November 1, 2017 (Vol. 37, No. 19)

Industry Watch: FDA Awards $10M in Grants for Rare Disease Natural History Studies

The FDA said on October 6, 2017 that it has awarded six research grants totaling more than $10 million for natural history studies in rare diseases. The $10.3 million includes $6.3 million over five years from the FDA’s Orphan Products Grants Program—the first time the FDA is providing funding through the program—and $3.5 million received through a partnership with the NIH’s National Center for Advancing Translational Sciences (NCATS). The $3.5 million accounted for most of the $4 million awarded to two of the six grant awardees, with the rest coming from the FDA.

The FDA said the research is intended to support medical product development by better understanding how rare diseases progress over time. A potential application of these studies, the agency said, is the opportunity to eventually use natural history models to augment the need for placebo arms in studies of drugs that target very rare disease, where trial recruitment can be challenging. Since becoming FDA commissioner this year, Dr. Gottlieb has cited the agency’s interest in natural history models. Addressing the Regulatory Affairs Professsionals Society (RAPS) 2017 Regulatory Conference on September 11, 2017 Dr. Gottlieb said the agency was collaborating with researchers to use computational tools to develop natural history models, based on placebo arms in Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, and muscular dystrophy. “If we’re able to make better use of rigorous, reliable natural history models, especially for rare diseases, it can help make clinical trial recruitment more efficient,” Dr. Gottlieb told RAPS conference attendees, according to a transcript posted on the FDA website. The FDA said it received more than 80 grant applications that were reviewed and evaluated for scientific and technical merit by more than 60 rare disease and natural history experts.

Discovery & Development: Evotec Buys Into AI-Driven Discovery by Investing in Exscientia

Evotec has made a €15-million investment to take a minority stake in Exscientia, a company focused on artificial intelligence (AI)-driven drug discovery. Through this investment, Evotec becomes the first strategic shareholder in the U.K.-based company.

The investment contributes to the momentum building behind AI-driven drug discovery. According to research provided by Global Market Insights (GBI), the healthcare-related AI market will post a 40% compound annual growth rate in the coming years. Overall, the market is expected to exceed $2.5 billion by 2024. GBI estimates that over 35% of this market, representing up to $4 billion in revenue, will be generated by the market’s drug-discovery segment.

The new arrangement between Evotec and Exscientia builds on a relationship that was initiated in 2016, when the companies began cooperating to advance small molecules and bispecific small molecules in immuno-oncology. Exscientia is one of several companies that uses AI to explore target-based approaches to drug discovery. Other such companies are Numerate (which recently announced partnerships with Servier and Takeda Pharmaceuticals) and Atomwise (which is working on “confidential” projects with AbbVie and Merck).

Another facet of AI-driven drug discovery was highlighted by Konica Minolta’s recent acquisition of Invicro, a quantitative biomarker company. By combining biomarker expertise with molecular digital imaging technology, Konica and Invicro intend to focus on the fields of immuno-oncology and neurodegenerative disease.

On yet another front of AI-driven drug discovery, there are companies such as TwoXAR and Berg Health that are leveraging of bioinformatics to unravel molecular networks and identify potential drug targets. Exscientia’s work with Evotec, noted previously, is representative of AI-driven efforts in multitarget drug discovery. Also, Exscientia recently announced a €250-million collaboration with Sanofi to develop bispecific small molecules to treat diabetes.

Genomics & Proteomics: New Indexing Solutions Exploit Latest Next-Gen Sequencers

NuGEN Technologies announced a new line of indexing solutions that are designed to enable researchers to exploit the latest generation of Illumina sequencers fully. The new enhancements include the launch of 96 unique dual-index pairs to address index hopping, the incorporation of molecular tags to measure PCR duplication levels accurately, and the release of a new Metaplex Module designed to scale multiplexing to thousands of samples per flow cell.

The “index hopping” or “barcode hopping” phenomenon, which occurs more frequently on patterned flow cells from Illumina’s NovaSeq and HiSeq 3000/4000 platforms, is a low-frequency event that leads to mis-assignment of reads to different samples. The addition of unique dual-index pairs to the library enables software to recognize when barcode hopping has occurred and eliminates the read from the analysis.

“The use of unique dual-index pairs is particularly critical when working with applications that require a high degree of sensitivity, such as detecting mutations in cell-fr ee DNA or rare transcripts in any RNA sample,” explains Doug Amorese, Ph.D., NuGEN’s CSO. “With the addition of unique dual index pairs to NuGEN’s DNA and RNA library preparation kits, greater confidence can be achieved for all samples.”

The sequencing enhancements—which feature 96 unique dual-indexes, or 192 different sequences—are currently available for a variety of preparation kits aimed at the creation of DNA- and RNA-seq libraries. Moreover, solutions for the Methyl-Seq product line will also be available soon.

The release of Illumina’s NovaSeq has led to a significant increase in the number of reads obtained in a single sequencing run. While this has reduced the cost of sequencing, it presents a challenge to researchers, since many samples must be pooled. NuGEN’s third innovation, the Metaplex Module, when used with the Allegro Targeted Genotyping system, can enable scaling up to over 3000 samples in a single lane.

“The ability to scale across hundreds to thousands of samples is a requirement for us to be able to provide a cost-effective solution to our customers,” concluded Davide Scaglione from IGA Technology Services, an applied genomics solutions provider based in Udine, Italy.

Bioprocessing: Mammalian Manufacturing Expansion Drives Lonza Purchase of Shire Site

By acquiring a clinical-stage site in Hayward, CA, from Shire for an undisclosed price, Lonza is growing its presence in mammalian manufacturing even beyond recent expansions.

The acquisition, announced October 3, 2017 will add the Hayward site’s 1,000-L and 2,000-L single-use bioreactors and associated downstream capabilities to Lonza’s three 1,000-L single-use bioreactors at its mammalian development and manufacturing site in Slough, U.K., focused on preclinical to early clinical supply.

“The site will significantly increase our single-use bioreactor capacity in the clinical development mammalian network,” Lonza spokeswoman Constance Ward tells GEN.

The 58,000-square-foot Hayward site has operated as a multiproduct cGMP facility since 1990. Shire inherited Hayward when it completed its $32-billion acquisition of Baxalta in 2016.

“Shire continually reviews its product supply network to ensure we are operating efficiently and ready to meet the needs of our patients today and in the future. To this end, Shire has divested the Hayward, California manufacturing facility to Lonza, a highly regarded supplier to the life sciences industry,” Shire spokeswoman Katie Joyce tells GEN.

The sale of Hayward does not signal a retreat from internal manufacturing, Joyce added: “Our internal network is robust and includes multiple US sites in Massachusetts, Georgia, and California, in addition to sites throughout the EU and in Singapore.”

More than 100 staffers are based at Hayward—all of whom will have the opportunity to continue in their positions, according to Lonza.

Slough also contains airlift bioreactors, one each of 200 L and 2,000 L, a stirred bioreactor of 800 L, associated purification suites, and process R&D services.

Molecular Diagnostics: Partnership Joins MolecularMD Dx Services, Indica Labs Imaging Expertise

MolecularMD said its diagnostic clinical testing solutions focused on cancer treatments will be combined with Indica Labs’ digital pathology imaging tools and services through a partnership agreement.

The two companies aim to efficiently transition preclinical research into diagnostic settings through the deployment of advanced image analysis workflows—with MolecularMD saying the partnership is envisioned to help accelerate drug-development programs. The partnership is also intended to help deliver accurate and effective patient stratification through integrated genomic and phenotypic biomarker analysis services, MolecularMD President and CEO Dan Snyder said in a statement.

“Indica Labs fills our clients’ needs for digital biomarker analysis and enhances our proposition to immuno-oncology development programs,” Snyder said. “These capabilities will provide unique advantages and accelerate pipeline decisions. The use of advanced algorithms for [immunohistochemistry] data interpretation holds the possibility of improved patient outcomes.”

He said Indica Labs’ capabilities will be combined with those of MolecularMD, which works with developers of biomarker assays seeking validation as companion diagnostics.

In addition to assay design and development services, the company offers sample banking and bridging strategies, clinical trial design, regulatory planning, analytical and clinical assay validation, full-service histology and pathology offerings; including IHC assay development, FDA submission services, and custom clinical GMP kit manufacturing.

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