Core Viewpoint - Ariel Investments' "Ariel Global Fund" reported a +7.38% return in Q2 2025, underperforming compared to the MSCI ACWI Index (+11.53%) and MSCI ACWI Value Index (+5.84%) [1] Group 1: Fund Performance - The second quarter of 2025 was marked by volatility, with stocks initially falling after the "Liberation Day" tariff announcement and then rebounding due to a pause in tariff implementation [1] - Enthusiasm for AI-themed stocks and strong corporate earnings contributed to new highs in global and U.S. indices [1] Group 2: Sanofi (NASDAQ:SNY) Analysis - Sanofi's stock experienced a one-month return of -7.26% and a 52-week decline of 18.46%, closing at $46.86 with a market capitalization of $114.201 billion on September 16, 2025 [2] - Concerns over potential U.S. tariffs on European pharmaceutical imports and mixed results from Phase 3 trials of Itepekimab negatively impacted Sanofi's performance [3] - Despite challenges, the company’s immunology pipeline is viewed as undervalued, with optimism surrounding the growth of Dupixent and upcoming Phase 3 outcomes for Amlitelimab [3] Group 3: Hedge Fund Interest - Sanofi was held by 24 hedge fund portfolios at the end of Q2 2025, a decrease from 27 in the previous quarter [4] - While Sanofi is recognized for its potential, certain AI stocks are considered to offer greater upside potential with less downside risk [4]

Financial Data and Key Metrics Changes - For the first half of 2025, the company reported total revenue of $4.9 million, primarily driven by collaborations with AstraZeneca and Sanofi, as well as governmental funding for research expenditures [28] - Operating expenses reached $30.3 million, with R&D expenses at $20.5 million, reflecting a 29% decrease compared to the prior year, while G&A expenses remained stable at $9.8 million [28] - As of June 30, 2025, the company had $70.4 million in cash, cash equivalents, and financial assets, providing a cash runway until the end of the third quarter of 2026 [28] Business Line Data and Key Metrics Changes - The company is focusing investments on three high-value clinical assets: IPH4502, Lacutamab, and Monalizumab, which are expected to create meaningful value [4][30] - IPH4502 is currently in phase one development, with enrollment progressing well and expected to complete by the end of Q1 2026 [11][14] - Lacutamab is close to completing the phase three protocol, with potential accelerated approval in Sézary syndrome anticipated by 2027 [21][25] Market Data and Key Metrics Changes - The company identified approximately 1,000 Sézary syndrome patients in the U.S., with around 300 new cases each year, representing a significant market opportunity for Lacutamab [24][25] - The total agreement with AstraZeneca for Monalizumab is worth up to $1.275 billion, with $450 million already received in upfront and milestone payments [27] Company Strategy and Development Direction - The company has made a strategic decision to streamline its organization and focus on high-value clinical assets to drive forward programs that can make a significant difference [4][30] - The company is actively working with investors and partners to secure funding for the phase three trial of Lacutamab, while also exploring options for IPH4502 [38][39] Management Comments on Operating Environment and Future Outlook - Management expressed confidence in the strategic refocus and the potential of the clinical pipeline to deliver value for patients and shareholders [30] - The restructuring plan is fully embedded into the cash runway, ensuring financial visibility through the end of Q3 2026 [54] Other Important Information - The Chief Scientific Officer, Eric Vivier, will transition to a role as an advisor to the R&D Committee of the Board of Directors, ensuring continued collaboration [5] - The company is exploring the potential of IPH4502 in urothelial cancer patients who have become refractory to enfortumab vedotin, with a focus on addressing high unmet medical needs [41] Q&A Session Summary Question: What should we take away on the potential of targeting NK cells now that ANKET® assets are not included in your prioritization today? - Management clarified that while NK cells are not the main priority, they are still working on NK cell engagers and will base future decisions on clinical data [32][33] Question: Any commentary on where Sanofi is with the assets that they currently are developing? - Management indicated that Sanofi continues to progress the BCMA-targeted ANKET® and updates are expected soon [37] Question: Regarding the phase three start for Lacutamab, should we still assume that unless you have a partner signed up ahead of the start of the study, it'll still be a wait and watch? - Management confirmed they are actively working with investors and partners to keep options open for moving forward with Lacutamab [38] Question: Based on the preclinical data that you have generated so far, what potential indications do you think IPH4502 will be effective? - Management highlighted a focus on urothelial cancer patients who are refractory to enfortumab vedotin, with potential for accelerated market approval [41] Question: Can you provide an initial estimate of the investment requirements if you decide to go to trial without a partner? - Management stated they would not normally communicate specific costs but indicated it would be similar to other oncology phase 3 trials [56]

Financial Data and Key Metrics Changes - For the first half of 2025, the company reported total revenue of $4.9 million, primarily driven by collaborations with AstraZeneca and Sanofi, as well as governmental funding for research expenditures [29] - Operating expenses reached $30.3 million, with R&D expenses at $20.5 million, reflecting a 29% decrease compared to the prior year, while G&A expenses remained stable at $9.8 million [29] - As of June 30, 2025, the company had $70.4 million in cash, cash equivalents, and financial assets, providing a cash runway until the end of the third quarter of 2026 [29] Business Line Data and Key Metrics Changes - The company is focusing investments on three high-value clinical assets: IPH4502, Lacutamab, and Monalizumab, which are expected to create meaningful value and transform care [5][31] - IPH4502 is currently in phase one development, with enrollment progressing well and expected to complete by the end of Q1 2026 [12][15] - Lacutamab is close to finalizing the phase three protocol, with potential for accelerated approval in Sézary syndrome [16][21] Market Data and Key Metrics Changes - The company identified approximately 1,000 Sézary syndrome patients in the U.S., with around 300 new cases each year, representing a significant market opportunity for Lacutamab [24] - The total agreement for Monalizumab with AstraZeneca is worth up to $1.275 billion, with $450 million already received in upfront and milestone payments [28] Company Strategy and Development Direction - The company has made a strategic decision to streamline its organization and focus on high-value clinical assets, aligning its strategy, science, and investments [5][31] - The company is exploring partnerships and investor support to advance Lacutamab towards phase three, with a focus on maximizing value for both patients and shareholders [21][39] Management Comments on Operating Environment and Future Outlook - Management expressed confidence in the strategic refocus and the potential of the clinical pipeline to deliver value for patients and shareholders [31] - The restructuring plan is fully embedded into the cash runway, ensuring financial visibility until the end of Q3 2026 [55] Other Important Information - The Chief Scientific Officer, Eric Vivier, will transition to a role as an advisor to the R&D Committee of the Board of Directors, ensuring continued collaboration [6] - The company is actively collecting additional market data for Lacutamab and plans to share insights at a focused investor event by the end of the year [26] Q&A Session Questions and Answers Question: What should we take away on the potential of targeting NK cells now that ANKET® assets are not included in your prioritization today? - Management clarified that while NK cells are not the main priority, they are still working on NK cell programs and will base future decisions on clinical data [33][35] Question: Any commentary on where Sanofi is with the assets that they currently are developing? - Management indicated that Sanofi continues to progress the BCMA-targeted ANKET® and updates are expected soon [38] Question: Regarding the phase three start for Lacutamab, should we still assume that unless you have a partner signed up ahead of the start of the study, it'll still be a wait and watch? - Management confirmed they are actively working with investors and partners to keep options open for advancing Lacutamab into phase three [39][40] Question: Based on the preclinical data that you have generated so far, what potential indications do you think IPH4502 will be effective? - Management highlighted that IPH4502 could be effective in urothelial cancer patients who became refractory to enfortumab vedotin, with potential for accelerated market approval [41][42] Question: Can you provide an update on how enrollment has been progressing for IPH4502? - Management reported that enrollment is going extremely well, with plans to finish by Q1 2026 and a pool of data expected from 50-60 patients [46][48]

Financial Data and Key Metrics Changes - For the first half of 2025, the company reported total revenue of EUR 4.9 million, primarily driven by collaborations with AstraZeneca and Sanofi, as well as governmental funding for research expenditures [29] - Operating expenses reached EUR 30.3 million, with EUR 20.5 million in R&D and EUR 9.8 million in G&A expenses; R&D expenses decreased by 29% compared to the prior year [29] - As of June 30, 2025, the company had EUR 70.4 million in cash, cash equivalents, and financial assets, providing a cash runway until the end of the third quarter of 2026 [29] Business Line Data and Key Metrics Changes - The company is focusing investments on three high-value clinical assets: IPH4502, lacutamab, and monalizumab, which are expected to create meaningful value [5][31] - IPH4502 is currently in phase one development, with enrollment on track to complete by the end of Q1 2026 [12] - Lacutamab has secured FDA breakthrough therapy designation and is preparing for phase III protocol submission [22][31] Market Data and Key Metrics Changes - The company identified approximately 1,000 Sézary syndrome patients in the U.S., with around 300 new cases each year, representing a significant market opportunity for lacutamab [25] - There are approximately 20,000 CTCL patients in the U.S., with an incidence of about 5,000 patients, suggesting a larger population than previously estimated [26] Company Strategy and Development Direction - The company has made a strategic decision to streamline its organization and focus on high-value clinical assets to drive forward programs that can make a significant difference [5][31] - The partnership with AstraZeneca for monalizumab is a significant value driver, with a total agreement worth up to $1.275 billion [28] Management Comments on Operating Environment and Future Outlook - Management expressed confidence in the strategic refocus and the potential of the clinical pipeline to deliver value for patients and shareholders [31] - The restructuring plan is fully embedded into the cash runway, ensuring financial visibility until the end of Q3 2026 [54] Other Important Information - The Chief Scientific Officer responsibilities have been assumed by the COO following the departure of the CSO, who will continue to support the company as an advisor [6][7] Q&A Session Summary Question: What should we take away on the potential of targeting NK cells now that ANKET assets are not included in your prioritization today? - Management clarified that while NK cells are not the main priority, they are still working on NK cell programs and will base future decisions on clinical data [34][35] Question: Any commentary on where Sanofi is with the assets that they currently are developing? - Management indicated that Sanofi continues to progress the BCMA-targeted ANKET and expects updates in the near future [37] Question: Regarding the phase III start for lacutamab, should we still assume that unless you have a partner signed up ahead of the start of the study, it'll still be a wait and watch? - Management is actively working with investors and partners to keep options open for moving forward with lacutamab [38][39] Question: Based on the preclinical data that you have generated so far, what potential indications do you think IPH4502 will be effective? - Management highlighted a focus on urothelial cancer patients who became refractory or resistant to PADCEV, with potential for accelerated market approval [40][41] Question: Can you provide an initial estimate of the investment requirements if you decide to go to trial without a partner? - Management refrained from providing specific cost estimates but indicated that it would be similar to standard oncology phase III trials [56]

Investment Rating - The report does not explicitly state an investment rating for the allergic rhinitis drug industry in China. Core Insights - The Chinese allergic rhinitis drug market is projected to grow from CNY 44 billion in 2019 to CNY 81 billion by 2024, with a compound annual growth rate (CAGR) of 12.9%. By 2030, the market is expected to reach CNY 229 billion, reflecting a growth rate of 19.0% [5]. - The report highlights the increasing importance of biological agents in treating moderate to severe allergic diseases, with significant advancements in drug development and clinical applications [20][23]. Summary by Sections Market Overview - The market for allergic rhinitis drugs in China is expected to grow from CNY 422 billion in 2019 to CNY 462.8 billion by 2024, with a CAGR of 1.9%, and is projected to reach CNY 567.7 billion by 2030 [16]. Treatment Landscape - Current treatment options for allergic rhinitis are categorized into first-line, second-line, and third-line therapies. First-line treatments include nasal corticosteroids and second-generation antihistamines [5][11]. - Immunotherapy is recommended as a first-line treatment for the underlying cause of allergic rhinitis, while symptomatic treatments focus on alleviating symptoms [11]. Drug Development - Biological agents, particularly monoclonal antibodies targeting IL-4Rα and IgE, are gaining traction in the treatment of allergic rhinitis. The first approved IL-4Rα biological agent, Suptuizumab, offers a new treatment option for patients [20][23]. - The report notes that the development of new biological agents is ongoing, with several candidates in various stages of clinical trials [20][23]. Patient Demographics and Treatment Needs - The report indicates that the treatment needs of allergic rhinitis patients vary based on the severity of their condition. A significant portion of patients requires comprehensive treatment strategies, especially those with moderate to severe persistent allergic rhinitis [19]. - The high conversion rate between allergic rhinitis and asthma underscores the importance of long-term management and early intervention in treatment [19]. Innovation and Market Dynamics - The report emphasizes the shift towards targeted biological therapies due to the limitations of traditional treatments. The market for anti-IgE antibodies is evolving with new formulations and biosimilars, enhancing treatment options for patients [23][24]. - The report also highlights the maturity of upstream technologies related to the production of antihistamines and biological agents, which supports industry growth [27][29].

Investment Rating - The industry investment rating is "Outperform" [1] Core Viewpoints - The global market for Inflammatory Bowel Disease (IBD) drugs is expected to reach $37 billion by 2030, with major pharmaceutical companies investing in this area [4][26] - There is a significant unmet clinical need for new therapies due to the complexity of IBD mechanisms and the high percentage of patients who do not respond to initial treatments [4][18] - The report emphasizes the importance of new targets and mechanisms in drug development, particularly focusing on TL1A, which has garnered interest from multiple multinational corporations (MNCs) [4][32] Summary by Sections IBD Treatment Overview - IBD includes Ulcerative Colitis (UC) and Crohn's Disease (CD), affecting over 3 million patients in the US and Europe, with no current cure available [4][10] - The market for IBD drugs is projected to grow at a compound annual growth rate (CAGR) of 5.88% from $23.26 billion in 2022 to $37 billion by 2030 [26][29] Market Dynamics - The sales proportion of TNF inhibitors is declining, while IL-23 inhibitors and JAK inhibitors are increasing in sales [4][29] - Ustekinumab is expected to contribute approximately $7.8 billion to the market by 2024, while Vedolizumab is projected to reach $6.107 billion [4][29] Clinical Needs and Drug Development - There is a pressing need for new therapies as up to 30% of patients do not respond to initial treatments, and 40% lose response over time [4][18] - The report suggests focusing on new targets and mechanisms, including companies like Abivax, Chenxin Pharmaceutical, and others for potential investment opportunities [4][32] Long-term Investment Strategy - The report recommends a strategic focus on leading innovative drug companies and those involved in the development of new therapies for IBD, highlighting companies such as Innovent Biologics, BeiGene, and others [4][32] - The report also notes the potential for significant market transactions in the IBD space, with several deals exceeding $5 billion in value [4][30]

Core Insights - Inflammatory Bowel Disease (IBD) includes Ulcerative Colitis (UC) and Crohn's Disease (CD), affecting over 3 million patients in the US and Europe, with no current cure available [1] - The global IBD drug market is expected to reach $37 billion by 2030, with a shift in sales from TNF inhibitors to IL-23 inhibitors and JAK inhibitors [2] - The emergence of new therapeutic targets and mechanisms is crucial due to the high percentage of patients who do not respond to initial treatments [2] Group 1: IBD Overview - IBD encompasses UC and CD, with symptoms that can lead to severe complications like bowel perforation [1] - Current first-line treatments for mild to moderate CD include corticosteroids and traditional immunosuppressants, while anti-TNF agents are preferred for moderate to severe cases [1] - There is a significant need for new therapies as up to 30% of patients do not respond to initial treatments, and up to 40% may lose response over time [1] Group 2: Market Dynamics - The sales proportion of TNF inhibitors is declining, while IL-23 inhibitors and JAK inhibitors are gaining market share [2] - Ustekinumab contributes approximately $7.8 billion to the IBD market, while Vedolizumab is projected to reach $6.107 billion in global sales by 2024 [2] - Major pharmaceutical companies like AbbVie, Johnson & Johnson, and Merck are actively involved in the IBD market [2] Group 3: Investment Opportunities - New therapeutic targets such as TL1A are being explored, with several phase 3 studies currently underway [2] - Companies to watch include Abivax, Chenxin Pharmaceutical, and others focusing on new mechanisms and dual antibodies [2] - The industry is expected to see significant growth driven by differentiated second-line therapies and innovative product development [2][3]

This document has been prepared by Innate Pharma S.A. (the "Company") solely for the purposes of a presentation to investors concerning the Company. This document is not to be reproduced by any person, nor to be distributed. This document contains forward-looking statements. The use of certain words, including "believe," "potential," "expect" and "will" and similar expressions, is intended to identify forward-looking statements. Although the Company believes its expectations are based on reasonable assumpti ...

Core Insights - Nurix Therapeutics announced the presentation of preclinical data for GS-6791, a novel IRAK4 protein degrader, which supports its advancement into clinical studies [1][2] - The findings were presented at the European Academy of Dermatology and Venereology (EADV) Congress, highlighting the potential of GS-6791 in treating inflammatory diseases [1][4] Preclinical Data - GS-6791 mediates sustained degradation of IRAK4, leading to significant inhibition of IL-1 and IL-36-driven responses in skin epithelial cell systems [2][5] - The drug demonstrated near-complete knockdown of IRAK4 in human blood and keratinocytes, with deep inhibition of cytokine pathways relevant to dermatologic diseases [5] Mechanism of Action - GS-6791 is characterized as a potent, orally available degrader of IRAK4, providing a differentiated pharmacologic profile compared to traditional kinase inhibitors [3][4] - By selectively degrading IRAK4, GS-6791 targets complex immune signaling pathways, potentially expanding treatment options for patients with inflammatory diseases [3][4] Collaboration with Gilead - Nurix and Gilead Sciences entered a strategic collaboration in June 2019 to develop targeted protein degradation therapies, with Nurix receiving $135 million to date [4] - For the IRAK4 program, Nurix is eligible for up to $420 million in potential milestone payments and royalties on net sales, with co-development options available for two programs in the U.S. [4][5] Clinical Development - Gilead exercised its option to license GS-6791 in March 2023, taking responsibility for further development [5] - The Investigational New Drug (IND) application for GS-6791 was cleared by the FDA in April 2025, with an ongoing Phase 1 trial assessing safety and pharmacodynamics in healthy volunteers [5]

Group 1 - Multinational pharmaceutical companies are increasingly investing in the U.S., with GlaxoSmithKline (GSK) committing to invest $30 billion over the next five years, viewing the U.S. as its top priority market [3][4] - Other pharmaceutical companies have also announced significant investments in the U.S., including Eli Lilly's $27 billion, Johnson & Johnson's $55 billion, and Merck's $9 billion plans [3][4][5] - The U.S. pharmaceutical industry heavily relies on overseas supply chains for active pharmaceutical ingredients (APIs) and generic drugs, raising concerns about the feasibility of reshoring production [4][6] Group 2 - The U.K. pharmaceutical industry faces significant investment loss risks due to ongoing disputes over drug pricing controls, with the new VPAG scheme requiring companies to return 23.5% to 35.6% of brand drug revenues to the NHS [7][8] - The British pharmaceutical industry association has warned that maintaining high rebate rates could lead to a loss of approximately £11 billion in R&D investment by 2033 [7][8] - Recent actions by multinational companies, such as Merck canceling a £1 billion research hub in London and AstraZeneca pausing expansion plans, highlight the impact of the U.K. government's slow progress on life sciences investment [8]