Interview: Mallinckrodt Deal Golden For Silence Therapeutics
Executive Summary
The gene silencing specialist has signed a collaboration that CEO David Horn Solomon tells Scrip will help push Silence up among its peers in the RNAi space.
After signing a deal with Mallinckrodt PLC on the first anniversary of becoming CEO of Silence Therapeutics PLC David Horn Solomon has been reflecting on how transformational the pact will be and the progress the UK-based RNA interference (RNAi) specialist has made in the last year.
The collaboration gives Mallinckrodt an exclusive worldwide license for one preclinical asset, SLN500, that targets a specific protein in the C3 complement pathway and an option for up to two additional assets with different complement protein targets. Silence will be responsible for taking SLN500 through preclinical studies and a Phase I trial, after which Mallinckrodt will take over clinical development and responsibility for global commercialization.
It is a very early stage alliance – and the firms only confirmed that it focuses on the complement cascade, without specifying which diseases they are targeting – but Silence is in line for some healthy initial payments and follow-ons that mean the collaboration is worth potentially over $2bn. In an interview with Scrip, Solomon noted that Silence is getting $20m upfront, plus $5m from an equity investment from Mallinckrodt which has bought 5.1 million shares for a 6.5% stake. The latter will also pay up to $10m in research milestones for SLN500 and for each optioned asset, in addition to funding for Phase I clinical development including GMP manufacturing.
After that, "the numbers keep going up," Solomon said. The collaboration provides for potential added clinical and regulatory payments of up to $100m for SLN500, as well as commercial milestones of up to $563m. Should Mallinckrodt opt to license one or two additional assets, Silence could receive up to $703m in similar payments per asset, plus tiered, low double-digit to high-teen royalties.
He added that the deal is "really transformational, validating our underlying technology and shows where we're going as a company.” It involved a competitive process "as we are always talking to pharma and Mallinckrodt came with an offer that was compelling."
The latter's chief scientific officer Steve Romano, former head of development of Pfizer Inc. is joining the Silence board and Solomon said, "I think he'll be a great sparring partner in the boardroom around our development programs, not only for the ones with them but our other ones in cardiovascular medicine and hematology as well."
The other projects he mentioned include Silence's lead candidate SLN124, a monthly subcutaneous injection which is going into a Phase Ib study in Europe in the second half of 2019 for the treatment of beta-thalassemia. Solomon is particularly excited about SLN360, which silences a component of lipoprotein a – Lp(a) – elevated levels of which have been associated with increased risk of cardiovascular disease.
SLN360 could be "the jewel in the crown," Solomon said, noting that a clinical trial authorization is anticipated to be filed in the second half of 2020. "Whether you're thin or fat, whether you diet and exercise or not, LP(a) levels are genetically determined and they are the predictive factor," he claimed, noting that other companies are also looking at the LP(a) area, citing Amgen Inc. and Arrowhead Pharmaceuticals Inc.'s gene-silencing partnership and Novartis AG and Ionis Pharmaceuticals Inc.'s cardiovascular antisense pact, "and it's bringing a lot of excitement to the field." (Also see "Deal Watch: Novartis Opts In On Lipoprotein A Candidate From Akcea" - Scrip, 25 Feb, 2019.)
He went on, "We think like the statins where the number six statin, AstraZeneca PLC's Crestor (rosuvastatin), was the big winner, that there is plenty of space for multiple LP(a) lowering medicines and everyone agrees that gene silencing is the way to do it because you can lower the protein in the serum by 90%, we've already shown that in monkey data.
"If you can do that in humans, we believe that will lower risk and cardiovascular deaths still account for 40% of deaths globally. Statins are great, but they alone are not the solution so we need more tools in the toolbox."
Following the first approval last year for an RNAi therapeutic, Onpattro (patisiran) from Alnylam Pharmaceuticals Inc. (with whom Silence settled a patent dispute at the end of last year), Solomon told Scrip that "gene silencing is the hot topic" and other companies, notably Arrowhead and another RNAi specialist Dicerna Pharmaceuticals Inc. "are soaring." He pointed out that in November 2017, Silence, Arrowhead and Dicerna all had the same market capitalization but "they got a quicker start in the clinic." (Also see "Alnylam Offering Value-Based Deals In EU For Breakthrough RNAi Drug Onpattro" - Scrip, 14 Nov, 2018.)
With the Mallinckrodt pact, SLN124 going into the clinic and the promise of SLN360, "we feel like we're in the midst of it now and I think investors acknowledge that." Shares soared 60% on the back of the news to 133.6 pence when the deal was announced (18 July) and continued to rise the day after.
Solomon signed off the Mallinckrodt deal a year to the day of his appointment as CEO and much has changed in that time, notably with the hiring in April of Giles Campion as head of R&D and chief medical officer – he occupied the same roles at Prosensa Holding BV, which was acquired by BioMarin Pharmaceutical Inc. in 2015 for $680m.
April also saw the return of industry veteran Iain Ross as chairman, having held the post from 2005 to 2010, while Solomon is hardly short of experience either, having been CEO of Denmark's Zealand Pharma AS from 2008 to 2015. He said that "the name of the game is stability and now we want to get beyond the idea that Silence has been silent. We have the foundation to build a very fine house. As you know, you get accretion in this business in two ways, through deals and results. We'll press on with deals first, and then we'll press on with results in the clinic."
Mallinckrodt's Acthar Fails For ALS
As for Mallinckrodt, the Silence collaboration was welcome news following the announcement earlier this week that it is permanently discontinuing a Phase IIb study of Acthar (corticotropin) gel for amyotrophic lateral sclerosis (ALS).
The company made the decision after a recommendation by the study's independent data and safety monitoring board following higher rates of pneumonia observed in ALS patients receiving Acthar Gel compared with those on placebo "and other adverse events specific to this patient population."
CSO Romano said, "It is critical to stress, however, that these findings do not impact the current positive benefit/risk profile of Acthar for use in current on-label indications," of which there are 19 approved by the FDA. These include infantile spasms and the treatment of acute exacerbations of multiple sclerosis in adults.