The Stock Exchange of Hong Kong Limited and the Securities and Futures Commission take no responsibility for the contents of this Application Proof, make no representation as to its accuracy or completeness and expressly disclaim any liability whatsoever for any loss howsoever arising from or in reliance upon the whole or any part of the contents of this Application Proof. Application Proof of If you are in any doubt about any of the contents of this Document, you should seek independent professional advice ...

Core Insights - Pyxis Oncology has completed target enrollment in the Phase 1 monotherapy dose expansion study of micvotabart pelidotin (MICVO) for 2L+ recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) in Q1 2026, with updated data expected mid-2026 [1][5] - The company has appointed Thomas Civik as Interim Chief Executive Officer, focusing on clinical execution and operations to deliver robust datasets [3][6] - Financial results for the year ended December 31, 2025, show revenues of $13.9 million, a decrease from $16.1 million in 2024, with a net loss of $79.6 million [8][10] Clinical Development Updates - The Phase 1 monotherapy study of MICVO in 2L+ R/M HNSCC reported a 46% confirmed objective response rate (ORR) and a 92% disease control rate (DCR) [4] - In combination with KEYTRUDA, MICVO showed a 71% confirmed ORR and a 100% DCR in 1L/2L+ R/M HNSCC [4] - The ongoing studies are designed to evaluate the impact of modified weight-based dosing on safety and efficacy, with results anticipated in mid-2026 [7][11] Financial Performance - Total revenues for 2025 were $13.9 million, down from $16.1 million in 2024, primarily due to changes in milestone revenues and royalty rights [10][15] - Research and development expenses increased to $73.7 million in 2025 from $58.7 million in 2024, attributed to higher clinical trial costs [10][16] - The company reported a net loss of $79.6 million for 2025, slightly higher than the $77.3 million loss in 2024 [10][16] Leadership and Corporate Updates - Thomas Civik was appointed as Interim CEO in February 2026, bringing extensive experience in advancing cancer therapeutics [6][10] - Heather Knowles joined as Senior Vice President, Head of Global Clinical Operations, enhancing the company's clinical development capabilities [10] - The company has also appointed Alex Kane as Senior Vice President, Investor Relations and Capital Markets, to strengthen investor engagement [10] Pipeline and Future Outlook - Pyxis Oncology expects to report updated data from the ongoing MICVO Phase 1/2 combination study with KEYTRUDA in the second half of 2026 [7][11] - The company has received Fast Track Designation from the FDA for MICVO in treating adult patients with R/M HNSCC [12]

Core Insights - Zymeworks Inc. announced the acceptance of an oral presentation and six abstracts for poster presentations at the upcoming AACR Annual Meeting, showcasing its R&D portfolio and advancements in biotherapeutics [1][2] Group 1: Oral Presentation Details - The oral presentation will focus on the Phase 1 trial results of ZW191, an antibody-drug conjugate (ADC) targeting folate receptor α, in patients with advanced solid tumors [3] - The presentation aims to reinforce the potential of ZW191 as a well-tolerated and effective treatment for heavily pretreated cancers, building on previous data shared at the AACR-EORTC-NCI conference [3] Group 2: Poster Presentation Highlights - ZW191 is under investigation for its efficacy in combination with standard-of-care drugs, showing strong anti-tumor activity in preclinical studies [4] - New ADC candidates, including ZW437 and ZW418, demonstrate significant activity against RAS-mutant cancers, indicating a promising pan-RAS inhibitor ADC platform [5][6] - ZW418 targets PTK7 in non-small cell lung cancer (NSCLC) and shows superior internalization and tumor penetration compared to existing therapies [7] - ZW427 targets Ly6E and exhibits potent anti-tumor activity across various RAS-mutated cancer models [8] - ZW439, targeting CLDN18.2, shows strong efficacy in pancreatic cancer, addressing a critical unmet need [9] Group 3: Company Overview - Zymeworks is a biotechnology company focused on developing innovative therapies for difficult-to-treat diseases, including cancer [15] - The company manages a portfolio of licensed healthcare assets and is advancing a pipeline of multifunctional biotherapeutics [15] - Zymeworks leverages its proprietary technologies to create differentiated antibody-based therapeutics, supported by strategic partnerships with global biopharmaceutical companies [15]

Financial Data and Key Metrics Changes - CytomX Therapeutics reported positive phase I dose expansion data for Varseta-M in late-line colorectal cancer, with a confirmed overall response rate of 32% at 10 mg/kg and 20% at 8.6 mg/kg [14][19] - The preliminary progression-free survival (PFS) improved from 5.8 months in May 2025 to 6.8-7.1 months [14][19] - The company aims to rapidly advance Varseta into its first registrational study, targeting a significant market opportunity in late-line colorectal cancer with over 45,000 addressable patients by 2040 [31][32] Business Line Data and Key Metrics Changes - Varseta-M is designed to target EpCAM, which is highly expressed in colorectal cancer, and aims to address the unmet need in this market [10][31] - The drug's development strategy includes aggressive advancement into earlier lines of therapy, potentially replacing irinotecan [31][32] Market Data and Key Metrics Changes - Colorectal cancer is projected to grow from 1.9 million diagnoses per year to over 3 million by 2040, with a significant market opportunity for Varseta-M [7][8] - The current standard of care in late-line metastatic colorectal cancer has low objective response rates, highlighting the need for more effective treatments [9][31] Company Strategy and Development Direction - CytomX plans to expand Varseta-M into early-line colorectal cancer and other EpCAM-positive tumors, leveraging the success in colorectal cancer as a foundation for broader applications [31][32] - The company is focused on optimizing dosing strategies and prophylactic measures to enhance the safety profile of Varseta-M [23][29] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the drug's performance and its potential to transform treatment paradigms in colorectal cancer [30][31] - The company is committed to rapid execution of registrational studies and anticipates sharing additional data in the near future [32][33] Other Important Information - The safety profile of Varseta-M has shown no evidence of classic EpCAM toxicities, and the incidence of grade 3 diarrhea has been reduced through updated prophylactic strategies [14][25] - The drug's pharmacokinetics support dose optimization based on adjusted ideal body weight to improve consistency and efficacy [27][28] Q&A Session Summary Question: What is the anticipated size of the pivotal trial? - Management indicated that the pivotal study size is still under consideration, but they are encouraged by the activity levels observed in late-line colorectal cancer [38][39] Question: What are the potential indications beyond colorectal cancer? - Management highlighted the potential for Varseta-M in other solid tumors, including gastric and pancreatic cancers, and expressed excitement about the broader applications of EpCAM targeting [40][41] Question: How will the prophylactic protocol be implemented in real-world settings? - Management noted that the dual prophylactic strategy of loperamide and budesonide is expected to be well-adhered to in clinical practice, especially given the convenience of oral administration [46][70] Question: Will progression-free survival be the primary endpoint in the pivotal trial? - Management confirmed that overall survival is expected to be the primary endpoint, although they are open to exploring other options as the data matures [48][49] Question: How does Varseta-M compare to other ADCs in development? - Management emphasized that Varseta-M is a first-in-class anti-EpCAM ADC and believes it may be the best-in-class option for colorectal cancer based on current data [53][54]

Financial Data and Key Metrics Changes - CytomX Therapeutics reported a confirmed overall response rate of 32% at a dose of 10 mg/kg and 20% at 8.6 mg/kg for Varseta-M, with a median progression-free survival (PFS) of 7.1 months and 6.8 months respectively [11][17] - The company noted an improvement in estimated PFS from 5.8 months in May 2025 to 6.8-7.1 months as of January 2026 [11][17] Business Line Data and Key Metrics Changes - Varseta-M is positioned as a first-in-class antibody-drug conjugate targeting EpCAM, specifically designed for colorectal cancer (CRC) [4][6] - The ongoing phase 1 study has enrolled a total of 93 patients, with a focus on dose optimization for the top two doses of 8.6 and 10 mg/kg [10][14] Market Data and Key Metrics Changes - Colorectal cancer is projected to see an increase in diagnoses from 1.9 million patients per year to over 3 million by 2040, representing a significant market opportunity [5][6] - The third-line setting alone is projected to have 45,000 addressable patients in the U.S. by 2040, indicating a multibillion-dollar market potential [6][30] Company Strategy and Development Direction - The company aims to aggressively advance Varseta-M into its first registrational study, targeting late-line CRC, with plans to expand into earlier lines of therapy and other EpCAM-positive tumors [12][30] - CytomX is focused on transforming CRC treatment paradigms and believes Varseta-M can replace existing therapies like Irinotecan [30][31] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the drug's performance and its potential to significantly impact patient outcomes in CRC, emphasizing the importance of the ongoing clinical data [29][30] - The company is committed to refining its prophylactic strategies to manage treatment-related adverse events, particularly diarrhea, which has been a significant concern [19][20] Other Important Information - The safety profile of Varseta-M has shown no evidence of classic EpCAM toxicities, and the company is implementing dual prophylaxis strategies to manage diarrhea effectively [11][19] - The pharmacokinetics of Varseta-M indicate a mean half-life of 6-8 days, supporting the dosing strategy based on adjusted ideal body weight [25] Q&A Session Summary Question: What is the anticipated size of the pivotal trial? - Management indicated that the pivotal study size is still under consideration, but they are encouraged by the activity levels observed in late-line CRC [35][38] Question: What are the potential indications beyond CRC for Varseta-M? - Management highlighted the potential for Varseta-M in other solid tumors, including gastric, pancreatic, lung, ovarian, and certain breast cancers, as EpCAM is expressed in many of these cancers [39][40] Question: How will the prophylactic protocol be implemented in real-world settings? - Management noted that the dual prophylactic regimen of loperamide and budesonide is expected to be well-adhered to in real-world settings, especially since both medications are oral [46][70] Question: Will PFS be the sole primary endpoint in the pivotal study? - Management confirmed that overall survival (OS) will be the primary endpoint, although they are considering all options to accelerate the development of Varseta-M [48][49] Question: How does Varseta-M compare to other ADCs in development? - Management emphasized that Varseta-M is a first-in-class ADC targeting EpCAM and believes it may be the best-in-class ADC for CRC based on current data [53][54]

Summary of Day One Biopharmaceuticals FY Conference Call Company Overview - **Company**: Day One Biopharmaceuticals (NasdaqGS:DAWN) - **Core Product**: OJEMDA, approved for pediatric low-grade glioma [3][4] Financial Performance - **2025 Revenue**: Over $155 million, marking the first full year of OJEMDA's launch - **Year-over-Year Growth**: 170% increase in revenue [4] - **Q4 2025 Revenue**: Over $52 million, with a 37% growth quarter-over-quarter [4] - **2026 Revenue Guidance**: Projected between $225 million and $250 million, indicating approximately 50% growth year-over-year [30] Key Metrics for Growth - **New Patient Starts (NPS)**: Increased by 25% in the second half of 2025 compared to the first half [12] - **Duration of Therapy**: Mean duration approximately 17 months, median duration 19 months, indicating strong patient retention [13] Pipeline Developments - **Emi-Le Program**: A B7-H4-targeted ADC for adenoid cystic carcinoma, with data expected mid-2026 [6] - **DAY301 Program**: A PTK7-targeted ADC, initial clinical data anticipated in the second half of 2026 [6][41] OJEMDA Launch Insights - **Frontline Enrollment**: Expected completion in the first half of 2026 [5] - **Second Line Use**: Increasing familiarity among physicians is driving more second-line usage of OJEMDA [15][21] - **Education and Data**: Ongoing education for KOLs and physicians is crucial for increasing patient starts and therapy persistence [22][27] Clinical Data and Impact - **Treatment-Free Interval**: Median time to next therapy after OJEMDA is approximately 43 months, with nearly 80% of children remaining off therapy after one year [25][27] - **Physician Engagement**: Positive data from ASCO and other conferences are expected to enhance physician confidence and patient management [23][28] Strategic Focus - **Durable Growth Story**: The company aims to establish OJEMDA as a standard of care in second-line treatment for pediatric low-grade glioma [60] - **Employee Commitment**: Acknowledgment of the team's efforts in executing the company's strategy and managing acquisitions effectively [60] Conclusion - Day One Biopharmaceuticals is positioned for significant growth driven by the successful launch of OJEMDA and a robust pipeline. The focus on education, data dissemination, and patient management strategies will be critical in achieving the projected revenue targets and expanding market presence.

Core Viewpoint - Kyntra Bio announced promising preliminary data on the anti-tumor activity of FG-3246 in combination with enzalutamide for patients with metastatic castration-resistant prostate cancer (mCRPC), with results to be presented at the 2026 ASCO GU symposium [1][2] Study Results - The Phase 1b/2 study showed a composite response rate of 21% in the overall cohort and 40% in patients who had progressed on only one prior androgen receptor pathway inhibitor (ARPI) [3] - Median radiographic progression-free survival (rPFS) was 7.0 months in the overall cohort, with a notable 10.1 months in patients who had only one prior ARPI [3][4] - Higher tumor uptake of FG-3180 indicated a trend towards a higher probability of PSA50 response (p=0.053), suggesting its potential as a biomarker for patient selection [3][4] Safety Profile - The combination therapy of FG-3246 and enzalutamide exhibited a safety profile similar to that observed in previous trials, with neutropenia risk mitigated through G-CSF prophylaxis [4][5] - Common treatment-related adverse events (TRAEs) included fatigue, peripheral neuropathy, anorexia, and dysgeusia, with some patients discontinuing treatment due to cumulative toxicities [5] Future Developments - Kyntra Bio is on track to provide interim analysis results from the Phase 2 monotherapy trial of FG-3246 in the second half of 2026, which will further explore the utility of FG-3180 as a patient selection biomarker [4][6] - FG-3246 is being developed as a first-in-class antibody-drug conjugate targeting CD46, with potential applications in other tumor types beyond mCRPC [7][9]

Core Insights - Defence Therapeutics Inc. is advancing its Accum® platform for antibody-drug conjugate (ADC) applications, as discussed in a recent Scientific Advisory Board meeting [1][2]. Group 1: Scientific Advisory Board Meeting - The meeting on January 30, 2026, focused on enhancing the strategic positioning of Accum® for ADC applications, bringing together experts in ADC chemistry, experimental design, and value creation [1][2]. - The discussion aimed to identify critical scientific questions, refine development priorities, and align data generation with the expectations of future clinical and pharmaceutical partners [2]. Group 2: Expert Contributions - Contributions from experts such as Rob Leanna, Danny Chui, and Brendan Hussey provided insights into ADC development, drug-linker chemistry, and clinical advancement, guiding the next phase of Accum® development [3]. - The multidisciplinary dialogue is expected to refine the Accum® ADC development roadmap, aligning platform capabilities with clinical development requirements and partnering considerations [4]. Group 3: Company Overview - Defence Therapeutics is committed to enhancing cancer treatment efficacy and safety through its Accum® precision drug delivery platform, aiming to improve the potency of ADCs and reduce side effects [5]. - The company seeks to collaborate with pharmaceutical and biotech partners to bring transformative therapies to patients [5].

Core Thesis - Pfizer Inc. is viewed positively due to its strategic acquisition of Seagen, which enhances its oncology portfolio and growth potential in the biopharmaceutical market [1][5]. Company Overview - Pfizer Inc. engages in the discovery, development, manufacturing, marketing, distribution, and sale of biopharmaceutical products both domestically and internationally [3]. Acquisition Impact - The $43 billion acquisition of Seagen in 2023 has significantly strengthened Pfizer's leadership in oncology and expanded its antibody-drug conjugate (ADC) portfolio [3]. - Seagen's key drugs, including Adcetris, Padcev, Turkysa, and Tiivdak, are projected to generate approximately $1.5 billion in revenue in the first half of 2025, underscoring the strategic importance of targeted chemotherapy within Pfizer's oncology business [4]. Revenue Growth Potential - The leading drugs from Seagen could collectively exceed $6 billion in annual sales by 2029, highlighting the substantial value added by the acquisition and the potential for long-term growth in targeted cancer therapies [5]. - Pfizer's strengthened position in a high-margin, high-growth segment of the pharmaceutical industry is expected to provide multiple catalysts for revenue growth [5]. Market Position and Investor Sentiment - As of the end of the third quarter, 84 hedge fund portfolios held Pfizer shares, an increase from 83 in the previous quarter, indicating a growing interest among institutional investors [7]. - Despite concerns regarding debt and revenue normalization, the bullish perspective on Pfizer's oncology growth through the Seagen acquisition remains strong [6].

MICVO Monotherapy Efficacy - MICVO monotherapy demonstrated a validated efficacy signal in 2L+ R/M HNSCC, with a 46% confirmed ORR and a 92% DCR (n=13, 5.4 mg/kg)[4] - In the Phase 1 monotherapy dose expansion study at 5.4 mg/kg, Arm 1 (post-PD1/post-Platinum) showed a 60% confirmed ORR (N=5)[32] - Arm 2 (post-PD1/post-EGFRi) in the monotherapy study showed a 25% confirmed ORR (N=4), exceeding the PI benchmark of 20%+[32] - MICVO monotherapy at 5.4 mg/kg demonstrated clear activity with deep responses and exceptional disease control[35] MICVO + KEYTRUDA® Combination Efficacy - MICVO combined with KEYTRUDA® showed a promising emerging efficacy profile in 1L/2L+ R/M HNSCC, with a 71% confirmed ORR and 100% DCR (n=7, 3.6 mg/kg & 4.4 mg/kg)[4] MICVO Safety and Tolerability - MICVO at 5.4 mg/kg in R/M HNSCC showed no Grade 4 or Grade 5 ADC payload TRAEs of interest[40] - Initial data supports a lack of overlapping toxicities observed between MICVO and KEYTRUDA®[52] Market and Clinical Development - FDA aligned on a 2L+ monotherapy pivotal trial design for MICVO[4] - The US R/M HNSCC market is large, growing, and relatively uncrowded, making it ripe for innovation[17] - Projected 2029 US market data shows a significant number of drug-treatable patients, with ~31K in 1L, ~21K in 2L, and ~8K in 3L[18]