partimefriend

Is this a compound-specific or a class effect of the therapy?” he wondered. In the SHASTA-2 study of patients with severe hypertriglyceridemia, plozasiran (Arrowhead Pharmaceuticals), a small interfering RNA designed to reduce APOC3 in the liver, did not result in a significant increase in hepatic fat, he noted

@ArtsStocks @RNAiAnalyst For Rosenson, the findings raise some questions, particularly around the long-term consequences of an increase in hepatic fat fraction.

Relevant to the $arwr ARO-DIMER-PA (combined ApoC3+PCSK9 RNAi triggers) project. Just a short 12month imaging study though. Also, unlike olezarsen which did not change LDLc in moderately elevated trig subjects, plozasiran lowered it by -20%. $ions

@ArtsStocks @RNAiAnalyst Also from the above article. The long-term implications of an increase in HbA1c with olezarsen aren’t known either, Rosenson said, although he added that this trend has been reported in most trials that lower triglycerides.

Unlike the tweet’s focus on plozasiran glycemic TEAEs (mostly in patients with baseline metabolic issues; overall HbA1c stable), olezarsen has a confirmed dose-dependent hepatic fat increase in CORE/CORE2 Phase 3: +2.28% (50 mg) & +4.18% (80 mg) vs +0.14% placebo on MRI-PDFF, with 27–40% of patients seeing ≥5-point rises (enough to cross steatosis threshold). This unresolved long-term signal isn’t seen with plozasiran (hepatic neutrality in available data). Both lower TG/pancreatitis risk well, but for lifelong use the cleaner hepatic profile matters. Context on both sides.

@RNAiAnalyst Unlike $ions Olezarsen: “Common Plozasirin -emergent adverse events included diabetes” $arwr

@auditor112017 @BioBoyScout Cost isn’t just synthesis — it’s total therapy burden. At 100k patients/year: Olezarsen: 96 kg API, 1.2M injections Plozasiran: 10 kg API, 400k injections ~9.6x more drug mass + 3x more delivery units for the ASO.

@BioBoyScout There is a cost advantage of producing ASOs over siRNA. Likely, both companies have taken that into consideration. $ions $arwr

New white paper out: Redemplo vs. Tryngolza - Why the price war doesn’t change the outcome. This is shaping up to be a functioning duopoly in a massive market. Both validate ApoC-III, and both can win at scale. drive.google.com/file/d/1Cuj64r… $ARWR $IONS #RNAi

$Arwr $wve this is the next catalyst! Inhbe Data coming from $Wve soon!

$Wve RENAISSANCE IN OBESITY TREATMENT INNOVATION Speakers: ▪Paul Bolno, MD, MBA, CEO, Wave Life Sciences ▪Angela Fitch, MD, FACP, Chief Medical Officer, Knownwell ▪Joe Nadglowski, President and CEO, Obesity Action Coalition schedule.sxsw.com/events/PP11628…

$ARWR data 🔥: Combo + tirzepatide: ~2x wt loss (-9.4% vs -4.8%), ~3x fat reduction (-23% visceral, -77% liver). Mono: -9.9% visceral fat +3.6% lean mass 💪 1st human adipose knockdown (-88% mRNA). Huge combo upside 🚀

$ARWR to GLP-1s: “Nice weight loss bro… but watch this.” → -9.4% combo vs -4.8% tirzepatide alone. Also triples visceral fat burn. In diabetics. Early days but… damn. 😤

Join @ArrowheadPharma $ARWR for a virtual KOL event on Jan. 6 at 11:30am ET with Dr. le Roux to discuss interim results of the Phase 1/2a studies evaluating ARO-INHBE and ARO-ALK7 in adults with obesity, with and without diabetes mellitus. Register: bit.ly/45oDDf3

$ARWR

$ARWR Not just a simple PR, it's KOL webinar!

$NVS Fiona Marshall PBR"We see Arrowhead’s TRiM™ technology as having great potential to achieve the type of widespread and effective delivery in key brain structures that will be necessary to see the full benefit of RNA medicines in neurodegeneration.” $ARWR

$Arwr Key Q from analysts: How is your anti-tau drug different from J&J’s failed antibody? J&J’s mAb is IV, barely reaches the brain, and only clears extracellular tau. We deliver siRNA straight into neurons → silence tau gene at the source, prevent tangles from ever forming

$ARWR INHBE and ALK7 updates $WVE “We also continue to make good progress on our first 2 obesity programs, ARO-INHBE and ARO-ALK7. Together, we have randomized 192 patients, all with a BMI greater than 30” “As ARO-inhibin E started about 2 quarters earlier, we have more mature data in that study. The study is nearly fully enrolled, and we are on schedule and currently planning to share initial data from this program around the first week of 2026. This is a rather robust first-in-man study that's collecting multiple measures of drug activity and pathway activity, and we are eager to share initial findings.”

@MarketTrendAdv That RNAI sentiment has been echoed for 10+ years. The wild card was early expectations. Buying $ARWR now remains a very strong bet. $ALNY is a very apt growth comparison re RNA Interference future projections . ~POC creates a radically different 🐂 market dynamic for Arrowhead.

$ARWR 🎵 I thought you should know, I really like this pipeline down in Arrowhead City, and all those prayers you thought you wasted on $ARWR must’ve finally made their way on through. Plozasiran’s savin’ hearts, strong like you, come November 18! ❤️

Boom! $ARWR files CTA for ARO-DIMER-PA: First dual RNAi nuking PCSK9 & APOC3 to tank LDL-C/TGs in hyperlipidemia pts. #RNAi ir.arrowheadpharma.com/news-releases/…

@auditor112017 @ArtsStocks @FrankHulskof @pikva63 @RNAiAnalyst It looks like I was confidently lied to by AI , I have removed the tweets.

@Partimefriend @ArtsStocks @FrankHulskof @pikva63 @RNAiAnalyst Looks like WO 2012/149495 belongs to $ions!

$ARWR vs $IONS: thoughts on patent dispute. 1st: unlikely to be relevant since main claim refers to treating LPL deficiency...in ANIMALS. Unless you interpret humans=animals, since all other claims are dependent claims...forget about it. Overall, remarkable that such broad drug target (method) claim issued. Targets per se are not patentable, but in this case, it came as a big surprise when Ionis found in clinical trials that LPL deficient PATIENTS responded to ApoC3 knockdown. I give them full credit for that. Main risk to Arrowhead is that since discovery was based on clinical observation, later claims get issued that cover LPL patients (considerable part of FCS market). Having said that, Ionis litigation, trying to prevent a better ApoC3 drug to reach market, will not go down well with patient and physician community. In a way, great advertisement for plozasiran.