A Study to Assess the Efficacy, Safety and Tolerability of AT673 Co-administered With Semaglutide in Adult Participants With Type 2 Diabetes (T2D) and Overweight or Obesity

This is a phase 2, double-blind, placebo-controlled study. Following screening, at their baseline visit, participants will initiate treatment with semaglutide at 0.25 mg/week and follow the product labelled dose escalation schedule until reaching the dose of 1.0 mg/week. Participants will remain on this dose until the end of study (EOS) visit.

At the baseline visit, participants will be randomized in a 1:1:1 ratio to receive AT673 25 mg, or 50 mg, or matching placebo, respectively, once weekly at the same time as semaglutide.

Participants will receive AT673 / placebo injections concurrently with Semaglutide during weekly clinic visits. Treatment with the AT673 / placebo will continue through the end of 13 weeks. This will be followed by a 4-week safety follow-up. The end of study visit will be at week 17.

Inclusion criteria

• Signed informed consent prior to start the Screening Visit procedures.
• Female and male participants ≥18 years of age at time of consent
• BMI g ≥27.0 kg/m2 at screening.
• HbA1c ≥7 and ≤10% (53-86 mmol/mol) at screening.
• Diagnosis of type 2 diabetes mellitus for ≥ 180 days prior to screening.
• Either treated with diet and exercise alone or on stable (at least 90 days prior to screening) treatment with metformin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, sulfonylurea, and/or DPP4 inhibitor as monotherapy or combination therapy, per approved local label.

a) Note: Participants treated with sulfonylureas and/or DPP4 inhibitors must discontinue these at least 24 hours prior to initiation of semaglutide.

• Participant has had at least 1 unsuccessful attempt at weight loss by diet and exercise in the opinion of the investigator.
• Women of childbearing potential (WOCBP) meeting the criteria below:

i) Non-lactating and has a negative pregnancy test at screening and baseline -AND- ii) Uses an acceptable method of contraception as determined by the Investigator or Sub-Investigator for the duration of the study and 30 days following the last dose of study drug

• Participants must, in the opinion of the Investigator, be suitable candidates to receive semaglutide (Wegovy®) as indicated according to the product label.

Exclusion criteria

• Participant has had gastric bypass or other bariatric surgery or endoscopic procedure or any metabolic procedures (e.g. duodenal resurfacing, intragastric balloon, etc.) except for the following:

• Liposuction and/or abdominoplasty that was performed > 1 year before screening
• Laparoscopic gastric band that was removed > 1 year before screening
• Intragastric balloon that was removed > 1 year before screening
• Duodenal-jejunal bypass sleeve that was removed > 1 year before screening.
• Participant has had a self-reported or medically recorded change in body weight > 5% within 3 months of screening OR has recorded change in body weight >3% between screening and randomization.
• Participant is currently using insulin or used insulin within 3 months before screening.
• Participant is currently using sulfonylureas and/or DPP4 inhibitors and is unable or unwilling to discontinue the use of these medications at least 24 hours prior to initiation of semaglutide.
• Participant has a form of diabetes other than type 2.

a. Note: Previous diagnosis of gestational diabetes is permitted so long as the participant meets all inclusion and none of the exclusion criteria.

• Participant is currently using or used within 3 months before screening any weight reducing medication including pramlintide, sibutramine, orlistat, zonisamide, topiramate, phentermine, naltrexone, bupropion.
• Participant is currently using or used within 6 months before screening any medication that contains a GLP-1R agonist component or a GIPR modulator (either by prescription or as part of a clinical study)
• For participants with a history of prior GLP-1R agonist use (> 6 months prior to screening):

• Participant has had a previous intolerance or hypersensitivity to GLP-1 receptor agonists or any of its excipients.
• Participant has previously discontinued a GLP-1 receptor agonist after continuous treatment for 6 months or longer due to not meeting personal weight loss goals.
• Participant is taking any medication that, may cause weight gain unless the participant has used these medications for more than 6 months at a stable dose prior to screening.
• Participant has hepatic liver enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase levels >2.5, or total bilirubin levels > 1.5 times the upper limit of normal (ULN) at screening.
• Participant's current alcohol intake exceeds 14 units/week for men or 7 units/week for women (1 unit = half pint of beer, 1 glass of wine, 1 measure of spirits).
• Participant has a recent history of illicit substance use (< 3 months) or in the opinion of the Investigator suspicion of current illicit substance use.
• Participant has uncontrolled hypertension at screening (SBP above or equal to 160 mmHg and/or diastolic blood pressure above or equal to 100 mmHg).
• A corrected QT interval (QTc) of > 450 msec in males or > 470 msec in females at screening, or history of long QT syndrome.
• Concurrent participation in another interventional study (e.g., of a drug, over the counter product, device) or within ≤90 days or 5 half-lives prior to Screening.
• Participant is unable to understand and communicate with the investigators; or to understand the protocol requirements, instructions, study-related restrictions, nature, scope, and possible consequences of the clinical study; or is unlikely to comply with the study requirements (e.g., uncooperative attitude and improbability of completing the clinical study).
• Participant is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff, or relative thereof directly involved in the conduct of the study, or employee of the sponsor, site, or Contract Research Organization (CRO).
• Participant whose obesity can be traced to a medical cause, suggestive of genetic or syndromic obesity of an endocrinologic disorder (e.g., hypothyroidism, Cushings syndrome, Prader-Willi syndrome).
• Participant has a history of an active or untreated malignancy or in remission from a clinically significant malignancy for less than 5 years, except for basal cell carcinoma.
• Participant has a glomerular filtration rate < 60 mL/min/1.73 m2.
• Participant has a history of major psychiatric disorders within 5 years or lifetime history of suicide attempt.
• Participant has any suicidal ideation of type 4 or 5 on the C-SSRS at screening.
• Participant with a personal or family history of medullary thyroid carcinoma or with multiple endocrine neoplasia (MEN) syndrome type 2.
• Participant with a previous history of chronic pancreatitis, or acute pancreatitis within 6 months prior to screening.
• In the opinion of the Investigator, any disorder, condition, inability or unwillingness not covered by the exclusion criteria that may interfere with study procedures, assessments or participant's safety.