A New Approach

Warp Drive Bio is a leading company exploiting the molecules and mechanisms of nature to create transformative medicines. The company operates on the core principle that nature is the world's most powerful inventor of therapeutic agents, unconstrained by the mechanistic and synthetic limitations of traditional medicinal chemistry. Warp Drive Bio is deploying two proprietary platforms to discover and develop novel molecules addressing new pharmacologic mechanisms.

"We are reimagining the possible: drugging undruggable targets.”

-Anna, Scientist

SMART™

Small Molecule-Assisted Receptor Targeting (SMART™)

Warp Drive Bio is developing a new drug modality, SMART, based on a mechanism discovered in nature. SMART enables small molecules to target human disease-causing proteins previously considered to be intractable to the traditional pharmaceutical modalities. It is estimated that >80% of human proteins cannot be targeted by conventional drug discovery approaches - small molecules and protein biologics - either because they are intracellular (inaccessible by biologics) or do not contain an involuted, hydrophobic binding site (required by small molecule drugs). SMART drugs, in essence take on a role of an "intracellular biologic" therapeutic.

SMART drug and presenter protein, such as FKBP,
cooperate to bind an undruggable target

SMART drugs are based on natural chemistry and offer a solution to this vast set of pharmaceutical opportunities. They are able to penetrate cells where they bind to an intracellular receptor (the "presenter protein"). The resulting complex (SMART drug plus presenter) can then bind and modulate a specific intracellular target. The surface properties of the SMART drug-presenter complex enable it to bind protein target surfaces through an interaction that recapitulates the mechanisms by which proteins naturally interact inside cells. SMART thus overcomes the limitations of small molecules to bind to such surfaces. SMART drugs combine the cell penetration properties of small molecules with the target-interaction mechanisms of proteins and can therefore access many of the >80% of human proteins that cannot be targeted by classical therapeutics.

Example of SMART modality in nature: Rapamycin

Rapamycin is the natural prototypical SMART drug. It enters cells and forms a complex with FKBP, which can then bind a flat undruggable surface on mTOR with high affinity and selectivity. This leads to inhibition of mTOR activity.

Lead SMART program: RAS

The initial focus of Warp Drive Bio's SMART discovery efforts is a series of drugs that antagonize RAS in various states and mutant forms. Although RAS has been studied for decades, it is a target that has been undruggable to date. The long-term goal of the Warp Drive Bio RAS program is to obtain durable treatment responses in the ~30% of cancer patients with RAS-driven disease. Beyond RAS, there are many biological targets with strong validation that have been undruggable. These targets represent a set of opportunities to develop important new medicines in diverse diseases, including oncology, inflammatory diseases and metabolic diseases.

Key Facts About RAS*

  • RAS genes are one of the most frequently mutated oncogenes in human cancer. 
  • Three million new cancers with RAS mutations are diagnosed worldwide every year.
  • RAS mutations are present in approximately 30% of human cancers.
  • RAS mutations are most frequent in pancreatic cancer (90%), colorectal cancer (40%), non-small cell lung cancer (30%), bladder cancer (30%), peritoneal cancer (30%), cholangiocarcinoma (25%), and melanoma (15%). 
*McArthur, G.A. Exploring the Pathway: The RAS/RAF/MEK/ERK Pathway Fact Sheet. American Society of Clinical Oncology. http://am.asco.org/exploring-pathway-rasrafmekerk-pathway-fact-sheet. Published May 31, 2015. Accessed April 6, 2016.

"We are not afraid to take on tremendous challenges in order to develop transformative medicines."

-Dylan, Associate Director

Genome Mining

Genome Mining for Natural Products

Warp Drive Bio is deploying a battery of state-of-the-art, genome mining technologies to access powerful natural product drugs that have been historically "hidden" within microbes. The history of natural product pharmaceuticals has taught that most natural products derived from microorganisms cannot be detected under normal laboratory conditions. Warp Drive Bio has assembled a vast genomic database of over 130,000 strains encoding more than three million biosynthetic gene clusters. To exploit this expansive genomic resource, Warp Drive Bio has developed a proprietary "genomic search engine" that enables hidden natural products to be revealed on the basis of their genomic signature. We then deploy our "genomes to molecule" synthetic biology platform to engineer and express novel natural products, so they can be isolated and tested for biological impact. Warp Drive Bio is thus opening for the first time the complete natural product armamentarium for drug discovery.

The initial focus of Warp Drive Bio's genome mining efforts is to identify all the natural products related to certain classes of known approved antibiotics (e.g., beta-lactams). The challenges of drug-resistant infections are creating a constant need for new antibacterial medicines and Warp Drive Bio is broadening the set of molecules from which those can be developed.

For more information on Warp Drive Bio's genome mining approach, see our SIMB 2015 talk entitled Rapid Engineering of Secondary Metabolite Gene Clusters in the Genomic Era and our SIMB 2016 talk entitled Surveying Thousands of Actinomycete Genomes for Novel Biosynthetic Clusters.

Central Dogma of Molecular Biology

Warp Drive Bio's Genomic Mining Platform

  • Genetic linkage: natural product biosynthetic genes are clustered in bacteria and fungi
  • Construction demystified: biosynthetic logic deciphered for many major natural product classes
  • Structural novelty can be assessed at the genome level

A major drawback to the traditional approach to natural product discovery is that only the predominant compounds produced in the fermentation step are readily identified, while compounds that are conditionally expressed go undetected. Reliance on this traditional discovery methodology has, for example, yielded the rediscovery of known antibiotics many times, with much time and effort wasted on "dereplication" of known compounds.

Warp Drive Bio's strategy to natural product drug discovery circumvents the limitations of previous approaches. Microbial genome sequencing has revealed the enormous biosynthetic capacity of actinomycetes, with about 90-95% of all biosynthetic pathways being "silent" or "cryptic" under standard laboratory fermentation conditions. Genomic search within known molecular classes is facilitated in bacteria and fungi because the genes that produce the antibiotic are clustered. From the sequence of the gene cluster, the biosynthetic logic of the natural product can be deciphered, thus allowing a prediction of the structural novelty of the molecule encoded by the cluster. Warp Drive Bio has developed proprietary state-of-the-art tools to rapidly identify and isolate the molecule from a novel biosynthetic gene cluster as a bioactive compound of interest, so that it can be advanced into biological assays and potential drug development.

The initial focus of Warp Drive Bio's genome mining efforts is to identify all the natural products related to certain classes of known approved antibiotics (e.g., beta-lactams). The challenges of drug-resistant infections are creating a constant need for new antibacterial medicines and Warp Drive Bio is broadening the set of molecules from which those can be developed.

The next generation of Warp Drive Bio natural products will be identified through our genome mining platform as new natural products with therapeutic value in diverse diseases, including infectious diseases (e.g., novel antibiotics) and cancer.

Our ultimate vision for this program is that we will identify the complete natural product armamentarium of the actinomycete family, thus creating a unique new set of pharmaceutical chemical diversity with broad application in the discovery of new human therapeutics.