Patisiran sodium

Shares in Intellia Therapeutics were down 27% on Thursday after reporting a serious, but symptom-free liver side effect tied to its experimental gene-editing therapy for transthyretin (TTR) amyloidosis with cardiomyopathy (ATTR-CM).Despite the safety signal, Cantor Fitzgerald's Rick Bienkowski said "we don't think it's quite time to panic yet, and see the sharp move as an overreaction."Nexiguran ziclumeran (nex-z), formerly known as NTLA-2001, is an in vivo CRISPR-based therapy designed to inactivate the TTR gene that encodes for the mutated TTR protein. The Phase III MAGNITUDE study is testing nex-z as a potential one-time treatment for ATTR amyloidosis. Intellia has so far enrolled about 365 patients, out of a total expected 765 participants, with over 200 having received the therapy.Enzyme levels improvingIn a US securities filing Wednesday, the biotech revealed that a single patient in the trial recently experienced asymptomatic Grade 4 liver transaminase elevations in lab tests. The liver enzyme levels "appear to be resolving without hospitalisation or medical intervention and have fallen to Grade 3 ALT and Grade 2 AST elevations," the company said, adding "we continue to monitor these events as the MAGNITUDE study progresses."The company noted that adverse events to date have been similar to those seen in earlier-stage testing, including infusion-related reactions and asymptomatic liver enzyme increases.Intellia reported two-year follow-up results a few weeks ago from a Phase I study in patients with hereditary ATTR amyloidosis with polyneuropathy, showing sustained 90% reductions in serum TTR, as well as clinical improvements in 14 of 18 patients, including five who had previously progressed on Alnylam's Onpattro (patisiran).Meanwhile, Intellia continues enrollment in its separate Phase III MAGNITUDE-2 trial for the disease's polyneuropathy form where the first patient was dosed last month. It expects to complete MAGNITUDE-2 to support a potential filing by 2028 and possible US launch the year after that.The company is also progressing the Phase III HAELO of its other CRISPR candidate, NTLA-2002, in hereditary angioedema. A regulatory filing is expected in the second half of 2026, potentially paving the way for a 2027 launch.The company recently narrowed its focus on both the nex-z and NTLA-2002 programmes, after announcing earlier this year that it would be axing 27% of its staff over the course of 2025.

A deal with CRISPR Therapeutics comes several weeks after Sirius Tx raised $50 million in a series B2 round. \n CRISPR Therapeutics is paying $25 million upfront to work on multiple siRNA targets with Sirius Tx with an early focus on the next-gen thrombotic disease asset SRSD107.That drug, Sirius’ lead program, works as a long-acting, next-generation anticoagulant for thromboembolic disorders which, after passing early phase 1 tests, is gearing up for midstage trials.The deal involves a $25 million upfront fee as well as an extra $70 million in equity from CRISPR to Sirius and allows the pair to work together on SRSD107 under a 50-50 cost and profit-sharing structure. CRISPR will lead sales work in the U.S. while Sirius will be responsible for commercialization in greater China.CRISPR can also pick up to two other siRNA targets for research work and, for each target, the biotech “will fund research and retain opt-in rights to lead clinical development and commercialization,” it said in a May 19 release, though it did not give any further details on targets.Sirius, meanwhile, is in line for future milestone payments as well as tiered royalties on drugs that make it to market.SRSD107 is a long-acting siRNA designed to selectively inhibit Factor XI (FXI), a key driver of pathological thrombosis with “minimal impact on normal hemostasis,” according to Sirius. Small interfering RNA is a type of RNA molecule that plays a crucial role in gene regulation with the promise of silencing disease-related genes.Alnylam has been leading the charge in siRNA research with six FDA approvals across a range of disorders using the tech. This began in 2018 with the first-ever green light for an siRNA therapy in the form of Onpattro for polyneuropathy of hATTR amyloidosis.This new deal dovetails with CRISPR’s work on its phase 1 asset CTX310, created out of its in vivo gene editing platform. The therapy is going after ANGPTL3, a gene that encodes for a key protein involved in the regulation of low-density lipoprotein and triglyceride levels, both known risk factors for atherosclerotic heart disease.“We are excited to partner with Sirius, and broaden our cardiovascular medicine portfolio, on the heels of promising top-line data that we recently shared for CTX310, which targets ANGPTL3,” said Samarth Kulkarni, Ph.D., chair and CEO of CRISPR, in a statement.“SRSD107, which targets Factor XI, has the potential to be a best-in-class therapy, offering infrequent dosing and improved patient outcomes,” Kulkarni added. “Sirius’ siRNA platform complements our existing capabilities and expands our therapeutic toolkit, enabling us to develop a broader range of transformative gene-based medicines.”Analysts at Jefferies said in a note to clients that “the deal makes sense as it expands [CRISPR’s] toolkit capabilities beyond gene editing core, aiming for both reversible and permanent approaches to disease.”The firm adds that the deal “adds versatility” to the biotech’s pipeline, and a potentially large list of targets.This includes atrial fibrillation; venous thromboembolism (VTE); cancer-associated thrombosis; chronic coronary artery disease; chronic Peripheral Vascular Disease; ESRD requiring hemodialysis; and for patients with undergoing major orthopedic surgery.  It’s been a good month for Sino-American biotech Sirius, coming several weeks after the company raised $50 million in a series B2, bringing its total investment to $150 million.The biotech, founded in 2021, has three clinical-stage programs, which include SRSD107, as well as a preclinical pipeline.