Science & Pipeline
A new way to treat cancer with high unmet medical needs
BiP (GRP78) is a key protein involved in survival mechanisms and associated to poor prognosis of patients
BiP (GRP78) is a master regulator of the Unfolded Protein Response (UPR), a pathway that cancer cells hijack to survive the high-stress conditions inherent to tumor growth. Its expression is highly elevated in numerous cancers and is directly correlated with a poor prognosis for patients. Thus, GRP78 has emerged as an exciting and clinically validated target to treat cancer.
BiP inhibitors feature a unique Mechanism of Action (MoA) that selectively inhibits BiP. This targeted inhibition applied to cancer patients disrupts the cancer cell's ability to manage protein folding, inducing a state of "unresolved ER Stress." Unable to resolve this stress, the cancer cell is pushed past a critical threshold and into apoptosis, or programmed cell death—effectively causing the cancer cell to "burn out." This approach is fundamentally different from previous, unsuccessful attempts to target this pathway with PERK/IRE1 inhibitors, which aimed to lower ER stress rather than amplify it to a lethal level.
This innovative MoA is paired with a precision medicine strategy. BiP is a non-invasive, measurable circulating biomarker that can be detected with a simple plasma ELISA test. This enables a targeted approach to clinical development, allowing for the selection and stratification of the patient population most likely to respond to treatment and significantly increasing the probability of success.
BiPER Therapeutics has developed innovative and unique BiP Inhibitors to provide solutions for patients
Pipeline
BPR001-615
BiPER Therapeutics’ lead program is a first-in-class small molecule targeting GRP78/ BiP. Overexpression of GRP78 is associated with very poor prognosis of patients in a broad range of cancer indications.
BPR001-615 has a unique, selective mechanism-of-action that selectively kills cancerous cells. BPR001 induces strong and lethal ER Stress through selective GRP78 binding and inhibition, leading to cancer cellular death via apoptosis and autophagy. As cancer cells express permanent and high ER Stress level to survive, proliferate and become resistant to standard of care therapies – by targeting this pathway, BPR001 is able to overcome this survival mechanism and this resistance, improving outcomes in both sensitive and resistant cancers.
BPR001 has demonstrated efficacy in a broad range of cancer indications in monotherapy and in combination associated with an excellent pharmacological and tolerability profile. Large body of in vivo and in vitro efficacy and tolerability data support the proof-of-concept for BPR001 use as an oral anti-cancer therapy.
In preclinical studies, patent-protected data demonstrate that BPR001-615 is effective in combination and enhances a wide range of therapies, including standard of care agents like chemotherapies, targeted therapies and immunotherapies.
BPR002
BPR002 is a first-in-class small molecule series inducing ER Stress associated with strong immunomodulation properties. BPR002 leads series are first-in-class ER stress inducers being selected on their immune-cell mediated cancer-cell killing properties.
Our BPR002 series shown preliminary immunomodulation properties which is consistent with recent studies that have uncovered a mechanism by which controlled ER Stress promotes malignant progression: by subverting the protective function of innate immune cells in the tumor microenvironment to cripple the development of anti-tumor immunity. Our strategy for BPR002 is to select candidates able to harness the intrinsic ability of immune system to recognize and eliminate malignant cells through ER Stress modulation.
BPR003
BiP is a multifunctional protein with activities far beyond its well-known role in the unfolded protein response (UPR) which is activated after endoplasmic reticulum (ER) stress in the cells. GRP78 influences how tumor cells survive, proliferate, and develop chemoresistance.
In some non-oncology indications, endogenous mechanisms of protection are frequently dysregulated. Lessons from tumor biology led us to clues about how to boost endogenous protective mechanisms in BiP-related dysregulations. Our goal with this third programme is to identify BiP modulators that will re establish the right homeostasis balance essential to enable healthy cells to cease being pathological and change the course of the disease
