Roche Paying $390m Up Front For Fibrosis-Fighting Promedior
Executive Summary
The deal, which includes up to $1bn for milestones, gives Roche Promedior’s PRM-151, a Phase III-ready asset for IPF that has also completed a Phase II study in myelofibrosis and could be effective in a broad range of fibrotic diseases.
After Bristol-Myers Squibb Co. declined to exercise its option to buy Promedior Inc. in mid-2018, the small biopharmaceutical company began to consider its options for financing Phase III development of its lead asset PRM-151 in idiopathic pulmonary fibrosis (IPF). Ultimately, Promedior opted to be acquired by another big pharma, announcing on 15 November that Roche will pay $390m up front and up to $1bn in development, regulatory and commercial milestone fees.
CEO and Lightstone Ventures general partner Jason Lettman told Scrip that Promedior has had an eventful year since the presentation of Phase II results for PRM-151 in IPF in May 2018 and the clinical trial’s publication in the Journal of the American Medical Association (JAMA), all of which led to increased investor and pharmaceutical partner interest in the company’s lead asset and its pentraxin-2 platform after Bristol-Myers opted out.
Bristol paid $150m up front in August 2015 for an option to acquire Promedior and access its anti-fibrotic therapies. (Also see "Bristol's Fibrotic Game Plan: Promedior Buy Hinges On Phase II Data" - Scrip, 31 Aug, 2015.) PRM-151 is a recombinant form of human pentraxin-2, an endogenous human protein that is active at the site of tissue damage. The therapy and other candidates in Promedior’s pentraxin-2 platform are designed to initiate a resolution process for the prevention and reversal of fibrosis in lung, kidney, liver, bone marrow and eye diseases. Preclinical candidate PRM-167 is being developed for ophthalmology indications.
“When you look at all of the work we’ve done in the early days preclinically, we’ve demonstrated that PRM-151 can both prevent and, probably more importantly, reverse fibrosis,” Lettman said. “That, for many years, was the holy grail in fibrosis and still is. There are very few drugs in development that have been able to do that and we showed in preclinical models an ability to do that in the eye, liver, kidney, bone marrow and, of course, the lungs.”
Eventful Period Gave Promedior Financing, Deal Options
In the time since Promedior presented and published its Phase II results for PRM-151 in IPF last year, the company also reported positive Phase II results for the candidate in myelofibrosis in June of this year and unveiled positive long-term results in IPF in May.
Before those disclosures, however, the US Food and Drug Administration granted a breakthrough therapy designation for PRM-151 in IPF in March, two and a half months after the agency and the company agreed on the Phase III clinical trial protocol for the biologic in the deadly lung disease. (Also see "Keeping Track: Approvals For Mayzent, Mavenclad, Duaklir, Jatenzo And Cimzia" - Pink Sheet, 31 Mar, 2019.)
“Through all of that we became more and more on the radar for big pharma, and Roche – given their deep expertise in the space – was tracking us very closely,” Lettman said.
He noted that Promedior was focused on remaining independent after Bristol decided not to exercise its option to buy the company. By the time Roche began to show interest, planning was under way for a venture capital crossover round followed by an initial public offering to fund a Phase III program in IPF and advance PRM-151 in additional indications. The financing plan had “significant interest from the investor community,” according to Lettman.
“The fortunate thing with the BMS transaction was that they provided $150m at the time to fund [Phase II] studies non-dilutively and that was a significant capital injection,” he said.
Prior to the deal with Bristol, Promedior had raised modest venture capital funding, including a $21.5 series D round in 2012. (Also see " Promedior's new $21.5M series D helps advance fibrosis portfolio, including IPF and mylelofibrosis " - Scrip, 8 Mar, 2012.) Between its VC funding and the large upfront fee from BMS, the company maintained a capital-efficient operation, Lettman explained. Even with a Phase III-ready candidate, it still has just eight full-time employees and several full-time consultants, he said.
Roche Will Use Its Resources To Advance PRM-151
Now, with Roche buying Promedior, the Swiss pharma will use its relatively vast resources to advance PRM-151 and the small firm’s other anti-fibrosis programs.
“What’s great about Roche is the way in which they align with our programs,” Lettman said, noting the acquirer’s existing presence in IPF with Esbriet (pirfenidone) – one of just two drugs approved in the US for the disease – and its established presence in respiratory diseases and hematology/oncology. The company also has programs in ophthalmology, which should support development of PRM-167.
PRM-151 – with its potential to treat IPF, myelofibrosis and beyond – fits well into Roche’s strategy of acquiring molecules that could be considered a pipeline-in-a-pill, including in fibrotic diseases where novel agents may be able to reverse organ damage. Global immunology business development head Patrick Schleck told Scrip in an interview in June that Roche is looking for opportunities where the company and its partners “may be able to go faster, broader and to multiple indications than perhaps either one of us would have been able to do on our own.” (Also see "Roche Dealmakers On The Immunology Technology They're Shopping For" - Scrip, 28 Jun, 2019.)
However, IPF remains the immediate focus for Promedior’s multi-indication PRM-151 pipeline. The company and the US FDA agreed to a Phase III trial protocol that is similar to the Phase II study design, with improvement in lung function as measured by forced vital capacity (FVC) as the primary endpoint. Other functional gains will be secondary endpoints, with emphasis on six-minute walk distance (6MWD), which was significantly improved for IPF patients in Phase II.
The 6MWD data may prove controversial as clinicians expressed ongoing skepticism regarding the meaningfulness of the endpoint when results for PRM-151 and other IPF candidates were presented at the American Thoracic Society meeting in May 2018 (see sidebar).
Beyond IPF, Lettman said Promedior is putting together a clinical protocol for a potential registrational clinical trial in myelofibrosis, which is likely to be a Phase IIb/III study.
“We are also pursuing other indications for PRM-151, such as [non-alcoholic steatohepatitis (NASH)] or kidney disease; we’re still in the process of determining what’s the ideal indication,” he explained. “But the good news is given how many patients we’ve treated and the fact that we now have patients on 151 beyond five years, we have a nice quick path to expand the program into other indications.”