Corporate Presentation June 2017

Transcription

1 Corporate Presentation June

2 Safe Harbor & Disclaimer Statement This presentation contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of These "forwardlooking statements" are based on management's current expectations of future events and are subject to a number of important risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: Intercept's ability to successfully commercialize Ocaliva (obeticholic acid) in PBC, and Intercept's ability to maintain its regulatory approval of Ocaliva in PBC in the United States and the European Union; the initiation, cost, timing, progress and results of Intercept's development activities, preclinical studies and clinical trials; the timing of and Intercept's ability to obtain and maintain regulatory approval of OCA in PBC and in indications other than PBC and any other product candidates it may develop such as INT-767; conditions that may be imposed by regulatory authorities on Intercept's marketing approvals for its product candidates such as the need for clinical outcomes data (and not just results based on achievement of a surrogate endpoint), and any related restrictions, limitations, and/or warnings in the label of any approved product candidates; Intercept's plans to research, develop and commercialize its product candidates; Intercept's ability to obtain and maintain intellectual property protection for its product candidates; Intercept's ability to successfully commercialize OCA in indications other than PBC and its other product candidates; the size and growth of the markets for Intercept's product candidates and its ability to serve those markets; the rate and degree of market acceptance of any of Intercept's products, which may be affected by the reimbursement that it may receive for its products from payors; the success of competing drugs that are or become available; the election by Intercept's collaborators to pursue research, development and commercialization activities; Intercept's ability to attract collaborators with development, regulatory and commercialization expertise; regulatory developments in the United States and other countries; the performance of third-party suppliers and manufacturers; Intercept's need for and ability to obtain additional financing; Intercept's estimates regarding expenses, future revenues and capital requirements and the accuracy thereof; Intercept's use of cash, short-term investments and the proceeds from the offering; Intercept's ability to attract and retain key scientific or management personnel; and other factors discussed under the heading "Risk Factors" contained in Intercept s Annual Report, Quarterly Reports and other filings with the Securities and Exchange Commission. All information in this presentation is as of the date hereof, and Intercept undertakes no duty to update this information unless required by law. This presentation presents adjusted operating expense, which is a non-gaap measure, both on a historical and projected basis. Adjusted operating expense should be considered in addition to, but not as a substitute for, operating expense that Intercept prepares and announces in accordance with GAAP. Intercept excludes certain items from adjusted operating expense, such as the one-time net expense of $45.0 million for the proposed settlement of the purported securities class action lawsuit, stock-based compensation and depreciation, that management does not believe affect Intercept's basic operations and that do not meet the GAAP definition of unusual or nonrecurring items. 2

3 Building a Specialty Focused Business in Progressive Non-Viral Liver Diseases Novel therapeutic approach in progressive non-viral liver diseases PBC: Ocaliva for Primary Biliary Cholangitis OCA is an approved, first in class farnesoid X receptor (FXR) agonist that is active in the liver and gut, with an extensive safety database (>1,600 clinical trial subjects, >675 patient years of exposure) Worldwide rights (outside of Japan, China and Korea) Patent terms projected to expire at various times through 2033 Indication for the treatment of PBC in adults with an inadequate response to UDCA, or as monotherapy in adults unable to tolerate UDCA $20.6M in 1Q 2017 world-wide net sales Steady growth expected; solid long-term market opportunity to make Ocaliva standard of care for second line treatment COBALT Phase 4 confirmatory outcomes trial ongoing Breakthrough therapy designation from FDA for NASH w/ liver fibrosis NASH: Significant Market Opportunity Phase 3 REGENERATE trial - Announced complete enrollment of interim analysis cohort in May 2017; Data expected in 1H 2019 Phase 2 CONTROL trial readout in mid-2017 Broad NASH clinical development program planned Significant Upside from Further OCA Indications and Pipeline Phase 2 AESOP trial in primary sclerosing cholangitis (PSC) readout in mid-2017 OCA in development for additional non-viral, progressive liver diseases INT-767 Phase 1 recently completed, Phase 2 in NASH w/ liver fibrosis expected to start in 2H

4 Pipeline Focused on Progressive Liver Diseases with High Unmet Need Product / Population Preclinical Phase 1 Phase 2 Phase 3 Approved OCA (FXR Agonist) Primary Biliary Cholangitis (PBC) Nonalcoholic Steatohepatitis (NASH) Primary Sclerosing Cholangitis (PSC) Biliary Atresia INT-767 (Dual FXR / TGR5 Agonist) NASH w/ fibrosis INT-777 (TGR5 Agonist) Own worldwide rights to all programs (except Japan, China & Korea for OCA) 4

5 Key Recent and Upcoming 2017 Milestones PBC WW Ocaliva net sales $20.6M 1Q 2017 Continue enrollment of Phase 4 COBALT trial 2017 Complete enrollment of interim analysis cohort in Phase 3 REGENERATE trial May 2017 NASH Report Phase 2 CONTROL results Mid-2017 Initiate Phase 3 OCA cirrhosis trial 2H 2017 Initiate INT-767 Phase 2 trial 2H 2017 PSC Report Phase 2 AESOP results Mid

6 Recently Discovered Role of Bile Acids and FXR Target Validation 1. Hofmann AF. Arch Intern Med. 1999;159: de Aguiar Vallim TQ et al. Cell Metab. 2013;17(5): Pellicciari R, Fiorucci S, Camaioni E, et al. J Med Chem Aug 15;45(17):

7 OCA is an FXR Agonist Active in the Liver and Intestine OCA is structurally similar to chenodeoxycholic acid (CDCA), the natural ligand for FXR 100-fold more potent than CDCA Due to OCA s unique properties, it recirculates with the bile pool enterohepatically OCA targets FXR directly in the liver, the site of injury in progressive non-viral liver diseases 7

8 The PBC Opportunity 8

9 Primary Biliary Cholangitis (PBC) Overview PREVALENCE: Disease of women (10:1) 1 in 1,000 women >40 years old DIAGNOSIS: Non-invasive diagnosis (blood test) Elevated alkaline phosphatase (ALP) & anti-mitochondrial antibody (AMA) Pruritus (itching) and fatigue are signature symptoms NATURAL HISTORY: Increased ALP is observed early in the disease Hepatocellular damage marked by increases in AST, ALT, GGT Elevation of bilirubin occurs with advanced disease Cholestasis Hepatocellular damage Fibrosis Cirrhosis Healthy Liver Cirrhotic Liver 9

10 Robust Obeticholic Acid Development Program in PBC Development program: 2 Phase 2, Phase 3 (POISE) and Phase 4 (COBALT) trials POISE: ~5x patients on OCA met the primary endpoint vs placebo at 12 months 48% OCA 10mg, 46% OCA 5-10mg, 10% pbo (p< both doses vs pbo) OCA significant response as of 2 weeks Pruritus most frequently reported AE associated with OCA treatment Open label extension phases: patients treatment for >5 years with durable benefit NDA based on exposure in >1,600 subjects with ~675 patient years exposure Enrollment: 217 patients at 59 centers in 13 countries. Primary endpoint: proportion of patients achieving ALP <1.67x ULN with 15% reduction from baseline and normal total bilirubin In the trial there were 16 patients (7%) who were intolerant and did not receive concomitant UDCA: 6 patients (8%) in the Ocaliva 10 mg arm, 5 patients (7%) in the Ocaliva titration arm, and 5 patients (7%) in the placebo arm. All patients allowed standard of care, including stable dose of ursodiol 10

11 Ocaliva Was Approved in June 2016 Granted accelerated approval in PBC in combination with ursodeoxycholic (UDCA) in adults with an inadequate response to UDCA or as monotherapy in adults unable to tolerate UDCA Approval based on a reduction in alkaline phosphatase (ALP) Launched June

12 ~19,000 PBC Patients In U.S. Initial Launch Focus 0.04% 47% 1 Launch focusing on patients matching POISE criteria 9% 3 130k 91% 93% 2 64% 33% 55k 50k 47k 30k 15k 4k Prevalence Diagnosed Under treater care UDCA Treated / UDCA discontinue intolerance or failure UDCA treated uncontrolled (ALP > ULN) UDCA treated uncontrolled (ALP > 1.67) UDCA discontinue tolerability / failure 1. Access to healthcare assumed in calculation at 88.6% 2. 8% of patients under treater care are intolerant or discontinued due to failure on UCDA. 85% of patients under treater care are currently treated with UDC 3. UDCA discontinue patients represent 9% of patients who are either UDCA treated or UDCA intolerant or discontinue ICPT Market Research Estimates based on FYE

13 1Q Ocaliva Commercial Update 450 U.S. Sales ex-u.s. Sales $ $ $ $4.7 $13.4 TRx $0.1 2Q 2016 $4.7 3Q Q Q Weekly U.S. Ocaliva Prescription Data* /2016 7/2016 8/2016 9/ / / /2016 1/2017 2/2017 3/2017 4/2017 5/2017 6/2017 *Source IMS 13

14 We ve Made Significant Progress on the U.S. Launch In the first 9 months of launch we accomplished: Good traction with high-decile physicians Increased education and awareness overall by hosting >350 PBC disease and branded speaker programs, reaching > 3000 physicians and office staff Achieved >282 million lives covered with average time from Rx to drug to patients ~3 weeks Now that we are entering the next phase of launch, we plan to focus beyond our high decile physicians: Expanding our efforts to reach deeper into our target list Recognizing that while these physicians represent a larger portion of overall market, they will require greater disease education We expect steady quarter over quarter growth 14

15 We Are Making Good Progress for Ocaliva Internationally Revenues $0.8M in 1Q 2017 sales Ex-U.S. to contribute modestly to Ocaliva sales in 2017 Germany & France key early access markets Pricing & Reimbursement We have made good progress in Europe & Canada Rapid reimbursement decision by NICE Formal publication of the guidance in April EASL 2017 New EASL treatment guidelines published; Ocaliva recommended as second line therapy 15

16 The NASH Opportunity 16

17 NASH: A Worldwide Health Issue Changes in the lifestyle and diet of the global population are fuelling a worldwide surge in obesity and the increasing prevalence of NAFLD/NASH NASH linked to increased dietary consumption of fructose and PUFAs 1 NASH expected to become the leading cause of liver transplant by Growing NASH-related HCC among liver transplants (8% in 2008 to 14% in 2012) 2, with up to 40% of HCC in non-cirrhotic patients 3,4 1: Wree, A. et al. Nat. Rev. Gastroenterol. Hepatol. 10, (2013) 2: Wong et al. Hepatology 2014; 59(6): : Tateishi et al. J of Gastroenterology. June : Dyson et al. J. Hepatology 2014; 60(1):

18 Broad and Comprehensive NASH Clinical Plan for OCA Trial Description Status Phase 3 REGENERATE Efficacy & Safety in NASH w/ Fibrosis Completed enrollment of interim analysis cohort in May 2017 Cirrhosis Program Efficacy & Safety in NASH w/ Cirrhosis Initiate in 2H 2017 Phase 2 Underway/ Planned CONTROL OCA & Statin Effects on LDL and Lipid Metabolism Data in mid-2017 Pediatric NASH Efficacy & Safety in Pediatric NASH Patients In planning NASH Registry In planning Phase 2 completed FLINT Japanese NASH Diabetes/NAFLD Efficacy & Safety in Non-Cirrhotic NASH Efficacy & Safety in Japanese NASH Patients Diabetes + NAFLD Euglycemic Clamp Tetri et al. The Lancet 2015; 385: Conducted by Sumitomo Dainippon Pharma Mudaliar et al, Gastroenterology 2013; 145:

19 Liver Fibrosis: Associated with Long-term Outcomes Liver Fibrosis, But No Other Histologic Features, Associates With Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease Paul Angulo, MD, David E. Kleiner, MD, PhD, Sanne Dam-Larsen, MD, PhD, Leon A. Adams, MBBS, PhD, Einar S. Bjornsson, MD, Phunchai Charatcharoenwitthaya, MD, Peter R. Mills, MD, Jill C. Keach, Heather D. Lafferty, MB, ChB, Alisha Stahler, Svanhildur Haflidadottir, MD, Flemming Bendtsen, MD, PhD x Hazard Ratio of Death or Liver Transplant 1, Fibrosis Stage 4 3.8x Fibrosis Stage 3 2.9x 2.6x Fibrosis Stage 2 Current Smoker 1.9x 1.6x Fibrosis Stage 1 Diabetes 0.3x Statin Use 1: Angulo et al, Gastroenterology 2015; 2: Retrospective analysis of 619 patients diagnosed with NAFLD over median follow-up of 12.6 years 19

20 OCA is the FXR Agonist That Has Met Primary and Key Secondary Histologic Endpoints in a Well-Controlled Phase 2 Trial Phase 2 FLINT 1 trial included 200 paired biopsies over 72 weeks Primary endpoint met: decrease in the NAS of at least two points with no increase in the fibrosis score OCA improved all components of NASH, including fibrosis, steatosis, inflammation & ballooning OCA was generally well tolerated based on safety and tolerability data A significantly greater proportion of OCA patients achieved an improvement of at least one fibrosis stage in both the primary analysis and a post-hoc analysis of high-risk patients 2, who are included in the Phase 3 REGENERATE trial Primary Analysis > 1 Stage Fibrosis Improvement High-Risk NASH Patients* >1 Stage Fibrosis Improvement 45% 40% 35% 35% 45% 40% 35% 39% 30% 30% 25% 20% 19% 25% 20% 21% 15% 15% 10% 10% 5% 0% n=102 p=0.004 n=98 OCA Placebo 5% 0% n=84 p=0.007 n=76 OCA Placebo 1: Data from FLINT trial published online in Tetri et al. The Lancet and Supplementary Appendix on November 7, 2014; All p-values compared to placebo. 2. Shringarpure R, MacConell L, Yan X, et al. AASLD and Industry Colloquium: Novel Targets and Therapies in Liver Disease. March 2015 *Patients with advanced fibrosis (stage 2 or 3), or those with both early fibrosis (stage 1) and concomitant diabetes, obesity or elevated ALT 20

21 REGENERATE: Randomized Global Phase 3 Trial to Evaluate the Impact on NASH with Fibrosis of Obeticholic Acid Treatment Placebo OCA 10 mg ~2,000 patients OCA 25 mg End of Study ~350 sites Entry Criteria 1 : Biopsy-confirmed NASH Fibrosis stage 2 or stage 3 72 week Interim Analysis Primary endpoints: Fibrosis Improvement with no worsening of NASH OR NASH Resolution 2 with no worsening of fibrosis Event-Driven Final Analysis* Interim histology analysis at 72 weeks in 750 patients planned to serve as basis for filing for approval Announced complete enrollment in May 2017; Data expected in 1H 2019 *EOS endpoint: Occurrence of pre-specified number of clinical events 1 Exploratory group of NASH patients with stage 1 liver fibrosis with comorbid risk factors (defined as diabetes, obesity or active liver inflammation (ALT >1.5X ULN)) will also be enrolled, but not included in the primary endpoint analyses 2 Hepatocyte ballooning score of 0 & residual or no inflammation ( objective definition ) 21

22 The PSC Opportunity 22

23 Primary Sclerosing Cholangitis (PSC): Overview EPIDEMIOLOGY: PSC is an autoimmune cholestatic liver disease PSC is a significant market opportunity Estimated prevalence in U.S. ~40,000 1 DISEASE COURSE: Typically more complicated & aggressive than PBC 2 ~75% of PSC patients have IBD, principally ulcerative colitis 3 Biliary obstructions & infections Cholangiocarcinoma & liver cancer TREATMENT: Orphan indication with high unmet need: no approved treatment UDCA often used, although not recommended by AASLD 4 Hirschfield, et al; The Lancet. June 2013 Regulatory pathway to be determined 1: ICPT Market Research 2: Robbins and Cotran pathological basis of disease 3: Bambha et al. Gastroenterology 2003; 125: : Chapman et al. Hepatology 2010; 51:

24 Phase 2 AESOP Trial: Assessment of Efficacy and Safety of OCA in PSC Placebo Screening < 30 days from Day 0 OCA 1.5 mg OCA 3 mg Open label LTSE OCA 5 mg OCA 10 mg Randomization Week 12 Titration Week 24 ~75 patients Primary endpoints: change from baseline in ALP; safety Completed enrollment Oct 2016; data expected mid

25 First Quarter 2017 Financial Results Quarter Ended 3/31/ Guidance Net Product Revenue $20.6 Gross : Net 10-15% 10-15% COGs De minimis De minimis Interest Expense $7.2 ~$30.0 GAAP Operating Expense $105.0 Adjusted Operating Expense 1 $90.1 $380 - $420 Cash Position $ Excludes non-cash items such as stock-based compensation and other non-cash items; see reconciliation table on slide 26 All values in millions 25

26 Reconciliation Table Three Months Ended March Total operating expense (GAAP) $105.0 $127.8 Adjustments: Stock based compensation Depreciation Litigation settlement Adjusted operating expense $90.1 $71.9 All values in millions 26

27 Appendix 27

28 Appendix: NASH 28

29 Updated REGENERATE Phase 3 Trial Design Interim Analysis End of Study N Primary Endpoints 1 Definition of NASH Resolution Inclusion Treatment Arms Treatment Duration N Primary Endpoint Treatment Duration Current Study Design ~750 Fibrosis improvement OR NASH resolution Hepatocyte ballooning score of 0 & residual or no inflammation 2 Biopsy proven NASH 3 with fibrosis stage 2 or 3 4 OCA 10mg OCA 25mg Placebo 72 weeks ~2,000 Occurrence of pre-specified number of clinical events comprising a composite outcomes endpoint Event driven 1 Primary endpoints defined as fibrosis improvement with no worsening of NASH OR NASH resolution with no worsening of fibrosis 2 Objective definition of NASH resolution 3 Central pathologist assessment of definite NASH and NAFLD Activity Score (NAS) > 4 4 NASH patients with stage 1 liver fibrosis with comorbid risk factors (defined as diabetes, obesity or active liver inflammation (ALT >1.5X ULN)) also being enrolled as an exploratory cohort 29

30 NAFLD: Progression to NASH w/ Fibrosis Evidence of NAFLD progression from steatosis to fibrosingsteatohepatitis using paired biopsies: implications for prognosis and clinical management Stuart McPherson, Tim Hardy, Elsbeth Henderson, Alastair D. Burt, Christopher P. Day, Quentin M. Anstee Over an average follow-up period of ~6 years 1,2 : NAFLD: Progression to NASH 2 NASH: Progression to Cirrhosis 2 50% 40% 44% 37% 50% 40% 35% 30% 20% 10% 0% Developed NASH Developed NASH + Fibrosis 22% Developed NASH w/ Stage 3 Fibrosis 30% 20% 10% 0% 10% 9% F1 F2 F3 1: McPherson et al, Journal of Hep, 2015; 2: 108 patients had serial biopsies (mean 6.4 years to repeat biopsy): 27 patients with baseline NAFLD and 81 patients with baseline NASH 30

31 Fibrosis Improvement and Progression OCA Pbo 40% 35% 30% Improvement in Fibrosis 35% P=0.004 Fibrosis Progression 25% 20% 15% 10% 5% 0% 19% N=102 N=98 > 1-stage Improvement 17% P= % N=92 N=83 Fibrosis Resolution 15% Not. sig. 18% N=67 N=68 Progressed to Bridging Not. sig. 2% 5% N=101 N=97 Progressed to Cirrhosis Intercept Subgroup Analyses 1: Data from FLINT trial published online in Tetri et al. The Lancet and Supplementary Appendix on November 7, : All p-values compared to placebo. P-values calculated with the Cochran-Mantel-Haenszel test, stratified by clinic and diabetes status. 31

32 NASH Resolution: Baseline NASH-Only Analysis ~20% of FLINT patients did not have definite NASH at baseline Post-hoc analysis excluding patients without baseline NASH demonstrates significant response vs. placebo on NASH resolution 25% 20% 15% 10% 5% 22% P=0.0832, Not. sig. % of Patients w/ NASH Resolution OCA 13% 19% P= % Pbo 0% N=102 N=98 All Completers N=94 N=87 All Completers with Definite or Borderline NASH at Baseline Intercept Subgroup Analysis 1: Data from FLINT study published online in Tetri et al. The Lancet and Supplementary Appendix on November 7, Of FLINT patients assessed for secondary endpoints, 10% (19/200) did not have definite/borderline-nash at baseline 2: All p-values compared to placebo. P-values calculated with the Cochran-Mantel-Haenszel test, stratified by clinic and diabetes status. 32

33 FLINT: Primary and Secondary Histological Endpoints 70% 60% 50% 61% 53% 45% 46% % of Patients w/ Improvement OCA Pbo P= P=0.001 P=0.006 P=0.03 P=0.004 not. sig. not. sig. 40% 30% 20% 10% 21% 38% 35% 31% 35% 19% 22% 13% 13% 12% 0% Primary Endpoint Steatosis Lobular Inflammation Ballooning Fibrosis NASH resolution Portal Inflammation 1: Data from Tetri et al. The Lancet. Published online November 7, : All p-values compared to placebo. P-values calculated with the Cochran-Mantel-Haenszel test, stratified by clinic and diabetes status. 33

34 Phase 2 CONTROL Trial : Combination of OCA And Statins for Monitoring of Lipids Atorvastatin 10mg Atorvastatin 20mg Titrated Atorvastatin Statin Use per EU/US Guidelines N=80 Placebo OCA 5 mg OCA 10 mg OCA 25 mg OCA 10 mg OCA 25 mg 2-year Open Label Extension Study Baseline lipid profile Week 16 Evaluate the impact of varying doses of OCA on LDL and lipid metabolism Evaluate the impact of low doses of statin therapy to modulate LDL in combination with OCA treatment Completed enrollment Nov 2016; data expected mid

35 Appendix: PBC 35

36 Interconnect Our Personalized Patient Support Program MD Prescribes OCALIVA for PBC Interconnect Support Services Specialty Pharmacy Network Patient Conduct Benefit Investigation Assist with appeals Administer financial assistance programs Patient education Compliance and persistency Confirm coverage Distribute product Report data Care Coordinator - Single Point of Contact Interconnect financial assistance programs includes: A $0 copay program for patients with commercial insurance. Access to Ocaliva at no cost for eligible uninsured or underinsured patients. Interconnect can also help refer patients with Medicare or Medicaid to an independent non-profit organization that provides financial assistance to PBC patients 36

37 Global PBC Opportunity Global Prevalence / OCA Candidate Assumptions US ROW 290k 276k Prevalence (rate / ~2016 pop.) 1,2 0.04% 0.035% Access to healthcare 3,4 89.6% 100% PBC Diagnostic rate (2016) 5 47% 49% Under treater care 5 91% 88% Treated w/ UDCA % 112k 112k UDCA discontinue Intolerant/failure 5 8.0% Inadequate responder ALP ULN 5,6 71.0% 134k 119k 112k Adequate responder ALP <ULN 5,6 29.0% 130k 116k 55k 48k 46k 55k 50k 47k Prevalence Access Diagnosed Under treater care UDCA Treated / UDCA discontinue intolerance or failure US EU5 Canada ANZ ROE 72k 29k 30k UDCA treated uncontrolled* (ALP > ULN) 37k 15k 15k UDCA treated uncontrolled* (ALP > 1.67) 1: Kim et al. J. Gastroenterology. 2000; 119(6): : CDA Epidemiology Research 3: US Census Bureau 2015 *: Does not include intolerant patients 4: OCED Health Data : Intercept Market Research 6: Lammers el al Gastroenterology Dec;147(6): Estimates based on FYE

38 Appendix: FXR 38

39 In Animal Models, OCA Activation of FXR has Shown Anti-Fibrotic Effects in the Liver OCA activation of FXR has anti-fibrotic effects in multiple animal models of chronic liver, intestinal and renal diseases and has demonstrated the ability to reverse fibrosis in a rat model of toxic cirrhosis 1-6 Effects of OCA on Fibrosis in TAA Rats 6 Vehicle OCA Representative macroscopic and microscopic (Sirius red stain with subsequent image analysis) illustration of a vehicle- vs. OCA-treated rat 1. Albanis E, Alvarez CE, Pruzanski M, et al. Hepatology Oct;42(4):605A-606A. 2. Vignozzi L, Morelli A, Filippi S, et al. J Sex Med Jan;8(1): Morelli A, Comeglio P, Filippi S, et al. Journal of Steroid Biochemistry and Molecular Biology 2012;132: Wang XX, Jiang T, Shen Y, et al. American Journal of Physiology-Renal Physiology 2009;297:F1587-F Wang XX, Jiang T, Shen Y, et al. Diabetes. 2010;59: Verbeke L, Mannaerts I, Schierwagen R, et al. Sci Rep Sep 16;6:

40 Is There a Rationale for the Therapeutic Potential of FGF19 in Non-viral Liver Diseases? Fibroblast growth factor 19 (FGF19) is an ileal protein hormone that plays a role in governing bile acid homeostasis and metabolic processes The primary source of endocrine FGF19 is the ileum, where FGF19 expression is controlled through FXR activation Bile acids released into the intestine after a meal bind to and activate FXR and thereby induce expression of FGF19 The therapeutic potential of FGF19 has been explored in PBC This compound did not advance to Phase 3 1 To date, no investigational compounds with an FGF19-driven mechanism of action have demonstrated efficacy in patients with NASH 1. NGM press release. March