February 15, 2017 (Vol. 37, No. 4)

Industry Watch: Bio-Rad Eyes Digital PCR Growth with RainDance Acquisition

Bio-Rad Laboratories has signaled its growing interest in digital PCR with its recent plans to acquire RainDance Technologies for an undisclosed price.

“We look forward to expanding our offering to provide life science and clinical diagnostics customers with solutions for a wide range of nucleic-acid detection applications,” Bio-Rad president and CEO Norman Schwartz said January 16 in a statement announcing the acquisition. “The company’s droplet-based solutions will extend our reach into next-generation sequencing (NGS) applications and strengthen our position in the area of Droplet Digital™ PCR.”

Droplet Digital PCR (ddPCR) is based on water-oil emulsion droplet technology in which a sample is fractionated into 20,000 droplets, with PCR amplification of the template molecules occurring in each individual droplet.

Bio-Rad introduced the first commercially available ddPCR platform in 2011, the QX100 Droplet Digital PCR System, and followed up two years later with its latest-version QX200. “The leading application right now is in the liquid biopsy technology space,” Shannon Hall, a Bio-Rad evp and president of the company’s life sciences group, told analysts November 1.

RainDance has focused on developing droplet microfluidic technology. The company’s digital PCR tools include its RainDrop® system introduced in 2013, followed by its RainDrop Plus™ system launched in November.

RainDance and Bio-Rad are two of four digital PCR manufacturers; the others are Life Technologies and Fluidigm. While Bio-Rad has significant market share, “RainDance technology is definitely faster than Bio-Rad and has the ability to partition droplets 500 times faster than Bio-Rad systems,” said Divyaa Ravishankar, senior industry analyst with Frost & Sullivan.

“[Bio-Rad] also gains access to some important accounts such as Myriad Genetics, which are high users of RainDance Technologies, and partnerships with Pacific Biosciences to co-develop assays,” Ravishankar added.

PacBio and RainDance launched a partnership in 2015 to co-develop and commercialize novel solutions for de novo whole genome assembly, by combining RainDance’s digital droplet technology and single-molecule barcoding capabilities with PacBio’s long-range DNA amplification technology.

Headquartered in Billerica, MA, RainDance also markets the ThunderStorm® and ThunderBolts™ systems used in sample enrichment for NGS.

Bio-Rad said it expects the RainDance acquisition to close during the first quarter of 2017.

Discovery & Development: Cancer Vaccine Development Elicits Strong Reaction

Cancer vaccines are getting more personal as they sharpen their focus on neoantigens, which are antigens that are new to the immune system. Neoantigens that arise when tumors develop are encoded by tumor-specific mutated genes. Because these neoantigens are unique to an individual’s tumor, they may serve to guide personalized anticancer therapies.

Cancer vaccines have long represented a promising approach, but they have tended to underperform. These disappointing cancer vaccines usually attempt to alert the immune system to antigenic targets that are common to tumors yet absent from normal tissues.

The new targets, the neoantigens, may be a game-changer. They may be used to alert the immune system to one Achilles’ heel after another. In fact, neoantigen-based approaches have performed well in several recent studies, encouraging developers and analysts alike. Several cancer vaccine developers—including BioNTech, Neon Therapeutics, and Gritstone Oncology—have attracted sizable investments. Also, GBI Research has projected that the cancer vaccine market is set to almost triple from $2.5 billion in 2015 to $7.5 billion by 2022.

Yet complications remain. Patient-specific antigens, next to antigens that are common across tumor types, may present a more difficult developmental challenge. Although neoantigens are becoming easier to identify, thanks to speedier and less-expensive sequencing technology, neoantigen-based cancer vaccines may be harder to cost-effectively manufacture at the necessary scale. Also, in the case of fast-growing cancers, development time may prove to be an issue. Finally, cancers that present relatively few neoantigen targets may be more apt to develop resistance.

Undeterred by these challenges, one cancer vaccine developer is neoantigen-enabling an antigen-presentation technology that has already been shown to remodel the tumor microenvironment. This company, Aduro Biotech, announced that it is combining its live, attenuated double-deleted Listeria (LADD) immunotherapy platform with a neoantigen identification technology developed at Stanford University.

With an exclusive license in place, Aduro will engineer personalized LADD-based cancer therapies (pLADD) to encode multiple neoantigens. The company plans to initially evaluate pLADD for the treatment of cancers of the gastrointestinal tract, including colorectal cancer. A Phase I trial is scheduled for later this year.

Genomics & Proteomics: Algae Biofuels Research Gets Renewed Contract

In an effort toward making significant progress in algae biofuels research, Synthetic Genomics and ExxonMobil have recently announced that they are extending their agreement to conduct further studies into understanding algae genetics, growth characteristics, and increasing oil production.  

“Together with ExxonMobil, we have made significant strides to identify and enhance algal strains capable of high oil production, while still maintaining desirable rates of growth,” said Oliver Fetzer, Ph.D., CEO of Synthetic Genomics. “The extension of our agreement reflects the tremendous progress made to date, and the promise in using our core synthetic biology technologies to build cell-production systems capable of reshaping industries.”

ExxonMobil and Synthetic Genomics have been jointly researching and developing oil from algae for use as a renewable, lower-emission alternative to traditional transportation fuels since launching this unique program back in 2009. Work continues toward developing strains of algae that demonstrate significantly improved photosynthetic efficiency and oil production through selection and genetic engineering of higher-performance algae strains. The renewed agreement will continue to focus on Synthetic Genomics’ core strengths in synthetic biology and builds on recent discoveries of biological pathways regulating lipid production and growth in advanced algal strains.

“Synthetic Genomics and ExxonMobil remain committed to advancing the scientific fundamentals of algal biofuels,” remarked Vijay Swarup, vp, R&D, ExxonMobil Research and Engineering Company. “We know this will be a long-term endeavor and are optimistic based on the results we have seen to date.”

This agreement comes amid a recent announcement by Scott Pruitt, President Trump’s pick to lead the EPA, that he would honor the intent of the U.S. biofuels program, yet he remained open to fine-tuning it. Mr. Pruitt’s comments may have belayed some concerns within the industry about his level of commit to alternative fuel sources, since he previously described the program as “flawed” and “unworkable.”

Global demand for transportation fuels is projected to rise by nearly 30% through 2040, and accelerating the reduction in emissions from the transportation sector will play a critical role in reducing global greenhouse gas emissions.  

Bioprocessing: Servier Taps MaSTherCell for CAR-T Cell Therapy Manufacturing Platform Development

Servier and CDMO MaSTherCell signed a master service agreement for the development of a CAR-T cell manufacturing platform that will enable industrial and commercial manufacturing of Servier allogeneic cell-therapy products. This is a critical step in development of these products for later stage clinical trials, according to Servier officials.

Cell therapies have shown promising results in treating cancers. However, successful development has been mainly limited to autologous therapies. This approach, where the patient’s cells are collected and then used to create a drug for that specific patient, is limited by the lack of possibility of industrialized manufacturing, thus restricting its access to few patients. Allogeneic therapies are developing rapidly but the challenges of their manufacturing scale-up still lie ahead.

“We at MaSTherCell see allogeneic T-cell therapy as a very encouraging area due to the offer of an off-the-shelf product, giving access to a high number of patients, with a reduced cost of goods,” said Denis Bedoret, CBO, MaSTherCell. “The ultimate objective is to deliver treatments at an affordable price for both the patients and health insurance organizations”.

One of the most advanced cell therapies is based on CAR-T technology, where the T cells are armed with a chimeric antigen receptor. Servier is developing UCART-19 with two clinical trials currently ongoing in Europe in relapsed or refractory B cell acute lymphoblastic leukemia (B-ALL), in pediatric and adult patients.

Servier says it selected MaSTherCell because of its leading global cell therapy CDMO position as well as its essential broad expertise in immunotherapy products. MaSTherCell has a track record of designing and delivering cost-effective cell-therapy manufacturing platforms, notes Marielle Anger-Leroy, director of biotechnology industrial development at Servier.

MaSTherCell anticipates that it will complete the development of the initial CAR-T platform in 2018. This will then be an efficient complement to the bioproduction facilities that Servier is developing at its site at Gidy, France, which will mainly focus on the production of antibodies, explains Anger-Leroy.

“The scale up of manufacturing for late-scale clinical trials still remains one of the biggest industry-wide challenges in the cell-therapy sector, and especially in a CAR-T field still in its infancy,” she adds. “Being pioneers with these innovative therapies means that we have to find the best partners to maximize the chances of delivering these therapies to patients with few alternative options.”

MaSTherCell is developing a platform that will facilitate the manufacture of Servier’s CAR-T candidate UCART19. Licensed by Servier from Cellectis, UCART19 is an allogeneic CAR-T cell product candidate for treatment of CD19-expressing hematological malignancies. As an allogeneic departure from the current autologous approach, UCART19 has the potential for convenient deployment. It is to be provided as a frozen, “off the shelf” T cell–based medicinal product.

Molecular Diagnostics: R&R Means Rescue & Repurposing for CGI and Lantern

Cancer Genetics (CGI) and Lantern Pharma will collaborate to rescue and repurpose drugs, leveraging the biomarker discovery, clinical trial testing, and companion diagnostic development capabilities of CGI with Lantern’s AI and big-data driven development approach.

The initial focus of the collaboration will be discovery services and further development of Lantern’s lead compounds, including Tavocept (LP-300) for non-small cell lung cancer (NSCLC). Tavocept has shown clinical efficacy in a small subset of NSCLC patients, in combination therapies. Lantern’s second candidate, LP-184, has demonstrated promising, early anti-tumor activity for multiple solid tumors, especially gynecologic tumors.

“Oncology compounds have undergone tremendous advancement in design, but have lacked the systematic analysis leveraging big-data and precision trial design and testing, which has led to inefficient processes and lackluster approval rates,” said Arun Asaithambi, Ph.D., co-founder and CEO of Lantern Pharma. “By developing targeted biomarker panels, in conjunction with Cancer Genetics, that can precisely sub-type patients based on the ability to be responsive to a treatment and then incorporating that into the selection and testing process, we can save years and tens of millions of dollars; thereby making treatments more personalized and more accessible.”

Lantern has identified biomarkers for both candidates. CGI will develop the biomarkers, perform laboratory validation testing and analysis, and develop potential companion diagnostics. Additionally, CGI will evaluate developing liquid-biopsy based tests for Tavocept patient selection and monitoring in NSCLC.

“Our collaboration with Lantern and their expertise in AI-driven drug development will enable a new level of usage and evaluation of our predictive biomarker and NGS panels. Repurposing and rescuing promising drug compounds for accelerated clinical trials is a key component to precision medicine and improving the productivity of drug discovery,” commented Panna Sharma, president and CEO of Cancer Genetics.

CGI recently signed multiple collaboration deals to develop liquid biopsy technologies. Said Sharma at the time, “CGI’s experience in developing, comparing, and validating biomarker assays for precision oncology is unmatched, and in high need, as liquid biopsies begin to create clinical interest and enable new, less-invasive methods for detection and monitoring.”  This came at the same time the company consolidated its workforce to achieve greater efficiency in administrative, finance and operational support functions.

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