IOS-1002 / ImmunOs Therap - LARVOL DELTA

Re-sensitizing PD-1/PD-L1 relapsed/refractory solid tumors: Phase 1a results of IOS-1002, a LILRB1/2 and KIR3DL1 checkpoint inhibitor, in combination with pembrolizumab. (ASCO 2026) - P=N/A | "IOS-1002 plus pembrolizumab demonstrated clinically meaningful efficacy in pretreated anti-PD-1/PD-L1-relapsed/refractory patients. Biomarker-driven patient selection using dual-high TIS and target receptor expression enhanced ORR to 75% and strongly predicted response depth, durability, and survival benefit. The favorable safety profile with no incremental immune-related toxicity, coupled with durable responses and high disease control rates, provides compelling rationale for Phase 1b expansion in biomarker-selected PD-1/PD-L1-refractory solid tumors."

Checkpoint inhibition • Combination therapy • IO biomarker • P1 data • Cervical Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • KIR3DL1 • LILRB1 • MUC16 • PD-1 • PD-L1

KEYNOTE-F49: A Clinical Study to Evaluate the Safety, Tolerability and Efficacy of IOS-1002 Administered Alone and in Combination With Pembrolizumab, a PD-1 Monoclonal Antibody in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=47 | Completed | Sponsor: ImmunOs Therapeutics AG | Active, not recruiting ➔ Completed | N=140 ➔ 47

Enrollment change • First-in-human • Trial completion • Oncology • Solid Tumor • LAG3 • PD-L1

Combos New and Old Counter PD-(L)1 Resistance, Treat Rare Cancers. (PubMed, Cancer Discov) - "The ERAP1 inhibitor GRWD5769 combined with cemiplimab, a PD-1 inhibitor, has shown preliminary promise in overcoming resistance to PD-(L)1 blockade by targeting antigen processing. Another resistance-mitigating strategy is potentially IOS-1002, an antagonist of two immunosuppressive receptors, LILRB1/2 and KIR3DL1, combined with anti-PD-1 pembrolizumab. As well, an update on the recently published DART (NCI/SWOG S1609) study indicates that the classic combination of ipilimumab with nivolumab may benefit even more rare cancers, including gestational trophoblastic neoplasia."

Journal • Gestational Trophoblastic Neoplasia • Oncology • KIR3DL1 • LILRB1

KEYNOTE-F49: A Clinical Study to Evaluate the Safety, Tolerability and Efficacy of IOS-1002 Administered Alone and in Combination With Pembrolizumab, a PD-1 Monoclonal Antibody in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=140 | Active, not recruiting | Sponsor: ImmunOs Therapeutics AG | Recruiting ➔ Active, not recruiting | Trial completion date: May 2025 ➔ Jul 2026 | Trial primary completion date: May 2025 ➔ Jul 2026

Enrollment closed • First-in-human • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • LAG3 • PD-L1

IOS-1002, a first-in-class multi-checkpoint inhibitor, shows encouraging clinical activity in combination with pembrolizumab in advanced solid tumors (ESMO 2025) - P1 | "Conclusions IOS-1002, a first-in-class multi-checkpoint inhibitor, shows encouraging clinical activity and favorable safety profile both as monotherapy and with pembrolizumab in patients with advanced solid tumors, including those resistant to PD-1/PD-L1 treatment. The unique mechanism targeting 3 innate immune checkpoints (LILRB1, LILRB2, KIR3DL1) differentiates IOS-1002 from other LILRB-targeting programs in development and may provide clinical benefit by activating multiple immune cell types."

Checkpoint inhibition • Clinical • Combination therapy • IO biomarker • Metastases • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • HLA-B • KIR3DL1 • LILRB1

ImmunOs Therapeutics Reports Promising Clinical Activity of IOS-1002 in Advanced Solid Tumors (The Manila Times) - "Combination arm with pembrolizumab (Keytruda) in Australia near to completion by end 2025...In the monotherapy arm, 6 out of 19 patients (32%) achieved Stable Disease, highlighting a favorable disease control rate. In the combination therapy cohort, 15 out of 21 evaluable patients (71%) achieved Disease Control. In total, 13 patients (61%) so far achieved Stable Disease including 10 patients still undergoing treatment. 2 additional patients (10%) have achieved Partial Responses, including one patient who experienced a metabolic Complete Response confirmed by PET imaging....Identified biomarkers and patient response characteristics will guide patient stratification for the planned Phase Ib clinical trial, anticipated to start in the second half of 2026. Additional information regarding the Phase Ib study design and objectives will be communicated prior to trial initiation."

New P1 trial • P1 data • Trial status • Solid Tumor

KEYNOTE-F49: A Clinical Study to Evaluate the Safety, Tolerability and Efficacy of IOS-1002 Administered Alone and in Combination with Pembrolizumab, a PD-1 Monoclonal Antibody in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=140 | Recruiting | Sponsor: ImmunOs Therapeutics AG | Trial primary completion date: May 2024 ➔ May 2025

Combination therapy • Metastases • Trial primary completion date • Oncology • Solid Tumor • LAG3 • PD-1 • PD-L1

ImmunOs Therapeutics AG Raises $11 Million and Further Strengthens Investor Base (GlobeNewswire) - "ImmunOs Therapeutics...today announced the closing of a Series C financing round of $11 million. The round was led by existing investors Gimv, Pfizer Ventures, Mission BioCapital, BioMed Partners and supported by new investor Double Point Ventures as well as other existing investors....Proceeds from the Series C will be used to further fund the ongoing clinical trial of ImmunOs’ lead program IOS-1002 to completion of the Phase Ia dose escalation clinical trial as a monotherapy and in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy KEYTRUDA (pembrolizumab)....'We look forward to the opportunity to review clinical data potentially in 2025.'"

Financing • Oncology • Solid Tumor

IOS-1002, a Stabilized HLA-B57 Open Format, Exerts Potent Anti-Tumor Activity. (PubMed, Cancers (Basel)) - "Lastly, IOS-1002 demonstrates efficacy in an ex vivo patient-derived tumor sample tumoroid model. IOS-1002 is a first-in-class multi-target and multi-functional human-derived HLA molecule that activates anti-tumor immunity and is currently under clinical evaluation."

Journal • Hepatitis C • Human Immunodeficiency Virus • Infectious Disease • Oncology • B2M • KIR3DL1 • LILRB1

ImmunOs Therapeutics Expands Phase I Clinical Trial of IOS-1002 in Combination with KEYTRUDA (pembrolizumab) for the Treatment of Solid Tumors (GlobeNewswire) - "ImmunOs Therapeutics AG...today announced the expansion of its ongoing Phase I clinical trial of IOS-1002 in combination with MSD (Merck & Co., Inc., Rahway, NJ, USA)'s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) for the treatment of advanced solid tumors....'We look forward to assessing the optimal treatment for our patients with advanced-stage cancer who have limited therapeutic options.'"

Trial status • Solid Tumor

KEYNOTE-F49: A Clinical Study to Evaluate the Safety, Tolerability and Efficacy of IOS-1002 Administered Alone and in Combination With Pembrolizumab, a PD-1 Monoclonal Antibody in Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=140 | Recruiting | Sponsor: ImmunOs Therapeutics AG | Phase classification: P1a/1b ➔ P1

Combination therapy • Metastases • Phase classification • Oncology • Solid Tumor • LAG3 • PD-1 • PD-L1

A phase Ia/Ib, first-in-human, dose-escalation study evaluating the safety, tolerability, and efficacy of IOS-1002, a LILRB1, LILRB2, and KIR3DL1 targeting HLA-derived fusion protein administered alone or in combination with a PD-1 antibody in patients with advanced solid tumors (ESMO 2023) - P1a/1b | "Dose Expansion (B): Following the toxicity and activity profile observed in part A, a tumor-specific cohort expansion study in up to 6 potential disease entities with 20 patients per cohort will be initiated, 3 as IOS-1002 monotherapy and 3 as IOS-1002 + PD-1 combination. Depending on the disease entity and line of treatment, the PD-1 cohort will include PD-1 naïve, pre-exposed and refractory patients, respectively."

Clinical • Combination therapy • Metastases • P1 data • Oncology • Solid Tumor • B2M • KIR3DL1 • LILRB1

ImmunOs Therapeutics Announces Clinical Trial Collaboration with Merck & Co., Inc., Rahway, NJ, USA (GlobeNewswire) - "ImmunOs Therapeutics AG...announced a clinical trial collaboration and supply agreement with Merck & Co., Inc., Rahway, NJ, USA to evaluate its lead compound IOS-1002 in combination with Merck & Co., Inc., Rahway, NJ, USA's anti-PD-1 therapy, KEYTRUDA^® (pembrolizumab), in an ongoing Phase 1a/b clinical trial for the treatment of patients with advanced solid tumors...ImmunOs is currently enrolling patients in the Phase 1a/b trial, initiated earlier this year, to evaluate the potential of IOS-1002 as a monotherapy and in combination with KEYTRUDA in adult patients with advanced solid tumors."

Enrollment status • Licensing / partnership • Solid Tumor

ImmunOs Therapeutics Announces Initiation of Dosing in Phase 1 Trial of Lead Compound IOS-1002 (GlobeNewswire) - "ImmunOs Therapeutics AG...announced the initiation of dosing of patients in a Phase 1 trial of its lead program IOS-1002 in Australia. IOS-1002 is a first-in-class checkpoint inhibitor targeting LILRB1 (ILT2), LILRB2 (ILT4), and KIR3DL1 for the treatment of advanced solid tumors. As a multi-functional agent based on a naturally occurring human leukocyte antigen (HLA) targeting multiple immune checkpoints, IOS-1002 is designed to activate both innate and adaptive immune cells and to trigger profound anti-tumor activity. The ongoing trial is expected to enroll over 120 patients."

Trial status • Oncology • Solid Tumor

IOS-1002-A Novel Multitarget Therapeutic Modulating 3 Checkpoint Pathways to Activate Both Adaptive and Innate Immunity (PEGS 2023) - No abstract available

A Clinical Study to Evaluate the Safety, Tolerability and Efficacy of IOS-1002 Administered Alone and in Combination With a PD-1 Monoclonal Antibody in Advanced Solid Tumors (clinicaltrials.gov) - P1a/1b | N=140 | Recruiting | Sponsor: ImmunOs Therapeutics AG | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Oncology • Solid Tumor • LAG3 • PD-1 • PD-L1

A Clinical Study to Evaluate the Safety, Tolerability and Efficacy of IOS-1002 Administered Alone and in Combination With a PD-1 Monoclonal Antibody in Advanced Solid Tumors (clinicaltrials.gov) - P1a/1b | N=140 | Not yet recruiting | Sponsor: ImmunOs Therapeutics AG

New P1 trial • Oncology • Solid Tumor • LAG3 • PD-1 • PD-L1

ImmunOs Therapeutics Receives Regulatory Approval for First-In-Human Trial of IOS-1002 (GlobeNewswire) - "ImmunOs Therapeutics AG...announced that the Company has received full ethical institutional approval from the Human Research Ethics Committee (HREC) and regulatory approval from the Therapeutic Goods Administration (TGA) to conduct a Phase 1 trial of its lead program IOS-1002 in Australia. The first patients are expected to be enrolled in Q1, 2023."

New P1 trial • Oncology • Solid Tumor

ImmunOs Therapeutics´ Lead Program Shows Strong Anti-Tumor Activity In Vivo and In Vitro (GlobeNewswire) - "ImmunOs Therapeutics AG...announced promising data for the Company´s lead program IOS-1002...Preclinical in vitro and in vivo data show that IOS-1002 is designed and engineered for stability and large-scale production; binds to three different immune checkpoint targets – LILRB1 (ILT2), LILRB2 (ILT4) and KIR3DL1 – resulting in the restoration of immune effector cell function; enhances phagocytosis in primary macrophages against solid tumors and blood cancers and increases the killing activity of primary human T cells and NK cells, as both monotherapy and combination therapy with anti-PD-1; demonstrates anti-tumor activity both as monotherapy and combination therapy. The presented data supports IOS-1002 as a first-in-class multi-functional agent which will enter a Phase 1 trial later this year."

New P1 trial • Preclinical • Oncology • Solid Tumor

iosH2 exerts potent anti-tumor activity by blocking LILRB1/2 and KIR3DL1 receptor signaling (SITC 2021) - "iosH2 is a first-in-class multi-functional agent that promotes key components of the innate and adaptive immune system leading to profound anti-tumor activity. Clinical development is underway and a phase I trial in preparation."

Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

ImmunOs Therapeutics Lead Program Shows Strong Anti-Tumor Activity In Vivo and In Vitro (GlobeNewswire) - “Highlights of the Poster Presentation: Preclinical in vitro and in vivo data show that IOS-1002. Binds to three different innate immune checkpoint targets – LILRB1 (ILT2), LILRB2 (ILT4) and KIR3DL1 – and restores immune effector cell function; results in measurable anti-tumor activity both as monotherapy and combination therapy; enhances phagocytosis in primary macrophages against solid tumors and blood cancers and increases the killing activity of primary human T cells and of NK cells, as both monotherapy and combination therapy with PD-1. The presented data confirm the mechanism of action of IOS-1002, providing an encouraging framework for a Phase I clinical trial that is currently in preparation.”

Preclinical • Oncology