Eli Lilly

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INTERVIEW: Obesity Therapies – Verdiva Bio, Oral Medications & Next-generation Mechanisms of Action – Part 1 

Agenda 

• Innovation across obesity therapies – oral medications and next-generation mechanisms of action in development 
• Market access and pricing considerations, including payer perspectives on oral vs injectable GLP-1s 
• Evolving weight loss treatment paradigm – subcutaneous vs oral market share  
• Verdiva Bio's oral GLP-1 agonist peptide VRB-101, cardiometabolic pipeline and once-weekly dosing strategy

Key Insights 

1. Expert predicts subcutaneous injections will maintain 66-75% market share in obesity therapies, with orals capturing the remainder, given the superior efficacy of injectables. Should orals launch with significantly lower pricing than injectables, which is expected, then more favorable payer coverage policies, as well as out-of-pocket expense considerations, could drive meaningfully higher oral market share 
2. On market expansion – lower-priced orals may open up coverage across Medicare, Medicaid and commercial insurance markets, potentially expanding access to obesity treatments 
3. Expert estimates 70-80% of the future obesity drug market may be driven by cosmetic rather than strictly medical needs within 5-10 years  
4. Pricing strategy will likely segment the market, with next-generation injectables positioned at a premium, first-generation injectables in the middle and orals as a lower-priced alternative  
5. Generic semaglutide in China and India within 1-2 years could significantly impact global pricing and market dynamics for weight loss medications 

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INTERVIEW: Obesity Therapies – Verdiva Bio, Oral Medications & Next-generation Mechanisms of Action – Part 2 

Agenda 

• Innovation across obesity therapies – oral medications and next-generation mechanisms of action in development 
• Market access and pricing considerations, including payer perspectives on oral vs injectable GLP-1s 
• Evolving weight loss treatment paradigm – subcutaneous vs oral market share  
• Verdiva Bio's oral GLP-1 agonist peptide VRB-101, cardiometabolic pipeline and once-weekly dosing strategy

Key Insights 

1. Orforglipron's lack of eating restrictions is seen as a major advantage over oral semaglutide, potentially giving it an edge in the competitive obesity drug market
2. Expert believes CagriSema will primarily compete with Zepbound, while retatrutide's superior weight loss results position it as the top performer for the foreseeable future. "The basic thing is retatrutide has hit the ball out of the ballpark. […] they're going to retain that crown for a long time to come"
3. Emerging oral weight loss medications are targeting individuals with lower body mass index, potentially expanding the market to include individuals who are not severely overweight
4. The CVS-Novo deal is likely a short-term arrangement, potentially just for one year, with limited impact due to CVS controlling only c30% of the commercial market
5. Future differentiation in the obesity drug market may focus on central nervous system impacts, including potential antidepressant and anti-addiction effects

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INTERVIEW: From Injection to Ingestion – Oral GLP-1s Pipeline Review & Implications for Injectables

Agenda 

• Clinical positioning of oral GLP-1 (glucagonlike peptide-1) AOMs (anti-obesity medications) vs current- and next-generation injectables and respective prescription volume expectations
• Review of Novo Nordisk's (CSE: NOVO B) high-dose Rybelsus (25mg, 50mg oral semaglutide) OASIS 1, 4 and PIONEERPLUS data and expectations for uptake, following potential launch in H1 2026
• Lilly’s (NYSE: LLY) orforglipron deep dive – phase 2 data review in obese non-type 2 diabetes and non-obese type 2 diabetes patient populations and expectations for phase ACHIEVE-1 and ATTAN-1 studies, respectively
• Wider oral AOM pipeline review – Novo Nordisk’s oral amycretin, Roche’s (VTX: ROG) CT-996 and Viking’s (NASDAQ: VKTX) VK-2735

Key Insights 

1. ACHIEVE-1’s HbA1c reduction is comparable to 1mg Ozempic, but slightly worse than 2mg, although trial design and baseline differences make comparisons difficult.
2. A higher proportion of patients achieved 6-6.5% HbA1c targets vs SUSTAIN FORTE, which will be a strong marketing point.
3. 12mg dose showing the best HbA1c reduction is exciting. It could improve tolerability and may be the workhorse dose.
4. ACHIEVE-1 data appears superior to Rybelsus and comparable, if slightly better, to 25mg oral semaglutide. However, orforglipron’s HbA1c appears worse vs tirzepatide.
5. Orforglipron tolerability is in-line with injectable semaglutide, if slightly better. No hepatic signal is a relief and the range of doses is important in tailoring to patients’ needs.
6. Given better reimbursement and access, expert expects higher-efficacy injectables such as tirzepatide to be preferred in type 2 diabetes.
7. Orforglipron’s sweet spot will be the 10-15% of lower baseline HbA1c and weight patients. Over time, orforglipron may be a natural replacement for metformin.
8. Orforglipron’s weight loss profile is “more promising and exciting” in non-type 2 diabetes patients. Expert expects Wegovy-esque efficacy in ATTAIN-1, i.e., c15% total weight loss or c12.5% placebo-adjusted.
9. Expert believes ATTAIN-1 will be using 45mg dosing, which could allow for even higher weight loss than Wegovy.
10. Assuming orforglipron will be cheaper due to its oral small molecule non-peptide nature, it will be a key player.
11. 60% of expert’s patients are on oral AOMs such as phentermine. Thus, c50% of patients may consider orforglipron, assuming no significant access barriers.
12. While patients may prefer next-generation higher-efficacy drugs such as retatrutide, only c11% of patients have BMI >40 and thus need 20%-plus weight loss.
13. Many patients may only need or want 10-15% weight loss, hence large opportunity for orforglipron.
14. Orals will also be key in opening up the primary care market.
15. There's a clear use case for orforglipron as a maintenance therapy following weight loss plateau on injectables.
16. Expert expects de-minimis uptake for high-dose oral semaglutide, given worse tolerability, potentially lower weight loss, and fasting requirements.

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