Philadelphia – Each year, a select few innovations in research and development from around the globe take center stage in Penn’s Vagelos Life Sciences & Management (LSM) dual-degree program as those projects are selected for its capstone course. This year, a project from the lab of Penn Dental Medicine’s Dr. Henry Daniell, Professor, Department of Biochemistry, using his plant-based platform for the production and oral delivery of protein therapies was among those innovations. Fourth-year LSM students developed and presented a comprehensive proposal for producing and marketing a drug Dr. Daniell has been studying to treat pulmonary arterial hypertension. These final capstone projects were recently presented at Wharton to an audience of more than 100 leaders from the healthcare industry, investment community, academia, and the public sector.
The LSM capstone course is an intensive, two-semester course in which students work in teams to develop a scientific and clinical assessment as part of a comprehensive business plan including commercialization and financing strategies for a breakthrough scientific innovation.
“Henry’s work was selected because it offers a novel scientific platform that provides the promise of potential breakthrough clinical advances in serious clinical conditions where improved therapeutic options are needed,” says Steven Nichtberger, MD, LSM Senior Fellow and Adjunct Professor in Wharton’s Department of Health Care Management, who leads the capstone course. He and a team of faculty select the four projects for the course each year.
Students formed the team named Verduro Therapeutics to create a plan on work from Dr. Daniell’s lab, proposing the development of orally delivered angiotensin-converting enzyme 2 (ACE2) for treatment of pulmonary arterial hypertension (PAH), a disease for which few therapy options exist.
In patients with pulmonary hypertension, the arteries of the lungs become constricted, which increases the workload on the right side of the heart to pump blood through the lungs. Over time, the right chamber of the heart, which usually is small, becomes enlarged and dysfunctional. ACE2 is a vasoprotective enzyme, promoting vasodilation and reducing inflammation in the renin-angiotensin system — the hormonal system that regulates blood pressure. Current drugs (double or triple sequential therapy) only manage symptoms and the median survival is 6 months (class IV), 2.5 years (class III) and 6 years (class II) with the average age of patients diagnosed with PAH being 42.
Dr. Daniell and his research colleagues have developed treatment to address the underlying pathology of PAH for prevention and reversal of this disease. They demonstrated that oral delivery of plant cells containing ACE2 or Ang-(1-7), another enzyme in the renin-angiotensin system, significantly improved cardiopulmonary structure and prevented or reversed pulmonary hypertension in suitable animal models. Studies showed that not only was right ventricular systolic blood pressure decreased, but the pulmonary blood flow was also improved. Interestingly, oral delivery of this drug fully restored right heart function and reduced maladaptive remodeling in diseased animals. This research, published in the journal Hypertension, received the best invention award from the American Heart Association in 2015.
With NIH SMARTT (Science Moving towArds Research Translation and Therapy) program funding, toxicology and pharmacokinetic studies have now been conducted at Stanford University. Dr. Daniell notes that results of the toxicology studies showed no toxicity in a 10-fold higher drug dose range. Regulatory approval studies and document preparation are in progress to file an investigational new drug (IND) application with the FDA for testing this drug in human patients.
While still in this preclinical stage within Dr. Daniell’s lab, the Verduro Therapeutics team outlined a full plan for the drug’s development from an overview of the platform technology to clinical development, marketing, pricing, and financing strategies.
“I was quite impressed with the work of the students and their presentation of the plan,” says Dr. Daniell, “they had such as strong understanding of the science of our work and the issues that would be involved in bringing a drug to market.”
That combination of skills with the goal of developing decision makers who can understand and advance scientific innovations as well as manage and promote them, is the basis for the LSM program, a unique undergraduate dual-degree program administered jointly between Penn’s College of Arts & Sciences and the Wharton School. Each year, the program enrolls approximately 24 exceptional students and offers them the opportunity to pursue an interdisciplinary curriculum combining bioscience and business, leading to the completion of two degrees: a Bachelor of Arts in a life science major, as well as a Bachelor of Science in Economics.
“For our students’ culminating capstone project, we are privileged to have access to incredible technologies typically a year or more before they form the basis for a company or a deal,” adds Dr. Nichtberger. “The work of the students is often integrated into the thinking of the companies that are subsequently formed.”
Among past capstone projects presented at their early stages was the gene therapy for inherited blindness (LUXTURNA™) and the immunotherapy for acute lymphoblastic leukemia (Kymriah™) that went on to be developed by Spark Therapeutics and Novartis, respectively.