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The biology of many diseases is often so complex that it can be hard to design new drugs with the desired therapeutic effect. In many cases, even if we can achieve the desired therapeutic effect, these treatments may cause undesirable, or even toxic, side effects. Addressing these drug targets through traditional methods has proven challenging for drug developers, leaving patients without access to vital therapeutic options. To overcome this challenge, Metaphore Biotechnologies developed a unique solution combining machine learning and molecular mimicry to design novel therapeutics. This solution unlocks complex signaling, multi-targeting, and modality switches to design therapeutics that address difficult-target biology for maximum patient impact.

Metaphore’s approach focuses on the pharmacophore, the essential set of features that govern how a drug and its target interact. By deeply mapping molecular interactions to identify these key functional features, Metaphore can mimic the pharmacophore and stamp it onto any therapeutic modality, retaining elements of the naturally occurring molecular interactions that are necessary to modulate specific drug targets. The platform can then program this new molecule with additional features that elicit a desired biological response aligned with required developability criteria, transforming it into a medicine.

Origins

In 2021, Metaphore’s founding team of Noubar Afeyan, Lovisa Afzelius, and Daniel Acker were inspired by how many organisms mimic others’ features for their own benefit. The team wondered if they could apply this concept at the molecular level to develop new medicines and better meet the needs of patients with limited therapeutic options.

This led them to ask, what if we could use mimicry, one of nature’s oldest tricks for gaining adaptive advantage, to solve hard therapeutic problems?

Metaphore grew out of this question, setting out to map interactions, mimic pharmacophores, and optimize properties to unlock opportunities for therapeutic breakthroughs.  

Breakthrough

Metaphore’s capabilities are built on its machine learning-guided platform called MIMIC™. The MIMIC platform systematically identifies a pharmacophore and measures its surface at single amino acid resolution to create a three-dimensional map of its features with exquisite accuracy. Then, the platform uses that map to develop new molecules that mimic the original pharmacophore, retaining the features that modulate drug targets, while also enabling Metaphore to further refine those essential features. With these essential features in hand, Metaphore can then program and fine-tune properties that control function, specificity, selectivity, and even multi-targeting.

The result is a unique medicine of virtually any therapeutic modality containing the mimicked pharmacophore. This flexibility means that MIMIC enables the unprecedented ability to tailor drugs to the biology of any given disease.

Metaphore’s solution simplifies drug design for diseases with complex biological origins, and provides drug developers more control over the interactions of a drug and its target. This approach also enables therapeutics to be precisely tuned to enhance safety, efficacy, and developability.

Advantage

Metaphore’s MIMIC is an elegant and powerful solution starting from experimentally determining the natural dynamics at the molecular interface – the specific, critical component of any drug-target interaction. This sets Metaphore apart from other approaches that derive insights from snapshots of natural dynamics, such as crystal structures. Furthermore, the unique technology behind Metaphore, radically reduces the scale of the computational challenge in AI/machine learning-guided drug design. This has several benefits, including enabling Metaphore to find many more discrete solutions to a problem, and make more accurate predictions of how changes in a pharmacophore would impact a drug’s ability to access a target or alter its effects.

Focus

Metaphore is initially applying this approach toward the design of novel biologics, wherein the key features of protein-protein interactions are retained in modalities that are highly engineerable and translatable. With the ability for immense control over any protein-protein interaction, Metaphore is building its pipeline to support patients with immunological or metabolic diseases. The MIMIC platform has the potential to advance human health across areas with significant unmet need and where greater control over complex biology will lead to significantly more effective and safer therapeutics for patients.