Revolutionary Bicycle® Radio-Conjugates Show Promise in Preclinical Trials: Bicycle Therapeutics and Orano Med Present Data at TIDES 2023

Bicycle Therapeutics Limited (NASDAQ: BCYC) and Orano Med have announced remarkable pre-clinical results for Pb-BCY20603, their innovative Bicycle® radio-conjugate (BRC™). This BRC™ binds to the tumor antigen MT1-MMP with high affinity and carries a chelate of lead-212, a potent alpha particle emitting radioisotope. This pioneering combination of Bicycle® technology and Orano Med’s radioligand therapy with lead-212 has the potential to revolutionize oncology. The results were presented at TIDES 2023 in San Diego, CA and have been made available for further review.

At TIDES 2023, Bicycle Therapeutics was encouraged by the preclinical results presented, which showed potent anti-tumor activity with the molecule. The prototype was over 1,000 times more potent than a comparator Bicycle toxin conjugate on a dose per dose basis, showcasing the power of targeted alpha therapy with lead-212 and the potential of Bicycles for precision guided delivery of radionuclide payloads. Kevin Lee, Ph.D., Chief Executive Officer of Bicycle Therapeutics, expressed excitement for the results.

Pb-BCY20603 demonstrated impressive tumor-targeting capabilities in rodent tumor xenograft studies, with radioactivity levels of over 45% Injected Dose (ID/g) 24 hours post injection. No adverse effects were observed in mice treated up to 30 μCi, with no significant changes in hematology readout compared to control animals.

Even more impressive were the anti-tumor effects seen after a single dose of 5 μCi, with complete tumor regressions observed after 3 dosing cycles of 10 μCi, given two weeks apart. This resulted in an increased median survival rate of 90% at the end of the 100-day study!

What makes this so remarkable is the differentiated tumor penetration displayed by Pb-BCY20603 compared to a comparator antibody, proving the advantage of smaller molecules over larger biologics.

Orano Med is dedicated to making lead-212 based therapies accessible to medical professionals and patients worldwide, and the promising preclinical results of Pb-BCY20603 demonstrate the potential of targeted alpha therapies to revolutionize cancer treatment.

Alpha therapies, combined with innovative vectors such as Bicycle peptides, have the potential to deliver increased cytotoxicity against cancer cells while limiting toxicity to surrounding healthy cells, creating a new horizon of hope for patients with difficult to treat cancers.

At the 2023 American Association for Cancer Research Annual Meeting, new evidence emerged to support the potential clinical utility of Bicycles. Two independent research teams presented data showing the precision-guided potential of Bicycles for imaging cancer.

Johns Hopkins researchers reported data from an EphA2 binding Bicycle in an orthotopic pancreatic cancer model, while a separate team from Clinical Cancer Research demonstrated specific and sensitive imaging of a Nectin-4 targeted Bicycle observed in human patients, despite the molecule not being optimized for this purpose. These findings suggest the ability of Bicycles to penetrate and bind to their targets deep into tumors, providing further confidence in the platform’s potential.

About Bicycle Therapeutics

Bicycle Therapeutics (NASDAQ: BCYC) is revolutionizing the way people approach drug development with their novel class of medicines, known as Bicycles. By constraining short peptides with small molecule scaffolds to form two loops, Bicycles can bind to targets with high affinity and selectivity, making them attractive candidates for drug development.

Currently, Bicycle is evaluating several Bicycles in clinical trials, such as BT5528, a second-generation Bicycle Toxin Conjugate (BTC™) targeting EphA2; BT8009, a second-generation BTC targeting Nectin-4; and BT7480, a Bicycle TICA™ targeting Nectin-4 and agonizing CD137.

Additionally, BT1718, a BTC that targets MT1-MMP, is being investigated in an ongoing Phase I/IIa clinical trial sponsored by the Cancer Research UK Centre for Drug Development. With their headquarters in Cambridge, UK, and many key functions and members of their leadership team located in Cambridge, MA, Bicycle Therapeutics is setting a new standard for drug development.

About Orano Med

Orano Med is a clinical-stage biotechnology company that is revolutionizing cancer treatment by harnessing the power of Targeted Alpha-Emitter Therapy (TAT). This innovative therapy utilizes the unique properties of lead-212 (212Pb), a rare alpha-emitting radioisotope with high potency against cancer cells.

The method works by combining the ability of biological molecules to target cancer cells with the short-range cell-killing capabilities of alpha-emitters. This enhances the cytotoxic potential towards cancer cells while limiting toxicity to nearby healthy cells.

Orano Med is investing in GMP-manufacturing capacities for 212Pb radiolabeled pharmaceuticals in North America and Europe and has 212Pb manufacturing facilities, laboratories, and R&D centers in France and in the US. Through this revolutionary approach, the company is providing new hope for cancer patients around the world.

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