Market Newsdesk

CHICAGO and VANCOUVER, British Columbia, Dec. 31, 2020 (GLOBE NEWSWIRE) — Green Thumb Industries Inc. (Green Thumb) (CSE: GTII) (OTCQX: GTBIF), a leading national cannabis consumer packaged goods company and owner of Rise™ retail stores, today announced the resignation of Alex Yemenidjian from its Board of Directors to pursue gaming license opportunities.

“We appreciate Alex’s contributions as a valued member of Green Thumb’s Board of Directors and wish him success in his future endeavors,” said Green Thumb Founder and Chief Executive Officer Ben Kovler.

“I continue to have the utmost confidence in Green Thumb as a significant shareholder and look forward to watching the company continue to serve as an industry leader,” said Yemenidjian.

 About Green Thumb Industries:

Green Thumb Industries Inc. (“Green Thumb”), a national cannabis consumer packaged goods company and retailer, promotes well-being through the power of cannabis while giving back to the communities in which it serves. Green Thumb manufactures and distributes a portfolio of branded cannabis products including Beboe, Dogwalkers, Dr. Solomon’s, incredibles, Rythm and The Feel Collection. The company also owns and operates rapidly growing national retail cannabis stores called Rise™ and Essence. Headquartered in Chicago, Illinois, Green Thumb has 13 manufacturing facilities, licenses for 96 retail locations and operations across 12 U.S. markets. Established in 2014, Green Thumb employs over 2,100 people and serves thousands of patients and customers each year. The company was named a Best Workplace 2018 by Crain’s Chicago Business and MG Retailer magazine in 2018 and 2019. More information is available at GTIgrows.com.

Investor Contact:		Media Contact:
Jennifer Dooley		Linda Marsicano
Chief Strategy Officer		VP, Corporate Communications
[email protected]		[email protected]
310-622-8257		773-354-2004

Source: Green Thumb Industries

TORONTO, Dec. 31, 2020 (GLOBE NEWSWIRE) — Guardian Capital LP (“Guardian Capital”) announces the confirmed amounts of the annual special year-end distributions (the “Special Distributions”) for the 2020 tax year for the Guardian Capital ETFs listed below:

Exchange-Traded Fund	Class of Units	TSX Trading Symbol	Confirmed Special Distribution Amount (per Unit)
Guardian Directed Equity Path ETF	Hedged	GDEP	$0.1376
Guardian Directed Equity Path ETF	Unhedged	GDEP.B	$0
Guardian Directed Premium Yield ETF	Hedged	GDPY	$0
Guardian Directed Premium Yield ETF	Unhedged	GDPY.B	$0
Guardian i3 Global Quality Growth ETF	Hedged	GIQG	$0.5002
Guardian i3 Global Quality Growth ETF	Unhedged	GIQG.B	$0.0384
Guardian i3 US Quality Growth ETF	Hedged	GIQU	$0.5299
Guardian i3 US Quality Growth ETF	Unhedged	GIQU.B	$0
Guardian i3 Global REIT ETF	Hedged	GIGR	$0.2951
Guardian i3 Global REIT ETF	Unhedged	GIGR.B	$0.0607

Each of the Guardian Capital ETFs is required to distribute any net income and capital gains that it has earned in the year. The Special Distributions will generally consist of capital gains and/or any excess net income at year-end.

With respect to the Hedged Class Special Distributions listed above, the revised amounts are predominantly the result of realized currency gains incurred by such ETFs since December 4, 2020, when estimated distributions were originally announced.

The Special Distributions will not be paid in cash, but will be reinvested and the resulting units immediately consolidated so that the number of units held by each investor will not change. Investors holding their units outside registered plans will have taxable amounts to report and will have an increase in the adjusted cost base of their investment. In all cases, the Special Distributions will be reinvested on or about December 31, 2020 to unitholders of record on December 30, 2020. The ex-dividend date in each case is December 29, 2020.

These confirmed amounts are for the Special Distributions only and do not include the ongoing regular monthly or quarterly cash distribution amounts which were announced on December 17, 2020, in a separate press release. These confirmed Special Distribution amounts replace the previous estimates announced on December 4, 2020.

The actual taxable amounts of all distributions for the Guardian Capital ETFs for 2020, including the tax characteristics of the distributions, will be reported to brokers (through CDS Clearing and Depository Services Inc. or “CDS”) and will be posted on the Guardian Capital website in early 2021.

For further information, please contact Guardian Capital at 416-350-8899 or visit www.guardiancapital.com/investmentsolutions.

About Guardian Capital LP

Guardian Capital LP is the manager and portfolio manager of the Guardian Capital Funds and each of the Guardian Capital ETFs. Additionally, Guardian Capital manages portfolios for defined benefit and defined contribution pension plans, insurance companies, foundations, endowments and third-party mutual funds. Guardian Capital is a wholly-owned subsidiary of Guardian Capital Group Limited.

About Guardian Capital Group Limited

Guardian Capital Group Limited is a diversified financial services company founded in 1962. Guardian operates in two main business areas, Asset Management and Financial Advisory. As of September 30, 2020, Guardian had C$32.7 billion of assets under management and C$20.8 billion of assets under administration. Guardian offers institutional and private wealth investment management services; financial services to international investors; services to financial advisors in its national mutual fund dealer, securities dealer, and insurance distribution network; and maintains and manages a proprietary investment portfolio, which had a fair market value of C$552 million at September 30, 2020. Its Common and Class A shares are listed on the Toronto Stock Exchange; in 2019, Guardian celebrated 50 years as a listed company. To learn more about Guardian, visit www.guardiancapital.com.

This communication is intended for informational purposes only and does not constitute an offer to sell or the solicitation of an offer to purchase Guardian Capital ETFs and is not, and should not be construed as, investment, tax, legal or accounting advice, and should not be relied upon in that regard. Commissions, management fees and expenses all may be associated with investments in exchange-traded funds (ETFs). Please read the prospectus before investing. ETFs are not guaranteed, their values change frequently and past performance may not be repeated. You will usually pay brokerage fees to your dealer if you purchase or sell units of an ETF on the TSX. If the units are purchased or sold on the TSX, investors may pay more than the current net asset value when buying units of the ETF and may receive less than the current net asset value when selling them.

SEOUL, SOUTH KOREA , Dec. 31, 2020 (GLOBE NEWSWIRE) — Korea’s leading enterprise blockchain technology company, ICONLOOP (https://www.iconloop.com/en/), today announced it is developing a blockchain-based mobile drivers license under regulatory sandbox approval in South Korea. South Korea’s Ministry of Science and ICT granted ICONLOOP permission to test its Decentralized Identity (DID) technology on mobile driver’s licenses with the goal of better preventing forgery and protecting personal data. 

In today’s centralized system, driver’s license information is stored on a single server, leaving it vulnerable to leaks or attacks. ICONLOOP’s pioneering Decentralized Identity technology solves this, allowing people to directly manage their own data by storing authenticated personal information on their mobile devices using the Zzeung app. When a user needs to submit their authenticated data, they can simply select and submit the necessary information.

“ICONLOOP emphasizes the self-sovereignty of personal data. The authentication processes that previously existed offline in the form of physical cards are now online via mobile apps like Zzeung, making it possible for users to manage their own authenticated information,” said Jonghyup Kim, CEO of ICONLOOP. “We are happy to work closely with regulators in South Korea to support efforts to responsibly manage and protect citizens’ personal data through advances in technology.” 

Mobile driver’s licenses are one of many use cases for ICONLOOP’s DID technology, which is already being used by the government of Jeju Island for contact tracing, and by online recruiting company SaraminHR to authenticate job applicants’ credentials. DID technology offers significant advantages to both organizations and end users in maintaining the safety of personal data. 

ICONLOOP’s mobile driver’s licenses are expected to be released in the second half of 2021. Since the adoption of the ICT Regulatory Sandbox, several services have been tested and launched, ranging from ride sharing to healthcare to virtual reality. 

ABOUT ICONLOOP

ICONLOOP (https://www.iconloop.com/) is a leading blockchain technology company in South Korea. The company’s technology is used for real-world applications in banking, healthcare, government, and more. The Financial Services Commission (FSC) has approved ICONLOOP’s decentralized identity (DID) authentication service into the ‘Innovative Financial Services and Regulations Sandbox.’ Headquartered in Seoul, the company has approximately 140 employees and raised over $15 million in funding from Korea Growth Investment Corporation (K-Growth), Kiwoom Investment, Danal Holdings, K-Clavis Investment, TS Investment, Korea Asset Investment Securities, and Pathfinder H.

COMPANY CONTACT: [email protected]

MEDIA CONTACT: Transform Group, [email protected]

VANCOUVER, British Columbia, Dec. 31, 2020 (GLOBE NEWSWIRE) — Digihost Technology Inc. (“Digihost” or the “Company”) (TSXV: DGHI; OTCPK: HSSHF) is pleased to announce the Company’s system upgrade through the acquisition of Antminer S19 Pro 110TH miners. With the most efficient miners currently in the market, each unit utilizing a hash rate of 110TH and a power usage of 3300 watts (34W/TH), Digihost will be integrating and adding 15.4 PH to the Company’s hash rate in the next few weeks. Digihost has acquired 76 PH in additional hash rate from newer and more efficient miners since the start of the year. The Company plans to continue the acquisition of the highest performing miners, further increasing the efficiency of the Company’s operations.

Alec Amar, President of the Company, commented, “Growth and acquisition of novel technologies, coupled with our in-house investment in R&D, continues to show our dedication to increasing value for our shareholders. Timing has never been so important and we plan to double our efforts to continuously acquire top tier miners and keep Digihost’s suite of offerings at the cutting-edge of blockchain technology and cost-efficiency.”

About Digihost Technology Inc.


Digihost Technology Inc. is a growth-oriented blockchain company primarily focused on Bitcoin mining. The Company’s mining facility is located in Buffalo, N.Y., and is equipped with an 18.7MVA 115,000-kilovolt-ampere outdoor substation with an option to increase the power output to 42MVA.

For further information, please contact:

Digihost Technology Inc.

Michel Amar, Chief Executive Officer
Email: [email protected]

Cautionary Statement


Trading in the securities of the Company should be considered highly speculative. No stock exchange, securities commission or other regulatory authority has approved or disapproved the information contained herein. Neither the TSX Venture Exchange nor its Regulation Services Provider (as that term is defined in the policies of the TSX Venture Exchange) accepts responsibility for the adequacy or accuracy of this release.

Forward-Looking Statements


This news release includes forward-looking statements that are subject to risks and uncertainties. Forward-looking statements involve known and unknown risks, uncertainties, and other factors that could cause the actual results of Digihost and its investee companies to be materially different from the historical results or from any future results expressed or implied by such forward-looking statements. All statements contained in this news release, other than statements of historical fact, are to be considered forward-looking. Although Digihost believes the expectations expressed in such forward-looking statements are based on reasonable assumptions, such statements are not guarantees of future performance and actual results or developments may differ materially from those in the forward-looking statements. Accordingly, readers should not place undue reliance on forward-looking information. Digihost does not undertake to update any forward-looking information except in accordance with applicable securities laws.

TORONTO, Dec. 31, 2020 (GLOBE NEWSWIRE) — McEwen Mining Inc. (NYSE: MUX) (TSX: MUX) is pleased to announce the highlights of a positive Feasibility Study (FS) for its 100%-owned Fenix Project, which is located in the State of Sinaloa, Mexico.

“The Fenix Feasibilty Study envisions a 9.5-year mine life with an attractive after-tax IRR of 28% using $1,500/oz gold and $17/oz silver. At current gold and silver prices, the project’s after-tax IRR almost doubles and the NPV more than triples versus the base case.

The project will incorporate an environmentally progressive method of tailings management, using inpit storage that creates multiple benefits, most importantly a secure containment of tailings enabling better reclamation results.

Average annual production is projected at 26,000


<sup>(1


)</sup>


oz gold in Phase 1 and 4,200,000


<sup>(


4


)</sup>


oz silver equivalent in Phase 2. The critical path environmental permits are in hand for the first phase of production. Our next steps will involve detailed engineering, assessment of procurement options, and the evaluation of financing alternatives,”
said Rob McEwen, Chairman and Chief Owner.

Fenix FS Highlights

		Base Case (1) $1,500/oz Gold, $17/oz Silver	Upside Case $1,900/oz Gold, $25/oz Silver
After-Tax IRR		28%	55%
After-Tax NPV (8% discount)		$32 million	$98 million
After-Tax Payback Period		3.6 years	2.8 years
Average After-Tax Cash Flow per Year of Full Production		$12 million	$25 million
	The FS for project Fenix development involves two phases:
	Phase 1: Years 1 to 6, Gold Production
	Average Annual Gold Production 26,000 oz Au $42 million initial capex $1,035 cash cost ( 2 ) and $1,042 AISC(3) per oz Au
	Phase 2: Years 7 to 9.5, Silver Production
	Average Annual Silver Production 4,200,000 oz AgEq. ( 4 ) $24 million incremental capex in Year 6. $14.20 cash cost (2) and $14.28 AISC(3) per oz AgEq.(4)

Feasibility Study Report

The complete Fenix Project FS NI 43-101 Technical Report will be available on www.sedar.com and www.mcewenmining.com within 45 days. The FS was prepared by GR Engineering Services Limited (“GRES”) of Belmont, Western Australia, in accordance with the requirements of Canadian National Instrument 43-101 “Standards of Disclosure for Mineral Projects” (“NI 43-101”) and SEC Industry Guide 7.

Permits

The current operation at El Gallo Gold is a fully permitted site; permit for the Phase 1 was granted by the Federal Environmental Authority (SEMARNAT) in September 2019, for the addition of a mill and leach circuit in the location of the existing facilities for the reprocessing of the heap leach pad material. The permit amendment also includes the backfilling of a previously mined pit with mill tailings, as part of an integrated concurrent closure plan for the El Gallo Gold Mine.

Further project advancement for Phase 2 is subject to permit approvals. Phase 2 project permitting will require authorization to expand the process plant footprint at El Gallo Gold and the haul road, and to augment the tailings volume to be deposited at the depleted pit.

The Fenix Project has CONAGUA approval for the extraction of groundwater and land-use permits for the construction of wells required for the life of Fenix Project.

Resource Estimates

Estimated resources for the Fenix Project are comprised only of material within the boundaries of conceptual pit shells, except for the El Gallo heap leach pad, which is considered completely available for reprocessing.

For the purposes of mine scheduling, the contained gold ounces in the Heap Leach Material has been depleted from the resource model estimate defined by drilling by an amount of 23 koz Au, to account for the production from heap leach operations and gold in circuit assessments between the timing of the resource estimate up until December 2020.

Table 1: Fenix Project Resources Estimate



<sup>(




5




)(




6




)</sup>

Heap Leach Material (7)	Tonnes		Silver Grade		Silver		Gold Grade		Gold
Potential COG = 0 g/t Au	Mt		(g/t)		koz		(g/t)		koz
Measured	8.8		1.59		451		0.59		167
Indicated	1.2		1.74		67		0.60		23
Measured and Indicated	10.0		1.61		518		0.59		190
Inferred	0.1		1.64		7		0.66		3
El Gallo Silver
In Optimized Pit Shell	Tonnes		Silver Grade		Silver		Gold Grade		Gold
Potential COG = 58 g/t Ag	Mt		(g/t)		koz		(g/t)		koz
Measured	1.0		155.38		4,791		0.08		3
Indicated	3.5		126.55		14,228		0.13		15
Measured and Indicated	4.5		132.76		19,019		0.12		18
Inferred	0.1		128.92		286		0.14		0.3
COMBINED RESOURCES
In Optimized Pit Shells	Tonnes		Silver Grade		Silver		Gold Grade		Gold
Potential COGs variable	Mt		(g/t)		koz		(g/t)		koz
Measured	9.8		16.68		5,242		0.54		170
Indicated	4.7		94.58		14,295		0.25		38
Measured and Indicated	14.5		41.98		19,536		0.45		208
Inferred	0.2		46.50		293		0.48		3

Table 2: Fenix Project Reserves Estimate



<sup>(




8




)</sup>

Heap Leach Material	Tonnes		Silver Grade		Silver		Gold Grade		Gold
	Mt		(g/t)		koz		(g/t)		koz
Proven	8.8		1.59		451		0.59		167
Probable	1.3		1.57		67		0.54		23
Proven + Probable	10.1		1.58		517		0.58		190
El Gallo Silver
Proven	0.7		165.71		3,708		0.05		1
Probable	3.7		126.61		15,017		0.13		16
Proven + Probable	4.4		132.82		18,725		0.12		17
COMBINED RESERVES
Proven	9.5		13.60		4,159		0.55		168
Probable	5.0		93.46		15,084		0.24		39
Proven + Probable	14.5		41.19		19,243		0.44		207

Table 3: Assumptions for Heap Leach Pad and El Gallo Silver Pit Optimization Phase 2



<sup>(6)




(




9




)</sup>

Assumptions for In-Pit Resource Shells	Deposits	Values
Gold Price	All	$1,300/oz
Silver Price	All	$16.00/oz
Mining Cost	Heap Leach Pad	$0.53/t
	El Gallo Silver	$12.06/t
Processing and G&A	Heap Leach Pad	$12.88/t
	El Gallo Silver – Oxides	$26.90/t
	El Gallo Silver– Sulfides	$25.93/t
Recovery – Au	Heap Leach Pad	85.90%
	El Gallo Silver	79.40%
Recovery – Ag	Heap Leach Pad	45.0%
	El Gallo Silver – Oxides	82.5%
	El Gallo Silver– Sulfides	88.1%
Cut-Off Grade	Heap Leach Pad	0 g/t Au
	El Gallo Silver	58 g/t Ag
Inter-Ramp Pit Slope Angle	El Gallo Silver	45 degrees

FOOTNOTES

(1) The Base Case utilizes the three-year moving average prices for gold and silver (approximate value). Estimated 26,000 oz Au per annum production assumes full production from years 2023 to 2027. Average after-tax cash flow per annum from full production years 2023 to 2031 is approximately $12 million per annum. Average after-tax cash flows per annum for the period from start-up of production to closure (2022 to 2032) is approximately $8.6 million per annum. These cash flows assume the use of all eligible tax loss carry forwards from the El Gallo Gold Mine.
(2) Cash cost is calculated by dividing total life-of-mine production costs, general and administrative expenses and royalties by total ounces produced.
(3) All-in sustaining costs (AISC) are calculated by dividing the sum of all cash costs plus sustaining capital and reclamation costs by total ounces produced.
(4) All references to AgEq are based on an 88 Ag oz to 1 Au oz ratio. For Phase 1 silver accounts for <2% of total production. For Phase 2 gold accounts for approximately 9% of total production. Average annual AgEq production is from years 2028 to 2031.
(5) Mineral Resources are not Mineral Reserves and do not have demonstrated economic viability. There is no certainty that all or any part of the Mineral Resources estimated will be converted into Mineral Reserves. Numbers in the table have been rounded to reflect the accuracy of the estimate and may not sum due to rounding.
(6) Resources stated as contained within a potentially economically minable open pit; pit optimization parameters are, USD$1,300/oz Au, and USD$16.00/oz Ag. In-pit resource estimates have been developed based on gold and silver recoveries from both historical and recent testwork programs. Resource estimates are effective as of Oct 31, 2018. Resources are inclusive of reserves.
(7) The heap leach pad spent ore resource number assumes a cut-off grade that permits processing of the entire pad, whereas blocks within the leach pad model will be mobilized while mining, which will make them difficult to segregate; sub-cut-off leach pad material will inherently have potential acid generating sulfide liabilities if placed in our waste dumps and so it will be prudent to process the entire leach pad and place tailings in a previously mined pit at an overall environmental and economic benefit.
(8) The reserves stated here satisfy the requirements of the CIM Definition Standards, and the CIM Estimation of Mineral Resources and Mineral Reserves Best Practice Guidelines of November 2019, and  have been converted only from those portions of the Mineral Resources that are classified as Measured or Indicated Mineral Resource categories after having been evaluated with consideration of all known modifying factors affecting economic viability.
(9) Cut-off grades vary by pit according to economic, recovery and metallurgical parameters.

The technical contents of this news release has been reviewed and approved by G. Peter Mah, P.Eng., COO of McEwen Mining and a Qualified Person as defined by Canadian Securities Administrators National Instrument 43-101 “Standards of Disclosure for Mineral Projects.”

The technical information in this news release related to resource and reserve estimates has been reviewed and approved by Luke Willis, P.Geo., McEwen Mining’s Director of Resource Modelling and Qualified Person as defined by Canadian Securities Administrators National Instrument 43-101 “Standards of Disclosure for Mineral Projects.”

CAUTIONARY NOTE TO US INVESTORS REGARDING RESOURCE ESTIMATION

McEwen Mining prepares its resource estimates in accordance with standards of the Canadian Institute of Mining, Metallurgy and Petroleum referred to in Canadian National Instrument 43-101 (NI 43-101). These standards are different from the standards generally permitted in reports filed with the SEC. Under NI 43-101, McEwen Mining reports measured, indicated and inferred resources, measurements, which are generally not permitted in filings made with the SEC. The estimation of measured resources and indicated resources involve greater uncertainty as to their existence and economic feasibility than the estimation of proven and probable reserves. U.S. investors are cautioned not to assume that any part of measured or indicated resources will ever be converted into economically mineable reserves. The estimation of inferred resources involves far greater uncertainty as to their existence and economic viability than the estimation of other categories of resources.

CAUTION CONCERNING FORWARD-LOOKING STATEMENTS

This news release contains certain forward-looking statements and information, including “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. The forward-looking statements and information expressed, as at the date of this news release, contain McEwen Mining Inc.’s (the “Company”) estimates, forecasts, projections, expectations or beliefs as to future events and results. Forward-looking statements and information are necessarily based upon a number of estimates and assumptions that, while considered reasonable by management, are inherently subject to significant business, economic and competitive uncertainties, risks and contingencies, and there can be no assurance that such statements and information will prove to be accurate. Therefore, actual results and future events could differ materially from those anticipated in such statements and information. Risks and uncertainties that could cause results or future events to differ materially from current expectations expressed or implied by the forward-looking statements and information include, but are not limited to, effects of the COVID-19 pandemic, fluctuations in the market price of precious metals, mining industry risks, political, economic, social and security risks associated with foreign operations, the ability of the corporation to receive or receive in a timely manner permits or other approvals required in connection with operations, risks associated with the construction of mining operations and commencement of production and the projected costs thereof, risks related to litigation, the state of the capital markets, environmental risks and hazards, uncertainty as to calculation of mineral resources and reserves, and other risks. Readers should not place undue reliance on forward-looking statements or information included herein, which speak only as of the date hereof. The Company undertakes no obligation to reissue or update forward-looking statements or information as a result of new information or events after the date hereof except as may be required by law. See McEwen Mining’s Annual Report on Form 10-K for the fiscal year ended December 31, 2019 and other filings with the Securities and Exchange Commission, under the caption “Risk Factors”, for additional information on risks, uncertainties and other factors relating to the forward-looking statements and information regarding the Company. All forward-looking statements and information made in this news release are qualified by this cautionary statement.

The NYSE and TSX have not reviewed and do not accept responsibility for the adequacy or accuracy of the contents of this news release, which has been prepared by management of McEwen Mining Inc.

ABOUT MCEWEN MINING

McEwen Mining is a diversified gold and silver producer and explorer focused in the Americas with operating mines in Nevada, Canada, Mexico and Argentina. It also owns a large copper deposit in Argentina.

CONTACT INFORMATION:
Investor Relations: (866)-441-0690 Toll Free (647)-258-0395 Mihaela Iancu ext. 320 [email protected]	Website: www.mcewenmining.com Facebook: facebook.com/mcewenmining Facebook: facebook.com/mcewenrob  Twitter: twitter.com/mcewenmining Twitter: twitter.com/robmcewenmux Instagram: instagram.com/mcewenmining	150 King Street West Suite 2800, P.O. Box 24 Toronto, ON, Canada M5H 1J9

 

Voting Rights and Capital

In conformity with the Disclosure Guidance and Transparency Rules, we hereby notify the market of the following:

Royal Dutch Shell plc’s capital as at 31 December 2020, consists of 4,101,239,499 A shares and 3,706,183,836 B shares, each with equal voting rights. Royal Dutch Shell plc holds no ordinary shares in Treasury.

The total number of A shares and B shares in issue as at 31 December 2020 is 7,807,423,335 and this figure may be used by shareholders as the denominator for the calculation by which they will determine if they are required to notify their interest in, or a change to their interest in, Royal Dutch Shell plc under the FCA’s Disclosure Guidance and Transparency Rules.

Enquiries
Shell Media Relations
International, UK, European Press: +44 (0)207 934 5550

LEI number of Royal Dutch Shell plc:  21380068P1DRHMJ8KU70
Classification: Total number of voting rights and capital

ACCORD is the second pivotal trial of AXS-05 in Alzheimer’s disease agitation

No treatments are currently approved for Alzheimer’s disease agitation

NEW YORK, Dec. 31, 2020 (GLOBE NEWSWIRE) — Axsome Therapeutics, Inc. (NASDAQ: AXSM), a biopharmaceutical company developing novel therapies for the management of central nervous system (CNS) disorders, announced the initiation of the ACCORD (Assessing Clinical Outcomes in Alzheimer’s Disease Agitation) study, a Phase 3, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of AXS-05 in the treatment of Alzheimer’s disease (AD) agitation. AXS-05 (45 mg dextromethorphan-105 mg bupropion modulated delivery tablet) is a novel, oral, investigational NMDA receptor antagonist with multimodal activity. There is currently no approved treatment for AD agitation.

ACCORD is being conducted using a randomized-withdrawal design, in which all patients are first treated with open-label AXS-05, with the patients experiencing a treatment response being subsequently randomized in a double-blind fashion to continued treatment with AXS-05 or to switch to placebo. Patients completing the ACCORD trial will be eligible to enter an open-label safety extension trial. Initiation of the safety extension trial is expected imminently. Topline results from the ACCORD trial are anticipated in the second half of 2022.

“Initiation of the ACCORD Phase 3 trial in Alzheimer’s disease agitation continues the expedited clinical development of AXS-05 for this serious condition. The potential for AXS-05, with its unique pharmacological profile, in this indication is supported by the positive results in our completed pivotal ADVANCE trial,” said Herriot Tabuteau, MD, Chief Executive Officer of Axsome. “Alzheimer’s disease agitation is a prevalent and debilitating condition that is associated with earlier nursing home placement, accelerated progression to severe dementia, and increased risk of death. There are currently no approved treatments for Alzheimer’s disease agitation. If successfully developed, AXS-05 has the potential to address this high unmet need and significantly improve the lives of patients and their caregivers.”

Initiation of the ACCORD Phase 3 trial follows a Breakthrough Therapy meeting with the U.S. Food and Drug Administration (FDA), announced in August, to discuss the development plan for AXS-05 in AD agitation. Results of the meeting confirmed the pivotal status of the previously completed ADVANCE trial of AXS-05 in AD agitation. The meeting followed the receipt in June of Breakthrough Therapy designation from the FDA for AXS-05 for the treatment of AD agitation, the second Breakthrough Therapy designation received by Axsome for AXS-05. The designation was supported by the positive results of the ADVANCE trial. A Breakthrough Therapy designation is granted to potentially expedite development and review timelines for a promising investigational medicine when preliminary clinical evidence indicates it may demonstrate substantial improvement on one or more clinically significant endpoints over available therapies for a serious or life-threatening condition.

About the ACCORD Trial

ACCORD (Assessing Clinical Outcomes in Alzheimer’s Disease Agitation) is a Phase 3, randomized, double-blind, multicenter, placebo-controlled, trial to evaluate the efficacy and safety of AXS-05 in patients with Alzheimer’s disease (AD) agitation. Enrolled patients will first enter a 9-week, open-label stabilization period, during which they will be treated with AXS-05 and monitored for a treatment response based on the Cohen-Mansfield Agitation Inventory (CMAI). Patients who experience a treatment response during the stabilization period will then be randomized into the double-blind treatment period, in a 1:1 ratio, to continue treatment with AXS-05 or to switch to placebo, for up to 26 weeks or until a relapse of agitation occurs. The primary endpoint will be the time from randomization to relapse. Assessments will include the CMAI, clinician- and caregiver-rated scales, and safety parameters.

About Alzheimer’s Disease (AD) Agitation

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, and behavioral and psychological symptoms including agitation. AD is the most common form of dementia and afflicts an estimated 6 million individuals in the United States, a number that is anticipated to increase to approximately 14 million by 2050 [1]. Agitation is reported in up to 70% of patients with AD and is characterized by emotional distress, aggressive behaviors, disruptive irritability, and disinhibition [2]. Agitation in patients with AD has been associated with increased caregiver burden, decreased functioning, accelerated cognitive decline, earlier nursing home placement, and increased mortality [2-4]. There are currently no therapies approved by the FDA for the treatment of agitation in patients with AD.

About AXS-05

AXS-05 (dextromethorphan-bupropion modulated delivery tablet) is a novel, oral, patent-protected, investigational NMDA receptor antagonist with multimodal activity under development for the treatment of major depressive disorder and other central nervous system (CNS) disorders. AXS-05 utilizes a proprietary formulation and dose of dextromethorphan and bupropion, and Axsome’s metabolic inhibition technology, to modulate the delivery of the components. The dextromethorphan component of AXS-05 is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, also known as a glutamate receptor modulator, which is a novel mechanism of action, meaning it works differently than currently approved therapies for major depressive disorder. The dextromethorphan component of AXS-05 is also a sigma-1 receptor agonist, nicotinic acetylcholine receptor antagonist, and inhibitor of the serotonin and norepinephrine transporters. The bupropion component of AXS-05 serves to increase the bioavailability of dextromethorphan, and is a norepinephrine and dopamine reuptake inhibitor, and a nicotinic acetylcholine receptor antagonist. AXS-05 is covered by more than 93 issued U.S. and international patents which provide protection out to 2040. AXS-05 has been granted U.S. Food and Drug Administration Breakthrough Therapy and Fast Track designations for Alzheimer’s disease agitation. AXS-05 is not approved by the FDA.

About Axsome Therapeutics, Inc.

Axsome Therapeutics, Inc. is a biopharmaceutical company developing novel therapies for the management of central nervous system (CNS) disorders for which there are limited treatment options. For the many people facing unsatisfactory treatments for CNS disorders, Axsome accelerates the invention and adoption of life-changing medicines. Axsome’s core CNS product candidate portfolio includes five clinical-stage candidates, AXS-05, AXS-07, AXS-09, AXS-12, and AXS-14. AXS-05 is being developed for major depressive disorder (MDD), Alzheimer’s disease (AD) agitation, and as a treatment for smoking cessation. AXS-07 is being developed for the acute treatment of migraine. AXS-12 is being developed for the treatment of narcolepsy. AXS-14 is being developed for fibromyalgia. AXS-05, AXS-07, AXS-09, AXS-12, and AXS-14 are investigational drug products not approved by the FDA. For more information, please visit the Company’s website at axsome.com. The Company may occasionally disseminate material, nonpublic information on the company website.

References

1. Alzheimer’s Association. 2020 Alzheimer’s Disease Facts and Figures. Alzheimers Dement 2020;16(3):391+.
2. Tractenberg RE, Weiner MF, Thal LJ. Estimating the prevalence of agitation in community-dwelling persons with Alzheimer’s disease. J Neuropsychiatry Clin Neurosci. 2002;14:11-18.
3. Porsteinsson AP, Antonsdottir IM. An update on the advancements in the treatment of agitation in Alzheimer’s disease. Expert Opin Pharmacother. 2017;18:611-620.
4. Rabins PV, Schwartz S, Black BS, Corcoran C, Fauth E, Mielke M, Christensen J, Lyketsos C, Tschanz J. Predictors of progression to severe Alzheimer’s disease in an incidence sample. Alzheimers Dement. 2013;9:204-207.

Forward Looking Statements

Certain matters discussed in this press release are “forward-looking statements”. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. In particular, the Company’s statements regarding trends and potential future results are examples of such forward-looking statements. The forward-looking statements include risks and uncertainties, including, but not limited to, the success, timing and cost of our ongoing clinical trials and anticipated clinical trials for our current product candidates, including statements regarding the timing of initiation, pace of enrollment and completion of the trials (including our ability to fully fund our disclosed clinical trials, which assumes no material changes to our currently projected expenses), futility analyses and receipt of interim results, which are not necessarily indicative of the final results of our ongoing clinical trials, and the number or type of studies or nature of results necessary to support the filing of a new drug application (“NDA”) for any of our current product candidates; our ability to fund additional clinical trials to continue the advancement of our product candidates; the timing of and our ability to obtain and maintain U.S. Food and Drug Administration (“FDA”) or other regulatory authority approval of, or other action with respect to, our product candidates (including, but not limited to, FDA’s agreement with the Company’s discontinuation of the bupropion treatment arm of the ADVANCE study in accordance with the independent data monitoring committee’s recommendations); the potential for the MOMENTUM clinical trial to provide a basis for approval of AXS-07 for the acute treatment of migraine in adults with or without aura, pursuant to our special protocol assessment; the potential for the ASCEND clinical trial, combined with the GEMINI clinical trial results, to provide a basis for approval of AXS-05 for the treatment of major depressive disorder and accelerate its development timeline and commercial path to patients; the Company’s ability to successfully defend its intellectual property or obtain the necessary licenses at a cost acceptable to the Company, if at all; the successful implementation of the Company’s research and development programs and collaborations; the success of the Company’s license agreements; the acceptance by the market of the Company’s product candidates, if approved; the Company’s anticipated capital requirements, including the Company’s anticipated cash runway; unforeseen circumstances or other disruptions to normal business operations arising from or related to COVID-19; and other factors, including general economic conditions and regulatory developments, not within the Company’s control. The factors discussed herein could cause actual results and developments to be materially different from those expressed in or implied by such statements. The forward-looking statements are made only as of the date of this press release and the Company undertakes no obligation to publicly update such forward-looking statements to reflect subsequent events or circumstance.

Axsome Contact:

Mark Jacobson
Chief Operating Officer
Axsome Therapeutics, Inc.
22 Cortlandt Street, 16^th Floor
New York, NY 10007
Tel: 212-332-3243
Email: [email protected]
www.axsome.com