Insider Brief
- Antiverse and Nxera Pharma have partnered to accelerate antibody discovery targeting GPCRs, combining AI-driven design and structural biology to tackle these elusive drug targets.
- GPCRs are linked to hundreds of diseases but remain underutilized in drug discovery; the partnership aims to address the 80% of GPCRs that lack effective therapies.
- Nxera’s stabilized GPCR structures will enhance Antiverse’s generative AI platform, enabling faster, more precise antibody development for life-changing treatments.
Antiverse and Nxera Pharma announced a collaboration to accelerate antibody discovery targeting some of the most elusive receptors in medicine: G-protein coupled receptors (GPCRs). In a LinkedIn post, the Antiverse team announced that the partnership combines Antiverse’s generative AI antibody design with Nxera’s platform for determining GPCR structures, a synergy expected to fast-track the development of life-changing therapies.
The deal, signed on November 5, grants Antiverse access to Nxera’s NxWave™ platform, enabling the computational design of antibodies against several GPCR targets. GPCRs, linked to hundreds of diseases, represent one of the most challenging but rewarding classes of drug targets. Despite their medical significance, a staggering 80% of the GPCR family remains untargeted by existing drugs, offering a vast opportunity for innovation.
Rethinking Antibody Design
Based in Cardiff, UK, Antiverse specializes in computational antibody design, leveraging artificial intelligence to create functional antibodies for complex targets in just six months. Unlike traditional approaches that rely on vast libraries of randomly generated antibodies, Antiverse employs generative AI to rationally design epitope-specific libraries. These tailored libraries significantly increase the specificity and success rate of finding effective antibodies, particularly for difficult targets like GPCRs.
The Antiverse team writes: “We are thrilled to be working with Nxera – with over 15 years of experience in GPCR target identification and structural determination, they bring a wealth of experience and expertise in GPCR drug discovery. Their platform, NxWave™, synergises incredibly well with our AI antibody design capabilities, by feeding our platform with structural data necessary to create novel antibody therapeutics. Together, we aim to design antibodies for some of the most challenging GPCR targets.”
Nxera Pharma: Pioneers in GPCR Structural Biology
Nxera Pharma, formerly Sosei Heptares, has a 15-year history in GPCR research. The company developed a proprietary method to stabilize GPCRs, enabling their crystal structures to be determined without deformation. This breakthrough, achieved through targeted mutations, has unlocked the potential for rational drug design targeting these receptors.
GPCRs, which span cell membranes, are notoriously difficult to study due to their hydrophobic environment. Traditional methods for isolating GPCRs often distort their structure, rendering rational drug design nearly impossible. Nxera’s NxWave™ platform addresses this by stabilizing GPCRs in their native conformation, allowing researchers to visualize their structures and design drugs more effectively.
The company’s track record includes determining the structures of GPCRs linked to diabetes, cancer, viral infections and inflammatory diseases. Their work on GLP-1, a GPCR targeted by blockbuster diabetes and obesity drugs, exemplifies the transformative potential of their platform.
Why GPCRs Are Difficult Targets
GPCRs represent one-third of all drug targets, generating nearly $1 trillion in annual sales. However, only a fraction of these receptors has been successfully targeted by drugs. According to the post, several factors contribute to their elusiveness:
- Limited Surface Accessibility: Most of a GPCR’s structure is buried within the cell membrane, leaving little room for drugs to bind effectively.
- High Similarity Across Subtypes: GPCRs often share structural features, increasing the risk of off-target effects, which can lead to severe side effects.
- Structural Complexity: Determining the exact shape of a GPCR is challenging due to its membrane-bound nature, complicating efforts to design drugs precisely.
Antibodies, which are larger and more specific than small molecules, offer a promising alternative. However, traditional antibody screening methods are hindered by steric interference from other cell surface proteins. This limitation makes finding GPCR-targeting antibodies particularly difficult.
As yet, teams have not been able to fully exploit GPCRs’ therapeutic potential, the team writes. Machine learning might be able to unlock it, they add.
“For the last two decades, empirical design has consumed most drug discovery efforts for these targets. This ‘brute-force’ approach to drug discovery has been fruitful for many targets, allowing researchers to create hundreds of transformative therapies. However, GPCRs are particularly challenging targets, and drugs that bind them are especially rare. Since empirical design relies on serendipity, many discovery campaigns using this method have failed.”
The Synergy: Antiverse and Nxera
The team writes that by joining forces, Antiverse and Nxera aim to overcome these obstacles. Nxera’s stabilized GPCR structures provide a foundation for Antiverse’s AI-driven design. Nxera’s ability to produce soluble forms of GPCRs also can lead to more precise antibody screening, which bypasses the steric hindrance encountered in cell-based assays.
Antiverse transitioned to a structure-based design approach earlier this year, further enhancing the compatibility between the two platforms. This shift allows Antiverse to design antibodies with conformational specificity, tailoring them to bind effectively to dynamic receptor states. When combined with Nxera’s structural data, this approach is expected to yield a new generation of highly specific GPCR-targeted therapies.
Broader Implications for Medicine
GPCRs are implicated in a wide array of diseases, from diabetes to cancer to autoimmune disorders. Unlocking their therapeutic potential could transform treatment paradigms across multiple fields, according to the post. For example, Nxera’s previous work on CCR9 — a GPCR involved in cancer metastasis and viral entry — demonstrates the potential for antibodies to address diseases with limited treatment options.
The collaboration between Antiverse and Nxera comes at a critical time, as the pharmaceutical industry increasingly turns to AI and structural biology to tackle previously intractable challenges. Antiverse’s ability to design functional antibodies within six months contrasts sharply with traditional drug discovery timelines, which can stretch over a decade. Meanwhile, Nxera’s stabilized GPCR structures are paving the way for a new era of rational drug design.
Future Outlook
This partnership underscores the growing role of AI in drug discovery, particularly for targets like GPCRs that have defied conventional approaches. By combining computational design with cutting-edge structural biology, Antiverse and Nxera aim to accelerate the development of therapies for some of the most challenging diseases.
The team writes: “Working together, our platforms will create many GPCR-targeted antibodies that could transform patients’ lives worldwide.”
The success of this collaboration could serve as a blueprint for similar partnerships, leveraging AI and structural biology to address unmet medical needs. For now, all eyes will be on Antiverse and Nxera as they embark on this ambitious journey to unlock the therapeutic potential of GPCRs.
