FS222 / Sino Biopharm - LARVOL DELTA

FS222-19101: FS222 First in Human Study in Patients With Advanced Malignancies (clinicaltrials.gov) - P1 | N=260 | Recruiting | Sponsor: invoX Pharma Limited | N=177 ➔ 260 | Trial completion date: May 2025 ➔ Oct 2027 | Trial primary completion date: May 2025 ➔ Oct 2027

Enrollment change • Trial completion date • Trial primary completion date • Oncology

FS222 is a CD137/PD-L1 tetravalent, bispecific antibody which elicits robust pharmacodynamic activity in advanced solid tumor patients in a FIH study (SITC 2024) - P1 | "Study is being conducted currently in the EU. Ethics approval has been obtained by appropriate processes."

Clinical • Metastases • PK/PD data • Oncology • Solid Tumor • CD8 • TNFRSF9

First-in-human study (FIH) of FS222, a next-generation tetravalent PD-L1/CD137 bispecific antibody: Safety, pharmacodynamics (PD), and antitumor activity in patients (pts) with advanced solid tumors including PD-1 refractory melanoma. (ASCO 2024) - P1 | "The novel PD-L1/CD137 bispecific antibody FS222 demonstrated PD activity across a broad range of doses. The safety profile was acceptable and manageable. Encouraging anti-tumor activity was observed, including in patients with PD-1 refractory cutaneous melanoma."

Clinical • Metastases • P1 data • PK/PD data • Colon Cancer • Colorectal Cancer • Cutaneous Melanoma • Febrile Neutropenia • Gastrointestinal Cancer • Hematological Disorders • Liposarcoma • Lung Cancer • Melanoma • Neutropenia • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • Thrombocytopenia • Triple Negative Breast Cancer • CD8 • PD-1 • TNFRSF9

invoX Pharma Presents Positive Clinical Data from Phase 1 Study of FS222 in Patients with Advanced Solid Tumours at the 2024 American Society of Clinical Oncology Annual Meeting (Businesswire) - P1 | N=177 | NCT04740424 | Sponsor: invoX Pharma Limited | "Today, invoX Pharma Limited...has presented updated findings from its ongoing phase 1 study of FS222...in patients with advanced solid tumours....These preliminary findings were presented today at the 2024 American Society of Clinical Oncology Annual Meeting....In the study, FS222 demonstrated encouraging anti-tumour activity in multiple tumour types. Responses (as defined by RECIST1.1 criteria) were observed in cutaneous melanoma (n=9), ovarian cancer (n=2), non-small cell lung cancer (NSCLC) (n=2), and one each for mucosal melanoma, triple negative breast cancer (TNBC), mesothelioma and MSS colorectal cancer. The rate of disease control (defined as the rate of complete responses, partial responses and stable disease combined) was 45.0% for all patients in the study. In 19 patients with metastatic/advanced cutaneous melanoma previously treated with a PD-1 antibody the overall response rate...was 47.4%..."

P1 data • Colorectal Cancer • Cutaneous Melanoma • Mesothelioma • Mucosal Melanoma • Non Small Cell Lung Cancer • Ovarian Cancer • Triple Negative Breast Cancer

52 RESEARCH RESULTS WILL BE PRESENTED AT 2024 ASCO ANNUAL MEETING (HKEXnews) - "The board of directors...of the Sino Biopharmaceutical Limited...announced that the Group’s category 1 innovative drugs 'Anlotinib (small molecule multi-targeting tyrosine kinase inhibitor)'...'Penpulimab (Anti PD-1)', and innovative pipelines under development 'FS222 (PD-L1/CD137 bispecific antibody)', 'Benmelstobart (Anti PD-L1)'...others will present 52 latest research results at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting..."

Clinical data • Endometrial Cancer • Head and Neck Cancer • Nasopharyngeal Carcinoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

FS222, A Tetravalent Bispecific CD137 and PD-L1 Targeting Antibody, Modulates Anti-Tumor Immunity Preclinically and Demonstrates Pharmacology in Patients in an Ongoing Phase I Trial (EACR 2023) - P1 | "Based on preclinical PK/PD, selected PD and biomarker endpoints have been incorporated into the FIH study design.ConclusionFS222 mechanism of action, as described in preclinical studies, appeared to translate to the emerging clinical pharmacology profile observed in patients in the Phase I study. Use of bioinformatics analysis pipelines enabled efficient handling of clinical pharmacology data."

IO biomarker • P1 data • Preclinical • Immune Modulation • Oncology • Solid Tumor • CD8 • FCGR2A • TNFRSF9

First-in-human study to evaluate the safety and clinical activity of FS222, a tetravalent bispecific antibody targeting PD-L1 and CD137, in patients with advanced solid tumors (ESMO-IO 2022) - P1 | "The CR remained persistent 10 months later. Conclusions Thus far, FS222 has demonstrated manageable tolerability and early signs of antitumor activity."

Clinical • IO biomarker • P1 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • TNFRSF9

F-star Therapeutics Presents Clinical Data on FS222, a CD137/PD-L1 Tetravalent Bispecific Antibody, at ESMO-IO 2022 Congress (GlobeNewswire) - P1 | N=177 | NCT04740424 | Sponsor: F-star Therapeutics Limited | "Phase 1 Interim Efficacy and Safety Results on FS222 as of the Cut-Off Date of July 20, 2022: 33 patients had been treated to date with FS222 at dose levels of: 300 μg (n=1), 1 mg (n=1), 3 mg (n=1), 10 mg (n=1), 30 mg (n=5), 0.75 mg/kg (n=15), and 1 mg/kg (n=9).Median time on study was 58 days (range 19-359 days) with 11 patients ongoing. One non-squamous NSCLC, PD-L1 naïve patient experienced a complete response (CR) at 8 weeks, at a dose of 1mg/kg. The CR has remained persistent for 40.9 weeks as of 20th July 2022. 6 patients had disease stabilization (SD), 16 had progressive disease (RECIST 1.1), 2 were discontinued before week 8, and 8 were awaiting their week 8 evaluation. FS222 showed a manageable safety profile with most adverse events (AEs) Grade 1-2. One patient experienced a DLT of Grade 3 febrile neutropenia. No patients discontinued FS222 due to an AE."

P1 data • Oncology • Solid Tumor

A First-in-Human Phase 1 Study of FS222, a CD137/PD-L1 tetravalent bispecific antibody, in patients with advanced malignancies. (ESMO-IO 2021) - P1 | "Legal entity responsible for the study F-star Therapeutics. Funding F-star Therapeutics."

Clinical • IO biomarker • P1 data • Oncology • Solid Tumor • TNFRSF9

F-star Therapeutics Reports Full-Year 2021 Financial Results and Provides Corporate Update (GlobeNewswire) - "Anticipated Program Milestones: In 2022: A clinical efficacy readout of FS118 in PD-1 acquired resistance head and neck cancer patients who have failed checkpoint therapies. Clinical update on FS222 Phase 1 trial. Program update on the Phase 1 trial of FS120. FS120 trial part B initiation, in combination with Merck’s pembrolizumab...R&D expense was $28.8M for the year ended December 31, 2021, compared to $14.1M for the 2020 year-end. The increase in R&D expense was due primarily to the expansion of our FS118 clinical trial into acquired resistance head & neck patients, as well as our CPI naïve trial in NSCLC and DLBCL, a full year of spend on the mono and combo SB11285 clinical trial, and continued progression of our FS120 and FS222 clinical programs."

Clinical • Clinical data • Commercial • Diffuse Large B Cell Lymphoma • Head and Neck Cancer • Hematological Malignancies • Lung Cancer • Lymphoma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

"A TiP update on FS222, a CD137/PD-L1 mAb2 #bispecific antibody in pts w/ advanced malignancies, to be presented at #ESMOImmuno21 Enrollment ongoing. Accelerated dose titration completed, and id of optimal patient groups, dose and schedule is on-going. https://t.co/7i4Mdf3eAV" (@Fstar_Inc)

Clinical • Oncology • TNFRSF9

F-star Therapeutics to Present FS222 Trial-in-Progress Update at ESMO Immuno-Oncology Congress 2021 (GlobeNewswire) - "The poster...describes the design of a first-in-human Phase 1 multi-center, multi-part, open label study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and clinical activity of FS222 in adult subjects with advanced malignancies....The clinical study comprises an Accelerated Dose Titration (ADT) component followed by a 3+3 dose escalation design and dose expansion cohorts (Part A). Part B consists of tumor specific efficacy expansion cohorts. Enrollment is ongoing at four sites including Vall D’Hebron Institute of Oncology (VHIO), Barcelona, Hospital Universitario 12 de Octubre (Madrid); South Texas Accelerated Therapeutics (START), Hospital Universitario Fundación Jimenéz Díaz, Madrid; and Clinica Universidad de Navarra (CUN), Pamplona."

Clinical protocol • Enrollment status • Colorectal Cancer • Esophageal Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor

F-star Therapeutics to Host Virtual R&D Day on December 6, 2021 (GlobeNewswire) - "Following a discussion of F-star’s R&D platform, Louis Kayitalire, M.D., Chief Medical Officer, will present on the vast potential of the company's clinical pipeline of tetravalent mAb2 bispecifics, each of which is directed against some of the most exciting targets in immuno-oncology drug development, including LAG-3 and CD137 (4-1BB)."

Clinical • Breast Cancer • Head and Neck Cancer • Hematological Malignancies • Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

IONTAS Collaboration With F-star Enters Oncology Phase 1 Clinical Trial (Businesswire) - “IONTAS Limited…announces that F-star Therapeutics, Inc...has dosed the first patients in a Phase 1 clinical trial, with FS222, a CD137/PD-L1 bispecific antibody. IONTAS applied its proprietary technology to generate a component utilized within FS222, which was subsequently licenced to F-star. The initiation of this trial adds to the growing portfolio of antibodies generated by IONTAS that are entering clinical trials.”

Trial status • Oncology

F-star Therapeutics Reports First Quarter 2021 Financial Results and Provides Corporate Update (GlobeNewswire) - "FS118: The phase 2 proof-of-concept trial of FS118 is proceeding on plan and the Company plans to provide an update on progress in the first half of 2022...FS222: The ongoing phase 1 clinical trial is proceeding on plan and the Company plans to provide an update on progress before the end of 2021...SB 11285: The Company plans to provide an update on the progress of SB 11285 in the phase 1 clinical trial in mid-2021."

Trial status • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma of Head and Neck

[VIRTUAL] FS222, a tetravalent bispecific antibody targeting CD137 and PD-L1, is designed for optimal CD137 interactions resulting in potent T cell activation without toxicity (AACR 2021) - "FS222 was designed to be a potent anti-human CD137/PD-L1 tetravalent conditional agonist with a unique combination of high affinity PD-L1 binding and moderate monovalent affinity, and highly avid binding, to CD137 on activated T cells. A favorable safety profile and immunopharmacology was observed with FS222 in a primate GLP toxicity study. Tetravalent binding by FS222 was required for optimal activity in pharmacology studies."

IO biomarker • Oncology • TNFRSF9

"#FstarTherapeutics Shows Differentiation of #FS222 in #AACR21 Poster $FSTX https://t.co/R0TUOvvzgv" (@1stOncology)

Oncology

F-star Therapeutics Shows Differentiation of FS222 in 2021 AACR Poster (GlobeNewswire) - "Tetravalent binding by FS222 demonstrated optimal activity in multiple preclinical pharmacology studies, outperforming classic heterodimeric bispecific antibodies. These data showed that there was no evidence of a hook effect, or bell-shaped dose response curve, in vitro, and coupled with FS222’s favorable safety profile, presents a potentially broad and differentiated therapeutic window."

Preclinical • Oncology

F-star Therapeutics Reports Full-Year 2020 Financial Results and Provides Corporate Update (GlobeNewswire) - "The European Patent Office (EPO) granted a patent in January 2021 with claims protecting the composition of matter of F-star’s FS118 molecule. The expiry date of the patent, not including any potential extensions to the standard 20-year term of protection, is expected to be June 2037...Mid- 2021, FS120: Update on accelerated dose titration; Mid- 2021, SB 11285, Update of Phase 1a/b including combination dosing with Tecentriq; Q4 2021, FS222, Update on accelerated dose titration and initiation of PK/PD expansion cohorts; H1 2022, FS118, Phase II ( PoC) early efficacy analysis."

Enrollment status • P1 data • P2 data • Patent • Head and Neck Cancer • Hematological Malignancies • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

FS222 First in Human Study in Patients With Advanced Malignancies (clinicaltrials.gov) - P1; N=177; Recruiting; Sponsor: F-star Beta Limited

Clinical • New P1 trial • Oncology • Solid Tumor

F-star Therapeutics Announces First Patient Dosed in FS222 Phase 1 Clinical Trial (GlobeNewswire) - "F-star Therapeutics, Inc...announces that the first patient has been dosed in its Phase 1 trial evaluating FS222, a potentially best-in-class bispecific antibody targeting CD137 and PD-L1...This multicenter, open-label, first-in-human trial will evaluate the safety, tolerability, and clinical activity of FS222 in adult patients diagnosed with advanced malignancies."

Trial status • Oncology • Solid Tumor

F-star Therapeutics Announces Clearance of Clinical Trial Application for FS222 (PRNewswire) - "F-star Therapeutic...announces the authorization of the Clinical Trial Application (CTA) in Spain for the initiation of a Phase 1, open label, first-in-human clinical study of FS222....In preclinical studies, FS222-mediated PD-L1 blockade that synergized with conditional CD137 agonism stimulated lymphocyte activation and showed antitumor responses beyond that achieved with PD-L1 inhibition alone."

European regulatory • New P1 trial • Preclinical • Oncology • Solid Tumor

Spring Bank Pharmaceuticals and F-star Therapeutics Agree to Combine to Pursue Mission of Creating Next Generation Immunotherapies (GlobeNewswire) - "The combined company plans to advance its pipeline through multiple clinical trials, including the following anticipated near-term milestones that offer significant potential value creation for Spring Bank’s stockholders: (i) Report Phase 1 results from the FS118 program (2020 Q4); (ii) Update on dose escalation in FS222 Phase 1 (2022 Q2); (iii) Report FS118 Phase 2 proof of concept readout (2022 Q4); (iv) Report initiation of tumor specific expansion cohorts in FS222 Phase 1 (2022 Q4); (v) Initiation of PK/PD expansion cohorts in the FS222 Phase 1 trial (2021 Q4); (vi) Update on FS118 Phase 2 proof of concept trial (2022 Q1)." "

P1 data • P2 data • Trial status • Oncology

Spring Bank Pharmaceuticals and F-star Therapeutics Agree to Combine to Pursue Mission of Creating Next Generation Immunotherapies (GlobeNewswire) - "Spring Bank Pharmaceuticals...and F-star Therapeutics, Limited...announced that the companies have entered into a definitive share exchange agreement pursuant to which Spring Bank will, subject to stockholder approval, acquire all of the outstanding share capital of F-star in exchange for newly issued shares of Spring Bank in an all-stock transaction. The combined company, operating under the name F-star Therapeutics, Inc., will advance its immuno-oncology pipeline of multiple tetravalent bispecific antibody programs, as well as Spring Bank’s STING (STimulator of INterferon Gene) agonist, SB 11285, currently in a Phase 1/2 clinical trial."

M&A • Oncology

[VIRTUAL] Clustering CD137 via cell-expressed PD-L1 crosslinking avoided Fc-mediated agonism and resulted in safe and potent conditional lymphocyte activation (AACR-II 2020) - "A favourable safety profile and immunopharmacology was observed with FS222 in a primate GLP toxicity study. FS222 did not show toxicity and the anti-mouse CD137/PD-L1 mAb2 had self-limiting immunopharmacology outside the tumor microenvironment, suggesting a well-tolerated and effective mechanism of action with a broad therapeutic window."

Oncology • PD-L1