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Call for Papers: Collection on Bispecific and Multispecific Antibodies

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Antibodies and antibody-derived bispecifics are one of the most successful therapeutic classes due to their excellent target specificity and tunable drug-like properties. The ability to tailor antibody functions using modern engineering approaches has ushered in a new wave of bi- and multi-specific antibody therapeutics that unlock novel target classes, biology, and mechanisms of action for the treatment of human diseases. In this collection of reviews, we invite The Antibody Society members, mAbs readers, and the broader scientific community to contribute review articles focused on bispecific and multispecific antibody-based molecules. The reviews should narrate the current state of the art in bi- and multi-specific antibody therapeutics, challenges and opportunities, 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 authors, title, abstract, and general outline of the intended review article.

The deadline for pre-submission enquiries is January 31, 2023.

We are particularly interested in reviews in the following topics:

•         Overview of bispecific and multispecific antibody platforms (includes but not limited to Fc engineering, heavy and light chain pairing methodologies, high throughput production methods, geometrical and valency considerations etc.).

•         Reviews on multispecific antibodies (beyond bispecifics i.e., more than two binding epitopes) and their applications.

•         Reviews on bispecifics and multispecific antibodies beyond oncology (i.e., neurology, infectious disease, ophthalmology, rare diseases etc.).

•         Reviews on various cell engagers (T cells, NK cells, macrophages etc.), overview of their design strategies, formats, applications and considerations for safety and tolerability in multiple disease areas.

•         Bispecific/Biparatopic and multispecific/multiparatopic targeting beyond antibodies (Antibody drug conjugates, antibody cytokine fusions, CAR-T/NK/M therapies, ProTACs etc) in various therapeutic areas.

•         Clinical development experience with bispecific and multispecific molecules with a focus on any or all of these areas: safety and tolerability, immunogenicity, biomarkers and/or bioanalytical assay development.

•         Reviews on tissue targeting via bispecific and multispecific antibodies, important considerations for safety, tolerability and preclinical and clinical development.

•         Focused review on developability of bispecific and multispecific molecules, CMC and manufacturing considerations. Bispecifics design and challenges in cell line development, upstream and downstream process development, analytical method development, product quality control strategy, process design and scale up, material demand and commercial manufacturing, regulatory guidance, etc.

Although these topics are especially of interest, we welcome well-written reviews in related areas as well. We intend to waive publication charges for up to 8 of the best review articles selected from pre-submission inquiries, which should consist of the title, abstract and general outline of the intended review article.

The deadline for submission of the completed review articles is August 15, 2023.

Please send pre-submission inquiries to Editor-in-Chief Dr. Janice Reichert (reichert.biotechconsulting@gmail.com), and Assistant Editors Drs. Nimish Gera (ngera@mythictx.com), Li Zhou (li.zhou@abbvie.com) and Jonathan Sockolosky (jonathan@curie.bio). Please feel free to contact us if you have any questions.

For examples of other mAbs Collections, please visit the journal website.

FDA approves teclistamab (Tecvayli) for relapsed or refractory multiple myeloma

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On October 25, 2022, the Food and Drug Administration granted accelerated approval to teclistamab-cqyv (Tecvayli, Janssen Biotech, Inc.) for adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. Teclistamab (TECVAYLI) is a T-cell redirecting IgG4λ bispecific antibody recognizing BCMA on target cells and CD3e on T cells. Generated from Ligand’s transgenic mouse (OmniAb) and Genmab’s DuoBody technology, the Fc was engineered with the stabilizing S228P mutation and L234A/L235A mutations to minimize its effector functions. Teclistamab was granted Orphan Drug designations for the treatment of MM in both the US and EU, and received the Breakthrough Therapy designation for the treatment of relapsed or refractory MM (RRMM) by the FDA, and a PRIority MEdicines (PRIME) designation by the EMA for treatment of adult patients with RRMM who previously received ≥3 prior lines of therapy. TECVAYLI (teclistamab) was granted conditional marketing authorization in the EU as monotherapy for the treatment of adult RRMM patients who previously received ≥3 prior lines of therapy in August 2022.

The authorizations for marketing were based on the results from the multicohort, open-label, Phase 1 and Phase 2 MajesTEC-1 studies (NCT03145181, NCT04557098, respectively), evaluating the safety and efficacy of teclistamab in adults with RRMM. The ongoing first-in-human dose escalation and dose expansion clinical study (NCT03145181) is assessing the efficacy of teclistamab in patients with RRMM, with the antibody administered IV (range: 0.3−19.2 μg/kg [once every 2 weeks] or 19.2−720 μg/kg [once per week]) or subcutaneously (range: 80−3000 μg/kg [once per week]) in different cohorts, with step-up dosing for 38.4 μg/kg or higher doses. Based on the dose escalation data, in the Phase 2 portion of the study patients received a weekly subcutaneous dose of teclistamab (1.5 mg/kg), after receiving step-up doses of 0.06 mg/kg and 0.3 mg/kg. Results of the MajesTEC-1 study showed that teclistamab induced durable responses that deepened over time in patients with triple-class exposed RRMM (n=165), with an overall response rate of 63%, including a complete response in 39.4% of the patients. The median duration of response and duration of progression-free survival were 18.4 months (95% confidence interval [CI], 14.9 to not estimable) and 11.3 months (95% CI, 8.8 to 17.1), respectively. Adverse events were consistent with this patient population and toxicities consistent with T-cell redirection were mostly Grade 1/2.

Interested in more information about approved antibody therapeutics? Explore our searchable table of antibody therapeutic products for details.

Tremelimumab combination with Imfinzi (durvalumab) approved by FDA for liver cancer

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On October 24, 2022, AstraZeneca announced that Imjudo (tremelimumab) in combination with Imfinzi (durvalumab) has been approved in the US for the treatment of adult patients with unresectable hepatocellular carcinoma (HCC), the most common type of liver cancer. Tremelimumab (CP-675,206), originally developed by Pfizer using Abgenix’s XenoMouseÔ technology, is a human IgG2ҡ antibody targeting CTLA-4. In 2011, MedImmune (now AstraZeneca) gained tremelimumab’s global development rights, while Pfizer retained the rights for use in certain combination therapies. Tremelimumab blocks the activity of the immune checkpoint CTLA-4, contributing to T-cell activation, fostering antitumor immune responses and cancer cell death. Tremelimumab and anti-PD-L1 durvalumab (Imfinzi) were granted Orphan Drug designation in the US for the treatment of hepatocellular carcinoma (HCC), and tremelimumab was also granted Orphan Drug designation for HCC in the EU. On October 24, 2022[JR1] , FDA approved the combination of tremelimumab with Imfinzi for unresectable advanced liver cancer based on the results of the Phase 3 HIMALAYA trial. Marketing applications for this combination for liver cancer is under review by regulatory authorities in other countries and regions. Moreover, based on the results of the POSEIDON trial, marketing applications for the combination of tremelimumab with Imfinzi and chemotherapy for first-line metastatic NSCLC are also under review.

HIMALAYA (NCT03298451) is a randomized, open-label, global Phase 3 trial evaluating the safety and efficacy of durvalumab monotherapy and the combination of durvalumab and tremelimumab versus sorafenib, a standard-of-care multi-kinase inhibitor, as first-line treatment in patients with unresectable HCC who had not received prior systemic therapy and were not eligible for localized treatment. The combination of durvalumab and tremelimumab, called the STRIDE regimen (Single Tremelimumab Regular Interval Durvalumab), comprises a single priming dose of 300 mg of tremelimumab added to 1500 mg of durvalumab followed by durvalumab every four weeks.[1] Patients were randomized to STRIDE (n=393), durvalumab (n=389), or sorafenib (n=389). The primary outcome measure was overall survival. Results of the HIMALAYA trial were presented at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium held January 20-22, 2022 in San Francisco. At data cutoff, the primary objective was met: OS was significantly improved for STRIDE vs sorafenib (hazard ratio [HR], 0.78; 96% confidence interval [CI], 0.65–0.92; p=0.0035. 3). In addition, the ORRs were higher for STRIDE and durvalumab (20.1% and 17.0%, respectively) than for sorafenib (5.1%).

Interested in more information about approved antibody therapeutics? Explore our searchable table of antibody therapeutic products for details.

Tezspire (tezepelumab) approved in the European Union for severe asthma

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On September 19, 2022, the European Commission (EC) approved AstraZeneca’s Tezspire (tezepelumab) as an add-on maintenance treatment in patients 12 years and older with severe asthma who are inadequately controlled with high dose inhaled corticosteroids plus another medicinal product in the European Union.

The EC’s approval was based on results from the PATHFINDER clinical trial program, which included the placebo-controlled NAVIGATOR Phase 3 trial (NCT03347279), which evaluated the effects of tezepelumab in adults and adolescents with severe uncontrolled asthma. In this study, patients received tezepelumab (210 mg; n=529) or placebo (n=532) SC every 4 weeks for 52 weeks. Tezspire demonstrated superiority across every primary and key secondary endpoint in patients with severe asthma, compared to placebo, when added to standard therapy in this study. For the tezepelumab group, the annualized rate of asthma exacerbations was 0.93 (95% CI, 0.80 to 1.07), while the rate was 2.10 (95% CI, 1.84 to 2.39) with placebo (rate ratio, 0.44; 95% CI, 0.37 to 0.53; P<0.001). Overall, data from the study indicated that, compared to those administered placebo, patients who received tezepelumab had fewer exacerbations and better lung function, asthma control, and health-related quality of life. Full results of the NAVIGATOR trial were published in The New England Journal of Medicine in May 2021.

Tezspire has been approved in the US and other countries for the treatment of severe asthma.

Interested in more information about approved antibody therapeutics? Explore our searchable table of antibody therapeutic products for details.

Vabysmo™ (faricimab) approved in the European Union for ophthalmic disorders

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On September 15, 2022, the European Commission approved Vabysmo ™ (faricimab) for the treatment of wet, or neovascular, age-related macular degeneration (AMD) and visual impairment due to diabetic macular edema (DME). Faricimab (RO6867461, RG7716) is an anti-vascular endothelial growth factor-A (VEGF-A) and anti-angiopoietin-2 (Ang-2) bispecific antibody derived from Roche’s CrossMab technology.

The approval in the European Union was based in part on results from four Phase 3 studies in wet AMD and DME. The TENAYA (NCT03823287) and LUCERNE (NCT03823300) studies evaluated the effects of faricimab (6.0 mg administered at fixed intervals of every two, three, or four months) and aflibercept (Eylea®) (2.0 mg administered at fixed two-month intervals) in wet AMD patients. The YOSEMITE (NCT03622580) and RHINE studies (NCT03622593) compared the effects of faricimab (6.0 mg administered at personalized treatment intervals (PTI) of up to four months or 6.0 mg administered at fixed two-month intervals) to those of aflibercept (2.0 mg administered at fixed two-month intervals) in DME patients. Results of the TENAYA and LUCERNE and YOSEMITE and RHINE studies were published in The Lancet.

Interested in more information? Explore our searchable table of antibody therapeutics approved in the EU or US for details.