[Translation] A Phase I study with a safety run-in of BI-1206 (a CD32b [FcγRIIB] monoclonal antibody) in combination with rituximab in patients with relapsed or refractory indolent B-cell non-Hodgkin's lymphoma

主要目的：评价BI-1206在第一阶段的安全性导入部分的安全性、耐受性；评价BI-1206与利妥昔单抗联合治疗复发性或难治性的惰性B细胞非霍奇金淋巴瘤（NHL）的安全性和耐受性；通过确立BI-1206的最大耐受剂量（MTD）（以静脉输注[IV]方式按周次给药，连续4周，与利妥昔单抗联合用药）来选择推荐的Ⅱ期剂量（RP2D）。如果药代动力学（PK）和药效学（PD）数据表明当前剂量为与国外临床研究17-BI-1206-02可比的最佳治疗剂量，则可在达到临床研究17-BI-1206-02获得的MTD之前，由队列审查委员会（CRC）决定暂停剂量递增，并基于PK和PD数据确定RP2D。

[Translation]

Primary objectives: To evaluate the safety and tolerability of BI-1206 in the safety lead-in part of Phase I; To evaluate the safety and tolerability of BI-1206 in combination with rituximab in the treatment of relapsed or refractory indolent B-cell non-Hodgkin's lymphoma (NHL); To select the recommended Phase II dose (RP2D) by establishing the maximum tolerated dose (MTD) of BI-1206 (administered weekly by intravenous infusion [IV] for 4 consecutive weeks in combination with rituximab). If the pharmacokinetic (PK) and pharmacodynamic (PD) data indicate that the current dose is the best therapeutic dose comparable to that obtained in the foreign clinical study 17-BI-1206-02, the cohort review committee (CRC) may decide to suspend dose escalation before the MTD obtained in the clinical study 17-BI-1206-02 is reached, and the RP2D may be determined based on the PK and PD data.

Start Date25 Jul 2022

Sponsor / Collaborator

CASI (China) Pharmaceuticals Technology Co., Ltd.

NCT04219254 / RecruitingPhase 1/2

A Phase 1/2a Clinical Trial of BI-1206, a Monoclonal Antibody to CD32b (FcγRIIB), in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors Previously Treated With Anti-PD-1 or Anti-PD-L1 Antibodies (KEYNOTE-A04)

Phase 1/2a Clinical Trial of BI-1206, a Monoclonal Antibody to CD32b (FcγRIIB), in Combination with Pembrolizumab in Subjects with Advanced Solid Tumors Previously Treated with Anti-PD-1 or Anti-PD-L1 Antibodies

Start Date29 Jun 2020

Sponsor / Collaborator

BioInvent International AB

[+1]

NCT03571568 / RecruitingPhase 1/2

Phase 1/2a Clinical Trial of BI-1206, a Monoclonal Antibody to CD32b (FcYRIIB), in Combination With Rituximab in Subjects With Indolent B-Cell Non-Hodgkin Lymphoma That Has Relapsed or is Refractory to Rituximab

Phase 1/2a Clinical Trial of BI-1206, a Monoclonal Antibody to CD32b (FcyRIIB), in Combination with Rituximab in Subjects with Indolent B-Cell Non-Hodgkin Lymphoma That has Relapsed or is Refractory to Rituximab

Start Date16 May 2018

Sponsor / Collaborator

BioInvent International AB

100 Clinical Results associated with BI-1206

100 Translational Medicine associated with BI-1206

100 Patents (Medical) associated with BI-1206

Literatures (Medical) associated with BI-1206

01 Dec 2022·Journal of hematology & oncology

Targeting FcγRIIB by antagonistic antibody BI-1206 improves the efficacy of rituximab-based therapies in aggressive mantle cell lymphoma

Letter

Author: Huang, Shengjian ; Wang, Michael ; Zhang, Rongjia ; Karlsson, Ingrid ; Teige, Ingrid ; Kovacek, Mathilda ; Nie, Lei ; Frendéus, Björn ; Jordan, Alexa ; Liu, Yang ; Li, Yijing ; Jiang, Vivian Changying ; Cai, Qingsong ; Che, Yuxuan ; Leeming, Angela ; Chen, Zhihong ; Mårtensson, Linda ; McIntosh, Joseph

Abstract:

Inevitable relapses remain as the major therapeutic challenge in patients with mantle cell lymphoma (MCL) despite FDA approval of multiple targeted therapies and immunotherapies. Fc gamma receptors (FcγRs) play important roles in regulating antibody-mediated immunity. FcγRIIB, the unique immune-checkpoint inhibitory member of the FcγR family, has been implicated in immune cell desensitization and tumor cell resistance to the anti-CD20 antibody rituximab and other antibody-mediated immunotherapies; however, little is known about its expression and its immune-modulatory function in patients with aggressive MCL, especially those with multi-resistance. In this study, we found that FcγRIIB was ubiquitously expressed in both MCL cell lines and primary patient samples. FcγRIIB expression is significantly higher in CAR T-relapsed patient samples (p < 0.0001) compared to ibrutinib/rituximab-naïve, sensitive or resistant samples. Rituximab-induced CD20 internalization in JeKo-1 cells was completely blocked by concurrent treatment with BI-1206, a recombinant human monoclonal antibody targeting FcγRIIB. Combinational therapies with rituximab-ibrutinib, rituximab-venetoclax and rituximab-CHOP also induced CD20 internalization which was again effectively blocked by BI-1206. BI-1206 significantly enhanced the in vivo anti-MCL efficacy of rituximab-ibrutinib (p = 0.05) and rituximab-venetoclax (p = 0.02), but not the rituximab-CHOP combination in JeKo-1 cell line-derived xenograft models. In patient-derived xenograft (PDX) models, BI-1206, as a single agent, showed high potency (p < 0.0001, compared to vehicle control) in one aggressive PDX model that is resistant to both ibrutinib and venetoclax but sensitive to the combination of rituximab and lenalidomide (the preclinical mimetic of R2 therapy). BI-1206 sensitized the efficacy of rituximab monotherapy in a PDX model with triple resistance to rituximab, ibrutinib and CAR T-therapies (p = 0.030). Moreover, BI-1206 significantly enhanced the efficacy of the rituximab-venetoclax combination (p < 0.05), which led to long-term tumor remission in 25% of mice. Altogether, these data support that targeting this new immune-checkpoint blockade enhances the therapeutic activity of rituximab-based regimens in aggressive MCL models with multi-resistance.

Graphical Abstract:

01 Sep 2020·Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, IncQ4 · AGRICULTURAL & FORESTRY SCIENCE

Preparation, identification, and functional analysis of monoclonal antibodies against atypical porcine pestivirus NS3 protein

Q4 · AGRICULTURAL & FORESTRY SCIENCE

Article

Author: Yang, Wenting ; Huang, Jingling ; Chen, Jianing ; Yan, Miaomiao ; Liu, Guangliang

Atypical porcine pestivirus (APPV) had been detected in many countries. However, to date, a commercial detection kit is not available because of a lack of specific monoclonal antibodies (mAbs) to APPV. We generated 7 mAbs targeting the NS3 protein of APPV. Isotyping results indicated that all of these mAbs are IgG1 with a kappa light chain. We analyzed the epitopes recognized by mAbs 2B6, 6G11, 8D1, 8D3, and 8F12, which recognized the same linear epitope (GRIKSAYSDE); the 6H3 and 7E10 mAbs recognized 2 different conformational epitopes. Applications of these antibodies were verified by ELISA, western blot, indirect immunofluorescence assay, and flow cytometry. The antibodies were functionally workable for these immunoassays except for 8F12, which could not be used in flow cytometry.

01 Sep 2016·Experimental parasitologyQ4 · MEDICINE

Insights into the biological features of the antigenic determinants recognized by four monoclonal antibodies in redia and adult stages of the liver fluke Fasciola hepatica

Q4 · MEDICINE

Article

Author: Hernández, Hilda ; Mosqueda, Maryani ; Sánchez, Jorge ; Rodríguez, Suanel Y ; Marcet, Ricardo ; Alfonso, Carlos ; Sarracent, Jorge ; Otero, Oscar ; Capó, Virginia ; Alba, Annia

Fasciola hepatica is a digenean trematode which infects a wide variety of domestic animals and also humans. Previous studies have demonstrated that four monoclonal antibodies (Mabs) against the total extract of F. hepatica redia (named as 1E4, 6G11, 4E5 and 4G11) also recognized the excretion - secretion antigens (ES Ag) of adult parasites, which is a biologically-relevant mixture of molecules with functional roles during infection and immune evasion on definitive hosts. In the present report we describe the partial characterization of the epitopes recognized by these Mabs by heat treatment, mercaptoethanol reduction, pronase proteolysis and sodium peryodate oxidation, which suggested their predominant protein and conformational nature. Also, a comparative study using immunodetection assays on crude extracts and on histological sections of both rediae and adults of F. hepatica were performed to explore the expression pattern of the antigenic determinants in these developmental stages. From these experiments it was found that the Mabs reacted most likely with the same proteins of approximately 64 and 105 kDa present on both rediae and adult's extracts. However, the 1E4, 6G11 and 4E5 Mabs also recognized other molecules of the total extract of F. hepatica adults, a fact that constitutes an evidence of the antigenic variation between both stages and points at a certain biological relevance of the recognized antigenic determinants. Immunolocalization studies on histological sections revealed that all Mabs reacted with the tegument of F. hepatica in both rediae and adults stages, while the epitopes recognized by 1E4, 6G11 and 4E5 antibodies were also preferentially localized in the intestinal caeca and in different organs of the reproductive system of adult specimens. The immunogenicity of these antigenic determinants, their conserved status among different stages of the life cycle of F. hepatica and their presence in both tegument and ES Ag of adult parasites, are suitable features that suggest their potential use for developing an epitope-based vaccine for fasciolosis control.

News (Medical) associated with BI-1206

12 Sep 2024

·www.bioinvent.com

BioInvent announces the enrollment of the first patient in triple combination arm of BI-1206, rituximab and Calquence® for the treatment of non-Hodgkin's lymphoma

First patient enrolled in Phase 2a study arm combining BI-1206 with rituximab and acalabrutinibwith initial data expected YE 2024 Clinical supply agreement for acalabrutinib with AstraZeneca in place Lund, Sweden – September 12, 2024 – BioInvent International AB (“BioInvent”) (Nasdaq Stockholm: BINV), a biotech company focused on the discovery and development of novel and first-in-class immune-modulatory antibodies for cancer immunotherapy, today announces it has enrolled the first patient in the triple combination arm of the Phase 1/2a study of its anti-FcgRIIB antibody, BI-1206 in non-Hodgkin's lymphoma (NHL). The Phase 2a study arm will combine the subcutaneous formulation of BI-1206 and rituximab with Calquence® (acalabrutinib), a selective inhibitor of Bruton's tyrosine kinase (BTK). Approximately 30 patients are expected to be enrolled in Spain, Germany, the US, and Brazil. Preliminary data are expected by the end of 2024. In February 2024 BioInvent signed a clinical supply agreement with AstraZeneca (LSE/STO/Nasdaq: AZN) to provide Calquence® for the combination arm. "The enrolment of the first patient in the study is an important milestone as we move forward to evaluate this triple combination as a potential new treatment option for patients with non-Hodgkin's lymphoma," said Martin Welschof, Chief Executive Officer of BioInvent. "The combination of BI-1206 and rituximab has already demonstrated promising signs of clinical efficacy with a favorable safety profile, and we have strong reasons to believe that the addition of acalabrutinib will increase response rates even further; the subcutaneous formulation of BI-1206 is expected to provide a great deal of flexibility and further improve the tolerability of the treatment." About BI-1206BI-1206 is one of BioInvent’s most advanced drug candidates and is developed to re-establish the clinical effect of existing cancer treatments such as pembrolizumab and rituximab, drugs with combined global sales of approximately USD 28.5 billion annually. The drug candidate is evaluated in two separate clinical programs, one for the treatment of non-Hodgkin’s lymphoma (NHL, a type of blood cancer) and one for the treatment of solid tumors. Two delivery formulations (intravenous (IV) and subcutaneous (SC)) of BI-1206 are being evaluated in parallel. BI-1206 in NHLAll patients in the ongoing Phase 1/2a study (NCT03571568) have previously been treated with one or more rituximab containing treatments. Latest results were presented in connection with EHA (European Hematology Association) congress in June 2024: the intravenous (IV) Phase 1 part (dose escalation) showcased responses across the dose range of 30-100 mg, including 5 patients with complete response (CR), 1 with partial response (PR) and 6 patients with stable disease (SD) out of 17 evaluable patients. First data from the subcutaneous (SC) Phase 1 part (dose escalation) showed 1 CR, 2 PR and 1 SD out of 4 evaluable patients. About BioInventBioInvent International AB (Nasdaq Stockholm: BINV) is a clinical-stage biotech company that discovers and develops novel and first-in-class immuno-modulatory antibodies for cancer therapy, with currently five drug candidates in six ongoing clinical programs in Phase 1/2 trials for the treatment of hematological cancer and solid tumors. The Company's validated, proprietary F.I.R.S.T™ technology platform identifies both targets and the antibodies that bind to them, generating many promising new immune-modulatory candidates to fuel the Company's own clinical development pipeline and providing licensing and partnering opportunities. The Company generates revenues from research collaborations and license agreements with multiple top-tier pharmaceutical companies, as well as from producing antibodies for third parties in the Company's fully integrated manufacturing unit. More information is available at www.bioinvent.com. Follow us on the social media platform X: @BioInvent. For further information, please contact:Cecilia Hofvander, Senior Director Investor RelationsPhone: +46 (0)46 286 85 50Email: cecilia.hofvander@bioinvent.comBioInvent International AB (publ)Co. Reg. No. Org nr: 556537-7263Visiting address: Ideongatan 1Mailing address: 223 70 LUNDPhone: +46 (0)46 286 85 50www.bioinvent.com The press release contains statements about the future, consisting of subjective assumptions and forecasts for future scenarios. Predictions for the future only apply as the date they are made and are, by their very nature, in the same way as research and development work in the biotech segment, associated with risk and uncertainty. With this in mind, the actual outcome may deviate significantly from the scenarios described in this press release.

Phase 1Phase 2ImmunotherapyClinical Result

30 May 2024

·www.biospace.com

BioInvent to Host Virtual KOL Event to Highlight Recently Presented Efficacy Data from BioInvent's Lead Candidates BI-1808 and BI-1206

BioInvent International (STO:BINV) Discussion on TNFR2 and FcyRIIB as promising targets in immuno-oncology on June 18, 2024 LUND, SWEDEN / ACCESSWIRE / May 30, 2024 / BioInvent International AB ("BioInvent") (Nasdaq Stockholm:BINV), a biotech company focused on the discovery and development of novel and first-in-class immune-modulatory antibodies for cancer immunotherapy, today announced that it will host a virtual KOL event on Tuesday, June 18, 2024 from 9:00-10:45 AM ET/3-4:45 PM CEST. To register, click here ( Events). The event will feature Alexander Eggermont, MD, PhD (University Medical Center Utrecht), who will join company management to discuss the recently disclosed positive clinical data for BioInvent's lead, first-in-class antibodies, BI-1808 and BI-1206, to be presented at ASCO and EHA. The data support the promise of FcyRIIB and TNFR2 as important immunotherapy targets. BI-1808 and BI-1206 are BioInvent's two lead programs in a broad pipeline of first- or best-in-class immunomodulatory antibodies for the treatment of cancer: BI-1808, an anti-TNFR2 antibody, showing promising single-agent efficacy in an ongoing Phase 1/2a trial as a single agent as well as in combination with pembrolizumab for patients with advanced malignancies. BI-1206, an anti-FcyRIIB antibody, currently being evaluated in two Phase 1/2a trials: in combination with rituximab for patients with non-Hodgkin's lymphoma (NHL) and in combination with pembrolizumab for patients with solid tumors. Recently disclosed data for BI-1206 show long-lasting responses in heavily pre-treated patients. The event will include an overview of the company's development strategy and highlight upcoming rich news flow for the rest of 2024. A live question and answer session will follow the formal presentation. About Alexander Eggermont, MD, PhD Alexander Eggermont, MD, PhD is an internationally recognized expert in surgical oncology, immunotherapy, melanoma, sarcoma and cancer drug development. He currently holds roles as Chief Scientific Officer at the Princess Máxima Center for Pediatric Oncology & Professor of Immunotherapy at the University Medical Center Utrecht, the Netherlands; Professor of Oncology (Classe Exceptionelle) at Paris-Saclay University, France; Coordinator, Comprehensive Cancer Center Program for Deutsche KrebsHilfe; and Strategic Advisor at the German Cancer Consortium (DKFZ). Prof. Eggermont was previously Director General of Gustave Roussy Comprehensive Cancer Center, Villejuif, France (2010-2019) and Professor of Oncology (Classe Exceptionelle) at Paris-Saclay University (2012-2020), France; Professor of Surgical Oncology (2003-2016) and Endowed Professor of International Networking in Cancer Research (2011-2018) at Erasmus University MC, Rotterdam, the Netherlands. He holds a PhD in tumor immunology from Erasmus University and is Fellow of the National Institutes of Health's National Cancer Institute (NIH-NCI, Stever Rosenberg Lab, Surgery Branch)). Prof. Eggermont has served as President of ECCO, President of the EORTC, was a member of the Board of Directors of ASCO, served on the Editorial Board of the Journal of Clinical Oncology, and is currently Editor-in-Chief of the European Journal of Cancer. Prof. Eggermont has published more than 1000 peer-reviewed papers and his expertise has been acknowledged by many professional awards throughout his career. About BioInvent BioInvent International AB (Nasdaq Stockholm:BINV) is a clinical-stage biotech company that discovers and develops novel and first-in-class immuno-modulatory antibodies for cancer therapy, with currently five drug candidates in six ongoing clinical programs in Phase 1/2 trials for the treatment of hematological cancer and solid tumors. The Company's validated, proprietary F.I.R.S.T™ technology platform identifies both targets and the antibodies that bind to them, generating many promising new immune-modulatory candidates to fuel the Company's own clinical development pipeline and providing licensing and partnering opportunities. The Company generates revenues from research collaborations and license agreements with multiple top-tier pharmaceutical companies, as well as from producing antibodies for third parties in the Company's fully integrated manufacturing unit. More information is available at . Follow on the social media platform X: @BioInvent. BioInvent International AB (publ) Co. Reg. No. Org nr: 556537-7263 Visiting address: Ideongatan 1 Mailing address: 223 70 LUND Phone: +46 (0)46 286 85 50 Attachments BioInvent to Host Virtual KOL Event to highlight recently presented efficacy data from BioInvent's lead candidates BI-1808 and BI-1206 SOURCE: BioInvent International View the original press release on accesswire.com

ImmunotherapyClinical StudyExecutive Change

24 May 2024

·www.biospace.com

BioInvent to Host Virtual KOL Event on June 18, 2024, to Discuss BioInvent's Lead Candidates BI-1808 and BI-1206

LUND, SWEDEN / ACCESSWIRE / May 24, 2024 / BioInvent International (STO:BINV) TNFR2 and FcyRIIB are promising targets in immuno-oncology. BioInvent International AB ("BioInvent") (Nasdaq Stockholm:BINV), a biotech company focused on the discovery and development of novel and first-in-class immune-modulatory antibodies for cancer immunotherapy, today announced that it will host a virtual KOL event on Tuesday, June 18, 2024 from 9:00-10:45 AM ET/3-4:45 PM CEST to discuss the recently presented clinical efficacy and safety data from its lead candidates BI-1808 and BI-1206, and TNFR2 and FcyRIIB as promising targets in immuno-oncology. To register, click here. Further details on the event to be announced. About BioInvent BioInvent International AB (Nasdaq Stockholm: BINV) is a clinical-stage biotech company that discovers and develops novel and first-in-class immuno-modulatory antibodies for cancer therapy, with currently five drug candidates in six ongoing clinical programs in Phase 1/2 trials for the treatment of hematological cancer and solid tumors. The Company's validated, proprietary F.I.R.S.T™ technology platform identifies both targets and the antibodies that bind to them, generating many promising new immune-modulatory candidates to fuel the Company's own clinical development pipeline and providing licensing and partnering opportunities. The Company generates revenues from research collaborations and license agreements with multiple top-tier pharmaceutical companies, as well as from producing antibodies for third parties in the Company's fully integrated manufacturing unit. More information is available at . Follow on the social media platform X: @BioInvent. Attachments BioInvent to Host Virtual KOL Event on June 18, 2024, to discuss BioInvent's lead candidates BI-1808 and BI-1206 SOURCE: BioInvent International View the original press release on accesswire.com

ImmunotherapyClinical Study

100 Deals associated with BI-1206

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Non-Hodgkin Lymphoma	Phase 2	GB	CASI (China) Pharmaceuticals Technology Co., Ltd.	30 Jan 2022
Advanced Malignant Solid Neoplasm	Phase 2	US	BioInvent International AB	29 Jun 2020
Advanced Malignant Solid Neoplasm	Phase 2	US	Merck Sharp & Dohme Corp.	29 Jun 2020
Advanced Malignant Solid Neoplasm	Phase 2	SE	Merck Sharp & Dohme Corp.	29 Jun 2020
Advanced Malignant Solid Neoplasm	Phase 2	SE	BioInvent International AB	29 Jun 2020
Solid tumor	Phase 2	US	BioInvent International AB	29 Jun 2020
Solid tumor	Phase 2	SE	BioInvent International AB	29 Jun 2020
B-Cell Lymphoma	Phase 2	US	BioInvent International AB	16 May 2018
B-Cell Lymphoma	Phase 2	PL	BioInvent International AB	16 May 2018
B-Cell Lymphoma	Phase 2	ES	BioInvent International AB	16 May 2018

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04219254 (Phase 1/2a clinical trial of BI-1206, ASCO2024)	Phase 1/2	Advanced Malignant Solid Neoplasm CD32b (FcγRIIB)	15	BI-1206 IV	ourqsrbeit(pbeoicjylc) = The most frequent related adverse events were infusion-related reactions, thrombocytopenia and elevated liver enzymes. All were transient without any clinical consequences, and adequate pre-medication with corticosteroids or split dose administration reduced the risk and/or intensity of these events. cttycncogy (idhefkgpwo ) View more	Positive	24 May 2024
EHA2024 Manual	Phase 1/2	Indolent B-Cell Non-Hodgkin Lymphoma CD32B (FCGRIIB)	-	BI-1206 Irituximab	cdehriqtry(btwkmvcdft) = the most frequent related treatment-emergent adverse events after BI-1206 IV wasthrombocytopenia and elevated transaminases. Thrombocytopenia ≥G3 occurred in 4 out of 10 subjectswithout premedication and 6 out of 13 subjects with premedication. No associated bleeding occurred. Allevents were resolved with a median duration of 5 days. Elevated liver enzymes ≥G3 occurred in 4 out of 10subjects without premedication and 3 out of 13 subjects with premedication. Events were resolved with amedian duration of 4 days without any clinical complication. xbapmiacyy (dtbdxhygfh ) View more	Positive	14 May 2024
EHA2024 Manual	Phase 1/2	Indolent B-Cell Non-Hodgkin Lymphoma CD32B (FCGRIIB)	-	BI-1206 +rituximab (SC)		Positive	14 May 2024

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