Abstract
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A decade ago this October, systems biology pioneer Leroy Hood, M.D., Ph.D., and the Institute for Systems Biology that he co-founded announced a collaboration with Ohio State University to develop what is now the P4 Medicine Institute. “P4” medicine was Hood’s visionary paradigm that healthcare must evolve from being reactionary to being “predictive, preventive, personalized, and participatory.”
That paradigm is also known as precision medicine, a market whose value was pegged at $38.92 billion in 2015—and is expected to more than double by 2022, to $88.64 billion, according to Market Research Future.
Here we profile 10 companies to watch for their ambitious, and so far successful, application of “omics” technologies and clinical genetic insights to deliver on the promise of precision medicine:
CEO and co-founder, Allelica
Thanks to biobanks and large-scale, case-control studies such as Genome Wide Association Studies (GWAS), millions of genetic variants have been linked to several complex diseases. When variants are combined in a polygenic risk score (PRS), they can potentially identify people at significantly increased genetic risk to develop a disease compared to the average population, allowing for personalization of preventive plans.
“The problem is that genetic labs don’t have the skills to perform genomic-prediction analysis pipeline based on polygenic risk score, because despite being a simple weighted sum of the alleles’ effects, polygenic risk score is complex and computationally intensive to implement,” Giordano Bottà, Ph.D., CEO and co-founder of Allelica, told Clinical OMICs.
Bottà, a molecular biologist, joined two co-founders—geneticist George Busby, Ph.D., and software engineer Paolo Di Domenico—to launch Allelica in January 2018. Allelica is a Rome-based provider of risk prediction and GWAS analysis services to researchers and biobanks, with a focus on providing PRS for common disease quickly and accurately, using a cloud-based, software-as-a-service (SaaS) model.
“Allelica built the in-cloud infrastructure to analyze large genomics data in a seamlessly, fast, and safe way. Moreover, Allelica performs statistical analysis to identify the most predictive set of variants and validate their predictive power on the UK Biobank,” Bottà added. “We built polygenic risk score that can identify people at more than three-fold risk of developing complex diseases compared to the average population, and we provide advanced models including covariates such as age, family history, and traditional risk factors.”
Allelica says its analysis combines its review of genetic risk with lifestyle and clinical factors. To read DNA, the company uses Illumina’s Infinium Global Screening Array scanning systems, which are designed to allow the genotyping of more than 750,000 genetic variants with an accuracy greater than 99.9 percent.
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President and CEO, Day Zero Diagnostics
Antibiotic resistance has long been recognized as a top global health threat. It causes more than 2 million infections and 23,000 deaths per year in the U.S., according to the Centers for Disease Control and Prevention.
Day Zero Diagnostics (DZD), based at the Pagliuca Harvard Life Lab, is developing one solution to this threat—a rapid, whole-genome sequencing (WGS)-based diagnostic designed to identify the species and antibiotic resistance profile of a bacterial infection within hours.
“Our primary development program is focused on creating a rapid diagnostic for sepsis that can provide both species ID and comprehensive antibiotic resistance profiles so physicians can use targeted antibiotics at the first opportunity,” DZD President and CEO Jong Lee, a co-founder of the company, said. “We also provide a WGS-based rapid response service to help hospital infection control teams more effectively address suspected nosocomial infections.”
DZD was founded in 2016 by researchers from Harvard and Massachusetts General Hospital. In January, DZD completed an $8.6 million Series A financing led by healthcare-focused venture capital firm Triventures, with additional funding from Sands Capital Ventures and Golden Seeds.
The proceeds will enable DZD to accelerate development of its computational approach and Blood2Bac sample preparation technology, designed to isolate and enrich for bacterial DNA at high sensitivity directly from complex clinical samples containing over a billion times more human DNA. One approach is called Keynome, a machine learning algorithm designed to predict the antibiotic resistance profiles of pathogens based on their genomic sequences. Keynome is being developed and trained on MicrohmDB, DZD’s proprietary database containing what the company said is one of the largest collections of pathogen genomic sequences, combined with their known phenotypic resistance profiles.
“Our work on nosocomial infections has led to the creation of new capabilities for automated detection of outbreaks from genomic data,” Lee added.
CEO and co-founder, Mammoth Biosciences
Guy Kawasaki, who popularized “evangelist” marketing at Apple a generation ago, famously urged companies to reduce their mission statements to a three- or four-word mantra. By that benchmark, year-old startup Mammoth Biosciences is already a success—its mission is to “democratize disease detection.”
For Mammoth, democratization means leveraging a CRISPR-enabled platform to develop an easy-to-use and affordable point-of-care test capable of detecting any biomarker or disease containing DNA or RNA, based on CRISPR technology licensed exclusively from the University of California (UC).
Mammoth’s co-founders include CRISPR pioneer Jennifer Doudna, Ph.D., of UC Berkeley, who chairs Mammoth’s Scientific Advisory Board. Since emerging from stealth mode in April 2018, Mammoth completed a $23 million Series A financing and in March added Cas14, licensed from UC Berkeley, to a toolkit of CRISPR enzymes that includes Cas12 and Cas13.
“Mammoth’s detection platform will bring CRISPR out of the lab and into daily life for hospital-based and at home use, changing our interactions with the health-care system as we know it,” Trevor Martin, CEO and co-founder of Mammoth, told Clinical OMICs. “The company is exploring various methods for delivering the tests, one of which could be a disposable, credit card-sized paper test strip, which could detect a variety of biomarkers, from common infectious diseases such as STDs to cancer.”
Users who complete the test would securely upload an anonymous photo of the strip to Mammoth’s corresponding application for remote analysis, then receive their confidential results and professional advice—all in under an hour, according to the company.
Mammoth says its real-time test will not require refrigeration or advanced instrumentation, making it a go-to option in developing countries, where doctors have limited access to advanced medical equipment. “Ultimately, the faster the diagnosis, the faster the treatment response will be, and the closer we are to making a healthier world,” Martin added.
Founder and CEO, My Personal Therapeutics
The power of precision medicine—where a driver mutation in a tumor is targeted with a specific drug treatment—falls short for patients with multiple mutations, for whom a single therapeutic may not be effective.
Treating those patients is the goal of My Personal Therapeutics, a London-based startup founded last year to commercialize a new approach it says will revolutionize cancer therapeutics.
At the heart of My Personal Therapeutics is its Personal Discovery Process (PDP), a methodology developed by researchers at the Icahn School of Medicine at Mount Sinai Center for Personalized Cancer Therapeutics over four years of clinical research, with technical input from the FDA.
PDP applies big data in order to build up to a half-million personalized “fruit fly avatars” designed to model individual patients at a high level of complexity. PDP also applies robotics to screen thousands of drugs in combinations, in order to identify drug cocktails designed to target the tumor while preserving the patient’s quality of life.
Those combinations, My Personal Therapeutics adds, almost always include non-cancer drugs.
“A variety of evidence, including our own, demonstrates that genetically simple models fail to accurately predict whether a drug will work in a patient,” said Laura Towart, founder and CEO. “My Personal Therapeutics is dedicated to the principle that complex models, built to reflect individual patients, provide better tools for empirical and large-scale screening of candidate therapeutics.”
On April 12, My Personal Therapeutics said it exclusively licensed PDP from Mount Sinai for global commercialization. The company also secured initial funding of an undisclosed amount, led by London-based Startup Funding Club and independent international investors.
Towart said My Personal Therapeutics is also developing TuMatch, an AI-powered service designed to suggest treatments specific to a patient’s tumor genetics, rapidly and at low cost.
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Co-founder and CEO of NextGen Jane
There are smart cars, smart refrigerators, smart TVs, and of course smartphones. So why not a smart tampon? Creating one is the focus of NextGen Jane, a diagnostic startup focused on reproductive health technology.
The company—which calls itself “Jane” for short—has created a technology designed to allow users to collect menstrual and cervicovaginal samples with an everyday household product, preserve nucleic acids and other analytes important for disease detection, and ship them off to a lab for in-depth sequencing analysis and disease detection.
“The NextGen Jane system allows for superior preservation of DNA and RNA of cells from the endometrium, cervix, fallopian tubes, and ovaries. NextGen Jane then builds proprietary algorithms to correlate specific genomic signals found in cells shed from your body to specific disease states,” said Ridhi Tariyal, co-founder and CEO.
On April 1, NextGen Jane announced the completion of a $9 million Series A financing. Material Impact led the round, along with Access Industries, Viking Global Investors, Liminal Ventures, and several angel investors. The 10 angels included two notable researchers—George Church, Ph.D., of Harvard Medical School, and Stephen Quake, Ph.D., of Stanford University.
NextGen Jane said the proceeds will enable the company to position itself for commercialization of its technology some time in 2020. The company sees several factors as driving market need. Many female reproductive disorders present with generic symptoms that are difficult to differentiate; women’s pain is sometimes dismissed or normalized, complicating efforts at diagnosis; and some parts of the U.S. are experiencing OB-GYN shortages.
The company also cites a desire by women for alternatives to in-clinic, invasive, and expensive conventional methods of diagnosing reproductive disorders.
Co-founder and scientific advisor, Onegevity
Onegevity Health launched in January, positioning itself as a provider of consumer-friendly health recommendations based on integrated analysis of customers’ longitudinal blood, genetics, and gut microbiome profiles through the company’s multi-omic AI platform.
“Onegevity is focused on solving the limitations of one-dimensional health analytics, i.e., only blood or genetics alone,” Joel Dudley, Ph.D., Onegevity co-founder and scientific advisor, told Clinical OMICs.
By integrating untargeted analyses of longitudinal bio-markers—including blood, metabolomics, the human genome, and microbiome profiles—Onegevity aims to offer consumers a comprehensive molecular portrait through its Health Intelligence Platform.
The company also partners with nutrition company Thorne, and its network of 35,000 physicians, to offer customers testing and analytical tools designed to improve preventative care and lower healthcare costs. Customers receive customized lifestyle, exercise, and diet recommendations, including clinically-studied supplements, and pre- and probiotics.
Behind the science and analysis at Onegevity are personal stories. Dudley has Crohn’s disease; his wife has irritable bowel syndrome; and family members of Onegevity’s other scientific co-founder, Chris Mason, Ph.D., have struggled with various gastrointestinal issues.
Onegevity’s first product, GutBio, combines its advanced Metagenome+ sequencing technology with AI-based personalized insights. GutBio aims to give customers what the company says is the most comprehensive, accurate, and insightful picture of their microbiome health, with recommendations based on research, technology, science, and machine learning.
“With a holistic picture of health, Onegevity can understand how changes at one level (e.g., the gut microbiome) can drive healthy changes at another (e.g., blood) and provide the user with metrics based on data from other individuals with a similar profile,” Dudley added
Onegevity will soon expand services to include whole-genome sequencing and blood testing, plus personalized products and services for new populations. It is working exclusively with partner Drawbridge Health to develop the OneDraw blood sampling system, designed to enable convenient and nearly painless blood-testing.
Co-founder, president and CEO, Sherlock
Sherlock Biosciences isn’t named for Sherlock Holmes, but for one of its foundational platform technologies, officially called “Specific High-sensitivity Enzymatic Reporter unLOCKing,” and licensed from the Broad Institute of MIT and Harvard. Just as Sir Arthur Conan Doyle’s fictional detective combed for clues using observation and deduction, SHERLOCK is designed to detect genetic fingerprints across multiple organisms or sample types, as described in four papers published in Science.
Sherlock is also developing INSPECTR (INternal Splint-Pairing Expression Cassette Translation Reaction), a synthetic biology-based molecular diagnostics platform that can be programmed to distinguish targets based on a single nucleotide without an instrument, at room temperature. INSPECTR was developed by co-founder James J. Collins, Ph.D., and colleagues at the Wyss Institute for Biologically Inspired Engineering at Harvard University, and licensed from Harvard’s Office of Technology Development.
Despite its advanced technologies, Sherlock’s goals are elementary: “Making diagnostic testing better, faster, and more affordable.” The company was launched in March with $35 million in initial financing, including a $17.5 million non-dilutive grant from the Open Philanthropy Project and other undisclosed investors.
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“At Sherlock Biosciences, we aim to disrupt molecular diagnostics with better, faster, more affordable tests that can target any genetic signature, including infectious diseases and oncology, as well as non-clinical applications, such as agricultural testing without the need of complex lab instruments, allowing for rapid results in virtually any setting,” noted Rahul K. Dhanda, company co-founder, president, and CEO.
Dhanda is among the diagnostic veterans and scientific trailblazers who co-founded Sherlock. They include CRISPR pioneer Feng Zhang, Ph.D., of The Broad Institute, who chairs Sherlock’s scientific advisory board.
“We are on the cusp of solving challenges ranging anywhere from faster pathogen detection and simpler testing for cancer to improved food safety,” Dhanda added. “We envision a world where our products will enable users to make more effective decisions wherever results are needed.”
CEO, Stemina Biomarker Discovery/NeuroPointDX
Being the mother of a son with autism spectrum disorder (ASD), Stemina Biomarker Discovery CEO Elizabeth L.R. Donley has experienced many of the frustrations of parents with children on the spectrum—from delays in diagnosis, to searches for effective solutions and treatments.
Stemina’s NeuroPointDX business unit aims to address the unmet need for earlier diagnosis and more precise treatment of ASD, with which 1 in 59 U.S. children are diagnosed.
“We are identifying children as young as 18 months for earlier intervention with behavioral therapy and developing paired therapies to treat the metabolic imbalances we see in children with ASD,” said Donley. “Some of these will be supplements or medical foods, and others will be targets for new drugs—or additional indications for existing drugs—all based on the underlying metabolic differences of the child with ASD.”
Donley said the NeuroPointDX ASD test can identify about 30 percent of children with ASD with an increased risk of the disorder.
Using proprietary analytical methods, the company has created tests to identify unique subtypes of metabolism in children with ASD. In a study published February 15 in the journal Biological Psychiatry, the company identified some of these subtypes, which are associated with dysregulation of amino acids and branched-chain amino acids.
The study offered the first results from the NIH-funded Children’s Autism Metabolome Project (CAMP), the largest clinical study of the metabolism of children with ASD. CAMP is a large-scale effort to define autism biomarkers based on metabolomic analyses of blood samples from 1,100 children ages 18 to 48 months.
“The size and design of this study is the first of its kind calculated to identify differences in metabolism in children in subtypes as small as 5 percent of the ASD cases,” Donley said. “Metabolism-based stratification of ASD offers the potential for earlier diagnosis and more precise interventions based on the child’s own metabolism.”
Co-founder and CEO, Trugenomix
Following their return from service in Iraq or Afghanistan, 422,167 veterans were screened for potential or provisional post-traumatic stress disorder (PTSD) as of June 30, 2015, according to a 2017 study published by the U.S. Department of Veterans Affairs. Up to 500,000 returning service men and women may have been diagnosed with PTSD, according to estimates cited by the Wounded Warrior Project and others.
That human cost of PTSD has compelled a Rockville, MD, startup to develop a diagnostic for the disorder. Tru-Genomix Health aims to commercialize a discovery made about a decade ago by scientists at the Icahn School of Medicine at Mount Sinai and the Max Planck Society in Germany. Researchers identified a panel of genes that predict if an individual has a predisposition to develop PTSD when exposed to trauma.
“TruGenomix Health is focused on advancing this technology and commercializing a blood test that can help provide solutions to improve the lives, health, and future of members of the military, veterans, and their families,” co-founder and CEO Yusuf Henriques said. “TruGenomix hopes to better target PTSD treatment in veterans and other trauma survivors, including survivors of car accidents, sexual trauma, and natural disasters.”
Henriques is a former U.S. Army combat medic whose military career was shortened by service-related injuries. In 2017, he co-founded TruGenomix with Tshaka Cunningham, Ph.D., the company’s chief scientific officer, and a former VA scientific program manager, and the company’s chief operating officer Charles Cathlin, an Air Force Academy graduate and former Chief of Staff of the Defense and Veterans Brain Injury Center. Cathlin served in the Air Force and later the Public Health Service, retiring in May 2018.
Last year, TruGenomix graduated from Illumina Accelerator’s seventh funding cycle. “We had access to several teams of top-shelf genomics and bioinformatics experts at Illumina and were able to build our screening tool in a highly scalable fashion using cutting-edge genomic sequencing technology,” Cunningham added.
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CEO, xCures
The drug-centric way in which treatments are developed, and the haphazard way in which knowledge about those treatments is captured and delivered to the point of care does not serve patients well, according to xCures.
The Los Altos, CA-based company has developed an AI-based precision oncology platform designed to tightly integrate research and care. The xCures platform runs a perpetual trial that captures Real World Evidence (RWE) to continuously learn from all patients, on all treatments, all the time.
The platform coordinates treatment recommendations across all patients and institutions to match patients with treatments that work, and packages RWE for use across oncology, with the goals of slashing the time and cost of drug development.
“Currently, clinical research and care exist in two separate worlds,” xCures CEO Mika Newton noted. “Cancer trials take too long, cost too much, and are too siloed. There are too many possible treatments, and not enough patients to test them. Thousands die unnecessarily because no one knows the optimal way to treat cancer using currently available drugs, especially off label and in combination. Testing these will require exponentially more patients than participate in research today.”
xCures solves this problem, Newton said, by enabling all patients to participate in research that directly informs their care. On March 12, xCures joined the nonprofit collaborative Cancer Commons in partnering with Oncoceutics to implement an Expanded Access program for its lead candidate, ONC201, an orally active small molecule DRD2 antagonist. The program includes an intermediate size Expanded Access protocol for ONC201 in patients with H3 K27M-mutant glioma, which has received FDA approval.
“xCures connects patients to the treatments most likely to help them. Data about outcomes is collected constantly, so treatments continuously improve,” Newton added. “Trials that put patients first is an idea whose time has come.”