In this interview, Dr. Ping Cao, co-founder and CEO of BridGene Biosciences, discusses targeting “hard to drug” proteins that evade traditional small-molecule therapies due to their complex structures and functions  BridGene, leveraging its proprietary IMTAC™ technology, seeks to innovate drug discovery by focusing on proteins essential in disease pathways yet difficult to target. This approach aims to pioneer new classes of medicines that can directly interact with and modulate protein functions, addressing significant unmet medical needs in areas like oncology and neurodegenerative diseases.

Moe: Tell us about BridGene Biosciences and its mission to target hard to drug proteins.

Dr. Ping Cao:
BridGene Biosciences was established to innovate drug discovery in areas where traditional methods have failed, particularly in targeting proteins that have been deemed hard to drug. These proteins, which play crucial roles in disease pathways, often evade traditional small molecule therapies due to their complex structures or the absence of targetable sites. BridGene aims to unlock new therapeutic avenues for diseases with limited or no effective treatments by focusing on these challenging targets. Our approach leverages advanced chemoproteomic technologies, such as our proprietary IMTAC™ platform, which allows us to explore and interact with the full breadth of the human proteome in ways that were not previously possible.

In pursuit of these hard to drug proteins, BridGene is seeking to expand the boundaries of current drug discovery and to pioneer new classes of medicines that can intervene in critical disease mechanisms directly at the protein level. This focus on hard-to-drug proteins involves a deep understanding of their roles in cellular signaling and disease progression, combined with innovative molecular design and screening approaches. Our efforts are mainly directed towards oncology, neurodegenerative diseases, and other areas where patients suffer from a substantial unmet medical need.

Moe: Could you explain the genesis of BGC515 and outline your plans for patient enrollment in the trial?

Dr. Ping Cao: BGC515 represents a significant breakthrough in our pursuit of addressing hard to drug targets. The development of BGC515 began with identifying a key target through our IMTAC™ platform. This discovery provided the foundational insight necessary to initiate the development of BGC515. Our Phase I trial is essential in evaluating this innovative therapy’s efficacy and safety, and we have strategically planned to involve several research centers across the U.S. and China to ensure a diverse patient demographic. We are in the final stages of site selection and expect to begin dosing our first patient within the next few months, targeting an initial cohort that reflects the standard enrollment numbers for early-phase oncology trials.

Dr. Ping Cao CEO of Bridgene Biosciences
Dr Ping Cao CEO of Bridgene Biosciences

Traditionally seen as hard to drug, these proteins are associated with less common tumors and genetic mutations, making it difficult to find a sufficient patient population that meets the trial criteria. To address this, we focus extensively on selecting trial sites in regions known for a higher prevalence of these conditions. Additionally, our teams conducted detailed feasibility studies to assess and predict patient availability, ensuring that each site can meet enrollment targets effectively and efficiently. Our proactive recruitment strategies also involve collaboration with treatment centers specializing in rare cancers, allowing us to identify and contact potential participants more directly. By leveraging advanced diagnostic tools and biomarker analysis, BridGene Biosciences can more accurately identify and enroll patients likely to benefit from targeting these undruggable proteins.

Moe: How does the IMTAC™ platform facilitate the pursuit of these hard to drug targets?

Dr. Ping Cao: The IMTAC™ platform is pivotal to BridGene’s strategy in addressing hard to drug targets because it enables an innovative approach to drug discovery by screening covalent small molecules directly within a live cell environment. This comprehensive screening is crucial as it assesses how small molecules interact with proteins under physiological conditions, where proteins exhibit their natural conformations and interactions. The platform utilizes a unique library of covalent, drug-like small molecules that can form covalent bonds with protein targets, and it has ability to detect interactions with proteins containing shallow or transient binding sites which are two kinds of main hard to drug targets . Lacking deep, well-defined pockets or transient pockets formed during protein-protein interaction in live cell environment make them resistant to conventional drug discovery methods. This method significantly enhances the likelihood of discovering effective modulators of hard to drug targets, opening new pathways for treating diseases with critical unmet needs.

Moe: Is BridGene collaborating with other companies to target hard to drug proteins? Are there any future partnerships in the works?

Dr. Ping Cao:
At BridGene Biosciences, we have forged strategic collaborations with prominent industry leaders such as Takeda and Galapagos to leverage our IMTAC™ technology in novel therapeutic areas. These collaborations are not just partnerships but are integral to our strategy of enhancing and accelerating the development of drugs targeting undruggable proteins. By combining our innovative platform and molecule library with the expertise and resources of these established pharmaceutical companies, we can advance our drug discovery projects more efficiently. The collaboration with Galapagos, for instance, focuses on identifying and developing compounds for multiple targets across various disease areas, leveraging their extensive research and development network to facilitate clinical trials and regulatory processes.

Looking forward, BridGene Biosciences is actively seeking to expand our collaborative efforts, and we are conducting discussions with potential partners in other therapeutic domains. These future partnerships are envisioned to explore a broader range of diseases, including rare genetic disorders and complex cancers, where our ability to target previously hard to drug proteins can bring new hope to patients. Each collaboration is carefully selected to ensure alignment with our mission to discover highly innovative therapeutic agents and to combine our strengths to maximize both scientific and clinical impacts.

Moe: What key safety and efficacy metrics are you focusing on in the early phases of the BGC515 study?

Dr. Ping Cao: In the early phases of the BGC515 study, our primary focus is on meticulously assessing the safety and preliminary efficacy of the compound. We rigorously monitor for adverse effects, employing established and novel biomarkers to ensure comprehensive safety evaluations. Efficacy metrics in these initial trials are designed to provide early indications of the compound’s therapeutic potential, including its ability to engage the target protein effectively and alter the progression of disease markers meaningfully. These early indicators help us refine dosing regimens and optimize the therapeutic approach as we progress to the later stages of the trial.

Drawing from insights gained in similar studies, we’ve tailored our study protocol to address the unique challenges and manage potential safety concerns that might arise preemptively. This includes a strategic escalation of dosing and intensive monitoring of patients for any signs of toxicity or unexpected biological responses. Our adaptive study design allows us to make real-time adjustments based on ongoing data analysis, which is crucial for maintaining patient safety and achieving optimal outcomes. This careful, data-driven approach ensures that we not only adhere to the highest safety standards but also maximize our chances of demonstrating the true efficacy of BGC515.

Moe: What regulatory challenges do you anticipate as you advance with BGC515, and how do you plan to address them?

Dr. Ping Cao:
Advancing BGC515 presents unique regulatory challenges, mainly because it represents a first-in-class molecule. Regulatory agencies often require extensive data to understand the mechanism of action, a detailed demonstration of both the biological pathway involvement, and the potential impacts beyond the intended effects. To navigate these complexities, our approach includes maintaining a proactive and transparent dialogue with regulatory  authorities such as the FDA. By sharing detailed preclinical and clinical data and engaging in early and ongoing consultations, we aim to align our development strategies with regulatory expectations, ensuring that all safety and efficacy concerns are thoroughly addressed.

We also are committed to implementing robust clinical trial designs and comprehensive risk management strategies to mitigate regulatory hurdles. This involves adhering to the highest standards of clinical practice and preparing for adaptive trial designs that can respond to regulatory feedback in realtime. As we progress through each trial phase, we will continually assess and refine our protocols to meet regulatory requirements and ensure patient safety remains at the forefront. Additionally, by leveraging insights from similar regulatory journeys undertaken by other first-in-class drugs, we plan to address possible challenges and preemptively streamline our pathway to approval.

Moe: Looking beyond BGC515, how does BridGene plan to leverage the IMTAC™ platform for future drug discovery?

Dr. Ping Cao:
The success of BGC515 has highlighted the potential of our IMTAC™ platform, particularly in targeting hard to drug proteins that are critical in various diseases but have been elusive to traditional therapeutic approaches. Building on this success, BridGene Biosciences plans to expand the application of the IMTAC™ platform to explore a broader range of therapeutic areas beyond oncology. Neuroscience is a particularly compelling field where hard to drug targets significantly influence disease progression. By applying our platform’s unique capability to identify and modulate these proteins, we aim to discover groundbreaking treatments for conditions such as Alzheimer’s and Parkinson’s, which affect millions globally but have limited effective therapies. Our future strategy also involves enhancing the IMTAC™ platform’s technology to increase efficiency and scope. This includes refining our library of small molecules to improve specificity and efficacy and developing more advanced screening techniques to identify potential drug candidates more rapidly. With these improvements, we anticipate faster cycle times in our discovery processes and a higher success rate in our preclinical and clinical developments. BridGene Biosciences is also actively seeking collaborations with academic and pharmaceutical partners who bring complementary expertise and resources, enabling a synergistic approach to tackling complex diseases with novel therapeutic agents.

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Moe Alsumidaie Chief Editor
Moe Alsumidaie is Chief Editor of The Clinical Trial Vanguard. Moe holds decades of experience in the clinical trials industry. Moe also serves as Head of Research at CliniBiz and Chief Data Scientist at Annex Clinical Corporation.