Mallinckrodt, Silence collab to go quiet, but a phase 2 cardiovascular win speaks loudly for the biotech

Silence Therapeutics used its full-year earnings results this morning to unveil a phase 2 win—but also the loss of one of its partnerships.

Mallinckrodt notified the British biotech earlier this month that it doesn’t plan to continue developing the siRNA drug SLN501 once an ongoing phase 1 trial has been completed, according to Silence. With Silence having already taken back the other two candidates covered by the collaboration, the partnership will be coming to an end.

The deal was originally worth $20 million upfront with $2 billion on the line for Silence for all three programs aimed at siRNA drug targets that would silence the complement cascade in complement-mediated disorders. For the SLN500 program, which produced SLN501, Silence was in line to receive $10 million in research milestones for each candidate advanced plus a further $663 million in clinical, regulatory and commercial milestones.

Silence received a $2 million payment from Mallinckrodt in April 2021 when preclinical development work for the SLN500 program advanced. A year later, Silence reported a $3 million milestone payment when a clinical trial application was filed for SLN501.

London-based Silence has other partners to keep it busy. AstraZeneca handed over a $10 million milestone payment last month when the first candidate from their collaboration entered the clinic. The two companies signed a multi-target pact in 2020 focused on using Silence’s mRNAi GOLD platform to develop siRNA therapeutics for cardiovascular, renal, metabolic and respiratory diseases.

That $10 million contributes to the more than $200 million that Silence now has on hand. The majority of this funding pile came from a private placement of American depository shares that brought in gross proceeds of around $120 million last month.

“We are excited to have multiple programs advancing in the clinic, supported by a substantial cash position that extends our estimated runway into 2026,” Chief Financial Officer Rhonda Hellums said in the earnings release. “We also continue to evaluate partnering opportunities that could provide additional non-dilutive funding and further extend our cash runway.”

Silence’s solely owned pipeline also gave the company cause to celebrate today. Zerlasiran was shown to induce a “highly significant” reduction in lipoprotein(a) at 36 weeks, hitting the phase 2 trial’s primary endpoint.

The siRNA drug is designed to lower the body’s production of the lipoprotein, a key genetic risk factor for cardiovascular disease. A 300-mg dose of zerlasiran was administered subcutaneously every 16 or 24 weeks, or 450 mgs every 24 weeks, to patients with a median baseline Lp(a) of approximately 215 nmol/L. Median percentage reduction in Lp(a) of 90% or greater was observed for both doses at Week 36, according to Silence, with no new safety concerns identified.

The trial is due to run for 60 weeks during which time the change of Lp(a) will continue to be observed as will other secondary endpoints related to the potential effects on other lipids and lipoproteins. Top-line 48-week data are due to read out in the second quarter.

“We are excited about the emerging phase 2 data, which are very consistent with phase 1 results and support a competitive profile for treating patients with high Lp(a),” Silence’s head of R&D Steven Romano, M.D., said in an accompanying release.