Friday, June 17, 2016

Gene Editing in CHO Cells

The team behind Cell Line Development & Engineering event have recently produced an exclusive whitepaper titled "Gene Editing in CHO Cells". Below you will find a brief summary of the whitepaper and download the complete whitepaper now.

Whitepaper Summary:

Recently, several exciting advances in CHO cell line engineering have received significant media and research attention due to efforts in genome sequencing, systems biology, and bioinformatics combined with the relatively new field of targeted gene editing platforms. Three key gene editing technologies have been at the forefront of the recent developments in CHO cell line engineering. Early efforts to introduce targeted site specific edits to the CHO genome focused on implementing the zinc finger nucleases (ZFNs) and the transcription activator-like effector nucleases (TALENs). The ZFN platform has been successfully deployed in a variety of post translational modification applications aimed at increasing specificity of recombinant protein production, but the efficiency of this platform can be limited in mammalian cell lines.

The clustered regularly interspaced short palindromic repeats associated 9 (CRISPR/Cas9) targeted gene editing system has recently exploded onto the research scene in almost every organism. This targeted gene editing platform allows for the creation of multiplexed edits in a single cost-effective step with a specificity previously unachievable in the genome editing arena. This complex is composed of short guide RNAs (sgRNAs) and a CRISPR-RNA that form a site specific construct that is complimentary to the target DNA, which introduces a double stranded DNA break upon binding. Repair of the break site by endogenous enzymes then creates a highly specific change to the DNA which can be customized for a variety of applications.

These advances in genome editing have helped enable high-throughput development of CHO cell lines that can be utilized as economically viable commercial expression vectors. The CRISPR/cas9 gene editing system has shown to be an extremely useful tool for customizing the metabolic pathways of CHO cell lines for use in biopharmaceutical production. One of the most useful applications of this exciting technology has been the creation of multiplexed targeted knock out screening systems. Previously, knock out experiments had to rely on mutagenesis, drug knock out, or media screening to identify the effect of a mutation on a desired cell type. These methods are inefficient and sometimes lead to less desirable off-target effects. It is now possible to develop very large gene knockout libraries to be targeted by CRISPR/cas9 using bioinformatics software specific to this platform.

Customizing metabolic pathways in CHO cell lines is of paramount importance for developing “cell factories” capable of biopharmaceutical production. Reducing the energy expenditure associated with mitochondria production and oxidative metabolism is one approach that has been shown to increase the efficiency of the cell by directing metabolism towards production of the target product. Modulating these pathways has traditionally been accomplished using interfering RNAs, but the specificity of the CRISPR/cas9 platform offers another tool with which researcher can customize the energy profile of CHO cell lines destined for biopharmaceutical production.

Future efforts in the field will be focused on increasing the efficiency of the CRISPR/cas9 system, as this platform is poised to become the model for the majority of biopharmaceutical development. Currently, 60 to 70% of all biopharmaceutical production is accomplished with recombinant mammalian cell lines, and this market share is expected to grow. Multiplexed editing efforts will also continue to increase the rate at which specific customizable CHO cell lines can be produced, as this process is highly critical to increasing the rate at which CHO cell line engineering moves forward.

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Friday, June 10, 2016

Innovative Development Strategies and Applications for Bispecific Antibodies

The team behind the Next Generation Protein Therapeutics Summit have recently produced an exclusive whitepaper titled "Innovative Development Strategies and Applications for Bispecific Antibodies". Below you will find a brief summary of the whitepaper and download the complete whitepaper now.

Whitepaper Summary:

The phenomenal growth of the bispecific antibody arena has culminated in 60 unique constructs, more than 30 in clinical development, and two on the market as therapeutics for a wide variety of cancer types and numerous diseases/disorders. Bispecific antibodies are specially engineered antibodies which simultaneously bind to two different epitopes on the same antigen or different antigens, increasing selectivity and effectiveness. [1]

The focus in incorporating bispecific antibodies within oncology applications has been in either blocking multiple and redundant signaling pathways involved in oncogenesis or redirecting immune effector cells to be in close proximity to tumor cells. In non-oncology applications, a major developmental effort has gone into blocking pro-inflammatory cytokines.[2, 3]

Despite successes in development there are some critical hurdles to overcome and there is a need for innovation and improvement. Manufacturability issues such as low expression yields and product instability/short half-life have hindered development. Challenges lie in the need for rapid discovery of lead bispecific antibodies with optimal selectivity for their targets, and a need for rapid purification techniques. Adverse effects from immunogenicity, mainly caused by a “cytokine storm,” can stifle clinical trials.[3]

Development efforts have provided some solutions to these hurdles. Researchers at Eli Lily are using mathematical modeling parameters to make predictions about how engineered antibody properties will affect binding to cell surface antigens, ultimately optimizing developability. [4]Another novel strategy involves monitoring target/ligand binding of bispecific antibodies through surface plasmon resonance (SPR), which allows users to view the dynamics of bispecific antibody binding and dissociation events with two targets. [5]

The short half-life of scFv-based bispecific antibodies is a major drawback compared to that of IgG-like bispecific antibodies. Successful half-life extension, and in some cases, recycling, has been achieved by attaching a variety of components: PEG chains [6], human serum albumin, and Fc fragments [1]. In another novel approach, human mesenchymal stromal cells (MSCs) can be genetically modified to produce and secrete bispecific antibodies that accumulate near tumors continuously throughout the lifetime of the patient.[7]

A plethora of unique applications are being investigated for bispecific antibodies. One is in delivery of therapeutic antibodies across the blood-brain barrier for neurological conditions. [8]Another innovative application involves engaging bispecific antibodies to deliver drug, nanoparticle or radiolabel payloads to tumor sites. [1]Bispecific antibody-based immunoassays are being developed for diagnosis of patients with various infectious diseases: SARS, hepatitis B, tuberculosis, as well as E. coli infections. [9]Another application involves tackling the rising threat of antibiotic resistance through specially designed constructs effective against antibiotic resistant bacteria such as Pseudomonas aeruginosa. [10]

This exciting and fast moving arena includes many creative design formats, and innovative solutions for numerous development and manufacturing issues. There are still many unmet needs, but the field is bound to yield many more successes.

  1. Fan, G., et al., Bispecific antibodies and their applications. Journal of Hematology & Oncology, 2015. 8(1): p. 1-14.
  2. Spiess, C., Q. Zhai, and P.J. Carter, Alternative molecular formats and therapeutic applications for bispecific antibodies. Mol Immunol, 2015. 67(2 Pt A): p. 95-106.
  3. Spasevska I, D.M., Klein C, Dumontet C, Advances in Bispecific Antibodies Engineering: Novel Concepts for Immunotherapies. J Blood Disord Transfus 2015. 6(243).
  4. Rhoden, J.J., G.L. Dyas, and V.J. Wroblewski, A Modeling and Experimental Investigation of the Effects of Antigen Density, Binding Affinity, and Antigen Expression Ratio on Bispecific Antibody Binding to Cell Surface Targets. J Biol Chem, 2016.
  5. Karllson, R., Applications of Surface Plasmon Resonance for Detection of Bispecific Antibody Activity. Biopharm International, 2015. 28(10): p. 38-45.
  6. Kontermann, R.E., Strategies for extended serum half-life of protein therapeutics. Curr Opin Biotechnol, 2011. 22(6): p. 868-76.
  7. Aliperta, R., et al., Bispecific antibody releasing-mesenchymal stromal cell machinery for retargeting T cells towards acute myeloid leukemia blasts. Blood Cancer Journal, 2015. 5: p. e348.
  8. Couch, J.A., et al., Addressing Safety Liabilities of TfR Bispecific Antibodies That Cross the Blood-Brain Barrier. Science Translational Medicine, 2013. 5(183): p. 183ra57-183ra57.
  9. Byrne, H., et al., A tale of two specificities: bispecific antibodies for therapeutic and diagnostic applications. Trends Biotechnol, 2013. 31(11): p. 621-32.
  10. DiGiandomenico, A., et al., A multifunctional bispecific antibody protects against Pseudomonas aeruginosa. Science Translational Medicine, 2014. 6(262): p. 262ra155-262ra155.

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Friday, June 3, 2016

Creating New Pathways for the Development, Translation, and Delivery of Immunotherapies

The team behind the Next Generation Protein Therapeutics Summit have recently produced an exclusive whitepaper titled "Creating New Pathways for the Development, Translation, and Delivery of Immunotherapies". Below you will find a brief summary of the whitepaper and download the complete whitepaper now

 Whitepaper Summary:

The last decade has seen substantial growth of immunotherapy treatments for cancer. The new immunotherapies have produced exciting results in terms of response rates to treatment for certain cancers, such as melanoma, which have been refractory to treatment, once substantial metastasis has occurred. The US Food and Drug Administration (FDA) has approved several antibodies against immune checkpoint inhibitors based on the encouraging results in clinical trials. Other types of immune therapies are also being developed which may also be useful in the treatment of cancer.

New antibody/cytokine fusion proteins, anti-CD 137 monoclonal antibodies (mabs) for stimulating cells of the immune system, more refined uses of cytokines in immunotherapy treatments, cancer vaccines, use of genetically engineered T cells to specifically target tumors, new techniques in stimulating the innate immune system and combinations of immunotherapies have great potential for being effective treatment options for cancer treatment in the future.

Challenges, however, remain to perfect these therapies for use in the clinic for cancer treatment. The nature of these challenges are scientific, clinical and regulatory. Scientific challenges include defining the appropriate tumor types for an appropriate immunotherapy, the conditions under which various cells of the immune system would be activated and determining how best to manipulate them to allow for maximum tumor cell destruction, finding better ways to circumvent cancer cell suppression of immune cell responses and using new techniques to prevent or ameliorate the nonspecific injury to normal tissue that can occur as a side effect of immunotherapeutic treatment.

Clinical challenges include ensuring there is adequate quality control in manufacturing process to supply the agent in pure enough form for clinical trials, obtaining enough patients that meet inclusion criteria, designing clinical trials that will yield adequate information to assess the safety and efficacy of the treatment and defining appropriate endpoints for a cancer clinical trial to effectively interpret clinical data gained from the clinical trial.

Regulatory challenges can occur at multiple levels for companies or entities trying to gain FDA approval for their immunotherapy technique or product. These challenges can be at the preclinical level, clinical or manufacturing levels. Adherence to regulations governing Good Laboratory Practices, Good Clinical Practices, and Good Manufacturing Practices can be problematic when trying to take immunological reagents or cellular treatments from the research laboratory to the cancer treatment clinic.

Despite the challenges when conducting research and treatment with immunotherapies, the intense level of research and data being generated with immunotherapies for cancer will ensure that a wide variety of new therapies will be possible in the coming years.

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Tuesday, May 3, 2016

Preparing for future bioprocessing challenges with the Cellca CHO Expression Platform

Therapeutic protein development and production is a very technically challenging, time consuming and expensive endeavor.

What are some of the challenges? There are numerous critical decisions that must be made with regard to mammalian cell line choice (CHO, NS0, etc.), appropriate gene and marker expression systems, cell culture medium and feed optimization, clone selection and scale-up strategies. Biopharmaceutical developers should be careful to choose options which deliver the following:

• Maximum protein titer
• Scalability (5L – 1000L)
• Long-term Stability
• Cost effectiveness
• Shortened development timelines
• No burdensome IP concerns

Why is it important and critical to understand these challenges? There are considerable economic considerations to be made; one should maximize financial budgets by minimizing expenditures on equipment and technologies required for in-house development and characterization of the therapeutic protein. It’s important to make efficient and productive investments in R&D; technology and process development requires highly trained and expert staff. There are also commercial or market considerations which will affect return on investments; to maximize IP and patent life the therapeutic protein must be developed and commercialized as quickly as possible to gain maximum market share in a highly competitive environment. First to market is paramount for biosimilar developers.

How has the CRO industry responded? “Turn-key” cell line development and bioanalytical testing CROs are currently open for business and accessible for outsourcing nearly all upstream, downstream and biomolecular analytical activities. Sartorius Stedim Biotech offer the most comprehensive, scalable and unique bioprocess portfolio to support Biosimilar development and manufacturing. With Sartorius Stedim Biotechs’ recent acquisition of Cellca (cell line development) and BioOutsource (bioanalytical and biosafety testing), there is now established a fully functional, and integrated CRO uniquely positioned to support clients development programs across the entire product lifecycle.

The result of outsourcing biopharmaceutical development and production to experienced CROs will have major positive implications for shortening the time to commercialization at significantly reduced costs.

To learn more about the industry leading Cellca CLD platform which delivers stable, high titre clones, (95% of projects have delivered titres >3.0g/litre) in a proven scalable fed batch manufacturing process in a cost and time efficient manner please join our talk by Dr. Brian Wendelburg at IBC Cell Line Development & Engineering Conference, San Francisco, 14th June at 1.25pm.

Author Bio:

Dr. Brian Wendelburg received his Ph.D. in Molecular Biophysics from the Institute of Molecular Biophysics at Florida State University. He then completed his postdoctoral training at the University of North Carolina’s Lineberger Comprehensive Cancer Center. His professional career has involved diverse roles in sales and business development activities at leading Biotech companies such as Cepheid, Affymetrix and Miltenyi Biotec where he gained a strong technical background in genomics, proteomics and cell and gene therapy applications. He joined the Sartorius-Stedim Biotech team in the spring of 2016 and is currently Sr. Field Marketing Manager for the BioOutsource and Cellca divisions.

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Tuesday, April 26, 2016

Cell Culture Media: Balancing Resources with Results

Why does medium matter?

It all starts with media. Without an appropriate growth medium, no biopharmaceutical process would exist. The proper medium allows for cells to grow and generate product. Going beyond the fact that cell culture processes would simply not exist without cell culture media, the medium (and associated feeds for fed-batch processes) represents a large portion of the cost of a biopharmaceutical process. Cell culture media are complex entities that encompass large quantities of raw materials as well as a high level of technical expertise, driving up the cost per litre.

What are the advantages of an optimized medium formulation compared to an off the shelf product? 

Many people will choose to start with standard off the shelf products for their cell culture processes. While there are a wide variety of products available on the market, there are several important reasons to consider using an optimized medium formulation instead. The first is to tailor a medium formulation specifically for your own cell line. Every cell line will respond differently to standard products, and optimizing a medium formulation is the best way to ensure that you use a medium that works best for your application and requirements. Additionally, as you generate different cell lines with varying genetic constructs for new products, your cells may begin to respond differently. Having an optimized medium formulation allows you to adapt to these changes while maintaining growth and productivity. Using a standard product also means you are bound to a single vendor with no access to proprietary formulations. With your own optimized medium, you have full access to the formulation, with the ability to manufacture it with a vendor of your choice.

What factors should I consider when developing an optimized medium?

As discussed previously, optimizing a medium formulation to get you the best growth and productivity is the main driving factor, and allows you to minimize the amount of medium used and therefore your overall COGS. It is important to also consider what the criteria are for your optimized medium. For many industries, having a fully chemically defined, non-animal origin medium is critical. This minimizes lot to lot variability and is highly desirable from a regulatory standpoint. Ease of use is also important to consider. This encompasses storage aspects, such as shelf life, and shipping and handling conditions. Ease of use also involves simplifying the process for the operator. As media and feeds become increasingly complex, how difficult does it become to formulate? Will operators have to perform risky pH adjustments with large volumes of corrosive reagents? Will high temperatures be needed to dissolve certain components, and can these high temperatures be achieved as the industry moves towards more single-use technologies? These and other factors must be considered when developing an optimized medium formulation.

What resources are required to develop an optimized medium?

The actual raw materials that form the bulk of a cell culture medium are generally inexpensive. The resources required for an optimized medium formulation that drive up the ultimate cost per liter are time, personnel, equipment, and expertise. With the increasing use of multivariate approaches (Design of Experiments, Principal Component Analysis), the use of high throughput systems become highly advantageous, reducing personnel requirements. Finally, expertise in media development is something that comes only with years of experience in the industry and cannot be bought with any amount of money.

So how do I develop an optimized medium formulation?

There are several approaches to media optimization. Some methods include titration, reverse engineering of other media, and metabolomics. While some of these methods are effective, when implemented on their own, they are time consuming, labor intensive, and heavily resource-dependent. A modern, DoE based approach to media development for CHO based processes is the CHOptimizer® Media Builder. CHOptimizer® consists of three distinct phases. The package is designed to be integrated into our ambr™15 system for automation and ease of use. In the first phase, four chemically defined, non-animal origin based media are blended in different ratios, according to a mixtures design DoE approach. Subsequent phases incorporate spent media analysis and fractional factorial DoE approaches to develop an optimized medium formulation, feed formulation, and corresponding feeding strategy. CHOptimizer® base media are developed using the expertise of Lonza Biologics, and combines a modern, high throughput approach with traditional ideas to deliver an optimized medium in a short timeline, with field based support. It also offers full access to the formulation for ultimate flexibility in the future.

To learn more about CHO media optimization join Sartorius Stedim Biotech’s workshop, chaired by Dr. Michael Gillmeister, Lonza at the IBC Cell Line Development & Engineering Conference, San Francisco, 13th June at 11.45am.

About the author:
Dr. Michael Gillmeister received his Ph.D. in Chemical and Biomolecular Engineering from the Johns Hopkins University in collaboration with the University of Maryland School of Medicine specializing in glycosylation, transient protein production, and neurobiology. In 2009, Mike joined the Gibco® research and development group and was responsible for next-generation media and sera projects. He then led media and process development projects to modulate product quality and maximize titer for PD-Direct® Custom Media Services using high-throughput and bioreactor technologies. Currently, Mike leads Protein Expression Media R&D and the CHOptimizer™ media optimization service for Lonza Walkersville.

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Wednesday, April 20, 2016

Australia's Future in Global Peptide Drug Development

Paul Watt, Chief Scientific Officer, Phylogica Ltd, Australia sat down with the TIDES team to discuss the future of global peptide drug development in Australia as well as the current challenges for intracellular drug delivery and the important roles that academic institutions have in the development and commercialization of peptide therapeutics. Below you will find a brief excerpt from this exclusive interview. To access the complete interview, click here.

In terms of investment and innovation, where do you see Australia's future in global peptide drug development?

Australians have had a long history in peptide discovery. For example the pioneering work of Professor Mario Geysen enabled the parallel synthesis of peptides in the early 80's. More recently Australia has accumulated multiple high achieving peptide scientists such as Paul Alewood (eg. synthesis toxin peptides including use of selenolanthionine bridges), Richard Lewis and Glenn King (ion channel active venom peptides) (including ion channel inhibitors). David Craik (cyclotides and structural biology of complex peptides), John Wade (neuropeptides/relaxins). Australian peptide innovation has been successfully commercialised with the establishment of multiple companies, including Mimotopes, Auspep, Protagonist and Phylogica. As many of these companies mature, I see a bright future in the development of the Australian peptide industry. In addition several peptides discovered in Australia have been subject of multiple alliances with big Pharma offering further commercial potential as they progress through clinical development.

To learn more from Paul, join him at TIDES, May 9-12, 2016 in Long Beach, CA. Where he will be discussing how to design oligonucleotides with better drug-like properties to accelerate your products from discovery/preclinical to the clinic and to market.  

Register for TIDES now and save $100, use the code B16180BLOG100.

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Monday, April 18, 2016

The Next Generation Protein Therapeutics Summit: Earn a complimentary pass as a Guest Blogger!

Earn a complimentary all-access pass to The Next Generation Protein Therapeutics Summit by serving as a Guest Blogger at the event. As a Guest Blogger, you’ll have access to the Next Generation Protein Therapeutics, and the co-located Cell Line Development & Engineering, and Bioconjugates: From Targets to Therapeutics events’ comprehensive agenda attracting the best insights from around the world, right in San Francisco, California in June.

The Next Generation Protein Therapeutics Summit
and the co-located 
Bioconjugates: From Targets to Therapeutics and Cell Line Development & Engineering
June 13 - 15, 2016
Parc 55 Hotel, San Francisco, CA

The Next Generation Protein Therapeutics Summit's image depicts Nanobody protein therapeutic molecule

We are looking for an industry expert with interest in the following topics:

• Speed of discovery and development
• Alternative administration routes
• Potency and payload capacity
• New potential targets in cancer
• Half-life
• Robustness of discovery and preclinical development of bispecific antibodies
• Generation of human bispecific antibodies
• Efficiency of CMC development
• Development of large scale, high yield and manufacturing process

• High-Throughput Platforms for Cell Line Development
• Advances in Host Cell Engineering
• Improving Processes and Product Quality
• Improving Biosimilarity
• Assuring Clonality and Stability
• Innovations in Alternative Expression Systems and Novel Host Cell Lines
• Cell Line Development and Modification for Novel Modalities 
• Genome Editing in CHO cells
• Cell Line Development and Modification for Difficult-to-Express Proteins
• Manufacturing Assessment Strategies
• Understanding CHO Metabolisms

• Intellectual Property and Linker Payloads 
• Progress in Combination Therapies 
• Breakthrough Discoveries and Advances in ADCs
• Analytical and Characterization Strategies 
• Eliminating Heterogeneity: Advancements in Site-Specific Conjugation 
• Innovations in ADC Design and Development
• Regulatory Considerations for ADCs 
• From Discovery to Commercialization: Readiness for Manufacturing & Commercialization
• Perfecting the Chemistry Behind Conjugation 
• Conjugate Vaccines and Novel Conjugate Technologies

...and who would like to learn more about protein therapeutics!

The premise is to provide protein therapeutics related articles, whitepapers, and overall original content with a strong focus on the whole protein engineering & design industry.
What You get is:

FREE pass to the conference (valued up to $2,999.00);
• Access to extensive social learning activities;
• Exclusive admission to a networking community in the industry of your interest!

You also have a chance to GAIN exposure through our blog with over 2000 unique visitors monthly and more than 20 related LinkedIn groups with over 65,000 subscribers combined!

Learn more about the The Next Generation Protein Therapeutics Summit event by visiting our website.

Interested & want to learn more about this opportunity? Please contact Ksenia Newton at Feel free to share your short biography, links to your blog or writing samples, along with a few sentences about why we should choose you to become the Guest Blogger for the Next Generation Protein Therapeutics Summit 2016!
We hope to have you join us in San Francisco!

* Guest Bloggers are responsible for their own travel and lodging.

* All content is subject to IBC approval.

Stay tuned: 

Visit the website:
Future of Biopharma Blog

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Wednesday, April 13, 2016

Peptides for CNS and Alzheimer's Disease Therapy

Exclusive TIDES 2016 interview with Dieter Willbold, Ph.D., Director, ICS-6 Structural Biochemistry, Forschungszentrum Jülich, Germany. Dr. Willbold gives us some exclusive insights into the topics he will be addressing onstage at the 18th annual TIDES in just 4 weeks time. Don't miss out on this record setting meeting; join over 800 global attendees over 4 days full of insights and learnings. Register for TIDES by Friday, 4/15 and save $300 - Use the code B16180BLOG.

Dr. Willbold Interview: 

What current challenges are you facing for advancing your promising peptide for Alzheimer's disease through clinical trials?

Our main focus at the moment is to finish all the necessary preclinical tox and safety tests in order to soon get permission for a clinical phase I study with our drug candidate.

One challenge for developing therapeutics like ours that target specific aggregate species, lies in the lack of suitable analytics to measure target engagement, because most methods don't differentiate between different aggregate sizes. In addition to cognitive behavioral tests, we ourselves have therefore developed novel methods to measure efficacy and target engagement .e.g. QIAD (short for quantitative determination of interference with aggregate size distribution; Brener et al., Scientific Reports 2015), which measures Abeta oligomer elimination efficiency.

What are the advantages of peptide therapeutics over small molecules, antibodies and other protein therapeutics?

Small molecules often lack specificity, and this can lead to serious side effects and autoimmune responses. On the other hand protein-based therapeutics like antibodies possess high target selectivity and are made of natural components, but they are very big and expensive molecules. They often suffer from low oral bioavailability.

Small peptides can offer the best of both worlds in some respects: They are more target specific than small molecules but easier to produce than protein based drugs. Our drug candidate is made solely from D-enantiomeric amino acid residues and has surprisingly good oral bioavailability.

Where do you see innovation happening in the peptide field over the next 5 years?

Innovation will certainly happen in the production of peptides (cost reduction) and in the formulation of peptides (increase oral bioavailability).


Reserve your seat today to attend TIDES 2016 in Long Beach, CA and hear Dr. Willbold deliver a live presentation "Efficiency and Oral Bioavailability of Abeta Oligomer Directed D-Enantiomeric Peptides Developed for Therapy of Alzheimer's Disease", where he will delve into small soluble Abeta oligomers are suspected to be the major toxic species responsible for development and progression of Alzheimer's disease (AD). We developed highly potent D-enantiomeric peptide compounds that specifically eliminate Abeta oligomers and improve cognitive performance and stop or slow down neurodegeneration of AD transgenic mice. Data on stability and oral bioavailability clearly support the superiority of D-peptides over L-peptides.

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Monday, April 11, 2016

Record Attendance Expected! Don't Miss IBC's 18th Annual TIDES

Register by Friday, April 15th and save $300! To save, use the code B16180BLOG100

Experts Provide Key Success Factors for Drug Development and Manufacturing:

Mixed-Incretin Receptor Biochemical Signaling at Multiple Receptors
Richard DiMarchi, Ph.D. Standiford H. Cox Professor of Chemistry, Indiana University

Drisapersen: Case Study
Robert Baffi, Ph.D. Executive VP, Technical Operations, BioMarin Pharmaceuticals

Quark's Long History of Oligonucleotide Development
Danny Zurr, Ph.D. Chairman and CEO, Quark Pharmaceuticals Inc. 

Technologies for Targeting Molecules to Sites of Diseases
John Reed MD, Ph.D Global Head of Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd.

TIDES 2016 is on pace for record attendance with 800+ global attendees expected to attend this year’s meeting, held May 9-12, 2016 in Long Beach, California – will you be there?

Register your team today and access the science, technologies and contracts you need to accelerate your oligonucleotide and peptide products through the clinic towards commercial success.

Your registration grants you access to:
  • 800+ attendees representing 25 countries help you forge new business and scientific collaborations
  • 100+ speaker presentations across 5 tracks provide a customized agenda of solutions for your company’s current challenges
  • 70+ exhibitors demonstrate the latest products and technologies to accelerate your therapeutic to market
  • 40+ poster presentations keep you abreast of cutting-edge industry and academic research

Plus, be sure to register this week to gain access to Attendee Connect powered by partneringONE, the digital networking platform that allows you to view the full attendee list, pre-schedule meetings, and send private messages to attendees before, during and after the event.

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Tuesday, April 5, 2016

Exclusive Interview with Dr. Bruce Riser, CEO, BLR-Bio, LLC

IBC's 18th Annual TIDES is the industry's #1 forum for oligonucleotide and peptide leaders to build successful partnerships and accelerate products from early discovery through late-stage development and commercialization. The TIDES team recently talked to Bruce L. Riser, Ph.D., CEO, BLR-Bio, LLC for an exclusive interview that delves into the topics he plans to discuss at the upcoming Oligonucleotide and Peptide Therapeutics event in Long Beach, CA.

What are the biggest challenges of bringing new agents with novel targets to the market?

BR: There are really two big challenges when bringing new agents with novel targets to the market. First, many investors and potential partners are not familiar with the target, or they do not have the comfort that exists with an established target. Second, there can be misperceptions in the scientific community and in the biopharmaceutical industry where an agent is associated with another type of development creating a negative halo. On the first challenge, it is easy to see a proven target and to line up, jumping on the bandwagon with others trying to either win the race to launch first or to attempt to find a niche in an already established area. The problem of course is that lining up with everyone else does not provide the opportunity to develop and launch a true breakthrough therapy that can change the treatment paradigms and have a breakthrough impact on peoples' lives. Instead, investors and companies that line up for the established target often find they are trailing others to the market and are never able to successfully establish themselves in the market. It really takes a visionary to see the potential of a new target and have the insight and strength to invest in it. The second challenge, dealing with miss-associations of a novel therapy with other developments can be truly vexing. Our peptides target the novel CCN signaling pathway, leveraging the unique qualities of CCN3 to target the control of ECM changes in response to injury, blocking fibrosis and creating an environment for re-establishment of complete tissue homeostasis. By creating peptide libraries and conducting diverse in vitro and in vivo screens we have identified specific regions with the CCN3 protein responsible for blocking single, or multiple, pathways to fibroblast and cancer growth, and fibrosis formation. Unlike other products such as antibodies directed against the pro-fibrotic CCN2, that appear to partially block a single pathway, our novel therapy regulates vs. simply blocking, thus allowing reestablishment of the body's healthy equilibrium.

With several peptide products in the pipeline in preclinical development and a wide range of possible disease applications, how have you selected your lead indication target(s)?

BR: Having several products covering a wide variety of diseases is great and choosing lead indications to pursue is a wonderful challenge to have. In reality, the two lead indications that we have chosen to pursue have as much to do with the research that we have done with my team as it does the extreme health care need. My long background in academia, clinical nephrology/public health, and pharmaceutical drug R&D has driven the way we do drug discovery at BLR Bio. First, working to clearly understand the pathways to disease before selecting a target, and trying not to get caught up by targets in vogue. Then, testing our peptides in multiple related diseases before moving into the clinic. Our pipeline was created out of our long-term interest in fibrosis and the extracellular matrix in biology and disease, particularly in renal fibrosis as a complication of diabetes an area of great medical need. This has led to the selection of diabetic nephropathy as a main target for one of our lead products. Since our target, and the peptide inhibitor of our target, are involved in many other forms of fibrosis and other disease involving the miss-regulation of matricellular signaling, this creates other exciting therapeutic indications down the road. These include NASH, IPF, MD, and scleroderma to name a few.

I began my career in cancer research, and we know now that the extracellular matrix and matricellular signaling proteins such as the CCNs are critical also in the formation and resolution of tumors. The pro-fibrotic CCNs, CCN2 and CCN4 in particular have been shown to be important for the establishment and likely invasion and metastases in numerous tumors. The opportunity to use CCN3-based therapy to, not only halt the cancer, but also to target the microenvironment is an exciting one. Our company is particularly excited about the potential in pancreatic cancer. We have an established relationship with thought leaders in the cancer field and are moving forward with development work, partnering with some of these world experts. To add to the excitement of the therapies, our company also is developing a diagnostic/theranostic based on the same technology platform. It holds the promise of either stand-alone or companion diagnostics for development.

What are the key advantages of peptide therapeutics over small molecules, antibodies and other protein therapeutics?

BR: As you know, peptide-based drugs are one of the most rapidly growing areas in therapeutic development. More than 100 peptide-based drugs are on the market with several effective in cancer treatment. There is good reason for this. In size, falling between small molecule drugs and "biologics", they have many of the benefits of both while shedding many of the deficiencies. For example, because of their small size they gain many delivery benefits over biologics. First, better penetration of tissue at the site of action. This is crucial in fibrotic disease and cancer where there is a very strong barrier to penetration. Second, it allows for many more delivery options, including oral formulation. The earlier assumption of poor metabolic stability of peptides has just not proven to be the case. Although there is often rapid clearance from circulation, the previous assumptions about required PK by classic definition has also proven to be not relevant, since a specific and sustained biological activity at the target receptor is characteristic of many peptides. Unlike small molecules they are based on sequences that have evolved to react with specific receptors and often at very low concentrations. This results in very low off target effects. Last, since they can be chemically synthesized the ease and cost to manufacture are more nearly like that of small molecules. The majority of approved peptides are in the 15 amino acids (aa) range or smaller, and they treat a broad range of diseases.

How do you see academia and industry collaborating in the future to advance promising peptide therapeutics into commercially viable products?

BR: First, we think that academia will play a significant role in the creation of new peptide-based therapies in the future. Since the last decade has seen a decline in the number of newly approved drugs from large pharma, and recently there has been a strong trend for these same companies to dramatically reduce their discovery effort, this creates a large opportunity for novel peptide therapies and academic-initiated translational research. This does not necessarily mean that the new paradigm will be that large strategic companies will license early stage assets directly from Universities. Rather, we anticipate that the most promising discoveries will lead to the creation of start-up companies and the building of defendable IP. Then, large pharmaceuticals will court these start-ups as they progress to become true biotechnology companies with completion of phase I, phase II clinical trials or beyond. We think that the best of these emerging biotech companies will then expand their ability to do discovery and early stage development. They will also be able to clearly evaluate and in-license additional opportunities in academia. These are exactly the skills now lacking in big pharma. These successful discovery biotech's will become the future pipelines for drugs that will go to the mid and large pharma companies centered on late development and marketing. I envision BLR Bio as becoming one of these discovery companies able to contribute significantly to filling this gap.

Want to hear more from Dr. Riser? Join him this May in Long Beach, CA for the 18th annual TIDES - Save $300 when you register using the code B16180BLOG100. Click here to register

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Tuesday, March 29, 2016

The Current Value of the Global Peptide Therapeutics Market

"The number of companies specializing in the manufacture of therapeutic peptides has been shrinking over the last 15 years with fewer new companies entering the market than those leaving it."  

IBC's 18th Annual TIDES is the industry's #1 forum for oligonucleotide and peptide leaders to build successful partnerships and accelerate products from early discovery through late-stage development and commercialization. The TIDES team recently talked to Rodney Lax, Ph.D., Business Consultant, PolyPeptide Group for an exclusive interview that delves into the topics he plans to discuss at the upcoming Oligonucleotide and Peptide Therapeutics event in Long Beach, CA. 

In this interview, Dr. Lax discusses:
  • - The current estimated value of the global peptide therapeutics market.
  • - The key factors that contribute to the constant growth of the global peptide therapeutics market.
  • - The advantages/disadvantages to a consolidated peptide manufacturing industry.
  • - Which emerging markets are leading the forefront of peptide therapeutics research and development
  • - Opportunities that are emerging due to recent advancements in manufacturing and delivery technology

 Access the complete interview here.

PLUS! As a blog reader, you are eligible to save $300 when registering for TIDES. Use the code B16180BLOG100 to activate your savings. Click here to register.

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Friday, March 25, 2016

Analytical Controls in an Evolving Technology and Regulatory Landscape

IBC's 18th Annual TIDES is the industry's #1 forum for oligonucleotide and peptide leaders to build successful partnerships and accelerate products from early discovery through late-stage development and commercialization. The TIDES team recently talked to Rachel Orr, Senior Scientist, GlaxoSmithKline R&D, United Kingdom for an exclusive interview that delves into analytical controls in an evolving technology and regulatory landscape, the topic of her presentation at the upcoming Oligonucleotide and Peptide Therapeutics event in Long Beach, CA.

1. What key analytical challenges do oligonucleotide developers need to overcome in order to achieve regulatory approval?

Oligonucleotides are inherently difficult to analyze - they are neither traditional, small nor large molecules, and the techniques and well established methodologies for pharmaceutical analysis are all focused on these distinct classes. In addition, there is very limited regulatory guidance when it comes to oligonucleotides, so there are no set rules to follow. There are often discussions as to whether oligonucleotide analysis should follow small molecule rules and regulations or align with biopharmaceuticals; opinions are divided.

With limited experience across the industry in marketing applications it is difficult to assess what is needed in order to gain regulatory approval and this is one of the biggest challenges in CMC oligonucleotide development. There is no recent precedence of global oligonucleotide marketing applications and as such it is difficult to ascertain what may and may not be acceptable. Close engagement with the regulators is something which helps to form strategies and controls and hopefully this will increase the likelihood of success of regulatory approvals going forwards.

2. How have advancements in technology improved the analytical process? Can you provide examples?

Since the last successful oligonucleotide marketing application there have been considerable enhancements in technologies. UHPLC is now common throughout the industry and techniques such as high resolution NMR and mass spectrometry are much more affordable and quick. These advances in technology mean that the resolution and robustness of methodologies can be much improved, however has a downside that the regulators may well expect us to present them with these improvements by first intent.

Increased understanding of non "typical" molecules throughout the industry has enabled wider thinking and collaboration between different pharmaceutical companies, with more people working together on the problem progress will inevitably come quicker. As more people engage with the concept of oligos and as technology continues to evolve, I anticipate a large shift in the way we look to control oligonucleotides analytically in coming years.

3. What are the most common mistakes that oligonucleotide drug developers encounter during CMC submissions?

Again, due to there being so few oligonucleotides which have gone through the full CMC process I think it is difficult to make too many sweeping statements, however the key issues that I have come across all stem from attempting to fit oligonucleotides into a box. Whether it is the small molecule group or the biopharmaceutical groups who take on the challenge of oligonucleotides, it is generally only a few "experts" within that team who work on the molecules. It is impossible to fit existing small or large molecule platforms onto oligonucleotides and a lot of time, resources and money can be wasted trying to do so! Due to the small pool of people working on the oligo projects it can also be challenging when it comes to elements such as wider reviews of submissions as the reviewers are not always as well informed about the challenges associated with oligonucleotide analysis. Education of these reviewers and key stakeholders is an activity that cannot be underestimated in time or importance! This emphasizes the benefits of cross-pharmaceutical company collaborations.

Want to hear more from industry experts like Rachel? See our exclusive TIDES speaker Q&A series here.

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Thursday, March 24, 2016

Accelerate Your Peptide from Discovery to Commercialization

Accelerate your peptide product from early discovery through late-stage development and commercialization by attending IBC's 18th Annual TIDES meeting, held May 9-12, 2016 in Long Beach, California.

TIDES offers two tracks dedicated for peptide scientists to learn about the latest strategies and technologies needed to overcome challenges in targeting, drug discovery and peptide design, process development, regulatory, scale-up manufacturing, investment landscape and more:

Keynote Speaker:
Richard DiMarchi, Standiford H. Cox Professor of Chemistry, Indiana University
Mixed-Incretin Receptor Biochemical Signaling at Multiple Receptors

Track 1: Peptide Chemistry, Manufacturing & Controls
Speaking Organizations Include: Lonza, Bachem, Teva, Novartis, Peptron

Track 2: Peptide Discovery, Preclinical and Clinical
Speaking Organizations Include: Corden, Galena, Neon, Celerion, Phylogica

Learn about the Therapeutic Landscape of Peptides in 2016 and Beyond:
Rodney Lax, Ph.D., Business Consultant, PolyPeptide Group
Redefining the Therapeutic Peptide Business in the 21st Century

Plus, TIDES offers the largest and most focused exhibit hall for the peptide industry, where you can access 70+ vendor booths, 40+ posters and evening cocktail networking receptions to help grow your business. You won't want to miss out on this rare opportunity to connect with 800+ like-minded researchers from across the world.

As a reader of our blog, you are eligible to save $300 when registering for TIDES - Simply use the code B16180BLOG100. Click here to register.  

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Monday, March 21, 2016

The Standardization of Single-use Components for Bioprocessing

The focus in the bioprocessing industry is shifting from acceptance of single-use technology to standardization. It is critical that components be included in the standardization discussion. The tubing connector is essential for secure, sterile, leak-free connections between various single-use systems and processes. A user can have the best filter, bag and tubing but this is all pointless if the connector is not reliable, easy-to-use or robust. Improving connector compatibility and interchangeability are great opportunities for standardization, particularly because of complications related to managing inventories.

Inventory Issues

Several inventory issues arise from lack of connector standardization:

• Increased ordering complexity because the user must define which tube set or assembly works with which part of the application. 
• Greater risks of specifying the wrong system or connection, resulting in downtime and last minute adjustments at the end user site.
• Longer lead times because systems suppliers are manufacturing lower volumes of multiple SKUs as opposed to higher volumes of fewer SKUs. This lowers the incentive and likelihood for a manufacturer to stock of these items.
• Increased stocking requirements for end users, including connectors of different genders and other components needed to create make-shift adapters.

Reducing Overhead Costs: Less is More

While overhead cost reductions might be difficult to quantify, they cannot be overlooked. Reduction in SKUs and inventory lowers the cost of managing and maintaining that inventory, which allows capital to be allocated to additional process improvements. One way to help simplify and reduce inventory is to use genderless connectors that enable transitions between tubing of different sizes. Using genderless connections (e.g. CPC’s interchangeable AseptiQuik® G connectors) eliminate the need for reducer fittings elsewhere in the process as the connectors can act as reducers.

Component Standardization

By focusing on the most versatile genderless connectors, component standardization will help bioprocessing companies make the best use of single-use technology. The right connectors will enable end users to:
• Streamline operations with easy-to-use, robust sterile connections
• Eliminate potential ordering mistakes and reduce inventory demands related to gendered connectors • Maintain more flexibility and lessen production bottlenecks with onsite connector assembly 
• Reduce overhead costs, freeing up capital for other projects

Ultimately, standardizing components by incorporating single-use genderless connectors lets end users accomplish more with fewer finished goods, saving time and money, and getting their biopharmaceutical products to market more efficiently. 

Author: Todd Andrews, Global Sales and Business Development Manager, Bioprocessing for CPC – Colder Products Company

The standardization of single-use components for bioprocessing byTodd Andrews, Colder Products Company

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Friday, March 4, 2016

Peptide Therapeutic Development in Korea

"Peptide therapeutics development in Korea has been focused on generic development, and peptide modification, or formulation technologies to make drugs have better pharmacokinetic properties, which result in the recent big license deal in this field in Korea."

Dong Seok Kim, Ph.D., Principal Scientist, Peptron, South Korea recently sat down with the TIDES team for an exclusive interview that previews some of the topics that will be discussed onsite this May.

In this interview, Dong Seok Kim discusses;
  • The key regulatory challenges that peptide developers face
  • The advantages of sustained release for oligonucleotide/peptide therapeutics
  • South Korea's future in global peptide drug development

Drug Repositioning for Neurodegenerative Diseases using SR-Exenatide

SmartDepot™ is Peptron's proprietary technology for the sustained release (SR) microsphere formulations of various agents to provide once weekly or longer dosing regimens. Peptron is currently developing for T2DM a SR-Exenatide (once every two weeks), PT302, which is evaluated in a phase 2 clinical trials. The therapeutic potential of Exenatide in neurodegenerative disorders is being evaluated in various disease models such as AD, PD, and TBI. SR-Exenatide is expected to maximize therapeutic effects, increase drug compliance, and extend patent coverage.

Save $500 and register for TIDES before March 11th - To activate your savings, use the code B16180BLOG100

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Thursday, March 3, 2016

Don’t Miss BPI West!

Last chance to register for BPI West is March 9th. Use the code BPIWEST16BL and save $100- Register now!

The clock is ticking. BPI West is just over a week away! Don't miss out on networking with industry experts, scientists and executives, along with emerging and established technology companies. Your registration will gain you access to:

• 700+ global attendees
• 80+ exhibitors highlighting new products and technologies
• 65+ scientific posters showcasing novel research
• 3 thought-leading keynote presentations
• BPI West Theater Presentations
• And More!

Download the brochure for full program details.

PLUS! We're excited to announce that Michael Egholm, President of Pall Biopharmaceuticals joins the upcoming BPI West event in Oakland on March 14th! Join us as he provides an update on the Significant Technology Advances Enabling Integrated Continuous BioProcessing during Monday's The Future of Continuous Processing pre-conference symposia. Best of all, this session is complimentary to all registered attendees!

Can't make it to all 4 days? We've got you covered with special one-day Exposition Hall & Keynotes passes starting at $150! Click here for more information.

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Monday, February 29, 2016

Innovative Technologies, People, and Organizations Drive the Future of Bioprocessing

By  S. Anne Montgomery, Editor in Chief, BioProcess International 

In the 14 years that BioProcess International (BPI) magazine has been around, the biopharmaceutical industry has experienced a dramatic confluence of technologies, analytics, and regulatory initiatives aimed toward accelerating development and commercialization of life-saving biotherapeutics. Although a number of these topics were “on the radar” before the turn of the century, by the time of BPI’s first issue in January of 2003, they were beginning to be discussed in earnest, and references to “disruptive technologies” began to appear in print, online, and conference discussions across development phases.

As revealed in BPI’s article archive the list is impressive and includes, notably
• single-use technologies
• quality-by-design
• process-analytical technologies
• advanced medicines/cell and gene therapies
• antibody–drug conjugates
• biosimilars and biobetters
• immunotherapies
• combination products
• companion diagnostics
• platform analytics and manufacturing technologies
• product life-cycle development
• continuous processing.

We have watched, too, as those innovations spread across the globe into regions not previously considered to be biomanufacturing hubs and as international regulatory agencies sought to harmonize pathways to approval. Different partnering models have emerged with both long- and short-term goals, but many in response to concerns about supply-chain integrity in an era of life-cycle management.

Presenting information and guidance for sorting through these choices of platforms, technologies, and manufacturing models is the continuing work of technical publications and conference presentations. BioProcess International magazine has always benefited from its close collaboration with the Informa conference groups (IIR/IBC) to create separate but compatible content and presentation vehicles. Many of the magazine’s editorial advisors also have served on the conference advisory panels, for example, and industry trends (and the best people to speak and write about them) identified by one group are shared with the other to bring as consistent a message to our readers and event attendees as possible.

Our two annual flagship events — now called BPI West and BPI — pull these interrelated topics together into week-long programs that you don’t want to miss if you need to stay on top of the latest interpretations of these trends. A quick look at the program for the upcoming BPI West (14–17 March 2016 in Oakland, CA) reveals the ongoing impact of the past decade’s advances on the current biopharmaceutical industry. The opening preconference symposia in themselves reflect key areas of attention: innovative approaches and technologies in process development and manufacturing, cell-therapy commercialization, ADC development, and continuous processing. Many elements of those topics were just promising ideas a decade ago, research topics that “might someday” be brought into commercial viability.

Another example is that the Basic Research and Discovery track of this year’s conference is far from the relatively “siloed” research presentations of the past. Speakers here now will stress the needed overlap of development strategies with early risk analysis and process optimization — with their goals (repeating across product classes and development stages) of shortening the times for lead optimization and transition into manufacturing. Enabling technologies incorporate analytical tools that in themselves introduce new questions: How much information is too much? What are we seeing now of contaminants and particulates in marketed products that we didn’t know were there before, and what does that mean for developers of follow-on products? What statistical knowledge for assessing this wealth of data is now required of those entering the industry that was not deemed necessary before?

I urge you to visit the conference site, download the program, and plan to attend sessions that will help you navigate the current and future worlds of biomanufacturing. Network with your peers, among whom are many veterans who helped build our current industry as well as a younger generation who are introducing fresh insights and new ways of implementing technologies and communication tools.

And as you contribute to advancing this new world biomedical approaches, take a look, also, at BPI’s third biennual awards program categories. Our awards are designed to reflect key milestones in the industry, highlight technologies that are making often-disruptive changes in how biopharmaceutical products and modalities are reaching those who desperately need them, and honor companies and people who are building a new world of healthcare options for both regional and global communities.

I have followed the biopharmaceutical industry as an editor since 1988, and I sometimes take a step back and marvel at how far this work has come. Technologies come and go — and some return again, with problems solved and new challenges revealed. Terminology may look the same, but its connotations are sometimes radically different to new generations. As always, communication is key, but exchange of knowledge must be based on shared understanding of terminology and technologies. Plan to join us in March and continue to contribute to these meaningful discussions. Make your mark on the future of biomanufacturing — we need your voice and we want to hear about your experiences.

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