabolic and liver diseases, it is important to avoid activity at the THR-α receptor, the predominant systemic receptor for thyroid hormone that is responsible for activity outside the liver including in heart and bone. The lack of selectivity of older thyromimetic compounds, chemically-related toxicities and undesirable distribution in the body led to safety concerns. Madrigal recognized that greater selectivity for thyroid hormone receptor (THR)-β and liver targeting might overcome these challenges and deliver the full therapeutic potential of THR-β agonism. Resmetirom has been shown to be highly selective based on 1) THR-β receptor functional selectivity based on both in vitro and in vivo assays and 2) specific uptake into the liver, its site of action, virtually avoiding any uptake into tissues outside the liver. In short and long term human and animal studies, resmetirom has been confirmed to be safe and devoid of activity at the THR-α receptor and without impact on bone or cardiac parameters. Resmetirom does not impact the thyroid axis hormones, including the central thyroid axis. Madrigal believes that resmetirom is the first orally administered, small-molecule, liver-directed, truly β-selective THR agonist.

About the Phase 3 Registration Program for the Treatment of NASH
(Non-alcoholic steatohepatitis)

Analyses from the resmetirom Phase 2 NASH study demonstrate that the magnitude of liver fat reduction accurately predicts NASH resolution and liver fibrosis reduction and, specifically, that the resmetirom doses being used in Madrigal’s Phase 3 MAESTRO-NASH trial could achieve the level of fat reduction predictive of NASH resolution and fibrosis reduction [Madrigal COVID and ABSTRACT Press Release_20200414].

The Phase 3 MAESTRO-NASH trial is expected to enroll 900 patients with biopsy-proven NASH (fibrosis stage 2 or 3), randomized 1:1:1 to receive resmetirom 80 mg once a day, 100 mg once a day, or placebo. After 52 weeks of treatment a second biopsy is performed. The primary surrogate endpoint on biopsy will be NASH resolution, with at least a 2-point reduction in NAS (NASH Activity Score), and with no worsening of fibrosis. Two key secondary endpoints are liver fibrosis improvement of at least one stage, with no worsening of NASH, and lowering of LDL-cholesterol [ClinicalTrials.gov/NCT03900429].

A second 52-week Phase 3 multi-center, double-blind, randomized, placebo-controlled study of resmetirom, MAESTRO-NAFLD-1, was initiated in December 2019 in 700 patients with non-alcoholic fatty liver disease (NAFLD), presumed NASH, randomized 1:1:1 to receive resmetirom 80 mg once a day, 100 mg once a day, or placebo. MAESTRO-NAFLD-1 also includes a 100 mg resmetirom open label arm in more than 100 non-cirrhotic NASH patients and additional open-label patients with compensated NASH cirrhosis. The trial was expanded to include more than 1,200 patients, in order to significantly enhance resmetirom’s safety database and provide further opportunity to study selected patient subgroups. Unlike MAESTRO-NASH, MAESTRO-NAFLD-1 is a non-biopsy study and represents a “real-life” NASH study. NASH or presumed NASH is documented using historical liver biopsy or non-invasive techniques including FibroScan and MRI-PDFF. Using non-invasive measures, MAESTRO-NAFLD-1 is designed to provide incremental safety information to support the NASH indication as well as provide additional data regarding clinically relevant key secondary efficacy endpoints to better characterize the potential clinical benefits of resmetirom on cardiovascular and liver related endpoints. These key secondary endpoints include LDL-cholesterol, apolipoprotein B and triglyceride (TG) lowering; reduction of liver fat as determined by magnetic resonance imaging, proton density fat fraction (MRI-PDFF); and reduction of PRO-C3, a NASH fibrosis biomarker. [ClinicalTrials.gov/NCT04197479] Additional secondary and exploratory endpoints will be assessed including reduction in liver enzymes, FibroScan scores and other fibrosis and inflammatory biomarkers.

These and other data, including safety parameters, form the basis for potential subpart H submission to FDA for accelerated approval for the treatment of NASH. The original 900 patients in the MAESTRO-NASH study will continue on therapy after the initial 52-week treatment period; up to another 1,100 patients are to be added using the same randomization plan and the study is expected to continue for up to 54 months to accrue and measure clinical events, most relevantly progression to cirrhosis. 

About
R
esmetirom
’
s
P
otential to
C
onfer
C
ardiovascular
Risk Reduction
in NASH patients

Additionally, resmetirom lowers multiple atherogenic lipids, including LDL cholesterol, apolipoprotein B, triglycerides, and lipoprotein (a), as demonstrated in Phase 2, a key differentiating factor compared with other NASH therapeutics. The magnitude of reduction of these lipids support a potential indication for treatment of hyperlipidemia in NASH patients and predicts a potential for benefit on cardiovascular (CV) events in NASH patients who die most frequently of CV, not liver disease.

Because of their diabetes, dyslipidemia, hypertension, obesity in concert with an inflamed, fatty liver, NASH patients, particularly those with advanced fibrosis, are at a substantially increased CV risk compared to the general population. Resmetirom’s ability to decrease liver fat, which is an independent risk factor for CV events, and resmetirom’s effect to reduce atherogenic lipids are being further evaluated in several key secondary endpoints in both MAESTRO Phase 3 clinical studies.

About Madrigal Pharmaceuticals

Madrigal Pharmaceuticals, Inc. (Nasdaq: MDGL) is a clinical-stage biopharmaceutical company pursuing novel therapeutics that target a specific thyroid hormone receptor pathway in the liver, which is a key regulatory mechanism common to a spectrum of cardio-metabolic and fatty liver diseases with high unmet medical need. Madrigal’s lead candidate, resmetirom, is a first-in-class, orally administered, small-molecule, liver-directed, thyroid hormone receptor (THR)-β selective agonist that is in currently in two Phase 3 clinical studies, MAESTRO-NASH and MAESTRO-NAGLD-1, designed to demonstrate multiple benefits across a broad spectrum of NASH (non-alcoholic steatohepatitis) and NAFLD (non-alcoholic fatty liver disease) patients. For more information, visit www.madrigalpharma.com.

Forward-Looking Statements

This communication contains “forward-looking statements”
made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, that are based on our beliefs and assumptions and on information currently available to us
, but are subject to factors beyond our control
. Forward-looking statements include but are not limited to statements or references concerning: our clinical trials
;
research and development activities
;
the timing and results associated with the future development of our lead product candidate, MGL-3196 (resmetirom); our primary and secondary study endpoints for resmetirom and the potential for achieving such endpoints and projections; optimal dosing levels for resmetirom; projections regarding potential future NASH resolution, safety, fibrosis treatment, cardiovascular effects
,
lipid treatment
or biomarker effects
with resmetirom;
the predictive power
of
liver fat reduction on NASH resolution with fibrosis reduction
or improvement; the achievement of enrollment objectives concerning patient number, safety database and/or timing for our studies; the predictive power of liver fibrosis reductionwith resmetirom using non-invasive tests, including the use of MRE; the predictive power of non-invasive tests generally, including for purposes of recruiting a NASH clinical trial; potential NASH or NAFLD patient risk profile benefits with resmetirom; and our possible or assumed future results of operations and expenses, business strategies and plans, capital needs and financing plans, trends, market sizing, competitive position, industry environment and potential growth opportunities, among other things. Forward-looking statements: reflect management’s current knowledge, assumptions, judgment and expectations regarding future performance or events; include all statements that are not historical facts; and can be identified by terms such as “allow,” “anticipates,” “be,” “believes,” “continue,” “could,” “demonstrates,” ”design,” “estimates,” “expects,” “forecasts,” “future,” “goal,” “hopeful,” ”inform,” “intends,” “may,” “might,” “plans,” “potential,” “predicts,” ”predictive,” “projects,” “seeks,” “should,” “will,” “would” or similar expressions and the negatives of those terms. Although management presently believes that the expectations reflected in such forward-looking statements are reasonable, it can give no assurance that such expectations will prove to be correct and you should be aware that actual results could differ materially from those contained in the forward-looking statements.

Forward-looking statements are subject to a number of risks and uncertainties including, but not limited to
:
our clinical development of resmetirom
;
enrollment uncertainties,
generally and in relation to COVID-19 shelter-in-place and social distancing measures and individual precautionary measures that may be implemented or continued for an uncertain period of time;
outcomes or trends from competitive studies
;
future topline data timing or results;
the risks of achieving potential benefits in stud
ies
that includes substantially more patients than our prior stud
ies;
the timing and outcomes of clinical studies of resmetirom
;
and the uncertainties inherent in clinical testing. Undue reliance should not be placed on forward- looking statements, which speak only as of the date they are made. Madrigal undertakes no obligation to update any forward-looking statements to reflect new information, events or circumstances after the date they are made, or to reflect the occurrence of unanticipated events. Please refer to Madrigal’s filings with the U.S. Securities and Exchange Commission for more detailed information regarding these risks and uncertainties and other factors that may cause actual results to differ materially from those expressed or implied.
We specifically discuss these risks and uncertainties in greater detail in the section entitled “Risk Factors” in our Annual Report on Form 10-K for
the year ended December 31, 2019
and our Quarterly Report on Form 10-Q for the period ended
June
30, 2020
, as well as in our other filings with the SEC.

Investor Contact:

Marc Schneebaum, Madrigal Pharmaceuticals, Inc. [email protected]

Media Contact:

Mike Beyer, Sam Brown Inc. [email protected] 312 961 2502