A Phase 3 Open-Label Study of Safety, Pharmacokinetics, and Activity of Weekly Subcutaneous Pegzilarginase in Subjects <24 Months Old With Arginase 1 Deficiency

This is an open-label, multicentre study to evaluate the safety, PK, and activity (PD) of weekly subcutaneous (SC) administration of pegzilarginase in subjects with ARG1-D who are < 24 months of age. The study consists of a screening period of up to 4 weeks, a subsequent 12-week treatment period, and a safety follow-up period of 8 weeks.

Start Date30 Aug 2024

Sponsor / Collaborator

Immedica Pharma AB

NCT05676853 / TerminatedPhase 3

A Phase 3 Open-Label Study of Safety of Weekly Subcutaneous Pegzilarginase in Subjects With Arginase 1 Deficiency

This is an open-label, multicenter study to evaluate the safety of weekly SC administration of pegzilarginase over 12 months in subjects with ARG1-D. The study consists of a screening period of up to 4 weeks, a subsequent 12-month treatment period, and a Safety Follow-Up Visit 2 weeks after the last treatment.

Start Date04 Apr 2023

Sponsor / Collaborator

Spyre Therapeutics, Inc.

EUCTR2018-004837-34-AT / Unknown statusPhase 3

PEACE (Pegzilarginase Effect on Arginase 1 Deficiency Clinical Endpoints): A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of the Efficacy and Safety of Pegzilarginase in Children and Adults with Arginase 1 Deficiency

Start Date18 Jun 2019

Sponsor / Collaborator-

100 Clinical Results associated with Pegzilarginase (Aeglea Biotherapeutics)

100 Translational Medicine associated with Pegzilarginase (Aeglea Biotherapeutics)

100 Patents (Medical) associated with Pegzilarginase (Aeglea Biotherapeutics)

Literatures (Medical) associated with Pegzilarginase (Aeglea Biotherapeutics)

01 Feb 2024·EClinicalMedicine

Efficacy and safety of pegzilarginase in arginase 1 deficiency (PEACE): a phase 3, randomized, double-blind, placebo-controlled, multi-centre trial

Article

Author: Russo, Rossana Sanchez ; Neuman, Linda ; Diaz, George A ; Gasperini, Serena ; Enns, Gregory M ; Bubb, Gillian ; Sloan, Leslie S

Background:

Arginase 1 Deficiency (ARG1-D) is a rare debilitating, progressive, inherited, metabolic disease characterized by marked increases in plasma arginine (pArg) and its metabolites, with increased morbidity, substantial reductions in quality of life, and premature mortality. Effective treatments that can lower arginine and improve clinical outcomes is currently lacking. Pegzilarginase is a novel human arginase 1 enzyme therapy. The present trial aimed to demonstrate efficacy of pegzilarginase on pArg and key mobility outcomes.

Methods:

This Phase 3 randomized, double-blind, placebo-controlled, parallel-group clinical trial (clinicaltrials.govNCT03921541, EudraCT 2018-004837-34), randomized patients with ARG1-D 2:1 to intravenously/subcutaneously once-weekly pegzilarginase or placebo in conjunction with their individualized disease management. It was conducted in 7 countries; United States, United Kingdom, Canada, Austria, France, Germany, Italy. Primary endpoint was change from baseline in pArg after 24 weeks; key secondary endpoints were change from baseline at Week 24 in Gross Motor Function Measure part E (GMFM-E) and 2-min walk test (2MWT). Full Analysis Set was used for the analyses.

Findings:

From 01 May 2019 to 29 March 2021, 32 patients were enrolled and randomized (pegzilarginase, n = 21; placebo, n = 11). Pegzilarginase lowered geometric mean pArg from 354.0 μmol/L to 86.4 μmol/L at Week 24 vs 464.7 to 426.6 μmol/L for placebo (95% CI: -67.1%, -83.5%; p < 0.0001) and normalized levels in 90.5% of patients (vs 0% with placebo). In addition, clinically relevant functional mobility improvements were demonstrated with pegzilarginase treatment. These effects were sustained long-term through additional 24 weeks of subsequent exposure. Pegzilarginase was well-tolerated, with adverse events being mostly transient and mild/moderate in severity.

Interpretation:

These results support pegzilarginase as the first potential treatment to normalize pArg in ARG1-D and achieve clinically meaningful improvements in functional mobility.

Funding:

Aeglea BioTherapeutics.

01 Jan 2022·Lung Cancer-Targets and Therapy

Arginine Deprivation in SCLC: Mechanisms and Perspectives for Therapy.

Review

Author: Carpentier, Joséphine ; Pavlyk, Iuliia ; Szlosarek, Peter W ; Hall, Peter E ; Mukherjee, Uma

Arginine deprivation has gained increasing traction as a novel and safe antimetabolite strategy for the treatment of several hard-to-treat cancers characterised by a critical dependency on arginine. Small cell lung cancer (SCLC) displays marked arginine auxotrophy due to inactivation of the rate-limiting enzyme argininosuccinate synthetase 1 (ASS1), and as a consequence may be targeted with pegylated arginine deiminase or ADI-PEG20 (pegargiminase) and human recombinant pegylated arginases (rhArgPEG, BCT-100 and pegzilarginase). Although preclinical studies reveal that ASS1-deficient SCLC cell lines are highly sensitive to arginine-degrading enzymes, there is a clear disconnect with the clinic with minimal activity seen to date that may be due in part to patient selection. Recent studies have explored resistance mechanisms to arginine depletion focusing on tumor adaptation, such as ASS1 re-expression and autophagy, stromal cell inputs including macrophage infiltration, and tumor heterogeneity. Here, we explore how arginine deprivation may be combined strategically with novel agents to improve SCLC management by modulating resistance and increasing the efficacy of existing agents. Moreover, recent work has identified an intriguing role for targeting arginine in combination with PD-1/PD-L1 immune checkpoint inhibitors and clinical trials are in progress. Thus, future studies of arginine-depleting agents with chemoimmunotherapy, the current standard of care for SCLC, may lead to enhanced disease control and much needed improvements in long-term survival for patients.

01 Jul 2021·Journal of inherited metabolic diseaseQ2 · MEDICINE

Clinical effect and safety profile of pegzilarginase in patients with arginase 1 deficiency

Q2 · MEDICINE

Article

Author: Schulze, Andreas ; Bubb, Gillian ; Zori, Roberto T. ; Diaz, George A. ; Quinn, Anthony G. ; Enns, Gregory M. ; Leão‐Teles, Elisa ; Merritt, J. Lawrence ; McNutt, Markey C. ; Bannick, Allison ; Potts, Susan L. ; Sloan, Leslie S. ; Batzios, Spyros

Abstract:

Hyperargininemia in patients with arginase 1 deficiency (ARG1‐D) is considered a key driver of disease manifestations, including spasticity, developmental delay, and seizures. Pegzilarginase (AEB1102) is an investigational enzyme therapy which is being developed as a novel arginine lowering approach. We report the safety and efficacy of intravenously (IV) administered pegzilarginase in pediatric and adult ARG1‐D patients (n = 16) from a Phase 1/2 study (101A) and the first 12 weeks of an open‐label extension study (102A). Substantial disease burden at baseline included lower‐limb spasticity, developmental delay, and previous hyperammonemic episodes in 75%, 56%, and 44% of patients, respectively. Baseline plasma arginine (pArg) was elevated (median 389 μM, range 238‐566) on standard disease management. Once weekly repeat dosing resulted in a median decrease of pArg of 277 μM after 20 cumulative doses (n = 14) with pArg in the normal range (40 to 115 μM) in 50% of patients at 168 hours post dose (mean pegzilarginase dose 0.10 mg/kg). Lowering pArg was accompanied by improvements in one or more key mobility assessments (6MWT, GMFM‐D & E) in 79% of patients. In 101A, seven hypersensitivity reactions occurred in four patients (out of 162 infusions administered). Other common treatment‐related adverse events (AEs) included vomiting, hyperammonemia, pruritus, and abdominal pain. Treatment‐related serious AEs that occurred in five patients were all observed in 101A. Pegzilarginase was effective in lowering pArg levels with an accompanying clinical response in patients with ARG1‐D. The improvements with pegzilarginase occurred in patients receiving standard treatment approaches, which suggests that pegzilarginase could offer benefit over existing disease management.

News (Medical) associated with Pegzilarginase (Aeglea Biotherapeutics)

18 Sep 2024

·www.immedica.com

Immedica initiates a phase 3 pediatric study for Loargys® (pegzilarginase) in arginase 1 deficiency

Stockholm, September 18, 2024: Immedica announces today that the first subject has been dosed in the phase 3 pediatric study (CAEB1102-301A) for Loargys® (pegzilarginase) in arginase 1 deficiency (ARG1-D). Loargys is approved in the EU and Great Britain for the treatment of ARG1-D in adults, adolescents and children aged 2 years and older. The initiation of a clinical study in children below 2 years of age is of high importance in this progressive disease exposing patients to elevated toxic levels of arginine from birth. Study CAEB1102-301A is a phase 3, open-label, single-arm, non-controlled, repeat dosing, international, multicenter study to evaluate the safety, pharmacokinetics, and activity (pharmacodynamics) of weekly subcutaneous administration of pegzilarginase over 12 weeks in subjects with ARG1-D who are < 24 months of age. “The approval of Loargys for patients with ARG1-D is addressing a high unmet medical need in this disease, providing the first disease-modifying treatment. However, Immedica is committed to serve all patients with the disease and to investigate the ability to treat patients as early as possible, before any effects of the disease in the crucial first years of life, a particularly important period of child development”, says Mattias Rudebeck, Head of Global Integrated Evidence Generation and Global Medical Head for Genetic and Metabolic Diseases at Immedica. Dr Arunabha Ghosh at Bradford Royal Infirmary in the United Kingdom and the international coordinating investigator for the study says: “As an experienced clinical study center for the previous pivotal study (PEACE) with pegzilarginase we have earned great insights in the efficacy and safety data for pegzilarginase in ARG1-D. Data enabling the initiation of treatment already in the first years of life could have substantial impact on the course of the disease in the future”. “Immedica is a fast-growing pharmaceutical company, and with the increased opportunities in our pipeline, our organization is evolving with the building of our new scientific function with senior experts in data generation strategies and clinical studies,” says Anders Edvell, Chief Executive Officer. He continues: “Over the last years, our company has entered into new types of product licensing and acquisition, and clinical studies can provide further product development and growth. In addition, real-world data is increasingly important, and a clinical research function will help provide balanced scientific data that can improve clinical care and meet the needs of regulators, payers, clinicians, and allied care professionals to make good healthcare decisions.” About CAEB1102-301A Study CAEB1102-301A is a phase 3, open-label, single-arm, non-controlled, repeat dosing, international, multicentre study to evaluate the safety, pharmacokinetics, and activity (pharmacodynamics) of weekly subcutaneous administration of pegzilarginase over 12 weeks in subjects with ARG1-D who are < 24 months of age. The study is part of the Paediatric Investigation Plan (PIP) for Loargys as agreed with the Paediatric Committee (PDCO) at the European Medicines Agency (EMA) and is planned to be performed in the United Kingdom, Austria and Portugal. About Loargys® Loargys (pegzilarginase) is a novel recombinant human enzyme and has been shown to rapidly and sustainably lower levels of the amino acid arginine and its toxic metabolites in plasma accompanied by improvements in clinical outcomes. Loargys is approved in the EU and Great Britain for the treatment of ARG1-D, also known as hyperargininaemia, in adults, adolescents and children aged 2 years and older, and is the first and only disease modifying treatment for ARG1-D. The EU product information for Loargys is found here. About ARG1-D ARG1-D is one of the eight urea cycle disorder (UCD) subtypes. It shares overlapping features with other UCDs and the most prominent is the impairment in excreting nitrogen. However, in ARG1-D, hyperammonemia is generally less severe and instead these patients show spasticity, which other subtypes do not. The principal defect in ARG1-D leads to accumulation of plasma arginine and its toxic metabolites, which occurs in almost all patients with this disorder. Patients are often diagnosed in late infancy or early childhood and the symptoms include spasticity, seizures, developmental delay, intellectual disability, and early mortality. About Immedica Immedica is a pharmaceutical company, headquartered in Stockholm, Sweden, focused on the commercialization of medicines for rare diseases and specialty care products. Immedica’s capabilities cover marketing and sales, compliance, pharmacovigilance, quality assurance, regulatory, medical affairs and market access, as well as a global distribution network serving patients in more than 50 countries. Immedica is fully dedicated to helping those living with diseases which have a large unmet medical need. Immedica’s therapeutic areas are within genetic & metabolic diseases, hematology & oncology and specialty care. Immedica was founded in 2018 by the investment company Impilo and Buy-in-Management. Today Immedica employs more than 120 people across Europe, the Middle East and the US. For more information visit www.immedica.com Immedica contact: Linda Holmström Head of Communication linda.holmstrom@immedica.com + 46 708 73 40 95 We believe we have an important role to fill in society – bringing new, innovative treatments to patients with rare diseases. Focus areas are within genetic & metabolic diseases, hematology & oncology and specialty care. We operate products from phase 2 and all the way to mature products. ESG is an integrated part of our business model. Stay up to date with our latest news. Telephone: +46 (0) 8 533 39 500 E-mail: info@immedica.com

Phase 3Drug Approval

29 Feb 2024

·www.prnewswire.com

Spyre Therapeutics Reports Fourth Quarter and Full Year 2023 Financial Results and Provides Corporate Update

Announced corporate name change to Spyre Therapeutics; appointment of Cameron Turtle, DPhil, as Chief Executive Officer; and began trading on Nasdaq under the symbol "SYRE" SPY001, an anti-α4β7 antibody engineered for infrequent, subcutaneous dosing, demonstrated an updated half-life of 22 days, a greater than three-fold increase relative to vedolizumab in non-human primate pharmacokinetic data recently presented at ECCO; remains on track to begin first-in-human studies in the first half of 2024, with interim proof-of-concept data expected year-end 2024 SPY002, an anti-TL1A antibody designed for enhanced potency to both TL1A monomers and trimers, and extended half-life compared to existing molecules, remains on track to begin first-in-human studies in the second half of 2024 Raised $180 million in private placement equity financing with participation from new and existing investors $340 million of cash, cash equivalents, marketable securities, and restricted cash as of December 31, 2023, with expected runway into the second half of 2026, through multiple clinical readouts WALTHAM, Mass., Feb. 29, 2024 /PRNewswire/ -- Spyre Therapeutics, Inc. ("Spyre" or the "Company") (NASDAQ:SYRE), a biotechnology company advancing a pipeline of investigational antibody therapeutics with the potential to transform the treatment of inflammatory bowel disease ("IBD"), today announced its fourth quarter and full year 2023 financial results and provided program and corporate updates. "In 2023, we built the foundation required to advance our mission of creating IBD therapies that provide meaningful improvements in both efficacy and convenience compared to today's standard of care. Beginning with a highly unique portfolio of three promising drug candidates to what we consider the most critical targets in IBD, including α4β7, TL1A, and IL-23, we capitalized the company with nearly $400 million from top-tier investors while also attracting a talented and passionate management team and Board of Directors," said Cameron Turtle, DPhil., Chief Executive Officer. "As we look forward to 2024, our ambitions will come into focus as we enter clinical studies across multiple programs and begin to demonstrate potential best-in-class properties of our investigational medicines. We anticipate initiating Phase 2 evaluation of rational therapeutic combinations in IBD patients in 2025." Development Pipeline Overview and Update The Company's approach combines best-in-class antibody engineering, rational therapeutic combinations, and precision immunology with the goal of maximizing efficacy, safety, and convenience of its IBD treatments under development. IBD is a chronic condition characterized by inflammation within the gastrointestinal tract, including two main disorders: ulcerative colitis ("UC") and Crohn's disease ("CD"). In the United States, it is estimated that approximately 2.4 million individuals are diagnosed with IBD. The Company has four programs in preclinical development, three of which are targets in IBD validated by third parties. The fourth program is a novel, undisclosed target. The Company is also researching rational combinations of its therapeutic antibody product candidates to target IBD. All three validated targets offer the potential for effective and safe treatment of UC and CD as a monotherapy or in combination, with the potential advantage of infrequent subcutaneous dosing. SPY001 – a highly potent and selective investigational anti-α4β7 monoclonal antibody engineered with half-life extension technology and formulated for high concentration and subcutaneous, infrequent dosing. In the third quarter of 2023, the Company selected the SPY001 development candidate, which is currently progressing through IND-enabling studies and is expected to enter first-in-human ("FIH") studies in the first half of 2024. In February 2024, expanded preclinical data for SPY001 was presented at the 19th Annual Congress of the European Crohn's and Colitis Organisation (ECCO), including head-to-head non-human primate pharmacokinetic data showing an updated half-life of 22 days, a greater than three-fold increase relative to vedolizumab. This data further supports our target human half-life for SPY001 of more than 35 days predicted by allometric scaling. Interim data from a healthy volunteer study are expected by the end of 2024. The Company expects pharmacokinetic data to demonstrate proof of concept for SPY001 to potentially be dosed subcutaneously in an every-eight-week or every-twelve-week dosing interval. SPY002 – a highly potent, selective, half-life extended, anti-TL1A investigational monoclonal antibody with potential best-in-class subnanomolar binding affinity for both the monomer and trimer forms of the target. The Company believes TL1A has emerged as one of the most promising targets in IBD and broader immunology indications. The Company has nominated two lead SPY002 development candidates and exercised its option to exclusively license related intellectual property rights under its agreement with Paragon Therapeutics. The Company's lead candidates bind both TL1A monomers and trimers and have in vitro subnanomolar potency and pharmacokinetic half-lives that potentially exceed all clinical-stage TL1A antibodies. In February 2024, preclinical data for a lead SPY002 development candidate was presented at the 19th Annual ECCO Congress demonstrating subnanomolar binding affinity and potency, as well as a pharmacokinetic half-life of 24 days in non-human primates, which represents a two to three-fold increase compared to clinical-stage anti-TL1As. The Company expects to begin FIH studies of one or both SPY002 candidates in the second half of 2024 with healthy volunteer interim data expected in the first half of 2025. If successful, one SPY002 candidate would then advance into additional clinical development. SPY003 – a highly potent and selective investigational monoclonal antibody targeting the p19 subunit of IL-23 engineered with half-life extension technology. The Company continues preclinical development efforts on a potential best-in-class IL-23 monoclonal antibody. Recent data from the Phase 3 SEQUENCE study of risankizumab versus ustekinumab in Crohn's disease validates the Company's targeting of the p19 subunit as it demonstrated superiority to targeting the p40 subunit common to IL-12 and IL-23. The Company expects to nominate a development candidate in mid-2024 and move into IND-enabling studies in the second half of 2024. Recent Corporate Updates In February 2024, the Company announced the appointment of Mark C. McKenna, former Chairman, President and CEO of Prometheus Biosciences, Inc., to its Board of Directors. Mr. McKenna's track record of corporate leadership, product development, and value creation will be instrumental to guide the Company as it advances its potentially best-in-class IBD portfolio. In December 2023, the Company announced $180 million in gross proceeds from a private placement equity financing with broad participation from both new and existing investors, extending cash runway into the second half of 2026. In November 2023, the Company announced its name change to Spyre Therapeutics and the appointment of Cameron Turtle as Chief Executive Officer and also a member of the Company's Board of Directors. The Company also announced the appointments of industry veterans Jeffrey Albers and Laurie Stelzer to its Board of Directors. In November 2023, the Company held a Special Meeting of Stockholders wherein all four proposals were approved, including the conversion of the Company's Series A Preferred Stock to common stock and an increase to the Company's authorized shares. Fourth Quarter 2023 Financial Results Cash Position: As of December 31, 2023, Spyre had available cash and cash equivalents, marketable securities, and restricted cash of $339.6 million. Net cash used in operating activities was $31.0 million for the fourth quarter of 2023. In December 2023, the Company raised $180.0 million in gross proceeds, before deducting $10.9 million in placement agent fees and other offering costs, from a private placement of equity securities. Research and Development (R&D) expenses: R&D expenses totaled $33.7 million for the fourth quarter of 2023 and $14.3 million for the fourth quarter of 2022. The increase was primarily related to increases in preclinical development and manufacturing expenses for the Company's IBD pipeline including expenses related to the annual equity grant under our agreement with Paragon, partially offset by a decrease in expenses associated with the Company's legacy rare disease pipeline. General and Administrative (G&A) expenses: G&A expenses totaled $14.1 million for the fourth quarter of 2023 and $5.1 million for the fourth quarter of 2022. This increase was primarily due to an increase in stock compensation expense, as well as legal and other professional service fees related to the Spyre acquisition. Gain on Sale of In-Process Research & Development Asset: During the fourth quarter of 2023, the Company recognized an additional $1.8 million gain on the sale of the global rights of pegzilarginase driven by the receipt of a cash reimbursement from Immedica for a previous expenditure. Other (expense) income: Other (expense) income for the fourth quarter totaled $17.3 million expense primarily driven by an increase in the Company's CVR liability related to the increased likelihood of certain milestone payments related to pegzilarginase reimbursement in European markets, partially offset by interest earned on the Company's cash and marketable securities. Net Loss: Net loss totaled $63.2 million and $18.8 million for the fourth quarters of 2023 and 2022, respectively, which includes non-cash stock compensation expense of $17.3 million and $1.4 million for the fourth quarters of 2023 and 2022, respectively. About Spyre Therapeutics Spyre Therapeutics is a biotechnology company that aims to create the next-generation of inflammatory bowel disease (IBD) products by combining best-in-class antibody engineering, rational therapeutic combinations, and precision medicine approaches. Spyre's pipeline includes investigational extended half-life antibodies targeting α4β7, TL1A, and IL-23. For more information, please visit . Follow Spyre Therapeutics on social media: @spyretx and LinkedIn. Safe Harbor / Forward Looking Statements This press release contains "forward-looking" statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. All statements contained in this press release, other than statements of historical fact are forward-looking statements. These forward-looking statements include statements regarding the Company's future results of operations and financial position, business strategy, including the Company's potential success of developing therapeutics for IBD, the sufficiency of the Company's funding to support the development of its assets, the length of time that the Company believes its existing cash resources will fund its operations, its market size, its potential growth opportunities, its preclinical and future clinical development activities, including the expected timing of nomination of development candidates and submission of investigational new drug applications, the efficacy and safety profile of its product candidates, the potential therapeutic benefits and economic value of its product candidates, the timing and results of preclinical studies and clinical trials, including the commencement of FIH studies, the timing of data and whether the data demonstrates proof of concept, and the Company's planned regulatory activities including filing of INDs to support development and potential commercialization of product candidates. The words "believe," "may," "will," "potentially," "estimate," "continue," "anticipate," "predict," "target," "intend," "could," "would," "should," "project," "plan," "expect," the negatives of these terms, and similar expressions that convey uncertainty of future events or outcomes are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including the expected or potential impact of macroeconomic conditions, including inflationary pressures, rising interest rates, general economic slowdown or a recession, changes in monetary policy, the prospect of a shutdown of the U.S. federal government, volatile market conditions, financial institution instability, as well as geopolitical instability, including the ongoing military conflict in Ukraine, conflict in Israel and surrounding areas, and geopolitical tensions in China on the Company's operations, the potential impacts of the BIOSECURE Act bill if passed into law and those risks described in the Company's Quarterly Reports on Form 10-Q, Annual Reports on Form 10-K, as well as in other filings and reports that the Company makes from time to time with the Securities and Exchange Commission. Moreover, the Company operates in a very competitive and rapidly changing environment, and new risks emerge from time to time. It is not possible for the Company's management to predict all risks, nor can the Company assess the impact of all factors on the business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements it may make. In light of these risks, uncertainties, and assumptions, the forward-looking events and circumstances discussed in this press release may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although the Company believes that the expectations reflected in the forward-looking statements are reasonable, the Company cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur. The Company undertakes no obligation to update publicly any forward-looking statement for any reason after the date of this press release to conform these statements to actual results, to reflect changes in the Company's expectations, or otherwise, except as required by law. You should read press release with the understanding that the Company's actual results, levels of activity, performance, events, outcomes, and the timing of results and outcomes, and other circumstances may be materially different from what the Company expects. SOURCE Spyre Therapeutics, Inc.

Executive ChangeFinancial StatementPhase 2

09 Nov 2023

·www.prnewswire.com

Aeglea BioTherapeutics Reports Third Quarter 2023 Financial Results and Provides Corporate Update

Continued progress across the Company's potentially best-in-class inflammatory bowel disease (IBD) portfolio SPY001, a half-life extended anti-α4β7 antibody, is on track for an expected IND filing in the first half of 2024, with interim healthy volunteer, proof of concept pharmacokinetic data expected year-end 2024 SPY002, a half-life extended anti-TL1A antibody with potential best-in-class picomolar binding affinity for both the monomer and trimer forms of the target, is on track for expected IND filing in the second half of 2024 Stockholder vote scheduled for November 21 to allow conversion of preferred stock to common stock Strengthened leadership team with the appointments of Scott Burrows as Chief Financial Officer and Heidy King-Jones as Chief Legal Officer and Corporate Secretary $205 million of cash, cash equivalents, marketable securities, and restricted cash as of September 30, 2023, with expected runway into 2026 WALTHAM, Mass., Nov. 9, 2023 /PRNewswire/ -- Aeglea BioTherapeutics, Inc. ("Aeglea" or the "Company") (NASDAQ:AGLE), a biotechnology company advancing a pipeline of antibody therapeutics with the potential to transform the treatment of inflammatory bowel disease ("IBD"), today announced its third quarter 2023 financial results and provided program and corporate updates. "We have made significant progress in our first quarter following the Spyre acquisition towards our goal of creating new, best-in-class medicines for patients with IBD. We believe that our combination strategy and pipeline, including SPY001, an extended half-life anti-α4β7 antibody, and SPY002 a dual monomer / trimer anti-TL1A antibody with picomolar affinity and extended half-life, offer the potential to meaningfully improve both efficacy and convenience relative to today's standard of care," said Cameron Turtle, D.Phil., Chief Operating Officer of Aeglea. "In addition to progressing our portfolio towards first-in-human studies next year, we have built out our team with passionate and experienced biotechnology leaders." Development Pipeline Overview and Update With its acquisition of Spyre Therapeutics, Inc. ("Spyre") in June 2023, Aeglea shifted its disease focus to IBD. The Company's approach combines best-in-class antibody engineering, rational therapeutic combinations, and precision immunology with the goal of maximizing efficacy, safety, and convenience of its IBD treatments under development. IBD is a chronic condition characterized by inflammation within the gastrointestinal tract, including two main disorders: ulcerative colitis ("UC") and Crohn's disease ("CD"). In the United States, it is estimated that approximately 2.4 million individuals are diagnosed with IBD. The Company has four product candidates in preclinical development, three of which are validated targets in IBD. The fourth product candidate is a novel, undisclosed target. SPY001 – a highly potent and selective anti-α4β7 monoclonal antibody engineered with half-life extension technology and formulated for high concentration, convenient dosing. SPY001 is currently progressing through IND-enabling studies and is expected to enter first-in-human ("FIH") studies in the first half of 2024. Interim data from a healthy volunteer study are expected by the end of 2024. The Company expects pharmacokinetic data to demonstrate proof of concept for its ability to potentially reach an every-eight-week or every-twelve-week dosing interval. SPY002 – a highly potent and selective anti-TL1A monoclonal antibody engineered with half-life extension technology. The Company believes TL1A has emerged as one of the most promising targets in IBD and broader immunology indications. The Company's extensive discovery campaign has identified lead clones which bind both TL1A monomers and trimers with picomolar affinity and have in vitro potency and pharmacokinetic half-lives that exceed all clinical-stage TL1A antibodies. The Company expects to begin FIH studies of the SPY002 program in the second half of 2024 with healthy volunteer interim data expected in the first half of 2025. SPY003 – a highly potent and selective monoclonal antibody targeting the p19 subunit of IL-23 engineered with half-life extension technology. The Company continues preclinical development efforts on a potential best-in-class IL-23 monoclonal antibody. Recent data from the Phase 3 SEQUENCE study of risankizumab versus ustekinumab in Crohn's disease validates the Company's targeting of the p19 subunit as it demonstrated superiority to targeting the p40 subunit of IL-23. An IND/CTN is expected in 2025. Corporate Updates In October 2023, the Company filed a definitive proxy statement regarding the Special Meeting of Stockholders to be held on November 21, 2023 (the "Special Meeting"). At the Special Meeting, stockholders are expected to vote on four proposals, including the conversion of the Company's Series A Preferred Stock to common stock and an increase to the Company's authorized shares. In September 2023, the Company strengthened its leadership team with the appointments of industry veterans Scott Burrows, as Chief Financial Officer, and Heidy Abreu King-Jones, as Chief Legal Officer and Corporate Secretary. In September 2023, the Company completed a reverse stock split of all outstanding shares of common stock at a ratio of 1-for-25, with trading on a split-adjusted basis on the Nasdaq Capital Market beginning on September 8, 2023. In July 2023, the Company sold the global rights to pegzilarginase to Immedica Pharma AB ("Immedica") for $15 million in upfront cash proceeds and up to $100 million in contingent milestone payments. In November 2023, holders of the Company's contingent value rights (CVRs) are expected to receive a payment representing the Immedica sale proceeds net of expenses and adjustments pursuant to the CVR agreement entered into in connection with Aeglea's acquisition of Spyre. Third Quarter 2023 Financial Results Cash Position: As of September 30, 2023, Aeglea had available cash and cash equivalents, marketable securities, and restricted cash of $204.9 million. Research and Development (R&D) expenses: R&D expenses totaled $24.7 million for the third quarter of 2023 and $12.0 million for the third quarter of 2022. This increase was primarily related to increases in preclinical development and manufacturing expenses for the Company's IBD pipeline, partially offset by a decrease in expenses associated with the legacy Aeglea rare disease pipeline. General and Administrative (G&A) expenses: G&A expenses totaled $8.6 million for the third quarter of 2023 and $7.0 million for the third quarter of 2022. This increase was primarily due to an increase in legal and employee separation costs. Gain on Sale of In-Process Research & Development Asset: During the third quarter of 2023, the Company recognized a $14.6 million gain on the sale of the global rights of pegzilarginase to Immedica. Other Income and Expenses: Other Income and Expenses were a net $21.8 million expense in the third quarter of 2023, primarily driven by a $25.4 million non-cash forward contract liability expense related to an increase in fair value of the underlying Series A Preferred Stock between June 30, 2023 and the forward contract's settlement on July 7, 2023. Net Loss: Net loss totaled $40.1 million and $18.2 million for the third quarter of 2023 and 2022, respectively, which includes non-cash stock compensation expense of $4.8 million and $1.6 million for the third quarter of 2023 and 2022, respectively. About Aeglea BioTherapeutics In June 2023, Aeglea completed the asset acquisition of Spyre and shifted its disease focus to IBD. Aeglea is advancing a pipeline of antibody therapeutics with the potential to transform the treatment of IBD. Aeglea's approach combines novel antibody engineering, rational therapeutic combinations, and precision immunology with the goal of maximizing efficacy, safety, and convenience of treatments for IBD. The company is developing antibodies targeting α4β7, TL1A, and IL-23. For more information, please visit . Follow Aeglea BioTherapeutics on social media: @aegleabio and LinkedIn. Safe Harbor / Forward Looking Statements This press release contains "forward-looking" statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. All statements contained in this press release, other than statements of historical fact are forward-looking statements. These forward-looking statements include statements regarding stockholder approval of the conversion rights of the Series A Preferred Stock, any future payouts under the non-transferable contingent value right agreement (the "CVR Agreement"), the Company's ability to achieve the expected benefits or opportunities and related timing with respect to its asset acquisition of Spyre or to monetize its legacy assets, its future results of operations and financial position, business strategy, including the success of its refocus towards developing therapeutics for IBD, the length of time that the Company believes its existing cash resources will fund its operations, its market size, its potential growth opportunities, its preclinical and future clinical development activities, including the expected timing of submission of investigational new drug applications, the efficacy and safety profile of its product candidates, the potential therapeutic benefits and economic value of its product candidates, the timing and results of preclinical studies and clinical trials, including the timing of interim data and whether the data demonstrates proof of concept, the expected impact of macroeconomic conditions, including inflationary pressures, rising interest rates, general economic slowdown or a recession, changes in monetary policy, the prospect of a shutdown of the U.S. federal government, volatile market conditions, financial institution instability, as well as geopolitical instability, including the ongoing military conflict in Ukraine, conflict in Israel and surrounding areas, and geopolitical tensions in China on its operations, and the receipt and timing of potential regulatory designations, approvals and commercialization of product candidates. The words "believe," "may," "will," "potentially," "estimate," "continue," "anticipate," "predict," "target," "intend," "could," "would," "should," "project," "plan," "expect," the negatives of these terms, and similar expressions that convey uncertainty of future events or outcomes are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including those described in the Company's Quarterly Reports on Form 10-Q, Annual Reports on Form 10-K, as well as in other filings and reports that the Company makes from time to time with the Securities and Exchange Commission. Moreover, the Company operates in a very competitive and rapidly changing environment, and new risks emerge from time to time. It is not possible for the Company's management to predict all risks, nor can the Company assess the impact of all factors on the business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements it may make. In light of these risks, uncertainties, and assumptions, the forward-looking events and circumstances discussed in this press release may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although the Company believes that the expectations reflected in the forward-looking statements are reasonable, the Company cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur. The Company undertakes no obligation to update publicly any forward-looking statement for any reason after the date of this press release to conform these statements to actual results, to reflect changes in the Company's expectations, or otherwise, except as required by law. You should read press release with the understanding that the Company's actual results, levels of activity, performance, events, outcomes, and the timing of results and outcomes, and other circumstances may be materially different from what the Company expects. SOURCE Aeglea BioTherapeutics, Inc.

Executive ChangeAcquisitionPhase 3Financial Statement

100 Deals associated with Pegzilarginase (Aeglea Biotherapeutics)

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KEGG	Wiki	ATC	Drug Bank
D11695	-	-	DB14780

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hyperargininemia	EU	Immedica Pharma AB	15 Dec 2023
Hyperargininemia	IS	Immedica Pharma AB	15 Dec 2023
Hyperargininemia	LI	Immedica Pharma AB	15 Dec 2023
Hyperargininemia	NO	Immedica Pharma AB	15 Dec 2023

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Extensive stage Small Cell Lung Cancer	Phase 2	US	Spyre Therapeutics, Inc.	21 Dec 2017
Extensive stage Small Cell Lung Cancer	Phase 2	PR	Spyre Therapeutics, Inc.	21 Dec 2017
Refractory acute myeloid leukemia	Phase 2	US	Spyre Therapeutics, Inc.	01 Aug 2016
Refractory acute myeloid leukemia	Phase 2	CA	Spyre Therapeutics, Inc.	01 Aug 2016
Refractory Myelodysplastic Syndrome	Phase 2	US	Spyre Therapeutics, Inc.	01 Aug 2016
Refractory Myelodysplastic Syndrome	Phase 2	CA	Spyre Therapeutics, Inc.	01 Aug 2016
Relapsing acute myeloid leukemia	Phase 2	US	Spyre Therapeutics, Inc.	01 Aug 2016
Relapsing acute myeloid leukemia	Phase 2	CA	Spyre Therapeutics, Inc.	01 Aug 2016
Advanced Malignant Solid Neoplasm	Phase 2	US	Spyre Therapeutics, Inc.	01 Oct 2015

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03921541 (PEACE, CTgov)	Phase 3	Hyperargininemia	32	Pegzilarginase (Pegzilarginase)	asldzqukzj(vopbbhaavg) = epgjitughy tqlgnkuhzl (ctsonbjimq, debbarwcmh - aihkrxraef) View more	-	19 Nov 2024
NCT03921541 (PEACE, CTgov)	Phase 3	Hyperargininemia	32	Placebo (Placebo)	asldzqukzj(vopbbhaavg) = gmzjwsofjj tqlgnkuhzl (ctsonbjimq, nftqzrpooq - erfmehwoki) View more	-	19 Nov 2024
NCT03921541 (PEACE, SSIEM2022)	Phase 3	Hyperargininemia plasma arginine (pArg)	32	Pegzilarginase	ndlxnaxjwo(hbttshawye) = xxzdskuptj xwgmxunguy (vfjiwqphmv )	Positive	30 Aug 2022
NCT02488044 \| NCT03378531 (Pubmed \| J Inherit Metab Dis) Manual	Phase 1/2	Hyperargininemia	16	pegzilarginase	dxpbnqdanf(hrihcwhgpf) = five patients were all observed in 101A qvhsjwbgqw (rfmfdeuekw ) View more	Positive	01 Jul 2021
EAN2020	Not Applicable	Hyperargininemia	-	Pegzilarginase	ukjvnfkiii(lgivqnyyld) = mean change 46m ckyacdecme (pvbgllsixv ) View more	-	22 May 2020
SSIEM2019	Phase 1/2	Hyperargininemia plasma arginine	16	Pegzilarginase	swvarszokw(zhcfilhpzk) = dhmgtkdkcl ygiuqoukra (ppalfumvcb )	-	25 Aug 2019
SITC2018	Phase 1	Neoplasms	-	Pegzilarginase	zgtlbijnmi(fbtmjuvkzk) = increased levels of granzyme A, IFN-g and TNF-a surapkzdvs (imdjodqwhu ) View more	Positive	06 Nov 2018
SITC2018	Phase 1	Neoplasms	-	aOX40 mAb		Positive	06 Nov 2018
SITC2018	Not Applicable	Neoplasms L-Arginine	-	Anti-PD-L1 Ab	liwevwcent(tnnokiofbr) = ykgvfdzgnk wswiqxbhlc (iafvdaszcm )	Positive	06 Nov 2018
NCT02561234 (AACR 12018 \| AACR 22018) Manual	Phase 1	HR-positive/HER2-low Solid Tumors	40	pegzilarginase	jpxjnsfcjn(iaxizcbxpi) = 0.33 mg/kg once weekly ixyybojtzu (zzgbgldoqc ) View more	Positive	01 Jul 2018
NCT02732184 (ASCO 12018 \| ASCO 22018) Manual	Phase 1	Refractory acute myeloid leukemia \| Myelodysplastic Syndromes	21	pegzilarginase	pstgejlcyd(dmahrruudl) = gzegvbhrim iaibysptnk (qvdpwnsyoj )	Positive	04 Jun 2018

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