December 6, 2019 PAP-Q4-19-NI-006
A: During the last decade, the biopharma industry has made significant advancements in the discovery and development of new therapeutics; however, there are still many patients suffering from diseases, and they are still looking for effective treatment options.
Most diseases involve complex mechanisms, including changes in the epigenome, the chemical modifications to DNA and related proteins that regulate the expression of genes within a person’s genome. An increased effort, represented by an increased number of scientific publications, has been dedicated to understanding epigenetic mechanisms and disease in recent years.
As we enter 2020 and beyond, more robust computational approaches are under development that will allow us to build even better predictive models of gene expression and expression regulation to continue to unveil complex mechanisms of disease. At DURECT, we believe that epigenetic therapy is increasingly promising, and are excited to move our epigenetic regulation program forward. Our lead asset DUR-928 has shown promising results for the treatment of alcoholic hepatitis (AH) and has great potential for the treatment of other diseases.
A: Isolator design will soon all implement in-line CATs, which will support evolution of the decontamination agent, opening the door to replace H2O2 with HNO3, which will reduce risk from residuals, reducing cycle time and safety risks. Use of PAT during final product formulation will reduce the wait for QC testing as in-process data, minimizing in-process storage time losses.
Camera technology is being used in AVI and during fill trials to eliminate drips/tailing that adversely impact closure integrity and risk of particulate transference on container handling systems. New speciation software is still in development, but once it is a proven technology, the vision of in-line viable and non-viable particle measurement, without a microbiological testing process step that delays batch processing for weeks, will be reality.
Serialization identity technologies that utilize invisible UV imprints on containers and closure seal surfaces will reduce risk of counterfeit drugs. The recent application of computer systems for translating the mechanism of disease interaction and modeling formulations to mitigate impact will eventually change how drugs are developed and delivered, by reducing time in drug development and speeding time from R&D to the clinic and from clinic to the patient.
A: Gene therapy is one of the fastest growing areas in health care, with the potential to cure rather than treat the most complex and rare diseases. There is an abundance of gene therapy candidates in the pipeline — estimated to be approaching 400 — and, in 2019, the U.S. FDA approved a third gene therapy. This regulatory acceptance has set a precedent for other advanced therapeutic programs and brought with it a huge demand to secure manufacturing capacity. Recognizing this trend, Catalent has extended its capabilities through the $1.2 billion acquisition of Paragon Bioservices.
Gene therapy manufacturing outsourcing has many advantages for drug developers, as relatively low volumes are required to fulfill each program’s demand. However, stringent regulatory requirements and high quality standards are required to manufacture these therapies safely and efficiently. Using a partner with deep experience, cGMP-compliant manufacturing capacity and commercial-ready process development expertise is far more cost-effective than building and managing a new facility from the ground up.
Viral vector technology is still evolving, with yields incrementally improving; however, the industry will need to see logarithmic increases to meet the current demand. The hope is that, in the future, 110-fold improvements like those achieved in the monoclonal antibody space will be observed.
A: We believe that technologies that harness the breadth and the depth of the immune system will play a key role in providing next-gen therapeutic solutions for patients suffering from autoimmunity, cancers, chronic infections and other inflammatory disorders.
Approaches that will have the greatest impact are those that go beyond incremental improvements for patients and aim for more transformational breakthroughs that build upon fundamental biological nodes of immune modulation and dysregulation. A key consideration for immunotherapies will likely focus on specificity of biological signals and on platforms that can exploit the same for therapeutic solutions.
To that end, Cue Biopharma has developed the Immuno-STAT™ biologics platform that builds upon nature’s “cues” for T cell activation and modulation. It is an excellent example of biological form following function that harnesses the intrinsic specificity of the immune system, thereby potentially eliminating the negative side effects of global indiscriminate immune modulation and/or the need for ex vivo manipulation of T cells. The Immuno-STAT platform builds upon a deep understanding of T cell biology and function, which we believe is potentially why this approach is poised to disrupt the biopharma industry.
A: Recent advances in the development and commercial use of gene and cell targeting therapies that are reliant upon lipid nanoparticle (LNP) delivery technologies have the potential to redefine treatment modalities across a range of disease areas. In particular, there is a surge in the number of customer projects relating to the development and production of complex parenteral drug products for the delivery of nucleic acids, such as mRNA. We expect that LNP-based delivery of genetic drugs will continue to enable the development of exciting new personalized drug treatments over the coming decade.
Another promising area of focus is tissue engineering, where technologies for 3D printed scaffolds, cell nutrition and advanced biomaterials are being combined to create new solutions that can repair or replace damaged tissue and organs. Evonik has established an R&D hub for tissue engineering in Singapore to strengthen its competencies in this arena to ensure we are ready to serve as a global development partner and solutions provider
A: In one word: Brazil. We see Brazil as a bourgeoning country to export APIs. Brazil already manufactures APIs for the local consumption. We see Brazil exporting its APIs and becoming an API manufacturing powerhouse supplying the global pharmaceutical industry over the next 10 years. Among the key strengths of Brazil are ANVISA standards, which are very high and recognized by the European Union, strong local API know-how, a talent pool of chemists and engineers and a competitive cost structure. C2 PHARMA is investing heavily to collaborate with Brazilian companies to market their APIs outside Brazil.
A: Manufacturing approaches, automation and increasing utilization of predictive and prescriptive analytics will change the game. It is an exciting time to be involved.
A: We are in the initial stages of applying AI in hit identification and optimization at Charles River, so it is a little early for definitive data on the levels of success for our partner programs.
In AI, the next steps forward will be on the implementation strategy and how AI technologies at different stages of the process can be seamlessly integrated within organizations. However, the challenge still remains to demonstrate the current and emerging applications of AI prospectively impacting the drug discovery process. A level of skepticism towards AI in drug discovery exists, primarily due to the associated hype, and this skepticism will gradually be alleviated through demonstrated success stories on live drug discovery programs. Despite this, we anticipate that the application of AI technologies in our organization will grow significantly in the near future. AI will have a major positive impact upon our ability to find hits for challenging targets, ultimately resulting in quicker timelines to transition projects into hit-to-lead and lead-optimization phases.
A: While there have been great advances in artificial intelligence (AI) technology over the past few years, the full impact of AI has yet to be truly felt in the biopharma industry.
Heading into 2020 and beyond, we believe we will see more practical applications of AI, such as machine learning algorithms optimized for distilling the most salient information from large data sets. In the oncology space specifically, there are a growing number of tissue banks that contain samples of tumors from thousands of patients. In order for researchers to fully benefit from resources such as these, AI-driven bioinformatics approaches will have to be developed and put to use when processing these samples to ensure that they are of maximum value. We're currently working with researchers at the Léon Bérard Cancer Center in Lyon, France to analyze gene expression in the human tumor microenvironment and the composition of tumor infiltrates based on tissue samples from cancer patients. The findings from this collaboration will be used for the selection and validation of innovative targets for early development of new drug candidates for hard-to-treat cancers.
James E. Brown, D.V.M. has served as President, Chief Executive Officer and a Director of DURECT since June 1998. He previously worked at ALZA Corporation as Vice President of Biopharmaceutical and Implant Research and Development from June 1995 to June 1998. Prior to that, Dr. Brown held various positions at Syntex Corporation and Joint Ventures. Dr. Brown holds a B.A. from San Jose State University and a D.V.M. (Doctor of Veterinary Medicine) from the University of California, Davis.
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