Summary of IO Biotech Conference Call Company Overview - **Company**: IO Biotech (NasdaqGS: IOBT) - **Lead Product**: Xylemio (IO-102, IO-103), developed on the TWIN platform - **Focus**: Advanced melanoma treatment and potential expansion into other indications Key Highlights 1. **Phase 3 Trial Results**: - Conducted a phase 3 trial for Xylemio in combination with anti-PD-1 pembrolizumab for first-line metastatic melanoma - Median Progression-Free Survival (PFS) was 19.4 months in the experimental arm compared to 11 months in the control arm, with a hazard ratio of 0.77 and a P-value of 0.056, narrowly missing statistical significance [3][7][10] 2. **Regulatory Discussions**: - Engaged with the FDA regarding the trial results; planning a new phase 3 trial due to the statistical miss - Ongoing discussions with European authorities to explore submission opportunities based on the trial data [4][10][29] 3. **Market Opportunity**: - Identified a significant unmet need in advanced melanoma, with 15,000 patients in the US and only 50% benefiting from current treatments - Xylemio is positioned as a potential combination partner not only with anti-PD-1 but also in other indications beyond melanoma [5][19] 4. **Subgroup Analysis**: - Excluding patients with prior anti-PD-1 treatment showed a PFS of 24.8 months, with a significant P-value of 0.037 - In PD-1 negative patients, median PFS was 16.6 months versus 3 months for anti-PD-1 alone, with a P-value of 0.006 [8][9] 5. **Safety Profile**: - Xylemio demonstrated a clean safety profile with no added toxicity compared to pembrolizumab alone [10][12] 6. **Future Trials**: - Plans to initiate a new phase 3 trial combining Xylemio with Opdivo, the standard of care in the US for metastatic melanoma, with a target enrollment of 400 to 800 patients [12][13][25] 7. **Pipeline Expansion**: - Xylemio is being tested in other indications, including lung cancer and head and neck cancer, with promising results - Ongoing studies for new targets such as Arginase 1 and TGF- with potential applications in various difficult-to-treat cancers [14][16][18][20] 8. **Patient-Centric Approach**: - Emphasis on patient convenience with an off-the-shelf therapy that is readily accessible [23] 9. **Market Strategy**: - Plans to submit applications in both Europe and the US based on trial data, with a focus on expanding into other indications and targets [19][24] 10. **Regulatory Differences**: - Noted differences in FDA and EMA guidelines affecting the approval process and strategy for submissions [29] Additional Insights - The excitement surrounding the trial results despite the statistical miss indicates strong investigator support and potential for future success - The company is exploring partnerships to enhance trial success and market entry strategies [26][28]

Group 1: Reviva Pharmaceuticals Holdings Inc. (RVPH) - RVPH experienced a significant after-hours rally, increasing 18.27% to $0.58 after a 35.1% surge during regular trading, with a trading volume of over 40.5 million shares, nearly nine times its daily average [2][3] - The company has a market cap of $47 million and is focused on its lead candidate brilaroxazine, which targets neuropsychiatric and respiratory conditions [3] Group 2: Penumbra Inc. (PEN) - PEN surged 7.97% in after-hours trading to $273.69, following a 1.55% gain during the regular session, with a market cap nearing $9.9 billion [4][5] - The company has increased its revenue guidance for FY25 to a range of $1.355 billion - $1.370 billion, indicating a growth of 13% to 15% over 2024 [6] Group 3: Palisade Bio Inc. (PALI) - PALI jumped 10% in after-hours trading to $1.87, extending a 29.8% surge during the regular session, driven by a $138 million public offering [7][8] - The company has a market cap of $15.8 million and is gaining attention due to recent clinical updates and licensing agreements [8] Group 4: IO Biotech Inc. (IOBT) - IOBT rose 5.08% in after-hours trading to $0.4571, following a 22.3% surge during the regular session, with heavy trading volume of 16.7 million shares [9] - The company announced plans to design a new registrational study for its cancer vaccine candidate Cylembio after receiving regulatory feedback from the FDA [10] Group 5: Rallybio Corp. (RLYB) - RLYB increased 11.2% in after-hours trading to $0.5688, reversing a modest dip during the regular session, with a market cap of $21.4 million [11][12] - The company recently completed dosing in its Phase 1 study for RLYB116 and received a $12.5 million milestone payment for progress on the REV102 program [12] Group 6: Vor Biopharma Inc. (VOR) - VOR rose 3.6% in after-hours trading to $38.00, recovering from a 6.6% decline during the regular session, with a market cap of $251 million [13][14] - The company is focusing on its trem-cel platform and CD33-directed therapies for acute myeloid leukemia, alongside new executive appointments [14]

Financial Data and Key Metrics Changes - The company reported revenue of RMB 446 million for 2025, representing a 48% year-over-year growth, although the first half was impacted by supply constraints [12][14] - Revenue from Nephicon alone reached RMB 520 million in August, indicating a strong recovery from earlier supply issues [13] - Full year revenue guidance for 2025 is set between RMB 1.6 billion to RMB 1.8 billion, with Nephicon expected to contribute RMB 1.2 billion to RMB 1.4 billion [13][14] - The gross margin on a cash basis was 76.4%, slightly lower than 2024 due to price reductions after NRDL inclusion, but expected to recover above 80% in the long run [14] - The non-IFRS net loss was approximately RMB 147 million, down 31% year-over-year, indicating improved operational efficiency [14] Business Line Data and Key Metrics Changes - Nephicon generated RMB 825 million in revenue from January to August, with strong market demand leading to a significant uptick in sales after regulatory approval [4][5] - The autoimmune disease franchise, particularly Velsipiti, is progressing well with NDA reviews and expected early 2026 approval [7][8] - XERAVA in the anti-infective segment showed steady growth, with revenue increasing by 37% year-over-year [23] Market Data and Key Metrics Changes - The company aims to expand Nephicon's market coverage to 1,000 hospitals, targeting approximately 30,000 new patients [18][20] - The estimated market for IgAN in China includes about 5 million patients, with significant growth potential as the company expands its reach [19][20] - The ulcerative colitis market is projected to grow, with peak sales for Velsipiti expected to reach RMB 5 billion [34] Company Strategy and Development Direction - The company is focused on a dual strategy of commercialization and in-house discovery, with significant investments in R&D to support long-term growth [35][72] - Plans include localizing production for various products and preparing for NRDL negotiations to enhance market access [72] - The company is also exploring partnerships and in-licensing opportunities to bolster its product pipeline and market presence [76] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in achieving operational profitability earlier than previously guided, now targeting Q4 2025 [15] - The company is optimistic about the upcoming regulatory approvals and market launches, which are expected to drive revenue growth [71][72] - Management highlighted the strong clinical data supporting their products, which positions them favorably in the market [82] Other Important Information - The company completed a strategic investment of USD 30.9 million in I Mab, becoming the largest shareholder with a 16.1% stake [12][70] - The company is advancing its proprietary mRNA technology platform, which is expected to enhance its R&D capabilities and product offerings [48][49] Q&A Session Summary Question: Peak sales for Etrasimod - Management noted that the potential for Etrasimod is higher than previously stated due to strong clinical data and an underdeveloped market, with preparations underway for commercial launch [80][82][86] Question: Development plans for EVER-one - Management confirmed that they are in the design stage for pivotal trials and are planning to initiate these studies in 2026, with ongoing discussions for potential partnerships [89][90][92]