Exhibit 99.1 New Ideas. Better Medicines. Presentation to Investors January 2020Exhibit 99.1 New Ideas. Better Medicines. Presentation to Investors January 2020
Forward‐Looking Statements This presentation contains forward‐looking statements that involve substantial risks and uncertainties. In some cases, you can identify forward‐looking statements by the following words: “may,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “anticipate,” “contemplate,” “believe,” “estimate,” “predict,” “project,” “seek,” “potential,” “continue,” “ongoing” or the negative of these terms or other comparable terminology, although not all forward‐looking statements contain these words. These statements relate to future events or our future financial performance or condition and involve known and unknown risks, uncertainties and other factors that could cause our actual results, levels of activity, performance or achievement to differ materially from those expressed or implied by these forward‐looking statements. These risks, uncertainties and other factors are described more fully in our periodic reports filed with the Securities and Exchange Commission (SEC), including our Annual Report on Form 10‐K for the year ended December 31, 2018, filed with the SEC on March 11, 2019, particularly in the sections titled “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations”. In light of the significant uncertainties in our forward‐looking statements, you should not place undue reliance on these statements or regard these statements as a representation or warranty by us or any other person that we will achieve our objectives and plans in any specified timeframe, or at all. The forward‐looking statements contained in this presentation represent our estimates and assumptions only as of the date of this presentation and, except as required by law, we undertake no obligation to update or revise publicly any forward‐looking statements, whether as a result of new information, future events or otherwise after the date of this presentation. This presentation also contains estimates, projections and other information concerning our industry, our business, and the markets for our drug candidates, as well as data regarding market research, estimates and forecasts prepared by our management. Information that is based on estimates, forecasts, projections, market research or similar methodologies is inherently subject to uncertainties and actual events or circumstances may differ materially from events and circumstances reflected in this information. 2Forward‐Looking Statements This presentation contains forward‐looking statements that involve substantial risks and uncertainties. In some cases, you can identify forward‐looking statements by the following words: “may,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “anticipate,” “contemplate,” “believe,” “estimate,” “predict,” “project,” “seek,” “potential,” “continue,” “ongoing” or the negative of these terms or other comparable terminology, although not all forward‐looking statements contain these words. These statements relate to future events or our future financial performance or condition and involve known and unknown risks, uncertainties and other factors that could cause our actual results, levels of activity, performance or achievement to differ materially from those expressed or implied by these forward‐looking statements. These risks, uncertainties and other factors are described more fully in our periodic reports filed with the Securities and Exchange Commission (SEC), including our Annual Report on Form 10‐K for the year ended December 31, 2018, filed with the SEC on March 11, 2019, particularly in the sections titled “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations”. In light of the significant uncertainties in our forward‐looking statements, you should not place undue reliance on these statements or regard these statements as a representation or warranty by us or any other person that we will achieve our objectives and plans in any specified timeframe, or at all. The forward‐looking statements contained in this presentation represent our estimates and assumptions only as of the date of this presentation and, except as required by law, we undertake no obligation to update or revise publicly any forward‐looking statements, whether as a result of new information, future events or otherwise after the date of this presentation. This presentation also contains estimates, projections and other information concerning our industry, our business, and the markets for our drug candidates, as well as data regarding market research, estimates and forecasts prepared by our management. Information that is based on estimates, forecasts, projections, market research or similar methodologies is inherently subject to uncertainties and actual events or circumstances may differ materially from events and circumstances reflected in this information. 2
ChemoCentryx (CCXI): Inhibiting Disease‐Driving Chemoattraction § Chemoattractant receptors (chemokine receptors and complement receptors) attract and Chemoattractant Extracellular activate destructive inflammatory (e.g. C5a, chemokine MCP‐1) cells in disease § CCXI platform: inhibition a given chemoattractant receptor with orally‐ Cell administered small molecule membrane Receptor (e.g. C5a Receptor, CCR2) § CCXI Doctrine: Precise mechanism – precise medicine • Anti‐inflammatory, not Intracellular immunosuppressive 3ChemoCentryx (CCXI): Inhibiting Disease‐Driving Chemoattraction § Chemoattractant receptors (chemokine receptors and complement receptors) attract and Chemoattractant Extracellular activate destructive inflammatory (e.g. C5a, chemokine MCP‐1) cells in disease § CCXI platform: inhibition a given chemoattractant receptor with orally‐ Cell administered small molecule membrane Receptor (e.g. C5a Receptor, CCR2) § CCXI Doctrine: Precise mechanism – precise medicine • Anti‐inflammatory, not Intracellular immunosuppressive 3
CCXI Value Creation: From Basic Science to Commercialization Advanced Establishing Precision Broad Pipeline of Programs Strong Global Approach Unique, Orally‐ Leads to Better Focused on Commercial Administered, Small Orphan Diseases Capabilities Medicines Molecule Therapeutics CCXI owns commercial Targeting indications with clear CCXI drug candidates selectively Landmark Phase III ADVOCATE rights in the U.S. regulatory pathways and multi‐ target a specific chemoattractant trial in ANCA vasculitis billion dollar market potential Building marketing, or chemokine receptor demonstrated superiority medical, quality capabilities Leaves rest of the Robust clinical data generated Topline data expected in 2020 for Vifor Pharma to pay CCXI immune system intact with avacopan and CCX140 four more trials: two each for teens to mid‐20s royalties avacopan and CCX140 on any Ex‐U.S. sales 4CCXI Value Creation: From Basic Science to Commercialization Advanced Establishing Precision Broad Pipeline of Programs Strong Global Approach Unique, Orally‐ Leads to Better Focused on Commercial Administered, Small Orphan Diseases Capabilities Medicines Molecule Therapeutics CCXI owns commercial Targeting indications with clear CCXI drug candidates selectively Landmark Phase III ADVOCATE rights in the U.S. regulatory pathways and multi‐ target a specific chemoattractant trial in ANCA vasculitis billion dollar market potential Building marketing, or chemokine receptor demonstrated superiority medical, quality capabilities Leaves rest of the Robust clinical data generated Topline data expected in 2020 for Vifor Pharma to pay CCXI immune system intact with avacopan and CCX140 four more trials: two each for teens to mid‐20s royalties avacopan and CCX140 on any Ex‐U.S. sales 4
ADVOCATE Phase III Data for ANCA Vasculitis: A Defining Moment for CCXI in 2019 § Data demonstrate avacopan’s superiority to standard of care in treating patients with ANCA vasculitis o NDA / EMA submissions planned for 2020 § Avacopan is the first chemoattractant inhibitor for autoimmune and inflammatory disease to demonstrate clinical benefit in a pivotal trial § C5a receptor biology validated; avacopan Delivering on Our Promise to Bring Avacopan potentially a pipeline in a drug: to the ANCA Vasculitis Community o Late‐stage trials in hidradenitis suppurativa (HS) and C3 glomerulopathy (C3G) o ADVOCATE success opens the door to potential additional opportunities in nephrology 5ADVOCATE Phase III Data for ANCA Vasculitis: A Defining Moment for CCXI in 2019 § Data demonstrate avacopan’s superiority to standard of care in treating patients with ANCA vasculitis o NDA / EMA submissions planned for 2020 § Avacopan is the first chemoattractant inhibitor for autoimmune and inflammatory disease to demonstrate clinical benefit in a pivotal trial § C5a receptor biology validated; avacopan Delivering on Our Promise to Bring Avacopan potentially a pipeline in a drug: to the ANCA Vasculitis Community o Late‐stage trials in hidradenitis suppurativa (HS) and C3 glomerulopathy (C3G) o ADVOCATE success opens the door to potential additional opportunities in nephrology 5
CCXI Broad Pipeline from Novel Discovery Platform DRUG/ THERAPEUTIC AREA TARGET INDICATION PRECLINICAL PHASE I PHASE II PHASE III NDA ANCA‐ASSOCIATED VASCULITIS Avacopan Complement (formerly Inhibition in C3 GLOMERULOPATHY CCX168) / Orphan Diseases C5aR HIDRADENITIS SUPPURATIVA ORPHAN KIDNEY DISEASE ‐FOCAL SEGMENTAL GLOMERULOSCLEROSIS Chronic and Orphan CCX140/CCR2 Kidney Diseases DIABETIC KIDNEY DISEASE, SUCCESSFULLY COMPLETED PHASE II Other Inflammatory CCX507/CCR9 IBD: ULCERATIVE COLITIS and Autoimmune Diseases CCR6 TH17 DRIVEN DISEASE, e.g. PUSTUALAR PSORIASIS Immuno‐Oncology ADVANCED PANCREATIC CANCER CCX872/ CCR2 OTHER ONCOLOGY INDICATIONS 6CCXI Broad Pipeline from Novel Discovery Platform DRUG/ THERAPEUTIC AREA TARGET INDICATION PRECLINICAL PHASE I PHASE II PHASE III NDA ANCA‐ASSOCIATED VASCULITIS Avacopan Complement (formerly Inhibition in C3 GLOMERULOPATHY CCX168) / Orphan Diseases C5aR HIDRADENITIS SUPPURATIVA ORPHAN KIDNEY DISEASE ‐FOCAL SEGMENTAL GLOMERULOSCLEROSIS Chronic and Orphan CCX140/CCR2 Kidney Diseases DIABETIC KIDNEY DISEASE, SUCCESSFULLY COMPLETED PHASE II Other Inflammatory CCX507/CCR9 IBD: ULCERATIVE COLITIS and Autoimmune Diseases CCR6 TH17 DRIVEN DISEASE, e.g. PUSTUALAR PSORIASIS Immuno‐Oncology ADVANCED PANCREATIC CANCER CCX872/ CCR2 OTHER ONCOLOGY INDICATIONS 6
Beyond ADVOCATE ‐ “2020 4‐Sight”: Four Data Readouts Anticipated in 2020 1 1 1 1 1 2 3 4 FSGS FSGS Hidradenitis C3G Suppurativa No Approved No Approved No Approved Treatment Treatment Approved Treatment Options Treatment Has Options Options Large Controlled Limited Efficacy CCX140 LUMINA‐2 ‘Phase IIb’ Avacopan CCX140 LUMINA‐1 ACCOLADE Trial Data Expected 2020; Data Expected Q2 2020 Data Expected Q3 2020 Potentially to Support Nephrotic Proteinuria ‘Phase IIb’ Avacopan Registration Potentially Registrational AURORA Trial 7Beyond ADVOCATE ‐ “2020 4‐Sight”: Four Data Readouts Anticipated in 2020 1 1 1 1 1 2 3 4 FSGS FSGS Hidradenitis C3G Suppurativa No Approved No Approved No Approved Treatment Treatment Approved Treatment Options Treatment Has Options Options Large Controlled Limited Efficacy CCX140 LUMINA‐2 ‘Phase IIb’ Avacopan CCX140 LUMINA‐1 ACCOLADE Trial Data Expected 2020; Data Expected Q2 2020 Data Expected Q3 2020 Potentially to Support Nephrotic Proteinuria ‘Phase IIb’ Avacopan Registration Potentially Registrational AURORA Trial 7
Avacopan (CCX168) A Unique Orally Administered Inhibitor of the Complement 5a Receptor (C5aR) 8Avacopan (CCX168) A Unique Orally Administered Inhibitor of the Complement 5a Receptor (C5aR) 8
Avacopan: Unique Orally Administered C5aR Inhibitor We believe avacopan avoids long‐term biological 1 consequences of ‘upstream’ complement inhibition 1 Avacopan does not block C5b‐9 production; leaving host defense 2 C5a Antibodies mechanism (MAC) in place Avacopan preserves beneficial Avacopan 3 functions of C5L2 pathway C5aR Avacopan approach targeting Reason for black box 4 ‘downstream’ complement warning for eculizumab pathway we believe is best 4 3 2 9Avacopan: Unique Orally Administered C5aR Inhibitor We believe avacopan avoids long‐term biological 1 consequences of ‘upstream’ complement inhibition 1 Avacopan does not block C5b‐9 production; leaving host defense 2 C5a Antibodies mechanism (MAC) in place Avacopan preserves beneficial Avacopan 3 functions of C5L2 pathway C5aR Avacopan approach targeting Reason for black box 4 ‘downstream’ complement warning for eculizumab pathway we believe is best 4 3 2 9
Avacopan Targets Only C5aR (C5aR1 / CD88); Why Preserving C5L2 (C5aR2) is Important • An Anti‐inflammatory Function for the Complement Anaphylatoxin C5a‐binding Protein, C5L2. Gerard et al, J. Biol Chem, 2005 • Disruption of the Complement Anaphylatoxin Receptor C5L2 Exacerbates Inflammation in Allergic Contact Dermatitis. Wang et al, Jour Immunol, 2013 • C5L2, the Second C5a Anaphylatoxin Receptor, Avacopan Suppresses LPS‐Induced Acute Lung Injury. Wang et al, Am Jour Resp Cell and Mol Bio, 2016 C5aR • C5a Receptor (CD88) Blockade Protects Against C5a internalization MPO‐ANCA Glomerulonephritis (GN). Xiao et al, Jour and destruction; other positive Am Soc Nephrology, 2014 (Paper contains data that signaling events C5L2 deficiency exacerbates GN) Avacopan does not impede the beneficial properties of C5a interacting with C5L2 10Avacopan Targets Only C5aR (C5aR1 / CD88); Why Preserving C5L2 (C5aR2) is Important • An Anti‐inflammatory Function for the Complement Anaphylatoxin C5a‐binding Protein, C5L2. Gerard et al, J. Biol Chem, 2005 • Disruption of the Complement Anaphylatoxin Receptor C5L2 Exacerbates Inflammation in Allergic Contact Dermatitis. Wang et al, Jour Immunol, 2013 • C5L2, the Second C5a Anaphylatoxin Receptor, Avacopan Suppresses LPS‐Induced Acute Lung Injury. Wang et al, Am Jour Resp Cell and Mol Bio, 2016 C5aR • C5a Receptor (CD88) Blockade Protects Against C5a internalization MPO‐ANCA Glomerulonephritis (GN). Xiao et al, Jour and destruction; other positive Am Soc Nephrology, 2014 (Paper contains data that signaling events C5L2 deficiency exacerbates GN) Avacopan does not impede the beneficial properties of C5a interacting with C5L2 10
Anti‐Neutrophil Cytoplasmic Auto‐antibody (ANCA) Vasculitis: A Complement C5a Activated Neutrophil‐Driven Disease Overview • Highly inflammatory and progressive autoimmune disease caused by the over‐activation of the complement system; generation of C5a • Kidney is a major target organ • Characterized by recurring flares, accruing into irreversible organ system damage (end‐stage renal disease) and death; relapse is common • Significantly impacts multiple aspects of physical function, emotional well‐being, and overall productivity Rationale for Avacopan Auto Antibodies→ Activation of Complement Cascade → Generation of C5a → C5a Binds C5a Receptor (C5aR) on Neutrophils → C5aR‐Activated Neutrophils Destroy Blood Vessels 11Anti‐Neutrophil Cytoplasmic Auto‐antibody (ANCA) Vasculitis: A Complement C5a Activated Neutrophil‐Driven Disease Overview • Highly inflammatory and progressive autoimmune disease caused by the over‐activation of the complement system; generation of C5a • Kidney is a major target organ • Characterized by recurring flares, accruing into irreversible organ system damage (end‐stage renal disease) and death; relapse is common • Significantly impacts multiple aspects of physical function, emotional well‐being, and overall productivity Rationale for Avacopan Auto Antibodies→ Activation of Complement Cascade → Generation of C5a → C5a Binds C5a Receptor (C5aR) on Neutrophils → C5aR‐Activated Neutrophils Destroy Blood Vessels 11
Anti‐Neutrophil Cytoplasmic Auto‐antibody (ANCA) Vasculitis: A Complement C5a Activated Neutrophil‐Driven Disease Overview • Highly inflammatory and progressive autoimmune disease caused by the over‐activation of the complement system; generation of C5a • Kidney is a major target organ • Characterized by recurring flares, accruing into irreversible organ system damage (end‐stage renal disease) and death; relapse is common • Significantly impacts multiple aspects of physical function, emotional well‐being, and overall productivity Rationale for Avacopan Current Treatments Auto Antibodies → High‐dose steroids Immuno‐suppressants Activation of Complement Cascade → for 6 months Generation of C5a → § Cyclophosphamide OR § Prednisone C5a Binds C5a Receptor (C5aR) on Neutrophils → § Methylprednisone§ Rituximab C5aR‐Activated Neutrophils Destroy Blood Vessels Status AAvacopan ANCA Vasculitis NDA Filing Anticipated Mid‐2020 12Anti‐Neutrophil Cytoplasmic Auto‐antibody (ANCA) Vasculitis: A Complement C5a Activated Neutrophil‐Driven Disease Overview • Highly inflammatory and progressive autoimmune disease caused by the over‐activation of the complement system; generation of C5a • Kidney is a major target organ • Characterized by recurring flares, accruing into irreversible organ system damage (end‐stage renal disease) and death; relapse is common • Significantly impacts multiple aspects of physical function, emotional well‐being, and overall productivity Rationale for Avacopan Current Treatments Auto Antibodies → High‐dose steroids Immuno‐suppressants Activation of Complement Cascade → for 6 months Generation of C5a → § Cyclophosphamide OR § Prednisone C5a Binds C5a Receptor (C5aR) on Neutrophils → § Methylprednisone§ Rituximab C5aR‐Activated Neutrophils Destroy Blood Vessels Status AAvacopan ANCA Vasculitis NDA Filing Anticipated Mid‐2020 12
The Time for an ANCA Vasculitis Treatment Paradigm Shift Has Arrived Major Unmet Needs – Current ANCA Vasculitis Chronic High‐Dose Steroid SOC Traditional Therapy is: Not Safe With Current SOC: • Prevent glucocorticoid‐related Steroids for 6 Months § 11‐16% die within 1st year of diagnosis* toxicity and infection (Tapered Regimen) § Prednisone§ Greatest risk to patients in first year § Methylprednisone comes from steroid‐induced infections Not Fast § Current treatments contribute ~60% of • Prevent damage and the mortality rate* preserve renal function Cyclophosphamide § Need to taper steroid = high relapse rate or Not Durable § Irreversible organ damage with relapse • Majority of patients at risk for Rituximab (especially in the kidney) relapse for many years * Little et al, 2010 Ann Rheum Dis 69:1036–1043, Flossmann et al 2011 Ann Rheum Dis 70:488–494. 13The Time for an ANCA Vasculitis Treatment Paradigm Shift Has Arrived Major Unmet Needs – Current ANCA Vasculitis Chronic High‐Dose Steroid SOC Traditional Therapy is: Not Safe With Current SOC: • Prevent glucocorticoid‐related Steroids for 6 Months § 11‐16% die within 1st year of diagnosis* toxicity and infection (Tapered Regimen) § Prednisone§ Greatest risk to patients in first year § Methylprednisone comes from steroid‐induced infections Not Fast § Current treatments contribute ~60% of • Prevent damage and the mortality rate* preserve renal function Cyclophosphamide § Need to taper steroid = high relapse rate or Not Durable § Irreversible organ damage with relapse • Majority of patients at risk for Rituximab (especially in the kidney) relapse for many years * Little et al, 2010 Ann Rheum Dis 69:1036–1043, Flossmann et al 2011 Ann Rheum Dis 70:488–494. 13
Avacopan’s Value Proposition: A Superior Profile in Treating ANCA Vasculitis Stop active Eliminate current Stop accumulated Improve patient vasculitis therapy‐ induced organ damage quality of life illness (as soon as possible) Reduction in vasculitis From chronic steroids, From both vasculitis and Validated quality of life 1 activity score (BVAS , From cyclophosphamide; from steroid therapy (QOL) instruments a signs and symptoms rituximab toxicity Patient reported 2 index) (measured by GTI ) (measured in part by outcomes (PROs) 3 VDI ; also renal parameters) 1. Birmingham Vasculitis Activity Score 2. Glucocorticoid Toxicity Index 3. Vascular Damage Index 14Avacopan’s Value Proposition: A Superior Profile in Treating ANCA Vasculitis Stop active Eliminate current Stop accumulated Improve patient vasculitis therapy‐ induced organ damage quality of life illness (as soon as possible) Reduction in vasculitis From chronic steroids, From both vasculitis and Validated quality of life 1 activity score (BVAS , From cyclophosphamide; from steroid therapy (QOL) instruments a signs and symptoms rituximab toxicity Patient reported 2 index) (measured by GTI ) (measured in part by outcomes (PROs) 3 VDI ; also renal parameters) 1. Birmingham Vasculitis Activity Score 2. Glucocorticoid Toxicity Index 3. Vascular Damage Index 14
Avacopan ADVOCATE Pivotal Phase III Trial Design BVAS Remission* BVAS Remission* Two primary endpoints: 1 2 at 26 Weeks at 52 Weeks (both analyzed after 52 weeks) Avacopan, 30 mg twice daily Dummy prednisone taper Test Group over 21 weeks (N=165) RTX, 4 weeks or CYC, 12 weeks followed by AZA Screening and Randomization Placebo Avacopan, twice daily Active Comparator / Prednisone, 60 mg/day with standard tapering SoC Group to zero over 21 weeks (N=165) RTX = Rituximab RTX, 4 weeks or CYC, 12 weeks followed by AZA AZA = Azathioprine 15 *BVAS Remission: BVAS of zero and no steroids for ≥4 weeksAvacopan ADVOCATE Pivotal Phase III Trial Design BVAS Remission* BVAS Remission* Two primary endpoints: 1 2 at 26 Weeks at 52 Weeks (both analyzed after 52 weeks) Avacopan, 30 mg twice daily Dummy prednisone taper Test Group over 21 weeks (N=165) RTX, 4 weeks or CYC, 12 weeks followed by AZA Screening and Randomization Placebo Avacopan, twice daily Active Comparator / Prednisone, 60 mg/day with standard tapering SoC Group to zero over 21 weeks (N=165) RTX = Rituximab RTX, 4 weeks or CYC, 12 weeks followed by AZA AZA = Azathioprine 15 *BVAS Remission: BVAS of zero and no steroids for ≥4 weeks
Primary and Key Secondary Endpoints and Statistical Design of ADVOCATE Trial Two Primary Endpoints (not Co‐Primaries) Secondary Endpoints ‐‐ Evaluated at Weeks 26 and 52 ‐‐ ‐‐Reduce the Total Burden of Disease ‐‐ Remission = BVAS score of zero and off steroids 4 weeks prior • Change in health‐related Quality of Life • Comparing avacopan with no chronic high dose steroid • Biological response measures: vs. steroid containing standard of care (SOC) o Glucocorticoid‐induced toxicity • Statistical null hypotheses tested in a predefined o Estimated glomerular filtration rate (eGFR) hierarchical manner (gatekeeping procedure) to preserve o Urinary albumin:creatinine ratio (UACR) Type I error o Urinary MCP‐1:creatinine ratio o Week 26 non‐inferiority (previous regulatory standard); if achieved, then o Change in Vasculitis Damage Index (VDI) o Week 52 non‐inferiority; if achieved, then • Incidence of withdrawals due to adverse event o Week 52 superiority 16Primary and Key Secondary Endpoints and Statistical Design of ADVOCATE Trial Two Primary Endpoints (not Co‐Primaries) Secondary Endpoints ‐‐ Evaluated at Weeks 26 and 52 ‐‐ ‐‐Reduce the Total Burden of Disease ‐‐ Remission = BVAS score of zero and off steroids 4 weeks prior • Change in health‐related Quality of Life • Comparing avacopan with no chronic high dose steroid • Biological response measures: vs. steroid containing standard of care (SOC) o Glucocorticoid‐induced toxicity • Statistical null hypotheses tested in a predefined o Estimated glomerular filtration rate (eGFR) hierarchical manner (gatekeeping procedure) to preserve o Urinary albumin:creatinine ratio (UACR) Type I error o Urinary MCP‐1:creatinine ratio o Week 26 non‐inferiority (previous regulatory standard); if achieved, then o Change in Vasculitis Damage Index (VDI) o Week 52 non‐inferiority; if achieved, then • Incidence of withdrawals due to adverse event o Week 52 superiority 16
ADVOCATE Demonstrates Avacopan’s Superiority Over Standard of Care Primary Endpoints: Can avacopan therapy fulfill the pre‐specified statistical null hypothesis for the primary BVAS endpoints of vasculitis Stop Stop active active vasculitis vasculitis remission at week 26 and sustained remission at week 52? ✔ Active 1 BVAS Remission Avacopan p Value Comparator / Eliminate Eliminate current current therapy therapy‐ ‐ SOC Control induced induced illness illness p<0.0001 72.3% 70.1% 26 Weeks non‐inferiority Stop Stop ac accumulated cumulated organ organ p=0.0066 65.7% 54.9% 52 Weeks damage damage superiority Numerically superior, statistically significant non‐inferior at Impr Improv ove pa e patien tient t quality quality of of 26 weeks Result lif life e Statistically superior sustained remission at 52 weeks 1 BVAS remission: BVAS of zero and no steroids for ≥4 weeks 17ADVOCATE Demonstrates Avacopan’s Superiority Over Standard of Care Primary Endpoints: Can avacopan therapy fulfill the pre‐specified statistical null hypothesis for the primary BVAS endpoints of vasculitis Stop Stop active active vasculitis vasculitis remission at week 26 and sustained remission at week 52? ✔ Active 1 BVAS Remission Avacopan p Value Comparator / Eliminate Eliminate current current therapy therapy‐ ‐ SOC Control induced induced illness illness p<0.0001 72.3% 70.1% 26 Weeks non‐inferiority Stop Stop ac accumulated cumulated organ organ p=0.0066 65.7% 54.9% 52 Weeks damage damage superiority Numerically superior, statistically significant non‐inferior at Impr Improv ove pa e patien tient t quality quality of of 26 weeks Result lif life e Statistically superior sustained remission at 52 weeks 1 BVAS remission: BVAS of zero and no steroids for ≥4 weeks 17
Avacopan Superior in Reducing Steroid‐Related Toxicities Glucocorticoid Related Toxicity GlucocorticoidToxicity Avacopan Control P Value Stop Stop active active vasculitis vasculitis Index (GTI) v2 (SOC) ✔ GTI Cumulative Worsening 39.7 56.6 p=0.0002 Score Eliminate Eliminate current current therapy therapy‐ ‐ induced induced illness illness ✔ GTI Aggregate 11.2 23.4 p=0.0082 Improvement Score Stop Stop ac accumulated cumulated organ organ § The GTI was developed to assess the comparative benefits of new, steroid‐sparing agents to allow investigators to accurately measure their ability to prevent or reverse damage damage glucocorticoid‐related toxicity § Avacopan groups also showed significantly reduced glucocorticoid AE’s based on EULAR‐recommended adverse event terms and those based on Investigator Impr Improv ove pa e patien tient t quality quality of of Assessment of causality § Overall safety profile acceptable to support development in ANCA vasculitis; overall lif life e rates of AE’s and SAE’s commensurate with other ANCA studies at 12 months Statistically significant reduction in steroid‐ Result related toxicity 18Avacopan Superior in Reducing Steroid‐Related Toxicities Glucocorticoid Related Toxicity GlucocorticoidToxicity Avacopan Control P Value Stop Stop active active vasculitis vasculitis Index (GTI) v2 (SOC) ✔ GTI Cumulative Worsening 39.7 56.6 p=0.0002 Score Eliminate Eliminate current current therapy therapy‐ ‐ induced induced illness illness ✔ GTI Aggregate 11.2 23.4 p=0.0082 Improvement Score Stop Stop ac accumulated cumulated organ organ § The GTI was developed to assess the comparative benefits of new, steroid‐sparing agents to allow investigators to accurately measure their ability to prevent or reverse damage damage glucocorticoid‐related toxicity § Avacopan groups also showed significantly reduced glucocorticoid AE’s based on EULAR‐recommended adverse event terms and those based on Investigator Impr Improv ove pa e patien tient t quality quality of of Assessment of causality § Overall safety profile acceptable to support development in ANCA vasculitis; overall lif life e rates of AE’s and SAE’s commensurate with other ANCA studies at 12 months Statistically significant reduction in steroid‐ Result related toxicity 18
Avacopan Demonstrates Significant Improvement in Renal Function Stop Stop active active vasculitis vasculitis Estimated Glomerular Filtration Rate (eGFR) ✔ Mean Change Expressed Avacopan Control P Value 2 in ml/min/1.73m (SOC) Eliminate Eliminate current current therapy therapy‐ ‐ Baseline change to week 26 5.8 2.8 induced induced illness illness ✔ p=0.0413 2 2 in eGFR mL/min/1.73 mL/min/1.73 Baseline change to week 52 7.3 4.0 p=0.0259 2 2 in eGFR mL/min/1.73 mL/min/1.73 Stop Stop ac accumulated cumulated organ organ ✔ damage damage Statistically significant improvement in renal Result function Impr Improv ove pa e patien tient t quality quality of of lif life e 19Avacopan Demonstrates Significant Improvement in Renal Function Stop Stop active active vasculitis vasculitis Estimated Glomerular Filtration Rate (eGFR) ✔ Mean Change Expressed Avacopan Control P Value 2 in ml/min/1.73m (SOC) Eliminate Eliminate current current therapy therapy‐ ‐ Baseline change to week 26 5.8 2.8 induced induced illness illness ✔ p=0.0413 2 2 in eGFR mL/min/1.73 mL/min/1.73 Baseline change to week 52 7.3 4.0 p=0.0259 2 2 in eGFR mL/min/1.73 mL/min/1.73 Stop Stop ac accumulated cumulated organ organ ✔ damage damage Statistically significant improvement in renal Result function Impr Improv ove pa e patien tient t quality quality of of lif life e 19
Avacopan: Marked Improvements in Kidney Function Change from Baseline in eGFR in Patients with Renal Change from Baseline in eGFR in Patients with eGFR Disease at Baseline (Pre‐specified) <30 at Baseline (Pre‐specified) Baseline eGFR ~21 in (Baseline eGFR ~45) in 20Avacopan: Marked Improvements in Kidney Function Change from Baseline in eGFR in Patients with Renal Change from Baseline in eGFR in Patients with eGFR Disease at Baseline (Pre‐specified) <30 at Baseline (Pre‐specified) Baseline eGFR ~21 in (Baseline eGFR ~45) in 20
Improving Kidney Function with Avacopan: Examples of Underserved Complement‐driven Kidney Disease Other Renal / Complement Lupus Nephritis Polycystic Kidney Disease Disorders • Uncontrolled complement system activation • PKD is a cystic renal disease characterized by • Several proteinuric disorders including implicated in kidney destruction and ESRD in growth of large cysts in the kidney Membranous nephropathy, IgAN, Alport syndrome etc. ~20‐40% of SLE patients • Genetic basis but role of complement in end • Complement dysregulation implicated in • Primarily affects young and predisposition to stage pathology broadly supported by animal pathology and progression to ESRD females data and human data • Few if any adequate therapies • Kidney transplant not uncommon, does not • Not orphan, though subtypes (such as cure disease autosomal recessive form) much less common • Also, complications of complement activation • Huge economic burden on HC systems in dialysis settings Rationale • Regulatory approval path may be open to new • Prevalence ~ 65,000 Rationale‐100,000 based on claims Rationale registration endpoints data Current Treatments Current Treatments New Paths to Registration? No Adequate Therapy • Experts opine on regulators’ No Adequate Therapy • Poorly controlled with broad acceptance of eGFR based trials immunosuppression not unlike traditional • Transplant based on strength of ADVOCATE ANCA Therapy (Glucocorticoids + CYC, etc) renal improvement data • Also mycophenolate, calcineurin inhibitors • May unlock marked new value • Widely acknowledged need for new, opportunities for avacopan targeted therapy 21Improving Kidney Function with Avacopan: Examples of Underserved Complement‐driven Kidney Disease Other Renal / Complement Lupus Nephritis Polycystic Kidney Disease Disorders • Uncontrolled complement system activation • PKD is a cystic renal disease characterized by • Several proteinuric disorders including implicated in kidney destruction and ESRD in growth of large cysts in the kidney Membranous nephropathy, IgAN, Alport syndrome etc. ~20‐40% of SLE patients • Genetic basis but role of complement in end • Complement dysregulation implicated in • Primarily affects young and predisposition to stage pathology broadly supported by animal pathology and progression to ESRD females data and human data • Few if any adequate therapies • Kidney transplant not uncommon, does not • Not orphan, though subtypes (such as cure disease autosomal recessive form) much less common • Also, complications of complement activation • Huge economic burden on HC systems in dialysis settings Rationale • Regulatory approval path may be open to new • Prevalence ~ 65,000 Rationale‐100,000 based on claims Rationale registration endpoints data Current Treatments Current Treatments New Paths to Registration? No Adequate Therapy • Experts opine on regulators’ No Adequate Therapy • Poorly controlled with broad acceptance of eGFR based trials immunosuppression not unlike traditional • Transplant based on strength of ADVOCATE ANCA Therapy (Glucocorticoids + CYC, etc) renal improvement data • Also mycophenolate, calcineurin inhibitors • May unlock marked new value • Widely acknowledged need for new, opportunities for avacopan targeted therapy 21
ADVOCATE Demonstrates Improvements in Validated Health‐Related Quality of Life Metrics § Avacopan group scored higher in all (10 of 10) measured domains and categories of the SF‐36 QOL instrument at both weeks 26 and 52 Stop Stop active active vasculitis vasculitis ✔ § Avacopan group statistically significantly higher in a majority (6/10) including: o Physical Component Score Eliminate Eliminate current current therapy therapy‐ ‐ o Physical Functioning induced induced illness illness o Role Physical ✔ o Role Emotional o Vitality o General Health Perception Stop Stop ac accumulated cumulated organ organ § The avacopan group also reported statistically significantly better outcomes ✔ damage damage on the EuroQOL‐5D‐5L instrument (Visual Analogue Scale and EQ Index) Impr Improv ove pa e patien tient t quality quality of of Statistically significant improvements in quality of life Result lif life e ✔ 22ADVOCATE Demonstrates Improvements in Validated Health‐Related Quality of Life Metrics § Avacopan group scored higher in all (10 of 10) measured domains and categories of the SF‐36 QOL instrument at both weeks 26 and 52 Stop Stop active active vasculitis vasculitis ✔ § Avacopan group statistically significantly higher in a majority (6/10) including: o Physical Component Score Eliminate Eliminate current current therapy therapy‐ ‐ o Physical Functioning induced induced illness illness o Role Physical ✔ o Role Emotional o Vitality o General Health Perception Stop Stop ac accumulated cumulated organ organ § The avacopan group also reported statistically significantly better outcomes ✔ damage damage on the EuroQOL‐5D‐5L instrument (Visual Analogue Scale and EQ Index) Impr Improv ove pa e patien tient t quality quality of of Statistically significant improvements in quality of life Result lif life e ✔ 22
ADVOCATE Demonstrates Avacopan’s Superiority Over Standard of Care… Numerically superior, statistically significant non‐inferior at Stop Stop active active vasculitis vasculitis 26 weeks Result ✔ Statistically superior sustained remission at 52 weeks Statistically significant reduction in Glucocorticoid Toxicity Eliminate Eliminate current current therapy therapy‐ ‐ Result Index (GTI) and other accepted assessments of induced induced illness illness ✔ glucocorticoid toxicity Stop Stop ac accumulated cumulated organ organ Statistically significant improvement in estimated Result ✔ damage damage glomerular filtration rate Impr Improv ove pa e patien tient t quality quality of of Result Statistically significant improvements in quality of life lif life e ✔ 23ADVOCATE Demonstrates Avacopan’s Superiority Over Standard of Care… Numerically superior, statistically significant non‐inferior at Stop Stop active active vasculitis vasculitis 26 weeks Result ✔ Statistically superior sustained remission at 52 weeks Statistically significant reduction in Glucocorticoid Toxicity Eliminate Eliminate current current therapy therapy‐ ‐ Result Index (GTI) and other accepted assessments of induced induced illness illness ✔ glucocorticoid toxicity Stop Stop ac accumulated cumulated organ organ Statistically significant improvement in estimated Result ✔ damage damage glomerular filtration rate Impr Improv ove pa e patien tient t quality quality of of Result Statistically significant improvements in quality of life lif life e ✔ 23
…and Provides Potential Path to Regulatory Approval § Statistical superiority over standard of care opens pathway to potential FDA and EMA regulatory approval § Data addressing total burden of disease further enhances value proposition o Improved renal function parameters (eGFR) o Reduced steroid‐induced toxicity o Improved health‐related Quality of Life o Safety profile vs glucocorticoid SOC Status Plan to File NDA with FDA in Mid‐2020 24…and Provides Potential Path to Regulatory Approval § Statistical superiority over standard of care opens pathway to potential FDA and EMA regulatory approval § Data addressing total burden of disease further enhances value proposition o Improved renal function parameters (eGFR) o Reduced steroid‐induced toxicity o Improved health‐related Quality of Life o Safety profile vs glucocorticoid SOC Status Plan to File NDA with FDA in Mid‐2020 24
̴ ̴ Avacopan’s Potential Multi‐Billion Commercial Opportunity Starts with ANCA Vasculitis ADVOCATE established 52 weeks as a reasonable minimum treatment Illustrative Example of Potential Annual Sales at Orphan Drug Pricing Prevalence of ANCA vasculitis 6,000 $200K/Pt/Year 5,000 40-75K 50-100K 4,000 3,000 ~5,000 new cases per ~4,000 new cases per year in EU year in U.S. 2,000 $50K/Pt/Year 1,000 § CCXI took strategic decision to build U.S. - commercial infrastructure 0 5,000 10,000 15,000 20,000 25,000 Patients § Partner Vifor Pharma will pay teens to ADVOCATE established 52 weeks as reasonable minimum treatment mid‐20’s royalties on any sales in international markets 25 Gross Sales ($MM)̴ ̴ Avacopan’s Potential Multi‐Billion Commercial Opportunity Starts with ANCA Vasculitis ADVOCATE established 52 weeks as a reasonable minimum treatment Illustrative Example of Potential Annual Sales at Orphan Drug Pricing Prevalence of ANCA vasculitis 6,000 $200K/Pt/Year 5,000 40-75K 50-100K 4,000 3,000 ~5,000 new cases per ~4,000 new cases per year in EU year in U.S. 2,000 $50K/Pt/Year 1,000 § CCXI took strategic decision to build U.S. - commercial infrastructure 0 5,000 10,000 15,000 20,000 25,000 Patients § Partner Vifor Pharma will pay teens to ADVOCATE established 52 weeks as reasonable minimum treatment mid‐20’s royalties on any sales in international markets 25 Gross Sales ($MM)
Preparing for U.S. Commercialization § Rheumatologists and nephrologists Market Penetration primarily manage ANCA vasculitis § Medical Science Liaisons (MSLs) to perform education and awareness role KOLs 30% of Market § Field Force of approximately 50‐75 to < 250 Top 80% of Market account for 80% of U.S. market Prescribers § ADVOCATE superiority data reveals ~2,750 Health avacopan’s considerable value Care Practitioners proposition 26Preparing for U.S. Commercialization § Rheumatologists and nephrologists Market Penetration primarily manage ANCA vasculitis § Medical Science Liaisons (MSLs) to perform education and awareness role KOLs 30% of Market § Field Force of approximately 50‐75 to < 250 Top 80% of Market account for 80% of U.S. market Prescribers § ADVOCATE superiority data reveals ~2,750 Health avacopan’s considerable value Care Practitioners proposition 26
Summary: Avacopan for ANCA Vasculitis § ADVOCATE trial demonstrates avacopan’s superiority over standard of care: o Fulfills pre‐specified primary endpoint null hypothesis of statistical non‐inferiority of remission of acute vasculitis at week 26 vs. standard of care o Demonstrates 52 week sustained remission statistical superiority over standard of care § Compelling evidence supports avacopan’s superior profile of therapy versus glucocorticoid standard of care o Reduction in overall burden of disease management and improvement in quality of life demonstrated through secondary endpoints including enhanced renal function and improved health‐related quality of life o Distinct benefit in reduction of steroid‐related toxicities § Regulatory path forward with FDA and EMA submissions expected in 2020 § CCXI preparing for commercialization in the U.S.; Vifor Pharma internationally 27Summary: Avacopan for ANCA Vasculitis § ADVOCATE trial demonstrates avacopan’s superiority over standard of care: o Fulfills pre‐specified primary endpoint null hypothesis of statistical non‐inferiority of remission of acute vasculitis at week 26 vs. standard of care o Demonstrates 52 week sustained remission statistical superiority over standard of care § Compelling evidence supports avacopan’s superior profile of therapy versus glucocorticoid standard of care o Reduction in overall burden of disease management and improvement in quality of life demonstrated through secondary endpoints including enhanced renal function and improved health‐related quality of life o Distinct benefit in reduction of steroid‐related toxicities § Regulatory path forward with FDA and EMA submissions expected in 2020 § CCXI preparing for commercialization in the U.S.; Vifor Pharma internationally 27
Avacopan for C3 Glomerulopathy (C3G) 28Avacopan for C3 Glomerulopathy (C3G) 28
Avacopan: Clinical Development in C3G Study Design Overview • Randomized (1:1), double‐blind, placebo controlled clinical trial in patients with a confirmed diagnosis of C3G • Uncontrolled activation of complement system leading to • Two strata: C5b‐9 level >244 ng/mL and C5b‐9 level ≤244 ng/mL complement protein deposition in the kidney (glomeruli), disrupting kidney function Primary Endpoint: • Can be life‐threatening; half of all with C3G have kidney failure • *Percent change in C3G Histologic Index (CHI) at 6 months • Kidney transplant does not cure disease; relapsing is common Secondary Endpoints: • Urinary protein:creatinine, MCP‐1:creatinine, QOL, and serum creatinine • Primarily affects the young; huge economic burden on HC systems measurements (for eGFR) over course of study Current Renal Biopsy Assessments (months) Rationale 0 6* 12 Treatments • Characterized by C3 but also C5 No Approved Therapies / C5a deposition in glomeruli Avacopan, 30 mg BID (n=22) • Non‐specific treatment • C5a contributes to approaches include blood Placebo BID (n=22) Avacopan, 30 mg BID inflammatory hypercellularity pressure control and broad in the glomeruli, leading to immunosuppression kidney damage Avacopan, 30 mg BID (n=22) FDA and EMA Orphan Drug • Avacopan targets C5aR, which Designations Placebo BID (n=22) Avacopan, 30 mg BID blocks the effects of C5a 29 Screening (Biopsy‐proven C3G) Baseline & Randomization Assess patient C5b‐9 levels Stratum 1 Stratum 2 C5b‐9 >244 C5b‐9 level ng/mL ≤244 ng/mLAvacopan: Clinical Development in C3G Study Design Overview • Randomized (1:1), double‐blind, placebo controlled clinical trial in patients with a confirmed diagnosis of C3G • Uncontrolled activation of complement system leading to • Two strata: C5b‐9 level >244 ng/mL and C5b‐9 level ≤244 ng/mL complement protein deposition in the kidney (glomeruli), disrupting kidney function Primary Endpoint: • Can be life‐threatening; half of all with C3G have kidney failure • *Percent change in C3G Histologic Index (CHI) at 6 months • Kidney transplant does not cure disease; relapsing is common Secondary Endpoints: • Urinary protein:creatinine, MCP‐1:creatinine, QOL, and serum creatinine • Primarily affects the young; huge economic burden on HC systems measurements (for eGFR) over course of study Current Renal Biopsy Assessments (months) Rationale 0 6* 12 Treatments • Characterized by C3 but also C5 No Approved Therapies / C5a deposition in glomeruli Avacopan, 30 mg BID (n=22) • Non‐specific treatment • C5a contributes to approaches include blood Placebo BID (n=22) Avacopan, 30 mg BID inflammatory hypercellularity pressure control and broad in the glomeruli, leading to immunosuppression kidney damage Avacopan, 30 mg BID (n=22) FDA and EMA Orphan Drug • Avacopan targets C5aR, which Designations Placebo BID (n=22) Avacopan, 30 mg BID blocks the effects of C5a 29 Screening (Biopsy‐proven C3G) Baseline & Randomization Assess patient C5b‐9 levels Stratum 1 Stratum 2 C5b‐9 >244 C5b‐9 level ng/mL ≤244 ng/mL
Avacopan for Hidradenitis Suppurativa (HS) 30Avacopan for Hidradenitis Suppurativa (HS) 30
Abundant Data on Complement in Hidradenitis Suppurativa (HS) 31Abundant Data on Complement in Hidradenitis Suppurativa (HS) 31
Avacopan for HS: AURORA Trial Data Read‐out Expected in Q3 2020: >300 Patients Enrolled Study Design Overview • Double‐blind, placebo controlled Phase IIb trial • Chronic, disabling autoimmune skin disease featuring • ~390 moderate to severe HS patients randomized (1:1:1) across ~100 sites painful, disfiguring nodules, boils and abscesses • Placebo crosses over to active at 12 weeks, follow all groups for additional 24 weeks • Progresses frequently; causes keloids, contractures and Primary Endpoint: immobility • Proportion on patients with clinical response (HiSCR) at 12 weeks • Most common in the armpit, groin and genital regions Secondary Endpoints: Current • % improvement baseline to week 12 Rationale Treatments • HS Quality of Life Instrument (HiSQOL) and SF36 • Neutrophil‐driven disease • Other validated secondary measurements in HS • Adalimumab is the only where C5a involvement is approved drug for HS; HiSCR (weeks) validated widely regarded as only 0 12 36 • C5a blockade with having moderate efficacy avacopan via C5aR offers a • Still, sales in adalimumab in Avacopan, 30 mg BID strong potential to control HS last year >$1B neutrophil activation Avacopan, 10 mg BID • Precedent for FDA Orphan • Oral application offers Drug Designation for advantages over injections Placebo Avacopan, 30 mg BID moderate or severe HS or infusions 32 Screening (Hurley Stage II‐III) Baseline & RandomizationAvacopan for HS: AURORA Trial Data Read‐out Expected in Q3 2020: >300 Patients Enrolled Study Design Overview • Double‐blind, placebo controlled Phase IIb trial • Chronic, disabling autoimmune skin disease featuring • ~390 moderate to severe HS patients randomized (1:1:1) across ~100 sites painful, disfiguring nodules, boils and abscesses • Placebo crosses over to active at 12 weeks, follow all groups for additional 24 weeks • Progresses frequently; causes keloids, contractures and Primary Endpoint: immobility • Proportion on patients with clinical response (HiSCR) at 12 weeks • Most common in the armpit, groin and genital regions Secondary Endpoints: Current • % improvement baseline to week 12 Rationale Treatments • HS Quality of Life Instrument (HiSQOL) and SF36 • Neutrophil‐driven disease • Other validated secondary measurements in HS • Adalimumab is the only where C5a involvement is approved drug for HS; HiSCR (weeks) validated widely regarded as only 0 12 36 • C5a blockade with having moderate efficacy avacopan via C5aR offers a • Still, sales in adalimumab in Avacopan, 30 mg BID strong potential to control HS last year >$1B neutrophil activation Avacopan, 10 mg BID • Precedent for FDA Orphan • Oral application offers Drug Designation for advantages over injections Placebo Avacopan, 30 mg BID moderate or severe HS or infusions 32 Screening (Hurley Stage II‐III) Baseline & Randomization
CCR2 Inhibitor CCX140 Targeted Approach to Chronic and Orphan Kidney Diseases CCX140 for Focal Segmental Glomerulosclerosis (FSGS) 33CCR2 Inhibitor CCX140 Targeted Approach to Chronic and Orphan Kidney Diseases CCX140 for Focal Segmental Glomerulosclerosis (FSGS) 33
CCR2 Inhibitor CCX140 in FSGS: LUMINA‐1 Data Expected in Q2 2020 LUMINA‐2: Nephrotic Range Proteinuria Primary FSGS Overview • ≥3 gram/day baseline proteinuria • Orphan indication ‐ kidney’s filtering units (glomeruli) have scarring • First presentation or new flare following prior effective treatment leading to permanent dysfunction • *Significant decrease in proteinuria from baseline approvable endpoint • Presents with proteinuria, in which protein is found in the urine due LUMINA‐1: Primary FSGS ≥1 gram/day baseline proteinuria to breakdown of normal filtration mechanism • Decrease in proteinuria from baseline potential accelerated approval endpoint • Can causes Nephrotic Syndrome often leading to End Stage Renal • Reduced in decline in eGFR anticipated full approval endpoint Disease (ESRD) Study Assessments –Reduction in Proteinuria from Baseline (weeks) 0 12 26 Rationale Current Treatments Rescue if no partial response; • CCX140 demonstrated significant Dose range (n=6‐13) otherwise continue reduction in proteinuria in Phase No Approved Therapies 5 mg QD‐ 15 mg BID 1 II diabetic nephropathy trial Expand to part 2 • Non-specific treatment approaches include • Histologic lesion from glomerular CCX140 steroids to control injury affecting specialized kidney 5 mg QD (n=10) proteinuria or immuno- filtering cells, especially podocytes Highest Safe Dose 10 mg QD (n=10) suppressants 12 wk. Open‐Label • CCR2 in FSGS kidney ‐ role for 15 mg QD (n=10) CCR2 in renal cell (podocyte) protection Placebo (n=10) 1 Pending favorable results 34 Screening LUMINA‐2 LUMINA‐1 Stratify by Single proteinuria level & Arm immunosuppressant treatment (Yes/No)CCR2 Inhibitor CCX140 in FSGS: LUMINA‐1 Data Expected in Q2 2020 LUMINA‐2: Nephrotic Range Proteinuria Primary FSGS Overview • ≥3 gram/day baseline proteinuria • Orphan indication ‐ kidney’s filtering units (glomeruli) have scarring • First presentation or new flare following prior effective treatment leading to permanent dysfunction • *Significant decrease in proteinuria from baseline approvable endpoint • Presents with proteinuria, in which protein is found in the urine due LUMINA‐1: Primary FSGS ≥1 gram/day baseline proteinuria to breakdown of normal filtration mechanism • Decrease in proteinuria from baseline potential accelerated approval endpoint • Can causes Nephrotic Syndrome often leading to End Stage Renal • Reduced in decline in eGFR anticipated full approval endpoint Disease (ESRD) Study Assessments –Reduction in Proteinuria from Baseline (weeks) 0 12 26 Rationale Current Treatments Rescue if no partial response; • CCX140 demonstrated significant Dose range (n=6‐13) otherwise continue reduction in proteinuria in Phase No Approved Therapies 5 mg QD‐ 15 mg BID 1 II diabetic nephropathy trial Expand to part 2 • Non-specific treatment approaches include • Histologic lesion from glomerular CCX140 steroids to control injury affecting specialized kidney 5 mg QD (n=10) proteinuria or immuno- filtering cells, especially podocytes Highest Safe Dose 10 mg QD (n=10) suppressants 12 wk. Open‐Label • CCR2 in FSGS kidney ‐ role for 15 mg QD (n=10) CCR2 in renal cell (podocyte) protection Placebo (n=10) 1 Pending favorable results 34 Screening LUMINA‐2 LUMINA‐1 Stratify by Single proteinuria level & Arm immunosuppressant treatment (Yes/No)
Avacopan and CCX140 – Potential for Paradigm Shift in Orphan Inflammatory Diseases Avacopan (C5aR Inhibitor): • Success in pivotal Phase III ADVOCATE trial in ANCA lays foundation for potential approval • First chemoattractant inhibitor to achieve pivotal trial success in autoimmune / inflammatory disease • Most precise mode of interaction in the complement intervention space • Excellent clinical track record over several years of controlled trials CCR2 Inhibitor CCX140: • Extensive clinical experience, including a successful 1yr Phase II trial • New science supports role of CCR2 in FSGS and in podocyte biology • FSGS clinical studies (LUMINA trials); LUMINA‐1 enrollment complete, data expected in Q2 2020 • Data in 2020 for LUMINA trials 35Avacopan and CCX140 – Potential for Paradigm Shift in Orphan Inflammatory Diseases Avacopan (C5aR Inhibitor): • Success in pivotal Phase III ADVOCATE trial in ANCA lays foundation for potential approval • First chemoattractant inhibitor to achieve pivotal trial success in autoimmune / inflammatory disease • Most precise mode of interaction in the complement intervention space • Excellent clinical track record over several years of controlled trials CCR2 Inhibitor CCX140: • Extensive clinical experience, including a successful 1yr Phase II trial • New science supports role of CCR2 in FSGS and in podocyte biology • FSGS clinical studies (LUMINA trials); LUMINA‐1 enrollment complete, data expected in Q2 2020 • Data in 2020 for LUMINA trials 35
History of Capital Efficiency and Current Strong Financial Position Financial Highlights End of Quarter Cash and Investments $205.8M cash and investments at September 30, 2019 Excludes $100M credit facility secured in 2020 History of non‐dilutive funding from successful partnering strategy / funding (while retaining 100% US rights) • Presence of anti‐neutrophil cytoplasmic auto‐antibodies (ANCA) $85M in May 2016 – avacopan • Leads to complement system activation and C5a generation $50M in December 2016 – CCX140 • C5a via C5aR is main activator of neutrophils • Neutrophils inflame and destroy blood vessels = vasculitis $20M in February 2017 – avacopan Asia (excl.China) $50M in January 2018 – avacopan CMA validation *Proforma gives effect to cash commitments and milestones earned but not received until $21.5M in June 2018 – China rights subsequent periods. 36 $ (MM)History of Capital Efficiency and Current Strong Financial Position Financial Highlights End of Quarter Cash and Investments $205.8M cash and investments at September 30, 2019 Excludes $100M credit facility secured in 2020 History of non‐dilutive funding from successful partnering strategy / funding (while retaining 100% US rights) • Presence of anti‐neutrophil cytoplasmic auto‐antibodies (ANCA) $85M in May 2016 – avacopan • Leads to complement system activation and C5a generation $50M in December 2016 – CCX140 • C5a via C5aR is main activator of neutrophils • Neutrophils inflame and destroy blood vessels = vasculitis $20M in February 2017 – avacopan Asia (excl.China) $50M in January 2018 – avacopan CMA validation *Proforma gives effect to cash commitments and milestones earned but not received until $21.5M in June 2018 – China rights subsequent periods. 36 $ (MM)
What’s Next? A Historic Year for CCXI ‘2020 4‐SIGHT’ Avacopan in ANCA Vasculitis 4 Topline Readouts Expected in 2020 1. LUMINA‐1 trial of CCX140 in Sub‐ • Full analysis of ADVOCATE data Nephrotic Primary Focal Segmental and publication Glomerulosclerosis (FSGS) in Q2 • Regulatory filings to FDA and EMA 2. AURORA trial of avacopan in Hidradenitis expected in 2020 Suppurativa (HS) in Q3 • Build CCXI commercial 3. LUMINA‐2 trial of CCX140 in Nephrotic infrastructure for U.S. Syndrome Primary FSGS • Ex‐US marketing alliance with Vifor 4. ACCOLADE trial of avacopan in C3 Pharma with excellent economics Glomerulopathy (C3G) 37What’s Next? A Historic Year for CCXI ‘2020 4‐SIGHT’ Avacopan in ANCA Vasculitis 4 Topline Readouts Expected in 2020 1. LUMINA‐1 trial of CCX140 in Sub‐ • Full analysis of ADVOCATE data Nephrotic Primary Focal Segmental and publication Glomerulosclerosis (FSGS) in Q2 • Regulatory filings to FDA and EMA 2. AURORA trial of avacopan in Hidradenitis expected in 2020 Suppurativa (HS) in Q3 • Build CCXI commercial 3. LUMINA‐2 trial of CCX140 in Nephrotic infrastructure for U.S. Syndrome Primary FSGS • Ex‐US marketing alliance with Vifor 4. ACCOLADE trial of avacopan in C3 Pharma with excellent economics Glomerulopathy (C3G) 37
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