Bicycle Therapeutics - Pipeline - Bicycle Therapeutics

Pipeline

Bicycle is developing several molecules in the clinic, and advancing many additional discovery-stage projects.

Bicycles are a novel molecule formed by constraining short linear peptides into a stabilized bi-cyclic structure using a central chemical scaffold.

The resulting structure enables Bicycles to effectively mimic protein-protein interactions. Bicycles combine the pharmacological properties normally associated with a biologic with the pharmacokinetic and synthetic advantages of a small molecule.

Bicycles can be readily conjugated to other chemical payloads, or to other Bicycles:

Bicycle Toxin Conjugates® contain a Bicycle targeted to a specific tumor antigen, a selectively cleavable linker, and a small molecule toxin payload
Bicycle Radio Conjugates contain a Bicycle targeted to a specific tumor antigen, a selectively cleavable linker and a highly potent radioisotope
Bicycles can be designed as immune cell agonists that are guided to the tumor under the direction of a tumor antigen targeting Bicycle

Bicycle Toxin Conjugates

Preclinical

IND-Enabling

Phase 1

Phase 2 / Expansion

Phase 3

zelenectide pevedotin

Phase

Phase 2/3

Target

Nectin-4

Target

Zelenectide pevedotin (zele, formerly BT8009) targets Nectin-4, a cell adhesion molecule from the Nectin and Nectin-like family, which has been shown to be overexpressed in tumor cells and is believed to play a role in tumor cell growth and proliferation. High in normal embryonic and fetal tissue, Nectin-4 declines in adulthood, showing a limited distribution in healthy tissues.

Toxin

The molecule is composed of our Nectin-4 targeting Bicycle®, a valine-citrulline, or val-cit, cleavable linker, and an MMAE cytotoxin payload.

Preclinical

Bicycle’s Nectin-4 toxin conjugates demonstrate promising target-dependent activity in preclinical models, including both cell- and patient-derived xenografts resistant to current standard of care treatments. In preclinical head-to-head comparisons with an ADC targeting Nectin-4, zele appeared to demonstrate superior anti-tumor activity, including complete regressions in both very large and small tumor models. In preclinical toxicity studies, zele showed only a subset of the toxicities typically associated with the MMAE cytotoxin payload, avoiding liver, GI and renal toxicity.

Clinical Plan

Zelenectide pevedotin is currently being evaluated in two Company-sponsored clinical trials. The Phase I/II Duravelo-1 trial is studying zele in several Nectin-4 driven tumors, while the Phase II/III Duravelo-2 trial is studying zele as a treatment for metastatic urothelial cancer.

Reduce

BT5528

Phase

Phase 2 / Expansion

Target

EphA2

Target

BT5528 targets EphA2 (or Ephrin type-A receptor 2), a member of the Ephrin superfamily of receptor tyrosine kinases, which regulates cell migration, adhesion, proliferation and differentiation during development. EphA2 is overexpressed in difficult to treat cancers, and expression of this kinase correlates with malignant progression and poor prognosis.

Toxin

The molecule is composed of our EphA2 targeting Bicycle®, a valine-citrulline (val-cit) cleavable linker and a monomethyl auristatin E (MMAE) cytotoxin payload.

Preclinical

Bicycle’s EphA2 toxin conjugates have demonstrated promising target-dependent activity in preclinical models, including both cell- and patient-derived xenografts that are resistant to current treatments.

Clinical Plan

BT5528 is currently being evaluated in a Company-sponsored Phase I/II clinical trial as a monotherapy. EphA2 IHC status for patients enrolled in the study are being recorded for future assessment as a potential predictor of efficacy.

Reduce

BT1718

CRUK

Phase

Phase 2 / Expansion

Target

MT1-MMP

Partner

Target

BT1718 targets Membrane Type 1 Matrix Metalloproteinase (MT1-MMP, also known as MMP-14) which has an established role in cell invasion and metastasis and is linked to poor outcomes in cancer patients. It is generally expressed at relatively low levels in normal adult tissues but overexpressed in many solid tumors.

Toxin

The molecule is composed of our MT1-MMP targeting Bicycle®, a hindered disulphide cleavable linker and a DM1 cytotoxin payload.

Preclinical

MT1-MMP is an attractive target for cytotoxin delivery due to high levels of expression on subsets of stromal and tumor cells in a range of cancers.

Clinical Plan

BT1718 is being investigated in an ongoing Phase I/IIa open label dose escalation and expansion clinical trial sponsored by CRUK.

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Bicycle Radio Conjugates

Preclinical

IND-Enabling

Phase 1

Phase 2 / Expansion

Phase 3

Select targets

DKFZ

Select targets

Novartis

Select targets

Bayer

Immuno-oncology

Preclinical

IND-Enabling

Phase 1

Phase 2 / Expansion

Phase 3

BT7480

Phase

Phase 1

Target

Nectin-4 / CD137

Target

BT7480 is a novel, fully synthetic Bicycle tumor-targeted immune cell agonist® (Bicycle TICA™) that contains three Bicycles. One targets Nectin-4, a cell adhesion molecule from the Nectin and Nectin-like family shown to be overexpressed on the surface of tumor cells. The others bind to and agonize CD137, a member of the TNFR family involved in the activation of several immune cell types, including T cells and NK cells.

Preclinical

In preclinical models, Nectin-4/CD137 Bicycle TICAs have shown powerful anti-tumor activity, enabled by potent and tumor antigen dependent CD137 agonism.

Clinical Plan

BT7480 is currently being evaluated in a Company-sponsored Phase I/II clinical trial as monotherapy.

Reduce

BT7455

BT7401

CRUK

Phase

Preclinical

Target

Multivalent CD137

Partner

Target

BT7401 is a novel, fully synthetic, multivalent, agonistic Bicycle® built from multiple CD137 monomeric Bicycles connected by stable linkers through a central hinge.

Potential Differentiation

Existing antibody approaches to agonize CD137 have demonstrated robust and durable anti-tumor effects in patients, but treatments have been limited by severe hepatotoxicity observed in clinical trials.

Preclinical

BT7401 has shown significant pharmacologic activity in preclinical models and no hepatotoxicity was seen in early preclinical toxicology studies. These findings indicate BT7401 may offer an improved therapeutic index when compared to antibody-based approaches.

Collaboration Partner

Cancer Research UK’s Centre for Drug Development is funding and sponsoring development of BT7401, which is currently in pre-clinical development, through to a Phase I/IIa clinical study. This collaboration aims to further characterize the clinical activity and therapeutic potential of BT7401.

Reduce

Undisclosed targets

Genentech

Expanded Access Policy

Bicycle is committed to developing innovative new medicines for patients with debilitating diseases.

As part of that commitment, Bicycle conducts, alone or with our partners, clinical trials of our investigational medicines to seek to demonstrate their safety and effectiveness for patients. The data generated from these clinical trials are integral to obtaining regulatory approval of our investigational medicines and such trials represent the best and most efficient way to develop our investigational medicines.

Patients who choose to participate in clinical trials play an essential role in developing new medicines. Clinical trials, including eligibility criteria, are listed at www.clinicaltrials.gov. Patients interested in learning if enrollment in a clinical trial is an option for them should consult with their treating physician.

As a general policy, Bicycle will not provide Expanded Access* to an investigational medicine until sufficient safety and efficacy information has been obtained in clinical trials. Therefore, Bicycle is currently unable to offer Expanded Access to any of its investigational medicines, as Bicycle is committed to conducting formal clinical trials.

Bicycle may update this Policy at any time, consistent with applicable law and regulations. The posting of this policy shall not serve as a guarantee of access to any specific investigational medicine for any patient. This website and policy may be updated with a hyperlink or other reference to an expanded access record on www.clinicaltrials.gov after such record becomes active.

For questions or additional information about this policy, please contact Bicycle’s Medical Information team at medinfo@bicycletx.com. Bicycle will endeavor to acknowledge any inquiries within five (5) business days of receipt.

* Expanded Access is a potential pathway for a patient with a serious or immediately life-threatening disease or condition to gain access to an investigational medical product (drug, biologic, or medical device) for treatment outside of clinical trials when no comparable or satisfactory alternative therapy options are available. Typically access is provided when a positive late stage trial has been reported or the Company has requested regulatory approval to go to market. Bicycle has no such products at this time and therefore it would be unsafe to offer such access.

Beyond^→

Pipeline

Bicycle Toxin Conjugates

Bicycle Radio Conjugates

Immuno-oncology

Expanded Access Policy

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