SYD1875 / Byondis - LARVOL DELTA

A framework for evaluating unexpected reactions in antibody-drug conjugates during clinical development: a case study of a promiscuous payload. (PubMed, MAbs) - "The strategy is illustrated by a real-world example of an ADC in clinical development, SYD1875, exhibiting an unexpected decrease in biological activity following 3 months of storage at the stressed condition...Subsequent bioanalytical and pharmacokinetic investigations demonstrated that, although the cross-link is also formed in vivo, its overall impact on systemic exposure was limited. The generalizable framework described in this report aims at facilitating the evaluation of anomalies in the product quality of an ADC and subsequent (clinical) risk assessment, thereby supporting decision making."

Journal

Understanding the Chemical Characteristics of Payloads and the Expression of Tumor-Associated Antigens of ADCs in Clinical Development. (PubMed, ACS Omega) - "Regarding the conjugation type, only trastuzumab deruxtecan, labetuzumab govitecan, sacituzumab govitecan, BYON3521, and SYD1875 used homogeneous conjugation. An interesting observation was that for some ADCs, TAA expression was higher in normal tissue than in the tumor. In summary, our analysis highlights that only a limited number of ADCs incorporate payloads with favorable physicochemical properties and that several ADCs currently under development target TAAs with higher expression in normal tissues than in the corresponding tumors."

Journal • Review • Oncology • EGFR • FOLR1 • HER-2

Phase I dose escalation trial to evaluate safety and preliminary efficacy of ACR246, an innovative 5T4- antibody drug conjugate (ADC), in patients (pts) with advanced solid tumors (ESMO 2024) - P1 | "Previously, several 5T4-ADCs were developed and advanced to phase 1 clinical trials, including PF-06263507, ASN004 and SYD1875. Dose limiting toxicity (DLT) will be assessed at each dose level. The DLT evaluation period will be 21 days."

Clinical • Metastases • P1 data • Oncology • Solid Tumor • TPBG

[VIRTUAL] Introduction to the preclinical profile of SYD1875, a novel site-specifically conjugated duocarmycin-based 5T4-targeting antibody-drug conjugate (AACR 2021) - P1 | "SYD1875 showed superior in vitro cytotoxicity and in vivo activity compared to A1-mcMMAF -also known as PF-6263507-, a 5T4-targeting ADC that is no longer in clinical development. The GLP toxicity study in cynomolgus monkey showed an acceptable toxicity and PK profile. A first-in-human dose-finding trial was initiated to evaluate safety and explore efficacy (NCT04202705)."

Preclinical • Oncology • TPBG

A First-in-human Dose-escalation and Expansion Study With the Antibody-drug Conjugate SYD1875 (clinicaltrials.gov) - P1 | N=31 | Completed | Sponsor: Byondis B.V. | Active, not recruiting ➔ Completed

Metastases • Trial completion • Oncology • Solid Tumor

A First-in-human Dose-escalation and Expansion Study With the Antibody-drug Conjugate SYD1875 (clinicaltrials.gov) - P1 | N=31 | Active, not recruiting | Sponsor: Byondis B.V. | Trial completion date: Jan 2024 ➔ Jan 2023 | Trial primary completion date: Jan 2023 ➔ Jun 2022

Trial completion date • Trial primary completion date • Oncology • Solid Tumor

A First-in-human Dose-escalation and Expansion Study With the Antibody-drug Conjugate SYD1875 (clinicaltrials.gov) - P1; N=31; Active, not recruiting; Sponsor: Byondis B.V.; Recruiting ➔ Active, not recruiting; N=90 ➔ 31

Clinical • Enrollment change • Enrollment closed • Oncology • Solid Tumor

[VIRTUAL] Preclinical Profile of SYD1875, a Novel Site- Specifically Conjugated Anti- 5T4 Antibody Drug Conjugate (ADC-USA 2021) - P1 | "Its preclinical profile supports the expectation that SYD1875 will be of benefit for a broad group of cancer patients. A first-in-human dose-finding trial is initiated to evaluate safety and explore efficacy (NCT04202705)."

Preclinical • Oncology • Solid Tumor • TPBG

A First-in-human Dose-escalation and Expansion Study With the Antibody-drug Conjugate SYD1875 (clinicaltrials.gov) - P1; N=90; Recruiting; Sponsor: Synthon Biopharmaceuticals BV; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

Newly added product (clinicaltrials.gov) - P1, Oncology

Pipeline update