Genetic Engineering & Biotechnology News

AUG 2017

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6 | AUGUST 2017 | GENengnews.com | Genetic Engineering & Biotechnology News Gail Dutton Bactevo's Totally Integrated Medicines En- gine (TIME) assays 100 million samples per hour. Running multiple assays in parallel, it harnesses next-generation synthetic bio- space libraries, identifies disease networks, and targets and deploys chem- and bioinfor- matics for knowledge mapping to create and advance in vivo-ready therapeutics while simultaneously performing ADME-Tox (ab- sorption, distribution, metabolism, excre- tion, and toxicity) lead profiling. In essence, TIME combines library gen- eration, candidate screening, and assay anal- ysis to support a high-throughput approach to drug discovery. TIME can perform a bat- tery of assays in weeks that otherwise would take years to complete, says David Wil- liams, Ph.D., Bactevo's CEO. In his estima- tion, TIME could shorten drug-development times by orders of magnitude. Dr. Williams suggests that in terms of the depth and quantity of information pro- duced, TIME is the Google of drug discov- ery. "It will radically increase the success rate and speed of medicine discovery by har- nessing an unprecedented depth of relevant phenotype and profiling data simultaneously," he adds. "We believe it will revolutionize the industry." The key benefit is the ability to select molecules more rationally. TIME generates a tremendous amount of data on safety and efficacy during the earliest stage of lead se- lection. As a consequence, explains Dr. Wil- liams, users can be more sure of the mole- cules they put into the clinic. "Also, users can perform the initial high- throughput screening on patient-derived cells or tissue, thus making a critical link with the disease," he notes. "This can change the whole paradigm of safety and efficacy during drug development." Natural and Synthetic Libraries Bactevo developed TIME by mining the natural products of bacteria to engineer product libraries that reflect the huge diver- sity of chemical structures that are synthe- sized by organisms across the bacterial king- dom. Using naturally occurring microbial products as a starting point increases the chances that any resulting drug candidates will have biological relevance and, thus, possess the potential to interact with mam- malian systems. The TIME platform was then extended to include the capability to create totally synthetic chemical libraries, with built-in medicinal properties. The synthetic librar- ies are generated as required and screened with multiple replicates and at different concentrations, allowing both positive and negative data to be used to generate what Bactevo calls "Total Structure Activity Re- lationships." That, in turn, provides the foundation for hit selection and chemical optimization. To perform the assays, TIME uses two approaches. The first synthesizes and screens billions of tagless molecules at up to millimol- ar concentrations within days. The second, complementary to the first, identifies and isolates biologically evolved small molecules. The resulting synthetic chemical library also can be inspired by hits obtained from the en- gineered bacteria, thus allowing the biologi- cally evolved chemical scaffolds to be further "evolved" to ideal drug candidates. Initial Focus: Mitochondrial Disease Bactevo is using TIME internally to de- velop its lead programs in mitochondrial disease. "The mitochondria is a major gate- keeper for other diseases," Dr. Williams points out. The program is designed to develop therapeutics to improve mitochondrial bio- genesis to address defects in mitochondrial function that result in the rare, progressive mitochondrial myopathy, encephalopathy, Bactevo Speeds Discovery with Multichannel Chemistry and Microdroplet-Based Screening TIME for Parallelized Drug Discovery Corporate Profile Bactevo has developed the Totally Integrated Medicines Engine (TIME), which combines microfluidics, nanofabrication, and artificial intelligence technologies to accelerate drug development. Two channels of chemistry feed a high-content screening platform that performs billions of assays in a single day. TIME may also support simultaneous drug-dose response and ADME-Tox assays, generating an enormous amount of upfront data. Insights Industry Watch Biopharma venture capital (VC) activity is poised for one of its strongest years if the dollar volume of deals continues as high as seen in the first half of 2017. Investors raised $1.876 billion in 93 biotech VC deals during the second quarter, according to the most recent quarterly MoneyTree™ Report from Pricewaterhouse- Coopers (PwC) and CB Insights, released July 12, 2017. That's 5.6% in dollars, and about 21% in number of deals, above the $1.776 billion in 77 biotech VC trans- actions recorded in Q2 2016. However, the second three months of 2017 lagged behind the first quarter, in which $2.821 billion in VC was raised in 112 deals. Q1 numbers were skewed by a pair of megadeals to- taling $1.1 billion—nearly all of which consisted of the $900 million raised by cancer diagnostics firm Grail. "If we continue to see one or two large deals like we have over the first two quarters, we could be looking at one of our strongest life science years in history," Greg Vlahos, PwC's US life-sciences venture capital leader, told GEN. "If you look at the total dollars for just the first two quarters, we're on pace for an extremely strong 2017 that has been buoyed by some of these megadeals we saw in Q1 and Q2." During the second quarter, a pair of additional nine- figure deals were completed, accounting for about 26% of the quarter's biotech VC financing. Guardant Health said May 11, 2017 that it racked up $360 million in new funding, while Rubius Therapeutics said June 21, 2017 that it raised $120 million in a "highly" oversubscribed private financing. Seven additional companies raised $45 million or more, accounting for $372.18 million or nearly 20% of the VC funding raised during Q2. WuXi NextCode raised $75 million, the most of the seven, followed by Intarcia Therapeutics ($54.68 million), Deciphera Pharmaceuticals ($52 million), Magenta Therapeu- tics and Syntimmune ($50 million each), Arsanis ($45.5 million), and TP Therapeutics ($45 million). "We're seeing dollars go to companies who normal- ly are at a later stage deal getting close to a liquidity event. As it takes a little longer for liquidity for some companies, we're seeing larger rounds go to these companies," Vlahos said. n Buoyed by Megadeals, Biotech VC Poised for One of Its Strongest Years Bactevo's CEO suggests that in terms of the depth and quantity of information produced, the company's TIME plat- form is the Google of drug discovery.

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