On June 22, 2020 Bicycle Therapeutics plc (NASDAQ: BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported that new translational data for BT5528 and preclinical data for tumor-targeted immune cell agonists (TICAs) will be presented during poster sessions at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II on June 22-24, 2020 (Press release, Bicycle Therapeutics, JUN 22, 2020, View Source [SID1234561314]).

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"The translational and preclinical data we are presenting at AACR (Free AACR Whitepaper) further inform the potential utility Bicycle-based therapeutic candidates have as a new modality that could shift the treatment paradigm for cancer, among other serious diseases," said Kevin Lee, Ph.D., Chief Executive Officer of Bicycle Therapeutics. "Our fit-for-purpose immunohistochemistry, or IHC, assay was developed for use in the BT5528 Phase I/II trial and is designed to help us maximize our chances of success in the clinic by guiding tumor type selection and patient enrollment criteria. Additionally, the preclinical data we continue to generate for our TICA molecules remains very encouraging, especially as we look to initiate clinical studies of BT7480 next year."

New translational data for BT5528, a second-generation Bicycle Toxin Conjugate (BTC) that targets EphA2, describe the development of Bicycle’s proprietary IHC assay. This assay will be used to support patient selection and assess EphA2 expression levels in tumor samples collected in the ongoing Phase I/II trial of BT5528. EphA2 is a well-known tumor antigen shown to be overexpressed in a range of difficult to treat solid tumor types. While many independent EphA2 IHC assays have been reported, Bicycle’s is the first to specifically detect the extracellular domain of EphA2 and to score its expression at both the tumor cytoplasm and tumor membrane, which is where BT5528 binds.

Bicycle TICAs are potent, fully synthetic compounds that represent an immuno-oncology approach engineered to overcome the limitations of other immunomodulatory mechanisms. At AACR (Free AACR Whitepaper), the Company will present new preclinical data for BT7480, a TICA targeting Nectin-4 and agonizing CD137 (4-1BB), indicating that anti-tumor responses in a syngeneic mouse model can be achieved with an intermittent dosing regimen, which suggests that continuous target coverage may be unnecessary for efficacy. Additional PK/PD and safety data for BT7480 from in vivo mouse and non-human primate models demonstrate potent, target-dependent anti-tumor activity. At dose levels tested, BT7480 has been shown to be well-tolerated in preclinical species, with no signs of toxicity issues associated with other immuno-oncology agonist therapies. IND-enabling activities for BT7480 are ongoing.

New preclinical data for EphA2/CD137 TICAs similarly indicate highly target dependent CD137 agonism, most notably in a syngeneic mouse model that showed robust antitumor activity. Complete responder animals in this model were subsequently re-challenged with the same tumor cell implantation and no tumor growth was observed, implying development of immunogenic memory. In further PK/PD experiments, intermittent plasma exposure of an EphA2/CD137 TICA produced robust anti-tumor activity, again implying continuous target coverage is not required for efficacy. Earlier this year, Bicycle selected BT7455, an EphA2/CD137 TICA, as another Bicycle-based immuno-oncology candidate to advance into clinical studies.

Details on Bicycle’s poster presentations at AACR (Free AACR Whitepaper) are as follows:

Session Title: Molecular Classification of Tumors for Diagnostics, Prognostics, and Therapeutic Outcomes 2
Session Category: Experimental and Molecular Therapeutics
Poster Title: A survey of EphA2 expression by immunohistochemistry (IHC) in tumor tissue microarrays (TMAs) to support BT5528 indication selection
Abstract #: 3302

Session Title: Immunomodulatory Agents and Interventions 2
Session Category: Immunology
Poster Title: BT7480, a novel fully synthetic tumor-targeted immune cell agonist (TICA) induces tumor localized 4-1BB agonism
Abstract #: 5241

Session Title: Immunomodulatory Agents and Interventions 3
Session Category: Immunology
Poster Title: A fully synthetic EphA2/4-1BB tumor-targeted immune cell agonist (TICA) induces tumor localized 4-1BB agonism
Abstract #: 4613

The posters are available on the Publications section of bicycletherapeutics.com.