Agios Pharmaceuticals, Inc. · NASDAQ:AGIO
Agios Pharmaceuticals — 2019 ASH Investor Reception
37 slides from Agios Pharmaceuticals's conference presentation, Dec 9, 2019
Slide 1: Agios 2019 ASH Investor Reception
Agios 2019 ASH Investor Reception December 9, 2019
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation and various remarks we make during this presentation contain forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding Agios’ plans, strategies and expect
Slide 3: Today's Agenda
Today’s Agenda • Opening Remarks – Andrew Hirsch, Chief Financial Officer & Head of Corporate Developement • Overview IDH Data – Chris Bowden, M.D., Chief Medical Officer • Overview of DRIVE PK and PK Deficiency Data – Eduard van Beers, M.D., Ph.D., University Medical Center Utrecht • Mitapivat Proo
Slide 4: 2019 Key Milestones Position Agios for Long-term Value Creation
2019 Key Milestones Position Agios for Long-term Value Creation Submit sNDA for Potential FDA approval TIBSOVO® in second line or later Begin dosing ✓ and commercialization of X cholangiocarcinoma ✓ monotherapy TIBSOVO® in untreated AML Complete enrollment in patients in AG-636 Phase 1 dose- escalat
Slide 5: Today's Key Takeaways
Today’s Key Takeaways Agios is leading the science behind IDH mutations in AML • Multiple pathways can predict for response (JAK2) or resistance (NRAS, PTPN11) to IDH1 inhibitors in AML • Both IDH-related and non-IDH related pathways potentially contributing to relapse to IDH1 inhibition as a monoth
Slide 6: Overview of ASH IDH Presentations
Overview of ASH IDH Presentations Dr. Chris Bowden, Chief Medical Officer
Slide 7: Leading the Science for IDH Mutations in Cancer
Leading the Science for IDH Mutations in Cancer 2008 2013 2017 2018-2019 Continuing to Agios founded drive the science Initiated clinical IDHIFA® TIBSOVO® & develop our 2009 trials for IDH approved for approved for IDH inhibitors for Nature paper on inhibitors R/R AML R/R AML and earlier lines of th
Slide 8: Four IDH-focused Presentations at ASH Highlight Our Scientific and Clinical Leadership
Four IDH-focused Presentations at ASH Highlight Our Scientific and Clinical Leadership in This Space High rate of IDH1 mutation clearance and measurable residual disease negativity in Presented: Sunday, patients with IDH1-mutant newly diagnosed acute myeloid leukemia treated with ivosidenib Dec. 8,
Slide 9: TIBSOVO Results in Durable Remissions as a Monotherapy in R/R AML
TIBSOVO® Results in Durable Remissions as a Monotherapy in R/R AML R/R AML 500 mg (n=179) CR+CRh rate, n (%) [95% CI] 57 (31.8) [25.1, 39.2] Time to CR/CRh, median (range) months 2.0 (0.9−5.6) Duration of CR/CRh, median [95% CI] months 8.2 [5.6, 12.0] CR rate, n (%) [95% CI] 43 (24.0) [18.0, 31.0] T
Slide 10: Objective of AML Translational Research
Objective of AML Translational Research Characterize the molecular predictors of response and mechanisms of relapse to ivosidenib monotherapy in mutant IDH1 relapsed/refractory AML using comprehensive genomic profiling • Hypothesis 1: Pre-therapy genetic profile predicts response – Mutations in sing
Slide 11: Translational Work Highlights Multiple Pathways at Baseline Predicting Response or Resistance
Translational Work Highlights Multiple Pathways at Baseline that Could Predict Response or Resistance to IDH1 Inhibitors NRAS PTPN11 NRASFLT3−TKD+ NRAS PTPN11 PTPN11 FLT3−TKD+FLT3−TKD+ FLT3−ITD KIT FLT3−ITD KIT FLT3−ITD KRAS KIT RTK KRAS KRAS Pathway JAK2RTK Pathway RTK Pathway JAK2 JAK2 p=0.004 p=0
Slide 12: Both IDH-related and Non-IDH-related Pathways Identified at Relapse
Both IDH-related and Non-IDH-related Pathways Identified at Relapse Further Underscoring Heterogeneity of R/R AML Pathway Patients with mutations emerging at relapse or progression by pathway, n (%) All Best response of CR or CRh n = 74 n = 26 IDH-related 17 (23%) 9 (35%) IDH1 second-site 10 (14) 5
Slide 13: Four IDH-focused Presentations at ASH Highlight Our Scientific and Clinical Leadership
Four IDH-focused Presentations at ASH Highlight Our Scientific and Clinical Leadership in This Space High rate of IDH1 mutation clearance and measurable residual disease negativity in Presented: Sunday, patients with IDH1-mutant newly diagnosed acute myeloid leukemia treated with ivosidenib Dec. 8,
Slide 14: TIBSOVO and Azacitidine Combination Results in Deep and Durable Remissions
TIBSOVO® and Azacitidine Combination Results in Deep and Durable Remissions in Newly Diagnosed AML Multiple orthogonal measures of MRD in bone marrow Response parameter All patients samples demonstrate high molecular remissions N=23 Mutation clearance CR, n (%) [95% CI] 14 (60.9) [38.5, 80.3] Time t
Slide 15: TIBSOVO and Azacitidine Combination Induced Response in Patients with RTK Pathway Mutations
TIBSOVO® and Azacitidine Combination Induced Response in Newly Diagnosed Patients with RTK Pathway Mutations Co-occurring baseline mutations identified by NGS (2% VAF cutoff; N=23) • No statistically significant relationship between baseline genetic variants and clinical response or primary resistan
Slide 16: Conclusions
Conclusions • TIBSOVO® as a monotherapy or in combination results in durable remissions in relapsed/refractory and newly diagnosed AML • AML is a heterogeneous disease, and in relapsed/refractory disease, multiple pathways at baseline can predict for response (JAK2) or resistance (NRAS, PTPN11) to I
Slide 17: What's Possible for IDHm Patients
What’s Possible for IDHm Patients NOW NEXT FUTURE Relapsed/Refractory AML 2L Cholangiocarcinoma IC-eligible frontline AML IC-ineligible frontline AML IC-ineligible frontline AML Low Grade Glioma (monotherapy) (combination) Relapsed/Refractory MDS 17
Slide 18: Overview of ASH PKR Presentations
Overview of ASH PKR Presentations Dr. Eduard van Beers, University Medical Center Utrecht
Slide 19: Long-term Safety & Efficacy Data from DRIVE PK Study of Mitapivat
Long-term Safety & Efficacy Data from DRIVE PK Study of Mitapivat in Adults in PK Deficiency PK-deficient adults who are not regularly transfused (ClinicalTrials.gov NCT02476916) Arm 1 Dose modifications alloweda 1:1 randomization Stratified by PKLR genotype 300 mg BID 6-month core (none excluded) d
Slide 20: 18 Patients Remain in Extension Phase of Study
18 Patients Remain in Extension Phase of Study ▪ Of the 52 patients enrolled in the study, 43 completed the core period (24 weeks) and 18 remained in the study as of March 27, 2019 Enrollment and disposition during core period and extension phase Enrolled Enrollment (N=52) Completed Discontinueda Co
Slide 21: Demographics Similar for Those in Extension Compared to the Total Cohort
Demographics Similar for Those in Extension Compared to the Total Cohort Total Continued Characteristic N=52 n=18 ▪ No differences in age, race, or sex were observed between patients who Male, n (%) 32 (61.5) 10 (55.6) continued in the extension period and Age at randomization, median (range), 34 (1
Slide 22: Mitapivat Was Generally Well Tolerated; No New Safety Signals
Mitapivat Was Generally Well Tolerated; No New Safety Signals Were Identified in Extension Most common AEs in patients who continued in the extension perioda AE, n (%) Continued n=18 Core Extension (n=18) (n=18) Headache 10 (55.6) 7 (38.9) Insomnia 5 (27.8) 5 (27.8) Fatigue 4 (22.2) 5 (27.8) Nasopha
Slide 23: Hemoglobin Response Maintained for More Than 3 Years
Hemoglobin Response Maintained for More Than 3 Years ▪ Improvements in hemoglobin and other markers of hemolysis including reticulocytes, indirect bilirubin, and haptoglobin achieved during the core period were sustained during the extension period (up to 42 months) 23 Data presented at ASH 2019
Slide 24: Conclusions
Conclusions • Mitapivat is a novel, first-in-class, PK-R activator with potential to be the first disease-altering therapy for patients with PK deficiency • Patients who responded to mitapivat had long-term clinically meaningful responses: – Improvements in hemoglobin and other hemolysis markers wer
Slide 25: Prevalence of Comorbidities and Complications in Adults with Pyruvate Kinase Deficiency
Prevalence of Comorbidities and Complications in Adults with Pyruvate Kinase Deficiency Dr. Eduard van Beers, University Medical Center Utrecht
Slide 26: Patients with PK Deficiency Have Higher Rates of Comorbidities & Complications
Patients with PK Deficiency Have Higher Rates of Comorbidities & Complications Regardless of Transfusion Status Results from the PK deficiency National History Study show that patients with PK deficiency, regardless of transfusion status, have higher rates of select comorbidities and complications t
Slide 27: Study Population and Inclusion Criteria
Study Population and Inclusion Criteria Patients with PK deficiency: Sufficient data on transfusion history to enable classification into one of three mutually exclusive cohorts: − Ever Regularly Transfused (ERT): Received transfusions, ≥6 in any year − Never Regularly Transfused (NRT): Received tra
Slide 28: Adults with PK Deficiency Had Higher Rates of Select Comorbidities & Complications
Adults with PK Deficiency Had Higher Rates of Select Comorbidities & Complications Adults with PK deficiency had higher lifetime rates of Adults with PK deficiency had higher rates of splenectomy, pulmonary hypertension, osteoporosis, and liver cirrhosis cholecystectomy, and gallstones over the prec
Slide 29: Mitapivat Development in Thalassemia
Mitapivat Development in Thalassemia Dr. Chris Bowden, Chief Medical Officer
Slide 30: Mitapivat Activates Both Wild-type and Mutant PKR
Mitapivat Activates Both Wild-type and Mutant PKR Hypothesis: Activation of wild-type PKR may improve RBC cell fitness and survival by increasing ATP levels in hemolytic anemias such as thalassemia Thalassemia Mitapivat Reduced levels of ⍺ or β globin Thalassemic Enhanced RBC energy Globin precipita
Slide 31: Mitapivat Improves Red Cell Parameters in a β-thalassemia Mouse Model
Mitapivat Improves Red Cell Parameters in a β-thalassemia Mouse Model Hemoglobin Reticulocytes Reticulocytes ATP RBC ATP Life Span 15 300 120,000 20 100,000 Retics (cells *104/uL) RBC Half Life (days) 260 15 ATP (ng/mL) 10 200 80,000 84,700 14.5 Hb (g/dl) 10.9 9.1 10.9 60,000 10 5 100 9.1 150 40,000
Slide 32: Phase 2 Study of Mitapivat in Non-transfusion-dependent Thalassemia
Design of Phase 2 Study of Mitapivat in Adults with Non-transfusion-dependent β- and α-thalassemia Dose escalation based on efficacy and safety Mitapivat 100 mg BID Mitapivat N=17 50 mg BID 24-week core period Safety follow-up Screening ≤42 days 2-year extension period 28 days after 6 weeks 18 weeks
Slide 33: Clinical Proof-of-concept for Mitapivat Established in Non-transfusion-dependent Thalassemia
Clinical Proof-of-concept for Mitapivat Established in Non-transfusion-dependent Thalassemia 7 of 8 efficacy evaluable patients achieved a hemoglobin increase of ≥1.0 g/dL from baseline in at least one assessment (weeks 4-12) In responding patients, the mean hemoglobin increase from baseline was 1.7
Slide 34: Illustrative Patient Case Study
Illustrative Patient Case Study: Male, 44 years old 10 9 Hb (g/dL) Hb (g/dL) 8 Increase of 1g/dL 7 from baseline 6 Lactate dehydrogenase 90 400 Reticulocytes (10x9/L) 80 350 70 (U/L) Reticulocytes (10^9/L) 60 300 50 Lactate dehydrogenase 250 (U/L) 40 30 200 110 Erythropoietin (mU/mL) 16.0 Soluble tr
Slide 35: What's Possible for PKR Activators
What’s Possible for PKR Activators NOW NEXT FUTURE Adult PK Deficiency Thalassemia Other Hemolytic Anemias Sickle Cell Disease Pediatric PK Deficiency 35
Slide 36: Today's Key Takeaways
Today’s Key Takeaways Agios is leading the science behind IDH mutations in AML • Multiple pathways can predict for response (JAK2) or resistance (NRAS, PTPN11) to IDH1 inhibitors in AML • Both IDH-related and non-IDH related pathways potentially contributing to relapse to IDH1 inhibition as a monoth
Slide 37: Agios
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