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Warp speed ahead
October 2016
by Lori Lesko  |  Email the author
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CAMBRIDGE, Mass.—Aimed at discovering innovative drugs while maneuvering on the core principle that nature is the most powerful inventor of new drugs, Warp Drive Bio Inc. is celebrating its first patent covering the company’s Small Molecule-Assisted Receptor Targeting (SMART) platform. This new patent, “Identifying New Therapeutic Agents,” issued Aug. 30 by the U.S. Patent and Trademark Office, is held exclusively by Warp Drive Bio.
 
“Warp Drive Bio is committed to developing groundbreaking therapeutics by exploiting its proprietary technology platforms,” Laurence Reid, president and CEO of Warp Drive Bio, stated in a news release. “The issuance of this key patent demonstrates the novelty of our approach to discover new drug candidates through our SMART platform.”
 
“This is the first fundamental patent to issue from our IP portfolio, and it’s an important plank in the foundation of our business,” Reid adds. “With this fundamental IP in place, we will continue to build a leading company searching for new transformative medicines to treat human disease.”
 
The company says its SMART program enables the discovery of small-molecule drugs targeting disease-causing proteins previously considered to be intractable to traditional pharmaceutical modalities. It is estimated that more than 80 percent of human proteins cannot be targeted by conventional drug discovery approaches such as small molecules and protein biologics, either because they do not contain a binding site required by small-molecule drugs or are intracellular and therefore inaccessible to biologics.
 
SMART drugs bind to an intracellular receptor, and that complex assumes the properties of an “intracellular biologic,” providing the opportunity for therapeutic modulation of the disease-causing protein, the company explains. This novel approach, and associated intellectual property, is enabling Warp Drive Bio researchers to address targets previously considered “undruggable.”
 
SMART drugs are based on natural chemistry, combining the cell penetration properties of small molecules with the target-interaction mechanisms of proteins and accessing many of the more than 80 percent of human proteins that cannot be targeted by classical therapeutics.
 
One example of SMART modality in nature is rapamycin, the natural prototypical SMART drug, company scientists say. 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.
 
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 roughly 30 percent of cancer patients with RAS-driven disease, the company says.
 
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 says it “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.”
 
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 the company says it is broadening the set of molecules from which those can be developed.”
 
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 to 95 percent 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, according to the company. 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.
 
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,” the company reports.
 
As noted on Warp Drive Bio’s website, “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.”
 
Code: E101605

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