Eli Lilly’s experimental obesity pill helped patients lose 9.6% of their body weight in a trial that moves the company one step closer to a potential approval https://t.co/Iaujssmvki ...

Core Viewpoint - Viking Therapeutics experienced a significant 40% drop in stock price following the release of Phase 2 results for its oral obesity treatment VK2735, despite demonstrating a strong 12.2% weight loss signal over 13 weeks [1][2]. Company Developments - The Phase 3 VANQUISH program was launched on June 25, 2025, with two large trials enrolling: VANQUISH-1 for 4,500 adults with obesity and VANQUISH-2 for 1,100 adults with type 2 diabetes, both lasting 78 weeks [4]. - The injectable formulation previously showed a 14.7% weight loss at 13 weeks with mild to moderate side effects that decreased over time, indicating potential for transitioning from injectables to oral pills for long-term management [5]. Market Opportunity - Goldman Sachs revised its 2030 obesity market forecast to $95 billion, suggesting that even a 2% market share could yield approximately $1.9 billion in annual revenue for Viking, which has a market cap of $2.9 billion [7]. - The company is exploring monthly dosing options for its injectable treatment, positioning itself alongside Novo Nordisk as one of the few to demonstrate efficacy in both oral and injectable forms [8]. Financial Position - Viking has $808 million in cash as of June 30, 2025, but faces a $300 million expense for its registrational program, making partnerships increasingly likely after further data analysis and FDA feedback [9]. - Wall Street maintains an average price target of $87 to $90 per share, indicating a potential 200% upside from current levels, attributed to a misunderstanding of trial design and tolerability issues [11]. Industry Context - The CDC reports that 40% of U.S. adults have obesity, highlighting a vast addressable market for obesity treatments [12]. - Big Pharma remains interested in obesity assets, with companies like AbbVie, Roche, and Amgen actively pursuing deals, making Viking's late-stage opportunity attractive, especially after the recent stock decline [10].

Core Viewpoint - Eli Lilly's obesity pill, orforglipron, has shown disappointing trial results compared to expectations, leading to a significant drop in stock price, although it has since recovered somewhat [2][3]. Drug Efficacy and Comparison - In a late-stage trial, orforglipron resulted in less weight loss (12.4% at the highest dose) and higher side effects than anticipated, while Novo Nordisk's oral semaglutide showed greater efficacy (up to 16.6% weight loss) [13][14]. - Analysts believe that orforglipron could still be a viable competitor in the weight loss market, especially due to its easier absorption and manufacturing advantages over Novo Nordisk's peptide-based drug [5][6]. Market Potential and Projections - Goldman Sachs analysts project that daily oral weight loss pills could capture 24% of the $95 billion global weight loss drug market by 2030, with Eli Lilly's orforglipron expected to hold a 60% share of the daily oral segment, translating to approximately $13.6 billion [7][8]. Manufacturing and Pricing Considerations - Eli Lilly's orforglipron is a small-molecule drug, making it easier and potentially cheaper to manufacture compared to Novo Nordisk's oral semaglutide, which is a peptide medication [5][22]. - Pricing strategies for both drugs remain uncertain, but analysts suggest that orforglipron could be priced lower than Novo Nordisk's offering, which may provide a competitive edge in a market where many health plans do not cover obesity treatments [6][23]. Side Effects and Tolerability - The side effects of orforglipron, primarily gastrointestinal, led to a 10.3% discontinuation rate at the highest dose, which is higher than the placebo group [17][19]. - Comparatively, Novo Nordisk's oral semaglutide had a higher incidence of gastrointestinal side effects, with 30.9% reporting vomiting and 46.6% reporting nausea [19]. Competitive Landscape - The obesity drug market is competitive, with other companies like Pfizer and Viking Therapeutics also developing oral medications, but Eli Lilly and Novo Nordisk are currently leading the race [9][27]. - Viking Therapeutics recently reported disappointing trial results, indicating that its drug may not be as effective as Eli Lilly's orforglipron [27][28].

Core Insights - Investors are disappointed with Viking Therapeutics Inc.'s VKTX data from its Phase 2 trial of an obesity pill, VK2735, which showed a mean body weight reduction of up to 12.2% after 13 weeks from baseline, but concerns over tolerability and higher discontinuation rates have led to a significant stock sell-off [1][3]. Group 1: Trial Results - Participants receiving VK2735 demonstrated a mean body weight reduction of up to 12.2% after 13 weeks from baseline [1]. - VK2735 showed up to a 10.9% reduction in body weight compared to the placebo, with no plateau observed for weight loss at 13 weeks [1]. - All doses of VK2735 greater than 15 mg demonstrated statistically significant differences relative to the placebo on key secondary endpoints, assessing the proportion of subjects who achieved at least 5% and 10% weight loss [2]. Group 2: Tolerability and Discontinuation - Concerns have arisen regarding the tolerability profile of VK2735, with higher rates of discontinuation compared to the Phase I study, which contributed to the stock sell-off [3]. - The 30 mg dose of VK2735 showed a placebo-like safety profile, while the 60 mg group reported higher adverse events and discontinuations [3]. - There is potential for improved tolerability in pivotal studies if the titration period is extended to four weeks instead of the two weeks used in the VENTURE-Oral study [4]. Group 3: Market Position and Future Outlook - Viking's obesity franchise is viewed favorably from an M&A perspective by big pharma, with William Blair previously naming Viking as a top pick for 2025 and reiterating an Outperform rating on its shares [4]. - The company is unlikely to pursue 90 mg or 120 mg doses due to cost-of-goods constraints, making the debate over their tolerability less relevant [4]. - Comparisons with Eli Lilly's tirzepatide indicate that VK2735's dose levels are inferior in terms of weight loss at 13 weeks, raising concerns about its competitive position in the market [5]. Group 4: Stock Performance - VKTX stock has experienced a significant decline, down 41.04% at $24.82 as of the last check on Tuesday [6].

Core Viewpoint - Viking Therapeutics is emerging as a potential competitor to Eli Lilly in the obesity treatment market, which is valued at $100 billion, particularly in light of recent challenges faced by Lilly's oral weight-loss pill [1][6]. Financial Performance of Eli Lilly - Eli Lilly reported a 38% revenue increase to $15.56 billion in the second quarter, with Mounjaro generating $5.2 billion (up 68%) and Zepbound delivering $3.38 billion (up 172% in the U.S.) [4]. - The company raised its full-year revenue guidance to $60 billion to $62 billion, with earnings per share expected between $21.75 and $23, reflecting a 61% increase in quarterly earnings to $6.31 per share and an 85% gross margin [5]. Challenges Faced by Eli Lilly - The results of the ATTAIN-1 trial for Orforglipron showed only 12.4% weight loss at the highest dose, which is lower than competitors like Novo Nordisk's Wegovy, which achieves 14% to 15% weight loss [6]. - This underperformance could limit Lilly's addressable oral market and weaken its mass-market capture strategy, impacting reimbursement rates [7]. Viking Therapeutics' Competitive Edge - Viking Therapeutics' VK-2735 is a dual GLP-1/GIP agonist that could disrupt Lilly's market position, with a subcutaneous formulation in Phase 3 and an oral version in Phase 2 [8][9]. - The subcutaneous version showed a 14.7% weight loss with better tolerability, while the oral version demonstrated weight loss persistence six days after the last dose, indicating potential durability [10]. Market Positioning and Timing - VK-2735 is targeting patients with a body mass index of 30 to 38, a segment that is likely to generate recurring revenue due to their desire for effective results without severe side effects [11]. - The timing of VK-2735's potential launch around 2027 could coincide with challenges for Lilly's Orforglipron, creating a significant competitive threat [12]. Valuation Concerns for Eli Lilly - Eli Lilly's market cap is based on a forward earnings multiple of 29, which assumes continued dominance in the obesity market, but the entry of VK-2735 could disrupt this expectation [13]. - Any loss of market share to Viking could significantly impact Lilly's growth and challenge its premium valuation, especially as its obesity treatments account for over half of its revenue [14][15]. Strategic Recommendations - Investors may consider taking profits from Lilly's recent performance and monitor Viking's Phase 2 oral results expected in the second half of 2025, as this could signal a significant shift in the market dynamics [16].

Core Insights - Novo Nordisk (NVO) has faced a significant setback due to a reduction in its 2025 sales and operating profit outlook, primarily driven by weaker-than-expected performance of its semaglutide-based drugs, Wegovy and Ozempic, particularly in the U.S. obesity market [1][2] - The company is actively pursuing litigation and regulatory actions to combat illegal sales of counterfeit semaglutide, which are impacting Wegovy's market uptake [1] - Despite recent challenges, NVO's stock has shown signs of recovery following a setback for Eli Lilly, presenting a potential opportunity for NVO to regain market momentum [3][4] Sales and Market Performance - Wegovy recorded sales of $5.41 billion (DKK 36.9 billion) in the first half of 2025, reflecting a 78% year-over-year increase driven by strong prescription growth [6] - The competition in the GLP-1 obesity segment is intensifying, particularly from Eli Lilly's Mounjaro and Zepbound, which have seen rapid sales growth despite being on the market for a shorter duration [2][14] - NVO's shares have gained 5.8% in August, despite guidance cuts, indicating a potential recovery in investor sentiment [9] Pipeline and Future Prospects - NVO is making progress with its pipeline, including next-generation obesity candidates like CagriSema and Amycretin, which are expected to target long-term market growth [11][12] - The FDA is reviewing an application for a 25 mg oral semaglutide for obesity, with a decision anticipated by year-end, which could provide NVO with a first-to-market advantage [8][9] - The company is also expanding its presence in rare diseases, with advancements in therapies for hemophilia A and B [10] Competitive Landscape - The obesity market is projected to expand to $100 billion by 2030, with NVO and Eli Lilly currently dominating the space [14] - Other companies, such as Amgen and Viking Therapeutics, are also advancing their GLP-1-based candidates, increasing competition in the market [15] - NVO's stock is currently trading at a premium to the industry, with a price/earnings ratio of 12.12, lower than the industry average of 13.73 [20] Financial Performance and Valuation - Year-to-date, NVO shares have declined by 42.1%, underperforming the industry and the S&P 500 [16][17] - Earnings estimates for 2025 have improved slightly from $3.86 to $3.89 per share, indicating a positive trend in financial expectations [22] - The company's return on equity stands at 78.64%, significantly higher than the large drugmaker industry average of 34.32% [26]

Core Insights - Aardvark Therapeutics announced positive preclinical data for ARD-201, indicating its potential for treating metabolic obesity and related conditions, particularly in weight maintenance after GLP-1RA therapy withdrawal [1][5][7] Company Overview - Aardvark Therapeutics is a clinical-stage biopharmaceutical company focused on developing small-molecule therapeutics aimed at treating metabolic diseases and hunger-related conditions [9] - The lead compound, ARD-101, is in Phase 3 clinical development for hyperphagia associated with Prader-Willi Syndrome, while ARD-201 is a fixed-dose combination of ARD-101 and a DPP-4 inhibitor [9] Preclinical Study Findings - In a validated diet-induced obesity mouse model, ARD-201 demonstrated a significant weight loss of approximately 19% after 30 days of treatment [2][5] - ARD-201 showed improved weight maintenance compared to negative controls and similar results to high-dose tirzepatide, a benchmark GLP-1RA therapy [2][5] - The combination of ARD-201 with low-dose tirzepatide resulted in continued weight loss compared to high-dose tirzepatide alone [5] Future Clinical Trials - Aardvark plans to initiate two Phase 2 clinical trials: the POWER trial focusing on weight rebound prevention after GLP-1RA therapy discontinuation, and the STRENGTH trial assessing weight loss as a monotherapy and in combination with GLP-1RA [6][10] - The POWER trial is expected to start in the second half of 2025, while the STRENGTH trial is planned for the first half of 2026 [10] Mechanism of Action - ARD-201 combines a DPP-4 inhibitor with ARD-101, targeting taste receptors in the gut to enhance satiety and reduce hunger by stimulating the release of signaling molecules like GLP-1 [7][9]

Financial Data and Key Metrics Changes - The company ended the second quarter with cash and cash equivalents totaling $48.6 million, with guidance indicating that current capital is projected to fund operations through at least Q1 2027 [29] - Research and development expenses for the three months ended June 30, 2025, were $14.3 million, compared to $4.1 million for the same period in 2024, primarily due to increased clinical trial costs and contract manufacturing [30] - The net loss for the three months ended June 30, 2025, totaled $17.6 million, compared to $7.9 million for the same period in 2024 [31] Business Line Data and Key Metrics Changes - The phase two a CBEYOND trial is advancing as planned, with enrollment completed ahead of schedule, and the 26-week visit for the last patient projected to occur shortly [7] - Approximately 50% of patients from the original study are eligible for enrollment in the extension study, with optimism that a majority will choose to participate [7][56] Market Data and Key Metrics Changes - The company identifies three market opportunities for Nimasumab: as a monotherapy for patients who cannot tolerate incretin therapeutics, as a combination partner to amplify efficacy, and as a maintenance therapy to sustain weight loss [22] - The obesity treatment market is evolving beyond caloric restriction to address broader metabolic impacts, indicating a shift in treatment paradigms [26] Company Strategy and Development Direction - The company aims to position Nimasumab as a next-generation backbone candidate for durable and combinable obesity care, addressing the limitations of current therapies [25] - The focus is on expanding therapeutic options in obesity treatment, particularly for patients who discontinue existing therapies due to side effects [24] Management's Comments on Operating Environment and Future Outlook - Management emphasizes the importance of disciplined execution and operational rigor as the company enters a crucial execution period [32] - The upcoming top-line data from the CBEYOND trial is expected to provide insights into the efficacy and safety of Nimasumab, guiding future development [34] Other Important Information - The company plans to host a KOL event at Nasdaq on September 4, focusing on clinical data expectations and market positioning [33] - The phase one SADMAD MAFLD data will be presented at EASD on September 19, reinforcing hepatic and metabolic benefits [33] Q&A Session Summary Question: What accounted for the increase in R&D expenses? - The increase was primarily due to contract manufacturing costs related to the phase two a resupply and the supply for the phase two b trial [41] Question: What are the expectations for Nimasumab's weight loss efficacy at week 26? - The goal is to demonstrate a clinically meaningful weight loss separation from placebo, ideally in the range of 5% to 8% [46] Question: What is the expected discontinuation rate within 26 weeks? - The company expects a discontinuation rate similar to trends seen in other obesity studies, around 25% to 30% [50] Question: What is the protocol for the independent board overseeing trial safety? - The board meets quarterly and reviews all adverse events and serious adverse events reported during the study [73] Question: Will there be a follow-up period after the extension study to track durability of weight loss? - Yes, there will be a 13-week follow-up period after the extension study, with data expected in 2026 [82]

Core Viewpoint - Eli Lilly's shares experienced a significant decline of over 14% following the release of disappointing trial data for its obesity treatment pill, orforglipron, which did not meet Wall Street's expectations for weight loss results [1][2]. Company Summary - Eli Lilly's orforglipron showed an average weight loss of just over 12% in late-stage trials, falling short of the anticipated 15% [2]. - The highest dosage of orforglipron resulted in more than 59% of patients losing at least 10% of their body weight, while nearly 40% lost at least 15% [3]. - CEO David Ricks stated that the company was not disappointed with the results, emphasizing that they aligned with the company's expectations despite being slightly below Wall Street's projections [4]. Industry Context - The competition among pharmaceutical companies, including Eli Lilly, Novo Nordisk, and Pfizer, to develop effective weight-loss pills has intensified, particularly following the success of Novo Nordisk's Ozempic and Wegovy [7]. - Eli Lilly plans to file for regulatory approval of orforglipron by the end of the year, while Novo Nordisk's treatment is under regulatory review, with a decision expected in late 2025 [7]. - Other companies, such as Roche and Viking Therapeutics, are also developing oral weight-loss drugs, reporting average weight loss of 6.1% and 8.2% in early- and mid-stage trials, respectively [8].

Financial Data and Key Metrics Changes - For Q2 2025, Lexicon Pharmaceuticals reported revenues of $28.9 million, a significant increase from $1.6 million in Q2 2024, primarily driven by $27.5 million in licensing revenue from Novo Nordisk [24] - The net income for Q2 2025 was $3.3 million, or $0.01 per share, compared to a net loss of $53.4 million, or $0.17 per share, in the same period of 2024 [25] - Total operating expenses decreased by $31.9 million quarter over quarter, reflecting the company's strategic repositioning as an R&D-focused entity [27] Business Line Data and Key Metrics Changes - Research and development expenses for Q2 2025 decreased to $15.7 million from $17.6 million in Q2 2024, mainly due to lower external research expenses on the PROGRESS clinical trial [25] - Selling, general, and administrative expenses decreased to $9.4 million in Q2 2025 from $39.2 million in 2024, attributed to reduced marketing efforts for MPEFA [25] Market Data and Key Metrics Changes - The company is actively pursuing regulatory approvals for sotagliflozin in various international markets, including the UAE, Saudi Arabia, Canada, Australia, New Zealand, and several Southeast Asian countries [31] - The ongoing Phase III SONATA study for sotagliflozin is the only registrational trial currently evaluating treatment in both obstructive and non-obstructive hypertrophic cardiomyopathy (HCM) [20] Company Strategy and Development Direction - Lexicon is focused on advancing its innovative portfolio of potential medicines, with a strategic pivot towards R&D that has taken shape in 2025 [6] - The company aims to maximize the potential of its drug candidates through partnerships, particularly with Novo Nordisk for LX9851 and Viatris for sotagliflozin [32] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the progress of their R&D programs and the potential for pilavapitan to become a transformative therapy for patients with neuropathic pain [14] - The company anticipates presenting full progress data for pilavapitan in Q3 2025 and is preparing for an end-of-Phase II meeting [33] Other Important Information - The company ended Q2 2025 with $168 million in cash and short-term investments, down from $238 million at the end of 2024 [26] - Lexicon expects to recognize the remaining $17.5 million of licensing revenue from the Novo agreement in the second half of 2025 [26] Q&A Session Summary Question: Can you walk us through the SOTA CROSS trial and its design? - Management explained that the SOTA CROSS trial is designed to evaluate therapeutic options for non-obstructive HCM, with a crossover design allowing patients to serve as their own control [42] Question: How does the company plan to take advantage of the push for non-opioid pain medications? - Management highlighted their engagement with legislative efforts supporting non-opioid medications and expressed optimism about the potential for pilavapitan in this context [48] Question: What is Novo's plan for the Phase I study in obesity? - Management indicated that Novo is expected to vigorously pursue the Phase I program for LX9851, with a focus on oral and combination therapies [56] Question: How does the recent Vertex announcement impact confidence in the pain market? - Management expressed increased confidence in their own neuropathic pain program, citing successful Phase II results with pilavapitan [72] Question: Will an echo be required for patients if sotagliflozin is approved? - Management stated that while an echo will be part of the study protocol, it may not be a major impediment for patient suitability if approved [78]