We develop drugs against diseases where the conventional approaches have failed.

We implement new scientific

concepts from BIOCOMPLEXITY and

P4 MEDICINE pioneered by our founders.

We chart new territories beyond

existing drug discovery paradigms.

We target the

undruggable proteome.

MISSION

TO DEVELOP A NEW CLASS OF DRUGS AGAINST UNCURABLE DISEASES BY

SOLVING THE PROBLEM OF THE "UNDRUGGABLE TARGETS"

Despite the breathtaking omics-technology revolution of the past two decades, drug discovery has stagnated. Of the 100,000 (or more) proteins in the entire human proteome, less than 800 are currently drug targets - the proteins that are blocked (or more rarely, activated) by pharmaceuticals to suppress a disease or improve health. In the past 20 years, the number of proteins known to be targeted by drugs has increased only moderately (from 500 targets in year 2000 to currently 700 targets) - despite the explosion of knowledge in molecular medicine. Even if deep phenomic profiling uncovers proteins that play pivotal role in diseases and thus may offer plausible molecular leverage for drugs to control disease course, our entire pharmacological armamentarium remains limited to the small set of 5-10% of human proteins that are 'druggable'. Drug discovery faces two formidable challenges:

Biology is complex: For many diseases, we do not even know what protein would represent a good target for a pharmacological intervention that stifles the disease process. An estimated 60% of failures in drug development are due to targeting biologically inappropriate targets. Burgeoning phenome profiling of large cohorts of patients holds great promise. But mechanistic reasoning to identify causative disease pathways that may present targets for treatment remains difficult. More than 80% of novel drugs are discovered without a priori knowledge of the precise molecular target but rather based on phenotype altering activity.
Chemistry is complicated: Even in the cases where we know the protein that could be a suitable target for a molecular intervention that would impact the disease course, often the target simply cannot be operated on by any currently known drug, be it a small chemical compound or a large biological (=recombinant protein or monoclonal antibody). Such a target protein is said to be "undruggable". Only an estimated 5% to 10% of the 100,000 or so proteins in the human proteome is considered "druggable" by today's approaches.

Thus, more than 90% of the 100,000 in the human proteome (which encompasses the 20,000 canonical proteins, and splice variants and microproteins encoded by "non-coding" RNAs, etc) are undruggable by current definition. But several thousand among them (and the list is growing thanks to deep phenomics) have been considered valuable therapeutic targets - if only they were druggable. These proteins are often part of large regulatory assemblies of multiple proteins (complexes or condensates) and simply lack the pockets that we normally identify in their 3-dimensional structure where a drug molecule, due to its complementary shape, can dock on, like a key inserting into a lock. Therefore, these proteins are beyond reach of drug-like chemicals or biologicals. This problem is not solved by burgeoning AI-driven design of molecules to target a well-defined docking site - because most proteins lack docking sites.

Our mission is to address these two challenges at the core of the current crisis of innovation in the pharmaceutical industry:

we will reach beyond the reductionist concept of target-based drug discovery, and learn to modulate complex phenotypic functions even without having a well-defined obvious target protein at hand; and
if a desirable target is known but is undruggable, we will step beyond the current paradigm of shape-complementarity that underlies current rational drug design, including AI-assisted methods.

P4BIOS introduces a new class of shape-shifting neo-peptides as drugs. This abrogates the perennial requirement that the target protein has a docking site. And we identify such drug molecules in a novel type of phenotypic screen for synthetic neo-peptides. We do so in a target-agnostic fashion but can also focus on pathogenic molecular pathways.

P4BIOS leverages its deep knowledge of biocomplexity with the latest phenomics technologies, guided by the P4 Medicine framework to develop a new genre of neo-peptide drug molecules. In addition, P4BIOS's neo-peptide high-throughput functional (phenotypic) screening platform will produce a new type of data that can be used to train foundation AI models that connect peptide sequences to biological activity without going through 3D molecular structures and thereby identity their cellular functions.

OUR STORY & OUR VISION

A New Type of Discovery for a New Class of Biologicals in a New Era of Medicine

P4BIOS was founded by a team of paradigm pushing scientists and bold business leaders that is determined to reduce this vision to practice and push the frontier of drug discovery in a new direction.

P4BIOS is grounded in the unique collective knowledge of its founding members who are not only experts in standard mechanistic understanding of diseases but also have been pioneers in the more holistic fields of biocomplexity and phenomics and who share a longstanding vision about the limitations of current paradigms in biology and specifically, in the pharma industry.

P4BIOS bridges intellectual domains of life sciences and medicine that are currently disjoint and much ignored by mainstream drug discovery. The P4BIOS team for several years deliberated the barriers of scientific advance in biomedicine, inspired by insights in biocomplexity and the new vision of P4 Medicine (predictive, preventive, personalized and participatory). It has developed a clear vista unto the world in the collective blind spot of current pharmaceutical industry that is holding back innovation. With this shared vision we have developed a rigorous and actionable research program that will complement current approaches and develop the new platform for the discovery of a new class of drugs.