Summary of Jade Biosciences Conference Call Company Overview - **Company**: Jade Biosciences (NasdaqCM:JBIO) - **Focus**: Development of therapies for autoimmune diseases, recently formed in June 2024 - **Key Assets**: Acquired three assets from Paragon Therapeutics, specializing in high affinity antibodies with half-life extension technology [1][2] Core Programs - **Lead Program**: JADE101, an anti-APRIL therapy targeting IgA nephropathy - **Market Potential**: Estimated at over $10 billion in the US [2] - **Mechanism**: Disease-modifying potential without unnecessary immunosuppression - **Dosing Schedule**: Aiming for one injection every eight weeks [2][4] - **Phase I Study**: Initiated with first cohort dosed, expected readout in the first half of next year [2][4] - **Second Program**: JADE201, a BAFF receptor targeting antibody - **Indication**: Initially targeting rheumatoid arthritis [3] - **Development Timeline**: First trial expected in the first half of next year [3] - **Third Program**: JADE03, details not extensively discussed, expected to enter the clinic in the first half of 2027 [4] Financial Position - **Funding**: - Initial reverse merger raised $300 million - Additional PIPE financing brought in $135 million [4] - **Cash Runway**: Pro forma cash position of approximately $356 million, expected to last into the first half of 2028 [42] Treatment Landscape for IgA Nephropathy - **Current Treatments**: Historically involved ACE inhibitors and steroids, evolving towards new therapies [6][7] - **KDIGO Guidelines**: New guidelines recommend treating all patients with agents that deplete pathogenic IgA and achieving ambitious proteinuria targets [8][9] - **Future Expectations**: Selective anti-APRIL therapies expected to become frontline treatments [8][9] Clinical Insights - **Biomarker Richness**: IgA nephropathy is biomarker-rich, aiding in the prediction of clinical efficacy [3][24] - **Phase III Trials**: Initial data from phase III trials of other therapies show promising results, with selective anti-APRIL showing a 51% reduction in proteinuria [12][20] JADE101 Design and Mechanism - **Potency**: JADE101 designed to have ultra-high binding affinity to APRIL, significantly higher than existing therapies [14][16] - **Half-Life Extension**: Incorporates YTE mutation for extended plasma exposure, aiming for convenient dosing [15][16] - **Clinical Activity**: Expected to provide significant clinical activity with minimal dosing frequency [23] JADE201 Development - **Mechanism**: Designed to deplete B-cells while blocking compensatory BAFF upregulation, enhancing therapeutic efficacy [35][36] - **Phase I Study**: Planned for rheumatoid arthritis patients, focusing on safety and pharmacokinetics [38] Regulatory Environment - **FDA Engagement**: Ongoing discussions with the FDA regarding the potential for accelerated approval based on proteinuria as a surrogate endpoint [31][32] Conclusion - Jade Biosciences is positioned to capitalize on significant market opportunities in autoimmune therapies, with a strong financial foundation and promising clinical programs aimed at addressing unmet medical needs in IgA nephropathy and other autoimmune conditions [4][42]

Core Insights - Novartis presented new data on ianalumab for Sjögren's disease, highlighting its potential to significantly improve disease activity and reduce patient burden in Phase III trials [1][2][4] Clinical Trial Results - Ianalumab 300 mg monthly showed a clinically meaningful benefit in the NEPTUNUS-1 and NEPTUNUS-2 Phase III trials, with a greater reduction in disease activity compared to placebo, sustained through Week 52 [2][4] - Statistically significant improvement in the primary endpoint, ESSDAI, was observed at Week 48, with numerical improvements noted as early as Week 16 [4][5] - Secondary outcome measures also showed consistent numerical improvements, including physician- and patient-reported outcomes, although some did not reach statistical significance [5][7] Mechanism of Action - Ianalumab is a fully human monoclonal antibody that depletes B-cells and inhibits their activation and survival via BAFF-R blockade, addressing the B-cell dysfunction central to Sjögren's disease [3][9] Future Plans - Novartis plans to submit ianalumab for regulatory approval globally in early 2026, aiming to establish it as the first targeted treatment for Sjögren's disease [5][4] Disease Overview - Sjögren's disease is a systemic autoimmune condition affecting approximately 0.25% of the population, with a higher prevalence in women, leading to significant symptoms such as dryness, fatigue, and pain [10]

Core Insights - Novartis presented new data on ianalumab for Sjögren's disease, highlighting its potential to significantly improve disease activity and reduce patient burden in Phase III trials [1][2][4] Group 1: Clinical Trial Results - Ianalumab 300 mg monthly showed a clinically meaningful benefit in the NEPTUNUS-1 and NEPTUNUS-2 Phase III trials, with significant improvements in disease activity measured by the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) [2][4] - The trials demonstrated statistically significant improvement in ESSDAI at week 48, with numerical improvements observed as early as Week 16 and sustained through Week 52 [4][6] - Patients receiving ianalumab exhibited consistent numerical improvements in secondary outcome measures, including physician- and patient-reported outcomes [5][6] Group 2: Mechanism of Action - Ianalumab is a fully human monoclonal antibody that depletes B-cells and inhibits their activation and survival via BAFF-R blockade, addressing the B-cell dysfunction that contributes to Sjögren's disease [3][12] Group 3: Safety Profile - The trial results indicated a favorable safety profile for ianalumab, with the overall incidence of adverse events comparable to placebo [8] Group 4: Future Plans - Novartis plans to submit ianalumab to health authorities globally in early 2026, aiming to introduce the first targeted treatment for Sjögren's disease [6][4] Group 5: Disease Overview - Sjögren's disease is a complex autoimmune condition affecting approximately 0.25% of the population, with a higher prevalence in women and a significant risk of lymphoma [13]

Financial Performance - Novartis reported a 7% increase in net sales and core operating income for Q3 2025, with a core margin of 39.3% [5][27] - Core EPS rose by 10% to $2.25, and free cash flow totaled $6.2 billion for the quarter [28][27] - For the first nine months, net sales grew by 11%, core operating income by 18%, and core EPS increased by 21% to $6.94 [28][29] Business Line Performance - Key brands showed strong growth: Kisqali grew 68%, Pluvicto 45%, Leqvio 54%, and Scemblix 95% in constant currency [6][10][14][16] - Kisqali's U.S. growth was particularly strong at 91%, with a market-leading position in both metastatic and early breast cancer [7][9] - Pluvicto's growth was driven by new patient starts, with U.S. sales up 53% [11][12] - Leqvio is on track for over $1 billion in sales, with significant growth in both the U.S. and international markets [14][15] - Scemblix is expected to become the most prescribed TKI in the U.S. [16] Market Performance - The U.S. experienced negative growth due to net true-ups related to Medicare Part D redesign, but underlying growth would have been 9% without these adjustments [27][28] - Outside the U.S., Kisqali saw 37% growth in constant currency, and Pluvicto is expanding in Europe, Canada, and Brazil [7][12] - The renal portfolio, particularly IGAN, grew 98% in the U.S., significantly outpacing market growth [20][21] Company Strategy and Industry Competition - Novartis is focused on driving growth through its priority brands and pipeline advancements, despite facing generic erosion from products like Entresto [5][28] - The company is pursuing strategic acquisitions, including Avidity Biosciences, to enhance its growth trajectory [35][36] - Novartis aims to maintain a core margin of around 40% despite expected short-term dilution from new product launches [35][36] Management Commentary on Operating Environment and Future Outlook - Management expressed confidence in mid to long-term growth, reaffirming guidance for high single-digit growth in net sales and low teens growth in core operating income for the full year [31][38] - The company anticipates challenges in the first half of 2026 due to generic competition but expects a stronger second half [33][34] - Management highlighted the importance of addressing pricing and reimbursement issues with the administration to support innovation [41][42] Other Important Information - Novartis is preparing for regulatory submissions for several products, including remibrutinib and ianalumab, with expectations for rapid uptake in the market [22][24] - The company is focused on enhancing its R&D capabilities and expanding its manufacturing base in the U.S. [43] Q&A Session Summary Question: Impact of Medicaid and tariffs on the industry - Management indicated that while some companies have reached agreements with the administration, Novartis is in ongoing discussions to find suitable solutions [41][42] Question: CapEx and cash flow modeling - Management clarified that the majority of the $23 billion commitment over five years is for R&D OpEx, with CapEx expected to remain stable at 2.5%-3% of sales [42][43] Question: Market reaction to ATR abstract - Management expressed confidence that detailed data presentation would improve market perception and emphasized the importance of patient benefits over statistical measures [46][47] Question: Pluvicto launch curve and peak sales ambition - Management stated that Pluvicto is on a strong growth trajectory, expecting to reach peak sales of $5 billion with ongoing efforts to tackle commercialization challenges [55][56][58] Question: Remibrutinib ramp-up and European adoption - Management highlighted the focus on payer negotiations and the potential for rapid uptake in the U.S. and Europe, emphasizing the innovative profile of remibrutinib [62][64] Question: Ianalumab study results and secondary endpoints - Management explained the statistical significance achieved in primary endpoints and the importance of patient-relevant outcomes for future discussions with physicians [68][71] Question: Cosentyx market share and new formulation - Management noted that there has been no significant impact from competitor launches and emphasized ongoing efforts to maintain market share in a growing market [74]

Financial Performance - In Q3 2025, net sales grew by 7% year-over-year, and core operating income also increased by 7%, with a core margin of 39.3% [4][26] - Excluding negative adjustments, underlying growth would have been 9% for net sales and 11% for core operating income, driven by priority brands and new launches [26][27] - Core EPS reached $2.25, reflecting a 10% increase, and free cash flow totaled $6.2 billion [27][28] - For the first nine months, net sales grew by 11%, core operating income increased by 18%, and core EPS was up 21% at $6.94 [27][28] Business Line Performance - Kisqali experienced a 68% growth in Q3, with U.S. growth at 91%, making it a leader in both metastatic and early breast cancer markets [5][6] - Pluvicto grew by 45% in constant currency, with U.S. sales up 53%, driven by new patient starts [10][11] - Leqvio sales increased by 54%, on track for over $1 billion in annual sales, with strong performance in both the U.S. and international markets [13][14] - Scemblix grew by 95% in constant currency, becoming the most prescribed TKI by NBRx in the U.S. [15] - Cosentyx had a mixed quarter, with a slight decline in growth due to one-time effects, but remains on track for mid-single-digit growth for the full year [16][17] Market Performance - Kisqali's early breast cancer indication is approved in 56 countries, with significant growth potential outside the U.S. [6][10] - Pluvicto is expected to reach peak sales potential with ongoing approvals in Japan and China [12] - Leqvio shows strong uptake in various international markets, particularly in China and the Middle East [14] - Scemblix is gaining traction in both first-line and second-line settings, with a strong launch momentum in Japan [15] Company Strategy and Industry Competition - The company is focused on driving growth through its priority brands while managing the impact of generic erosion from key products [4][5] - The proposed acquisition of Avidity Biosciences is expected to enhance long-term growth prospects and support mid-single-digit growth over the long term [33][34] - The company is committed to maintaining a strong pipeline and investing in R&D to support future growth [28][29] Management Commentary on Operating Environment and Future Outlook - Management expressed confidence in navigating generic headwinds and reaffirmed guidance for high single-digit growth in net sales and low teens growth in core operating income for the full year [29][30] - The company anticipates a challenging first half of 2026 due to the impact of generics but expects to emerge stronger in the second half [31][32] - Management highlighted the importance of addressing pricing and reimbursement challenges in the current regulatory environment [38][61] Other Important Information - The company achieved significant pipeline milestones, including FDA approvals and positive phase 3 results for several key products [4][20] - Management emphasized the importance of cash flow for reinvestment and shareholder returns, with a new $10 billion share buyback program announced [28][29] Q&A Session Summary Question: Industry response to Medicaid and tariffs - Management noted ongoing discussions with the administration and emphasized the need for solutions that address underlying industry issues [38] Question: CapEx over the next five years - Management clarified that the majority of the $23 billion commitment is for R&D OpEx, with no significant increase in CapEx expected [39][40] Question: Market reaction to ATR abstract - Management expressed confidence that detailed data presentation would improve market appreciation of the product [43][44] Question: Impact of Ocrevus subcutaneous launch on Cosentyx - Management indicated no significant impact from Ocrevus, with Cosentyx maintaining its market share [69][70] Question: Pluvicto launch curve and peak sales ambition - Management stated that Pluvicto is on a strong growth trajectory, with expectations of reaching $5 billion in peak sales [52][56]

Core Insights - Novartis is set to present data from 27 abstracts related to its Immunology portfolio at the 2025 ACR Convergence, including pivotal Phase III results for ianalumab in Sjögren's disease and biomarker data for rapcabtagene autoleucel in systemic lupus erythematosus [1][6] Group 1: Ianalumab and Sjögren's Disease - Ianalumab is an investigational therapy that may become the first targeted treatment for Sjögren's disease, which currently has no FDA-approved therapies [2][5] - The NEPTUNUS-1 and NEPTUNUS-2 trials demonstrated significant reductions in disease activity for patients with Sjögren's disease [5][6] - The dual mode of action of ianalumab involves targeting B cells and blocking B cell activating factor receptor signaling [7] Group 2: Rapcabtagene Autoleucel - Rapcabtagene autoleucel is a novel CAR-T cell therapy being evaluated for its potential to reset the immune system in several refractory autoimmune diseases [3][6] - Biomarker data from a Phase 1/2 study suggests a reset of the B cell compartment in severe refractory systemic lupus erythematosus [6][7] Group 3: Cosentyx Data - Real-world data on Cosentyx (secukinumab) will be presented, focusing on its use in psoriatic arthritis [3][6] - A retrospective study comparing the incidence of psoriatic arthritis in patients treated with different interleukin inhibitors will also be discussed [7] Group 4: Investor Engagement - Following the ACR event, Novartis will host a conference call on October 30, 2025, to update investors on its Immunology pipeline [4][6]

Investment Rating - The report maintains a "Buy" rating for Galaxy Entertainment, highlighting the resilience of the gaming industry and the long-term growth potential of the company [6]. Core Insights - Galaxy Entertainment achieved a net revenue of HKD 12 billion in Q2 2025, representing an 8% quarter-on-quarter increase and a 10% year-on-year increase. The adjusted EBITDA was HKD 3.2 billion, with a 7% quarter-on-quarter increase but a 1% year-on-year decline. Key revenue metrics have recovered to 82%, 130%, 138%, and 31% of 2019 levels for total gross revenue, mass market revenue, slot machine revenue, and VIP turnover, respectively [6][8]. - The company has a net cash position of HKD 30.3 billion as of June 30, 2025, and announced an interim dividend of HKD 0.70 per share, with a payout ratio of 58%, up from 50% in 2024 [6][8]. Summary by Sections 1. Overseas Social Services - Galaxy Entertainment's Q2 2025 performance shows a recovery in various revenue streams, with EBITDA returning to 79% of 2019 levels. The Capella Hotel is in trial operation, with full opening expected soon. The Macau Galaxy Phase IV project is progressing, with completion expected in 2027 [6][8]. 2. Overseas Pharmaceuticals - The 2025 medical insurance directory and commercial insurance innovative drug directory preliminary review has been published, with 534 out of 718 submissions passing the initial review. The new directory includes several CAR-T products and other innovative drugs [10][12]. 3. Domestic Pharmaceutical Companies - Crystal Holdings expects a revenue of at least HKD 500 million in H1 2025, a year-on-year increase of approximately 387%. In contrast, Jinxin Reproductive expects a net loss of no more than HKD 1.09 billion due to asset impairments [11][12]. 4. Overseas Pharmaceutical Company Updates - Insmed's DPP-1 inhibitor, BRINSUPRI, has received FDA approval for treating non-cystic fibrosis bronchiectasis. Novartis's BAFF-R monoclonal antibody has met primary endpoints in two Phase III studies for treating active Sjögren's syndrome [13][14]. 5. Investment Recommendations - The report suggests focusing on innovative drugs and pharmaceutical companies with strong clinical pipelines, including companies like BeiGene, Innovent Biologics, and others [15]. 6. Market Performance - The Hang Seng Healthcare Index rose by 3.50%, outperforming the Hang Seng Index by 1.75 percentage points, indicating a positive market sentiment towards healthcare stocks [8].

Core Insights - Novartis announced positive top-line results from the Phase III trial VAYHIT2, evaluating ianalumab plus eltrombopag in patients with primary immune thrombocytopenia (ITP) previously treated with corticosteroids, showing significant prolongation of time to treatment failure (TTF) [1][6] - The study demonstrated a higher rate of sustained improvements in platelet count at six months for patients treated with ianalumab plus eltrombopag, indicating potential for long-term disease control [2][6] - Ianalumab is being investigated for various B cell-driven autoimmune diseases, with ongoing trials expected to yield further data in 2026 and 2027 [1][4] Company Overview - Ianalumab (VAY736) is a fully human monoclonal antibody targeting B cells, showing promising efficacy and safety in treating autoimmune diseases such as ITP and Sjögren's disease [5][6] - Novartis has received Orphan Drug Designation for ianalumab from both the US FDA and the European Medicines Agency, highlighting its potential in treating rare diseases [4][5] - The company aims to reduce the treatment burden for ITP patients by offering a regimen of four once-monthly doses, potentially allowing extended time off treatment [4][6] Industry Context - Primary immune thrombocytopenia (ITP) is a rare autoimmune disorder characterized by low platelet counts, leading to increased bleeding risk and chronic fatigue, necessitating new treatment options [3][7] - Current ITP treatments often require lifelong management, creating a significant treatment burden for patients, which underscores the need for therapies that provide durable responses [3][8] - The VAYHIT2 trial results suggest that ianalumab may address unmet needs in the ITP treatment landscape by offering a novel mechanism of action and improved patient quality of life [3][8]

Investment Ratings - Bristol-Myers Squibb (BMY): Neutral [6] - Eli Lilly (LLY): Buy [10] - Novartis (NOVN): Neutral [16] - Sanofi (SNY): Neutral [17] - Biogen (BIIB): Buy [20] - Insmed Therapeutics (INSM): Buy [25] - Jazz Pharmaceuticals (JAZZ): Buy [29] - MoonLake Immunotherapeutics (MLTX): Buy [36] Core Insights - The report emphasizes the importance of idiosyncratic catalysts in the biopharma sector, particularly in the context of macroeconomic volatility and healthcare policy uncertainty [1] - Key catalysts to watch in 3Q25 include pivotal studies from various companies, with a focus on Alzheimer's disease, obesity, Sjogren's syndrome, multiple sclerosis, and gastroesophageal adenocarcinoma [1][5] - The report highlights the potential for significant market opportunities based on upcoming trial results and regulatory approvals, particularly for drugs like Cobenfy, orforglipron, ianalumab, tolebrutinib, and zanidatamab [1][5][10][18][30] Summary by Company Bristol-Myers Squibb (BMY) - Monitoring Phase 3 data from the Cobenfy ADEPT-2 trial in Alzheimer's disease psychosis, with a primary completion date in July [8] - The trial's success could have implications for a large patient population, with approximately 6 million Alzheimer's patients in the U.S. [8][9] Eli Lilly (LLY) - Focus on the ATTAIN-1 trial for orforglipron in obesity without diabetes, with results expected in July [10] - Anticipated weight loss efficacy in the 12-15% range, with safety and tolerability being key metrics [13] Novartis (NOVN) - Key focus on ianalumab's readouts in Sjogren's syndrome and immune thrombocytopenia, with a potential peak sales opportunity of approximately $2 billion [18] Sanofi (SNY) - Expected data from the Phase 3 PERSEUS trial of tolebrutinib in primary progressive multiple sclerosis, with a primary completion date in July [19] Biogen (BIIB) - Monitoring Leqembi's commercial trajectory in early-onset Alzheimer's disease, with a potential peak sales of approximately $800 million [21] Insmed Therapeutics (INSM) - Regulatory review of brensocatib for bronchiectasis, with a PDUFA date of August 12 [25] - Potential for significant upside if approved with a broad label [27] Jazz Pharmaceuticals (JAZZ) - Anticipating topline data from the HERIZON-GEA-01 trial for zanidatamab in gastroesophageal adenocarcinoma, with a potential peak sales opportunity exceeding $2 billion [30] MoonLake Immunotherapeutics (MLTX) - Reporting topline results from the Ph. 3 VELA trials for sonelokimab in hidradenitis suppurativa, with expectations for best-in-class efficacy [36]