Liquidia Corporation (Liquidia), a biopharmaceutical company, focuses on the development, manufacture, and commercialization of products that address unmet patient needs, with focus directed towards rare cardiopulmonary diseases, such as pulmonary arterial hypertension (‘PAH’) and pulmonary hypertension associated with interstitial lung disease (‘PH-ILD’).
The company operates through its wholly owned operating subsidiaries, Liquidia Technologies and Liquidia PAH. The company generates revenue...
Liquidia Corporation (Liquidia), a biopharmaceutical company, focuses on the development, manufacture, and commercialization of products that address unmet patient needs, with focus directed towards rare cardiopulmonary diseases, such as pulmonary arterial hypertension (‘PAH’) and pulmonary hypertension associated with interstitial lung disease (‘PH-ILD’).
The company operates through its wholly owned operating subsidiaries, Liquidia Technologies and Liquidia PAH. The company generates revenue pursuant to a promotion agreement between Liquidia PAH and Sandoz Inc. (‘Sandoz’), dated as of August 1, 2018, as amended (the ‘Promotion Agreement’), sharing profit derived from the sale of Sandoz’s substitutable generic treprostinil injection (‘Treprostinil Injection’) in the United States. Liquidia PAH has the exclusive rights to conduct commercial activities to encourage the appropriate use of Treprostinil Injection. The company employs a targeted sales force calling on physicians and hospital pharmacies involved in the treatment of PAH and PH-ILD in the United States, as well as key stakeholders involved in the distribution and reimbursement of medicines to treat these patients. The company established its commercial presence in the field to support Treprostinil Injection and has since expanded its presence to support the potential launch of YUTREPIA (treprostinil) inhalation powder (‘YUTREPIA’), further validating its reputation as a company committed to supporting PAH and PH-ILD patients.
The company conducts research, development, and manufacturing of novel products by applying its subject matter expertise in cardiopulmonary diseases and its proprietary PRINT technology, a particle engineering platform, to enable precise production of uniform drug particles designed to improve the safety, efficacy, and performance of a wide range of therapies. Through the development of the company’s own products and research with third parties, it has experience applying PRINT across multiple routes of administration and drug payloads, including inhaled therapies, vaccines, biologics, nucleic acids, and ophthalmic implants, among others.
The company’s lead product candidate is YUTREPIA for the treatment of PAH and PH-ILD. YUTREPIA is an inhaled dry powder formulation of treprostinil designed with PRINT to improve the therapeutic profile of treprostinil by enhancing deep lung delivery while using a convenient, low-effort dry-powder inhaler (‘DPI’), and by achieving higher dose levels than the labeled doses of current inhaled therapies. On August 16, 2024, the United States Food and Drug Administration (the ‘FDA’) granted tentative approval for the company’s New Drug Application (‘NDA’) for YUTREPIA for the treatment of PAH and PH-ILD and simultaneously determined that Tyvaso DPI, approved on May 23, 2022, qualifies for a three-year New Clinical Investigation exclusivity for the chronic use of dry powder formulations of treprostinil for the approved indications.
The company is also developing L606, an investigational, liposomal formulation of treprostinil administered twice daily with a short-duration next-generation nebulizer, which it licensed from Pharmosa Biopharm Inc. (‘Pharmosa’). L606 is currently being evaluated in an open-label study in the United States for the treatment of PAH and PH-ILD, with a planned pivotal study for the treatment of PH-ILD.
Products and Product Candidates
YUTREPIA (treprostinil) Inhalation Powder to Treat PAH and PH-ILD
The company’s lead investigational drug, YUTREPIA (treprostinil) inhalation powder, is an inhaled dry-powder formulation of treprostinil designed to improve the therapeutic profile of treprostinil by enhancing deep lung delivery and achieving higher dose levels than the labeled doses of current inhaled therapies while using a convenient, easy-to-use dry-powder inhaler, the RS00 Model 8 DPI. YUTREPIA was initially tentatively approved by the FDA for the treatment of PAH in November 2021. In August 2024, the FDA granted tentative approval for the company’s NDA for YUTREPIA for the treatment of both PAH and PH-ILD and simultaneously determined that Tyvaso DPI, approved on May 23, 2022, qualifies for a three-year New Clinical Investigation exclusivity for the chronic use of dry powder formulations of treprostinil for the approved indications.
Each particle of YUTREPIA has been designed using the company’s PRINT technology to have uniform size and shape to achieve enhanced aerosolization and deposition in the lungs. The RS00 Model 8 DPI device used to deliver YUTREPIA is robust with regard to position and accidental movements and has been used globally to deliver drugs to patients with compromised lung function, like asthma, COPD, and cystic fibrosis. By contrast, Tyvaso DPI uses a high-resistance device that has only been used previously in patients with diabetes.
YUTREPIA has been safely titrated to doses higher than the target labeled doses of Tyvaso and Tyvaso DPI. Historically, the labeled dose range for inhaled treprostinil has been 9-12 nebulized breaths per session (‘bps’) for Tyvaso and the corresponding doses of Tyvaso DPI (up to 64 mcg, comparable to 12 bps). In contrast, YUTREPIA has been studied in PAH patients up to 291.5 mcg four times a day (comparable to at least 33 bps of Tyvaso), and in PH-ILD patients, as high as 318 mcg (comparable to at least 36 bps of Tyvaso) as part of an ongoing open-label clinical study. The different combinations of YUTREPIA’s four proposed capsule strengths allow customized dosing and titration based on a patient’s disease progression. This expanded dose range of YUTREPIA may allow patients to remain on inhaled treprostinil therapy longer before transitioning to more invasive parenteral therapies.
The company has developed YUTREPIA under the 505(b)(2) regulatory pathway using the nebulized form of treprostinil, Tyvaso, as the reference listed drug. This regulatory pathway allows the company to rely in part on the FDA’s previous findings of efficacy and safety of Tyvaso and the active ingredient treprostinil. The company submitted its NDA for YUTREPIA in January 2020. In November 2021, the FDA issued a tentative approval of YUTREPIA, which indicated that the NDA had met all the requirements for final approval but cannot yet be marketed. In July 2023, the company filed an amendment to its NDA to add PH-ILD to the labeled indications for YUTREPIA. The FDA issued a tentative approval of the amended NDA for both PAH and PH-ILD in August 2024. Final FDA approval of the NDA for YUTREPIA is delayed until the expiration on May 23, 2025, of New Clinical Investigation exclusivity that was granted to Tyvaso DPI.
The company’s NDA submission was based in part upon the results of its pivotal, open-label Phase 3 clinical trial, Investigation of the Safety and Pharmacology of Dry Powder Inhalation of Treprostinil, for YUTREPIA (‘INSPIRE’). Of the 121 patients enrolled in the study, 55 were Transition patients and 66 were Prostacyclin Naïve patients. Transition patients started at a dose comparable to their prior nebulized treprostinil dose and were titrated to higher doses as warranted by their clinical disease. Prostacyclin Naïve patients started on a dose of 26.5 mcg of YUTREPIA, with most (>80%) titrating to a 79.5 mcg dose or higher within the first two months of treatment.
The company is actively conducting and considering other clinical trials to generate additional data to support the use of YUTREPIA. In December 2023, it enrolled the first PH-ILD patient in the Open-Label Prospective Multicenter Study to Evaluate Safety and Tolerability of Dry Powder Inhaled Treprostinil in Pulmonary Hypertension, referred to as the ASCENT study.
Treprostinil Injection, a Generic Version of Remodulin
Remodulin is treprostinil administered through continuous intravenous and subcutaneous infusion, as approved by the FDA in 2002 and 2004, and marketed by United Therapeutics. Patients must use external pumps manufactured by third parties to deliver Remodulin. Smiths Medical ASD, Inc. (‘Smiths Medical’) manufactured the pumps used by most patients in the United States to administer Remodulin, including the CADD-MS 3 infusion pump used to deliver subcutaneous Remodulin, and the CADD-Legacy pump to deliver intravenous Remodulin. An estimated 3,000 patients are treated annually with parenteral, infused treprostinil split between the two routes of administration.
In August 2018, Sandoz partnered with Liquidia PAH (then known as RareGen) on an exclusive basis to market and commercialize its generic Treprostinil Injection, which was subsequently launched as the first-to-file, fully substitutable generic treprostinil for parenteral administration in March 2019. Liquidia PAH promotes the appropriate use of Treprostinil Injection for the treatment of PAH in the United States and works jointly with Sandoz on the commercial strategy for the product. Sandoz retains all rights in and to Treprostinil Injection. As the Abbreviated New Drug Application (‘ANDA’) holder for Treprostinil Injection, Sandoz maintains responsibility for compliance with FDA regulatory and healthcare laws, including any regulatory communications with the FDA or any other regulatory authorities with respect to Treprostinil Injection. In consideration for Liquidia PAH conducting certain responsibilities associated with the commercialization of Treprostinil Injection, Liquidia PAH receives a portion of the net profits generated from the sales of the product.
In December 2022, the company entered into a Device Development and Supply Agreement (the ‘Pump Development Agreement’) with Sandoz and Mainbridge Health Partners LLC (‘Mainbridge’) to support the development of a new subcutaneous pump for infusion of Treprostinil Injection in order to replace the existing CADD-MS 3 infusion pumps. Mainbridge is performing development, validation, and testing activities required for the pump and related consumables. The company and Sandoz are also evaluating alternative pump options for the subcutaneous administration of Treprostinil Injection, but it does not yet have any agreements in place with respect to the development of any alternative pumps. The company and Sandoz are splitting the costs to develop a new pump equally.
L606
In June 2023, the company entered into the Pharmosa License Agreement pursuant to which it was granted an exclusive license in North America to develop and commercialize L606, an inhaled, sustained-release liposomal formulation of treprostinil currently being evaluated in a clinical trial for the treatment of PAH and PH-ILD. L606 is a complement to the company’s pipeline and furthers its mission to provide innovative treatment options that improve the lives of patients with improved product profiles.
L606 offers potential substantial benefits to patients with less frequent dosing than current inhaled products, improved tolerability with lower peak exposures, and rapid delivery with a next-generation nebulizer. Liposomes, as a pulmonary drug delivery system, have been reported to enhance the therapeutic benefits of drugs and to reduce the potential for systemic adverse effects. The L606 suspension uses Pharmosa’s proprietary liposomal formulation to encapsulate treprostinil, which can be released slowly under a controlled manner/rate into the lung. This control enables modulation of drug release to achieve optimized drug exposure over an extended period of time, and reduces local irritation on the respiratory tract.
L606 is supplied in six different dose strengths in disposable ampules, packaged as fourteen ampules in a foil pouch representing one week’s supply of drug. L606 is administered with the L606 inhalation system (mesh-vibrating nebulizer), which is currently undergoing testing. Before each treatment session, a L606 ampule would be opened and the suspension would be transferred into the medication chamber of the L606 nebulizer for oral inhalation. The L606 formulation inhalation system consists of an electronic, lightweight, and virtually silent mesh-vibrating nebulizer which can deliver a dose in less than 2 minutes using breath-actuated smart technology and patients' normal breathing pattern. The vibrating mesh technology generates fine-particle aerosols of the L606 formulation. Pharmosa has demonstrated clinically that L606 can be used with devices supplied by different manufacturers, providing the company the option to improve the patient device experience without changing the intended dose administered.
The company is conducting in the United States an open-label study to assess the safety of L606 in patients with PAH and patients with PH-ILD transitioning from Tyvaso (nebulizer or dry-powder inhaler) or patients with PAH naïve to prostacyclins. The open-label study was fully enrolled during 2024 with 28 patients and includes some patients who have been successfully treated with L606 for longer than one year. L606 continues to be well tolerated up to the company’s maximum dose of 318 mcg twice daily, which is approximately 2 to 2.5-fold higher than comparable target dosing of Tyvaso (9 to 12 bps) four times daily.
The company is preparing to conduct a global placebo-controlled efficacy study in PH-ILD. The clinical design will include approximately 340 patients across more than 100 sites in at least 20 countries. The primary outcome measure will be six-minute walk distance. To initiate the study, the company must also support regulatory submissions related to the proprietary nebulizer which will be used in combination with L606.
PRINT Technology
YUTREPIA leverages PRINT technology to produce dry-powder drug particles that enhance deep-lung delivery. YUTREPIA drug particles are uniform in size (~1µm) and shape, having been engineered for enhanced aerosolization and deep-lung deposition. In vitro studies suggest that the uniformity of size and shape allows the company’s inhaled particles to target delivery into the lungs with less deposition in the upper airways. The dry-powder formulation aerosolizes into free-flowing particles upon inhalation, allowing for the use of a low-effort inhaler.
Development, Regulatory and Commercial Strategy
The company intends to develop and commercialize a pipeline of drugs by applying its expertise in the development of cardio-pulmonary medicines and leveraging the advantages of its proprietary PRINT technology. Outside of the United States, the company may pursue regulatory approval and commercialization of its product candidates in collaboration with pharmaceutical companies with regional expertise.
The company intends to manufacture its product candidates using a combination of in-house capabilities and external contract manufacturing organizations (‘CMOs’), depending on the program requirements. For example, its current plans are for the dry powder formulation of YUTREPIA to be manufactured internally using PRINT Technology and for CMOs to produce, package, and distribute YUTREPIA finished goods on a commercial scale. Conversely, L606 is planned to be manufactured exclusively by CMOs using the proprietary formulation methods provided by Pharmosa.
The company intends to focus its commercial efforts initially on the U.S. market in the treatment of PAH and PH-ILD. It employs a targeted sales force, calling on physicians involved in the treatment of PAH and PH-ILD in the United States, as well as key stakeholders involved in the distribution and reimbursement of therapies for PAH and PH-ILD. The company’s commercial efforts focus on the highly concentrated target market of PAH and PH-ILD centers of excellence and high prescribers of approved therapies.
Manufacturing and Supply
In August 2021, the FDA completed an on-site Pre-Approval Inspection (‘PAI’) of the company’s Morrisville, North Carolina facility in connection with the review of the YUTREPIA NDA. The 5-day PAI concluded with no Form 483 Inspectional Observations issued. This was the company’s first inspection of the Morrisville site by the FDA. The company utilizes contract manufacturers to finish production and package its drug product for clinical and commercial use.
The company depends on third-party suppliers and CMOs for commercial inventory and clinical supplies of YUTREPIA, including active pharmaceutical ingredients which are used in its product candidates. For example, it currently relies on a sole supplier, LGM Pharma, LLC (‘LGM’), for treprostinil, the active pharmaceutical ingredient of YUTREPIA, and it currently relies on a sole supplier, Plastiape S.p.A (‘Plastiape’), for RS00 Model 8 DPI, the device used to administer YUTREPIA. The company also relies on a sole supplier, Lonza Tampa LLC (‘Lonza’), for encapsulation and packaging services for YUTREPIA. If and when the company receives final marketing approval for YUTREPIA, it expects to continue to rely on third-party CMOs to manufacture, package, and distribute some or all of its supply of YUTREPIA on a commercial scale.
Supply of Treprostinil Injection is managed directly by the company’s partner Sandoz, which retains the ANDA, manages inventory, and records gross revenue on product sales. Sandoz is either the manufacturer or contracted party for the entire supply chain. The company collaborates with Sandoz on a regular basis to plan appropriate inventory production and management based on the demand for Treprostinil Injection and observations in the field. Additionally, the company has contracted with its manufacturing partner Chengdu to supply the RG 3mL Medication Cartridge for use with CADD-MS 3 infusion pumps and enable subcutaneous administration of Treprostinil Injection. The pumps used to administer Treprostinil Injection are currently all manufactured by ICU Medical, with whom the company has no contractual relationship. The company has entered into the Pump Development Agreement with Sandoz and Mainbridge for the development of a new pump for the subcutaneous administration of treprostinil.
L606 is manufactured exclusively by CMOs using the proprietary liposomal formulation methods provided by Pharmosa. Under the License Agreement, Pharmosa will manufacture clinical and commercial supplies of L606 and support Liquidia in establishing a redundant global supply chain. The proprietary nebulizer used to administer L606 will be manufactured by a third party. The company is continuing to evaluate several options for the nebulizer that it will plan to use for L606.
Collaboration and Licensing Agreements
Pharmosa License Agreement
In June 2023, the company entered into a license agreement with Pharmosa pursuant to which it was granted an exclusive license in North America to develop and commercialize L606, an inhaled, sustained-release formulation of treprostinil currently being evaluated in a clinical trial for the treatment of PAH and PH-ILD, and a non-exclusive license for the manufacture, development, and use (but not commercialization) of such licensed product in most countries outside North America (the ‘Pharmosa License Agreement’). On October 2, 2024, the company and Pharmosa entered into a First Amendment to the Pharmosa License Agreement (the ‘First Amendment’) which, among other things, expands the company’s licensed territory beyond North America to include key markets in Europe, Japan, and elsewhere.
Sandoz Promotion Agreement
Liquidia PAH entered into a Promotion Agreement with Sandoz on August 1, 2018, as amended on May 8, 2020, September 4, 2020, November 18, 2022, and March 10, 2023, which engaged Liquidia PAH on an exclusive basis to promote the appropriate use of Sandoz’s Treprostinil Injection for the treatment of PAH in the United States, including its commonwealths, territories, possessions, and military bases. Liquidia PAH works jointly with Sandoz on the commercial strategy for Treprostinil Injection and on identifying, manufacturing, and developing medical devices, including pumps and cartridges, that may be used to administer Treprostinil Injection.
The University of North Carolina at Chapel Hill
In December 2008, the company entered into the Amended and Restated License Agreement with The University of North Carolina at Chapel Hill (‘UNC’) for the use of certain patent rights and technology relating to initial innovations of the company’s PRINT technology (the ‘UNC License’). Under the terms of the UNC License, the company has an exclusive license to such patent rights and technology for its drug products. The UNC License grants the company the right to grant sublicenses to the technology, as well as control the litigation of any infringement claim instituted by or against it in respect of the licensed patent rights.
Aerie Pharmaceuticals
The company has exclusively licensed its PRINT technology to Aerie Pharmaceuticals, Inc. (‘Aerie’), which in 2017 acquired most of the assets of Envisia Therapeutics, Inc., for broad usage in the design and commercialization of small molecule and biologic ophthalmic therapies. In November 2022, Alcon Inc. (‘Alcon’) completed its acquisition of Aerie to help bolster Alcon’s presence in the ophthalmic pharmaceutical space and, as a result, retains Aerie’s exclusive license to the use of the company’s PRINT technology for ophthalmic therapies.
GlaxoSmithKline
In March 2023, the company and GSK plc (‘GSK’) entered into a Research License Agreement (the ‘GSK License Agreement’) which supersedes and replaces the company’s prior agreements with GSK. Pursuant to the GSK License Agreement, the company has granted GSK a non-exclusive, non-sublicensable (except to affiliates), royalty-free license to use its PRINT technology for the sole purpose of conducting pre-clinical research and pre-clinical development of inhaled formulations of GSK’s Molecules in the Field and in the Territory (capitalized terms are as defined in the GSK License Agreement). The company and GSK will each own and retain all rights, title, and interest in and to all inventions, discoveries, and other subject matter (including Know-How (as defined in the GSK License Agreement)) together with all intellectual property rights therein which are owned or controlled by such party as of the date of the GSK License Agreement or which are invented or acquired by or on behalf of such party independent of the GSK License Agreement.
Intellectual Property
The company has a total of 127 patents and pending patent applications in its patent portfolio which protect its PRINT technology and drug products in development. As of December 31, 2024, the company was the sole owner of 20 patents in the United States and 42 patents in foreign jurisdictions, as well as 11 additional pending patent applications, including provisional patent applications, in the United States, Europe, Japan, and other jurisdictions. In addition to the patents and patent applications owned solely by the company, its patent portfolio also includes 42 patents and 12 patent applications licensed from third parties. As of December 31, 2024, the company had an exclusive, worldwide license from UNC to 14 U.S. patents and 7 foreign patents, as well as one additional patent application in the United States or selected foreign jurisdictions. Five of the patents and one patent application in the portfolio licensed from UNC are jointly owned by the company. Also, as of December 31, 2024, the company had an exclusive, worldwide license from Pharmosa Biopharm to four U.S. patents and 17 foreign patents, as well as 11 additional patent applications in the United States or selected foreign jurisdictions. YUTREPIA is specifically protected by 16 issued patents in the United States, the longest-lived of which will expire in 2037.
The company’s trademarks, trade names, and service marks, such as Liquidia, the Liquidia logo, YUTREPIA, and PRINT, are protected under applicable intellectual property laws and are the property of Liquidia Technologies, Inc.
Research and Development Expenses
The company’s research and development expenses were $47.8 million for the year ended December 31, 2024.
History
Liquidia Corporation was founded in 2004. The company was incorporated in Delaware in 2020.
