alomfilimab (SAR445256) / Sanofi - LARVOL DELTA

Safety and Efficacy of KY1044 and Atezolizumab in Advanced Cancer (clinicaltrials.gov) - P1/2 | N=222 | Terminated | Sponsor: Kymab Limited | Active, not recruiting ➔ Terminated; Early discontinuation based on strategic sponsor decision not driven by any safety concerns.

Combination therapy • Metastases • Trial termination • Breast Cancer • Cervical Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Hormone Receptor Breast Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

Safety and Efficacy of KY1044 and Atezolizumab in Advanced Cancer (clinicaltrials.gov) - P1/2 | N=280 | Active, not recruiting | Sponsor: Kymab Limited | Trial completion date: Apr 2024 ➔ Aug 2024 | Trial primary completion date: Apr 2024 ➔ Aug 2024

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Breast Cancer • Cervical Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Hormone Receptor Breast Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

Safety and Efficacy of KY1044 and Atezolizumab in Advanced Cancer (clinicaltrials.gov) - P1/2 | N=280 | Active, not recruiting | Sponsor: Kymab Limited | Trial completion date: Nov 2024 ➔ Apr 2024 | Trial primary completion date: Nov 2024 ➔ Apr 2024

Combination therapy • IO biomarker • Metastases • Trial completion date • Trial primary completion date • Breast Cancer • Cervical Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Hormone Receptor Breast Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • CD8 • FOXP3 • ICOS

Safety and Efficacy of KY1044 and Atezolizumab in Advanced Cancer (clinicaltrials.gov) - P1/2 | N=280 | Active, not recruiting | Sponsor: Kymab Limited | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • IO biomarker • Metastases • Breast Cancer • Cervical Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Hormone Receptor Breast Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • CD8 • FOXP3 • ICOS

SAR445256 (KY1044) in combination with atezolizumab in patients (pts) with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) (ESMO 2022) - P1/2 | "In Ph1, a 59-year-old male pt with HPV+ HNSCC who progressed on 5 prior lines of therapy (including nivolumab), experienced a PR (42% tumor shrinkage), still holding as of C26D1, and on treatment for >20 months as of 10Feb2022. Ph2 assessment is planned in 2 cohorts: HNSCC pts PD-L1 naïve and pretreated. Note: Atezolizumab will continue to be provided by Roche for the RP2D part of this study as well."

Clinical • Combination therapy • IO biomarker • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • ICOS

Safety and Efficacy of KY1044 and Atezolizumab in Advanced Cancer (clinicaltrials.gov) - P1/2 | N=280 | Recruiting | Sponsor: Kymab Limited | N=412 ➔ 280 | Trial completion date: May 2023 ➔ Nov 2024 | Trial primary completion date: May 2023 ➔ Nov 2024

Combination therapy • Enrollment change • IO biomarker • Trial completion date • Trial primary completion date • Breast Cancer • Cervical Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Hormone Receptor Breast Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • CD8 • FOXP3 • ICOS

[VIRTUAL] KY1044 to target the ICOS pathways inducing intratumoral Treg depletion and agonism of effector T cells: Preliminary pharmacodynamic markers from a phase 1/2 multicenter trial. (ASCO 2021) - P1/2 | "A Phase 1/2 clinical trial (NCT03829501) is currently assessing the safety and preliminary efficacy of KY1044, as a single agent and in combination with atezolizumab, in subjects with advanced relapsed/refractory malignancies . LongitudinalPDdata confirmed the expected KY1044 MoA, namely ICOS Treg depletion and increased CD8/ICOS Treg ratio in the TME as well as T cell co-stimulation . The observed PD responses are currently being further explored in a more homogenous patient population."

Clinical • IO biomarker • P1/2 data • PK/PD data • Immune Modulation • Inflammation • Oncology • CD8 • CSF2 • FOXP3 • ICOS

[VIRTUAL] A phase 1/2 open-label study of KY1044, an anti-ICOS antibody with dual mechanism of action, as single agent and in combination with atezolizumab, in adult patients with advanced malignancies. (ASCO 2021) - P1/2 | "KY1044 is well tolerated as single agent and in combination with atezolizumab . Objective responses have been observed in this phase 1 part of the study . The phase 1 expansion and phase 2 part of the study is ongoing."

Clinical • Combination therapy • P1/2 data • Breast Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatology • Immunology • Myositis • Oncology • Pancreatic Cancer • Penile Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

A first-in-human study of KY1044, a fully human anti-ICOS IgG1 antibody as monotherapy and in combination with atezolizumab in patients with selected advanced malignancies. (ASCO 2019) - P1/2; "An intensive biomarker plan is integral to the study design to underpin the phenotypic and molecular changes in both peripheral blood and tumor. Clinical trial information: NCT03829501"

Clinical • Combination therapy • IO biomarker • Monotherapy • P1 data • PD(L)-1 Biomarker • Oncology

Sanofi to showcase data from its transformative oncology pipeline at 2021 ASCO Meeting (GlobeNewswire) - “Early clinical data for amcenestrant, our investigational oral selective estrogen receptor degrader (SERD), show potential to become a new endocrine backbone therapy in ER+ HER2- breast cancer…Data analyses reinforce Libtayo® (cemiplimab-rwlc) as a standard of care in advanced non-melanoma skin cancer indications and in advanced non-small cell lung cancer, including new data in historically underrepresented patients with brain metastases… Longer term data and new analyses for Sarclisa® (isatuximab-irfc) further strengthen its efficacy profile, including for elderly patients and patients with high-risk cytogenetic abnormalities…Biomarker research for tusamitamab ravtansine, an early-stage, potential first-in-class investigational anti-CEACAM5 antibody drug conjugate for advanced non-small cell lung cancer.”

Clinical data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Sanofi completes Kymab acquisition (Sanofi Press Release) - "Sanofi announced today the successful completion of its acquisition of Kymab Group Ltd., adding KY1005 to its pipeline, a fully human monoclonal antibody targeting key immune system regulator OX40L. The acquisition continues to build on Sanofi’s leading presence in immunology...Kymab’s pipeline also includes the oncology asset KY1044, an ICOS agonist monoclonal antibody, currently in early Phase1/2 development as monotherapy and in combination with an anti-PD-L1."

M&A • Atopic Dermatitis • Immunology • Lupus • Oncology • Psoriasis • Psoriatic Arthritis

Sanofi to acquire Kymab, adding KY1005 to its pipeline, a human monoclonal antibody targeting key immune system regulator OX40L (GlobeNewswire) - "Sanofi and Kymab...have entered into an agreement under which Sanofi will acquire Kymab for an upfront payment of approximately $1.1 billion...Kymab’s pipeline also includes the oncology asset KY1044, an ICOS agonist monoclonal antibody, currently in early Phase 1/2 development as monotherapy and in combination with an anti-PD-L1....Sanofi expects to complete the acquisition in the first half of 2021. "

M&A • Oncology

The combination of immune checkpoint blockers with the anti-ICOS KY1044 antibody results in a strong tumor response (AACR 2018) - "Together, this highlights the potential of targeting and depleting TRegs to enhance anti-tumour responses.The Inducible T-cell costimulator (ICOS/CD278) is related to the CD28 superfamily and is induced when T cells get activated. In summary, our data demonstrate that targeting ICOS with KY1044 is a valid approach for manipulating the immune system and for inducing a strong anti-tumour response in several indications. The data presented here also warrant the assessment of KY1044 in cancer patients in a clinical trial."

Checkpoint inhibition • IO Biomarker • PD(L)-1 Biomarker • Oncology

An antibody targeting ICOS increases intratumoral cytotoxic to regulatory T cell ratio and induces tumor regression. (PubMed, Cancer Immunol Res) - "KY1044 demonstrated monotherapy antitumor efficacy and improved anti-PD-L1 efficacy. In summary, we demonstrated that using KY1044, one can exploit the differential expression of ICOS on T cell subtypes to improve the intratumoral immune contexture and restore an antitumor immune response."

IO Biomarker • Journal • Immune Modulation • Inflammation • Oncology • CD8 • ICOS

A novel antibody targeting ICOS increases intratumoural cytotoxic to regulatory T cell ratio and induces tumour regression (CRI-CIMT-EATI-AACR 2019) - "Altogether, KY1044 improved the intratumoral TEFF:TReg ratio and increased activation of TEFF cells, resulting in monotherapy efficacy or in synergistic combinatorial efficacy when administrated with the immune checkpoint blocker anti-PD-L1. In summary, our data demonstrate that targeting ICOS with KY1044 can favourably alter the intratumoral immune contexture, promoting an anti-tumour response."

IO Biomarker • PD(L)-1 Biomarker

Kymab Outlines Positive New Findings for its KY1044 Anti-ICOS Program at the CICON 2019 Annual Meeting (GlobeNewswire, Kymab Group Ltd) - "Kymab Outlines Positive New Findings for its KY1044 Anti-ICOS Program at the CICON 2019 Annual Meeting. KY1044 increases the ratio of intratumoral cytotoxic-to-regulatory T cells and induces tumor regression. Phase 1/2, open-label, multicenter study ongoing to evaluate KY1044 as a single agent and in combination with anti-PD-L1 (atezolizumab) in adult patients with advanced malignancies ."

Clinical data • IO Biomarker • PD(L)-1 Biomarker • Preclinical

Kymab Presents Poster Detailing Adaptive Phase 1/2 Clinical Trial for its KY1044 Anti-ICOS Program at ASCO 2019 Annual Meeting (GlobeNewswire, Kymab Group Ltd) - Kymab Presents Poster Detailing Adaptive Phase 1/2 Clinical Trial for its KY1044 Anti-ICOS Program at ASCO 2019 Annual Meeting . Phase 1/2, open label, multicenter study to evaluate the safety, efficacy and tolerability of KY1044 as single agent and in combination with anti-PD-L1 (atezolizumab) in adult patients with selected advanced malignancies. Title: A first-in-human study of KY1044, a fully human anti-ICOS IgG1 antibody as monotherapy and in combination with atezolizumab in patients with selected advanced malignancies.

Clinical • Enrollment status

Differential expression of ICOS on circulating immune cells and tumor infiltrating lymphocytes in patient with solid tumors (AACR 2019) - "Using these approaches, we confirmed high ICOS expression in several solid tumor types. ICOS expression was also shown to be higher on immune cells in the TME compared to the periphery. Finally, ICOS expression was found to be more abundant on the surface of intratumoral TReg than on CD8+ T effector cells, confirming the data obtained in preclinical syngeneic tumor models (AACR2018 abstract #2792)."

Clinical • IO Biomarker • Tumor-Infiltrating Lymphocyte

Safety and Efficacy of KY1044 and Atezolizumab in Advanced Cancer (clinicaltrials.gov) - P1/2; N=412; Recruiting; Sponsor: Kymab Limited

Clinical • Combination therapy • New P1/2 trial

"@Kymabltd to present a poster on #ICOS expression in solid tumours #AACR2019 #KY1044 #TRegs" (@rcasainson)

Biomarker • IO Biomarker