5 minute read
Jan. 23, 2024

Leaving Academia to Discover a Billion-Dollar Drug: Reflections from a Thirty-Year Path to Momelotinib’s Approval

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Drug Hunter Team

In September, the U.S. Food and Drug Administration approved momelotinib (Ojjaara), a JAK/ALK2 inhibitor and potentially game-changing treatment for myelofibrosis. In July 2022, the molecule was at the center of a $1.9 billion deal when GlaxoSmithKline acquired Sierra Oncology. While waiting for the FDA’s decision, one of the drug’s creators expressed that he had only one regret: he didn’t start focusing on drug discovery sooner. 

Prof. Andrew Wilks is an accomplished academic scientist and serial entrepreneur who is the founder or co-founder of 10 companies focused on novel therapeutics. He discovered the JAK enzyme family, gave them their name, and founded one of Australia’s most successful biotech companies, Cytopia, the originator of momelotinib.

Wilks and momelotinib co-inventor Dr. Christopher Burns earlier this year spoke with Drug Hunter CEO Dennis Hu and a crowd of 120 webinar attendees about the road to this pivotal moment in their careers

Wilks said he spent the early portion of his career as an academic, focused more on discovery for discovery’s sake. Later in his career, Wilks realized the reward of using his scientific abilities for the benefit of patients suffering from difficult-to-treat conditions. 

“I was the most snooty and self-indulgent academic for the longest time,” Wilks jokingly told the webinar audience. “I arrived quite late at the idea that you could actually make a difference with more of a translational mindset.” 

A Potential Game-Changer for the Treatment of Myelofibrosis

With momelotinib, Burns and Wilks are making up for lost time. The treatment holds promise for easing the suffering and extending the lives of those with myelofibrosis, a rare form of bone marrow cancer that affects roughly 1.5 of every 100,000 people in the United States each year. The disease is characterized by a buildup of fibrous scar tissue in the bone marrow. As the amount of scar tissue increases, it disrupts the body’s normal production of red blood cells, leading to severe anemia causing debilitating weakness and fatigue. Another myelofibrosis symptom includes enlarged spleen (splenomegaly), creating intense discomfort for patients. 

At the webinar, Wilks and Burns presented data on how momelotinib could change the lives of patients suffering from myelofibrosis. Momelotinib appears to be differentiated from other JAK1/2 inhibitors by significantly reducing anemia while maintaining efficacy in myelofibrosis, thanks to its unique and unexpected mechanism of action incorporating ALK2 activity.

But Burns was also inspired by the anecdotal stories from people who are finding renewed vigor through treatment with momelotinib. 

“This was really one of those few times in my career where you get data that is profoundly moving and really makes you think you’re onto something,” he said. “We are getting stories of people that had been bedridden who are now back out living their lives, enjoying retirement or getting back to work, so that was really wonderful news to hear.” 

Discovering “Just Another Kinase”

The long road to momelotinib started in 1988 when Wilks was looking for receptor kinases involved in blood cell differentiation. His work led to what he described as a torrent of new kinases. Two of them had atypical structures, lacking the transmembrane domains that the receptor kinases he was looking for should have. So he named the family Just Another Kinase – or JAK1 and JAK2 – and set them aside.

A few years later, Wilks prepared to publish a paper on his kinase discoveries and realized he couldn’t use this acronym based on such a flippant name. He had to find another way to justify the acronym, he said. 

He found what he was looking for amidst the Roman gods. Wilks had learned that Janus, the Roman god of doorways, had two faces so he could always look out and in at the same time. 

“Metaphorically speaking, with the two kinase domains, I kind of justified the whole acronym as the Janus Kinases,” he said. 

Thus, the newly discovered JAK1 and JAK2 were no longer Just Another Kinase, but instead the Janus Kinases that today are well-established targets for industrial drug discovery.

The “Baked Bean” Years

Today, several JAK inhibitors have become billion-dollar-a-year blockbusters, and in February 2022, GlobalData’s analyst consensus data forecasted sales from momelotinib to exceed $350 million by 2027. But the commercial potential of JAK inhibitor was far from obvious in the ‘90s. In 1997, Wilks had formed the company Cytopia to pursue making a difference with his discovery, but this was long before $50M+ startup fundraising rounds were a common occurrence.

“I immediately fell on hard times,” he said. “That’s what my wife calls the baked bean years. We went through quite a traumatic time trying to set up Cytopia.” 

Seed money led to some investors, but money quickly became scarce. “The only income I had for a time was when I came in sixth in the Australian Lightning Chess Championships and won $123,” he said.

Then around 2000, Wilks met Burns through a mutual academic acquaintance and the journey toward momelotinib accelerated. Wilks calls meeting Burns “one of the most fortuitous encounters that I’ve ever had in my career” and refers to him as “the Cher to my Sonny, although that’s probably the wrong metaphor.”

A Satisfying Conclusion to a Winding Thirty-Year Journey

It took another two decades and a journey through several companies (YM Biosciences, Gilead, Sierra Oncology) before momelotinib’s pivotal clinical data was obtained in myelofibrosis. For Wilks, the data on momelotinib is confirmation that his decision to leave academia to make a difference for patients with life-threatening conditions was the right one, even if it did require living through those baked bean years. 

Burns is hopeful for the molecule because momelotinib has a unique safety profile compared to other approved JAK inhibitors that sometimes lead to treatment-related adverse effects such as  anemia, which requires blood transfusions to treat.

“That’s not only important in terms of quality of life,” Burns said. “There’s a lot of evidence showing that patients who are anemic with myelofibrosis have a worse outcome – lower survival. So this is a really profound benefit of momelotinib and something that we see as very, very exciting.”

Register for Flash Talks and Learn More About Momelotinib

You can register for future Drug Hunter Flash Talks here or read more about momelotinib in “Why Did GSK Pay $1.9B for Another JAK Inhibitor?” here.


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