On March 2, 2023 Aeglea BioTherapeutics, Inc. (NASDAQ:AGLE), a clinical-stage biotechnology company developing a new generation of human enzyme therapeutics as innovative solutions for rare metabolic diseases, reported financial results for the fourth quarter and full year 2022, and provided program updates (Press release, Aeglea BioTherapeutics, MAR 2, 2023, View Source [SID1234628044]).

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"Since joining the company, I have been impressed by the programs and the potential impact that they may have on patient lives. In 2023, we are highly focused on execution, specifically the generation of data from our pegtarviliase Phase 1/2 clinical trial in Classical Homocystinuria and, assuming success with those data, preparations to advance into a potential pivotal trial," said Jeffrey Goldberg, president and chief executive officer of Aeglea. "We are also continuing to work with our partner Immedica Pharma AB to support the EMA [European Medicines Agency] review process for the Marketing Authorization Application for pegzilarginase for the treatment of Arginase 1 Deficiency. A decision by the EMA regarding the approval of the pegzilarginase Marketing Authorization Application is expected in late 2023. By delivering on these objectives, I believe we will be in a strong position to bring forward solutions that can positively impact the lives of our patient communities."

Program and Corporate Updates

Pegtarviliase in Homocystinuria

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Received Fast Track Designation from the U.S. Food and Drug Administration (FDA). Fast Track Designation is designed to expedite the FDA’s review of innovative, new drugs that demonstrate the potential to address unmet medical need.
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Announced in late November 2022 the completion of dosing of two patients in the third cohort of the Phase 1/2 clinical trial. Patients in the third cohort receive 1.35 mg/kg of pegtarviliase administered subcutaneously once weekly.

Pegzilarginase in Arginase 1 Deficiency

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Transitioning patients who participated in the PEACE Phase 3 long-term extension (LTE) and Phase 1/2 open-label extension (OLE) studies into one simplified open-label trial. The PEACE LTE and Phase 1/2 OLE studies were closed in the first quarter of 2023.
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Continuing to progress the review of the Marketing Authorization Application submission with the EMA for the potential approval of pegzilarginase. EMA approval can facilitate possible patient access and regulatory approval in many other geographies, including Latin America and the Middle East.

Corporate

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Appointed Jeffrey Goldberg, a highly experienced executive with strong operational and rare disease background, as president and chief executive officer.
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Strengthened senior management team with the promotions of Linda Neuman, MD, MBA, to chief medical officer and Cortney Caudill, MBA, to the newly created role of chief product officer. Ms. Caudill will serve as a strategic leader and team supervisor of Aeglea’s clinical programs.

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Implemented changes to corporate structure to increase operational efficiency. Additionally, the company halted preclinical work on Cystinuria and other unnamed pipeline programs. The company will evaluate potential strategic options for these programs in order to maximize their value.

Upcoming Events

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ACMG Annual Clinical Genetics Meeting, Salt Lake City, Utah
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Long-Term Efficacy and Safety of Pegzilarginase for Arginase 1 Deficiency: 2 Years of Experience in the Phase 2 Extension Study
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Featured platform presentation on March 16, 2023 at 8:45-9:00 am MST

Fourth Quarter 2022 Financial Results

Aeglea recognized development fee revenues of $0.2 million in the fourth quarter of 2022, as a result of its license and supply agreement with Immedica Pharma AB for the commercial rights to pegzilarginase in Europe and several countries in the Middle East (License and Supply Agreement). The revenues recorded in the fourth quarter of 2022 are related to manufacturing services. Aeglea recognized $3.6 million for the fourth quarter of 2021 in development fee revenues.

Research and development expenses totaled $14.3 million for the fourth quarter of 2022 and $16.8 million for the fourth quarter of 2021. The decrease was primarily related to a decrease in Biologics License Application (BLA) activities for pegzilarginase and reductions in headcount and recruiting activities.

General and administrative expenses totaled $5.0 million for the fourth quarter of 2022 and $7.3 million for the fourth quarter of 2021. This decrease was primarily due to a reduction in commercialization activities for pegzilarginase and a reduction in headcount and related expenses.

Net loss totaled $18.8 million and $20.4 million for the fourth quarter of 2022 and 2021, respectively, which includes non-cash stock compensation expense of $1.4 million and $2.1 million for the fourth quarter of 2022 and 2021, respectively.

Full Year 2022 Financial Results

As of December 31, 2022, Aeglea had available cash, cash equivalents, marketable securities and restricted cash of $57.3 million. The company expects its cash, cash equivalents and marketable securities will enable it to fund its operating expenses and capital expenditure requirements into the fourth quarter of 2023.

Aeglea recognized development fee revenues of $2.3 million in the year ended December 31, 2022, as a result of its License and Supply Agreement. The revenues recorded in the year ended December 31, 2022 are primarily related to the PEACE Phase 3 clinical trial and the submission of the BLA. Aeglea recognized $18.7 million in license and development fee revenues for the year ended December 31, 2021.

Research and development expenses totaled $58.6 million for the year ended December 31, 2022 and $57.1 million for the year ended December 31, 2021. The increase was primarily associated with activities involved in closing the PEACE Phase 3 trial and initiation activities for the new open-label study for the treatment of patients with Arginase 1 Deficiency and Investigational New Drug-enabling activities conducted for AGLE-325 in the first half of the year. These increases were partially offset by decreases due to the completion of non-clinical toxicology studies for pegtarviliase and a reduction in preclinical lab activities.

General and administrative expenses totaled $28.5 million for the year ended December 31, 2022 and $27.3 million for the year ended December 31, 2021. This increase was primarily due to an increase in commercial capabilities and infrastructure expenses in the first half of the year.

Net loss totaled $83.8 million and $65.8 million for the years ended December 31, 2022 and 2021, respectively, which includes non-cash stock compensation expense of $7.1 million and $8.0 million for the years ended December 31, 2022 and 2021, respectively

About Pegtarviliase in Homocystinuria

Pegtarviliase is a novel recombinant human enzyme, which is engineered to reduce elevated levels of total homocysteine circulating in the plasma by degrading the amino acid homocysteine and its dimer. Pegtarviliase is currently being studied in a Phase 1/2 clinical trial for the treatment of patients with Classical Homocystinuria, a rare inherited disorder of methionine metabolism that results in elevated levels of total homocysteine. Homocysteine accumulation plays a key role in multiple progressive and serious disease-related complications, including lens dislocation, skeletal abnormalities, vascular complications and neurologic effects, as well as the potential for sudden and early death. In preclinical studies, pegtarviliase improved important disease-related abnormalities and survival in a mouse model of Homocystinuria. Pegtarviliase has received both U.S. and EU Orphan Drug Designation as well as U.S. Rare Pediatric Disease and Fast Track Designations.

About Pegzilarginase in Arginase 1 Deficiency

Pegzilarginase is a novel recombinant human enzyme engineered to degrade the amino acid arginine and has been shown to rapidly and sustainably lower levels of the amino acid arginine in plasma. Aeglea is developing pegzilarginase for the treatment of people with Arginase 1 Deficiency (ARG1-D), a rare debilitating and progressive disease characterized by the accumulation of arginine. ARG1-D presents in early childhood and patients experience spasticity, seizures, developmental delay, intellectual disability and early mortality. The PEACE Phase 3 clinical trial met its primary endpoint with a 76.7% reduction in mean plasma arginine compared to placebo. Additionally, 90.5% of pegzilarginase treated patients achieved normal plasma arginine levels.