Trial Outcomes & Findings for Study of Subcutaneously Administered ENT-03 for the Treatment of Obesity and Diabetes (NCT NCT05925920)

Last Updated: 2026-06-01

Results Overview

Treatment Emergent Adverse events (TEAEs) were collected from Day 1 (dosing visit ) through End of Study visit (Day 14 post-dose). TEAEs were defined as any AE with onset on or after the date of study drug administration. TEAEs were recorded by the investigator based on subject report, clinical observation, physical examination, vital signs, laboratory assessments, and ECG findings. Severity was graded per NCI CTCAE v5.0. Relatedness to study drug was assessed by the investigator. TEAEs of special interest included nausea, vomiting, and injection site reactions.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

49 participants

Primary outcome timeframe

From Day 1 (dosing visit) through Day 14 (End of Study visit), approximately 3 to 4 weeks

Results posted on

2026-06-01

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort 1 (no T2D): ENT-03S 3 mg Single subcutaneous dose of 3 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 2 (no T2D): ENT-03S 6 mg Single subcutaneous dose of 6 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 3 (no T2D): ENT-03S 12.5 mg Single subcutaneous dose of 12.5 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 4 (no T2D): ENT-03S 25 mg Single subcutaneous dose of 25 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 5 (no T2D): ENT-03S 50 mg Single subcutaneous dose of 50 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 6 (T2D): ENT-03S 50 mg Single subcutaneous dose of 50 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) and Type 2 diabetes (HbA1c 6.5-8.5%), on no antidiabetic medications or stable metformin. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 7 (T2D): ENT-03S 75 mg Single subcutaneous dose of 75 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) and Type 2 diabetes (HbA1c 6.5-8.5%), on no antidiabetic medications or stable metformin. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Placebo (All Cohorts) Single subcutaneous dose of placebo administered across all 7 cohorts (Cohorts 1-5: subjects with obesity without Type 2 diabetes; Cohorts 6-7: subjects with obesity and Type 2 diabetes). Each cohort enrolled 2 placebo subjects using a 5:2 active:placebo randomization ratio with sentinel dosing. Placebo subjects from all cohorts are pooled in this arm as no active intervention was administered. Total N=14.
Overall Study STARTED	5	5	5	5	5	5	5	14
Overall Study COMPLETED	5	5	5	5	5	5	5	12
Overall Study NOT COMPLETED	0	0	0	0	0	0	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1 (no T2D): ENT-03S 3 mg Single subcutaneous dose of 3 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 2 (no T2D): ENT-03S 6 mg Single subcutaneous dose of 6 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 3 (no T2D): ENT-03S 12.5 mg Single subcutaneous dose of 12.5 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 4 (no T2D): ENT-03S 25 mg Single subcutaneous dose of 25 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 5 (no T2D): ENT-03S 50 mg Single subcutaneous dose of 50 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 6 (T2D): ENT-03S 50 mg Single subcutaneous dose of 50 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) and Type 2 diabetes (HbA1c 6.5-8.5%), on no antidiabetic medications or stable metformin. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 7 (T2D): ENT-03S 75 mg Single subcutaneous dose of 75 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) and Type 2 diabetes (HbA1c 6.5-8.5%), on no antidiabetic medications or stable metformin. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Placebo (All Cohorts) Single subcutaneous dose of placebo administered across all 7 cohorts (Cohorts 1-5: subjects with obesity without Type 2 diabetes; Cohorts 6-7: subjects with obesity and Type 2 diabetes). Each cohort enrolled 2 placebo subjects using a 5:2 active:placebo randomization ratio with sentinel dosing. Placebo subjects from all cohorts are pooled in this arm as no active intervention was administered. Total N=14.
Overall Study Withdrawal by Subject	0	0	0	0	0	0	0	2

Baseline Characteristics

Study of Subcutaneously Administered ENT-03 for the Treatment of Obesity and Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 (no T2D): ENT-03S 3 mg n=5 Participants Single subcutaneous dose of 3 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 2 (no T2D): ENT-03S 6 mg n=5 Participants Single subcutaneous dose of 6 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 3 (no T2D): ENT-03S 12.5 mg n=5 Participants Single subcutaneous dose of 12.5 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 4 (no T2D): ENT-03S 25 mg n=5 Participants Single subcutaneous dose of 25 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 5 (no T2D): ENT-03S 50 mg n=5 Participants Single subcutaneous dose of 50 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 6 (T2D): ENT-03S 50 mg n=5 Participants Single subcutaneous dose of 50 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) and Type 2 diabetes (HbA1c 6.5-8.5%), on no antidiabetic medications or stable metformin. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 7 (T2D): ENT-03S 75 mg n=5 Participants Single subcutaneous dose of 75 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) and Type 2 diabetes (HbA1c 6.5-8.5%), on no antidiabetic medications or stable metformin. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Placebo (All Cohorts) n=14 Participants Single subcutaneous dose of placebo administered across all 7 cohorts (Cohorts 1-5: subjects with obesity without Type 2 diabetes; Cohorts 6-7: subjects with obesity and Type 2 diabetes). Each cohort enrolled 2 placebo subjects using a 5:2 active:placebo randomization ratio with sentinel dosing. Placebo subjects from all cohorts are pooled in this arm as no active intervention was administered. Total N=14.	Total n=49 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=24 Participants	0 Participants n=24 Participants	0 Participants n=48 Participants	0 Participants n=100 Participants	0 Participants n=201 Participants	0 Participants n=1000 Participants	0 Participants n=58 Participants	0 Participants n=61 Participants	0 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=24 Participants	5 Participants n=24 Participants	5 Participants n=48 Participants	4 Participants n=100 Participants	5 Participants n=201 Participants	3 Participants n=1000 Participants	3 Participants n=58 Participants	12 Participants n=61 Participants	42 Participants
Age, Categorical >=65 years	0 Participants n=24 Participants	0 Participants n=24 Participants	0 Participants n=48 Participants	1 Participants n=100 Participants	0 Participants n=201 Participants	2 Participants n=1000 Participants	2 Participants n=58 Participants	2 Participants n=61 Participants	7 Participants
Age, Continuous	51.7 years STANDARD_DEVIATION 10.90 • n=24 Participants	46.7 years STANDARD_DEVIATION 11.51 • n=24 Participants	50.4 years STANDARD_DEVIATION 10.13 • n=48 Participants	58.7 years STANDARD_DEVIATION 8.00 • n=100 Participants	50.3 years STANDARD_DEVIATION 10.66 • n=201 Participants	60.4 years STANDARD_DEVIATION 5.22 • n=1000 Participants	54.7 years STANDARD_DEVIATION 10.83 • n=58 Participants	51.6 years STANDARD_DEVIATION 10.98 • n=61 Participants	54.0 years STANDARD_DEVIATION 10.30
Sex: Female, Male Female	2 Participants n=24 Participants	2 Participants n=24 Participants	2 Participants n=48 Participants	3 Participants n=100 Participants	4 Participants n=201 Participants	4 Participants n=1000 Participants	2 Participants n=58 Participants	5 Participants n=61 Participants	24 Participants
Sex: Female, Male Male	3 Participants n=24 Participants	3 Participants n=24 Participants	3 Participants n=48 Participants	2 Participants n=100 Participants	1 Participants n=201 Participants	1 Participants n=1000 Participants	3 Participants n=58 Participants	9 Participants n=61 Participants	25 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=24 Participants	0 Participants n=24 Participants	0 Participants n=48 Participants	0 Participants n=100 Participants	0 Participants n=201 Participants	0 Participants n=1000 Participants	0 Participants n=58 Participants	0 Participants n=61 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants n=24 Participants	0 Participants n=24 Participants	0 Participants n=48 Participants	1 Participants n=100 Participants	0 Participants n=201 Participants	0 Participants n=1000 Participants	0 Participants n=58 Participants	0 Participants n=61 Participants	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=24 Participants	0 Participants n=24 Participants	0 Participants n=48 Participants	0 Participants n=100 Participants	0 Participants n=201 Participants	0 Participants n=1000 Participants	0 Participants n=58 Participants	0 Participants n=61 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants n=24 Participants	0 Participants n=24 Participants	0 Participants n=48 Participants	1 Participants n=100 Participants	0 Participants n=201 Participants	0 Participants n=1000 Participants	1 Participants n=58 Participants	4 Participants n=61 Participants	6 Participants
Race (NIH/OMB) White	5 Participants n=24 Participants	4 Participants n=24 Participants	5 Participants n=48 Participants	2 Participants n=100 Participants	4 Participants n=201 Participants	4 Participants n=1000 Participants	3 Participants n=58 Participants	8 Participants n=61 Participants	35 Participants
Race (NIH/OMB) More than one race	0 Participants n=24 Participants	0 Participants n=24 Participants	0 Participants n=48 Participants	0 Participants n=100 Participants	0 Participants n=201 Participants	0 Participants n=1000 Participants	1 Participants n=58 Participants	0 Participants n=61 Participants	1 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=24 Participants	1 Participants n=24 Participants	0 Participants n=48 Participants	1 Participants n=100 Participants	1 Participants n=201 Participants	1 Participants n=1000 Participants	0 Participants n=58 Participants	2 Participants n=61 Participants	6 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=24 Participants	3 Participants n=24 Participants	3 Participants n=48 Participants	2 Participants n=100 Participants	3 Participants n=201 Participants	4 Participants n=1000 Participants	2 Participants n=58 Participants	7 Participants n=61 Participants	28 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=24 Participants	2 Participants n=24 Participants	2 Participants n=48 Participants	3 Participants n=100 Participants	2 Participants n=201 Participants	1 Participants n=1000 Participants	3 Participants n=58 Participants	7 Participants n=61 Participants	21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=24 Participants	0 Participants n=24 Participants	0 Participants n=48 Participants	0 Participants n=100 Participants	0 Participants n=201 Participants	0 Participants n=1000 Participants	0 Participants n=58 Participants	0 Participants n=61 Participants	0 Participants
Region of Enrollment United States	5 Participants n=24 Participants	5 Participants n=24 Participants	5 Participants n=48 Participants	5 Participants n=100 Participants	5 Participants n=201 Participants	5 Participants n=1000 Participants	5 Participants n=58 Participants	14 Participants n=61 Participants	49 Participants

PRIMARY outcome

Timeframe: From Day 1 (dosing visit) through Day 14 (End of Study visit), approximately 3 to 4 weeks

Outcome measures

Outcome measures
Measure	Cohort 1 (no T2D): ENT-03S 3 mg n=5 Participants Single subcutaneous dose of 3 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 2 (no T2D): ENT-03S 6 mg n=5 Participants Single subcutaneous dose of 6 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 3 (no T2D): ENT-03S 12.5 mg n=5 Participants Single subcutaneous dose of 12.5 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 4 (no T2D): ENT-03S 25 mg n=5 Participants Single subcutaneous dose of 25 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 5 (no T2D): ENT-03S 50 mg n=5 Participants Single subcutaneous dose of 50 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 6 (T2D): ENT-03S 50 mg n=5 Participants Single subcutaneous dose of 50 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) and Type 2 diabetes (HbA1c 6.5-8.5%), on no antidiabetic medications or stable metformin. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 7 (T2D): ENT-03S 75 mg n=5 Participants Single subcutaneous dose of 75 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) and Type 2 diabetes (HbA1c 6.5-8.5%), on no antidiabetic medications or stable metformin. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Placebo (All Cohorts) n=14 Participants Single subcutaneous dose of placebo administered across all 7 cohorts (Cohorts 1-5: subjects with obesity without Type 2 diabetes; Cohorts 6-7: subjects with obesity and Type 2 diabetes). Each cohort enrolled 2 placebo subjects using a 5:2 active:placebo randomization ratio with sentinel dosing. Placebo subjects from all cohorts are pooled in this arm as no active intervention was administered. Total N=14.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	1 Participants	2 Participants	3 Participants	4 Participants	3 Participants	2 Participants	1 Participants	4 Participants

PRIMARY outcome

Timeframe: Baseline (pre-dose Day 1), Day 4 (72 hours post-dose), and Day 8 (168 hours post-dose, End of Study)

QTcF (Fridericia-corrected QT interval) was assessed via 12-lead resting ECG at baseline (pre-dose Day 1) and at 72 hours post-dose (Day 4) and 168 hours post-dose (Day 8, End of Study).

Outcome measures

Outcome measures
Measure	Cohort 1 (no T2D): ENT-03S 3 mg n=5 Participants Single subcutaneous dose of 3 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 2 (no T2D): ENT-03S 6 mg n=5 Participants Single subcutaneous dose of 6 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 3 (no T2D): ENT-03S 12.5 mg n=5 Participants Single subcutaneous dose of 12.5 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 4 (no T2D): ENT-03S 25 mg n=5 Participants Single subcutaneous dose of 25 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 5 (no T2D): ENT-03S 50 mg n=5 Participants Single subcutaneous dose of 50 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 6 (T2D): ENT-03S 50 mg n=5 Participants Single subcutaneous dose of 50 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) and Type 2 diabetes (HbA1c 6.5-8.5%), on no antidiabetic medications or stable metformin. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 7 (T2D): ENT-03S 75 mg n=5 Participants Single subcutaneous dose of 75 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) and Type 2 diabetes (HbA1c 6.5-8.5%), on no antidiabetic medications or stable metformin. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Placebo (All Cohorts) n=14 Participants Single subcutaneous dose of placebo administered across all 7 cohorts (Cohorts 1-5: subjects with obesity without Type 2 diabetes; Cohorts 6-7: subjects with obesity and Type 2 diabetes). Each cohort enrolled 2 placebo subjects using a 5:2 active:placebo randomization ratio with sentinel dosing. Placebo subjects from all cohorts are pooled in this arm as no active intervention was administered. Total N=14.
Safety and Tolerability of ENT-03 Day 8 (end of study)	-3.0 milliseconds Standard Deviation 20.16	-14.0 milliseconds Standard Deviation 15.75	-8.8 milliseconds Standard Deviation 24.69	-9.2 milliseconds Standard Deviation 22.84	-0.6 milliseconds Standard Deviation 24.99	-4.2 milliseconds Standard Deviation 9.86	-4.2 milliseconds Standard Deviation 25.38	-10.8 milliseconds Standard Deviation 20.75
Safety and Tolerability of ENT-03 Day 4	-7.4 milliseconds Standard Deviation 23.52	-16.0 milliseconds Standard Deviation 3.96	-6.8 milliseconds Standard Deviation 19.42	-6.4 milliseconds Standard Deviation 19.42	-3.4 milliseconds Standard Deviation 13.37	-13.4 milliseconds Standard Deviation 10.62	-4.0 milliseconds Standard Deviation 14.54	-4.0 milliseconds Standard Deviation 13.90

SECONDARY outcome

Timeframe: Pre-dose (0 hours) and at 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose. Note: Cohorts 1 and 2 had samples collected through 72 hours; Cohort 3 through 120 hours; Cohorts 4-7 through 168 hours.

maximum measured plasma concentration

Outcome measures

Outcome measures
Measure	Cohort 1 (no T2D): ENT-03S 3 mg n=5 Participants Single subcutaneous dose of 3 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 2 (no T2D): ENT-03S 6 mg n=5 Participants Single subcutaneous dose of 6 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 3 (no T2D): ENT-03S 12.5 mg n=5 Participants Single subcutaneous dose of 12.5 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 4 (no T2D): ENT-03S 25 mg n=5 Participants Single subcutaneous dose of 25 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 5 (no T2D): ENT-03S 50 mg n=5 Participants Single subcutaneous dose of 50 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 6 (T2D): ENT-03S 50 mg n=5 Participants Single subcutaneous dose of 50 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) and Type 2 diabetes (HbA1c 6.5-8.5%), on no antidiabetic medications or stable metformin. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 7 (T2D): ENT-03S 75 mg n=5 Participants Single subcutaneous dose of 75 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) and Type 2 diabetes (HbA1c 6.5-8.5%), on no antidiabetic medications or stable metformin. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Placebo (All Cohorts) n=14 Participants Single subcutaneous dose of placebo administered across all 7 cohorts (Cohorts 1-5: subjects with obesity without Type 2 diabetes; Cohorts 6-7: subjects with obesity and Type 2 diabetes). Each cohort enrolled 2 placebo subjects using a 5:2 active:placebo randomization ratio with sentinel dosing. Placebo subjects from all cohorts are pooled in this arm as no active intervention was administered. Total N=14.
Pharmacokinetic Endpoints: Maximum Plasma Concentration	624.81 ng/mL Standard Deviation 113.90	1245.40 ng/mL Standard Deviation 282.40	2612.00 ng/mL Standard Deviation 173.40	4860.00 ng/mL Standard Deviation 375.60	11042.00 ng/mL Standard Deviation 1951.70	11002.00 ng/mL Standard Deviation 1962.70	12284.00 ng/mL Standard Deviation 2985.70	NA ng/mL Standard Deviation NA All 14 placebo subjects had ENT-03S plasma concentrations below the lower limit of quantitation (BQL) at all timepoints; therefore, Cmax was not calculable for the placebo arm.

SECONDARY outcome

Timeframe: 0, 0.5, 1, 1.5, 2, 4, 8, 12, and 24 hours post-dose (Cohorts 3-7); 0, 1, 2, 4, 8, 12, and 24 hours post-dose (Cohorts 1-2)

area under the concentration versus time curve over 24 hours

Outcome measures

Outcome measures
Measure	Cohort 1 (no T2D): ENT-03S 3 mg n=5 Participants Single subcutaneous dose of 3 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 2 (no T2D): ENT-03S 6 mg n=5 Participants Single subcutaneous dose of 6 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 3 (no T2D): ENT-03S 12.5 mg n=5 Participants Single subcutaneous dose of 12.5 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 4 (no T2D): ENT-03S 25 mg n=5 Participants Single subcutaneous dose of 25 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 5 (no T2D): ENT-03S 50 mg n=5 Participants Single subcutaneous dose of 50 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 6 (T2D): ENT-03S 50 mg n=5 Participants Single subcutaneous dose of 50 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) and Type 2 diabetes (HbA1c 6.5-8.5%), on no antidiabetic medications or stable metformin. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 7 (T2D): ENT-03S 75 mg n=5 Participants Single subcutaneous dose of 75 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) and Type 2 diabetes (HbA1c 6.5-8.5%), on no antidiabetic medications or stable metformin. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Placebo (All Cohorts) n=14 Participants Single subcutaneous dose of placebo administered across all 7 cohorts (Cohorts 1-5: subjects with obesity without Type 2 diabetes; Cohorts 6-7: subjects with obesity and Type 2 diabetes). Each cohort enrolled 2 placebo subjects using a 5:2 active:placebo randomization ratio with sentinel dosing. Placebo subjects from all cohorts are pooled in this arm as no active intervention was administered. Total N=14.
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours Post-Dose (AUC₀-₂₄)	9,801.4 (hr*ng/mL) Standard Deviation 2272.0	19841.6 (hr*ng/mL) Standard Deviation 4264.3	43206.2 (hr*ng/mL) Standard Deviation 3252.4	84534.5 (hr*ng/mL) Standard Deviation 5604.1	179984.5 (hr*ng/mL) Standard Deviation 35145.8	179575.0 (hr*ng/mL) Standard Deviation 23127.7	217109.0 (hr*ng/mL) Standard Deviation 40915.4	NA (hr*ng/mL) Standard Deviation NA All 14 placebo subjects had ENT-03S plasma concentrations below the lower limit of quantitation (BQL) at all timepoints; therefore, AUC₀-₂₄ was not calculable for the placebo arm.

SECONDARY outcome

Timeframe: Sampling through 72 hours post-dose (Cohorts 1-2), 120 hours (Cohort 3), and 168 hours (Cohorts 4-7).

time required for drug concentration to decrease to 50% of maximum concentration

Outcome measures

Outcome measures
Measure	Cohort 1 (no T2D): ENT-03S 3 mg n=5 Participants Single subcutaneous dose of 3 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 2 (no T2D): ENT-03S 6 mg n=5 Participants Single subcutaneous dose of 6 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 3 (no T2D): ENT-03S 12.5 mg n=5 Participants Single subcutaneous dose of 12.5 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 4 (no T2D): ENT-03S 25 mg n=5 Participants Single subcutaneous dose of 25 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 5 (no T2D): ENT-03S 50 mg n=5 Participants Single subcutaneous dose of 50 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 6 (T2D): ENT-03S 50 mg n=5 Participants Single subcutaneous dose of 50 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) and Type 2 diabetes (HbA1c 6.5-8.5%), on no antidiabetic medications or stable metformin. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 7 (T2D): ENT-03S 75 mg n=5 Participants Single subcutaneous dose of 75 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) and Type 2 diabetes (HbA1c 6.5-8.5%), on no antidiabetic medications or stable metformin. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Placebo (All Cohorts) n=14 Participants Single subcutaneous dose of placebo administered across all 7 cohorts (Cohorts 1-5: subjects with obesity without Type 2 diabetes; Cohorts 6-7: subjects with obesity and Type 2 diabetes). Each cohort enrolled 2 placebo subjects using a 5:2 active:placebo randomization ratio with sentinel dosing. Placebo subjects from all cohorts are pooled in this arm as no active intervention was administered. Total N=14.
Pharmacokinetic Endpoint: Half-life	29.1 hours Standard Deviation 3.1	27.5 hours Standard Deviation 5.4	45.8 hours Standard Deviation 9.5	52.8 hours Standard Deviation 9.5	66.1 hours Standard Deviation 13.0	52.0 hours Standard Deviation 6.6	72.3 hours Standard Deviation 7.1	NA hours Standard Deviation NA All 14 placebo subjects had ENT-03S plasma concentrations below the lower limit of quantitation (BQL) at all timepoints; therefore, t½ not calculable for the placebo arm

SECONDARY outcome

Timeframe: Baseline (pre-dose Day 1) and Day 8 (168 hours post-dose, End of Study)

Body weight (kg) was measured at baseline (last measurement prior to first dose administration on Day 1) and at 168 hours post-dose (Day 8, End of Study). Change from baseline was calculated as the Day 8 value minus the baseline value.

Outcome measures

Outcome measures
Measure	Cohort 1 (no T2D): ENT-03S 3 mg n=5 Participants Single subcutaneous dose of 3 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 2 (no T2D): ENT-03S 6 mg n=5 Participants Single subcutaneous dose of 6 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 3 (no T2D): ENT-03S 12.5 mg n=5 Participants Single subcutaneous dose of 12.5 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 4 (no T2D): ENT-03S 25 mg n=5 Participants Single subcutaneous dose of 25 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 5 (no T2D): ENT-03S 50 mg n=5 Participants Single subcutaneous dose of 50 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 6 (T2D): ENT-03S 50 mg n=5 Participants Single subcutaneous dose of 50 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) and Type 2 diabetes (HbA1c 6.5-8.5%), on no antidiabetic medications or stable metformin. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 7 (T2D): ENT-03S 75 mg n=5 Participants Single subcutaneous dose of 75 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) and Type 2 diabetes (HbA1c 6.5-8.5%), on no antidiabetic medications or stable metformin. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Placebo (All Cohorts) n=12 Participants Single subcutaneous dose of placebo administered across all 7 cohorts (Cohorts 1-5: subjects with obesity without Type 2 diabetes; Cohorts 6-7: subjects with obesity and Type 2 diabetes). Each cohort enrolled 2 placebo subjects using a 5:2 active:placebo randomization ratio with sentinel dosing. Placebo subjects from all cohorts are pooled in this arm as no active intervention was administered. Total N=14.
Change in Body Weight From Baseline to Day 8	-0.54 KG Standard Deviation 0.68	-0.83 KG Standard Deviation 1.30	-0.55 KG Standard Deviation 0.89	-0.54 KG Standard Deviation 0.81	-0.83 KG Standard Deviation 1.30	-0.55 KG Standard Deviation 0.89	0.59 KG Standard Deviation 0.64	-0.52 KG Standard Deviation 0.64

SECONDARY outcome

Timeframe: Baseline (pre-dose Day 1) and Day 8 (168 hours post-dose, End of Study)

Fasting leptin (ng/mL) was measured at baseline (last measurement prior to first dose administration on Day 1) and at post-dose visits. For Cohorts 1-3, assessments were performed at 24 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), and 168 hours post-dose (Day 8, End of Study). For Cohorts 4-7, assessments were performed at 72 hours (Day 4) and 168 hours post-dose (Day 8, End of Study) only. Change from baseline was calculated as the visit value minus the baseline value.

Outcome measures

Outcome measures
Measure	Cohort 1 (no T2D): ENT-03S 3 mg n=5 Participants Single subcutaneous dose of 3 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 2 (no T2D): ENT-03S 6 mg n=5 Participants Single subcutaneous dose of 6 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 3 (no T2D): ENT-03S 12.5 mg n=5 Participants Single subcutaneous dose of 12.5 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 4 (no T2D): ENT-03S 25 mg n=5 Participants Single subcutaneous dose of 25 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 5 (no T2D): ENT-03S 50 mg n=5 Participants Single subcutaneous dose of 50 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 6 (T2D): ENT-03S 50 mg n=5 Participants Single subcutaneous dose of 50 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) and Type 2 diabetes (HbA1c 6.5-8.5%), on no antidiabetic medications or stable metformin. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 7 (T2D): ENT-03S 75 mg n=5 Participants Single subcutaneous dose of 75 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) and Type 2 diabetes (HbA1c 6.5-8.5%), on no antidiabetic medications or stable metformin. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Placebo (All Cohorts) n=12 Participants Single subcutaneous dose of placebo administered across all 7 cohorts (Cohorts 1-5: subjects with obesity without Type 2 diabetes; Cohorts 6-7: subjects with obesity and Type 2 diabetes). Each cohort enrolled 2 placebo subjects using a 5:2 active:placebo randomization ratio with sentinel dosing. Placebo subjects from all cohorts are pooled in this arm as no active intervention was administered. Total N=14.
Pharmacodynamic Endpoint: Change in Fasting Leptin From Baseline to Day 8	3.20 ug/mL Standard Deviation 18.96	0.46 ug/mL Standard Deviation 3.28	-7.88 ug/mL Standard Deviation 8.83	2.04 ug/mL Standard Deviation 10.08	-10.00 ug/mL Standard Deviation 8.06	4.66 ug/mL Standard Deviation 7.50	-3.80 ug/mL Standard Deviation 9.14	-4.20 ug/mL Standard Deviation 11.47

SECONDARY outcome

Timeframe: Baseline (pre-dose Day 1) and Day 8 (168 hours post-dose, End of Study)

Fasting plasma glucose (mg/dL) was measured at baseline (last measurement prior to first dose administration on Day 1) and at post-dose visits. For Cohorts 1-3, assessments were performed at 24 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), and 168 hours post-dose (Day 8, End of Study). For Cohorts 4-7, assessments were performed at 72 hours (Day 4) and 168 hours post-dose (Day 8, End of Study) only. Change from baseline was calculated as the visit value minus the baseline value.

Outcome measures

Outcome measures
Measure	Cohort 1 (no T2D): ENT-03S 3 mg n=5 Participants Single subcutaneous dose of 3 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 2 (no T2D): ENT-03S 6 mg n=5 Participants Single subcutaneous dose of 6 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 3 (no T2D): ENT-03S 12.5 mg n=5 Participants Single subcutaneous dose of 12.5 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 4 (no T2D): ENT-03S 25 mg n=5 Participants Single subcutaneous dose of 25 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 5 (no T2D): ENT-03S 50 mg n=5 Participants Single subcutaneous dose of 50 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) without Type 2 diabetes. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 6 (T2D): ENT-03S 50 mg n=5 Participants Single subcutaneous dose of 50 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) and Type 2 diabetes (HbA1c 6.5-8.5%), on no antidiabetic medications or stable metformin. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Cohort 7 (T2D): ENT-03S 75 mg n=5 Participants Single subcutaneous dose of 75 mg ENT-03S administered to subjects with obesity (BMI 30-35 kg/m²) and Type 2 diabetes (HbA1c 6.5-8.5%), on no antidiabetic medications or stable metformin. Cohort enrolled using sentinel dosing (2 active:1 placebo), followed by remaining subjects at 5:2 active:placebo ratio. N=5.	Placebo (All Cohorts) n=12 Participants Single subcutaneous dose of placebo administered across all 7 cohorts (Cohorts 1-5: subjects with obesity without Type 2 diabetes; Cohorts 6-7: subjects with obesity and Type 2 diabetes). Each cohort enrolled 2 placebo subjects using a 5:2 active:placebo randomization ratio with sentinel dosing. Placebo subjects from all cohorts are pooled in this arm as no active intervention was administered. Total N=14.
Pharmacodynamic Endpoint: Change in Fasting Plasma Glucose From Baseline to Day 8	9.4 mg/dL Standard Deviation 1.14	-4.8 mg/dL Standard Deviation 7.79	-1.2 mg/dL Standard Deviation 3.83	2.6 mg/dL Standard Deviation 9.48	-2.6 mg/dL Standard Deviation 4.10	12.8 mg/dL Standard Deviation 15.40	1.0 mg/dL Standard Deviation 11.81	-2.3 mg/dL Standard Deviation 11.44

SECONDARY outcome

Timeframe: Baseline (pre-dose Day 1) and Day 8 (168 hours post-dose, End of Study)

Fasting serum insulin (μIU/mL) was measured at baseline (last measurement prior to first dose administration on Day 1) and at post-dose visits. For Cohorts 1-3, assessments were performed at 24 hours (Day 2), 48 hours (Day 3), 72 hours (Day 4), and 168 hours post-dose (Day 8, End of Study). For Cohorts 4-7, assessments were performed at 72 hours (Day 4) and 168 hours post-dose (Day 8, End of Study) only. Change from baseline was calculated as the visit value minus the baseline value.