November 23, 2025 11:31 PM GMT Eli Lilly & Co. | North America Obesity Medications: The Broadening – Where do we go from here? | What's Changed | | | | --- | --- | --- | | Eli Lilly & Co. (LLY.N) | From | To | | Price Target | $1,171.00 | $1,290.00 | Earlier this year we outlined our views on "The Broadening" of the GLP-1 market driven by a number of factors, which are playing out. We refresh our LLY model to incorporate these recent developments, in addition to insights from our physician survey; our PT go ...

Core Insights - Amylin, a previously overlooked target, is emerging as a significant player in the multi-billion dollar weight loss market, particularly with the recent data from Novo Nordisk's cagrilintide and its combination with semaglutide showing promising weight loss results [1][2][3] Group 1: Clinical Developments - Novo Nordisk's cagrilintide achieved an average weight loss of 11.8% after 68 weeks of treatment in the REDEFINE 1 study [1] - The combination formulation CagriSema, which includes cagrilintide and semaglutide, demonstrated an average weight loss of 20.4%, significantly outperforming monotherapy [1][9] - Novo Nordisk has registered a Phase 2 clinical trial for NNC0662-0419, a GLP-1/GIP/Amylin triple agonist [1] Group 2: Industry Movements - Pfizer announced a $4.9 billion cash acquisition of Metsera to strengthen its weight loss pipeline, leading to a significant surge in Metsera's stock price [1] - Major pharmaceutical companies like Roche, AstraZeneca, Eli Lilly, and AbbVie are increasingly investing in Amylin through collaborations and acquisitions [2][11] Group 3: Mechanism and Competitive Advantage - Amylin is not a new target; it was discovered in 1987 but faced challenges in earlier formulations due to short half-lives and side effects [3][4] - New generation Amylin analogs have significantly improved half-lives, allowing for less frequent dosing, which enhances patient compliance [5][10] - Amylin's mechanism offers complementary effects to GLP-1, potentially leading to better patient outcomes through combined therapies [8][9] Group 4: Future Directions - The industry consensus is shifting towards collaborative strategies rather than isolated competition, with companies exploring combinations of Amylin and GLP-1 for enhanced efficacy [12][16] - Innovations in drug delivery systems, such as long-acting formulations and oral delivery methods, are being prioritized to improve patient adherence and treatment outcomes [15][16]

Core Insights - Amylin, a previously overlooked target, is emerging as a significant player in the multi-billion dollar weight loss market, particularly with the recent data from Novo Nordisk's cagrilintide and its combination with semaglutide showing promising weight loss results [1][2][6] Group 1: Clinical Data and Results - Novo Nordisk's cagrilintide demonstrated an average weight loss of 11.8% after 68 weeks of treatment in the REDEFINE 1 study [1] - The combination formulation CagriSema, which includes cagrilintide and semaglutide, achieved an average weight loss of 20.4%, significantly outperforming monotherapy [1][8] - Cagrilintide showed lower gastrointestinal side effects compared to semaglutide, indicating better patient compliance [5][7] Group 2: Market Dynamics and Competitive Landscape - The competition in the GLP-1 space is intensifying, leading companies to explore Amylin as a complementary target rather than a replacement [2][7] - Major pharmaceutical companies like Pfizer, Eli Lilly, and Roche are investing heavily in Amylin, indicating a strategic shift towards multi-target approaches [6][9] - The acquisition of Metsera by Pfizer for $4.9 billion, aimed at enhancing its weight loss pipeline, reflects the growing interest in Amylin [1][9] Group 3: Mechanism and Advantages - Amylin's mechanism of action includes appetite suppression and improved insulin sensitivity, which complements GLP-1's effects [7][8] - Clinical data suggest that Amylin drugs may have better tolerability and muscle mass retention compared to GLP-1 drugs, addressing common side effects like nausea and gastrointestinal issues [7][8][11] - The potential for synergistic effects when combining Amylin with GLP-1 has been highlighted, with early clinical evidence supporting enhanced treatment outcomes [8][9] Group 4: Future Directions and Innovations - Companies are focusing on multi-target collaborations and innovative delivery methods to enhance the efficacy and patient compliance of Amylin drugs [11][12] - Oral formulations and long-acting delivery systems are being explored to improve patient experience and adherence to treatment [12][13] - The competitive landscape suggests that successful entrants will need to innovate rather than replicate existing models, emphasizing the importance of understanding clinical needs [13]

Core Insights - The report from Open Source Securities highlights the significant investments by leading companies in the amylin molecule space, indicating a competitive landscape with promising early data on safety and weight loss efficacy [1][2] Group 1: Industry Developments - Major pharmaceutical companies like AbbVie and Roche are making substantial investments in amylin molecules, with AbbVie paying an upfront fee of $350 million and potential milestone payments of up to $1.875 billion for Gubra's amylin molecule [1] - Roche has entered a collaboration with Zealand Pharmaceuticals for the development of petrelintide, committing an upfront payment of $1.65 billion and milestone payments of up to $3.6 billion, sharing profits in the US and Europe [1] - Eli Lilly is also expanding its amylin-related molecule portfolio, including a new dual agonist DACRA molecule with a potential payment structure similar to its previous deals [1] Group 2: Product Performance - Early data for amylin single-agent therapies show excellent safety profiles and significant weight loss, with Eli Lilly's Eloralintide demonstrating a maximum weight loss of 11.3% at 12 weeks [2] - The gastrointestinal safety profile of Eloralintide is impressive, with adverse events like diarrhea, nausea, and vomiting occurring in less than 10% of patients [2] - Several amylin molecules in development have half-lives ranging from 10 to 19 days, supporting the potential for monthly dosing regimens [2] Group 3: Future Catalysts - The next 6-12 months are expected to be rich in data readouts for amylin pipelines, with major companies like Roche, Eli Lilly, and AstraZeneca set to release phase 2 trial data [3] - Novo Nordisk is anticipated to present phase 1 data for two new amylin molecules, while other companies like AbbVie/Gubra and Metsera are expected to provide 12-week data [3] - Companies such as Viking, Structure, and Jiuyuan Gene are recommended for monitoring due to their clinical trial progress in the amylin space [3]

Group 1 - The Hang Seng Healthcare Index (HSHCI) increased by 0.37% as of August 4, 2025, with notable gains from companies such as Cloudmed (01952) up 8.70% and Crystal Technology (02228) up 7.19% [3] - The Hang Seng Healthcare ETF (513060) experienced a decline of 0.59%, with a latest price of 0.67 yuan, but showed a 3.36% increase over the past week as of August 1, 2025 [3] - The liquidity of the Hang Seng Healthcare ETF was active, with a turnover rate of 25.84% and a trading volume of 1.911 billion yuan [3] Group 2 - Global advancements in the weight loss sector are gaining attention, with multinational pharmaceutical companies like AbbVie, Roche, and Eli Lilly accelerating their amylin-related pipelines [4] - Eli Lilly's Eloralintide showed promising weight loss results in Phase 1 clinical trials, achieving a maximum weight loss of 11.3% over 12 weeks with a low incidence of gastrointestinal adverse effects [4] - The amylin molecules in development have half-lives ranging from 10 to 18 days, potentially allowing for monthly dosing and improving patient compliance [4] Group 3 - The latest financing buy-in amount for the Hang Seng Healthcare ETF reached 164 million yuan, with a financing balance of 209 million yuan [5] - Over the past two years, the net value of the Hang Seng Healthcare ETF has increased by 28.35%, with a maximum single-month return of 28.34% since inception [5] - The ETF has a Sharpe ratio of 2.39 for the past year, indicating strong risk-adjusted returns [5] Group 4 - The management fee for the Hang Seng Healthcare ETF is 0.50%, and the custody fee is 0.15% [6] - The ETF's tracking error over the past year is 0.060%, the highest tracking precision among comparable funds [6] - The latest P/E ratio for the Hang Seng Healthcare Index is 31.37, indicating it is at a historical low compared to the past three years [6] Group 5 - The top ten weighted stocks in the Hang Seng Healthcare Index account for 62.03% of the index, including companies like BeiGene (06160) and WuXi Biologics (02269) [6]

Investment Rating - The industry investment rating is "Positive" (maintained) [2] Core Insights - The report highlights the significant potential of the amylin market, with major pharmaceutical companies making substantial investments in amylin molecules, indicating a strong growth trajectory [6][9] - Amylin products are showing promising early clinical data in terms of safety and weight loss efficacy, with specific examples demonstrating competitive advantages over existing treatments [7][22] - A dense pipeline of catalysts is expected in the next 6-12 months, with multiple companies set to release critical clinical trial data that could validate the product profiles of amylin candidates [8][29] Summary by Sections Recent Major BD Transactions - AbbVie and Roche have made significant investments in amylin molecules, with AbbVie paying an upfront fee of $350 million and potential milestone payments of up to $1.875 billion for Gubra's amylin molecule [6][17] - Roche has partnered with Zealand to develop petrelintide, with an upfront payment of $1.65 billion and milestone payments reaching $3.6 billion [6][17] Amylin Product Profile - Early data for amylin monotherapy shows excellent safety and weight loss results, with examples like Eli Lilly's Eloralintide demonstrating a maximum weight loss of 11.3% at 12 weeks [7][22] - The report notes that the majority of weight loss from Eloralintide is fat, with preclinical data showing up to 91% of weight loss being fat [23][28] Future Catalysts - A significant number of amylin pipeline data readouts are expected in the next 6-12 months, with major companies like Roche, Eli Lilly, and AstraZeneca anticipated to release phase 2 trial data [8][29] - Companies such as Viking, Structure, and others are also highlighted for their clinical trial progress in the amylin space [8][29] Investment Recommendations - The report recommends focusing on companies like Borui Pharmaceutical and Zhongsheng Pharmaceutical, which are expected to accelerate their presence in the amylin market [9][31] - Beneficiary companies include Viking, Structure, Metsera, and Jiuyuan Gene, which are positioned to gain from advancements in the amylin sector [9][31]

Company Strategy & Market Opportunity - Lilly aims to provide freedom from diabetes, eliminate serious health issues caused by obesity, and reduce cardiovascular deaths[10] - The company estimates a significant addressable market of over 170 million patients by 2030 for obesity and related conditions[13] - Outside of the US, the addressable market is expected to be approximately 1 billion patients[15] Orforglipron Development Program - Orforglipron, a GLP-1 small molecule, has a broad development plan including studies for Type 2 Diabetes, obesity, hypertension, and obstructive sleep apnea[20] - In the ACHIEVE-1 trial, all three doses of orforglipron achieved superiority versus placebo in reducing HbA1c levels in patients with Type 2 Diabetes[27] - ACHIEVE-1 trial data showed significant reductions in HbA1c observed as early as 4 weeks, with approximately 3/4 of patients achieving an ADA HbA1c target of less than 7%, and 2/3 reaching HbA1c ≤6.5%[27] - ACHIEVE-1 trial also demonstrated dose-dependent reduction in body weight, with approximately 2/3 of patients achieving ≥5% weight reduction and approximately 1/3 achieving ≥10% weight reduction[30] - Topline results for ATTAIN-1, an orforglipron trial in obesity, are expected in Q3 2025[39] Retatrutide Development Program - Retatrutide is undergoing global development with the TRIUMPH program for obesity and related complications, and the TRANSCEND program for Type 2 Diabetes[41] - Topline results for TRIUMPH-4, a retatrutide trial in knee osteoarthritis pain and overweight or obesity, are expected in Q4 2025[48] Tirzepatide & Early Phase Pipeline - The SURPASS-CVOT trial is designed to evaluate tirzepatide against dulaglutide in patients with established cardiovascular disease[51] - Eloralintide, a selective amylin receptor agonist, showed weight loss up to 11.3% in Phase 1 trials and is well-tolerated with less than 10% incidence of GI side effects[60]

Investment Rating - The report maintains an "Overweight" rating for the pharmaceutical and biotechnology industry [1] Core Insights - The report highlights significant data disclosures from the 2025 ADA conference, emphasizing the potential of weight loss and muscle gain drugs, particularly in the Amylin and oral medication segments [10][16] - The report suggests focusing on differentiated drug development in weight loss, particularly the combination of multi-target GLP-1 with Amylin for enhanced efficacy [10][16] Industry Trends - The A-share pharmaceutical index has increased by 1.6% this week and 6.2% year-to-date, while the H-share biotechnology index has seen a rise of 2.7% this week and 52.7% year-to-date [9] - Notable stock performances include Shenzhou Cell (+30%), Haooubo (+27%), and Huaren Health (+25%) in the A-share market, while JunTai Holdings (+63%) and Jingyou Pharmaceutical (+62%) led in the H-share market [9] Research and Development Progress - Significant advancements in innovative drugs and modified drugs have been reported, with a focus on approvals and clinical submissions [6] - The report details the approval of the GLP-1R/GCGR dual agonist "Masitide" by Innovent Biologics, marking it as the first of its kind globally for obesity management [10][16] Specific Recommendations - The report ranks sub-industries as follows: Innovative drugs > CXO > Traditional Chinese medicine > Medical devices > Pharmacies > Pharmaceutical commerce [11] - Recommended stocks based on growth potential include: BGI, Innovent Biologics, and Hengrui Medicine, while undervalued stocks in traditional Chinese medicine include: Zhaoli Pharmaceutical and Dong'e Ejiao [11]