Lyra Therapeutics Stock

Lyra Therapeutics, Inc. operates as a clinical-stage biotechnology company. The company focuses on the development and commercialization of therapies for the localized treatment of patients with chronic rhinosinusitis, or CRS.

The company's proprietary technology is designed to consistently deliver medicines directly to the affected tissue for sustained periods with a single administration. Its product candidates, LYR-210 and LYR-220, are bioresorbable polymeric matrices designed to be administered in a brief, non-invasive, in-office procedure and intended to deliver up to six months of continuous anti-inflammatory drug therapy to the sinonasal passages for the treatment of CRS. The drug embedded within LYR-210 and LYR-220 is mometasone furoate, or MF, which is the active ingredient in various U.S. Food and Drug Administration, or FDA, approved drugs and has a well-established efficacy and safety profile.

On September 26, 2022, the company entered into an amended License and Collaboration Agreement, or the LianBio License Agreement with LianBio Inflammatory Limited, or LianBio to develop and commercialize LYR-210 in Greater China (mainland China, Hong Kong, Taiwan, and Macau), South Korea, Singapore and Thailand. LianBio will be responsible for the clinical development and commercialization of LYR-210 in the licensed territories, and the company will retain all rights to LYR-210 in all other geographies. As part of the LianBio License Agreement, LianBio will also have the first right to obtain development and commercial rights in the licensed territories to the company's LYR-220 product candidate.

The company's innovative and proprietary drug delivery technology is designed to locally and continuously deliver small molecule drugs to the affected tissue over a sustained period of time from a single administration. The technology consists of three interrelated components: a biocompatible mesh scaffold, which is designed to maximize surface area for drug release while maintaining underlying tissue function; an engineered elastomeric matrix, a polymeric matrix composed of polymers having elastic characteristics, which has advanced physical properties resulting in implants with 'shape memory' that dynamically adapt to nasal anatomy; and a versatile polymer-drug complex, which can be customized for the treatment of various chronic diseases treatable with ENT delivery to achieve the desired drug dose and drug elution rate.

LYR-210

LYR-210 is designed to treat CRS patients both with and without nasal polyps who have failed previous medical management and have not undergone endoscopic sinus surgery. A pivotal Phase 3 program of LYR-210, called the ENLIGHTEN program, consists of two pivotal trials and is ongoing.

LYR-220

The company is developing its second pipeline product candidate, LYR-220, for use in CRS patients who continue to require treatment to manage CRS symptoms despite having had sinus surgery. LYR-220 is also designed to utilize MF, and employs a larger matrix designed for patients whose nasal cavity is enlarged due to sinus surgery. A Phase 2 clinical trial of LYR-220, called BEACON, is ongoing.

Strategy

The key elements of the company's strategy are to complete the development and secure FDA approval of LYR-210 for the treatment of CRS; advance its second product candidate, LYR-220, through clinical development to provide a comprehensive solution for CRS patients who have failed medical management and surgery; and build a commercialization infrastructure in the U.S. market for LYR-210 and LYR-220.

Solution for CRS

LYR-210 is an anti-inflammatory implantable drug matrix that is designed to consistently and locally elute MF to the inflamed mucosal tissue for up to six months in surgically naïve CRS patients who fail medical management. MF, the active ingredient in various FDA-approved drugs, has a well-established efficacy and safety profile, which will support the development process for LYR-210. LYR-210 is designed to enable sustained drug delivery at difficult-to-access nasal inflammation sites without the need for patient compliance, while avoiding the systemic side effects associated with oral steroids. LYR-210 is designed to be administered in a brief, non-invasive, in-office procedure by an ENT physician under endoscopic visualization via a single-use applicator. The company is developing its second pipeline product candidate, LYR-220, for use in CRS patients who continue to require treatment to manage CRS symptoms despite having had sinus surgery. LYR-220 is also designed to utilize MF, and employs a larger matrix designed for patients whose nasal cavity is enlarged due to sinus surgery. LYR-220 is designed as a potential preferred alternative to revision sinus surgery and post-surgical medical management.

LYR-210 and LYR-220, if approved, would be the only products able to deliver up to six months of continuous topical treatment in a single administration to treat the broad spectrum of CRS patients who fail medical management, including pre- and post-surgery patients.

Clinical Pipeline

LYR-210 for the Treatment of CRS

LYR-210, if successfully developed and approved, has the potential to become a preferred alternative to surgery for the treatment of CRS. It is the only product candidate that the company is aware of that is designed to provide up to six months of local delivery of anti-inflammatory medication with a single administration. The brief, non-invasive, in-office procedure allows for its implantation without the need for surgery. Further, the company's studies have shown that LYR-210 has the potential to be an effective treatment for both patients with and without polyps. LYR-210 has the potential to be a safe, effective, and broadly applicable CRS treatment, designed to enhance patient comfort and physician experience and eliminate patient compliance issues associated with other CRS treatments, such as intranasal steroid sprays, while achieving reduced costs compared to other CRS treatments, such as sinus surgery.

LYR-210 is an investigational local drug delivery system designed to fit within, and conform to, the confined space of a surgically naïve patient's middle meatus, an air-containing space that plays a fundamental role in drainage of the paranasal sinuses. LYR-210 consists of MF, the active ingredient in various FDA-approved drugs, embedded in biocompatible polymers to aid in the controlled and sustained delivery of MF to the sinonasal mucosal tissue from a single drug administration. LYR-210 has a tubular braid configuration with a uniform diamond pattern throughout and is 13 mm in diameter and 10 mm in length in the unconstrained state. It has elastic properties to promote patient comfort and is designed to be self-retaining against the mucosal tissue to allow effective drug transfer.

LYR-210 is intended to be administered bilaterally into the non-operated middle meatus by an ENT physician under endoscopic visualization via a provided, single use applicator. It is designed for office-based administration performed with topical anesthesia. Once administered, LYR-210 is designed to gradually release MF to the inflamed mucosal tissue for up to six months from a single administration. LYR-210 can be removed at six months or earlier at the physician's discretion using standard instruments and, if needed, replaced with a new LYR-210. LYR-210 is made with bioresorbable polymers that, if left in place, would gradually dissolve over time.

The LYR-210 Phase 3 program consists of two pivotal trials - ENLIGHTEN I and ENLIGHTEN II. ENLIGHTEN I is a 52-week, multi-center, randomized, blinded, sham-controlled trial designed to evaluate the efficacy and safety of LYR-210 in approximately 180 surgically naïve CRS who have failed prior medical management. The trial consists of three stages - a 2- to 4-week screening and run-in stage, a 24-week treatment stage followed by a 28-week safety extension stage. In the treatment stage, patients are randomized 2:1 to receive LYR-210 (7,500 µg) or sham-procedure. At the end of the treatment stage, patients in the control group receive crossover LYR-210 treatment while patients in the LYR-210 group are re-randomized 1:1 to either receive a crossover sham-procedure or a repeat treatment with LYR-210 (7,500 µg). The ENLIGHTEN I trial was initiated in February 2022.

ENLIGHTEN II is a 24-week, multi-center, randomized, blinded, sham-controlled trial designed to evaluate the efficacy and safety of LYR-210 in approximately 180 surgically naïve CRS patients who have failed prior medical management. The trial consists of two stages - a 2- to 4-week screening and run-in stage and a 24-week treatment stage. ENLIGHTEN II was initiated in September 2022.

On November 8, 2022, the company announced a pause in enrollment of ENLIGHTEN II to align with internal manufacturing timelines for clinical trial supply. The company will focus its resources on the timely completion of ENLIGHTEN I during this period. Moving forward, the company intends to utilize its internal manufacturing capabilities in order to supply the entire ENLIGHTEN clinical program and mitigate any further risk to overall program timelines. Focusing on the company's internal manufacturing capabilities reduces risk associated with technology transfer to third parties. The company expects to resume enrollment in ENLIGHTEN II in the second quarter of 2023.

The company's Phase 2 LANTERN clinical trial for LYR-210 was initiated in May 2019. In December 2020, the company reported positive topline results from its Phase 2 LANTERN clinical trial.

LYR-220 for the Treatment of CRS

The company is developing its second pipeline product candidate, LYR-220, for use in CRS patients who continue to require treatment to manage CRS symptoms despite having had sinus surgery. LYR-220 is a new investigative therapy for CRS patients with and without nasal polyps that have failed medical management and have had a prior endoscopic sinus surgery. In the treatment paradigm, LYR-220, if approved, is positioned for use in patients post-surgical intervention who continue to have recurrent CRS symptoms or relapse, as a potential preferred alternative to revision surgery. LYR-220 is also designed to utilize MF, and employs a larger matrix designed for patients whose nasal cavity is enlarged due to sinus surgery. The company estimates that 40% of patients that present to an ENT physician with CRS have had a prior surgery. These patients represent the addressable market for LYR-220.

LYR-220 is meaningfully differentiated from approved products because, if successfully developed and approved, it would be the only product able to deliver up to six months of topical treatment in a single administration to treat both polyp and non-polyp post-surgery CRS patients who fail medical management. Further, with respect to the mAbs, LYR-220 is differentiated because it would provide localized delivery so as to avoid systemic side effects with the added benefit of being a significantly more economical treatment alternative.

In November 2021, the company initiated the Phase 2 BEACON clinical trial for LYR-220 which is a controlled, randomized, parallel-group study to evaluate safety, tolerability, pharmacokinetics, and efficacy comparing two designs of LYR-220 to control over a 24-week period in approximately 40 symptomatic adult CRS subjects who have had a prior bilateral sinus surgery. The trial consists of two parts - Part 1 is designed to assess the feasibility of placement and procedural refinements in up to 10 patients who will receive one of two designs of LYR-220; in Part 2, approximately 40 patients will be randomized 1:1 to receive either one of two designs of LYR-220 or sham procedure. The primary endpoint of the trial is incidence of product-related unexpected serious adverse events. Other safety endpoints include incidence of serious and non-serious adverse events, new or worsening of abnormal clinically significant findings in lab values, ophthalmology exams, and nasal endoscopies. Efficacy endpoints include change from baseline in 3CS, SNOT-22 and other CRS symptoms, change from baseline (CFBL) in ethmoid opacification by CT, and use of rescue treatments.

In September 2022, the company announced positive initial data from the Part 1, non-randomized portion of the BEACON trial, demonstrating the feasibility and tolerability of LYR-220 placement bilaterally in this patient population. All six patients were treated for at least six weeks and no serious or unexpected product related adverse events have been reported. Enrollment is complete in the Part 2, randomized stage of the BEACON trial.

Intellectual Property

Patents and Patent Applications

As of December 31, 2022, the company owned 24 issued U.S. patents, 16 foreign issued patents, 4 PCT pending applications, 7 U.S. pending applications, and 24 foreign pending applications, out of which 17 issued U.S. patents, 16 foreign issued patents, 7 U.S. pending applications, and 24 foreign pending applications are directed to its technology, LYR-210, and LYR-220.

All technology to the company's business has been developed in-house and is protected with patents and patent applications in three major lineages, along with the beginning of a fourth, more recent lineage of patent applications. The first lineage dates from 2009 and provides protection potentially until 2030, exclusive of possible patent term adjustments or extensions or other forms of exclusivity. This first lineage includes issued patents in the U.S., Europe, Japan, Canada, and Great Britain that are not limited to any particular drug, site of delivery, or patient condition, but specify features of the implant, delivery system, method, and polymers. The second lineage dates from 2015 and provides protection potentially until 2036, exclusive of possible patent term adjustments or extensions or other forms of exclusivity. This second lineage includes issued patents with ENT-specific method claims directed to the specific drug, site of delivery (i.e., middle meatus), and patient condition, with allowed and issued cases in the U.S., China, and Japan along with numerous pending applications in the U.S., Europe, Japan, Canada, China, and Great Britain. The third lineage dates from 2017 with the prospect of patent protection potentially until 2038, exclusive of possible patent term adjustments or extensions or other forms of exclusivity. This third lineage attempts to capture the products drug release features and patient results from the recent clinical trial. It includes allowed cases in Australia and Great Britain, along with pending applications in the U.S., Canada, Australia, Europe, Korea, Singapore, China, and Japan. The fourth lineage dates from 2021 and provides protection potentially until 2042, exclusive of possible patent term adjustments or extensions or other forms of exclusivity. The fourth lineage is directed to a higher drug load (7500 ug). The lineage stems from a patent application filed under the Patent Cooperation Treaty that will enter the National Phase in September of 2023.

Trademarks and Trade Secrets

The company also relies upon trade secrets, know-how, and continuing technological innovation, and may pursue licensing opportunities in the future, to develop and maintain its competitive position. The company seeks to protect its proprietary rights through a variety of methods, including confidentiality agreements, invention assignment agreements, and non-solicitation and non-compete agreements with suppliers, employees, consultants, and others who may have access to proprietary information.

Government Regulation and Product Approval

In the United States, the company is subject to extensive regulation by the FDA, which regulates drugs under the Federal Food, Drug, and Cosmetic Act, or the FDCA, and its implementing regulations, and other federal, state, and local regulatory authorities. The company's regulatory strategy is to pursue development of LYR-210 as a Section 505(b)(2) New Drug Application (NDA).

Research and Development Expenses

The company's research and development expenses were $38.8 million for the year ended December 31, 2022.

History

The company was founded in 2005. It was incorporated under the laws of the state of Delaware in November 2005 under the name WMR Biomedical, Inc. In 2018, the company changed its name to Lyra Therapeutics, Inc.