The Antibody Society

Join us on Tuesday Feb 4th to learn which antibodies to watch in 2025! Drs. Silvia Crescioli and Janice Reichert will briefly review approvals from 2024 and product candidates with recent marketing applications under consideration, providing insight into the factors influencing the emerging trends in this field, before exploring the investigational antibody therapeutics forecast to enter regulatory review by the end of 2025. These product candidates include numerous innovative bispecific antibodies and antibody-drug conjugates. They also discuss clinical phase transition and overall approval success rates for antibody therapeutics, which are crucial to the biopharmaceutical industry. Registration is open: https://hubs.ly/Q033Ty2f0

In a paper newly published in mAbs, Ichnos Glenmark Innovation-based authors report results showing that biparatopic binding of ISB 1442 to CD38 in trans enables increased cell antibody density and increased avidity. From the abstract: ISB 1442 is a bispecific biparatopic antibody in clinical development to treat hematological malignancies. It consists of two adjacent anti-CD38 arms targeting non-overlapping epitopes that preferentially drive binding to tumor cells and a low-affinity anti-CD47 arm to enable avidity-induced blocking of proximal CD47 receptors.  Here, we describe the discovery, optimization and characterization of the ISB 1442 antigen binding fragment (Fab) arms, their assembly to 2 + 1 format, and present the high-resolution co-crystal structures of the two anti-CD38 Fabs, in complex with CD38. This, with biophysical and functional assays, elucidated the underlying mechanism of action of ISB 1442. In solution phase, ISB 1442 forms a 2:2 complex with CD38 as determined by size-exclusion chromatography with multi-angle light scattering and electron microscopy. The predicted antibody-antigen stoichiometries at different CD38 surface densities were experimentally validated by surface plasmon resonance and cell binding assays. The specific design and structural features of ISB 1442 enable: 1) enhanced trans binding to adjacent CD38 molecules to increase Fc density at the cancer cell surface; 2) prevention of avid cis binding to monomeric CD38 to minimize blockade by soluble shed CD38; and 3) greater binding avidity, with a slower off-rate at high CD38 density, for increased specificity. The superior CD38 targeting of ISB 1442, at both high and low receptor densities, by its biparatopic design, will enhance proximal CD47 blockade and thus counteract a major tumor escape mechanism in multiple myeloma patients. #mabs https://lnkd.in/e2SheMkg

Insightful new article reports R&D success rates of leading pharmaceutical companies: an empirical analysis of FDA approvals (2006–2022). Highlights of the article are: We analyzed the likelihood of first approval for 2,092 compounds and 19,927 clinical trials conducted by 18 leading pharma companies (2006-2022). Our study reveals an average LoA rate of 14.3% (median 13.8%). LoA rates differ across the leading 18 pharmaceutical companies, broadly ranging from 8% to 23%. https://lnkd.in/e-vKpcqx

In clinical trials news, Tubulis GmbH announced that its second drug candidate, TUB-030, has entered clinical evaluation with successful dosing of the first patient in the 5-STAR 1-01 Phase I/IIa trial (NCT06657222). The study is evaluating TUB-030, Tubulis’ next-generation antibody-drug conjugate (ADC), in patients with advanced solid tumors. The ADC targets 5T4, an oncofetal antigen expressed in a broad range of solid tumors. The program was developed using Tubulis’ proprietary Tubutecan linker-payload platform, which enables superior biophysical properties for precise and sustained on-tumor payload delivery. #mabs https://lnkd.in/deMnGWb7

Adcendo ApS has posted details for a first-in-human, Phase 1/2 study (NCT06797999) to evaluate ADCE-D01 in patients with metastatic and/or unresectable soft tissue sarcoma. ADCE-D01 is an antibody-drug conjugate composed of a humanized anti-human UPARAP antibody linked to a topoisomerase I inhibitor. The study will enroll an estimated 270 patients and has an estimated start date in Feb 2025. #mabs https://lnkd.in/eemAYtqk

Congratulations, Scholar Rock! The company announced the submission of a Biologics License Application to the U.S. Food and Drug Administration for apitegromab, a muscle-targeted therapy designed and developed to provide clinically meaningful improvement in motor function for people living with SMA who are receiving SMN-targeted treatments. Apitegromab is an investigational human monoclonal antibody inhibiting myostatin activation by selectively binding the pro- and latent forms of myostatin in the skeletal muscle. The FDA has granted apitegromab Fast Track, Orphan Drug and Rare Pediatric Disease Designations in SMA The company remains on track to file a Marketing Authorisation Application to the European Medicines Agency in 1Q 2025. #mabs https://lnkd.in/ervVE2XD

In additional news regarding anti-IL-5 depemokimab, GSK plc announced that the European Medicines Agency has accepted for review the Marketing Authorisation Application for the use of depemokimab in two indications. The submitted indications are for add-on maintenance treatment of asthma in adult and adolescent patients aged 12 years and older with type 2 inflammation characterised by an eosinophilic phenotype who are inadequately controlled on medium to high dose corticosteroids plus another asthma controller and also as an add-on treatment in adult patients with inadequately controlled chronic rhinosinusitis with nasal polyps. #mabs https://lnkd.in/eFaquEnJ

In regulatory affairs news, GSK announced that new drug applications have been accepted for review by the China National Medical Products Administration and submitted to the Japanese Ministry of Health, Labour and Welfare for use of depemokimab in two indications. Depemokimab (GSK3511294) is a humanized monoclonal IgG1k antibody targeting interleukin-5. YTE mutations in the Fc provide extended half-life and allow twice-yearly dosing. In China, the submitted indications are for an add-on maintenance treatment of asthma in adult and adolescent patients aged 12 and older with type 2 inflammation characterised by blood eosinophil count, and add-on maintenance treatment of adult patients with inadequately controlled CRSwNP. In Japan, the submitted indications are for treatment of severe or refractory bronchial asthma and CRSwNP inadequately controlled with standard treatment. #mabs https://lnkd.in/eFNhXh_Q

In business news, Helicore Biopharma Inc., a biopharmaceutical company focused on the discovery and development of first-in-class glucose-dependent insulinotropic peptide (GIP) antagonists for obesity and related conditions, announced today its emergence from stealth mode with $65 million in Series A financing. The round was co-led by founding investor Versant Ventures and by OrbiMed, with participation from Longitude Capital and Wellington Management. Helicore’s most advanced asset, HCR-188, is a clinical stage monoclonal antibody designed to bind GIP. The company’s portfolio includes GIP antibody conjugates, including GLP-1 and other combinations, designed to address specific obesity subpopulations. #mabs https://lnkd.in/eUD4PWe5

We’re pleased to share that The Antibody Society has partnered with hubXchange as a media partner! Through this collaboration, members of The Antibody Society will receive complimentary passes to join HubXchange’s expertly curated Antibody Therapeutics Xchange events in 2025. These one-day events feature highly interactive, limited-capacity roundtables, 1:1 meetings, and fantastic networking opportunities for senior scientists and executives. Upcoming HubXchange Antibody Therapeutics Events in 2025 📍 San Diego – February 19, 2025 📍 Philadelphia – April 14, 2025 📍 Boston – June 23, 2025 📍 San Francisco – September 22, 2025 📍 Europe – November 24, 2025 If you’re a member of The Antibody Society, log in to the “Members Only” section and click on “Member Discount Codes” to access the link for your complimentary pass. https://lnkd.in/e6wEmZiW If you would like to attend the upcoming event in San Diego on February 19, 2025, registration is now open! Use this link to secure your spot: https://lnkd.in/eWeV_ZuK