March Spotlight

BPI Staff

March 23, 2018

12 Min Read

Iyer-266x300.jpgWelcome New Editorial Advisor

Kavita Ramalingam Iyer is associate director and product lead of GRACS-CMC for vaccines at Merck Sharp & Dohme Corp. She received her PhD in biotechnology from Anna University (India) and completed a postdoctoral fellowship at the University of Minnesota (focusing on antibody engineering and synthetic biology) before joining Merck in 2008.

Kavita has over 10 years of pharmaceutical industry experience leading chemistry, manufacturing, and controls (CMC) development; manufacturing; establishment of good manufacturing practice (GMP) facilities; technology transfer; talent development; strategic initiatives; and performing site audits. She is a certified lean/six-sigma black belt. As regulatory lead for investigational and marketed vaccine and biologics products within Merck’s Global Regulatory Affairs and Clinical Supply (GRACS) organization, she is responsible for managing product dossier life cycles; developing, shaping, and implementing CMC regulatory strategies in compliance with global regulations; developing regulatory documentation to support worldwide registration; serving as the lead regulatory/CMC representative on matrix teams; and mentoring early development and crossfunctional teams. Iyer is a Merck regulatory/CMC representative in the BioPhorum Operations Group (BPOG) and has given several conference talks and published multiple position papers in collaboration with industry experts addressing emerging regulations and guidance documents on product development, registration, and postapproval changes. As a BPOG delegate, she has collaborated with other industry experts on workshops for health agencies in Latin America focusing on the complexity and impact of postapproval changes and harmonization of regulatory requirements.

In her free time, Iyer enjoys traveling, cooking, music, Indian classical dance, socializing, and community outreach activities.

Niche Disorder: Huntington’s Disease by Alison D. Center

Huntington’s disease (HD) is a fatal genetic disorder that causes a progressive breakdown of nerve cells in a sufferer’s brain. The associated HTT gene makes the “huntingtin” protein, which appears to be important for neuron function and is essential for prenatal brain development. The HTT gene contains a particular CAG (cytosine, adenine, and guanine) trinucleotide repeat DNA segment that normally repeats 10–35 times; in people with Huntington’s disease, the segment repeats 36–120 times or more, causing production of an abnormally long version of the protein. That gets broken into toxic fragments that bind together and accumulate in neurons, disrupting normal function and leading to cell death (1).

Huntington’s disease is incurable and causes a patient’s physical and mental abilities to deteriorate in middle age. Children of HD parents face a 50/50 chance of inheriting the faulty gene. According to the Huntington’s Disease Society of America (HDSA), some 30,000 Americans are symptomatic and more than 200,000 are at risk of inheriting the disease. In about 10% of cases, children or adolescents will be affected by juvenile Huntington’s disease (JHD), which typically progresses more rapidly than adult-onset HD.

Treatment Options: No treatment is yet approved to stop or reverse Huntington’s disease. Some medications (e.g., antipsychotics, antidepressants, and tranquilizers) help control symptoms. And patients who exercise tend to do better than those who do not (1).

HD scientists are exploring the use of experimental gene-editing to edit or delete the HD mutation. Clustered regularly interspaced short palindromic repeats (CRISPR) technology uses a guide RNA and the Cas9 cutting enzyme to identify and delete a gene or to make cuts that render it unreadable (2).

An Emory University team led by Xiao-Jiang Li has found that using CRISPR–Cas9 shows potentially beneficial effects in HD mice. The team injected viruses carrying the guide RNA and Cas9 into the HD-damaged parts of mouse brains. After a few weeks, the CRISPR– Cas9 components had spread and disabled the defective HD gene, diminishing stress on the neurons. After three months, the amount of huntingtin protein clumps built up in brain cells had decreased, and the treated mice improved in movement tests. Even older mice that had developed symptoms improved after treatment (2). Most people with HD have one copy of the mutant gene and one copy of a healthy gene, so there is some concern that the latter could be damaged by such treatment.

Two other groups are working to improve the CRISPR–Cas9 technique. At Massachusetts General Hospital, Jong-Min Lee and colleagues made an allelespecific deletion to edit only the dysfunctional copy of the HTT gene. And at Children’s Hospital of Philadelphia, Beverly Davidson and colleagues have used a similar approach to target only the mutant gene by making smaller cuts with Cas9 (2).

Meanwhile, an ongoing study by Ionis Pharmaceuticals is focused on an antisense oligonucleotide (ASO) Huntington-lowering drug. ASO drugs work by attaching themselves to the messenger ribonucleic acid (mRNA) between a gene and cellular protein-making mechanisms, thus disabling the mRNA from doing its job so that less huntingtin protein is made. Dosages must be carefully determined because this approach lowers both the normal and disease-causing forms of the protein (3).

Organization: “The pace of scientific progress, especially in the area of gene editing, is very exciting for families affected by hereditary diseases like Huntington’s disease, which affects more than 30,000 Americans,” says Louise Vetter (HDSA president and CEO). “Being able to lower the impact of mutant huntingtin in the body and potentially edit it out with technologies like CRISPR–Cas9 would be a huge breakthrough in efforts to improve the lives of everyone affected by HD and ultimately stop the disease.”

HDSA is a nonprofit organization dedicated to improving the lives of everyone affected by Huntington’s disease through treatment, community services, education, advocacy, and research. The organization was founded in 1967 by Marjorie Guthrie, the wife of legendary folk singer Woody Guthrie, who died from HD complications at age 55. Chapters and affiliates support HDSA’s mission by bringing community-based services, awareness, and grassroots fundraising to families affected by HD. HDSA has 41 treatment centers of excellence, 65 social workers, and more than 160 support groups across the United States.

Vetter says, “Today, HD families ask not if there will be a treatment or cure, but when. Our responsibility at HDSA is to ensure that we provide credible and meaningful information regarding the exciting research that is underway so that families have realistic expectations and can gain access to the best care to manage their disease even while the pace of science moves forward.”

1 HTT gene (huntingtin). Genetics Home Reference. U.S. National Library of Medicine;

2 Fox L. A Step Forward for Gene Editing: CRISPR-Cas9 and HD — Evolving CRISPR-Cas9 Techniques Can Now Be Used to Edit the HD Gene in a Living Mouse Brain. HDBuzz 26 July 2017;

3 Carroll J. Update Confirms Huntington’s Disease “Gene Silencing” Trial on Track: Ionis Says Its Trial of Httrx, Intended to Lower Huntingtin Protein, Is Fully Recruited and Plans to Extend It. HDBuzz. 22 June 2017;

BIO-Europe 2017 Breaks Records

In November, BIO-Europe 2017, the largest global life-science partnering event in Europe, brought together an all-time high of >4,000 industry executives as part of Berlin Science Week 2017, an international gathering that brought people from the world’s most innovative scientific institutions together. The 23rd annual BIO-Europe event broke records for the number of one-to-one partnering meetings — nearly 24,200, up 9% from 2016. CEOs and decision makers from 2,199 companies and 61 countries discussed asset deals and strategic collaborations. There were 5,142 licensing opportunities on offer, with 152 company presentations and 106 exhibitors.

“Partnering is a critical ingredient in successful strategic planning by companies spanning all aspects of drug development, so the incredible success of BIO-Europe bodes well for the future of healthcare,” said Anna Chrisman, managing director of EBD Group and KNect365 Life Sciences. “The event attracts and facilitates partnering among not only traditional pharma, biotech, and academia, but also the new players in the spectrum: startup biotech companies, innovators in cell and gene therapy and digital medicine, and many more. Berlin was an outstanding host as one of the leading life-science and healthcare industry centers in the world.”

Highlights of the conference included a “Startup Slam” pitching competition where emerging entrepreneurs could pitch their companies to potential partners and investors. Once again sponsored by Johnson & Johnson Innovation, this event was won by Thomas de Vlaam (CEO and founder of Amylon Therapeutics). His startup company targets central nervous system (CNS) disorders through an ultragenetics approach.

“BIO-Europe 2017 was a unique chance for the city of Berlin, the Cluster HealthCapital [organization], and the outstanding scientific institutes and companies from Berlin,” said Kai Bindseil, manager of HealthCapital Berlin-Brandenburg at Berlin Partner for Business and Technology. “We are looking forward to welcoming this show back to Berlin soon.”

Following up on valuable contacts and deals made in Berlin, many attendees are going on to BIO-Europe Spring in Amsterdam, the Netherlands, this month. Hosted by Health~Holland, this springtime counterpart of BIOEurope annually attracts >2,500 attendees. Planning also is under way for BIO-Europe 2018 in Copenhagen, Denmark (5–7 November 2018), in partnership with Copenhagen Capacity and Invest in Skåne.

“Health~Holland is honored to welcome BIO-Europe Spring 2018 to the Netherlands, a country known for partnerships, innovation, and collaboration,” says Hans Schikan, biotech entrepreneur and top team member of Top Sector Life Sciences and Health. “Let’s meet, connect and join forces.”

Catalent Acquires Cook Pharmica

Drug-delivery specialist and contract manufacturer Catalent, Inc., acquired Cook Pharmica LLC, an integrated provider of drug-substance and drug-product manufacturing and related services in October for US$950 million ($750 million to be paid at closing and the balance to be paid in equal installments over the next four years). This brings Cook’s 875,000-ft2 development and manufacturing facility in Bloomington, IN, into Catalent’s global network that includes a biologics development and biomanufacturing facility in Madison, WI; fill-finish services in Brussels, Belgium and Limoges, France; SMARTag conjugation technology in Emeryville, CA; and a network of analytical laboratories. Founded in 2004 as a division of the Cook Group, Cook Pharmica generated $179 million in revenue for fiscal year 2017.

“The complementary biologics development, biomanufacturing, and fill–finish capabilities of Catalent and Cook Pharmica will provide biopharmaceutical companies with a single, integrated partner to support a wide range of clinical and commercial needs,” says John Chiminski (Catalent’s chair and CEO). He says that the combined company plans to invest aggressively in all sites. “This acquisition is a recognition of the hard work, dedication, and community spirit of the team who has helped Cook Pharmica grow — and of the Bloomington area, which is such a terrific home for this fast-growing business. We look forward to strengthening Cook Pharmica’s partnership with the community in the years to come as we further strengthen our leadership position in biologics.”

Cobra Biologics Tops 2017 Bionow Awards

International contract development and manufacturing organization (CDMO) Cobra Biologics Ltd. has been named company of the year in addition to winning a technical service award at the 16th annual Bionow Awards on 30 November 2017. These awards recognize excellence, outstanding achievement, and enterprise in the North of England. Not-for-profit membership organization Bionow supports the area’s burgeoning life sciences sector, which currently includes about 1,000 science and healthcare companies.

Cobra’s technical service award recognized delivery of technical services related to process development and manufacture of plasmid DNA for gene-therapy products in clinical trials. The company has drawn a significant increase in demand worldwide for those services, with 99% of its customers headquartered outside of the United Kingdom. This award was judged on the degree of innovation, impact, and quality of the service.

The AstraZeneca-sponsored Bionow company-of-the-year award was presented to Cobra CEO Peter Coleman, who accepted it on behalf of his company’s dedicated staff. Among them, Cobra’s GMP production manager Sarah Davies was named runner-up in the “promising technologist of the year” category for her work in overseeing technology transfer of a viral-vector process from a small-scale, non-GMP manufacturer to manufacture commercial supplies.

Coleman said: “Our team has worked incredibly hard to get to where we are now, and as a result we have a bright and promising future. Sarah Davies is a great example of how Cobra works alongside its customers to meet the needs of patients worldwide.”

UK Regenerative Medicine Thrived in 2017

In its 2017 annual review, the Cell and Gene Therapy Catapult (CGTC) shared an overview of its own work and the United Kingdom’s thriving cell and gene therapy sector. The company operates as an independent center of excellence to advance the growth of the UK regenerative medicine industry by bridging the gap between scientific research and full-scale commercialization. It seeks to establish the country as the go-to place development of living medicines.

In 2017, CGTC acquired Catapult Therapy TCR (Cell Medica’s subsidiary for developing WT1 TCR T-cell therapy). Autolus and Cell Medica became the first companies to occupy space at the CGTC manufacturing center, alongside Fisher BioServices’s CyroHub. Asymptote and CGTC have developed new benchtop thawing devices. The company is sharing expertise and technology with collaborators in the United States, Canada, China, Japan, and South Korea. And it is conducting ongoing research at laboratories in Guy’s Hospital (London, UK).

CEO Keith Thompson says, “We are encouraged to see the global standing of our sector highlighted by agreements in leading advanced-therapy countries such as the United States and Japan, along with highly innovative collaborators in the United Kingdom, from fledgling biotechs to big pharma giants. But there is still much we can do. Our manufacturing center in Stevenage will serve as a vital bridge to help advanced-therapy companies commercialize their treatments.”

Last year also brought increasing investment and an expansion in infrastructure in the United Kingdom. The £55-million large-scale GMP manufacturing center has doubled its capacity with an additional £12-million investment from the UK government’s Industrial Strategy Challenge Fund. Thompson says that cell therapy products have a bright future for the benefits they promise patients needing innovative options for their complex and challenging diseases. CGTC’s annual review can be accessed online at

Rentschler Becomes a European Corporation

Last fall, German contract development and manufacturing organization (CDMO) Rentschler Biotechnologie GmbH announced its transition from a German limited-liability corporation to a European corporation (SE) with the new name of Rentschler Biopharma. The company has grown considerably in the recent years and invested in facilities to more than double its capacity. With that expansion have come new hires, about 200 new employees in 2016–2017. It plans to fill about 100 more in 2018.

“We emphasize our long-term international corporate identity while the core business remains unaffected,” commented owner Nikolaus F. Rentschler. “This legal form of company strengthens our position as a full-service CDMO and ensures our place as a leader in this industry. Our proven service offering along the entire value chain — from bioprocess development through biomanufacturing to fill and finish of biopharmaceuticals — remains unchanged. This applies to our company sites and manufacturing facilities as well as existing client relations.”

The Rentschler Biopharma SE name debuted at the November 2017 Bio-Europe partnering conference in Berlin, Germany. This family-owned company employs about 800 people.

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