Breakthrough Clinical Results
Palatin Technologies announced positive preclinical results for PL7737, an oral MC4R agonist, demonstrating significant weight loss in obese rodent models. Both as a monotherapy and in combination with tirzepatide, PL7737 showed rapid and substantial weight reduction. The company plans to submit an IND application in Q4 2025 and initiate Phase 1 clinical trials in late 2025, with data expected in the first half of 2026. PL7737 is also being investigated for hypothalamic obesity, and Palatin is developing other MC4R agonists for various obesity types.
Key Highlights
- Significant weight loss observed in obese rodent models with oral PL7737, both alone and in combination with tirzepatide.
- IND submission planned for Q4 2025, with Phase 1 clinical data expected in 1H 2026.
- PL7737 is also being investigated as a treatment for hypothalamic obesity.
- Palatin is developing a pipeline of novel MC4R agonists with a unique mechanism of action compared to incretin-based therapies.
Incidence and Prevalence
Global Obesity Prevalence and Incidence
The worldwide prevalence of obesity has experienced a dramatic increase, more than doubling between 1990 and 2022. Specifically, obesity rates have risen from 4.8% to 14.0% in men and from 8.8% to 18.5% in women during this period.
In the United States, a 2007 review documented that obesity prevalence increased substantially from 13% to 32% between the 1960s and 2004. This review projected that by 2015, 75% of adults would be overweight or obese, with 41% classified as obese. The annual increases in prevalence have ranged from 0.3 to 0.9 percentage points across different population groups.
Geographic variations in obesity prevalence are significant. In Europe, obesity prevalence (defined as body mass index ≥ 30 kg/m²) ranges from 4.0% to 28.3% in men and from 6.2% to 36.5% in women. Central, Eastern, and Southern Europe show higher prevalence rates compared to Western and Northern Europe. Similarly, the Middle East, Central and Eastern Europe, and North America have higher prevalence rates of overweight and obesity compared to other regions.
A study of six Low and Middle-Income Countries (LMICs) including China, India, Mexico, Russia, South Africa, and Ghana found a mean BMI of 24.4 in the pooled sample. Country-specific mean BMI values varied considerably: 20.8 in India, 23.4 in Ghana, 23.9 in China, 28.4 in Mexico, 28.6 in Russia, and 30.5 in South Africa. In this pooled sample, the prevalence of overweight was 13% and obesity was 24%.
The increasing prevalence of obesity over the past two decades is primarily attributed to environmental factors. Particularly, obesity is related to increased consumption of high-fat foods. Several factors are positively associated with obesity prevalence, including the percentage of people aged 40-59 (β=0.07), urbanization rate (β=0.11), percentage of internet users (β=0.01), percentage of alcohol users (β=0.16), milk consumption per capita (β=0.15), and percentage of depression (β=0.58).
Conversely, factors negatively associated with obesity prevalence include per capita consumption of fruits and vegetables (β=-0.15) and smoking rate (β=-0.02).
A concerning trend is the relationship between Human Development Index (HDI) and obesity. A positive relation exists between HDI and obesity prevalence, suggesting that if low HDI countries advance to become high HDI countries, their obesity rates could increase significantly by 7.45%.
Minority and low-socioeconomic-status groups are disproportionately affected by obesity at all ages, highlighting the complex and dynamic associations of obesity with gender, age, ethnicity, and socioeconomic status.
The global research focus on obesity has intensified, with 415,126 papers on obesity/overweight published globally during 1990-2013, with 3.56% affiliated to Middle East countries.
Key Unmet Needs and Target Populations for Obesity
Populations with Significant Unmet Needs
Obesity is a multi-systemic disease with complex etiology that serves as a major risk factor for various cancers and metabolic disorders, including type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD/NASH). Several populations face particular challenges:
- Patients with obesity and depression represent interconnected health concerns demanding high levels of treatment and costs in healthcare systems
- Individuals with obesity and T2DM who could benefit from SGLT2 inhibitors which have shown efficacy in improving liver function parameters
- Obese youth with type 2 diabetes who have more IgM-bound gut bacteria, suggesting a role for gut microbiota in the immuno-pathogenesis of obesity
- Patients with obesity and cancer who may benefit from immune checkpoint inhibition (ICI) therapy
- Individuals with high body mass index (BMI) who don't respond adequately to current treatments
- Patients experiencing obesity-related brain changes with decreased gray matter volume (GMV) in reward circuit and sensorimotor processing areas
Treatment Limitations and Challenges
Current treatment limitations include serious side effects, numerous contraindications, and lack of acceptance. Specific challenges include:
- GLP-1 receptor agonists are associated with gastrointestinal adverse events and some patients do not respond to treatment
- Traditional regression models often fail to capture complex interactions between genetic, environmental, and behavioral factors
- Limited research on the weight maintenance phase and objective measurements of food intake
- Reliance on verbal reports to examine food intake, which can be susceptible to subjectivity
Emerging Therapeutic Approaches
Several promising approaches are being developed to address these unmet needs:
- eHealth interventions that simultaneously address obesity and mental health, particularly those that are supported and guided throughout the intervention
- Natural products like Caulerpa racemosa in kombucha drink form, showing potential to improve lipid profiles
- Targeting specific immune pathways such as CXCL5 which can promote T cell infiltration into tumors
- Neuropeptide Y (NPY) and peptide YY targeting G-protein-coupled Y receptors for modulating bodyweight
- Advanced machine-learning models like ANN-PSO providing detailed obesity risk profiles
- Combination therapies such as NPY2R agonist BI 1820237 with low-dose liraglutide showing additive effects
Treatment Efficacy Insights
Recent research has revealed important insights about treatment efficacy:
- GLP-1 receptor agonists show varying weight reduction effects, from 4.25 kg (Liraglutide) to 22.6 kg (Retatrutide)
- At 52 weeks, weight reduction effects were 7.03 kg for mono-agonists, 11.07 kg for dual-agonists, and 24.15 kg for tri-agonists
- A significant negative correlation exists between age and weight reduction effect of GLP-1RAs
- Exercise interventions significantly decreased body mass index and body fat of overweight/obese breast cancer survivors
- The weight-adjusted waist index (WWI) shows better association with mortality risk than BMI in patients with metabolic dysfunction-associated steatotic liver disease
Drug used in other indications
PL7737 Clinical Trials for Non-Obesity Indications
After a comprehensive review of available clinical trial data, there is no information available regarding PL7737 being trialed for indications other than obesity. The compound PL7737 does not appear in current clinical trial registries for any medical conditions.
While numerous pharmaceutical compounds are currently under investigation for various health conditions beyond obesity, including:
- R-147176 (an ARB-derivative)
- Exenatide and other GLP-1 receptor agonists like efpeglenatide
- Ghrelin receptor modulators
- Retatrutide (LY3437943)
- Clenbuterol in modified delivery systems
- Lorcaserin and phentermine/topiramate combinations
None of these compounds are identified as PL7737, and there are no documented intervention models or clinical trials specifically for PL7737 in non-obesity indications.
The absence of PL7737 in clinical trial databases suggests that either:
- The compound is in early preclinical development stages
- It is being investigated under a different designation in various research settings
- Clinical trials for indications beyond obesity have not yet been registered or initiated
Without specific trial information, details regarding intervention methodologies, dosing regimens, or treatment protocols for PL7737 in non-obesity indications cannot be determined.
Researchers interested in PL7737's potential applications beyond obesity would need to consult the most recent clinical trial registries, pharmaceutical pipelines, or contact the developing company directly for the most current information on this compound's development status.