· In vivo antitumor efficacy with significant tumor growth inhibition in multiple models with varying levels of FOLR1 expression
· Highly promising safety results in non-human primates, enabling a broad therapeutic window
· High conjugation yields, along with 100% DAR8 homogeneity and stability, major drivers of the successful ongoing manufacturing process
· IND submission planned in Q4 2023
Lyon - France, March 14, 2023 (22h30 CET)
Mablink Bioscience (“Mablink”), a biotechnology company dedicated to advancing cancer therapy with next-generation antibody-drug conjugates (ADCs), today announced that preclinical efficacy and safety data on its lead ADC candidate, MBK-103, will be presented at the American Association for Cancer Research (“AACR“) Meeting 2023 on April 17, 2023, in Orlando, Florida.
Mablink's poster will include in vivo efficacy data in mouse models and safety data in non-human primates (see abstract).
Mablink presented the proof-of-concept results it obtained with its proprietary ADC platform PSARLink™ in previous scientific articles and posters. PSARLink™ ADCs present an enhanced hydrophilicity and plasma-stability which translates into an improved tolerability and a prolonged half-life, similar to the unconjugated antibody. The increased drug-exposure in rodent models correlates with an improved anti-tumoral efficacy.
MBK-103 is the first development candidate coming from the PSARLink™ platform and it confirms the pharmacological improvement observed in the PoC experiments.
MBK-103, an antibody-drug conjugate targeting the Folate receptor alpha (FOLR1 or FRα), demonstrated excellent ex vivo stability in human plasma, which should lead to a lower off-target toxicity.
Significant tumor growth inhibition was achieved in more than 10 in vivo mouse tumor models at low doses (1-3 mg/kg) with varying levels of FRα expression. The distinct mode of action of exatecan (anti-topo-I, the payload) and the unique characteristics of the proprietary drug-linker platform resulted in potent anti-tumor efficacy obtained notably in colorectal cancer, where tubulin inhibitors have shown poor therapeutic efficacy.
The compound was also well tolerated in cynomolgus monkeys at the highest non-severely toxic dose (HNSTD) of 50 mg/kg administered repeatedly. These promising data are a significant differentiator in the ADC’s landscape.
High conjugation yields along with 100% homogeneity are key drivers of the successful ongoing manufacturing process in preparation of initiating clinical trials, since Mablink plans to submit a Clinical Trial Application (CTA)in the fourth quarter of 2023.
“We are excited about MBK-103 as a new generation ADC therapeutic candidate driven by a promising therapeutic index,” said Jean-Guillaume Lafay, CEO of Mablink, “Our ongoing IND-enabling study program to support first-in-human trials with MBK-103 is delivering as expected and we plan to submit our CTA in the fourth quarter of 2023.
Details about the poster presentation
Title: MBK-103, a potent novel conjugation platform-based antibody-drug conjugate, changing therapeutic options in folate receptor alpha positive cancer patients
Poster Board number: 24
Abstract Presentation Number: 1544
Presenter: Lenka Kyrych Sadilkova, PhD
Session category: Experimental and Molecular Therapeutics
Session title: Antibody Drug Conjugates
Session date and time: Monday Apr 17, 2023, 9:00 AM - 12:30 PM
About Mablink Bioscience
Mablink Bioscience is a biotechnology company developing the next generation of an emerging class of cancer drugs called antibody-drug conjugates (ADCs). Mablink’s patented hydrophilic drug-linker technology, PSARLinkTM, enables the design of homogeneous, plasma-stable, next generation ADCs with high DAR (drug-to-antibody ratio) while maintaining excellent pharmacological properties and tolerability.
For more information, please visit https://mablink.com
MBK-103, an antibody-drug conjugate targeting the Folate receptor alpha (FOLR1 or FRα), is based on Mablink’s PSARLinkTM proprietary hydrophilic drug-linker platform. It consists of: (i) an Fc-attenuated humanized IgG1 monoclonal antibody, that binds selectively to FRα; (ii) a polysarcosine hydrophobicity masking entity that allows for a high drug-antibody-ratio (DAR) of 8, while improving the pharmacokinetics and tolerability of the drug; (iii) a proprietary dipeptide cleavable unit and (iv) exatecan, a potent topoisomerase I inhibitor as the payload.
FRα is a clinically validated target, that is overexpressed extracellularly in numerous solid tumors with high unmet medical need. Ovarian, non-small cell lung and breast adenocarcinoma are among the indications with the highest frequency of FRα-positive patients with every second patient showing upregulated topoisomerase I expression.