IO Biotech(IOBT) - 2025 Q2 - Quarterly Results

Introduction & Disclaimer This section outlines the standard disclaimer for forward-looking statements and presents the agenda for the conference call Disclaimer & Forward-Looking Statements This section provides a standard disclaimer for forward-looking statements, highlighting inherent risks and uncertainties without guaranteeing future results - Forward-looking statements are based on current beliefs and expectations of management, involving risks, potential changes in circumstances, assumptions, and uncertainties[5] - Actual results and developments could be materially different from those expressed or implied by forward-looking statements due to known or unknown risks and uncertainties[5] Agenda for Today's Call The agenda outlines the key topics to be discussed during the conference call, including an introduction, detailed Phase 3 data for Cylembio, an overview of the first-line advanced melanoma treatment landscape, and company milestones Agenda Topics | Topic | | :--- | | Introduction | | Cylembio Phase 3 Data | | First-line Advanced Melanoma Treatment Landscape | | Company Milestones | Cylembio Overview & Phase 3 Results This section provides an overview of Cylembio, presents its Phase 3 trial results, explains its mechanism of action, and details the company's pipeline Cylembio Product Overview Cylembio (imsapepimut and etimupepimut, adjuvanted) is an investigational drug candidate for non-resectable/advanced melanoma, with Phase 3 results demonstrating clinical improvement - Cylembio is an investigational drug candidate that has not been approved for marketing by the US FDA or other regulatory authorities[9] - Cylembio in combination with pembrolizumab demonstrated clinical improvement across subgroups, with plans to engage with the FDA in Fall 2025 for potential BLA submission[11] Cylembio Phase 3 Topline Data | Metric | Cylembio + Pembrolizumab | Pembrolizumab Alone | | :--- | :--- | :--- | | Months mPFS | 19.4 | 11.0 | | HR (95% CI) | 0.77 (0.58-1.00) | | | p-value | 0.056* | | Statistical significance threshold for this study was p=0.045 Phase 3 Trial Topline Results The Phase 3 trial for Cylembio plus pembrolizumab demonstrated improved median Progression-Free Survival, with notable benefits in specific subgroups and a favorable safety profile Phase 3 Trial Key Endpoints | Endpoint | Cylembio + Pembrolizumab | Pembrolizumab Alone | HR (95% CI) | p-value | | :--- | :--- | :--- | :--- | :--- | | Median PFS (ITT) | 19.4 months | 11.0 months | 0.77 (0.58-1.00) | 0.056 | | Median PFS (excl. prior anti-PD1) | 24.8 months | 11.0 months | 0.74 (0.56-0.98) | 0.037 (nominal) | | Median PFS (PD-L1 negative) | 16.6 months | 3.0 months | 0.54 (0.35-0.85) | 0.006 (nominal) | | Overall Survival (trend, not mature) | Favoring combination arm | | 0.79 (0.57, 1.10) | | Statistical significance threshold for this study was p=0.045 - Cylembio demonstrated PFS benefit regardless of prespecified subgroups or stratification factors[17][53] - The treatment was well-tolerated with no significant added systemic toxicity compared to pembrolizumab alone[17][53] Clinical Trial Design This section details the Phase 3 clinical trial design, including patient enrollment, eligibility criteria, and primary and secondary endpoints - The Phase 3 clinical trial enrolled 407 patients across over 100 sites in Europe, Australia, South Africa, Israel, and the US[28] - Eligibility criteria included advanced melanoma (unresectable stage III or metastatic stage IV) and measurable disease (RECIST 1.1)[28] - The primary endpoint was Progression-Free Survival (PFS) by central review, with secondary/exploratory endpoints including Overall Response Rate (ORR), Disease Control Rate (DCR), Overall Survival (OS), Duration of Response (DoR), and incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)[28] Progression-Free Survival (PFS) Analysis This section presents the Progression-Free Survival analysis, highlighting the median PFS and early separation of treatment arms - PFS curves showed early separation at 3 months, widening over time, indicating a sustained benefit for the Cylembio combination arm[30][31] PFS Analysis Results | Arm | Median PFS (months) | Events | | :--- | :--- | :--- | | Cylembio + Pembro | 19.4 | 99 | | Pembro | 11.0 | 119 | | HR (95% CI) | 0.77 (0.58 to 1.00) | | | Log-rank p-value | 0.0558 | | *Statistical significance threshold for this study was p=0.045 Baseline Characteristics & Subgroup Analysis This section analyzes baseline patient characteristics and consistent PFS improvements observed across various demographic and clinical subgroups - Baseline characteristics were balanced across treatment arms and reflected real-world melanoma patient populations[33][34] - Consistent improvement in PFS was observed across the majority of subgroups, including age, disease stage, BRAF mutation status, PD-L1 status, geographical region, ECOG status, LDH levels, prior treatment, melanoma subtype, and baseline tumor size[35][38][41][45] Subgroup Analysis of PFS | Subgroup | Cylembio + Pembro Events (Patients) | Pembro Events (Patients) | Unstratified HR (95% CI) | | :--- | :--- | :--- | :--- | | Overall | 99 (203) | 119 (204) | 0.77 [0.59; 1.01] | | PD-L1 Negative | 34 (67) | 49 (63) | 0.54 [0.35; 0.85] | | PD-L1 Positive | 63 (129) | 63 (127) | 0.93 [0.65; 1.32] | | Excluding prior anti-PD1 exposure | N/A (mPFS 24.8 months) | N/A (mPFS 11.0 months) | 0.74 (0.56-0.98) (nominal p=0.037) | | Excluding acral/mucosal patients | N/A (mPFS 22.1 months) | N/A (mPFS 11.1 months) | N/A | Overall Survival (OS) Trend This section presents the early, not yet mature, Overall Survival data, indicating a favorable trend for the Cylembio combination arm - Overall Survival (OS) data is not yet mature, but a trend favoring the Cylembio combination arm was observed, with early separation of survival curves that widened over time[48][49] Overall Survival Trend | Arm | Events | Median OS (months) | | :--- | :--- | :--- | | IO + Pembro | 58 | 31.9 | | Pembro | 77 | N/A | | HR (95% CI) | 0.79 (0.57, 1.10) | | Safety Data This section provides safety data, demonstrating that Cylembio did not significantly increase systemic toxicity compared to monotherapy - Treatment with Cylembio did not add significant systemic toxicity compared to patients treated with pembrolizumab monotherapy[51] Safety Profile Comparison | Safety Metric | IO102-IO103 + Pembrolizumab (N=200) | Pembrolizumab (N=198) | | :--- | :--- | :--- | | Patients with AEs, n (%) | 194 (97.0) | 187 (94.4) | | Patients with treatment-related AEs, n (%) | 171 (85.5) | 161 (81.3) | | Patients with SAEs, n (%) | 64 (32.0) | 64 (32.3) | | Patients with treatment-related SAEs, n (%) | 19 (9.5) | 25 (12.6) | | Patients with AEs leading to death, n (%) | 4 (2.0) | 5 (2.5) | | Patients with immune-mediated AEs (imAE), n (%) | 68 (34.0) | 76 (38.4) | | Patients with injection site reactions, n (%) | 112 (56.0) | 2 (1.0) | Mechanism of Action: T-win® Vaccine Platform IO Biotech's T-win® cancer vaccine platform activates T cells with a dual mechanism to target tumor and immune-suppressive cells, modulating the tumor micro-environment - The T-win® vaccine activates T cells with a dual mechanism to attack both target-expressing tumor cells and immune-suppressive cells (e.g., IDO1, PD-L1)[20] - The platform aims to provide a new therapeutic strategy with the potential to improve outcomes for cancer patients by killing tumor cells and turning the tumor micro-environment hostile to cancer[21] Pipeline Overview IO Biotech's pipeline includes three T-win® product candidates in various clinical phases for multiple cancer indications, alongside preclinical candidates IO Biotech Pipeline | Product Candidates | Targets | Line of therapy/indication | Phase | Takeaways & next steps | | :--- | :--- | :--- | :--- | :--- | | Cylembio® (IOB-013) | IDO1, PD-L1 | First Line Advanced Melanoma | Phase 3 | Demonstrates clinical improvement in mPFS, narrowly missed statistical significance. Plans to discuss data with FDA in Fall 2025; potential US BLA submission | | Cylembio® (IOB-022) | IDO1, PD-L1 | First Line Solid Tumors (Lung (NSCLC), Head & Neck (SCCHN)) | Phase 2 | SCCHN: Primary endpoint met. NSCLC: Encouraging data | | Cylembio® (IOB-032) | IDO1, PD-L1 | Neoadjuvant / Adjuvant Solid Tumors (Melanoma, Head & Neck (SCCHN)) | Phase 2 | Enrollment completed in 2025. Initial data in 2H25 | | IO112 | Arginase 1 | Solid Tumors (Indications TBD) | Pre-clinical | Next pipeline candidate expected to enter clinical development | | IO170 | TGF-B1 | Solid Tumors (Indications TBD) | Pre-clinical | Early-stage pipeline candidate | Advanced Melanoma Treatment Landscape This section analyzes the advanced melanoma treatment landscape, including patient needs, market opportunity, and competitive positioning Melanoma Patient Journey & Unmet Needs This section highlights the significant unmet medical needs in unresectable or metastatic melanoma due to current treatment limitations - Unresectable or Metastatic Melanoma affects ~15,000 patients annually in the U.S., representing a high unmet medical need due to lack of efficacy and toxicity issues with available standard of care[14] - Cylembio, if approved, has the potential to address this high unmet medical need by providing patients and healthcare professionals with a new treatment option[14] Market Opportunity & Forecast This section details the growing global melanoma market, driven by increasing incidence and a high unmet need for more effective therapies - Melanoma incidence is increasing globally, with ~331,000 patients newly diagnosed and ~58,000 patient deaths annually[56] - The 5-year survival rate for patients in stage IV is 30%, and ~50% of patients progress within one year of treatment, indicating a significant unmet need for more effective options[56][58] Melanoma Drug Sales Forecast | Metric | 2024 (USD billions) | 2030 (USD billions) | CAGR | | :--- | :--- | :--- | :--- | | US Melanoma Drug Sales | 8.4 | 13.2 | +9% | | Global Melanoma Drug Sales | 9.4 | 14 | | Competitive Landscape This section positions Cylembio favorably within the first-line advanced melanoma market, acknowledging the caveats of cross-trial comparisons - If approved, Cylembio would be well-positioned for the treatment of first-line advanced melanoma[59] Median PFS Comparison of Therapies | Drug (Combination) | Median PFS | | :--- | :--- | | Cylembio + Pembro | 19.4m | | Pembro (KN-006) | 11.6m | | Opdualag (Nivo+Rela) | 10.2m | | Ipi/Nivo (CM-067) | 11.5m | | Nivo | 4.6m | | Ipi | 6.9m | - Comparisons across clinical trials should be interpreted with caution due to differences in study design, patient populations, endpoints, and other factors[60] Company Milestones & Financials This section outlines key company milestones, including regulatory plans and pipeline advancements, alongside its current financial position Key Milestones This section details anticipated key milestones through 2026, encompassing regulatory submissions, clinical data readouts, and preclinical candidate advancements - Discussions with FDA for Cylembio (1L Advanced Melanoma) are planned for Fall 2025, with potential US BLA submission and launch thereafter[63] - Potential EU Marketing Authorization Application (MAA) submission for Cylembio (1L Advanced Melanoma) is expected in 2026[63] - Initial data from Cylembio's neoadjuvant/adjuvant Phase 2 cohorts is expected in H2 2025, with final data from first-line Phase 2 for NSCLC and SCCHN also anticipated[63] - IND submission for IO112 (Solid Tumors) and IND enabling studies for IO170 (Solid Tumors) are planned for 2026[63] Financial Position The company maintains a cash runway into Q1 2026, supported by its Q2 cash balance and a recent EIB loan tranche - Cash position extends into Q1 2026[62] Financial Metrics | Metric | Value | | :--- | :--- | | Q2 Cash Balance | $28 million | | EIB Loan | Second tranche received on July 4, 2025 |