The Antibody Society

More on ADCs... Thanks for sharing, Dr Mridul Das!

In a paper recently published in mAbs, MIT / Ragon Institute of Mass General Brigham, MIT, and Harvard-based authors reveal how combinatorial Fc modifications affect complementary antibody functionality. From the abstract: Therapeutic monoclonal antibodies (mAbs) can be functionally enhanced via Fc engineering. To determine whether pairs of mAbs with different Fc modifications can be combined for functional complementarity, we investigated the in vitro activity of two HIV-1 mAb libraries, each equipped with 60 engineered Fc variants. Our findings demonstrate that the impact of Fc engineering on Fc functionality is dependent on the specific Fab clone. Notably, combinations of Fc variants of the same Fab specificity exhibited limited enhancement in functional breadth compared to combinations involving two distinct Fabs. This suggests that the strategic selection of complementary Fc modifications can enhance both functional activity and breadth. Furthermore, while some combinations of Fc variants displayed additive functional effects, others were detrimental, suggesting that the functional outcome of Fc mutations is not easily predicted. Collectively, these results provide preliminary evidence supporting the potential of complementary Fc modifications in mAb combinations. Future studies will be essential to identify the optimal Fc modifications that maximize in vivo efficacy. #mabs https://lnkd.in/eCw3YM-f

Congratulations, Innovent Biologics!

In a paper newly published in mAbs, GSK-based authors review techniques for quantifying antibody binding and discuss the therapeutic implications. From the abstract: The binding kinetics of an antibody for its target antigen represent key determinants of its biological function and success as a novel biotherapeutic. Defining these interactions and kinetics is critical for understanding the pharmacological and pharmacodynamic profiles of antibodies in therapeutic applications, with line of sight to clinical translation. In this review, we discuss the latest developments in approaches to measure and modulate antibody-antigen interactions, including antibody engineering, novel antibody formats, current, and emerging technologies for measuring antibody-antigen binding interactions, and emerging perspectives within the field. We also explore how emerging computational methods are set to become powerful tools for modeling antibody-binding interactions under physiologically relevant conditions. Finally, we consider the therapeutic implications of modulating target engagement in terms of pharmacodynamics and pharmacokinetics. #mabs https://lnkd.in/eVAeub5b

Nice! Thanks for sharing, Diagonal Therapeutics.

In business news, Bambusa Therapeutics, Inc. announced the successful completion of its oversubscribed Series A financing of approximately $90 million. The round was led by new investor RA Capital Management, with participation from new investors including Janus Henderson Investors, Redmile Group, Invus, and ADAR1 Capital Management. All existing investors also participated. The funding will support the advancement of Bambusa's lead programs through Phase I trials and drive further pipeline development. Since its founding in May 2024, Bambusa has built a robust pipeline of long-acting bispecific antibodies, leveraging validated targets and biological synergy to create best-in-disease therapies for I&I indications. Two of Bambusa's four programs are on track to enter the clinic in Q1 2025 and mid-2025, respectively. BBT001, Bambusa's lead candidate, is a bispecific antibody incorporating a number of features intended to supplant the current standard of care for a range of dermatological conditions. BBT002 is a bispecific antibody created as a "platform in a molecule" with applications across respiratory, dermatology, and gastroenterology indications. Bambusa's additional development candidates, BBT003 and BB004, also have best-in-disease potential in the inflammatory bowel diseases and rheumatological indications. #mabs https://lnkd.in/eBsf5MZr

Congratulations to Lundbeck! The company announced that the US Food and Drug Administration has granted Fast Track Designation to Lundbeck’s investigational drug, amlenetug (Lu AF82422), a potential new treatment option targeting Multiple System Atrophy (MSA). Lundbeck has recently initiated MASCOT, a phase III trial to assess efficacy and safety of amlenetug for the treatment of MSA. Amlenetug is a human IgG1 monoclonal antibody that recognizes all major species of alpha-synuclein. #mabs https://lnkd.in/dtdWc_BR

Thanks for the follow up and summary of the story, Ian Wilkinson! While AI and ML have great potential and tremendous progress has been made in the past 5 years (and we look forward to advances in the use of these technologies in the future), challenges WRT claims about de novo discovery and transparency are not new. For a viewpoint circa 2019, see the Perspective article "De novo discovery of antibody drugs – great promise demands scrutiny". From the abstract: We live in an era of rapidly advancing computing capacity and algorithmic sophistication. “Big data” and “artificial intelligence” find progressively wider use in all spheres of human activity, including healthcare. A diverse array of computational technologies is being applied with increasing frequency to antibody drug research and development (R&D). Their successful applications are met with great interest due to the potential for accelerating and streamlining the antibody R&D process. While this excitement is very likely justified in the long term, it is less likely that the transition from the first use to routine practice will escape challenges that other new technologies had experienced before they began to blossom. This transition typically requires many cycles of iterative learning that rely on the deconstruction of the technology to understand its pitfalls and define vectors for optimization. https://lnkd.in/e5qmzaYe

Congratulations to CSL! The company announced that the European Commission has approved ANDEMBRY® (garadacimab), the first and only once-monthly treatment targeting factor XIIa to prevent attacks of hereditary angioedema in adult and adolescent patients aged 12 years and older. ANDEMBRY inhibits plasma protein factor XIIa, which initiates the cascade of events leading to angioedema at various sites of the body. ANDEMBRY comes with a convenient patient-centric pre-filled pen (auto-injector) enabling subcutaneous self-injection. ANDEMBRY was approved by the Australian Therapeutic Goods Administration on January 14, 2025, the United Kingdom's Medicines and Healthcare products Regulatory Agency on January 24, 2025. #mabs https://lnkd.in/eUgfrP6q