Any worries by Promedior Inc. investors after Bristol-Myers Squibb Co. (BMS) backed away last year from its option to acquire the firm were resolved in a big way by last week's news that Roche Holding AG is taking over the company in a transaction valued as high as $1.39 billion.
Basel, Switzerland-based Roche is paying $390 million of the amount up front and the remainder as development, regulatory and commercial milestones are met. Privately held, Lexington, Mass.-based Promedior's lead asset is PRM-151, a recombinant form of human pentraxin-2 (PTX-2) protein that won breakthrough designation from the FDA earlier this year for idiopathic pulmonary fibrosis (IPF). The compound has shown prevention and reversal of fibrosis in human trials, with phase II results published last year in the Journal of the American Medical Association. Specifically, "master regulator" PTX-2 works upstream in the fibrosis cascade as an agonist and macrophage polarization factor, starting a resolution process in the body.
Promedior CEO Jason Lettmann, also general partner of Lightstone Ventures, told BioWorld that "following the [BMS] news, we really hunkered back down," and experimental results were substantially beefed up during the past year or so. "It was really a nice cadence of news and strengthening of our data [that] helped drive the acquisition," he said, adding that Promedior has "been chatting with Roche over many months. If you look at their franchises, the strategic fit with where we were headed couldn't be stronger."
In September 2015, BMS pledged up to $1.3 billion, including a $150 million up-front payment, for an exclusive right to acquire Promedior and worldwide rights to PRM-151. But the pharma giant, with bigger fish to fry later, decided not to exercise the option. At the start of the year, BMS agreed to pay $74 billion for Summit, N.J.-based Celgene Corp. (See BioWorld, Sept. 1, 2015, and Jan. 4, 2019.)
Lettmann noted that the "long, winding road" to the Roche buyout is hardly unusual in the biotech world. For fibrosis patients, there "hasn't been much reason to be hopeful" although "some great scientific advancements" have been made, he said. Promedior "came together at a time in which no one thought fibrosis or scarring is something that you could actually reverse," he said. "It's a very complex biology." His firm has narrowed its research to possible solutions in "an incredible range of disease [where] the core, underlying principle is fibrosis." PRM-151 has shown promising data in MF, as well. The compound is phase II-ready in nonalcoholic steatohepatitis and fibrotic liver disease. In ophthalmology, Promedior has next-in-line PRM-167 undergoing preclinical work.
Asked how his firm will integrate with Roche, Lettmann said that "for now, it'll be business as usual, as we get through the regulatory process," with a closing of the deal forecast in the first quarter of next year. Promedior has developed powerful expertise in guiding the PTX-2 effort thus far, he said. "Roche sees that, and we're working through a transition plan to figure that out and we'll have it nailed down over the next few months."
IPF is a chronic disease of lung scarring and affects about 200,000 people in the U.S., with about 30,000 new cases each year. Fifty percent of patients die three to five years after they are diagnosed. Investigations continue on academic as well as industry fronts. Last month, Yale University led a study in which researchers examined differentially affected regions in lungs obtained from people with IPF and found that what looks like normal lung is already undergoing changes in certain genes. Tracking how the genes change as the IPF moves ahead could lead to new targets, they noted. Findings were published in JCI Insight, part of the Journal of Clinical Investigation (JCI).
Other work on would-be new targets is ongoing at the University of Alabama at Birmingham, where investigators challenged a common theory that IPF results from recurrent injury to alveolar epithelium, followed by dysregulated repair. Reported, like the Yale research, in the JCI, findings show that the recruited monocyte-derived macrophages, which have an increased flux in the mevalonate metabolic pathway without any experimental injury can induce lung fibrosis in a mouse model. In cases of prior lung injury, the increased flux through the mevalonate pathway exacerbates the resulting fibrosis; the mechanism polarizes macrophages to a profibrotic state that causes pathogenic macrophage/fibroblast signaling. The team concluded that taking aim at the mevalonate pathway could end the role of culprit macrophages in dysregulated fibrotic repair.
On the industry side, IPF efforts and deals continue. Over the summer, Seongnam, Korea-based Bridge Biotherapeutics Inc. nailed down a deal with Boehringer Ingelheim GmbH (BI) to develop the former's phase I autotaxin inhibitor, BBT-877, for fibrosing interstitial lung diseases, including IPF. BI, of Ingelheim, Germany, is providing up-front and near-term payments of €45 million (then US$50.4 million) and Bridge could collect more than €1.1 billion in additional payments if development, regulatory and commercial milestones are achieved, plus staggered royalties into the double digits. BBT-877 is due to enter phase II trials within the next 12 months, the companies said, and the first target is IPF, already of interest for BI with its marketed antifibrotic tyrosine kinase inhibitor, Ofev (nintedanib), which slows disease progression by reducing the decline in lung function. It's approved for IPF in more than 70 countries, including the U.S., the EU and Japan. (See BioWorld, July 19, 2019.)