Full Press Release Details
Nasdaq: ETNB April 2025
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statements" within the meaning of the federal securities laws, which statements are subject to substantial risks and uncertainties and are based on estimates and assumptions. Other than statements of historical facts, all statements included
in this presentation are forward-looking statements, including statements concerning our plans, objectives, goals, strategies, future events, plans or intentions relating to product candidates, potential market opportunities, estimates of market
size, estimates of market growth, estimates of market share, the potential clinical benefit, complementary benefits to other therapies, effect on histology and safety and tolerability profile of pegozafermin (formerly BIO89-100), the clinical
potential of pegozafermin, 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, including the expected histology data from the Phase 3 trials in MASH with Advance Fibrosis (F2-F3) and MASH with Compensated Cirrhosis (F4) and the expected topline results from the Phase 3 trial in SHTG, the timing of
anticipated milestones, the timing of regulatory meetings, the timing and likelihood of success, plans and objectives of management for future operations and future results of anticipated product development efforts and our liquidity and capital
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obtained the industry, market and competitive position data used throughout this presentation from our own internal estimates and research, as well as from industry and general publications, and research, surveys and studies conducted by third
parties. Internal estimates are derived from publicly available information released by industry analysts and third-party sources, our internal research and our industry experience, and are based on assumptions made by us based on such data and our
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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 Pegozafermin (long-acting FGF21) Potential
Best-in-class profile Well-positioned for targets three significant with robust fibrosis benefit and commercial success market opportunities favorable tolerability/safety FGF21 is the leading mechanism of Reversal of fibrosis and cirrhosis
Highly experienced team well- action in MASH with Advanced Fibrosis across F2-F4 MASH patients positioned for Phase 3 trials and (F2-F3) and Compensated Cirrhosis (F4) commercialization - F2-F3: 3.5x vs. placebo (relative risk); 20%
fibrosis improvement Global manufacturing strategy MASH with Advanced Fibrosis (F2-F3) over placebo provides resilience and flexibility Phase 3 trial with topline histology data - F4: 45% fibrosis improvement over Commercial
liquid product expected in 1H 2027 placebo presentation with potential to co- formulate with incretin therapies MASH with Compensated Cirrhosis (F4) Potential best-in-class safety and Phase 3 trial with topline histology data
tolerability Strong balance sheet with $440 expected in 2028 million in cash as of Dec. 31, 2024 - Potential best-in-class GI - Additional gross proceeds of tolerability profile Severe Hypertriglyceridemia (SHTG) $287.5 million
from the Jan 2025 - No statistically significant or clinical Synergistic program to MASH follow-on offering meaningful changes in bone Phase 3 fully enrolled with topline biomarkers and DXA data expected in 1Q 2026 2
Advancing Pegozafermin Through Late-Stage Clinical Development
ANTICIPATED KEY INDICATION TRIAL PRECLINICAL PHASE 1 PHASE 2 PHASE 3 MILESTONES Histology MASH * Phase 3 trial in F2/F3: Histology & Outcomes - Ongoing data 1H 2027 Breakthrough Therapy & Histology PRIME * Phase 3 trial in F4:
Histology & Outcomes - Ongoing data designations 2028 Topline Data SHTG Phase 3 trial in SHTG: 52-Week Trial - Fully Enrolled 1Q 2026 * Histology data from both ENLIGHTEN-Fibrosis (F2-F3) and ENLIGHTEN-Cirrhosis (F4) are intended to
support accelerated approval in the US and conditional approval in Europe, based on previously obtained alignment with the FDA and EMA 3
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 COM patents
covering pegozafermin expire in 2038. Other patents and patent applications covering method, formulation and other claims could extend exclusivity to 2044.*** * Receptor agonism measured in L6 cells expressing -klotho and either FGF Receptor
1c, 2c, 3c, or 4 via pERK functional assay ** Table represents mean data from multiple experiments 4 *** Expiry dates do not give effect to any available patent term adjustments or extensions that may be available and assume issuance with respect to
Global Manufacturing Strategy Provides Resilience and Flexibility
Resilient and diversified supply chain with alternative CDMOs for each step in the supply chain mitigates against macroeconomic and geopolitical environment changes Northway Biotech ("BTPH") BiBo Biopharma Engineering EU-based
CDMO partner since 2018 In 2024, began commercial-scale DS for all clinical drug substance (DS) manufacturing on existing 30kL line supplies in China 3kL FDA-approved facility could Installation of three additional 30kL
support initial commercial launch, if lines underway; provides needed; ability to expand to 30kL manufacturing capabilities to meet capacity peak commercial supply forecast Drug Product manufactured in the United States Tariff Exposure (assuming
pharmaceuticals are not exempt) Minimal, if any, expected with current manufacturing strategy Bulk Drug Substance (BDS) can be manufactured at CDMOs in either UK or EU and Drug Product (DP) is manufactured in the US; both BDS and DP
are a significant % of the COGS 5
Pegozafermin Offers Potential Best-in-Class Therapeutic for Advanced
MASH REDUCES LIVER FAT FAVORABLE TOLERABILITY & IMPROVES REVERSES LIVER FIBROSIS RESOLVES MASH CONVENIENT DOSING INSULIN to improve patient RESISTANCE persistence and compliance IMPROVES DYSLIPIDEMIA * If approved 7
ENLIVEN Phase 2b Trial Evaluated Weekly (QW) and Every-Two-Week (Q2W)
Dosing in Non-cirrhotic Patients BLINDED PRIMARY ENDPOINTS MAIN STUDY EXTENSION PHASE (24 weeks) (24 weeks) 1-stage fibrosis improvement 1 with no worsening of MASH Placebo (QW or Q2W) PLACEB PLO* ACEBO (QWQ2 orW Q2W) MASH
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
WEEK 24 Pegozafermin Demonstrated Statistical Significance on Fibrosis
Improvement at 30mg QW and 44mg Q2W Dose Rigorous Biopsy Reading Methodology Independent 3-reader consensus methodology, that minimizes placebo response rate and more accurately measures drug effect Fibrosis Improvement Without Worsening of MASH at
Week 24 p=0.008 40% Treatment with PGZ Delayed p=0.008 Progression to Cirrhosis p=0.1 27% 30% 26% In the placebo group, 22% 7 of 37 (19%) of the F3 20% patients progressed 19% 20% 15% 7% In the pooled PGZ group, 10% 6 of 69 (9%) of
the F3 patients progressed 0% ITT Population Placebo 15mg QW 30mg QW 44mg Q2W n=192 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. 9 Source: Full Analysis Set (ITT); Multiple imputation analysis via Cochran-Mantel-Haenszel (CMH); test stratified by type 2 diabetes mellitus (T2DM) status (yes vs. no) and fibrosis stage
Comparative Clinical Data in Non-Cirrhotic (F2/F3) Patients 1
Stage Fibrosis Improvement with No Worsening of MASH 1 Pegozafermin Efruxifermin Efimosfermin Survodutide Rezdiffra Tirzepatide Denifanstat VK2809 Semaglutide FGF21 FGF21 FGF21 GLP-1/Glucagon TR- Agonist GLP-1/GIP FASN TR- Agonist GLP-1
Phase 2b Phase 2b Phase 2 Phase 2 Phase 3 Phase 2 Phase 2b Phase 2b Phase 3 24 Weeks 24 Weeks 24 Weeks 48 Weeks 52 Weeks 52 Weeks 52 Weeks 52 Weeks 72 Weeks 2 3 reader panel 2 readers 2 readers Single reader 2 readers 2 readers Single reader 2
readers 24% 21% 21% 21% 20% 19% 19% 19% 17% 16% 15% 14% 12% 10% 2.4mg 30mg 44mg 28mg 50mg 300mg 4.8mg 6mg 80mg 100mg 10mg 15mg 50mg Combined (n=534) QW Q2W (n=38) (n=34) (n=31) (n=72) (n=74) (n=316) (n=321) (n=47) (n=48) (n=81) (n=137) (n=66) (n=51)
1 1 stage fibrosis improvement with no worsening of NAS. Fibrosis improvement by 1 stage with no worsening of NAFLD activity score. 2 Each slide is read by two readers (a pair), who were randomly selected out of six centralized
pathologies 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- 10 head clinical
trials have been conducted.
Relative Risk: A Better Method for Cross-Trial Effectiveness
Comparisons As Presented by Michael Charlton MD at MASH-TAG Jan 10, 2025 RELATIVE RISK: The comparative probability of achieving the primary efficacy endpoint. Used to estimate the strength of 1 association between treatment and an outcome. Outcome
risk should be similar between studies. ACTIVE PLACEBO Responders A B Nonresponders C D RR <1 Decreased likelihood of outcome with treatment A/(A+C) RR = RR =1 No benefit B/(B+D) RR >1 Increased likelihood of outcome with treatment 1 Doi et
al., J of Clin Epidemiology, Volume 142, 271-279 11
Relative Risk: Comparative Clinical Data in Non-Cirrhotic (F2/F3)
Patients Pegozafermin Outperforms Other Drugs Based on Relative Risk In absence of H2H studies, Relative Risk, or drug response as a multiple of placebo, offers robust window for cross-trial comparisons by controlling for variability amongst
readers, patient characteristics/selection, duration, and biopsy reading methodology 1 Pegozafermin Efruxifermin Efimosfermin Survodutide Rezdiffra Tirzepatide Denifanstat VK2809 Semaglutide FGF21 FGF21 FGF21 GLP-1/Glucagon TR- Agonist
GLP-1/GIP FASN TR- Agonist GLP-1 Phase 2b Phase 2b Phase 2 Phase 2 Phase 3 Phase 2 Phase 2b Phase 2b Phase 3 24 Weeks 24 Weeks 24 Weeks 48 Weeks 52 Weeks 52 Weeks 52 Weeks 52 Weeks 72 Weeks 3 reader panel 2 readers 2 readers Single reader 2
readers 2 readers Single reader 2 readers 3.6 3.5 2.1 2.1 2.0 2.0 2.0 1.9 1.8 1.7 1.7 1.7 1.6 1.5 30mg 44mg 28mg 50mg 300mg 4.8mg 6mg 80mg 100mg 10mg 15mg 50mg Combined 2.4mg QW Q2W (n=38) (n=34) (n=31) (n=72) (n=74) (n=316) (n=321) (n=47) (n=48)
(n=81) (n=137) (n=534) (n=66) (n=51) *Relative risk, or drug response as multiple of placebo response, is calculated by dividing drug response by placebo response 1 1 stage fibrosis improvement with no worsening of NAS. Fibrosis improvement
by 1 stage with no worsening of NAFLD activity score. 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- 12 head clinical trials have been conducted.
Pegozafermin Differentiates as a Leading Therapy for F2-F3 MASH Based
on the Highest SUCRA Score (Hepatology Journal) COMPARISON OF PHARMACOLOGICAL THERAPIES IN MASH FOR FIBROSIS REGRESSION AND MASH RESOLUTION Data Sources 29 randomized controlled trials 9,234 Patients with MASH Source: Souza, Matheus, et. al. 2025.
"Comparison of Pharmacological Therapies in Metabolic Dysfunction-Associated Steatohepatitis for Fibrosis Regression and MASH Resolution: Systematic Review and Network Meta-Analysis." Hepatology, February 4.
WEEK 24 Pegozafermin Demonstrated Statistical Significance on MASH
Resolution at All Doses MASH 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). 14
WEEK 24 Pegozafermin Demonstrated Statistical Significance on the
Combined Endpoint of Fibrosis Improvement and MASH Resolution Both Fibrosis Improvement and 2-Point Improvement in NAS and MRI-PDFF MASH 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. 15 ***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. 16 ***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. 17 ***p<0.001 versus placebo.
WEEK 24 Pegozafermin Demonstrated Significant Reductions in