Full Press Release Details
Nasdaq: ETNB December 2023
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potential indications for pegozafermin, the association of clinical data with potential clinical benefit in other indications, the anticipated timing, design, endpoints, and conduct of our future and ongoing clinical trials for pegozafermin, the
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are cautioned not to give undue weight to such estimates. This presentation discusses product candidates that are under preclinical or clinical evaluation and that have not yet been approved for marketing by the U.S. Food and Drug Administration or
any other regulatory authority. Until finalized in a clinical study report, clinical trial data presented herein remain subject to adjustment as a result of clinical site audits and other review processes. No representation is made as to the safety
or effectiveness of these product candidates for the use for which such product candidates are being studied. 1
Corporate Highlights Potential Best-in-Class FGF21 in Two Phase 3
programs, each of which * represents a significant market opportunity Nonalcoholic Steatohepatitis (NASH) Program 1 Strongest fibrosis data in category with favorable tolerability and dosing convenience First FGF21 with positive 48
wk data; additive benefits in patients on background GLP-1 therapy Regulatory alignment on Phase 3 program including potentially accelerated approval using histology in pre-cirrhotic (F2-F3) and cirrhotic (F4) patients; trials expected to
initiate in 1H24 Severe Hypertriglyceridemia (SHTG) Program Substantially de-risked Phase 3 with topline data anticipated in 2025 3 Strong balance sheet with $448 million in cash Intended commercial product presentation available;
composition of 2 matter patent expires in 2038 Highly experienced leadership team with track record of execution 1 Efficacy comparison based on relative risk ratios and not based on head-to-head results 2 Patent expiration date excludes any patent
term extension or new patents 3 Cash, cash equivalents and short-term investments as of September 30, 2023; excludes in-the-money warrants of approximately $50 million that expire on June 30, 2024 2 * If approved
Advancing Pegozafermin in Clinical Development INDICATION TRIAL
PRECLINICAL PHASE 1 PHASE 2 PHASE 3 NASH Phase 3 trial in F2/F3: Histology & Outcomes - 1Q24 Breakthrough Therapy designation Phase 3 trial in F4: Histology & Outcomes - 2Q24 Phase 3 trial - Ongoing SHTG 3
Pegozafermin Data Published in Prestigious Journals 4
Pegozafermin is an FGF21 Analog Optimally Engineered to Balance Efficacy
and Long Dosing Interval glycoPEG(20kD) FGF21 Pegozafermin EC (nM) EC (nM) 50 50 Strong and flexible linker RECEPTOR Mean S.D. Mean S.D. (glycoPEGylation technology) Position 182 KLB nd nd KLB/FGFR1 4.5 1.0 0.3 0.07
N-terminus C-terminus FGF21 XX KLB/FGFR2 4.5 0.9 1.1 0.4 KLB/FGFR3 1.8 0.3 1.2 0.4 Mutations in positions 173 and 176 KLB/FGFR4 nd nd (glycoPEG attached at position 173) nd - not determined; rhFGF19 EC at FGFR4 =
1.7 0.4 50 Proprietary glycoPEGylation technology commercially validated with approved products Increases half-life of native FGF21 (<2 hours) to 55-100 hours based on single ascending dose study Low nanomolar
potency against FGF receptors 1c, 2c, 3c, similar to native FGF21 Composition of Matter patent expiring in 2038 * Receptor agonism measured in L6 cells expressing -klotho and either FGF Receptor 1c, 2c, 3c, or 4 via pERK functional
assay 5 ** Table represents mean data from multiple experiments
* Pegozafermin Offers Potential Best-in-Class Therapeutic for NASH
REDUCES LIVER FAT FAVORABLE TOLERABILITY & IMPROVES REVERSES LIVER FIBROSIS RESOLVES NASH CONVENIENT DOSING INSULIN to improve patient RESISTANCE persistence and compliance IMPROVES DYSLIPIDEMIA * If approved 7
ENLIVEN Trial Evaluated Weekly (QW) and Every-Two-Week (Q2W) Dosing in
Patients with NASH F2-F3 BLINDED PRIMARY ENDPOINTS MAIN STUDY EXTENSION PHASE (24 weeks) (24 weeks) 1-stage fibrosis improvement 1 with no worsening of NASH Placebo (QW or Q2W) PLACEB PLO* ACEBO (QWQ2 orW Q2W) NASH resolution
with no 2 worsening of fibrosis Pegozafermin 15mg QW Pegozafermin 15mg QW KEY SECONDARY Pegozafermin 30mg QW Pegozafermin 30mg QW EFFICACY ENDPOINTS 2-point change in NAS with no Pegozafermin 44mg Q2W Pegozafermin 44mg Q2W worsening
of fibrosis B B Non-invasive liver markers (liver fat, liver injury, fibrosis markers) Week 12 Week 24 Week 48 B Liver Biopsy MRI-PDFF Primary endpoint 1 Improvement in liver fibrosis by 1 stage and no worsening of steatohepatitis
defined as no increase in NAS for ballooning, inflammation, or steatosis (FDA draft guidance). 2 Resolution of steatohepatitis is defined as absent fatty liver disease or isolated or simple steatosis without steatohepatitis and a NAS score of 0-1
for inflammation, 0 for ballooning and any value for steatosis (FDA draft guidance). *Some placebo patients were re-randomized in the extension phase to receive pegozafermin. 8 NAS, NAFLD Activity Score; MRI-PDFF, Magnetic resonance
imaging-estimated proton density fat fraction; QW: Every week; Q2W: Every 2 weeks SCREENING RANDOMIZATION
Baseline Characteristics Well Balanced Across Dose Groups Parameter
Placebo 15mg QW 30mg QW 44mg Q2W Total Mean or % (n=71) (n=21) (n=73) (n=57) (n=222) Age (years) 56 55 55 55 56 Female 55% 43% 69% 65% 61% 2 BMI (kg/m ) 38 38 35 36 37 Type 2 Diabetes 69% 86% 62% 61% 66% Fibrosis Stage (% F3) 66% 43% 64% 53% 60%
NAFLD Activity Score 5.0 4.8 5.3 5.2 5.1 Liver Fat Content (MRI-PDFF) 16.7% 15.8% 16.7% 15.8% 16.4% Liver Stiffness (VCTE, kPa) 14.1 11.2 12.5 13.2 13.0 PRO-C3 (ng/mL) 50 62 54 52 53 ALT (U/L) 50 61 60 56 56 AST (U/L) 41 48 47 42 44 HbA1c, overall
population (%) 6.6 7.0 6.6 6.7 6.7 Triglycerides (mg/dL) 170 186 175 165 172 Baseline characteristics were consistent in full analysis set (n=192) and the safety set (n=222) Source: Randomized Analysis Set. ALT, alanine aminotransferase; AST,
aspartate aminotransferase; NAFLD, nonalcoholic fatty liver disease; PRO-C3, N-terminal type III collagen propeptide; VCTE, Vibration-controlled transient elastography. 9
WEEK 24 Pegozafermin Demonstrated Statistical Significance on Fibrosis
Improvement at 30mg QW and 44mg Q2W Dose Fibrosis Improvement Without Worsening of NASH at Week 24 p=0.008 40% p=0.008 p=0.1 30% 27% 26% 22% 20% 19% 20% 15% 10% 7% 0% Placebo 15mg QW 30mg QW 44mg Q2W n=61 n=14 n=66 n=51 * Relative Risk 1.0 2.9 3.5
3.6 *Relative risk presented is calculated by dividing the drug response by placebo response. Relative risk calculated using statistical methods show similar results. Source: Full Analysis Set; multiple imputation analysis via
Cochran-Mantel-Haenszel (CMH) test stratified by type 2 diabetes mellitus (T2DM) status (yes vs. no) and fibrosis stage (F2 vs. F3). 10
Comparative Clinical Data in Non-Cirrhotic Patients 1 Stage
Fibrosis Improvement with No Worsening of NASH (placebo-adjusted) 2 Pegozafermin Ocaliva Resmetirom Lanifibranor Semaglutide Efruxifermin Phase 3 | 52 weeks Phase 2b | 24 weeks Phase 3 | 72 weeks Phase 2b | 24 weeks Phase 2 | 72 weeks Phase
2b | 24 weeks 1 Multiple Imputation Completers Analysis Drug response as multiple of 3.5 3.6 2.3 1.7 1.9 1.1 1.6 1.3 2.0 2.0 placebo response* 21% 20% 19% 19% 17% 12% 13% 10% 10% 3% p<0.05 p<0.05 p=0.008 p=0.008 p<0.001 p=0.0002 p<0.0001
p=ns p=0.04 p=ns 50mg 30mg QW 44mg Q2W 25mg 80mg 100mg 800mg 1200mg 0.4mg QD 28mg (n=34) (n=66) (n=51) (n=308) (n=316) (n=321) (n=63) (n=69) (n=56) (n=38) *Drug response as multiple of placebo response is calculated by dividing drug response by
placebo response 1 2 Results same for Completer Analysis Set; 1 stage fibrosis improvement with no worsening of NAS; Program discontinued; ns= not significant Note: These data are derived from different clinical trials at different
points in time, with differences in trial design and patient populations. As a result, cross-trial comparisons cannot be made, and no head-to-head clinical trials have been conducted. 11
WEEK 24 Pegozafermin Demonstrated Statistical Significance on NASH
Resolution at All Doses NASH Resolution Without Worsening of Fibrosis at Week 24 p=0.0005 p=0.0009 50% p<0.0001 40% 37% 30% 26% 23% 20% 35% 24% 21% 10% 2% 0% Placebo 15mg QW 30mg QW 44mg Q2W n=61 n=14 n=66 n=51 * Relative Risk 1.0 18.8 11.8 13.5
* Relative risk presented is calculated by dividing the drug response by placebo response. Relative risk calculated using statistical methods show similar results. Source: Full Analysis Set; multiple imputation analysis via Cochran-Mantel-Haenszel
(CMH) test stratified by T2DM status (yes vs. no) and fibrosis stage (F2 vs. F3). 12
Comparative Clinical Data in Non-Cirrhotic Patients NASH Resolution
with No Worsening of Fibrosis 2 Pegozafermin Ocalivia Resmetirom Lanifibranor Semaglutide Efruxifermin Phase 2b | 24 weeks Phase 3 | 72 weeks Phase 3 | 52 weeks Phase 2b | 24 weeks Phase 2 | 72 weeks Phase 2b | 24 weeks 1 Multiple Imputation
Completers Analysis Drug response as multiple of 11.8 13.5 1.9 2.6 3.0 1.7 2.1 3.5 3.1 5.1 placebo response* 61% 44% 32% 26% 24% 21% 20% 17% 16% 3% p=ns p=0.0009 p=0.0005 p<0.0001 p<0.0001 p=0.039 p=0.002 p<0.001 p<0.01 p<0.001 30mg
QW 44mg Q2W 25mg 80mg 100mg 800mg 1200mg 0.4mg 28mg 50mg (n=66) (n=51) (n=308) (n=316) (n=321) (n=56) (n=38) (n=34) (n=63) (n=69) * Drug response as multiple of placebo response is calculated by dividing drug response by placebo response 1 2 Results
same for Completer Analysis Set; NASH resolution with 2 point reduction in NAS and no worsening of fibrosis Program discontinued 13 Note: These data are derived from different clinical trials at different points in time, with
differences in trial design and patient populations. As a result, cross-trial comparisons cannot be made, and no head-to-head clinical trials have been conducted.
WEEK 24 Pegozafermin Demonstrated Statistical Significance on the
Combined Endpoint of Fibrosis Improvement and NASH Resolution Both Fibrosis Improvement and 2-Point Improvement in NAS and MRI-PDFF NASH Resolution at Week 24 Response and ALT Response 30% 80% *** 60% *** 60% *** 20% 52% 20% *** 14% 40% 10%
20% 9% 0% 0% 0% Placebo 30mg QW 44mg Q2W Placebo 30mg QW 44mg Q2W n=61 n=66 n=51 n=61 n=66 n=51 Source: Full Analysis Set; multiple imputation analysis via Cochran-Mantel-Haenszel (CMH) test stratified by T2DM status (yes vs. no) and fibrosis stage
(F2 vs. F3). MRI-PDFF responder defined as 30% reduction in liver fat content; ALT responder defined as 17U/L reduction. 14 ***p<0.001 versus placebo. Patients Patients
WEEK 24 Pegozafermin Demonstrated Robust Liver Fat Reduction with High
Responder Rates by MRI-PDFF 1 Mean Relative Reduction in Liver Fat vs Baseline Patients Achieving 30% and 50% Reduction in 2 at Week 24 Hepatic Fat Fraction Versus Baseline Placebo 30mg QW 44mg Q2W N=48 N=49 N=35 100% 0% -10% 80%
30% *** 85% *** -20% 77% reduction -15% 60% -30% -40% 40% *** 50% *** 67% 66% -50% reduction *** 31% 20% -50% *** -60% -55% 13% -70% 0% Placebo 30mg QW 44mg Q2W N=48 N=44 N=33 1 2 Analysis via mixed model repeated measure (MMRM).
Analysis via Cochran-Mantel-Haenszel (CMH) test stratified by T2DM status (yes vs. no) and fibrosis stage (F2 vs. F3). MRI-PDFF Analysis Set in patients with >10% liver fat at baseline. 15 ***p<0.001 versus placebo Change from baseline
WEEK 24 Pegozafermin Demonstrated Significant Improvements in Markers
of Liver Injury/Inflammation (ALT and AST) Mean Relative Reduction in ALT vs Mean Relative Reduction in AST vs Baseline at Week 24 Baseline at Week 24 Placebo 30mg QW 44mg Q2W Placebo 30mg QW 44mg Q2W n=61 n=66 n=51 n=61 n=66 n=51 0% 0% -10% -5%
-10% -5% -20% -20% -30% -30% *** -32% *** -34% -40% -40% *** -39% *** -42% -50% -50% ALT *** *** 24% 59% 65% 1 normalization 1 ALT normalization defined as patients with ALT 30 U/L at baseline (n=133) with end-of-study ALT <30 U/L. Source:
Full Analysis Set: Analysis via mixed model with repeated measure (MMRM). Data presented as LS Means. 16 ***p<0.001 versus placebo.
WEEK 24 Pegozafermin Demonstrated Significant Reductions in
Non-Invasive Markers (NITs) of Liver Inflammation and Fibrosis cT1 - Absolute Change from VCTE - Absolute Change from FAST - Percent Change from Baseline at Week 24 (ms) Baseline at Week 24 (kPa) Baseline at Week 24 0 0% 0.8 0.5 -6 -6% -20 -20% -0.5
-40 -40% -1.5 -60 -60% *** *** -2.5 -70 -56% *** -80 ** -57% -2.4 *** -3.1 *** -92 -100 -3.5 -80% Placebo 30mg QW 44mg Q2W Placebo 30mg QW 44mg Q2W Placebo 30mg QW 44mg Q2W n=57 n=61 n=49 n=61 n=66 n=51 n=61 n=66 n=51 Placebo-adjusted -86 -64
Placebo-adjusted -3.9 -3.2 Placebo-adjusted -50% -51% Source: Full Analysis Set for FibroScan and PRO-C3 assessments and MRI-PDFF analysis set for cT1, Analysis via MMRM for cT1 and PRO-C3, ANCOVA for VCTE. A patient is designated a cT1 responder
with 80 msec reduction as compared to baseline. cT1 analysis was performed at sites where available. 17 *p<0.05, **p<0.01, ***p<0.001 versus placebo.
WEEK 24 Pegozafermin Demonstrated Significant Improvements on Non-
Invasive Markers (NITs) for Fibrosis ELF - Absolute Change from FIB-4 - Absolute Change from PRO-C3 - Percent Change from Baseline at Week 24 (ms) Baseline at Week 24 (kPa) Baseline at Week 24 0.3 0.2 6% 0.2 0.1 5% 0.1 0.0 -5% -0.1 -0.2 -15% -0.3
*** *** *** -0.3 -0.3 *** -17% -18% *** -0.3 *** -0.4 -0.4 -0.5 -25% Placebo 30mg QW 44mg Q2W Placebo 30mg QW 44mg Q2W Placebo 30mg QW 44mg Q2W n=61 n=66 n=51 n=61 n=66 n=51 n=61 n=66 n=51 Placebo-adjusted -0.5 -0.5 Placebo-adjusted -0.4 -0.4
Placebo-adjusted -25% -24% Source: Full Analysis Set. NITs reported as LS means with changes from baseline (absolute or %) 18 ***p<0.001 versus placebo.
WEEK 48 Pegozafermin Demonstrated Sustained Benefits Across Key Liver
NITs and Metabolic Markers At 48 Weeks of Treatment BACKGROUND KEY RESULTS After the Main Study (week 24), patients entered Robust effects were observed at week 48 on liver a 24-week blinded Extension Phase for a total of fat
reduction, markers of liver fibrosis, 48 weeks of treatment inflammation and injury, and metabolic markers Liver benefits at week 48 assessed by NITs only. Maintenance of benefit was seen through week 48 Repeat biopsies were not
conducted Benefit sustained in patients on background GLP-1 Some placebo patients (n=19) were re- therapy and in patients with compensated randomized at week 24 to receive pegozafermin cirrhosis (F4) 30mg QW during the Extension
Phase Favorable safety and tolerability profile 19
ENLIVEN Patient Disposition and Analysis Sets DOSED Safety Analysis Set
Ineligible per 3-panel read N=219 Stage F1 (n=7) Stage F4 (n=14) Stage F2/F3 but NAS <4 (n=6) F2/F3, NAS 4 N=192 Full Analysis Set (FAS) Placebo 15mg QW 30mg QW 44mg Q2W n=61 n=14 n=66 n=51 Extension Placebo 30mg QW
Phase Full 15mg QW 30mg QW 44mg Q2W n=35 n=19 n=14 n=50 n=45 Analysis Set (eFAS) Analysis Sets were prospectively defined MRI-PDFF Analysis Set = all patients in FAS with baseline and at least one post-baseline MRI-PDFF assessment (n=181).