The Antibody Society

the official website of the antibody society

An international non-profit supporting antibody-related research and development.

TEVIMBRA (tislelizumab-jsgr) granted first FDA approval for esophageal squamous cell carcinoma

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On March 13, 2024, the U.S. Food and Drug Administration (FDA) approved TEVIMBRA (tislelizumab-jsgr) as monotherapy for the treatment of adult patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) after prior systemic chemotherapy that did not include a PD-(L)1 inhibitor. TEVIMBRA, a humanized IgG4 antibody engineered with modifications that stabilize the hinge region and abrogate binding to Fc receptors, was approved as an orphan drug for this indication.

FDA’s approval is based on the Phase 3 RATIONALE 302 trial (NCT03430843), which met its primary endpoint in the intention-to-treat (ITT) population, with a median overall survival (OS) in the TEVIMBRA arm or 8.6 months (95% CI: 7.5, 10.4) compared to 6.3 months (95% CI: 5.3, 7.0) in the chemotherapy arm (p=0.0001; hazard ratio [HR]=0.70 [95% CI: 0.57, 0.85]). The results showed a statistically significant and clinically meaningful survival benefit for TEVIMBRA compared with chemotherapy and the safety profile of TEVIMBRA was favorable over chemotherapy.

In 2019, China’s National Medical Products Administration granted the first global approval of tislelizumab. In 2023, the product received approval by the European Commission for advanced or metastatic ESCC after prior chemotherapy, and it received a positive opinion by the Committee for Medicinal Products for Human Use of the European Medicines Agency in February 2024 as a treatment for non-small cell lung cancer across three indications.

Biologics license applications for tislelizumab as first-line treatment for patients with unresectable, recurrent, locally advanced, or metastatic ESCC and patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma are currently undergoing FDA review. The target action dates for these applications are in July and December 2024, respectively.

Details for all approved antibody therapeutics and those in regulatory review can be found in our searchable table.

Learn how to harness the power of ADCs in our next webinar!

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Join us for our next webinar!

Antibody-drug conjugates (ADCs) have emerged as an important class of targeted therapeutics, combining the targeting specificity of antibodies with the potency of cytotoxic drugs. Recent advances in ADC research have led to improved stability, efficacy, and safety. There is a clear trend within Antibody therapeutics towards ADCs with the improvement of novel technologies to address a growing cancer population worldwide.

However, developing effective ADCs is expensive and poses unique informatics challenges. Researchers must integrate data across multiple modalities – from antibody discovery and engineering to small molecule payload development and optimization. Seamless collaboration between immunologists, protein engineers, chemists, and pharmacologists are essential.

The Signals™ Research Suite is the first integrated informatics platform purpose-built to accelerate multi-modal drug development like ADCs and is composed of a trio of scientific software applications:

  • Signals™ Notebook: The premier cloud-based electronic lab notebook that facilitates creation and communication about molecules of interest via hierarchical editing language for macromolecules (HELM), powered Chemdraw®.
  • Signals™ VitroVivo: For data analysis, visualization, and curve fitting bioassay results for standardized and consistent results, powered by Spotfire®.
  • Signals™ Inventa: Enabling multi-assay or multi-study comparison, powered by Spotfire, with the ability to find the best candidate to move forward, accelerating decision making. Researchers gain better visibility into ADC candidate profiling and can quickly determine structure-activity and structure-property relationships across modalities to select optimal conjugation sites and pairings.

Attendees will gain insights into the latest trends and challenges in ADC development, informed by recent research and advancements in the field. The presentation will also emphasize the importance of integrating various data types and sources in the ADC development process, showcasing how the Signals Research Suite facilitates this integration, thereby driving more efficient, safer drug development.

About the speaker:

Dr. Wisotsky attended the University of California, Santa Cruz with a focus on molecular and cellular biology. He obtained his Ph.D. at the University of California, Riverside for Neuroscience where he worked on taste detection from molecular mechanism to behavioral outcomes in fruit flies. Subsequently Zev joined startup companies with the focus to support scientists getting their science done more efficiently. He has worked within pre-sales teams to discover, consult, and deliver software solutions that meet customer needs both scientifically and technically. Today he is a Revvity Senior Principle Marketing Manager for Biologics in the Signals Suite.

Registration is open!

 

Don’t miss the February AIRR-C Seminar Series, covering antibody evolution and language model-based embeddings

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February 2024 Seminar Banner

Registration for the February 22nd (4:00 PM – 5:30 PM CET) AIRR-C Seminar Series session is open. Following the usual format of the series, an established and an early career scientist will discuss their AIRR-seq related research. Brian Hie, of Stanford University, will present “Learning to read and write antibody evolution”. Next, Mamie Wang, of Yale University, will present “Language model-based B cell receptor sequence embeddings can effectively encode receptor specificity”. Register now!

Visit the AIRR Community Seminar Series website to learn more about this monthly series and access the recordings of past sessions.

Call for papers – Deadline for inquiry submissions is April 1!

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The Antibody Society’s latest analysis of the current early-stage clinical pipeline of antibody therapeutics shows that the biopharmaceutical industry is engaging in innovative research and development. For both cancer and non-cancer indications, ~60% of the antibody therapeutics in early-stage clinical development target novel antigens, and a growing portion of those against well-validated targets have been designed in novel formats (e.g., bispecifics, bispecific biparatopics, antibody-drug conjugates (ADCs), Fc engineered, hybrid isotype, immunoconjugates).

For mAbs’ next Collection, we invite The Antibody Society members, mAbs readers, and the broader scientific community to contribute review articles focused on innovative approaches for antibody therapeutic discovery. The reviews should narrate the state of the art on innovative formats, targets, or platforms for antibody therapeutic discovery, and speculate on new vistas for the field.

mAbs will waive publication charges for up to 8 of the best review articles selected from pre-submission inquiries, which should include the proposed authors, title, abstract, and general outline of the intended review article.

The deadline for pre-submission inquiries is April 1, 2024.
Authors will be notified of the Editors’ decision by April 15, 2024.
The deadline for submission of the completed review articles is December 15, 2024.

We are particularly interested in reviews on the following topics:

  • Novel platforms for antibody therapeutic discovery (e.g., novel target/epitope selection, novel approaches for enhancing or reducing Fc effector function, novel methods for enhancing antibody therapeutics half-life).
  • Novel targets or formats for cancer immunotherapy (i.e., novel antigens and formats for targeting tumors, immune cells, and the tumor microenvironment), design strategies for novel approaches in cancer immunotherapy.
  • Novel targets or formats beyond oncology (e.g., autoimmune diseases, cardiovascular/hemostasis, neurology, infectious disease, ophthalmology, rare diseases).
  • Novel immune-modulating antibodies (i.e., novel immune checkpoints and immune agonists), relevant design strategies, formats, applications and considerations for safety and tolerability in multiple disease areas.
  • Innovative format combinations (e.g., Bispecific/Multispecific ADCs, Bispecific/Multispecific checkpoint inhibitors), design strategies for these molecules and considerations for safety.
  • Novel formats for well-validated targets, relevant design strategies and considerations for efficacy, biodistribution and safety.

Although these topics are especially of interest, we welcome well-written reviews in related areas as well.

Please send pre-submission inquiries that include the authors, title, abstract, and general outline of the intended review article to Editor-in-Chief Dr. Janice Reichert (reichert.biotechconsulting@gmail.com) and Guest Editors Drs. Silvia Crescioli (silvia.crescioli@antibodysociety.org) and Kristina Ilieva-Babinsky (k.m.ilieva@gmail.com), and Prof. Jamie Spangler (jamie.spangler@jhu.edu). Please feel free to contact us if you have any questions.

Examples of other mAbs Collections can be found here.

Crovalimab approved in China

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On February 8, 2024, Chugai Pharmaceutical Co., Ltd. announced that crovalimab (Chinese product name : 派圣凯®) was approved in the People’s Republic of China for treatment of adults and adolescents with paroxysmal nocturnal hemoglobinuria (PNH) not been previously treated with complement inhibitors. The regulatory application was filed by a China affiliate of F. Hoffmann-La Roche Ltd. because Roche is responsible for the development of crovalimab outside Japan and Taiwan. China is the first country in the world to approve crovalimab. Marketing applications for crovalimab have been submitted to regulatory agencies in the US, EU, and Japan.

Crovalimab (SKY59, RG6107, RO7112689) is a complement C5 inhibiting, humanized IgG1k antibody without effector functions that was engineered (M428L/N434A) to have enhanced affinity to FcRn at an acidic pH to extend its plasma half-life. Based on Chugai’s Recycling Antibody® technology, crovalimab is engineered to bind its antigen repeatedly, enabling sustained complement inhibition at a low dose administered subcutaneously (SC) every 4 weeks. Moreover, crovalimab binds a different epitope of C5 compared to existing antibody drugs, suggesting that it represents an alternative option for patients with PNH with a specific C5 gene mutation.

Crovalimab was granted Breakthrough Therapy for PNH by NMPA and the marketing application for crovalimab, which included data from the China-specific Phase 3 COMMODORE 3 study (NCT04654468), was accepted by NMPA under Priority Review.

COMMODORE 3 was a multicenter single-arm trial studying crovalimab in C5 inhibitor-naive patients with PNH in China. Patients (n=51) received crovalimab according to a weight-based dosing schedule, including loading (intravenous (IV) dose on Days 1 and 4, weekly SC doses starting from Day 2) and SC maintenance doses (every 4 weeks starting from Week 5); treatment continued after 24 weeks in patients with clinical benefit. The co-primary efficacy endpoints of hemolysis control and transfusion avoidance (TA) were met. The mean proportion of participants with hemolysis control from Week 5 through to Week 25 was 78.7% (95% CI: 67.8%, 86.6%).1 The difference between the proportion of participants with TA within 24 weeks prior to screening (0.0%) and the proportion of participants with TA from baseline through to Week 25 (51.0%) was statistically significant (p<0.0001). [1]

The global Phase 3 COMMODORE 1 (NCT04432584) and 2 (NCT04434092) studies assessed the efficacy and safety of crovalimab versus eculizumab in participants with PNH that are C5 inhibitor-experienced patients or not previously treated with complement inhibitors, respectively. COMMODORE 1 assessed safety, pharmacokinetics, pharmacodynamics, and exploratory efficacy of crovalimab. Data from the study support the favorable benefit–risk profile of crovalimab, including allowing for SC administration with the option to self-administer. [2] Data from the COMMODORE 2 study presented at European Hematology Association meeting in June 2023 in Frankfurt, Germany demonstrated that SC crovalimab Q4W was non-inferior in disease control to IV eculizumab Q2W with comparable safety for patients who have not been treated with C5 inhibitors. [3]

  1. Liu H, Xia L, Weng J, Zhang F, He C, Gao S, Jia J, Chang AC, Lundberg P, Camelia S. Sima CS, et al. Results from the first Phase 3 crovalimab (c5-inhibitor) study (commodore 3): efficacy and safety in complement inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria (PNH). Presentation at: ASH Annual Meeting and Exposition; New Orleans, 2022 Dec 10-13; Abstract #293. doi.org/10.1182/blood-2022-162452.
  2. Scheinberg P, Cle D, Edwards J, Giai V, Hus M, Kim JS, Barrenetxea Lekue C, Nagy Z, Nur E, Panse J, et al. Phase III randomized, multicenter, open-label COMMODORE 1 trial: comparison of crovalimab vs eculizumab in complement inhibitor-experienced patients with paroxysmal nocturnal hemoglobinuria (PNH). Hemasphere. 2023; 7(Suppl ): e45540d8. 2023 Aug 8. doi: 10.1097/01.HS9.0000967644.45540.d8
  3. Röth A, He G, Brodsky A, Chai-Adisaksopha CC, Dumagay T, Demichelis R, Höglund M, Kelly R, Lee J-H, Nishimura J-I, et al. The PHASE III, randomized COMMODORE 2 trial: results from a multicenter study of crovalimab vs eculizumab in paroxysmal nocturnal hemoglobinuria (PNH) patients naive to complement inhibitors. Hemasphere. 2023; 7(Suppl ): e72750f1.