11 May 2023
Bicycle Therapeutics plc (NASDAQ: BCYC) and Orano Med, two biotechnology companies respectively, announce pre-clinical results.
Bicycle is pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle®) technology and Orano Med is developing innovative radioligand therapies with lead-212 in oncology. The companies today announced co-authored preclinical results of Pb-BCY20603, a Bicycle® radio-conjugate (BRC™) that binds with high affinity to the tumor antigen MT1-MMP and carries a chelate of lead-212, a potent alpha particle emitting radioisotope. The results were presented at TIDES 2023 in San Diego, CA and can be accessed here.
“We are encouraged by the preclinical results that were presented at TIDES 2023 and are excited by the potent anti-tumor activity observed with this molecule,” said Kevin Lee, Ph.D., Chief Executive Officer of Bicycle Therapeutics. “We estimate that on a dose per dose basis this prototype is over 1,000 times more potent than a comparator Bicycle toxin conjugate, demonstrating just how powerful targeted alpha therapy with lead-212 may be and providing further evidence that the unique properties of Bicycles make them a potentially powerful modality for precision guided delivery of radionuclide payloads.”
Pb-BCY20603 showed tumor targeting in rodent tumor xenograft studies, with radioactivity levels of >45% Injected Dose (ID/g) 24 hours post injection. No body weight loss was seen in mice treated up to 30 μCi, and no significant changes were observed in hematology readout compared to vehicle treated mice. Pb-BCY20603 showed potent anti-tumor activity after a single dose of 5 μCi. Complete tumor regressions were seen after 3 dosing cycles of 10 μCi, given two weeks apart. Median survival was increased for each dosing group with 90% survival observed for the 3 cycles of 10 μCi, treatment at the end of the 100-day study. Importantly, the Bicycle displayed differentiated tumor penetration compared to a comparator antibody, highlighting an advantage of smaller molecules over larger biologics.
“The promising preclinical results of Pb-BCY20603 confirm the potential of targeted alpha therapies to open new perspectives for patients with difficult to treat cancers,” said Julien Dodet, Chief Executive Officer of Orano Med. “We are convinced that alpha therapies, combined with innovative vectors such as Bicycle peptides, are the future of radiopharmaceutical therapies, providing an increased cytotoxic potential against cancer cells with limited toxicity to surrounding healthy cells. This reinforces Orano Med’s commitment to make lead-212 based therapies available to the medical community and patients worldwide.”
These data build on previously published studies demonstrating the precision-guided potential of Bicycles. Imaging data were also reported from two separate independent research groups. At the 2023 American Association for Cancer Research Annual Meeting, an independent team from Johns Hopkins published data from an EphA2 binding Bicycle in an orthotopic pancreatic cancer model (Sharma, et. al., Non-invasive detection of pancreatic adenocarcinoma using Ga-88 labelled EphA2 targeting peptide). In addition, a separate independent research team (Duan, et al., Clinical Cancer Research, 2023) demonstrated specific and sensitive imaging of a Nectin-4 targeted Bicycle observed in Nectin-4 positive metastases in human patients, despite the molecule not being optimized for this purpose. These data provide further evidence to support the ability of Bicycles to fully penetrate and bind to their targets deep into tumors providing additional confidence in the platform’s potential clinical utility.