Viking Therapeutics' VK2735: A Game-Changer in Oral Weight Management

The obesity drug market is undergoing a seismic transformation, driven by the rise of GLP-1/GIP dual agonists and the urgent demand for effective, long-term weight management solutions. At the forefront of this evolution is Viking Therapeutics' VK2735, a once-daily oral dual agonist of the glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. With recent Phase 2 trial results demonstrating robust weight loss and a manageable safety profile, VK2735 has emerged as a compelling candidate to disrupt the $150 billion obesity market by 2030. This article evaluates the investment potential of VK2735, balancing its clinical promise against competitive and commercial challenges.

Clinical Efficacy: Dose-Responsive Weight Loss and Long-Term Potential

Viking's Phase 2 VENTURE-Oral Dosing trial, announced in August 2025, delivered headline-grabbing results. The 120 mg dose of VK2735 achieved a 12.2% mean weight loss over 13 weeks, compared to 1.3% in the placebo group. This outperforms many existing therapies and aligns with the efficacy of Eli Lilly's Zepbound (tirzepatide) and Novo Nordisk's Wegovy (semaglutide) in similar timeframes. Notably, the trial observed a dose-response relationship, with all doses >15 mg showing statistically significant weight loss starting at Week 1.

The low-dose maintenance cohort further strengthens VK2735's appeal. Patients titrated to 90 mg for four weeks, then down to 30 mg for seven weeks, maintained weight loss without rebound. This suggests that lower doses could sustain results, potentially reducing side effects and improving long-term adherence—a critical factor for chronic therapies.

Safety Profile: Tolerability Challenges and Mitigation Strategies

While efficacy is strong, tolerability remains a hurdle. The trial reported a 28% discontinuation rate in the VK2735 group, primarily due to gastrointestinal (GI) adverse events like nausea (58%), vomiting (26%), and constipation (43%). However, these events were mostly mild to moderate and decreased in frequency after the third week. Viking's data also showed that weekly rates of nausea/vomiting dropped below 5% post-Week 3, indicating potential for improved tolerability with optimized dosing.

The company is addressing these challenges by refining titration strategies and advancing the injectable formulation of VK2735, which demonstrated 14.7% weight loss in prior Phase 2 trials with a more favorable safety profile. The injectable version, currently in Phase 3 (VANQUISH-1 and VANQUISH-2), could offer a once-monthly dosing regimen, reducing GI exposure and improving adherence.

Competitive Landscape: Navigating a Crowded Market

The obesity drug market is dominated by injectable GLP-1/GIP agonists like Zepbound and Wegovy, which have established strong clinical and commercial footholds. Zepbound, for instance, generated $1.91 billion in U.S. revenue in Q4 2024, while Wegovy's 2024 sales hit $5.7 billion. Both therapies boast lower discontinuation rates and broader patient access, thanks to Novo Nordisk's and Eli Lilly's robust manufacturing and distribution networks.

However, Viking's oral formulation of VK2735 offers a key differentiator. Oral therapies are projected to capture 25% of the anti-obesity market by 2030, driven by patient preference for convenience. If Viking can optimize dosing to reduce GI side effects, VK2735 could carve out a niche in the oral segment, particularly for patients who reject injections.

Financials and Strategic Positioning

Viking Therapeutics reported $808 million in cash reserves as of June 2025, sufficient to fund Phase 3 trials for VK2735 and other programs. Despite a $65.6 million net loss in Q2 2025, the company's balance sheet remains strong, supported by a $150 million manufacturing deal with CordenPharma to produce over one billion oral pills and millions of injectable doses annually. This ensures scalability if VK2735 gains regulatory approval.

The company's pipeline diversification also mitigates risk. Viking is developing VK2809 for NASH and dual amylin/calcitonin receptor agonists (DACRAs) for obesity, creating multiple revenue streams. These programs could reduce reliance on the competitive GLP-1/GIP space and provide long-term value.

Investment Risks and Opportunities

The primary risks for VK2735 include regulatory uncertainty, intense competition, and persistent tolerability issues. The recent stock sell-off following the Phase 2 oral trial's discontinuation rate highlights investor skepticism. However, Viking's injectable Phase 3 trials (expected to report in 2026) could serve as a catalyst, particularly if they demonstrate improved safety and once-monthly dosing.

For investors, the key inflection points are:
1. Phase 3 results for the injectable formulation (VANQUISH-1/2).
2. Optimized dosing strategies for the oral version to reduce GI side effects.
3. FDA approval timelines and commercialization readiness.

If successful, VK2735 could capture a 10–15% market share in the obesity segment by 2030, translating to $3–5 billion in annual revenue. This would significantly boost Viking's valuation, currently trading at a discount to its peers.

Conclusion: A High-Risk, High-Reward Play

Viking Therapeutics' VK2735 represents a high-conviction investment opportunity in the obesity drug space. While the oral formulation faces tolerability hurdles, the injectable version's Phase 3 progress and Viking's manufacturing capabilities position the company to compete with industry giants. For risk-tolerant investors, a strategic entry point could be post-Phase 3 readouts, particularly if the injectable formulation demonstrates superior efficacy and safety.

In a market where obesity is increasingly recognized as a chronic disease, VK2735's dual-agonist mechanism and oral convenience could redefine treatment paradigms. However, success hinges on Viking's ability to navigate clinical and commercial challenges—a test of resilience that could yield outsized rewards for those who stay the course.