More than a decade after one of its early splashes in therapeutic development caused ripples in the U.S. patent tide pool, the Wisconsin Alumni Research Foundation, better known as WARF, is taking a more seasoned approach to drug discovery and development.
In February, the organization formally launched WARF Therapeutics with the mission of identifying biological discoveries at the University of Wisconsin-Madison (UW-Madison) with potential relevance to human disease. WARF Therapeutics plans to invest in validated targets, design and develop drug-like molecules and, ultimately, partner those assets with venture investors, pharmaceutical companies and biotechs. The program is led by Jon Young, a 25-year veteran in medicinal chemistry and drug discovery and development whose resume spans tenure at Merck Research Laboratories, Celgene Corp. and Regulus Therapeutics Inc.
In March, WARF Therapeutics disclosed its first partnership, with Sanford Burnham Prebys Medical Discovery Institute, a nonprofit focused on understanding basic human biology and disease and advancing discoveries with the potential to improve human health.
More recently, WARF Therapeutics tapped the biopharma world to bolster its advisory board, naming four members with deep expertise in translational medicine and preclinical drug discovery. They include Deepak Dalvie, senior director in drug metabolism and pharmacokinetics at Celgene, now a unit of Bristol-Myers Squibb Co., of New York, and a former research fellow at New York-based Pfizer Inc.; Mark Deeg, most recently chief medical officer for Regulus, of La Jolla, Calif., and former chief medical and safety officer at Chorus, a research division of Indianapolis-based Eli Lilly and Co.; Christopher Dinsmore, entrepreneur-in-residence at Third Rock Ventures and former vice president and head of chemistry at Forma Therapeutics Inc., of Watertown, Mass., and executive director at Merck Research Laboratories, a unit of Merck & Co. Inc., of Kenilworth, N.J.; and Paul Secrist, senior vice president and head of discovery research at Lifemine Therapeutics Inc., of Cambridge, Mass., and former director of cancer biosciences at Astrazeneca plc, of Cambridge, U.K.
The four joined Jennifer O’Neil, vice president of translational oncology at Akrevia Therapeutics Inc., of Cambridge, Mass., and a former Merck Research scientist.
Founded in 1925 as the first technology transfer organization (TTO) in the U.S., WARF oversees the cycle of research, discovery, commercialization and investment for UW-Madison, managing more than 2,000 patents and an investment portfolio of $2.7 billion that is wielded to further university research, pursue patents for discoveries and license inventions to industry.
“Historically, therapeutic innovations were largely treated like every other innovation here on campus, from agriculture to engineering and just about anything in between,” said Young, who joined WARF Therapeutics in September 2018. “For quite some time, that approach was sufficient.”
WARF Therapeutics evolved ‘out of necessity’
WARF generated more than $500 million in royalties from patents related to warfarin (Coumadin) and the secondary hyperparathyroidism drug Zemplar (paricalcitol, Abbvie Inc.) before they lost exclusivity.
The organization also famously clashed with biopharma in the early 2000s over three stem cell patents issued by the U.S. PTO to UW-Madison scientist James Thomson based on his work in isolating and maintaining primate and human embryonic stem cells (hESCs) in culture. The patents, assigned to WARF, which initially charged steep licensing fees, became the object of nearly a decade of legal battles with the Foundation for Taxpayer and Consumer Rights (now Consumer Watchdog) and the Public Patent Foundation, which filed requests with the PTO to revoke them. In 2007, weeks before the PTO issued a preliminary denial of the patents and agreed to re-examine the claims. WARF moderated its demands for licensing deals with outside scientists. In the ensuing years, WARF’s decision to ease licensing fees and restrictions and the ability of researchers to source hESCs elsewhere mitigated the controversy over the now-expired patents.
The experience was instructive for WARF. In 2016, the organization tapped Erik Iverson, former president of business and operations at the Infectious Disease Research Institute in Seattle, to succeed long-time managing director Carl Gulbrandsen upon his retirement. An adjunct professor in biotechnology law at the University of Washington and the first attorney dedicated to the Bill & Melinda Gates Foundation's global health and agricultural programs, Iverson came to WARF with street cred in life science discoveries and intellectual property management and a stated desire to work closely with UW-Madison researchers and bolster WARF’s dwindling patent income stream.
That was no small task. The PTO no longer grants patents on naturally occurring molecules or targets and biopharma has shown little appetite to license those types of early discoveries, Young pointed out. The TTO was forced to consider how to advance translational research to clinical proof of concept, where industry is more likely to become engaged, rather than relying solely on academic publishing and patent claims.
“From those conversations and, quite frankly, out of necessity, WARF Therapeutics began to evolve,” he told BioWorld.
Beginning last year, Young and officials associated with WARF and UW-Madison visited with more than a dozen academic drug discovery centers to learn about their models, processes, infrastructure and funding mechanisms. Young also harnessed his pharma experience, reaching out to industry colleagues “to set the goal posts” that WARF Therapeutics would need to surmount in its programs.
“A key lesson we learned was that WARF Therapeutics needed to be staffed with industry-trained drug hunters to generate the data packages that pharma and biotechs were seeking in a licensed asset,” Young said.
Young and Brian Dyck, San Diego-based director and head of chemistry, are chasing down those leads. WARF Therapeutics also houses three licensing and business development (BD) staff but leans heavily on the virtual organizational model, according to Young. He cited the partnership with Sanford Burnham Prebys in San Diego, an institution with 60 industry-trained employees whose experience bridges target validation to clinical trials.
“That’s where a lot of our science is going to be executed,” Young explained, noting that WARF Therapeutics also has agreements with contract research organizations outside the U.S. The advisory board will help WARF Therapeutics to vet translational research, build its portfolio and, potentially, find “landing spots” for some of its discoveries following in vivo proof-of-concept studies in animal models of disease.
“I don’t think we’re typically going to take these assets through IND tox studies unless we already have a partner lined up,” Young said, though he suggested opportunities may emerge to license novel molecules with validated mechanisms if they plug gaps in biopharma preclinical pipelines.
Building ‘a vigorous portfolio for years to come’
The BD staff already is shopping the first five early stage assets in WARF Therapeutics’ portfolio: three oncology programs and one each in neuroscience and ophthalmology. An undisclosed oncology target has advanced to lead identification while the others remain at the screening and hit validation stage. The advisory board is actively reviewing proposals for five additional assets, some or all of which may enter the portfolio early next year.
“We’re agnostic in terms of modality and therapeutic area, so we could look at small molecules, proteins, bispecifics, engineered cells and gene therapy,” Young pointed out. “We’re mostly interested in identifying the best available targets with the deepest validation and therapeutic hypothesis. Ultimately, those types of discoveries will help to fill unmet medical needs.”
Young has been crisscrossing the UW-Madison campus to “get the word out” about WARF Therapeutics, and those meetings have “helped to fan the flames” among tenured professors and post-docs alike.
“We’re open to all comers – anyone who has a great research proposal,” he said. Based on initial interest, “we’ll have a vigorous portfolio for years to come.”
The WARF Therapeutics business model is a bit unconventional for large U.S. TTOs, which are more engaged in BD than in years past but for the most part continue to rely on royalties from licensing deals and spin-outs rather than investing dollars up front. In fiscal year 2016, AUTM (formerly the Association of University Technology Managers) reported that 7,021 U.S. patents were issued to U.S. universities and 7,730 licenses and options were executed, 16,487 U.S. patent applications were filed, 1,024 startups were formed and 800 commercial products were developed.
Naturally, discoveries in human therapeutics represent just a fraction of those numbers, but misaligned incentives in some early life science deals engendered animosity between academic TTOs and biopharma that only began to heal over the past decade. Because drug discovery is a marathon, not a sprint, balancing short- and long-term return on investment remains problematic – a lesson that isn’t lost on Young.
Still, he maintained, the dynamics between academia and biopharma have greatly improved.
“The attitude of pharmaceutical companies toward external research has changed dramatically. Many pharmas now acknowledge that the best discoveries are happening outside their walls and they have to figure out how to harness these,” he said.
“It doesn’t matter whether you’re in academic drug discovery, biotech or pharma, the most important lesson that’s come out of drug discovery in the last 15 years is the importance of program selection,” Young added. In general, TTOs seek to leverage the most promising discoveries to emerge from their institutions and to position them for commercial success. For WARF Therapeutics, Young said, that process means “investing in target validation to help de-risk the program before we get too far down the road.”