Regulus Therapeutics: Pioneering A New Approach to Developing Therapeutics based on microRNAs

Balkrishen Bhat , Ph.D

Regulus Therapeutics LLC is a biopharmaceutical company formed to discover, develop and commercialize microRNA (miRNA) therapeutics. Regulus aspires to successfully translate one of the most important new properties in biology into a novel new approach for innovative medicine and to build the leading microRNA company. Regulus was created as a joint venture between Alnylam Pharmaceuticals, a leader in RNAi therapeutics, and Isis Pharmaceuticals, a leader in antisense technologies and therapeutics. Isis and Alnylam scientists and collaborators were the first to discover miRNA antagonist strategies that work in vivo in animal studies (Krutzfeldt et al. Nature 438, 685-689 (2005); Esau et al. Cell Metab., 3, 87-98 (2006)). Isis and Alnylam have also created and consolidated key intellectual property (IP) for the development and commercialization of miRNA therapeutics. Regulus’ IP estate includes over 900 patents and patent applications, including 600 issued patents and pertaining to chemical modification of oligonucleotides for therapeutic applications. In addition, Regulus has collaborations with more than 60 academic researchers to build on the company’s understanding of microRNAs and recently formed a major alliance with GlaxoSmithKline to explore new therapeutic areas for microRNA therapeutics. Regulus, founded in September 2007, maintains facilities in Carlsbad, California. For more information, visit www.regulusrx.com.

  How to Use Nucleic Acids to Personalize Medicine

Charles R. Cantor, Ph.D.

In this talk I will describe three ways that sensitive detection and manipulation of DNA and RNA may lead to improved medical practice. Two employ SEQUENOM's automated mass spectrometry (MS) platform, which detects specific nucleic acid sequence with unmatched sensitivity and quantitative precision, Several hundred known oncogene mutations can inform about choices of therapies since many newer therapies depend on or are rendered ineffective by the presence of these mutations. The heterogeneity of tumor samples makes mutation detection difficult by most methods because these mutations are present in only a small fraction of the cells. However they can be detected by MS, and it appears that this will be clinically quite useful. Even better would be methods of detecting such mutations non-invasively, and while this is not yet a mature approach for cancer, I will show that it is working very well for non-invasive prenatal diagnostics. The final example deals with the use of specific nucleic acid sequences as therapeutic targets. Approaches such as antisense and RNAi are well known but they suffer from the need to deliver relatively large amounts of reagents in a highly specific manner. I will describe a new approach based on nucleic acid mediated protein complementation that has the potential to deliver much moiré potent payloads.

Using Protein Medicinal Chemistry to Create Science and Business Value

Stephen W. Kaldor, Ph.D.

Ambrx is a privately held, San Diego-based biotechnology company with a unique biologics platform and a rapidly expanding portfolio of protein and antibody drug candidates including ARX-201, a long-acting growth hormone analog currently in clinical trials. Ambrx employs its patented ReCODETM technology to site-specifically introduce synthetic amino acids into biologics. By combining the power of recombinant DNA technologies with the flexibility of medicinal chemistry Structure-Activity-Relationship approaches, Ambrx produces best-in-class biologics that are highly optimized for drug characteristics. Ambrx is well funded and has ongoing drug discovery and development collaborations with Merck, Lilly, and Merck-Serono. In this talk, I will present an overview of Ambrx science and also indicate how Ambrx is striving to harness industry trends (e.g. large pharma outsourcing of drug discovery and accelerating interest in biologics company acquisitions) to create business value.

Clinical and Translation Research in Singapore :

Opportunities for Pharmaceutical, Biotechnology, and Academic Collaborations

Judith L. Swain, M.D. and Edward W. Holmes, M.D.

Singapore is a vibrant Asian country that is small (4.5 million residents), nimble, and economically successful. Over the last 10 years Singapore has made significant investments in basic biomedical research to complement the well developed pharmaceutical manufacturing sector in the country. Approximately 2 years ago, as part of the second phase of development of the Biomedical Sciences, the government decided to investment approximately S$1.55 billion (approx $1B U.S) over 4 years in translational and clinical research to complement the ongoing investment in basic biomedical sciences. This investment is being utilized in three areas: 1) human capital development including the training of physician scientists and clinical investigators; 2) infrastructure for clinical and translational research including new translational laboratory facilities, small and large animal facilities, and investigational medicine units; and 3) development of new translational and clinical research programs in five major disease areas (cancer, cardiovascular/metabolic, neuroscience, infectious diseases, eye disease). As part of the strategic initiative in translational and clinical research, two academic medical centers are being established, with one on the campus of the National University of Singapore School of Medicine, and the other on the Duke-NUS Graduate Medical School campus. Furthermore, an Academic Clinical Research Organization is being established to coordinate multicenter clinical trials throughout the nation, which will facilitate interaction with industry. Finally, two new national centers, one for cancer and the other for cardiovascular diseases, are being established in addition to the national centers already present in Singapore . Thus the landscape for collaboration with Singapore is excellent not only for academic partners, but also for partners in the pharmaceutical and biotechnology industries.

Small Molecule Drug Discovery in the Modern World

Mike Varney, Ph.D.

The presentation will focus on three main topics: 1) The characteristics of a successful Small Molecule, 2) The characteristics of a successful Small Molecule Project, and 3) The characteristics of a successful Small Molecule Drug Discovery organization. Using these concepts as a guide, Genentech is building its Small Molecule Drug Discovery organization to take advantage of recent advances in chemical and biological insights and technologies.

The Pfizer Incubator: Strategic Investment in Early-Stage Technologies

Mark J. Benedyk , Ph.D. 

With a growing awareness of the need for new medicines, and a series of patent expirations on the horizon, large pharmaceutical companies are turning to biotechnology companies to supplement their pipeline needs going forwards. With this in mind, The Pfizer Incubator, LLC (TPI), has been formed as a vehicle to identify and develop novel products and technologies. TPI is focused on the development of new companies that build on innovative products and technologies that are licensed from academic research centers or from small, already formed startup companies. In contrast to standard venture investments by large pharma, the TPI model allows entrepreneurs to grow their companies in an operating environment where many of the day-to-day needs of the company are immediately met, allowing them to focus on development of scientific projects without many of the distractions that often arise in newly formed companies. This talk will introduce TPI in the context of the current funding environment for early-stage technology companies and describe the focus of companies currently housed in TPI.