Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 3rd Annual Congress on Rare Diseases and Orphan Drugs
(10 Plenary Forums - 1 Event)
San Antonio, Texas, USA.

Day 2 :

Keynote Forum

Sara Tylosky

Farmacon, USA

Keynote: Pediatric rare disease enrollment case study in Latin America

Time : 10:00-10:45

OMICS International Rare Diseases 2017 International Conference Keynote Speaker Sara Tylosky photo
Biography:

Sara G Tylosky has over 20 years of experience in strategic management and global marketing in the pharmaceutical and biotech industries. Working with large pharmas to start- up biotechs, her enrollment and training consultancy in Phase 2-4 trials through the boutique CRO Farmacon has allowed companies to reach enrollment early and reduce study costs. By bringing real-time feedback and uncovering issues, her team helps insure targets stay on track. She holds a Master’s in Business from Florida Atlantic University and an undergraduate degree from Whitman College.

Abstract:

Statement of the Problem: The paucity and scattered rare disease patient population across the globe and with more than 50% of rare diseases affecting the pediatric population are the major factors that impede successful and faster enrollment into pediatric rare disease trials, therefore slowing down innovative treatment options. Particularly in Latin America, many rare disease patients have not been in a clinical trial before and many go misdiagnosed or not diagnosed at all. In 2016, there were only 25 ongoing pediatric rare disease clinical trials in Latin America in 7 countries, and yet Latin America as a whole represents 626.7 million people, or about twice the population of the United States and 8.63% of the entire world. With a growing middle class in Latin America and the US Latino population representing 17% of that population, pediatric rare disease trials in Latin America are worth their weight to be studied.

Methodology: This case study explores the unique study enrollment challenges in Latin America and shares three solutions within a global Phase 3 pediatric rare disease trial for a major pharmaceutical company.

Findings: Even with the most seasoned CROs and strong site feasibility reports, more than 80%; 7 of all clinical trials do not meet critical milestones and more than 50% of sites do not enroll a single subject, increasing costs of the study and delaying data capture. This project demanded innovative thinking and creative problem solving from not only Sponsors, Investigators, CROs, but also from the referring physicians, families and most critically, patient advocacy groups.

Conclusion & Significance: By applying detective skills, relationship building, data based motivation tools and having a deep understanding of the cultural landscape, communication and innovative management practices were integrated for successful enrollment, which can be duplicated in future trials.

Break: Networking and Refreshments Break 10:45-11:05 @ Texas D Foyer

Keynote Forum

Sujatha Kannan

Johns Hopkins University School of Medicine, USA

Keynote: OP-101: A novel therapy for treatment of childhood cerebral Adrenoleukodystrophy
OMICS International Rare Diseases 2017 International Conference Keynote Speaker Sujatha Kannan photo
Biography:

Sujatha Kannan MD is an Associate Professor in Anesthesiology and Critical Care Medicine and Co-Director of the Pediatric Neurocritical Care Program at the Charlotte Bloomberg Children’s Center at Johns Hopkins University, Baltimore, MD. She is also the CMO of Orpheris Inc. Orpheris is focused on the treatment of neuroinflammatory orphan diseases that result in death or severe disabilities, ccALD, neonatal brain injury, Huntington's disease, Rett syndrome and autism spectrum disorders. Orpheris' patented hydroxyl dendrimer technology selectively targets inflammation in injured glial cells implicated in a number of brain diseases. Controlling inflammation through targeting injured glia with OP-101 is a potent weapon against CNS disorders. OP-101 is the company's first potential drug candidate utilizing hydroxyl dendrimer technology to deliver therapeutic doses of an anti-inflammatory drug across the blood brain barrier to reduce inflammation in glial cells.

Abstract:

X-linked adrenoleukodystrophy (ALD) is an ultra-rare disorder (incidence of 1:17,000 males) caused by mutation of the ABCD1 gene, resulting in high levels of circulating very long chain fatty acids (VLCFA). The childhood cerebral form (ccALD) occurs in ~35% of X-ALD boys between the ages of 2-10 years, and is characterized by oxidative stress, neuroinflammation and microglial activation leading to a rapidly progressive cerebral demyelination fatal within 2-3 years. Hematopoietic stem cell transplant (HSCT), the only currently approved therapy, is effective in arresting neuroinflammation and demyelination only if provided early. There is a crucial need for therapies for patients who are diagnosed late or are not eligible for HSCT (~50% patients), and for arresting disease progression during HSCT. Rapid progression of neuroinflammation as characterized by MRI imaging correlates with loss of neurological function. Gadolinium enhancement on MRI indicating an impairment of the blood brain barrier (BBB) is a characteristic feature in rapidly progressing ccALD. Therefore, reducing or inhibiting neuroinflammation caused by activated microglia can lead to disease stabilization in ccALD patients not eligible for HSCT. OP-101 is a new chemical entity consisting of N-acetyl cysteine (NAC) covalently coupled to a metabolically- stable inactive dendrimer. Studies in several small and large pre-clinical models have demonstrated the selective endocytosis uptake of OP-101 by activated microglia/ and astrocytes upon intravenous administration, localizing only in brain regions where there is with neuroinflammation-induced BBB impairment of the blood brain barrier. OP-101 releases NAC intracellularly in activated microglia and astrocytes, which then acts to reduce the attenuating oxidative stress and inflammation, in these cells and leads producing to significant improvements in neurobehavioral outcomes in the preclinical models, unlike the free drug. Macrophages isolated from ccALD patients and stimulated with VLCFA have significantly reduced cytokine expression and glutamate secretion with increased glutathione levels, when treated ex vivo with OP-101. Pilot toxicity studies in juvenile rats show that no toxicity of OP-101 is safe at doses as high as even at 1000 mg/kg IV QOD. A phase 1/2/3 placebo controlled trial for patients with ccALD who are not eligible for HSCT is planned to start in 2018.

OMICS International Rare Diseases 2017 International Conference Keynote Speaker Romina Ortiz photo
Biography:

Romina Ortiz completed her Bachelor’s and Master’s degrees at Johns Hopkins University in Neuroscience and Molecular Microbiology and Immunology, respectively. Her thesis focused on the interplay between the microbiome and hormones in autoimmune disease. She is a Co-founder of Rare Genomics Institute (RG), COO and VP of Patient Advocacy at RG. In 2016, she was awarded the Patient Advocacy Leadership award by Sanofi Genzyme. She trains volunteers on the topics of Genetics and Sequencing, directs a Patient Advocacy Program in next generation sequencing and research services to undiagnosed and rare disease patients and currently directs a philanthropic program with Illumina called iHope, offering free whole genome sequencing to children in need of a diagnosis. Her goal is to integrate phenotypic medical information with genomic data to identify the genetic cause to disease and accelerate the path to treatment and a cure.

Abstract:

From the Orphan Drug Act of 1983, a rare disease is a condition that affects fewer than 200,000 people in the United States. In the European Union, the condition must only affect fewer than 1 in 2,000 people. While the numbers seem small, there is an estimated 350 million people that suffer from rare diseases, with 25-30 million belonging to the US alone and so far there have been over 7,000 different rare diseases identified. To put this in perspective, there are more Americans affected by rare disease than for HIV, Heart Disease or Stroke combined. It is important to understand that by nature rare diseases are difficult to diagnose, and consequently are not tracked. Thus, it is hard to accurately determine the number of rare diseases and their impact on a population. The average length of tume from onset of symptoms to an accurate rare disease diagnosis is nearly 5 years, and patients see an average of over 7 different physicians before a diagnosis is made. This delay in diagnosis results in chronic physical, emotional and socioeconomic burden to both the patient and their family. A European Cost of Illness Study interrogating published literature on the cost of 10 selected rare diseases found that overall, the availability of data on economic burden for rare diseases was correlated with the availability of therapies, not the severity of the disease. Also, most rare diseases reviewed were found to have significant economic burden and indirect costs (many associated with loss of productivity) exceeded the level of direct costs. Rare Genomics has served over 500 undiagnosed patients since 2011, helping them access next generation sequencing to accelerate their pathway to a cure. We have seen the same patterns reported for rare diseases in our own patients including heterogeneous disease marked by a range of severity across a variety of biological systems. The most common systems affected are neurologic, respiratory, gastrointestinal, muscular and cardiovascular. The average RG patient has also seen a range of physicians, the top three specialties consulted are: neurologist, clinical geneticist, opthamologist and gastroenterologist. Lastly, undiagnosed/rare disease patients typically have already undergone a gamete of testing, the most common tests are: MRI, DNA microarray and single/panel sequencing. Because 80% of rare disease are genetic in origin, we hope that by providing support and access to next generation sequencing, we can help reduce the time and burden these families must undergo before identifying appropriate treatment for their disease. 

  • Orphan Drugs- development trends and strategies | Clinical Research on Orphan Drugs | Rare Diseases in Cancer
Speaker

Chair

Tony Zbeidy

Orphan-Europe, France

Session Introduction

Tony Zbeidy

Orphan-Europe, France

Title: The Middle East: A mine for orphan drugs development
Speaker
Biography:

Tony Zbeidy is a globe trotter French-Lebanese national and a US Graduate Medical Doctor who initially studied in Lebanon and obtained a BS in Biology. He travelled to US, obtained an MD and moved to UK training and working in Romford, Harold Wood and Basildon Hospitals. In 2001, he moved to France and joined Sanofi (Aventis at that time) as Medical Information Officer; in 2003, joined Orphan-Europe as Medical Advisor and 3 years later, established Orphan-Europe FZ LLC subsidiary in Dubai Healthcare City in 2006 as GM MENA, representing 1/3rd of Orphan-Europe total turnover in 2015 and growing. He has a distinguished achievement, having established alone the Middle East Metabolic Group (MEMG) and is organizing its annual meeting since 2004. In 2011, major pharma companies acting in the field of rare disorders such as Genzyme, Biomarin, Nutricia, Merck-Serono, SOBI, Nestle, Synageva, etc, joined in and in 2015, it represented 250 selected metabolic and genetic specialists from the MENA region.

Abstract:

The Middle East and North Africa region, commonly known as MENA, is nowadays the space for geopolitical conflicts and wars. Despite this fact, the MENA region proved most resistant to the recent economic crisis, especially in the rare disorders domain, continuously presenting a relatively steady market growth. Such situation makes of MENA a high potential space for investments in Orphan Drug development. But what makes MENA of particular interest for the development of Orphan Drugs? And what did many governments in the MENA region, which indirectly boosted this potential higher than ever? MENA is a unique region presenting a high consanguinity rate. Knowing that most rare disorders are recessive and that the incidence of recessive disorders correlates with the level of consanguinity, MENA became a mine for patient recruitment and Orphan Drugs clinical development. Moreover, the global awareness around rare disorders drove the governments in the region to put in place national screening programs over the past ten years. Solid from 16 years’ experience in the Rare Disorders Business in MENA and witness of the regional metamorphosis over time, our presentation will illustrate the business rationale dividing MENA target territories into six clusters, reporting regional consanguinity rates and detailing the principal screening programs put in place in the region. Thus, this presentation is intended an open window for rare disorder drug developers to Market Access the MENA region from its different angles being clinical, business, or both.

Break: Lunch Break 13:00-14:00 @ Brazos
Speaker
Biography:

Aya Narita is a Child Neurologist and has her expertise in diagnosis and treatment for neuronopathic lysosomal storage diseases and other neurodegenerative disease. She has a special interest in development of pharmacological chaperone therapy, and has been a Principal Investigator for Investigator-initiated clinical trials.

Abstract:

Gaucher disease (GD) is a lysosomal storage disease caused by mutations in GBA1 that encodes glucocere-brosidase (GCase). The resultant defective GCase leads to accumulation of the substrates, glucosylceramide and glucosylsphingosine. GD has three clinical variants: type 1 is primarily a non-neuronopathic disease whereas type 2 and type 3 are a continuum of neuronopathic ranging from acute (type 2) to subacute (type 3) progressive central nervous system (CNS) degenerative diseases. Visceral (hepatosplenomegaly), hematological (anemia and thrombocytopenia) and bone disease occur in all forms of GD. Enzyme-replacement therapy and substrate-reduction therapy are approved for patients with GD. While these therapies address most of non-neurological manifestations, none are effective against the CNS disease because of its inability to cross the blood-brain barrier. To settle this problem, pharmacological chaperone therapy (PCT) is being investigated. PCT is based on oral administration of small-molecule stabilizer of mutant proteins. Pharmacological chaperones (PCs) selectively bind to the misfolded enzyme in the ER, facilitating the correct folding of the protein and inducing functional recovery. In 2009, ambroxol, a commercially available expectorant, was identified as a PC candidate, and we started to evaluate the safety, tolerability and neurological efficacy of ambroxol in patients with neuronopathic GD. High-dose oral ambroxol had good tolerability, significantly increased lymphocyte GCase activity and decreased glucosylsphingosine levels in the cerebrospinal fluid. Drug resistant myoclonus and seizures also markedly improved. These results suggested that PCT with ambroxol is promising therapy for neuronopathic GD. 

Dung-Fang Lee

The University of Texas Health Science Center at Houston, USA

Title: Modeling Li-Fraumeni syndrome by induced pluripotent stem cells
Speaker
Biography:

Dung-Fang Lee is dedicated to understand cancer pathological mechanisms by using patient-specific iPSCs and/or engineered ESCs. He has established the first human Li-Fraumeni syndrome (LFS) disease model by using LFS patient-specific iPSCs to delineate the pathological mechanisms caused by mutant p53 in osteosarcoma and continues to apply TALENs and CRISPR/Cas9 genome editing tools to create variant p53 mutations in pluripotent stem cells (PSCs; e.g., iPSCs and ESCs) in order to explore the role of mutant p53 in osteosarcomagenesis. He also works on modeling other familial cancer syndromes with osteosarcoma predisposition by both iPSCs and PSCs. Currently, he applies whole genome sequencing, screening approaches and systems-level analyses to explore early genomic alterations and to understand dynamic alterations of the genomic landscape of LFS-associated osteosarcomas.

Abstract:

Li-Fraumeni syndrome (LFS) is a genetically inherited autosomal dominant cancer syndrome characterized by multiple tumors within an individual, early tumor onset and multiple affected family members. In contrast to other inherited cancer syndromes, which are predominantly characterized by site-specific cancers, LFS patients present with a variety of tumor types, including osteosarcoma, soft tissue sarcoma, breast cancer, brain tumors, leukemia, and adrenocortical carcinoma. Germline mutations in the p53 tumor suppressor gene are responsible for LFS. Mutations in p53 are found in 50-70% of human tumors. Although there has been extensive research on cancer cell lines and even mouse models of LFS to study the role of p53, these model systems do not fully recapitulate the range of human tumors or their properties. Here, we established human LFS disease model by using LFS patient induced pluripotent stem cells (iPSCs), to delineate the pathological mechanisms caused by mutant p53 in osteosarcoma. The osteoblasts, differentiated from LFS iPSC-derived mesenchymal stem cells (MSCs), recapitulate osteosarcoma features including defective osteoblastic differentiation and tumorigenic ability, suggesting that my established LFS disease model is a “disease in a dish” platform for elucidating p53 mutant-mediated disease pathogenesis. The gene expression patterns of LFS osteoblasts are similar to those of tumor samples obtained from osteosarcoma patients and these tumorigenic features strongly correlate with shorter tumor recurrence times and poorer patient survival rates. Our functional studies implicate the essential H19 gene in normal osteogenesis and inhibition of tumorigenesis. In order to decipher the underlying mechanisms by which H19 mediates osteogenesis and tumor suppression, we characterized and analyzed the human imprinted gene network (IGN) and revealed the unidentified role of p53 in regulating the IGN culminating in osteogenic differentiation defects and tumorigenesis. In summary, these findings imply the feasibility of studying inherited human cancer syndromes with iPSCs.

Speaker
Biography:

David Dongliang Ge is the CEO and President of Apostle Inc., in Sunnyvale, CA, focusing on novel bioinformatics-enabled nanotechnologies for cancer early detection. Previously, he was the President of BioSciKin Co. and Simcere Diagnostics Co., China focusing on the licensing and sales of diagnostic technologies. Between 2011 and 2016, he was the Director of Bioinformatics at Gilead Sciences, where he founded and provided leadership to the bioinformatics group and provided the strategic input to related infrastructure and process. He and his group led the phylogenomic analytical support for the critical regulatory approval of Sovaldi, a world-leading anti-HCV drug. In 2014 and 2015, he was invited to be a Member of the US National Human Genome Research Institute Special Emphasis Panel. Prior to Gilead, he was appointed as Assistant Professor of Biostatistics and Bioinformatics and Assistant Professor in Medicine at Duke University School of Medicine. He has received his PhD in Biostatistics and Genetic Epidemiology from Peking Union Medical College and Chinese Academy of Medical Sciences in 2004. He has authored or co-authored over 70 peer-reviewed articles.

Abstract:

The biotechnology industry has quickly entered an era when fast evolving genome technologies, historical precision medicine initiatives and disruptive bioinformatics techniques synergistically start to provide pivotal and strategic support for new drug and diagnostics development. Unprecedented amount of data is being generated to help discover and develop new generations of medications. Using real-world examples, this talk covers several of the most important bioinformatic considerations in this strategy, which include: How do we efficiently manage the massive amount of data at different levels of precision to ensure a seamless data flow? How do we annotate and present these data to make it more comprehensible and deliverable? How do we design and execute the new clinical trials more efficiently and improve the success rate? Where are we and where are we going in this new precision medicine era?

Break: Networking and Refreshments Break 16:15-16:35 @ Texas D Foyer