SAN DIEGO – At Biocom's 10th Annual Global Life Sciences Partnering Conference, a panel of players intimately familiar with last year's approval of myelofibrosis treatment Inrebic (fedratinib) explained the backstory of how they got the JAK2 kinase inhibitor off an FDA clinical hold, wrangled the rights to the drug back from the big pharma owner that had acquired the drug from Targegen Inc. and eventually helped the drug gain FDA approval after selling the rights to another large company.

The players:

  • John Hood, who was the director of medical research and co-inventor of Inrebic at Targegen and helped reacquire the drug as CEO of Impact Biomedicines Inc.
  • Sandra Dillon, a patient on Inrebic, which was the only medication that responded to her myelofibrosis
  • Catriona Jamieson, Dillon's doctor at the UC San Diego Moores Cancer Center who was an investigator in the clinical trials of Inrebic
  • Curtis Scribner, a regulatory consultant who previously worked at the FDA for 10 years

The story starts innocently enough. Paris-based Sanofi SA acquired Targegen in 2010 for $560 million in up-front and milestone payments, gaining access to the drug (then known as TG-101348). A few years later, in 2013, data from the phase III Jakarta trial looked solid enough to get the drug approved, but late that year the FDA put the drug on clinical hold after potential cases of Wernicke encephalopathy (WE) were found in eight patients.

Sanofi terminated the program just days after the clinical hold was instituted. Hood said he suspects the reason Sanofi gave up so quickly was because the company would have to pay a large earn-out to former Targegen shareholders.

With the clinical hold in effect, Dillon was taken off the medication, which had helped her go from feeling like she had the flu all the time and "barely being able to stay awake" to feeling "like a rockstar."

"We tried a number of other drugs, and they didn't work for me," Dillon told the audience. "I started getting sick again, sicker than I had been before [starting Inrebic] to the point where I had to get blood transfusions because I wasn't able to make my own red blood cells well enough anymore."

Jamieson was calling Hood almost every Wednesday – her clinic day – to tell him about her patients that needed the drug back. Eventually Hood decided to leave his job and try to get rights to the drug back, putting up $250,000 of his own money to hold an option on the drug. "This is a situation where there were patients who were dying because the drug wasn't available. There isn't really a plan B at that point. You just do what you have to do," Hood said.

Hood secured $22.5 million financing from Medicxi to launch Impact and was able to negotiate rights to the drug from Sanofi. "To Sanofi's credit they actually moved pretty rapidly," Hood said. "If you've done deals with pharma, you know getting pharma to move rapidly – those words just don't even go together."

Jamieson and Hood were convinced that the WE was caused by thiamine depletion due to high metabolic rate in patients and not the drug itself. But they had to convince the FDA of that.

Enter Scribner, who had previously helped Jamieson get a compassionate use exemption from the FDA for one of her patients, but "Sanofi screwed around long enough that the patient died. And I was not pleased. I was pissed. This is a story of being pissed, quite frankly," Scribner told the audience.

Scribner joined Impact as a consultant and Hood and Scribner began meeting with the FDA. "At the final meeting, it was contentious. John [Hood] was very angry and wrote a letter [after the meeting]. Thankfully, I got to see the letter before he sent it," Scribner said. Scribner cleaned up Hood's self-described "insanely inflammatory" letter and instead of sending it to just the project manager at the FDA, he also sent it to the division director who wasn't at the meeting.

Fortunately, the division director overruled the division's findings and lifted the clinical hold in August 2017, about nine months after Impact acquired the rights to the drug.

"That was the most unbelievable, incredible day," Dillon recalled of the day Jamieson bounded into the exam room to tell her she could get back on the drug.

With the phase III complete, the drug was ready for an NDA to be submitted to the FDA, but it made more sense to sell the company quickly and let the acquirer file the NDA.

To put itself in the best negotiating position, Impact sold royalties on the drug – with an option for the acquirer to buy them back – through a $90 million structured financing deal with Oberland Capital that included two milestone-based payments of $20 million each and set up $35 million to $50 million more in notes from Oberland that were tied to the FDA approval. "We had to be a credible thing for us to be able to take it to market ourselves," Hood told the audience.

Celgene Corp. announced the acquisition of Impact for up to $7 billion a few months later and the drug was approved about a year and a half later.

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