Remibrutinib

California-based Santa Ana Bio has dosed the first cohort in a first-in-human trial of SAB01, a bispecific antibody designed to deplete mast cells selectively by co-engaging KIT and Siglec-6. The molecule's design addresses the following: existing KIT-targeted antibodies produce rapid responses in conditions such as chronic urticaria but also hit hematopoietic stem cells and melanocytes, generating off-target toxicity. Because KIT and Siglec-6 are co-expressed on mast cells but not found together on any other cell type, SAB01's avidity-driven dual engagement is intended to restrict activity to mast cells while sparing other KIT-expressing populations. The Phase I study (NCT07815561) is a randomized, double-blind, placebo-controlled, single ascending dose trial enrolling up to 88 healthy adults, randomized 6:2 to SAB01 or placebo. Primary objectives are safety, pharmacokinetics (PK), and pharmacodynamics (PD). No efficacy or outcome data are available at this stage; additional cohorts may be added based on emerging safety and PK/PD findings. Sanofi's Dupixent (dupilumab), an IL-4/IL-13 receptor blocker, received FDA approval for chronic spontaneous urticaria (CSU) in adults and adolescents in April 2025 and was subsequently extended to children aged 2 to 11. Novartis's Rhapsido (remibrutinib), a BTK inhibitor, was approved for antihistamine-refractory CSU in adults in September 2025 as the first oral targeted therapy in that setting. Separately, barzolvolimab, a monospecific anti-KIT antibody in development at Celldex Therapeutics, has shown on-target effects in other KIT-expressing tissues, including hair-color changes and neutropenia. Santa Ana said the Phase I initiation marks its first entry into the clinic. The company's broader pipeline includes SAB05, a CD40-targeted glucocorticoid antibody-drug conjugate advancing through investigational new drug-enabling studies, with a clinic entry targeted for 2027. Safety, PK, and PD data from the SAB01 single ascending dose study will inform decisions on whether and how to enroll any further cohorts. Spot something wrong? Report an issue with this article

iStock, lerbank Back-to-back failures of multiple late-phase trials have raised questions about how Novartis has deployed capital in pursuit of drugs to drive growth through the 2030s. Novartis went into September looking forward to three readouts that analysts had identified as central to its mid- to long-term growth prospects. Days later, the Swiss drugmaker was reeling from the failures of two of the pivotal trials, offsetting success in the other study and adding to pressures created by a recent decision to suspend CAR T efforts in response to three patient deaths. Guggenheim Securities analysts set out what was at stake for Novartis ahead of the run of readouts. In an Aug. 17 note to investors, the analysts called readouts on pelacarsen, remibrutinib and del-desiran major clinical catalysts that “will be important for gaining confidence in Novartis’ mid- and long-term sales potential.” The run of key readouts started well, with Novartis reporting that its BTK inhibitor remibrutini—approved last September as Rhapsido for chronic spontaneous urticaria—lowered annualized relapse rates in a pair of Phase 3 multiple sclerosis trials. However, within days of the success, Novartis revealed that its antisense therapy pelacarsen showed no significant benefit on cardiovascular risk and that the antibody-oligonucleotide conjugate del-desiran flunked a muscle-wasting disease study. Cardiovascular disease Novartis’ cholesterol-lowering medicine fails Phase 3, clouding Lp(a) horizons The failure of Novartis’ pelacarsen to translate its Lp(a)-lowering effects to clinical benefits “marks a meaningful setback” for other companies taking a similar approach to cardiovascular risk, analysts say—including Eli Lilly and Amgen. September 8, 2026 · 2 min read · Tristan Manalac Read more Novartis acquired del-desiran last year in the $12 billion buyout of Avidity Biosciences. The risk that Novartis will fail to realize a return on the buyout has intensified investor scrutiny of leadership’s M&A strategy. Successive Novartis chairs have failed on acquisitions, and the company must change how it oversees deals, David Samra, managing director at Artisan Partners, told Reuters . Artisan is a major shareholder in Novartis. CEO Vasant Narasimhan has done a “very good job” running Novartis, Samra said, but the board has failed to properly scrutinize deals. Samra named Novartis’ $2.9 billion takeover of MorphoSys in 2024 as another poor deal. Between acquiring a controlling stake in MorphoSys in May and closing the deal in October, Novartis recorded an $800 million impairment related to an assessment of the biotech’s data. Novartis’ patent cliff The M&A misfires and recent back-to-back Phase 3 flops may have long-term consequences. In a July 21 note, Guggenheim analysts called the pelacarsen, remibrutinib and del-desiran readouts “critical” to Novartis’ post-2030 growth. The focus on the post-2030 period reflects the need to replace products that could power sales through the rest of this decade before stuttering in the face of off-patent rivals. U.S. patents on Cosentyx, Kisqali and Kesimpta are scheduled to expire from 2029 to 2031. The products were Novartis’ three best-selling drugs in the first half of 2026, accounting for almost 38% of total sales. Novartis’ fourth best-selling product, Entresto, has already lost exclusivity. Entresto sales halved in the second quarter, but the drug still generated $1.2 billion over that three-month period. Recent setbacks raise questions about Novartis’ preparations for the 2029 to 2031 patent expirations. The current leadership team has a track record of successfully navigating such challenges, with Novartis’ sales rising this year amid a loss-of-exclusivity period that CFO Mukul Mehta recently called the largest the company has ever faced. Appointed CEO in 2018, Narasimhan equipped Novartis to grow through the expirations now eroding sales through moves like the $2.1 billion takeover of Endocyte, which developed Pluvicto. Sales of the radiopharmaceutical rose 57% to $1.3 billion in the first half of the year, making it Novartis’ fifth best-selling drug. Pluvicto is the only drug in the top five with a patent loss after 2031. Recent developments raise doubts about whether Novartis’ deals for the next set of potential growth drivers will be as successful. Novartis’ agreement to license pelacarsen from Ionis predated Narasimhan’s appointment as CEO, although the drug candidate moved into a Phase 3 cardiovascular outcomes study on the executive’s watch. Pelacarsen’s chances of helping Novartis grow through the 2030s appear to have shrunk to zero. Analysts at BMO Capital Markets, Guggenheim and TD Cowen removed the drug candidate from their models for Novartis and partner Ionis in response to the Phase 3 flop. Novartis’ investor relations team “does not foresee future development” of pelacarsen, Guggenheim analysts said in a Sept. 9 note to investors. Justifying Avidity Novartis “plans to continue exploring del-desiran and potentially conduct further studies to support a path to market,” the Guggenheim analysts said. Even so, the failure of the Phase 3 HARBOR trial led the Guggenheim team to cut risk-adjusted 2033 sales estimate for del-desiran in myotonic dystrophy type 1 from $1.76 billion to $960 million, using a 60% probability of success. Guggenheim analysts said in their Aug. 17 note that “success for del-desiran in HARBOR is crucial for validating the Avidity deal.” Novartis’ investor relations team took a different view, telling the analysts that either del-desiran or del-brax, another antibody-oligonucleotide conjugate from Avidity, could justify the acquisition. Earnings Novartis stays ‘geography-agnostic’ in dealmaking amid flurry of China deals Novartis will continue to be on the lookout for bolt-on deals below $2 billion, CEO Vas Narasimhan said Tuesday on the pharma’s second quarter earnings call—though major pickups aren’t completely off the table. July 21, 2026 · 2 min read · Tristan Manalac Read more Analysts see del-brax, a potential treatment for facioscapulohumeral muscular dystrophy, having lower peak sales than del-desiran. The analyst estimates Novartis presented at the time of the Avidity deal showed peak sales forecasts of up to $6 billion for del-desiran and $4 billion for del-brax. After the del-desiran flop, Guggenheim analysts cut their 2033 risk-adjusted sales estimate for del-brax from $1.76 billion to $600 million, using a 50% probability of success. Novartis reported Phase 1/2 data on the candidate in June. While Novartis’ base case is that the drug will be ready for an approval filing in 2028, the company plans to talk to the FDA about an earlier submission based on biomarker data, Narasimhan said in July. Novartis acquired a third drug candidate, the Duchenne muscular dystrophy prospect del-zota, in the Avidity buyout, but the asset is unlikely to justify the takeover alone. Guggenheim analysts forecast risk-adjusted del-zota sales of $430 million in 2033 at a 95% probability of success.