Spyre Therapeutics, Inc. · NASDAQ:SYRE
Spyre Therapeutics — Aeglea BioTherapeutics — Investor Presentation (December 2019)
32 slides from Spyre Therapeutics's investor presentation, Dec 3, 2019
Slide 1: Aeglea Corporate Overview December 2019
Aeglea Corporate Overview December 2019 Aeglea Bio Therapeutics External Exhibit 99.1
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation and the accompanying oral presentation contain “forward-looking” statements that are based on our management’s beliefs and assumptions and on information currently available to management. Forward-looking statements include all statements other than state
Slide 3: Clinical-Stage Biotechnology Company Engineering Next Generation Human Enzymes
Specificity Activity Stability Clinical-Stage Biotechnology Company that Engineers Next Generation Human Enzymes with Enhanced Properties and Novel Activity to Provide Solutions for Diseases with Unmet Medical Need Aeglea BioTherapeutics, Inc. | NASDAQ: AGLE | Austin, Texas Employees 75 IND-Enabling
Slide 4: Pipeline Building Using a Unique Drug Hunting Approach
IND Enabling Phase 1 Phase 2 Phase 3 Discovery Product & Target Indication Pegzilarginase Arginine Arginase 1 Deficiency SCLC – Combination Cancer Metabolism AEB2109 Methionine AEB3103 Cysteine/Cystine Pegzilarginase Arginine Research Programs AEB4104 Homocysteine/ Homocystine Homocystinuria Cystinu
Slide 5: Strong Momentum with Multiple Near-term Catalysts
Strong Momentum with Multiple Near-term Catalysts Recent Milestones Anticipated Milestones Pegzilarginase: ARG1-D Statistically significant arginine reduction at 20-doses vs baseline (p<0.001) Compelling Phase 1/2 & OLE (20-dose) efficacy data demonstrated 79% clinical responder rate First patient d
Slide 6: Highly Experienced Leadership Team in Drug Discovery & Development
Highly Experienced Leadership Team in Drug Discovery & Development Anthony G. Quinn, MD PhD Chief Executive Officer Leslie Sloan, PhD Chief Operating Officer Charles N. York II, MBA Chief Financial Officer Scott Rowlinson, PhD Vice President of Research Ravi M. Rao, MD PhD Chief Medical Officer Mich
Slide 7: Arginase Deficiency
Arginase 1 Deficiency A serious progressive disease with early mortality and high unmet medical need due to an autosomal recessive disorder of arginine metabolism Pegzilarginase: Lead Program Aeglea [Logo] 6
Slide 8: Pegzilarginase: An Innovative Approach to Treat Arginase Deficiency
Pegzilarginase: An Innovative Approach to Treat Arginase 1 Deficiency Indication Arginase 1 Deficiency (ARG1-D) Patient Population (Addressable Markets) Greater than 1,000 patients Greater than 200 patients identified to date Diagnosis (Blood Arginine Levels) Symptomatic cases: spasticity, developme
Slide 9: Pegzilarginase Consistently, Substantially, and Sustainably Controlled Plasma Arginine
** Current Treatment Guidance Pegzilarginase Consistently, Substantially, and Sustainably Controlled Plasma Arginine 101A and Open Label Extension (OLE) All patients demonstrated a marked and sustained reduction in plasma arginine from baseline Statistically significant reductions in arginine from b
Slide 10: Overall Clinical Response Rate of 79% After 20 Doses
Overall Clinical Response Rate of 79% After 20 Doses 79% (11 of 14) patients were defined as responders at dose 20 based on a ≥1 MCID improvement in at least one of the 6MWT, GMFM-D or GMFM-E assessments All 5 patients (100%) who reached dose 44 maintained their dose 20 overall clinical response sta
Slide 11: Clinically Impactful Improvements at Patient Level with Pegzilarginase
Clinically Impactful Improvements at Patient Level with Pegzilarginase Assessment Normal Population Baseline After 20 doses (MCID) Plasma arginine 40-115 µM 363 µM 108.5 µM (last 4 using PEACE criteria) 6MWT 310 – 664 meters 174 meters 176 meters GMFM-D Max = 39 21 27 (1.8X) GMFM-E Max = 72 27 35 (2
Slide 12: Safety: Pegzilarginase was well tolerated
Safety Pegzilarginase was well tolerated Hypersensitivity and hyperammonemia were the most common treatment-related SAEs, and were expected and manageable More than 650 doses were administered to 16 patients (mean of 41 doses per patient) More than 200 injections were administered to 10 patients sub
Slide 13: PEACE Pivotal Phase 3: Trial Design
PEACE Pivotal Phase 3: Trial Design Dose adjustments in the double-blind treatment period can be made to optimize plasma arginine control for levels outside the range of 50-150µM. If needed, weekly doses can be increased to 0.15 and 0.2 mg/kg or reduced to 0.05mg/kg Single, global pivotal Phase 3 tr
Slide 14: Significant Momentum in Patient Identification
Significant Momentum in Patient Identification 2017 September 2018 September 2019 50+ Patients 140+ Patients 200+ Patients Patients Rest of World 20+ Patients 100+ Patients 80+ Europe United States Patients 13 Aeglea Bio Therapeutics External [Aeglea Logo]
Slide 15: ARG1-D: Key Highlights and Next Steps
ARG1-D: Key Highlights and Next Steps PEACE is a single, global pivotal trial designed with input from FDA and EMA Phase 1/2 & OLE data demonstrates clinical impact Primary endpoint: arginine reduction Secondary endpoints: clinical outcomes, safety and PK 30 patients, randomized 2:1 (pegzilarginase:
Slide 16: AEB4104 Homocystinuria due to CBS deficiency
AEB4104 Homocystinuria due to Cystathionine beta synthase (CBS) deficiency [Aeglea Logo]
Slide 17: AEB4104 Program: An Innovative Approach to Treat Homocystinuria
AEB4104 Program: An Innovative Approach to Treat Homocystinuria Indication Cystathionine beta synthase (CBS) deficiency and other forms Patient Population (Addressable Markets) Greater than 5,000 patients Unmet Medical Need Very high - no effective therapy for many patients Early mortality and serio
Slide 18: Increased Mortality and Severe Complication Risk in Patients with Homocystinuria
Increased Mortality and Severe Complication Risk in Patients with Homocystinuria 629 patients with Homocystinuria due to CBS deficiency from a natural history study1 1Mudd et al, 1985 CBS – Cystathionine β-synthase Severity of enzyme deficiency impacts homocysteine levels, mortality and risk of seri
Slide 19: Increased Mortality and Severe Complication Risk in Patients with Homocystinuria
Increased Mortality and Severe Complication Risk in Patients with Homocystinuria Mortality Mortality risk in non-B6-responsive patients at age 20 was 20% compared to <5% in B6-responsive patients Osteoporosis risk was ~50% in non-B6-responsive patients and ~25% in B6-responsive patients at age 12 Le
Slide 20: Patient Needs Not Adequately Addressed by Current Disease Management
Patient Needs Not Adequately Addressed by Current Disease Management Current standard of care: B6 (pyridoxine) for responsive patients Low-methionine diet + amino acid supplements Betaine Current disease management is inadequate: Limited effectiveness Non-compliance Poor tolerability of amino acid s
Slide 21: AEB4104 Program: Therapeutic Approach to Improve Control of Total Plasma Homocysteine
AEB4104 Program: Therapeutic Approach to Improve Control of Total Plasma Homocysteine AEB4104 Program Candidate Reduces Plasma Total Homocysteine (tHcy) in Preclinical Model of Homocystinuria Candidate from AEB4104 candidate is an engineered CGL enzyme designed to change its native substrate specifi
Slide 22: AEB4104: Improved Survival & Correction of Disease Manifestations in Preclinical Model
AEB4104 Program: Improved Survival & Correction of Disease Manifestations in a Preclinical Model of Homocystinuria Patients Reverses Severe Liver Abnormalities (AEB4104 Program Candidate) Reductions in total plasma homocysteine (tHcy) leads to improvements in disease related abnormalities and 100% s
Slide 23: AEB4104: Improved Survival & Correction of Disease Manifestations in Preclinical Model
AEB4104 Program: Improved Survival & Correction of Disease Manifestations in a Preclinical Model of Homocystinuria Patients Reverses Severe Liver Abnormalities (AEB4104 Program Candidate) Reductions in total plasma homocysteine (tHcy) leads to improvements in disease related abnormalities and 100% s
Slide 24: AEB4104 Program for Homocystinuria – Phase 1/2 Trial
AEB4104 Program for Homocystinuria – Phase 1/2 Trial Homocysteine reduction and removal of betaine/diet restriction provides a path to approval Key Inclusion Criteria Plasma tHcy >80 µm ≥12 yrs of age Endpoints Safety and tolerability PK Reduction in plasma total homocysteine (tHcy) levels Anticipat
Slide 25: AEB5100 Cystinuria
AEB5100 Cystinuria Yeaeglea
Slide 26: AEB5100 Program: An Innovative Approach to Treat Cystinuria
AEB5100 Program: An Innovative Approach to Treat Cystinuria Indication Cystinuria Patient Population (Addressable Markets) Greater than 10,000 patients Unmet Medical Need Severe, recurrent flank/abdominal pain and hematuria from an early age Multiple hospitalizations and invasive procedures includin
Slide 27: Patient Needs Not Adequately Addressed by Current Disease Management
Patient Needs Not Adequately Addressed by Current Disease Management Limited impact of approved therapies for Cystinuria Current standard of care: Very high fluid intake (>3.5 liters/day) Diet modification to reduce cystine consumption Urine alkalization to improve cystine solubility Thiol binding d
Slide 28: Novel Therapeutic Approach for Cystinuria – Enzymatic Reduction of Cystine
Novel Therapeutic Approach for Cystinuria – Enzymatic Reduction of Cystine Biyani and Cartledge EAU-EBU Update Series 4 (2006) 175-183 Leslie and Nazzal Renal Calculi (Cystinuria, Cystine Stones) (2018) Healthy Low cystine in urine Healthy Functional Transporter kidney tubule blood vessel = low cyst
Slide 29: AEB5100 Program: Novel Human Enzyme Solution for Cystinuria
There are no naturally occurring human enzymes that efficiently degrade cystine AEB5100 Program: Novel Human Enzyme Solution for Cystinuria Cramer SL et al, 2017 Nature Medicine 23:120-7 Creating Novel Cystine Degrading Activity1 ¥ total cysteine (µM) normalized to creatinine (mM) * p<0.005 ** p<0.0
Slide 30: AEB5100 Program: Prevention of Kidney Stone Formation in Cystinuria Mouse Model
AEB5100 Program: Prevention of Kidney Stone Formation in Cystinuria Mouse Model Administration of AEB5100 candidate markedly reduces kidney stone formation in preclinical model Volume of Kidney Stones Study ongoing Slc3a1 -/- mouse model 5-6 weeks old at dosing start Slc3a1 mice received 65% of norm
Slide 31: Financial Summary
Financial Summary $ Millions Three Months Ended 09/30/2019 Nine Months Ended 09/30/2019 Grant Revenue $ - $ - R&D Expense $17.8 $47.0 G&A Expense $4.3 $11.4 Net Loss $21.6 $56.8 Expected funding runway: through 1Q2021 Cash and marketable securities at September 30, 2019: $90.2 million1 (no debt) Sha
Slide 32: = aeglea”
= aeglea” BIOTHERAPEUTICS ©Aeglea BioTherapeutics | EXTERNAL
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