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Madrigal sees a stock sell-off; ex-Novartis exec heads to Daiichi

Today, a brief rundown of news from Madrigal Pharmaceuticals and Daiichi Sankyo, as well as updates from Johnson & Johnson, AC Immune and Novartis that you may have missed. Shares of Madrigal Pharmaceuticals fell by double digits on Thursday despite quarterly

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This guide cannot diagnose a condition or recommend a personal treatment plan. Discuss medical questions with a qualified professional.

Today, a brief rundown of news from Madrigal Pharmaceuticals and Daiichi Sankyo, as well as updates from Johnson & Johnson, AC Immune and Novartis that you may have missed. Shares of Madrigal Pharmaceuticals fell by double digits on Thursday despite quarterly numbers for its liver disease drug Rezdiffra that again surpassed consensus estimates. Rezdiffra fourth-quarter sales of $321 million topped those projections by $10 million and there was “nothing to nitpick” in the company’s results, as “all metrics ... were positive,” wrote Cantor Fitzgerald Prakhar Agrawal. Still, a “whisper” of higher expectations among buyside investors and a “higher-than-expected” projected decline in sales next quarter may have triggered the stock sell-off, added Evercore ISI analyst Michael DiFiore in a separate note. Despite the pullback, DiFiore wrote that his team remains positive on the drug’s “fundamental trajectory.” Madrigal shares, which have soared during Rezdiffra’s launch, have lost about a quarter of their value so far this year. Former Novartis executive John Tsai has been named the new global head of research and development at Japanese pharmaceutical giant and antibody-drug conjugate specialist Daiichi Sankyo . Tsai was Novartis’ chief medical officer for four years until he departed in May 2022 amid an organizational reshuffling. He then served as an executive partner at venture firm Syncona Capital Management . At Daiichi Sankyo, Tsai will replace Ken Takeshita , who’s been running the company’s drug research since 2021. The change will become official on April 1. Johnson & Johnson will invest more than $1 billion in a new cell therapy manufacturing facility in Montgomery County, Pennsylvania. The planned facility announced Wednesday is part of a broader commitment by the company to pour $55 billion into U.S. production through early 2029 — one of many pledges drugmakers have made to avoid Trump administration tariffs. J&J said the plant will be staffed with more than 500 workers. J&J has also temporarily paused enrollment in a mid-stage trial testing an Alzheimer’s vaccine it’s co-developing with AC Immune . In a regulatory filing Thursday, AC Immune said that enrollment was stopped while J&J evaluates “certain aspects of the trial,” which is testing the shot in pre-symptomatic Alzheimer’s. AC Immune added that the trial has already met an early goal and that the stoppage wasn’t triggered by any new safety findings. Jefferies analyst Lucy Codrington speculated that the decision was related to “recruitment challenges” and also noted that AC Immune’s “key assets,” among them a different type of Alzheimer’s shot, remain on track. Novartis will work with biotech startup Unnatural Products to develop a macrocyclic peptide drug, the companies said Wednesday . Macrocyclic peptides are popular among drug startups and designed to merge into a single medicine the strengths of small molecules and biologics. Unnatural is designing these therapies in an effort to get after historically “undruggable” targets. The companies didn’t specify which target the program in the deal is aimed at, but said Unnatural will receive $100 million in upfront cash from Novartis and is eligible for another $1.7 billion if the drug progresses.

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01What the Artificial Neuron Cannot Do

Hersam’s next goal is a small circuit — perhaps 10 artificial neurons — where each one fires differently, and together they accomplish what would require thousands of conventional transistors. “ Silicon achieves complexity by having billions of identical devices,” Hersam said. “The brain is the opposite. It’s heterogeneous. The complexity is at the device level.” But Gaudet sees a gap no circuit design can yet fill: Biological neurons grow new connections and prune old ones, strengthening pathways that are used and weakening those that aren’t. Hersam’s lab’s printed neurons — or any other neuromorphic technology that mimics neuronal dynamics — can’t achieve that level of complexity yet. Brown is careful about the distance remaining between these printed neurons and the real thing. “Neurons are just so flexible,” he said. “They can totally change what they’re doing based on whether they’ve learned something and based on your emotional state. There’s a lot of hidden mysteries.” Sangwan suspects the device has more to reveal. “It’s a nonlinear dynamical system,” he said. “We don’t fully know how many different variables you need to explain it. It’s just the beginning.” Hersam, Sangwan, Brown, Holla, and Gaudet reported having no relevant financial disclosures. Disclosure information for study authors is available in the original study publication.

Source: www.medscape.com ↗
02China: Threat or opportunity?

One of the biggest biotech news stories of recent years is China’s continued rise as a biotech and life sciences powerhouse. China conducts a quarter of all clinical trials and drug development and has almost 1,500 new drugs in development.¹ Many China-based biotechs have benefitted from government funds, out-licencing deals with large pharmas and venture capital funding. However, policymakers in the US and EU have concerns about the possible threat to their region’s biosecurity and competitiveness as centres for health and life science research. Given China’s increased importance, ICON Biotech conducted the same biotech sector survey with 100 China-based biotech leaders. The results show that Chinese biotechs face many of the same challenges as biotechs located elsewhere. They share the same funding challenges and burdens associated with increasingly complex clinical trials and regulations.

Source: www.biopharmadive.com ↗
03What Comes Next

With data expected in the fourth quarter of 2026, we are prioritizing histology alongside patient-reported outcomes using the Celiac Disease Symptom Diary, one of only two instruments developed in line with U.S. Food and Drug Administration (FDA) guidance, to capture changes in symptoms such as abdominal pain and nausea. Ultimately, the broader aim is to give gastroenterologists and patients a therapeutic option for a disease that has long been managed without one. The future of drug development will not be defined by statistical significance alone, but by whether new therapies also improve the daily burden of living with celiac disease. “The first therapy to cross the line could change the field,” Geller concluded. “It would help establish celiac as a serious medical condition with options beyond a restrictive diet and open the door for what comes next.” Dr. Paul Lizzul is chief medical officer at First Tracks Biotherapeutics, a clinical ‑ stage biotechnology company advancing antibody therapeutics that modulate immune pathways implicated in autoimmune and inflammatory diseases. Marilyn Geller serves as an advisor to First Tracks Bio. Footnotes Abadie V, Jabri B. IL-15: a central regulator of celiac disease immunopathology. Immunol Rev . 2014;260(1):221-234. https://doi.org/10.1111/imr.12191. Yokoyama S, Watanabe N, Sato N, et al. Antibody-mediated blockade of IL-15 reverses the autoimmune intestinal damage in transgenic mice that overexpress IL-15 in enterocytes. Proc Natl Acad Sci U S A . 2009;106(37):15849-15854. https://doi/full/10.1073/pnas.0908834106. Anthony S, Schluns KS. Emerging roles for IL-15 in the activation and function of T-cells during immune stimulation. Research and Reports in Biology . 2015;6:25-37. https://doi.org/10.2147/RRB.S57685.

Source: www.biopharmadive.com ↗
04Lifestyle Matters: How do environmental and lifestyle factors influence Alzheimer’s disease?

Dr. Harrison and Finnish neuroscientist Dr. Miia Kivipelto explore the complex interplay between genetics and lifestyle in Alzheimer's development. Learn how the groundbreaking FINGER study demonstrates potential prevention strategies, and discover the latest evidence on how environmental factors, diet, and chronic conditions influence Alzheimer's risk.

Source: www.biopharmadive.com ↗
05Why Muscle Cells Might Do Some Heavy Lifting

Brown was studying gene therapy in the 1990s when he designed a technology to turn mRNA expression on or off in different cells. For the new mouse study, published in Nature Biotechnology , he adapted the technology to turn off mRNA expression in dendritic cells, muscle cells, or liver cells. The researchers then vaccinated the mice with each version, delivering the vaccines both intravenously and intramuscularly. “The results were pretty stunning,” Brown said. When mRNA expression was turned off in muscle cells, T-cell response went down, suggesting muscle cells play a role in immunity. When expression was turned off in liver cells, T-cell expression tripled — indicating liver cells dampen immunity. Turning off expression in dendritic cells had no effect on T-cell activation, though it did reduce the number of killer T cells by as much as half. (Interestingly, no such reduction occurred when the antigen was SARS-CoV-2 spike. Brown is now investigating why different antigens had varying effects.) Knowing all this is crucial for designing effective mRNA vaccines and therapies. That’s because different mRNA therapies require different strategies. Cancer vaccines must boost tumor-fighting killer (CD8+) T cells. For genetic disease treatments, scientists want to avoid triggering the immune system to prevent killing the very cells the mRNA is meant to modify. “Understanding the immunology is extremely important for this class of drug,” Brown said. The finding doesn’t mean dendritic cells aren’t important for mRNA vaccines to work. “It just means that the mRNA doesn’t have to get into those cells to induce an immune response,” Brown said. Instead, the antigen can be transferred to those dendritic cells.

Source: www.medscape.com ↗
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Peptide Therapy Guide Editorial Team

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