FS120 / Sino Biopharm - LARVOL DELTA

FS120, an OX40/CD137 tetravalent bispecific dual agonist antibody, synergistically increases the antitumor activity of anti-PD-1 in preclinical studies (SITC 2021) - P1 | "In combination with anti-PD-1, FS120 surrogate increased the antitumor efficacy with pharmacodynamic changes related specifically to T cell activation, when compared to monotherapies. These data support the development of FS120 in combination with anti-PD-1 in patients with hard-to-treat cancers who may not benefit fully from either treatment as a monotherapy."

Preclinical • Oncology • CD4 • CD8 • FCGR2A • GZMB • IFNG • TNFRSF9

OX40/CD137 dual agonism potentiates anti-tumour immunity by driving functional reprogramming and instability of regulatory T (Treg) cells (SITC 2022) - P1 | "This mode of action is distinct from anti-PD-1 therapy. These findings support a combination therapy approach exploiting the distinct anti-tumour immune activities of FS120 and anti-PD-1 in cancer patients."

Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD4 • CD8 • FOXP3 • IFNG • TNFA • TNFRSF9

[VIRTUAL] A first-in-human phase I study of FS120, an OX40/CD137 tetravalent bispecific antibody, in patients with advanced malignancies (ESMO 2021) - P1 | "Exploratory translational endpoints will also be included in the study. Study enrolment began December 2020."

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

FS120 First in Human Study in Patients With Advanced Malignancies (clinicaltrials.gov) - P1 | N=277 | Recruiting | Sponsor: F-star Therapeutics Limited | N=70 ➔ 277

Combination therapy • Enrollment change • Oncology • Solid Tumor

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

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

F-star Therapeutics to Present at The Society for Immunotherapy of Cancer (SITC) 2021 Conference (GlobeNewswire) - "In her presentation, Dr. Morrow explains how bispecific antibodies can unlock new biology via mechanisms that combination approaches cannot. F-star’s FS118 is a dual checkpoint inhibitor targeting PD-L1 and LAG-3 that drives LAG-3 shedding and receptor down-regulation, via bispecific activity....FS120 in combination with anti-PD-1 (pembrolizumab) was shown to enhance T cell activity in multiple human primary immune assays. In combination with an anti-PD-1, FS120 surrogate increased antitumor efficacy in a mouse tumor model with pharmacodynamic changes related specifically to T cell activation, when compared to monotherapies, either alone or in combination."

Preclinical • Oncology

F-star Therapeutics to Present FS120 Phase 1 Trial-in-Progress Update at ESMO 2021 (GlobeNewswire) - "F-star Therapeutics, Inc...announces that the Company will present a trial in progress update on FS120, a first-in-class OX40 and CD137 tetravalent dual T cell agonist, at the European Society for Medical Oncology 2021 Conference, taking place virtually, September 16th-21st...describes the design of a first-in-human Phase 1 clinical trial (NCT04648202) to assess the safety, pharmacokinetics/pharmacodynamics (PK/PD) and efficacy of FS120 in patients with advanced malignancies. This study comprises an Accelerated Dose Titration (ADT) component followed by a 3+3 design. Enrollment of the ADT portion of the study is complete, and the Company anticipates providing a further update on the study progress later this year."

Clinical protocol • Trial status • Oncology

F-star Therapeutics to Present FS120 Phase 1 Trial-in-Progress Update at ESMO 2021 (GlobeNewswire) - “FS120 was well tolerated in NHP with a HNSTD (highest non-severely toxic dose) of 30mg/kg with limited and minimal changes in clinical chemistry measurements relating to liver model function. Pharmacodynamic biomarkers indicative of FS120 pharmacology, including increases in proliferation of CD4+ and CD8+ T cell and NK cell models, were observed in the NHP study and plateaued at the highest dose level. These pharmacodynamic markers are being used in the clinical study to determine a pharmacologically active dose in humans. Safety and PK/PD data from this study will be used to trigger the initiation of the previously announced FS120 and KEYTRUDA® (pembrolizumab) combination study, scheduled to start in Q3 2022.”

New trial • Preclinical • Oncology

F-star Therapeutics Announces Collaboration with MSD to Evaluate FS120 in Combination with KEYTRUDA (GlobeNewswire) - "F-star Therapeutics, Inc...announced that it has entered into a clinical trial collaboration and supply agreement with MSD (Merck & Co., Inc., Kenilworth, NJ, USA), to evaluate the combination of FS120, F-star’s first-in-class dual-agonist tetravalent bispecific antibody targeting CD137 and OX40, with KEYTRUDA® (pembrolizumab), MSD’s anti-PD-1 therapy....Under the terms of the agreement, MSD will supply KEYTRUDA for a combination arm that will be included in the adaptive Phase 1 clinical protocol of FS120, sponsored by F-star, that was initiated in December of 2020."

Licensing / partnership • Trial status • Oncology • Solid Tumor

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

FS120 First in Human Study in Patients With Advanced Malignancies (clinicaltrials.gov) - P1; N=70; Recruiting; Sponsor: F-star Beta Limited

Clinical • New P1 trial • Oncology • Solid Tumor

F-star Therapeutics Announces First Patient Dosed in First-in-Class FS120 Phase 1 Clinical Trial (PRNewswire) - "F-star Therapeutics, Inc...today announces that the first patient has been dosed in its Phase 1 trial evaluating FS120, a first-in-class dual-agonist tetravalent bispecific antibody targeting CD137 (4-1BB, TNFRSF9) and OX40 (CD134, TNFRSF4)."

Trial status • Oncology

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) Update on SB 11285 monotherapy cohorts (2020 Q4); (ii) Update on accelerated dose titration from the FS120 Phase 1 trial (2021 Q2); (iii) Initial read out from the SB 11285-atezolizumab combination cohort (2021 H1); (iv) Initiation of FS120 PD-1 combination trial (2022 Q2)."

Clinical data • New trial • P1 data • 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

A CD137/OX40 Bispecific Antibody Induces Potent Antitumor Activity That Is Dependent on Target Co-Engagement. (PubMed, Cancer Immunol Res) - "When compared to a crosslink-independent CD137 agonist monoclonal antibody, the FS120 surrogate induced lower liver T cell infiltration. These data support initiation of clinical development of FS120, a first-in-class dual agonist bispecific antibody for the treatment of human cancer."

IO Biomarker • Journal • CD8 • TNFA • TNFRSF4

F-star Therapeutics announces data on potent anti-tumor activity of FS120 published in Cancer Immunology Research (Businesswire) - “F-star Therapeutics Ltd…announces the publication of preclinical data on the potent anti-tumor activity of FS120, a first-in-class dual-agonist tetravalent bispecific antibody targeting CD137 and OX40, in leading peer-reviewed journal Cancer Immunology Research. Preclinical data from the article show that FS120 delays tumor growth by improving the activation and proliferation of peripheral T cells. These data also reinforce the superiority of dual agonist targeting over alternative TNFR-targeting agonists and support the clinical development of FS120 to treat patients with cancer…Preclinical data from this study show that FS120 can activate both CD4+ and CD8+ T-cells in an FcγR-independent mechanism, therefore promoting focused immune stimulation.”

Preclinical

F-star Therapeutics announces FDA acceptance of IND application for FS120 (Businesswire) - “F-star Therapeutics Ltd…announces that the United States Food and Drug Administration (FDA) has accepted its Investigational New Drug (IND) application for FS120, F-star’s proprietary tetravalent bispecific antibody targeting CD137 and OX40….F-star expects to enroll 70 patients in a Phase 1 dose escalation clinical trial to assess the safety, tolerability and efficacy of FS120 in patients with advanced malignancies.”

Enrollment status • IND

Crosslink-Independent CD137 Agonism is Associated with Liver Inflammation (SITC 2019) - "The CD137 antibody clone present in urelumab, which induced hepatotoxicity in the clinic, showed crosslink-independent activity and was more potent as compared to the clone present in utomilumab, which was well tolerated in the clinic. CD137 agonist antibodies associated with increased liver inflammation were found to be crosslink-independent, suggesting this factor may contribute to their hepatotoxicity risk. FS120 surrogate did not show increased liver T cell infiltration suggesting this has the potential to be a well-tolerated and effective mechanism of crosslinking and agonising CD137, as well as OX40, and is independent of FcgR-mediated crosslinking."

F-star presents new data on OX40/CD137 tetravalent bispecific antibody at the SITC 2019 Annual Meeting (Businesswire) - “F-star Therapeutics…announces that new preclinical data on FS120, a mAb² product candidate targeting OX40 and CD137, will be presented at the Society for Immunotherapy of Cancer (SITC) 2019 Annual Meeting in National Harbor, Maryland, United States, being held from 06 - 10 November 2019…. Some CD137 agonist antibodies have been shown to induce adverse effects either in clinical or in preclinical studies as they constitutively activate T cells and thus release cytotoxic immunity outside of the tumor. In contrast, FS120 is designed to mitigate off-target toxicity through conditional, crosslink-dependent activation upon binding to both OX40 and CD137, which are predominantly present on T cells in the tumor microenvironment. F-star expects to submit an IND application for FS120 during the fourth quarter of 2019.”

IND • Preclinical

Dual agonist bispecific antibody targeting OX40 and CD137 mediates anti-tumor immunity and synergizes with PD-1/PD-L1 blockade to improve survival in a syngeneic mouse model (AACR 2019) - "In addition, we show data that indicates PD-1/PD-L1 pathway plays a role in limiting the activity of an anti-OX40/CD137 mAb2. Taken together, these results demonstrate the potential for FS120, as a single agent or in combination, to drive an effective anti-tumor immune response in cancer patients."

F-star presents new data on its tetravalent bispecific antibodies at the AACR 2019 Annual Meeting (Businesswire) - "The preclinical presentations illustrate the synergistic benefit of F-star’s tetravalent mAb² and how both FS120 and FS222 individually outperform combinations of single agents in multiple assays...F-star will also share preclinical data on a third programme, FS118, a potentially first-in-class bispecific antagonist of LAG-3 (Lymphocyte-Activation Gene 3) and PD-L1. The poster describes FS118’s potential to increase response rates by overcoming the LAG-3-mediated tumour evasion mechanism that often takes place following single agent checkpoint blockade."

Preclinical