Market Newsdesk

LEBANON, Tenn., March 30, 2023 (GLOBE NEWSWIRE) — Tritium DCFC Limited (Tritium) (Nasdaq: DCFC), a global leader in direct current (DC) fast chargers for electric vehicles (EVs), today announced it is now accepting orders for the company’s first product offering for the National Electric Vehicle Infrastructure (NEVI) Formula Program. The charging system will include four of Tritium’s 150kW PKM150 charging stations, along with two power rectifiers.

“The NEVI program has opened up an unprecedented opportunity to advance the e-mobility transition in the United States, leading to a manufacturing boom in the country,” said Tritium CEO Jane Hunter. “As we continue to scale production at our Tennessee facility, Tritium is proud to deliver a product that allows states to put these funds to use and provide U.S. drivers with the EV infrastructure they need.
As the demand for reliable and accessible fast charging continues to grow across the country, Tritium will remain an industry leader, providing innovative and effective product solutions.
”

President Biden established the NEVI program upon signing the Bipartisan Infrastructure Law in 2021. The NEVI program provides $5 billion in funding over five years to help build a coast-to-coast network of qualifying DC fast chargers.

Last September, the Federal Highway Administration (FHWA) approved the Electric Vehicle Infrastructure Deployment Plans for all 50 states, Washington DC, and Puerto Rico, granting them access to FY22 and FY23 NEVI funding. Ohio, Pennsylvania, Colorado, Alaska, and Hawaii have begun to allocate their first rounds of NEVI funding, and most other states are anticipated to provide access to funding in 2023. This initial round of funding totals more than $1.5 billion to help build EV chargers covering approximately 75,000 miles of federal highway nationwide.

Yesterday, Tritium had the pleasure of welcoming White House Senior Advisor and Infrastructure Coordinator Mitch Landrieu to our Tennessee facility. Mr. Landrieu was given a tour of our state-of-the-art factory and engaged in a productive roundtable discussion with Tritium leadership and state and local officials. The discussion covered topics such as workforce development needs and opportunities in Middle Tennessee to further advance the e-mobility sector, as well as the Bipartisan Infrastructure Law and how the NEVI program is creating manufacturing opportunities across the country, including for companies like Tritium.

Tritium’s first NEVI product is expected to achieve the FHWA’s Build America, Buy America Act waiver milestones, which includes two phases announced by the FHWA last month. First, starting March 23, 2023, manufacturers were required to conduct final assembly and all manufacturing processes for any iron or steel charger enclosures or housing in the United States. By July 2024, manufacturers must also domestically source at least 55% of the cost of components used in charging equipment.

Tritium’s NEVI charging system delivers 150kW of power to four EVs simultaneously through a reliable and modular fast charger system. Thanks to multiple chargers and power rectifier units, the Tritium NEVI solution provides high site reliability and uptime.

“Tritium’s first NEVI-compliant product is a testament to our dedication to delivering comprehensive solutions for our U.S. customers,” said Mike Calise, Tritium President of the Americas. “Our new charging system is designed to achieve NEVI program requirements, demonstrating our commitment to advancing the U.S. e-mobility transition and helping charging site operators meet the NEVI program’s 97% uptime requirement. As the industry continues to grow, Tritium is proud to lead the way with cutting-edge products and unparalleled customer service.”

Tritium expects to expand its offerings for the Bipartisan Infrastructure Law programs, including the NEVI program and Charging and Fueling Infrastructure (CFI) discretionary grant program, as the company’s new products enter the market.

About Tritium

Founded in 2001, Tritium (NASDAQ: DCFC) designs and manufactures proprietary hardware and software to create advanced and reliable DC fast chargers for electric vehicles. Tritium’s compact and robust chargers are designed to look great on Main Street and thrive in harsh conditions, through technology engineered to be easy to install, own, and use. Tritium is focused on continuous innovation in support of our customers around the world.

For more information, visit tritiumcharging.com

Forward Looking Statements

This press release includes “forward-looking statements.” The Company’s actual results may differ from its expectations, estimates and projections and consequently, you should not rely on these forward-looking statements as predictions of future events. Words such as “expect,” “estimate,” “project,” “budget,” “forecast,” “anticipate,” “intend,” “plan,” “may,” “will,” “could,” “should,” “believe,” “predict,” “potential,” “continue,” “aim” and similar expressions are intended to identify such forward-looking statements. These forward-looking statements include, without limitation, the Company’s expectations, hopes, beliefs, intentions or strategies for the future. These forward-looking statements involve significant risks and uncertainties that could cause the actual results to differ materially from the expected results. You should carefully consider the risks and uncertainties described in the documents filed by the Company from time to time with the U.S. Securities and Exchange Commission. These filings identify and address other important risks and uncertainties that could cause actual events and results to differ materially from those contained in the forward-looking statements. Most of these factors are outside the Company’s control and are difficult to predict. The Company cautions not to place undue reliance upon any forward-looking statements, including projections, which speak only as of the date made. The Company does not undertake or accept any obligation to release publicly any updates or revisions to any forward-looking statements to reflect any change in its expectations or any change in events, conditions or circumstances on which any such statement is based.

Media Contacts

Jack Ulrich
[email protected]

Investor Contact

Cary Segall
[email protected]

A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/822f9219-601e-4cfa-8d9e-17ddfbe39bca

BOSTON and LONDON, March 30, 2023 (GLOBE NEWSWIRE) — Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, today announced that the company will make a virtual presentation at the Guggenheim Genomic Medicines and Rare Disease Day on Tuesday, April 4, 2023 at 1:35pm ET.

A live webcast of the presentation will be available under “News & Events” in the Investors & Media section of the company’s website at www.orchard-tx.com. A replay will be archived on the Orchard website following the event.

About Orchard

At Orchard Therapeutics, our vision is to end the devastation caused by genetic and other severe diseases. We aim to do this by discovering, developing and commercializing new treatments that tap into the curative potential of hematopoietic stem cell (HSC) gene therapy. In this approach, a patient’s own blood stem cells are genetically modified outside of the body and then reinserted, with the goal of correcting the underlying cause of disease in a single treatment.

In 2018, the company acquired GSK’s rare disease gene therapy portfolio, which originated from a pioneering collaboration between GSK and the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy. Today, Orchard is advancing a pipeline spanning pre-clinical, clinical and commercial stage HSC gene therapies designed to address serious diseases where the burden is immense for patients, families and society and current treatment options are limited or do not exist.

Orchard has its global headquarters in London and U.S. headquarters in Boston. For more information, please visit www.orchard-tx.com, and follow us on Twitter and LinkedIn.

Availability of Other Information About Orchard

Investors and others should note that Orchard communicates with its investors and the public using the company website (www.orchard-tx.com), the investor relations website (ir.orchard-tx.com), and on social media (Twitter and LinkedIn), including but not limited to investor presentations and investor fact sheets, U.S. Securities and Exchange Commission filings, press releases, public conference calls and webcasts. The information that Orchard posts on these channels and websites could be deemed to be material information. As a result, Orchard encourages investors, the media, and others interested in Orchard to review the information that is posted on these channels, including the investor relations website, on a regular basis. This list of channels may be updated from time to time on Orchard’s investor relations website and may include additional social media channels. The contents of Orchard’s website or these channels, or any other website that may be accessed from its website or these channels, shall not be deemed incorporated by reference in any filing under the Securities Act of 1933.

Contacts

Investors

Renee Leck
Senior Director, Investor Relations
+1 862-242-0764
[email protected]

• LUMRYZ™ NDA amendment filed March 1 requesting FDA final approval

• Received FDA authorization to import LUMRYZ in advance of final approval decision; shortens timeline between potential approval and product availability

• Secured $200 million of capital to fund the launch of LUMRYZ and extended the maturity of $96.2 million of the convertible notes to 2027

• Launch preparations on track to support U.S. commercial launch of LUMRYZ

• Management to host a conference call today at 8:30 a.m. ET

DUBLIN, Ireland, March 30, 2023 (GLOBE NEWSWIRE) — Avadel Pharmaceuticals plc (Nasdaq: AVDL), a biopharmaceutical company focused on transforming medicines to transform lives, today provided a corporate update and announced its financial results for the fourth quarter ended December 31, 2022.

“2023 is shaping up to be a significant year for Avadel. I am proud of all that our team has recently accomplished, including submitting an amendment to the FDA requesting final approval for LUMRYZ and securing the FDA’s approval of our PLAIR request, which has allowed us to import product into the U.S. ahead of a final approval decision. Collectively, these milestones move us closer to the potential commercialization of LUMRYZ,” said Greg Divis, Chief Executive Officer of Avadel Pharmaceuticals. “In parallel, the completion of multiple strategic financings in the current market environment reinforces the potential of LUMRYZ and positions us for long-term success as we enter a pivotal stage of growth for the company. I want to thank all stakeholders including patients, healthcare practitioners, and our investors for their strong support during this process. We look forward to our continued progress as we execute on our strategic plan to bring LUMRYZ to the $3 billion plus once-at-bedtime oxybate market.”

Fourth Quarter and Recent Company Highlights

• Recently, Avadel made significant progress advancing LUMRYZ toward a final approval decision and preparing for U.S. commercial launch.
  • On March 1^st, the company submitted a minor amendment to the U.S. Food and Drug Administration (“FDA”) requesting final approval of LUMRYZ for the treatment of cataplexy or excessive daytime sleepiness (EDS) in adults with narcolepsy.
    • The Company filed the amendment shortly after Jazz Pharmaceuticals filed a submission with the FDA requesting the delisting of the REMS Patent from FDA’s Orange Book in response to the unanimous 3-0 panel decision of the United States Court of Appeals for the Federal Circuit on February 24, affirming the previous ruling from the U.S. District Court for the Federal District of Delaware.
  • The FDA approved Avadel’s Pre-Launch Activities Important Requests (PLAIR) for LUMRYZ. Through PLAIR, Avadel is able to import tentatively approved LUMRYZ to the U.S. ahead of a final approval decision.
    • Importation of LUMRYZ, prior to a potential final approval, enables Avadel to shorten the duration of time between a final FDA approval and commercial availability for people with narcolepsy.
  • Advancements in commercial preparations ahead of potential U.S. launch of LUMRYZ, including finalization of specialty pharmacy network, patient services center and the LUMRYZ REMS program.
  • Continued engagement with key stakeholders including sleep specialists and payers while expanding our customer facing teams including medical science liaisons, sales leadership, territory business managers, and field reimbursement specialists.
• Successfully executed multiple strategic financing activities and secured $200 million of capital to fund the launch of LUMRYZ.
  • Entered into a royalty agreement with RTW Investments (RTW) for up to $75 million to support the potential commercialization of LUMRYZ.
    • Under the terms of the royalty agreement, RTW will provide up to $75 million non-dilutive synthetic royalty financing commitment to Avadel in return for tiered rate, cash royalty payments based on net sales of LUMRYZ in the U.S.
  • Completed an equity offering with gross proceeds of $125 million, before deducting underwriting discounts, commissions and estimated offering expenses.
  • Exchanged $96.2 million of convertible notes with a new maturity date of April 3, 2027.
• Announced multiple data sets supporting the LUMRYZ product profile, including:
  • The publication of real-world data describing the risk of accidental dosing errors with immediate-release twice-nightly oxybate, including an analysis on post-marketing safety surveillance data from the FDA Adverse Event Reporting System (FAERS).
  • Multiple presentations at the American Neurological Association (ANA) annual meeting in October describing demographic characteristics and comorbidities of patients with narcolepsy and reinforcing positive data from completed Phase 3 REST-ON trial and patient and clinician preference for once-nightly over twice-nightly dosing.
  • Posters at the American College of Chest Physicians (CHEST) meeting in October featuring updated results from patient preference and nocturnal adverse event questionnaires from the RESTORE study with 94% of patients who switched from twice-nightly oxybates stating prefer for the once-at-bedtime dosing regime, as well as confirming challenges related to the middle-of-the-night dose.
• Expanded patent exclusivity for LUMRYZ with 5 additional U.S. patents for a current total of 13 patents, providing Orange Book-listable patent protection into early 2042.

Overview of Fourth Quarter Results

R&D expenses were $6.2 million in the quarter ended December 31, 2022, compared to $2.1 million for the same period in 2021. The period-over-period increase was primarily attributed to an increase in purchases of the active pharmaceutical ingredient used in the manufacture of LUMRYZ.

SG&A expenses were $17.0 million in the quarter ended December 31, 2022, compared to $21.0 million for the same period in 2021. The period-over-period decrease is the result of a number of factors including lower marketing and commercial spend. These decreases were partially offset by higher legal costs.

Net loss for the quarter ended December 31, 2022, was $27.5 million, or ($0.44) per diluted share, compared to net loss of $22.3 million, or ($0.38) per diluted share, for the same period in 2021.

Cash, cash equivalents and marketable securities were $96.5 million as of December 31, 2022. The Company extended the maturity of $96.2 million of its convertible notes to April 2027 and $21.2 million will mature in October 2023.

Conference Call

Avadel will host a conference all and live audio webcast to discuss its fourth quarter and full year quarter 2022 financial results and provide a corporate update today at 8:30 a.m. ET. To access the live conference call, please register here. A live audio webcast of the call and accompanying slide presentation will also be available in the investor relations section of the Company’s website, www.avadel.com. A replay of the webcast will be archived on Avadel’s website for 90 days following the event.

About LUMRYZ

LUMRYZ is an investigational formulation of sodium oxybate leveraging our proprietary drug delivery technology and designed to be taken once at bedtime for the treatment of cataplexy or excessive daytime sleepiness (EDS) in adults with narcolepsy.

In March 2020, Avadel completed the REST-ON study, a randomized, double-blind, placebo-controlled, pivotal Phase 3 trial, to assess the efficacy and safety of LUMRYZ in patients with narcolepsy. Among the three co-primary endpoints, LUMRYZ demonstrated statistically significant and clinically meaningful results in EDS, the clinician’s overall assessment of the patient’s functioning, and reduction in cataplexy attacks, for all three evaluated does when compared to placebo.

In January 2018, the U.S. Food and Drug Administration (FDA) granted LUMRYZ Orphan Drug Designation for the treatment of narcolepsy based on the plausible hypothesis that LUMRYZ may be safer than the twice-nightly formulation of sodium oxybate already approved by the FDA due to the ramifications associated with dosing regimen of that product. LUMRYZ is currently under review by the FDA.

On July 18, 2022, the FDA tentatively approved the LUMRYZ NDA for the treatment of cataplexy or EDS in adults with narcolepsy. Avadel submitted a minor amendment to the FDA on March 1, 2023, requesting final approval of LUMRYZ. This minor amendment submission occurred shortly after the delisting of the REMS Patent from FDA’s Orange Book by Jazz Pharmaceuticals in response to the unanimous 3-0 panel decision by the United States Court of Appeals for the Federal Circuit on February 24, affirming the previous ruling from the United States District Court for the Federal District of Delaware, ordering Jazz to do so.

Avadel is currently evaluating the long-term safety and tolerability of LUMRYZ in the open-label RESTORE clinical study. For more information, visit: www.restore-narcolepsy-study.com.

About Avadel Pharmaceuticals plc

Avadel Pharmaceuticals plc (Nasdaq: AVDL) is a biopharmaceutical company focused on transforming medicines to transform lives. Our approach includes applying innovative solutions to the development of medications that address the challenges patients face with current treatment options. Our current lead drug candidate, LUMRYZ, is an investigational formulation of sodium oxybate leveraging our proprietary drug delivery technology and designed to be taken once at bedtime for the treatment of cataplexy or EDS in adults with narcolepsy. For more information, please visit www.avadel.com.

Cautionary Disclosure Regarding Forward-Looking Statements

This press release includes “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. These forward-looking statements relate to our future expectations, beliefs, plans, strategies, objectives, results, conditions, financial performance, prospects, or other events. Such forward-looking statements include, but are not limited to, expectations regarding the FDA’s potential final approval of LUMRYZ, including the timing of thereof, the Company’s preparation for launch of LUMRYZ, the potential time savings between a potential final FDA approval and commercial launch of LUMRYZ attributable to the FDA’s approval of the PLAIR; the market acceptance of LUMRYZ (if approved), the total addressable market size for sodium oxybate, the Company’s anticipated uses of capital, including the proceeds from the recent financing; the expected maturity of the Company’s convertible notes; and the anticipated duration and scope of patent exclusivity for LUMRYZ. In some cases, forward-looking statements can be identified by the use of words such as “will,” “may,” “could,” “believe,” “potential,” “can,” “would,” “seek,” “expect,” “look forward,” “on track,” “guidance,” “anticipate,” “estimate,” “project,” “investigational,” “pipeline,” “launch,” “next steps” and similar expressions, and the negatives thereof (if applicable).

The Company’s forward-looking statements are based on estimates and assumptions that are made within the bounds of our knowledge of our business and operations and that we consider reasonable. However, the Company’s business and operations are subject to significant risks, and, as a result, there can be no assurance that actual results and the results of the company’s business and operations will not differ materially from the results contemplated in such forward-looking statements. Factors that could cause actual results to differ from expectations in the Company’s forward-looking statements include the risks and uncertainties described in the “Risk Factors” section of Part I, Item 1A of the Company’s Annual Report on Form 10-K for the year ended December 31, 2022, which was filed with the Securities and Exchange Commission (SEC) on March 29, 2023, and subsequent SEC filings.

Forward-looking statements speak only as of the date they are made and are not guarantees of future performance. Accordingly, you should not place undue reliance on forward-looking statements. The Company does not undertake any obligation to publicly update or revise our forward-looking statements, except as required by law.

Investor Contact:

Courtney Turiano
Stern Investor Relations, Inc.
[email protected]
(212) 698-8687

Media Contact:

Gabriella Greig
Real Chemistry
[email protected]
(203) 249-2688

AVADEL PHARMACEUTICALS PLC
CONDENSED CONSOLIDATED STATEMENTS OF LOSS
(In thousands, except per share data)
(Unaudited)
		Three Months Ended								Twelve Months Ended
		December 31,								December 31,
			2022				2021				2022				2021
Operating expenses:
Research and development expenses		$	6,235			$	2,110			$	20,700			$	17,104
Selling, general and administrative expenses			16,981				21,026				74,516				68,495
Restructuring (income) expense			(178	)			—				3,345				(53	)
Total operating expenses			23,038				23,136				98,561				85,546
Operating loss			(23,038	)			(23,136	)			(98,561	)			(85,546	)
Investment and other (expense) income, net			(1,072	)			646				(536	)			2,343
Interest expense			(3,255	)			(4,154	)			(12,342	)			(9,942	)
Loss before income taxes			(27,365	)			(26,644	)			(111,439	)			(93,145	)
Income tax provision (benefit)			85				(4,343	)			26,025				(15,816	)
Net loss		$	(27,450	)		$	(22,301	)		$	(137,464	)		$	(77,329	)
Net loss per share – basic		$	(0.44	)		$	(0.38	)		$	(2.29	)		$	(1.32	)
Net loss per share – diluted			(0.44	)			(0.38	)			(2.29	)			(1.32	)
Weighted average number of shares outstanding – basic			62,276				58,620				60,094				58,535
Weighted average number of shares outstanding – diluted			62,276				58,620				60,094				58,535

AVADEL PHARMACEUTICALS PLC
CONDENSED CONSOLIDATED BALANCE SHEETS
(In thousands, except per share data)
		December 31,				December 31,
		2022				2021
ASSETS
Current assets:
Cash and cash equivalents		$	73,981			$	50,708
Marketable securities			22,518				106,513
Research and development tax credit receivable			2,248				2,443
Prepaid expenses and other current assets			2,096				32,826
Total current assets			100,843				192,490
Property and equipment, net			839				285
Operating lease right-of-use assets			1,713				2,652
Goodwill			16,836				16,836
Research and development tax credit receivable			1,232				1,225
Other non-current assets			11,322				33,777
Total assets		$	132,785			$	247,265
LIABILITIES AND SHAREHOLDERS’ EQUITY
Current liabilities:
Current portion of long-term debt		$	37,668			$	—
Current portion of operating lease liability			960				900
Accounts payable			7,890				7,679
Accrued expenses			7,334				7,151
Other current liabilities			1,941				5,270
Total current liabilities			55,793				21,000
Long-term debt			91,614				142,397
Long-term operating lease liability			780				1,707
Other non-current liabilities			5,743				3,917
Total liabilities			153,930				169,021
Shareholders’ (deficit) equity:
Preferred shares, nominal value of $0.01 per share; 50,000 shares authorized; 488 issued and outstanding at December 31, 2022 and 2021, respectively			5				5
Ordinary shares, nominal value of $0.01 per share; 500,000 shares authorized; 62,878 and 58,620 issued and outstanding at December 31, 2022 and 2021, respectively			628				586
Additional paid-in capital			589,783				549,349
Accumulated deficit			(585,220	)			(447,756	)
Accumulated other comprehensive loss			(26,341	)			(23,940	)
Total shareholders’ (deficit) equity			(21,145	)			78,244
Total liabilities and shareholders’ (deficit) equity		$	132,785			$	247,265

AVADEL PHARMACEUTICALS PLC
CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS
(In thousands)
		Twelve Months Ended
		December 31,
			2022				2021
Cash flows from operating activities:
Net loss		$	(137,464	)		$	(77,329	)
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation and amortization			1,493				815
Amortization of debt discount and debt issuance costs			6,052				1,248
Changes in deferred tax			26,025				(15,666	)
Share-based compensation expense			7,013				8,872
Other adjustments			2,042				1,055
Net changes in assets and liabilities
Prepaid expenses and other current assets			30,815				(439	)
Research and development tax credit receivable			30				2,796
Accounts payable & other current liabilities			(3,108	)			4,232
Accrued expenses			227				895
Other assets and liabilities			(3,429	)			(3,789	)
Net cash used in operating activities			(70,304	)			(77,310	)
Cash flows from investing activities:
Purchases of property and equipment			(716	)			(26	)
Proceeds from the disposition of the Hospital Products			—				16,500
Proceeds from sales of marketable securities			83,828				102,224
Purchases of marketable securities			(3,414	)			(61,769	)
Net cash provided by investing activities			79,698				56,929
Cash flows from financing activities:
Payments for debt issuance costs			(4,804	)			—
Payments for extinguishment of February 2023 Notes			(8,653	)			—
Proceeds from stock option exercises and employee share purchase plan			2,682				263
Proceeds from issuance of shares off the at-the-market offering program			25,318				—
Net cash provided by financing activities			14,543				263
Effect of foreign currency exchange rate changes on cash and cash equivalents			(664	)			(896	)
Net change in cash and cash equivalents			23,273				(21,014	)
Cash and cash equivalents at January 1			50,708				71,722
Cash and cash equivalents at December 31		$	73,981			$	50,708

Company announces initial topline OLINVYK data including GI and cognitive outcomes, and length of stay data from ~200 patient real-world clinical outcomes study

TRV045, a novel S1P receptor modulator, continues to advance as a potential treatment for epilepsy, diabetic neuropathic pain and other CNS disorders, with two proof-of-concept studies expected to complete enrollment by mid-2023

Cash balance of $38.3
million at year end 2022

Company to host conference call today, March 30, 2023 at 8:00 a.m. ET

CHESTERBROOK, Pa., March 30, 2023 (GLOBE NEWSWIRE) — Trevena, Inc. (Nasdaq: TRVN), a biopharmaceutical company focused on the development and commercialization of novel medicines for patients with central nervous system (CNS) disorders, today reported its financial results for the fourth quarter ended December 31, 2022 and provided an overview of its recent operational highlights.

“We are excited to report initial topline data from the OLINVYK real-world outcomes studies, VOLITION and ARTEMIS. The GI and cognitive results build upon the extensive data set for OLINVYK, and we look forward to reporting respiratory outcome data as soon as it is available,” said Carrie Bourdow, President and CEO of Trevena. “We are also pleased to now have two proof-of-concept studies underway for TRV045, and we expect to report top-line data later this year.”

Fourth Quarter 2022 and Recent Corporate Highlights

• Initial topline data from new real-world VOLITION study demonstrated over 50% GI complete response and less than 4% incidence of symptoms suggestive of delirium in patients treated with OLINVYK. The VOLITION study, a 203-patient, real world, open-label, multi-site study led by clinical outcomes research experts from Cleveland Clinic and Wake Forest Baptist Health Medical Center, demonstrated a 52.2% GI complete response rate. A complete GI response was defined as a patient who did not vomit and did not require the use of antiemetics throughout the post-operative period. As reference, in pooled data for the Company’s pivotal Phase 3 studies of OLINVYK, the GI complete response rate was 46.2% (0.35mg) and 39.7% (0.50mg). As reflected in the OLINVYK label, nausea and vomiting were two of the most common adverse events reported in the controlled clinical trials.

  Over 90% of OLINVYK-treated patients in VOLITION reported feeling “alert and calm” from the morning of the first post-operative day and at every observation point thereafter, based on the Richmond Agitation-Sedation Scale, and only 3.9% of OLINVYK-treated patients exhibited symptoms suggesting delirium at any point in the 48-hour post-operative period, based on the validated 3D-Confusion Assessment Method (3D-CAM) screening tool. Sedation is an established risk of opioids including OLINVYK. Analysis of respiratory data from VOLITION is not yet available, and the Company expects to report these data mid-2023.

• Initial topline data from electronic medical records (EMR) based study, ARTEMIS, demonstrated a statistically significant 1.6-day reduction in average hospital length of stay vs matched patients treated with other IV opioids at Wake Forest Baptist Health. OLINVYK-treated patients in VOLITION were matched with comparable patients treated with other IV opioids, undergoing similar surgical procedures at VOLITION study sites during the same period of time that the VOLITION study was enrolled. EMR data analysis is currently available from the single largest contributing site, Wake Forest Baptist Health, representing 96 OLINVYK treated patients and 457 matched patients. Based on this initial data, OLINVYK-treated patients had a statistically significant 1.6-day (~27%) reduction in average overall hospital length of stay compared to matched patients treated with other IV opioids(P=0.0001). There was no statistically significant difference in the average duration of time in the post-anesthesia care unit (PACU), with 2.4 hours observed for both OLINVYK-treated and matched patients (P=0.8174). While an EMR analysis does not provide definitive data of group differences as seen in a prospectively randomized study, the Company believes the EMR data bring a unique perspective to understanding how drugs may perform in the real world.

• OLINVYK commercial team advances targeted customer outreach. In the fourth quarter of 2022, the commercial team signed contracts with three new specialty distributors that focus primarily on ambulatory surgery centers (ASCs). Hospital outpatient and ASCs are becoming an increasingly important setting of care. The Company remains flexible and adaptive as it sees a shift in customer inquiries and requests for OLINVYK in the hospital outpatient setting.

• Jiangsu Nhwa, Trevena’s partner in China, expects a regulatory decision for OLINVYK in the first half of this year. We continue to work closely with NHWA in support of potential approval of OLINVYK in China. If approved, Trevena would be eligible to receive a $3 million milestone payment from NHWA and would expect an additional $15 million of non-dilutive funding from R-Bridge Healthcare payable upon first commercial sale in China. 

• Initiated two proof-of-concept studies for TRV045, a novel S1P receptor modulator selective for the S1P receptor subtype 1. The Company advanced the clinical development program for TRV045, its novel S1P receptor modulator, initiating two proof-of-concept studies. These studies will help inform the Company’s future development path for TRV045 which has shown promising anti-inflammatory data in nonclinical models suggesting a potential disease-modifying role in CNS disorders.
  • TRV045 Target Engagement Study. The first study is a randomized, double-blind, placebo-controlled, four-way cross-over study designed to test the mechanism of action and measure evidence of target engagement for TRV045. The study will use a validated set of analgesic tests to evaluate potential central and peripheral nervous system effects and to provide insight into the potential anti-inflammatory actions of TRV045.
  • TRV045 Transcranial Magnetic Stimulation Study. The second study is a randomized, double-blind, placebo-controlled, two-way cross-over, multiple dose study designed to evaluate the pharmacodynamic effects of TRV045 on the cortical excitability in healthy male adults. The study will use Transcranial Magnetic Stimulation Electromyography (TMS-EMG) and Electroencephalography (TMS-EEG) to measure the potential effect of TRV045 on brain function, relevant to epilepsy and other CNS disorders.

Both studies are expected to complete enrollment by mid-2023, and the Company expects to report top-line data in 3Q 2023

Financial Results for Fourth Quarter 2022

For the fourth quarter of 2022, the Company reported a net loss attributable to common stockholders of $7.0 million, or $0.73 per share, compared to $14.0 million, or $2.12 per share in the fourth quarter of 2021. For the full year ended December 31, 2022, net loss attributable to common stockholders was $53.7 million, or $7.59 per share, compared to $51.6 million, or $7.90 per share.

Cash and cash equivalents were $38.3 million as of December 31, 2022, which the Company believes will be sufficient to fund the Company’s operating expenses and capital expenditure requirements into the fourth quarter of 2023.

Conference Call and Webcast Information

The Company will host a conference call and webcast with the investment community on March 30, 2023, at 8:00 a.m. Eastern Time featuring remarks by Carrie Bourdow, President and Chief Executive Officer, Patricia Drake, Chief Commercial Officer, Mark Demitrack, M.D., Senior Vice President and Chief Medical Officer, and Barry Shin, Chief Financial Officer.

Title:	Trevena Fourth Quarter 2022 Financial Results Conference Call & Webcast
Date:	Thursday, March 30, 2023
Time:	8:00 a.m. ET
Conference Call Details:	Toll-Free: 1-877-704-4453 International: 1-201-389-0920 Conference ID: 13736610
The conference call will be webcast live from the Company’s website and will be available via the following links: Webcast:
	https://viavid.webcasts.com/starthere.jsp?ei=1600316&tp_key=4a1d148855 https://www.trevena.com/investors/events-presentations/ir-calendar

The webcast should be accessed 15 minutes prior to the conference call start time. A replay of the webcast will be available following the conclusion of the live broadcast and will be accessible on the Company’s website.

About OLINVYK

^®

 (oliceridine) injection

OLINVYK is a new chemical entity approved by the FDA in August 2020. OLINVYK contains oliceridine, an opioid, which is a Schedule II controlled substance with a high potential for abuse similar to other opioids. It is indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate. OLINVYK is available in 1 mg/1 mL and 2 mg/2 mL single-dose vials, and a 30 mg/30 mL single-patient-use vial for patient-controlled analgesia (PCA). Approved PCA doses are 0.35 mg and 0.5 mg and doses greater than 3 mg should not be administered. The cumulative daily dose should not exceed 27 mg. Please see Important Safety Information, including the BOXED WARNING, and full prescribing information at www.OLINVYK.com.

IMPORTANT SAFETY INFORMATION

WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CENTRAL NERVOUS SYSTEM (CNS) DEPRESSANTS

ADDICTION, ABUSE, AND MISUSE – OLINVYK exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk before prescribing OLINVYK, and monitor all patients regularly for the development of behaviors or conditions.

LIFE-THREATENING RESPIRATORY DEPRESSION – Serious, life-threatening, or fatal respiratory depression may occur with use of OLINVYK. Monitor for respiratory depression, especially during initiation of OLINVYK or following a dose increase.

NEONATAL OPIOID WITHDRAWAL SYNDROME – Prolonged use of OLINVYK during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.

RISK FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS – Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation.

INDICATIONS AND USAGE

OLINVYK is an opioid agonist indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate.

Limitations of Use

Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve OLINVYK for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]:

• Have not been tolerated, or are not expected to be tolerated
• Have not provided adequate analgesia, or are not expected to provide adequate analgesia.

The cumulative total daily dose should not exceed 27 mg, as total daily doses greater than 27 mg may increase the risk for QTc interval prolongation.

CONTRAINDICATIONS

OLINVYK is contraindicated in patients with:

• Significant respiratory depression
• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment
• Known or suspected gastrointestinal obstruction, including paralytic ileus
• Known hypersensitivity to oliceridine (e.g., anaphylaxis)

WARNINGS AND PRECAUTIONS

• OLINVYK contains oliceridine, a Schedule II controlled substance, that exposes users to the risks of addiction, abuse, and misuse. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed OLINVYK. Assess risk, counsel, and monitor all patients receiving opioids.
• Serious, life-threatening respiratory depression has been reported with the use of opioids, even when used as recommended, especially in patients with chronic pulmonary disease, or in elderly, cachectic and debilitated patients. The risk is greatest during initiation of OLINVYK therapy, following a dose increase, or when used with other drugs that depress respiration. Proper dosing of OLINVYK is essential, especially when converting patients from another opioid product to avoid overdose. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status.
• Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia with risk increasing in a dose-dependent fashion. In patients who present with CSA, consider decreasing the dose of opioid using best practices for opioid taper.
• Prolonged use of opioids during pregnancy can result in withdrawal in the neonate that may be life-threatening. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using OLINVYK for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
• Profound sedation, respiratory depression, coma, and death may result from the concomitant use of OLINVYK with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, or alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate, prescribe the lowest effective dose, and minimize the duration.
• OLINVYK was shown to have mild QTc interval prolongation in thorough QT studies where patients were dosed up to 27 mg. Total cumulative daily doses exceeding 27 mg per day were not studied and may increase the risk for QTc interval prolongation. Therefore, the cumulative total daily dose of OLINVYK should not exceed 27 mg.
• Increased plasma concentrations of OLINVYK may occur in patients with decreased Cytochrome P450 (CYP) 2D6 function or normal metabolizers taking moderate or strong CYP2D6 inhibitors; also in patients taking a moderate or strong CYP3A4 inhibitor, in patients with decreased CYP2D6 function who are also receiving a moderate or strong CYP3A4 inhibitor, or with discontinuation of a CYP3A4 inducer. These patients may require less frequent dosing and should be closely monitored for respiratory depression and sedation at frequent intervals. Concomitant use of OLINVYK with CYP3A4 inducers or discontinuation of a moderate or strong CYP3A4 inhibitor can lower the expected concentration, which may decrease efficacy, and may require supplemental doses.
• Cases of adrenal insufficiency have been reported with opioid use (usually greater than one month). Presentation and symptoms may be nonspecific and include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If confirmed, treat with physiologic replacement doses of corticosteroids and wean patient from the opioid.
• OLINVYK may cause severe hypotension, including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics). Monitor these patients for signs of hypotension. In patients with circulatory shock, avoid the use of OLINVYK as it may cause vasodilation that can further reduce cardiac output and blood pressure.
• Avoid the use of OLINVYK in patients with impaired consciousness or coma. OLINVYK should be used with caution in patients who may be susceptible to the intracranial effects of CO₂ retention, such as those with evidence of increased intracranial pressure or brain tumors, as a reduction in respiratory drive and the resultant CO₂ retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy.
• As with all opioids, OLINVYK may cause spasm of the sphincter of Oddi, and may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.
• OLINVYK may increase the frequency of seizures in patients with seizure disorders and may increase the risk of seizures in vulnerable patients. Monitor patients with a history of seizure disorders for worsened seizure control.
• Do not abruptly discontinue OLINVYK in a patient physically dependent on opioids. Gradually taper the dosage to avoid a withdrawal syndrome and return of pain. Avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving OLINVYK, as they may reduce the analgesic effect and/or precipitate withdrawal symptoms.
• OLINVYK may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery.
• Although self-administration of opioids by patient-controlled analgesia (PCA) may allow each patient to individually titrate to an acceptable level of analgesia, PCA administration has resulted in adverse outcomes and episodes of respiratory depression. Health care providers and family members monitoring patients receiving PCA analgesia should be instructed in the need for appropriate monitoring for excessive sedation, respiratory depression, or other adverse effects of opioid medications.

ADVERSE REACTIONS

Adverse reactions are described in greater detail in the Prescribing Information.

The most common (incidence ≥10%) adverse reactions in Phase 3 controlled clinical trials were nausea, vomiting, dizziness, headache, constipation, pruritus, and hypoxia.

MEDICAL INFORMATION

For medical inquiries or to report an adverse event, other safety-related information or product complaints for a company product, please contact the Trevena Medical Information Contact Center at 1-844-465-4686 or email [email protected].

You are encouraged to report suspected adverse events of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

Please see Full Prescribing Information, including Boxed Warning.

About TRV045

TRV045 is a novel, selective sphingosine-1-phosphate subtype 1 (S1P₁) receptor modulator being developed as a potential treatment for acute and chronic neuropathic pain secondary to diabetic peripheral neuropathy. Through a collaboration with the National Institutes of Health, Trevena is also exploring TRV045 as a potential treatment for epilepsy.

S1P receptors are located throughout the body, including the central nervous system, where they are believed to play a role in modulating neurotransmission and membrane excitability.

Trevena’s discovery efforts have identified a family of compounds that are highly selective for the S1P₁ receptor. TRV045 reversed thermal hyperalgesia, a measure of neuropathic pain, in nonclinical models of diabetic peripheral neuropathy and chemotherapy-induced peripheral neuropathy. TRV045 was not associated with lymphopenia and produced no changes in blood pressure, heart rate, or respiratory function at or above pharmacologically active doses in nonclinical studies. TRV045 is an investigational product and is not yet approved by the FDA.

About Trevena

Trevena, Inc. is a biopharmaceutical company focused on the development and commercialization of innovative medicines for patients with CNS disorders. The Company has one approved product in the United States, OLINVYK^® (oliceridine) injection, indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate. The Company’s novel pipeline is based on Nobel Prize winning research and includes three differentiated investigational drug candidates: TRV045 for diabetic neuropathic pain and epilepsy, TRV250 for the acute treatment of migraine and TRV734 for maintenance treatment of opioid use disorder.

For more information, please visit www.Trevena.com 

About Jiangsu Nhwa:

Jiangsu Nhwa Pharmaceutical Co., Ltd. (SZ002262), founded in 1978, is a leading CNS company in China. Over the past 40 years, Nhwa is exclusively dedicated to developing innovative and differentiated pipeline in the areas of anesthesia, analgesia, psychiatry and neurology via in-house R&D and global partnership.

As a fully integrated pharmaceutical company with more than 4000 employees, Nhwa has comprehensive capabilities in research, clinical development, manufacturing and commercialization of CNS drugs. In recent years, Nhwa has further strengthened its leadership in CNS field in China by providing the services of precision diagnosis of CNS disorders (Shanghai N-yuen Biotechnology Company), and investing the largest Chinese CNS internet health platform (Happy Mood).

Forward-Looking Statements

Any statements in this press release about future expectations, plans and prospects for the Company, including statements about the Company’s strategy, future operations, clinical development and trials of its therapeutic candidates, plans for potential future product candidates and other statements containing the words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “suggest,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the status, timing, costs, results and interpretation of the Company’s clinical trials or any future trials of any of the Company’s investigational drug candidates; the uncertainties inherent in conducting clinical trials; expectations for regulatory interactions, submissions and approvals, including the Company’s assessment of discussions with FDA; available funding; uncertainties related to the Company’s intellectual property; uncertainties related to the ongoing COVID-19 pandemic, other matters that could affect the availability or commercial potential of the Company’s therapeutic candidates and approved product; and other factors discussed in the Risk Factors set forth in the Company’s Annual Report on Form 10-K and Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission (SEC) and in other filings the Company makes with the SEC from time to time. In addition, the forward-looking statements included in this press release represent the Company’s views only as of the date hereof. The Company anticipates that subsequent events and developments may cause the Company’s views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so, except as may be required by law.

For more information, please contact:

Investor Contact:

Dan Ferry

Managing Director

LifeSci Advisors, LLC

[email protected]

(617) 430-7576

Company Contact:

Bob Yoder

SVP and Chief Business Officer

Trevena, Inc.

(610) 354-8840

TREVENA, INC.
Condensed Statements of Operations
(Unaudited, in thousands except share and per share data)
		Three Months Ended Dec 31,								Year Ended Dec 31,
			2022				2021				2022				2021
Product revenue		$	–			$	(1	)		$	(438	)		$	498
License revenue			–				–				20				69
Total revenue			–				(1	)			(418	)			567
Operating expenses:
Cost of goods sold			228				334				3,018				954
Selling, general and administrative			5,723				9,761				34,728				38,112
Research and development			3,396				3,937				18,211				13,426
Total operating expenses			9,347				14,032				55,957				52,492
Loss from operations			(9,347	)			(14,033	)			(56,375	)			(51,925	)
Other income			2,342				80				2,705				337
Loss before income tax expense			(7,005	)			(13,953	)			(53,670	)			(51,588	)
Unrealized gain on marketable securities			–				–				1				–
Net loss		$	(7,005	)		$	(13,953	)		$	(53,669	)		$	(51,588	)
Per share information:
Net loss per share of common stock, basic and diluted		($0.73		)		($2.12		)		($7.59		)		($7.90		)
Weighted average shares outstanding, basic and diluted			9,594,072				6,586,251				7,072,362				6,529,074

TREVENA, INC.
Condensed Balance Sheets
(Unaudited, in thousands)
		December 31, 2022				December 31, 2021
Assets
Current assets:
Cash and cash equivalents		$	38,320			$	66,923
Inventories			906				2,352
Prepaid expenses and other current assets			1,782				1,448
Total current assets			41,008				70,723
Restricted cash			1,960				1,311
Property and equipment, net			1,488				1,841
Right-of-use lease assets			4,224				4,706
Other assets			–				1,543
Total assets		$	48,680			$	80,124
Liabilities and stockholders’ equity
Current liabilities:
Accounts payable, net		$	2,372			$	4,547
Accrued expenses and other current liabilities			5,461				3,847
Current portion of lease liabilities			899				792
Total current liabilities			8,732				9,186
Loans payable, net			13,430				–
Leases, net of current portion			5,436				6,309
Warrant liability			5,483				–
Total liabilities			33,081				15,495
Common stock			8				7
Additional paid-in capital			563,362				558,724
Accumulated deficit			(547,772	)			(494,102	)
Accumulated other comprehensive income (loss)			1				–
Total stockholders’ equity			15,599				64,629
Total liabilities and stockholders’ equity		$	48,680			$	80,124

 

 

Study successfully achieved both primary and secondary objectives

ANAVEX®2-73 treatment resulted in improvements of all efficacy endpoints over 48 Weeks

Anavex plans to proceed to ANAVEX®2-73 pivotal trial for Parkinson’s disease

NEW YORK, March 30, 2023 (GLOBE NEWSWIRE) — Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders including Alzheimer’s disease, Parkinson’s disease, Rett syndrome and other Central Nervous System (CNS) disorders, reports preliminary 48-week open-label extension Parkinson’s disease dementia ANAVEX®2-73-PDD-EP-001 Phase 2 study data which demonstrated longitudinal beneficial effects of ANAVEX®2-73 on the prespecified primary and secondary objectives, as well as planned primary and key secondary endpoints which will be utilized in a forthcoming pivotal study of ANAVEX®2-73 in Parkinson’s disease.

ANAVEX®2-73 (blarcamesine) is an oral small-molecule activator of the sigma-1 receptor (SIGMAR1), which data suggests is pivotal to restoring neural cell homeostasis and promoting neuroplasticity.¹

Parkinson’s disease (PD) is a chronic, debilitating CNS disease and the second largest age-related disorder after Alzheimer’s disease.² This study demonstrates for the first-time that patients’ clinical symptoms consistently improve longitudinally during the 48-week ANAVEX2-73-PDD-EP-001 Phase 2 study under active ANAVEX®2-73 treatment in Parkinson’s disease.

The 48-week ANAVEX2-73-PDD-EP-001 (NCT04575259) Phase 2 study assessed safety, tolerability and efficacy, measuring among others, Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS)³ Parts I, II, III, REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ), Clinical Global Impression – Improvement (CGI-I), as well as cognitive efficacy endpoint Montreal Cognitive Assessment (MoCA) over a 48-week period.

Preliminary analysis reveals that ANAVEX®2-73 (blarcamesine) was found to be generally safe and well tolerated; and safety findings in this study are consistent with the known safety profile of ANAVEX®2-73. In respect to efficacy, across all efficacy endpoints, patients performed better while on ANAVEX®2-73.

The 48-week Open Label Extension (OLE) ANAVEX2-73-PDD-EP-001 Phase 2 study was offered to participants after completion of the double-blind placebo-controlled ANAVEX2-73-PDD-001 Phase 2 study. Study participants were allowed to stay on a stable regimen of anti-Parkinson’s disease medications (including levodopa, dopamine agonists, MAO-B inhibitors, or entacapone).

Previously, in the double-blind ANAVEX2-73-PDD-001 Phase 2 study, ANAVEX®2-73 treatment demonstrated statistically significant improvements compared to placebo (ITT population) for MDS-UPDRS Total score. From baseline to the end of the trial at 14 weeks, the MDS-UPDRS Total score improved by -10.98 points in the ANAVEX®2-73 high dose group and worsened by 3.53 points in the placebo group, an adjusted mean difference of -14.51 points (p = 0.034). This corresponds to a relative improvement of 18.9% over 14 weeks.⁴ This data was also consistent with expression levels of pathological dysregulated neurodegenerative genes, including Parkinson’s disease genes, which were significantly restored by the therapeutic effect of ANAVEX®2-73 (p<0.005).⁵

Due to the COVID-19 pandemic, the start of the extension phase was delayed, on average, by approximately 41 weeks at the end of the preceding double-blind placebo-controlled study (DB). This led to a reduced enrollment rate for the extension phase. The period between the end of the double-blind phase to the start of the extension phase, where patients were not on ANAVEX®2-73 treatment, is known as a ‘drug holiday’. The drug holiday period of treatment separation provided an opportunity to compare the trajectory of clinical scores between no ANAVEX®2-73 treatment (drug holiday) and ANAVEX®2-73 treatment in the extension phase.

All efficacy endpoints, which includes the MDS-UPDRS Part II + III and Clinical Global Impression – Improvement (CGI-I) measured at the end of trial of the double-blind study (DB EOT), the OLE Baseline, OLE Week 24, and OLE Week 48, showed a worsening during the drug holiday. However, a consistent improvement was observed during the extension phase when patients resumed ANAVEX®2-73 treatment. These results are consistent with the pattern observed for all efficacy measures in the extension phase (see Chart and Table).⁶

Clinical Endpoints		Change at OLE Baseline from DB EOT			Change at Week 24 from OLE Baseline			Change at Week 48 from OLE Baseline
MDS-UPDRS Part III	Mean (SE)	4.394 (2.155)	N=33		-2.583 (2.474)	N=24		-3.95 (4.067)		N=20
	Median	0			-0.5			-1
MDS-UPDRS Part II + III	Mean (SE)	6.667 (2.800)	N=33		-3.870 (3.403)	N=23		-2.20 (5.314)		N=20
	Median	0			-1			-0.5
MDS-UPDRS Total score	Mean (SE)	9.818 (3.387)	N=33		-4.739 (4.262)	N=23		-2.25 (6.656)		N=20
	Median	4			0			-3.5
RBDSQ	Mean (SE)	0.784 (0.439)	N=37		-1.667 (0.424)	N=24		-0.524 (0.620)		N=21
	Median	0			-1			-1
CGI-I	Mean (SE)	0.629 (0.184)	N=35		-0.542 (0.295)	N=24		-0.7 (0.309)		N=20
	Median	0			0			-1
MoCA	Mean (SE)	-1.45455 (0.433)	N=33		-0.2912 (0.519)	N=24		-1.2 (0.537)		N=20
	Median	-1			0			-0.5
OLE = Open Label Extension study; DB = Double-Blind study; EOT = End of Trial
The calculations were done with all available data at reference time points
These results should be interpreted cautiously due to the nature of the study and the small sample sizes
MDS-UPDRS = Movement Disorder Society-Unified Parkinson Disease Rating Scale
RBDSQ = REM Sleep Behavior Disorder Screening Questionnaire
CGI-I = Clinical Global Impression – Improvement
MoCA = Montreal Cognitive Assessment (cognitive decline slowing in OLE)
Except for MoCA, Positive scores respresent decline; Negative scores represent improvement

 

The two endpoints, MDS-UPDRS Part II + III and Clinical Global Impression – Improvement (CGI-I) measured in this study are the planned primary and key secondary endpoints in Anavex’s forthcoming pivotal 6-month Parkinson’s disease study.

“It is encouraging that the patients’ clinical symptoms consistently improved longitudinally over time during the extension phase under active ANAVEX®2-73 treatment,” said Christopher U Missling, PhD, President & CEO of Anavex. “This data suggests ANAVEX®2-73’s potential capability to slow and potentially reverse the life altering symptoms of Parkinson’s disease, an urgent unmet global need.”

Moreover, at the request of the participants completing the 48-week open-label extension study, patient requested treatment with ANAVEX®2-73 is continuing beyond the open-label 48-weeks through the compassionate use Special Access Scheme. Currently, participants in the compassionate use program for ANAVEX®2-73 have been on average, for over 2 years and counting.

The Michael J. Fox Foundation (MJFF) awarded Anavex a research grant for an imaging-focused Parkinson’s disease clinical trial with ANAVEX®2-73.⁷ MJFF previously awarded Anavex a research grant, which fully funded a preclinical study that established ANAVEX®2-73 as a potentially disease-modifying treatment for Parkinson’s disease.⁸

Anavex Life Sciences’ therapeutic product platform includes orally available small molecule lead drug candidate ANAVEX®2-73 for the treatment of Alzheimer’s disease, Parkinson’s disease and Rett syndrome and ANAVEX®3-71 for schizophrenia, Alzheimer’s disease, and frontotemporal dementia.

About Parkinson’s Disease (PD)

Parkinson’s disease is a chronic and progressive neurological disorder that is characterized by well-known motor symptoms including tremors, stiffness of limbs, slowness of movements, and difficulties with posture and balance, as well as by non-motor symptoms. It is the second most common neurological disorder and approximately one million people in the United States, and more that 10 million people worldwide, live with this disease. Parkinson’s disease is more common in people over 60 years of age and its prevalence is expected to increase significantly as the average age of the population increases. Current Parkinson’s treatments are only effective in managing symptoms of the disease, mainly through the use of levodopa and dopamine agonists. As the disease progresses and dopaminergic neurons continue to be lost, these drugs eventually become less effective at treating the symptoms.

About Anavex Life Sciences Corp.

Anavex Life Sciences Corp. (Nasdaq: AVXL) is a publicly traded biopharmaceutical company dedicated to the development of novel therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders, including Alzheimer’s disease, Parkinson’s disease, Rett syndrome, and other central nervous system (CNS) diseases, pain, and various types of cancer. Anavex’s lead drug candidate, ANAVEX®2-73 (blarcamesine), has successfully completed a Phase 2a and recently a Phase 2b/3 clinical trial for Alzheimer’s disease, a Phase 2 proof-of-concept study in Parkinson’s disease dementia, and both a Phase 2 and a Phase 3 study in adult patients with Rett syndrome. ANAVEX®2-73 is an orally available drug candidate that restores cellular homeostasis by targeting sigma-1 and muscarinic receptors. Preclinical studies demonstrated its potential to halt and/or reverse the course of Alzheimer’s disease. ANAVEX®2-73 also exhibited anticonvulsant, anti-amnesic, neuroprotective, and anti-depressant properties in animal models, indicating its potential to treat additional CNS disorders, including epilepsy. The Michael J. Fox Foundation for Parkinson’s Research previously awarded Anavex a research grant, which fully funded a preclinical study to develop ANAVEX®2-73 for the treatment of Parkinson’s disease. ANAVEX®3-71, which targets sigma-1 and M1 muscarinic receptors, is a promising clinical stage drug candidate demonstrating disease-modifying activity against the major hallmarks of Alzheimer’s disease in transgenic (3xTg-AD) mice, including cognitive deficits, amyloid, and tau pathologies. In preclinical trials, ANAVEX®3-71 has shown beneficial effects on mitochondrial dysfunction and neuroinflammation. Further information is available at www.anavex.com. You can also connect with the company on Twitter,Facebook, Instagram, and LinkedIn.

Forward-Looking Statements

Statements in this press release that are not strictly historical in nature are forward-looking statements. These statements are only predictions based on current information and expectations and involve a number of risks and uncertainties. Actual events or results may differ materially from those projected in any of such statements due to various factors, including the risks set forth in the Company’s most recent Annual Report on Form 10-K filed with the SEC. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement and Anavex Life Sciences Corp. undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof.

For Further Information:

Anavex Life Sciences Corp.
Research & Business Development
Toll-free: 1-844-689-3939
Email: [email protected]

Investors:

Andrew J. Barwicki
Investor Relations
Tel: 516-662-9461
Email: [email protected]

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¹ Advances in Experimental Medicine and Biology Volume 964 (2017) Sigma Receptors: Their Role in Disease and as Therapeutic Targets.
² Reeve A, Simcox E, Turnbull D. Ageing and Parkinson’s disease: why is advancing age the biggest risk factor? Ageing Res Rev. 2014 Mar;14(100):19-30. doi: 10.1016/j.arr.2014.01.004. Epub 2014 Feb 3. PMID: 24503004; PMCID: PMC3989046; Mhyre TR, Boyd JT, Hamill RW, Maguire-Zeiss KA. Parkinson’s disease. Subcell Biochem. 2012;65:389-455. doi: 10.1007/978-94-007-5416-4_16. PMID: 23225012; PMCID: PMC4372387.
³ The Movement Disorder Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS) is a commonly used tool to measure Parkinson disease (PD) progression.
⁴ https://www.anavex.com/post/anavex-life-sciences-announces-presentation-of-phase-2-clinical-biomarker-data-from-pdd-study
⁵ https://www.anavex.com/post/anavex-announces-first-entire-clinical-alzheimer-s-gene-pathway-data-of-anavex-2-73-at-aaic-2022
⁶ The observed worsening (increase) of MDS-UPDRS scores in this study during drug holiday is consistent with the literature, e.g.: Holden SK, Finseth T, Sillau SH, Berman BD. Progression of MDS-UPDRS Scores Over Five Years in De Novo Parkinson Disease from the Parkinson’s Progression Markers Initiative Cohort. Mov Disord Clin Pract. 2018 Jan-Feb;5(1):47-53. doi: 10.1002/mdc3.12553. Epub 2017 Sep 22; Simuni T, Siderowf A, Lasch S, Coffey CS, Caspell-Garcia C, Jennings D, Tanner CM, Trojanowski JQ, Shaw LM, Seibyl J, Schuff N, Singleton A, Kieburtz K, Toga AW, Mollenhauer B, Galasko D, Chahine LM, Weintraub D, Foroud T, Tosun D, Poston K, Arnedo V, Frasier M, Sherer T, Chowdhury S, Marek K; Parkinson’s Progression Marker Initiative*. Longitudinal Change of Clinical and Biological Measures in Early Parkinson’s Disease: Parkinson’s Progression Markers Initiative Cohort. Mov Disord. 2018 May;33(5):771-782. doi: 10.1002/mds.27361.
⁷https://www.anavex.com/anavex-life-sciences-receives-michael-j-fox-foundation-grant-for-clinical-study-of-anavex2-73-blarcamesine-in-people-with-parkinsons-disease/
⁸https://www.anavex.com/parkinsons-disease-data-mjf-conference/; https://www.anavex.com/anavex-awarded-grant-from-the-michael-j-fox-foundation-for-parkinsons-research/

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