Skye Bioscience : Corporate Presentation View Presentation ( 260511 Skye Corporate Presentation )

Published: 2026-05-12 13:56:09 ET SKYE

Published on 05/12/2026 at 01:56 pm EDT

May 2O26

Developing Innovative Medicines

to Treat Obesity

and Other Metabolic Diseases

Nasdaq: SKYE

skwe

All drugs are investigational and subject to regulatory approval.

CBeyond data established potential path for combination strategy with existing incretin therapies

Nimacimab

Semaglutide

Additive

Weight Loss

Improved Durability of Weight Loss

Favorable Tolerability Profile

Skye has developed a combination strategy for nimacimab + semaglutide that has the potential to provide a compelling new therapeutic option for patients.

52-Week

Combination Data

High-Dose

Rationale

Commercial Scalability

High-Dose

Feasibility

Attractive Target Product Profile

Regulatory

Alignment

All drugs are investigational and subject to regulatory approval.

Since launching nimacimab in obesity, Skye has delivered a series of field-firsts for peripheral CB1

FIELD FIRST

First-in-class modality

Allosteric GPCR antibody designed

for peripheral CB1 inhibition to improve energy metabolism while

minimizing brain exposure.

CLINICAL FIRST

First human obesity

program with clean safety

First clinical obesity program to evaluate a CB1 monoclonal antibody and create a direct readout for the mechanism without any

neuropsychiatric events.

COMBINATION FIRST

First CB1 + GLP-1 dataset

First reported clinical test of a CB1

mechanism in combination with a GLP-1, establishing proof of

combination activity.

Human-CB1 knock-in DIO workflow + quantitative biodistribution + APC Platform

INFRASTRUCTURE

All drugs are investigational and subject to regulatory approval.

Meaningful combo efficacy, clean safety, and a clear dosing path

Meaningful combination signal

+3.0%

incremental weight loss vs semaglutide

alone at 26 weeks

22.3%

mean weight loss at 52 weeks, with no plateau observed

Significant waist circumference

improvement

Improved lean-to-fat mass ratio

LEARNING 1

Clean safety and tolerability

nimacimab-associated neuropsychiatric signal through 52 weeks

No additive GI burden

with semaglutide

Combination-ready at tested exposure

LEARNING 2

Solvable development variable

200 mg

weekly monotherapy underexposed

peripheral tissues

Next step: higher exposure

Higher-dose expansion study underway

ENHANZE supports higher-exposure SC delivery

LEARNING 3

Meaningful combination efficacy. Clean safety. Clear dosing path.

Nimacimab: complementary, not competitive - potential scalable add-on to enhance incretin therapy

All drugs are investigational and subject to regulatory approval.

GLP-1

Pricing Cliff

$400/month 2026

2031

Semaglutide patents due to expire in 10 countries globally in 2026 (Canada, India, Brazil, etc.).

US patent expiry expected in

2031.

New entrants to the GLP-1 space will not be able to compete with generic semaglutide.

$<50/month

Generic Semaglutide

Obesity is becoming a chronic, multi-line treatment market - and a meaningful proportion of patients already exposed to incretins will need a safer, mechanistically distinct therapy that can deepen response, improve quality of weight loss, or sustain control when the current standard of care leaves clinically important residual disease. Nimacimab is being developed to be that product.

All drugs are investigational and subject to regulatory approval.

Nimacimab: complementary, not competitive - potential scalable add-on to enhance incretin therapy

Patient Demographic

GLP-1 Experienced patients who:

Lose <10% WL

Intolerant to GLP-1

Plateaued WL

Need >20% WL

Current Treatment

Options

Naltrexone/ bupropion (Contrave)

Phentermine/

topiramate (Qysmia)

Orlistat (Xenical/Alli)

Dosing Regimen

Once-weekly (QW)

Potentially once-monthly as maintenance dose

Pricing Structure

$274/month after projected 60% discount

Combined with generic

semaglutide

Total combination cost less than $300/month

A Highly Peripherally-restricted CB1-inhibiting Antibody that Stands Apart from Small-molecule CB1 Inhibitors

Active CB1 engagement promotes inflammation, fibrosis, and metabolic dysfunction; blocking

peripheral CB1 can potentially reverse negatively-trending pathologies

CB1

Adipose Tissue

Kidneys

Triglyceride accumulation

Lipolysis

Inflammation

Fibrosis

Insulin signaling

De novo lipogenesis

Liver & Pancreas

Digestive System

GI motility

Appetite hormones

All drugs are investigational and subject to regulatory approval.

Metabolic Disorders/ Obesity

Metabolic Disorders/ Diabetes

Metabolic Disorders/ Diabetes + MASH

Metabolic Disorders/ Obesity

Long Half-life

Stable antibody with half-life of 18-21 days (potential Q2W or monthly dosing)

Single mutation in the hinge region that prevents antibody Fab exchange

Exclusion from Brain

Multiple NHP studies: background levels in CNS/brain (even at high doses)

All drugs are investigational and subject to regulatory approval.

No accumulation of antibody in CNS/brain despite multiple weekly doses

NOAEL > 75 mg/kg. MTD not reached

Differentiated

Inhibitor

Functions as both an antagonist and an inverse agonist

Binds allosteric site and non-competitively inhibits CB1, independent of agonist

Potential Safe &

Effective Drug

Achieve ~7x peripheral CB1 inhibition while ~600x below CB1 inhibition in brain

Allosteric binding maintains peripheral CB1 inhibition with increased endocannabinoids

Supports a favorable therapeutic index to safely and effectively treat obesity

2-AG or AEA

Peripheral Restriction

Negative Allosteric Modulator

All drugs are investigational and subject to regulatory approval.

Significantly less brain penetration than small molecules currently in development

Unlike small molecules currently in development, nimacimab retains potency even in the presence of competition

All drugs are investigational and subject to regulatory approval.

Based on both cAMP and b-arrestin assays

cAMP-based Assay

β-Arrestin-based Assay

CB1 Inhibitor

IC50 (nM)

Nimacimab

4.96

AM6545 (neutral antagonist)

19.95

Rimonabant

17.6

Monlunabant

1.4

CB1 Inhibitor

IC50 (nM)

Nimacimab

10.83

AM6545 (neutral antagonist)

47.62

Rimonabant

5.36

Monlunabant

0.07

Monlunabant Nimacimab

2-AG or AEA

Monlunabant

competes with AEA/2-AG for binding to the orthosteric site

All drugs are investigational and subject to regulatory approval.

Nimacimab non-competitively binds allosteric site; AEA/2-AG binds the orthosteric site

2-AG or AEA

CB1 Inhibitor

Agonist: CP55940

Reduction in Fold Potency

EC80(50 nM)

40x EC80(2000 nM)

Nimacimab IC50(nM)

7.9

12.7

1.6

Monlunabant IC50(nM)

0.2

21.44

107

All drugs are investigational and subject to regulatory approval.

01 02 03 04

Peripheral Modulation of Appetite Regulating Hormones

Leptin Ghrelin

Improvement

and Restoration of

Glycemic Control

Reduced fasting insulin

and glucose tolerance

Enhanced Lipid

Metabolism

Reduction of Obesity-

Induced Inflammation

Decreased steatosis

and serum cholesterol

Decreased

inflammation and

fibrotic markers

Ghrelin

Leptin

Cumulative Food Intake

All drugs are investigational and subject to regulatory approval.

Serum was collected on day 35, and Ghrelin, and Leptin levels were determined with Bio Plex Multi-Plex immunoassay. n=8 per group. One-way ANOVA followed by Tukey's multiple comparisons test. *p<0.05, **p<0.01 ***p<0.001, ****p<0.0001, # p< 0.05, , # # # # p< 0.001 vs control diet. Cumulative food intake, mixed-effect analysis with time and treatment as main factors, followed by Tukey's multiple comparisons test. Data are expressed as mean ± SEM. n=8-9 per group. **p<0.01 vs control DIO.

Fasting Glucose B

All drugs are investigational and subject to regulatory approval.

D Glucose Tolerance Test E

Fasting Insulin

GTT AUC

C HOMA-IR

F Insulin Tolerance Test

On day 25 of treatment, animals were fasted for 4 h and glucose levels were measured before they were injected 2g/kg glucose. Effect of nimacimab and semaglutide treatments on fasting blood glucose (A), fasting insulin levels (B), HOMA-IR (C), and iPGTT (D). Individual baseline levels of glucose were subtracted to calculate the area under the curve (AUC) (E). On day 28, animals were fasted for 4 h before receiving an intraperitoneal insulin injection (dose 0.75 U/kg at 5 mL/kg) and blood glucose was checked via tail prick to run an ITT (F). For (A), (B), (C), and (E) One-way ANOVA followed by Tukey's multiple comparisons test. For (D) and (F), two-way repeated measurements ANOVA analysis with time and treatment as main factors, followed by Tukey's multiple comparisons test. Data are expressed as mean ± SEM. n=8 per group. * p<0.05, **p<0.01, p<0.001, ****p<0.0001 vs vehicle and # p< 0.05, # # p<0.01, # # #

16 p<0.001, # # # p<0.0001 vs control diet.

Nimacimab Increases Energy Expenditure

DIO mice (n=6) placed in PhenoMaster metabolic cages were dosed nimacimab 240 mg/kg or vehicle (control DIO) Q3D for 14 days. O2consumption, CO2production, food/water intake, and activity were recorded. Nimacimab treatment resulted in a significant increase in energy expenditure and a reduction in food intake, leading to a significant reduction in energy balance, in line with significant body weight loss. Locomotion was not changed by nimacimab treatment.

Control Diet

Vehicle

Nimacimab 24 mg/kg

Nimacimab 75 mg/kg

Hepatic Steatosis Grading

% of Steatosis Area in Liver

Serum Cholesterol

Semaglutide 0.04 mg/kg

All drugs are investigational and subject to regulatory approval.

H&E

(A) H&E-stained liver sections were scored by a pathologist, who was blinded to the treatment groups, 0-3 based on the % of hepatocytes with fat. 0 = no steatosis (<5%), 1 = mild (5-33%), 2 = moderate (>33-66%), and 3 = severe steatosis (>66%). (B) Quantification of steatosis percent area using a computer-aided analysis with Cellprofiler. (C) Cholesterol levels were measured in serum using a commercial kit (Quimica Clinica Aplicada). (D) Representative images of H&E-stained hepatic tissue showing differences in fat deposition among treatment groups. Data are expressed as mean ± SEM. n=4-5 For (B) and (C) One-way ANOVA followed by Tukey's multiple comparisons test. *p<0.05, **p<0.01,

18 ***p<0.001, ****p<0.0001. # # # # p< 0.0001, # # # p< 0.001 vs control diet.

Adipocyte Macrophages

Hepatic Macrophages C Hepatic Fibrosis

Control

Diet

Vehicle

Nimacimab

24 mg/kg

Nimacimab

75 mg/kg

Semaglutide

0.04 mg/kg

All drugs are investigational and subject to regulatory approval.

F4/80

D iWAT

Liver

Nimacimab

24 mg/kg

Nimacimab

75 mg/kg

Semaglutide

0.04 mg/kg

Control

Diet

Vehicle

F4/80

Quantification of F4/80 positive cells (macrophages) in adipose tissue (A) and liver (B) was performed with ImageJ. (C) Quantification of collagen deposition from Sirius red staining (% area) to assess fibrosis. (D) Representative images of F4/80 staining in iWAT and liver. For (A), (B) , and (F) One-way ANOVA

followed by Tukey's multiple comparisons test. *p<0.05, **p<0.01 ***p<0.001, ****p<0.0001, # # # # p< 0.0001, # # # p< 0.001 vs control diet. Data are expressed as mean ± SEM. n=3-7.

A hCB1 Genotyping

hCB1 C57BL/6 wt C57BL/6

Homo Het wt

Mouse CB1 Human CB1

C Dose Curves from Multiple Diet-Induced Obese Studies

In hCB1 transgenic mice, the human CB1 gene was knocked in, disrupting the mouse CB1 gene.

Vehicle

THC (10mg/Kg) THC (20mg/Kg)

Basal

30 min

Basal

30 min

wt C57BL/6 hCB1 C57BL/6 Days

All drugs are investigational and subject to regulatory approval.

B Validation of functional CB1 receptors (THC-induced hypothermia) and weight gain with HFD

Body Temperature (ºC)

Nimacimab 2.4 mg/kg Q3D (n=8) Nimacimab 24 mg/kg Q3D (n=16) Nimacimab 75 mg/kg Q3D (n=16) Nimacimab 240 mg/kg Q3D (n=24)

(A) Representative qPCR genotyping result of hCB1 transgenic mice. (B) Wild-type mice (wt) and homozygous hCB1 C57BL/6 were used to induce THC-mediated hypothermia (n=3 per group)

and fed a high-fat diet (HFD) to measure weight gain. (C) Mice with DIO fed a high-fat diet were dosed with nimacimab (2.4 mg/kg, 24 mg/kg, 75 mg/kg, or 240 mg/kg IP, Q3D). The control

DIO's daily average change in body weight was subtracted from each animal's individual change in body weight to calculate % change in body weight from baseline, vehicle adjusted.

Disclaimer

Skye Bioscience Inc. published this content on May 12, 2026, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on May 12, 2026 at 17:55 UTC.