51社区

Rick Hawkins, BSED 鈥�75, spent the morning of Nov. 2 at 51社区鈥檚 Edison Biotechnology Institute (EBI), hearing about the latest research occurring in Dr. John Kopchick鈥檚 lab, where decades earlier a scientific breakthrough put OHIO on the map in the study of obesity, diabetes, cancer and aging.

It was that breakthrough that 30 years ago brought Hawkins, an OHIO alumnus and changemaker in the field of drug development, to Kopchick, a distinguished professor in the Heritage College of Osteopathic Medicine鈥檚 Department of Biomedical Sciences and Goll-Ohio Eminent Scholar. This dynamic duo would spend the next decade turning Kopchick鈥檚 discovery into pegvisomant, known by its brand name Somavert庐, a treatment for a rare and life-shortening disease.

鈥淲ithout Rick Hawkins and a lot of serendipity,鈥� says Kopchick, 鈥淪omavert would not exist.鈥�

As Hawkins puts it: 鈥淛ohn and I were meant for each other.鈥�

The story behind Somavert is the story of two trailblazers whose work鈥攁s individuals and in partnership鈥攈as saved lives, advanced science, and generated prestige and record-breaking drug royalties for 51社区. It鈥檚 a story of extraordinary innovation, Bobcat connections and unwavering determination in the face of, at times, seemingly insurmountable hurdles. And it鈥檚 a story that continues to unfold.

The discoverer

Kopchick came to Athens in 1987, lured from a position with pharmaceutical giant Merck by an offer to become one of Ohio鈥檚 first eminent scholars鈥攁n endowed professorship funded by the state and OHIO alumni Milton, AB 鈥�35, and Lawrence, BBA 鈥�66, Goll鈥攁nd an opportunity to work at EBI.

The institute had one of the few labs in the world capable of producing transgenic animals, whereby cloned genes are transferred from the laboratory to mice through DNA microinjections. It was a revolutionary breakthrough in biomedical research discovered by an OHIO research group led by Professor Thomas Wagner, who in 1981 made global headlines after successfully producing and patenting the technology behind it.

Using transgenic mice, Kopchick began experimenting with growth hormone, a protein that captured his attention because of its ability to dissolve fat while increasing muscle and bone mass, but that also is associated with elevated risk of diabetes and cancer.

鈥淲e started out saying, let鈥檚 see if we could change the growth hormone molecule in specific places and retain the good things鈥攖he ability to make bones grow, decrease fat, build muscle鈥攁nd do away with any of the bad actions,鈥� he recalls.

Kopchick and the graduate students in his lab began altering each of the protein鈥檚 191 amino acids. The team screened the effects of each alteration by injecting the modified genes into mice, hoping to get a larger mouse resistant to diabetes and cancer. One change made by student Wen Chen, MS 鈥�87, PHD 鈥�91, brought the unexpected: a dwarf or mini-mouse.

鈥淚 didn鈥檛 believe it, so I had the student go back and repeat the whole thing,鈥� Kopchick says. 鈥淪ure enough, he was getting these small animals. One amino acid change made it a growth hormone receptor antagonist.鈥�

Kopchick knew they had stumbled onto something big鈥攁n inhibitor, some of the blockbusters of the pharmaceutical industry. Working with OHIO鈥檚 Technology Transfer Office, they applied for and received several patents on the discovery.

Kopchick began contacting pharmaceutical companies, hoping to license the discovery and develop it into a drug. He zeroed in on its potential uses for the treatment of diabetes, cancer or acromegaly, a rare condition in which the pituitary gland produces too much growth hormone, causing excessive growth of organs and bones and, if untreated, premature death.

鈥淚 visited just about all of the major pharmaceutical companies,鈥� Kopchick remembers. 鈥淣one of them were interested, and I couldn鈥檛 believe it.鈥�

His discovery was the first-ever large molecule antagonist, which, in the early stages of development, caused apprehension in the pharmaceutical and scientific communities. Efforts to even get the work published proved challenging鈥攗ntil 1991, , aptly illustrated in OHIO鈥檚 signature green and white, on the cover of its December issue.

During one of their bi-weekly basketball games and weight-lifting sessions, Kopchick mentioned his struggles to license the discovery to his friend, Joe Dean, BSED 鈥�61, MED 鈥�62, an assistant OHIO football coach. Dean immediately thought of one of his former players: Rick Hawkins.

鈥淛oe told me that Rick is very successful in the drug development business,鈥� Kopchick recalls of that fateful conversation. 鈥淚 said, 鈥楾hat鈥檚 exactly what we need. We made the discovery. I know what we have to do to get to the endpoint, but I don鈥檛 know how to do it.鈥欌��

Dean wrote Hawkins鈥� phone number on a Post-it庐鈥攁 piece of paper that wound up in his dirty shorts in the laundry. Kopchick鈥檚 wife, Char, discovered it that evening in the washing machine and prompted him to make the call.

The developer

Like Kopchick, Hawkins started his career in the pharmaceutical industry, working for Johnson & Johnson while finishing the final credits for his OHIO degree. He spent 10 years with J&J, learning, he says, 鈥渄rug development from one of the finest companies on the planet.鈥�

Even in the earliest days of his career, Hawkins鈥� entrepreneurial mindset began to emerge.

鈥淚 used to say: It only takes 12 years and $1.2 billion to get a drug approved. The process is so inefficient,鈥� he recalls.

Hawkins began advocating for making certain aspects of drug development independent of the big pharmaceutical companies鈥攁ll as a means of expediting the process. In 1981, he set out to do just that.

Using a small bank loan and quickly maxed-out credit cards, Hawkins founded Pharmaco, an Austin, Texas-based company that provided drug development services, like analytical chemistry and clinical trials, to big pharma and established himself as a pioneer in the contract research organization (CRO) sector.

鈥淚f you learn how to be successful at one thing and use that as the foundation to whatever you take on next, it can be very powerful and sustaining,鈥� Hawkins says of his career trajectory.

Hawkins鈥� road to success began as an all-conference high school athlete in Fairfield County, Ohio, where his biology teacher, Max Beougher, BSED 鈥�58, inspired him to study biology in college. Two other OHIO graduates from his community, Milt Taylor, BSCOM 鈥�50, and Mark Wylie, BSED 鈥�49, made those college dreams come true, helping Hawkins secure a full scholarship to play football for the Bobcats after an injury his senior year put that dream in jeopardy.

鈥淚 came to 51社区 as an athlete, had to evolve into being a student-athlete and then become a lifelong student in order to be in the business I鈥檝e been in,鈥� says Hawkins. 鈥淚 learned all of that in Athens, Ohio.鈥�

Hawkins describes his OHIO student experience as 鈥渁n awakening鈥濃�攁 time to engage in a diverse community and be exposed to new perspectives, and during . As a defensive back on the Peden Stadium field, he learned the value of teamwork, how trust is paramount to success and that 鈥測ou better come prepared and bring your best game no matter what.鈥�

He used those experiences and lessons to build a culture at Pharmaco centered on service and saw immediate success, growing the company to more than 2,000 employees. In 1991, Hawkins sold Pharmaco, which later merged with Pharmaceutical Product Development, a global CRO that, in December, was purchased for $17.4 billion.

鈥淭he roots of entrepreneurism are different for everyone,鈥� Hawkins says. 鈥淔or me, it was a combination of being demanding of myself as an athlete and then in business, wanting to be successful and then figuring out what the formula is for that. But it鈥檚 also an attitude that you can do it. 鈥� To me, a 鈥榥o鈥� was only a delayed 鈥榶es.鈥欌��

It was just after selling Pharmaco that Hawkins received that phone call from Kopchick, who told him about his discovery and the all the rejections from big pharma and followed up by sending him a proposal. Weeks later, a sleepless night and inquiries from Kopchick prompted Hawkins to start reading.

鈥淚 read all night long, and what struck me based on my experience in rare disease drug development at J&J was that this compound should be effective in acromegaly,鈥� Hawkins says. 鈥淲ithin 24 hours, I was on a plane to Athens, and within a month, I had licensed John鈥檚 discovery from 51社区.鈥�

The difficulties

Using proceeds from the sale of Pharmaco, Hawkins began funding further research into Kopchick鈥檚 discovery and building a staff to develop what would become Somavert.

In 1994, Hawkins and business partner Chip Scarlett established Sensus Drug Development Corp. Using his drug development knowledge, business acumen and ability to attract investors, Hawkins started pushing Kopchick鈥檚 discovery toward the marketplace.

鈥淒rug development is an extremely difficult business, fraught with all kinds of things that can go wrong,鈥� Hawkins says. 鈥淲ith Somavert, there were multiple absolutely daunting barriers to getting this drug approved.鈥�

A growth hormone receptor antagonist was a completely new class of medicines, was being targeted for a rare disease鈥攁nd was being developed alongside some high-profile failures in protein therapeutics, which made it extremely difficult to raise capital.

鈥淚t costs a lot of money to develop any drug, and very few people believed in the rare disease market at the time,鈥� Hawkins says. 鈥淚 was attempting to raise capital for Sensus under those circumstances.鈥�

Hawkins also found himself having to wheel and deal with other companies.

He negotiated a licensing agreement for technology called pegylation that allowed Kopchick鈥檚 compound to slowly filter through the kidneys, extending its half-life. And, with the persuasive help of the founder of the acromegaly patient advocacy group, Hawkins executed another agreement for technology owned by Genentech鈥攐ne of a few companies producing recombinant human growth hormone or manufacturing large proteins at all鈥攁nd got the company to agree to produce Kopchick鈥檚 compound.

Genentech made enough of the compound to get the drug through its first trials, but the amount of money it wanted to be Sensus鈥� manufacturing partner for its final trial, and to eventually produce what would become Somavert, was onerous at best.

鈥淚 literally was on a plane all over the world trying to find someone to do this,鈥� Hawkins recalls. 鈥淭here was no one on the planet manufacturing proteins on a contract basis.鈥�

Somavert鈥檚 most daunting hurdle was, for Hawkins, an opportunity. Armed with research on all the companies that were developing protein therapeutics鈥攁ll of which were going to face the same obstacle when it came to manufacturing鈥攈e took a business plan to Corning.

Hawkins left Corning with millions to develop a facility that would manufacture recombinant proteins, helping to found what would become Corning Life Sciences Inc. and establishing him, again, as a pioneer鈥攖his time in the protein contract manufacturing sector.

Efforts to construct that facility in Ohio and Texas were unsuccessful, but government officials in North Carolina provided Hawkins the land, tax incentives and assistance in securing permits for Covance Biotechnology Services Inc. in Research Triangle Park.

鈥淲e pulled that thing out of the ground in the shortest period of time,鈥� Hawkins says. 鈥淣ot only did they make Somavert鈥攁nd enough to get it across the finish line鈥攂ut we got multiple new contracts, FDA inspectors to approve it, and we sold it to Akzo Nobel.鈥�

In 2001, Pharmacia Corp. bought Sensus and was later purchased by Pfizer. In 2003, the FDA approved Somavert for the treatment of acromegaly. Annual worldwide sales of the drug reached $277 million in 2020.

鈥淣o one knows this story鈥攈ow difficult it was and all the challenges we had to overcome,鈥� says Hawkins.

The impact

Hawkins and Kopchick have been celebrating the success of their discovery-turned-drug for the past 20 years. And they have much to celebrate.

Somavert royalty payments, which ended in 2019, have netted OHIO and its inventors $105 million and have been reinvested in the University (see below).

The impact it鈥檚 had on Kopchick鈥攏amed an OHIO Distinguished Professor of Molecular Biology in 2012鈥攃an be seen throughout EBI, where the walls are adorned with publications he鈥檚 been featured in, places he鈥檚 spoken and awards he鈥檚 received.

鈥淚鈥檓 known worldwide, and I鈥檓 a 3 million United miler,鈥� Kopchick says, referring to the number of miles he鈥檚 traveled training endocrinologists on the use of Somavert and delivering his 鈥淕rowth Hormone, Mini Mice, Football, Dirty Shorts and a New Drug鈥� presentation. 鈥淓very word in that title,鈥� he says, 鈥渨as very important for the development and discovery of this drug.鈥�

Among the most notable of Kopchick鈥檚 many awards are a 2008 AMVETS Silver Helmet Award, the British Society for Endocrinology鈥檚 2011 Transatlantic Medal and the Endocrine Society鈥檚 2019 Laureate Award for Outstanding Innovation. In 2013, Kopchick was elected president of the Growth Hormone Research Society, and his work and reputation have attracted scholars from around the world to study in his OHIO lab.

鈥淛ohn is a real force in the endocrine drug world,鈥� says Hawkins, who鈥檚 seen Kopchick鈥檚 students dominate the podium at international endocrinology conferences with their presentations and research. 鈥淚n his lab, he creates a culture that allows those around him to be successful. That theme has been at the core of my career and why I鈥檝e been successful.鈥�

For all of their success, what means the most to Hawkins and Kopchick is what Somavert has meant to those with acromegaly.

鈥淭here鈥檚 nothing more humbling than to have a patient sitting in your office, looking at you and saying, 鈥楾hank you.鈥� Nothing,鈥� Kopchick says. 鈥淚t still gives me chills whenever I talk about it.鈥�

For Hawkins, who was awarded OHIO鈥檚 Konneker Medal for Commercialization and Entrepreneurship in 2014, bringing Somavert to the marketplace is a full-circle moment鈥攁 chance to contribute to the future of a university that paved the way for his future.

鈥淲orking with one of the preeminent molecular biologists in the world, at 51社区, to develop this compound that does so much good for patients and at the same time rewards John and 51社区 in a profound way gives me so much pleasure. I can鈥檛 even tell you,鈥� he says.

The next chapter

Today, Hawkins is CEO and chairman of Lumos Pharma, a biopharmaceutical company developing therapeutics for rare diseases. The company鈥檚 latest endeavor? A growth hormone-stimulating drug for the treatment of Pediatric Growth Hormone Deficiency (PGHD). The compound is the opposite of Kopchick鈥檚 antagonist but was brought to Hawkins鈥� attention by Kopchick.

Kopchick learned about the compound from Dr. Michael Thorner, professor emeritus of medicine at the University of Virginia, who contributed to the clinical trials for Somavert and served on Sensus鈥� advisory board. Like Kopchick with Somavert, Thorner couldn鈥檛 find a pharmaceutical company interested in bringing it to market.

鈥淚 said, 鈥榃hy don鈥檛 you call my buddy, Rick Hawkins?鈥欌�� Kopchick recalls. 鈥淓xactly what Joe Dean told me.鈥�

Hawkins entered a licensing agreement with Thorner, and Lumos Pharma is running a global Phase 2 trial of LUM-201, which, if successful, will allow children with PGHD to take a once-a-day orally administered medication instead of the daily injections of recombinant human growth hormone they鈥檙e subjected to now.

Back in Athens, Kopchick and his team of students, postdoctoral fellows and investigators at EBI are continuing their research on growth hormone as it relates to obesity, diabetes, cancer and aging.

Their work over the past 30 years has resulted in significant external research funding for OHIO, particularly, Kopchick says, for aging studies. While working on Kopchick鈥檚 growth hormone receptor antagonist, the team also generated a growth hormone receptor 鈥渒nock-out鈥� mouse, which lived to be nearly five years old and continues to hold the record for the longest-lived laboratory mouse.

Some of the lab鈥檚 most promising work right now: 鈥淕rowth hormone receptor antagonists for cancer,鈥� Kopchick says.

His lab works with a Columbus-based company and has developed an improved version of Kopchick鈥檚 growth hormone receptor antagonist that inhibits tumor growth and, when combined with chemotherapy, eradicates certain types of tumors. In December, Kopchick was one of only three university innovators throughout the state invited to and designed to connect university research with private sector investment.

And Kopchick and Hawkins will take center stage when OHIO hosts the Federation of American Societies for Experimental Biology鈥檚 2022 Growth Hormone/Prolactin Family in Biology Disease Conference. Slated for May 15-19, the conference will bring clinicians, scientists and industry representatives to Athens to explore the latest developments in their fields鈥攁nd to hear the story of Somavert.