Danuglipron

Welcome back to Endpoints Weekly, and welcome to November. This week kicked off with quarterly earnings results from a handful of companies, including Eli Lilly, Merck, Novartis and Bristol Myers Squibb. Then on Thursday, Novo Nordisk made waves when it announced that it submitted an unsolicited bid for the obesity biotech Metsera, a month after Pfizer disclosed its plans to acquire it. The Endpoints team is following the saga closely, so stay tuned for more details. Novartis also made headlines this week for its $12 billion offer to buy out a neuromuscular drug developer. And Ryan Cross has an exclusive on a low-profile biotech targeting one of the immune system’s natural defenses to potentially treat autoimmune disease. We’ll have reporters covering earnings results next week from Pfizer, Novo Nordisk, Moderna and more. Until then, have a great weekend!  — Nicole DeFeudis 🤼 Novo Nordisk shocked the industry this week by announcing it made an unsolicited bid for obesity biotech Metsera for $6.5 billion upfront. Pfizer, which had announced its intent to buy out Metsera last month for $4.9 billion upfront, almost immediately came out swinging, saying Novo’s bid was “in violation” of antitrust law. This is going to be one of those stories where things can change quickly — evidenced by Pfizer suing Metsera and Novo late Friday — and we’ll have you covered from every angle. From Novo’s side, the bid comes ahead of new CEO Maziar Mike Doustdar’s first earnings call next week. The Danish drugmaker has been in the midst of “turning the [bleeping] tanker,” as Logan Roy from HBO’s “Succession” would say. As Elizabeth Cairns and Kyle LaHucik wrote earlier this week , Novo has faced significant pressure from GLP-1 competitor Eli Lilly, laying off thousands of staffers and cutting back on pipeline projects. But with this week’s Metsera offer, Doustdar appears to be chasing the deals his predecessors wouldn’t , Liz writes. For Pfizer, analysts say CEO Albert Bourla could be leveraging his relationship with President Donald Trump, with a company statement emphasizing the anticompetitive nature of the bid by letting Novo Nordisk take over “an emerging American challenger.” The stakes for Pfizer are high, as it dropped an oral GLP-1 called danuglipron when it caused intolerable liver side effects in one patient earlier this year. The back-and-forth will also pose a test to Trump’s FTC , Jared Whitlock writes. Metsera, meanwhile, appears content to let Novo and Pfizer duke it out to try to drive up the price. The biotech also put out a statement this week that said it views Novo’s offer as a “superior proposal,” which would legally give Pfizer until Nov. 4 to submit a counterbid. But Pfizer noted in its own statement that the Novo offer is “illusory and cannot qualify as a superior proposal” and subsequently sued to enforce the transaction. What’s next in this unfolding saga? Kyle LaHucik takes a look at six burning questions going forward, while Elizabeth Cairns asks what Metsera might bring to Novo . We also broke down the news on an emergency session of Post-Hoc Live , where Kyle and Drew Armstrong chatted with analyst Evan Seigerman. Pfizer is expected to report its third-quarter earnings on Nov. 4. 💰 Novartis has offered about $12 billion to acquire Avidity Biosciences, a neuromuscular drugmaker that’s months away from submitting its lead candidate to the FDA. It’s the second-largest deal announcement of the year. But Novartis CEO Vas Narasimhan said during the company’s third-quarter earnings call on Thursday that the deal could have been “twice as big” if they had waited for a Phase 3 readout, which is expected to come next year. “In our view, the phase-appropriate risk was reasonable given the data that we’ve seen,” Narasimhan said. Novartis is getting three candidates in late-stage testing for Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy (FSHD), and myotonic dystrophy type 1 (DM1). Meanwhile, Avidity plans to spin out its early-stage R&D work in precision cardiology into a separate company that will maintain partnerships with Bristol Myers Squibb and Eli Lilly. The spinout will be led by Avidity’s current chief program officer Kathleen Gallagher. The new company will be publicly traded and get $270 million in cash to support its pipeline. 📊 Biopharma companies are diving headfirst into earnings season, with several big names reporting third-quarter results this week. Here are some of the highlights: 🧬 A new startup called Neutrolis is taking a look at how one of the strangest ways the immune system defends our bodies from invaders can be leveraged to create new drugs. Ryan Cross took an in-depth look at this process that involves neutrophil extracellular traps, or NETs, as Neutrolis has put together more than $50 million in seed and Series A financing. Along with the funding, Neutrolis put out data this week from a Phase 1 study, showing the drug can quickly chop up NETs and potentially help those with autoimmune disorders get a “reset.” Most promising was the data from one patient. Within six hours of infusing him with the treatment, more than 80% of the rashes that covered him from head to toe were cleared, arthritis in multiple joints was resolved, and inflammation in his eyes was reduced. ✅ BridgeBio touted multiple late-stage wins this week, including in a rare disease called limb-girdle muscular dystrophy type 2I/R9. At the study’s interim analysis, BridgeBio’s drug BBP-418 showed a positive result on a specific protein that was originally expected to be used as a surrogate endpoint to seek accelerated approval. But because BBP-418 also hit statistical significance on multiple endpoints, BridgeBio will now ask the FDA whether there is a path to full approval. In another study, BridgeBio’s oral drug encaleret hit the primary endpoint for a genetic thyroid disorder called autosomal dominant hypocalcemia type 1, or ADH1. Based on the data, the biotech said it plans to file for full FDA approval in the first half of next year. Read more from Max Gelman here .

Novo Nordisk is looking to trump Pfizer's $7.3-billion agreement to acquire obesity drug developer Metsera with a sweetened bid potentially worth up to $9 billion. Under the proposal announced Thursday, Novo would acquire Metsera for $56.50 per share in cash, or around $6.5 billion, with the latter also eligible for contingent value rights (CVRs) of up to $21.25 per share in cash, or approximately $2.5 billion. Last month, Pfizer agreed to buy Metsera for $47.50 per share in cash at closing, for an initial payment of about $4.9 billion, with additional CVRs of up to $22.50 per share tied to key clinical and regulatory milestones. The deal is positioned as giving Pfizer a new push in the fast-growing obesity drug market, having faltered with its own programmes, such as the oral GLP-1 programme danuglipron. Following the announcement, documents released by Metsera indicated that it had earlier received a numerically better offer than Pfizer's from an undisclosed company, but decided against pursuing this given potential regulatory issues and timelines around the payment of CVRs.  Pfizer hits back… In response to Novo's announcement, Pfizer called the move "reckless and unprecedented," noting that "it is an attempt by a company with a dominant market position to suppress competition in violation of law by taking over an emerging American challenger." Metsera's pipeline is headed by the ultra-long-acting GLP-1 receptor agonist MET-097i, with recent data from a pair of Phase IIb studies supporting progression of the drug into Phase III testing in late 2025. Other assets under development include the early-stage monthly amylin analogue MET-233i, as well as two oral GLP-1 candidates expected to soon enter clinical testing. Novo said that a purchase of Metsera would be in line with its long-term strategy in obesity and diabetes. The Danish drugmaker did not disclose the CVR terms, but indicated that they would be linked to certain clinical and regulatory milestones. Meanwhile, under Pfizer's offer, Metsera shareholders stand to receive $5 per share upon the start of a Phase III trial of the MET-097i/MET-233i combination, $7 per share upon FDA approval of monthly MET-097i monotherapy, and $10.50 per share if the monthly MET-097i/MET-233i combo wins FDA approval. …and questions legality Pfizer also criticised the make-up of Novo's bid, suggesting that it is structured in order "to circumvent antitrust laws," while it carries substantial regulatory and executional risk. "The proposal is illusory and cannot qualify as a superior proposal…and Pfizer is prepared to pursue all legal avenues to enforce its rights under its agreement," the company said. However, Metsera responded to Novo's offer by deeming that it is "superior" to the agreement with Pfizer, which at this time remains in place. Metsera explained that Pfizer has a four-day period during which the parties can negotiate terms of the deal that would reinstate it as a "superior" bid. The unsolicited bid from Novo comes amid a turbulent year for the Danish drugmaker, culminating in the replacement of its CEO, a global streamlining and more recently, an overhaul of its board. The changes follow pressure from Novo's majority shareholder, the Novo Nordisk Foundation, which is looking to inject more urgency into the company's response to the "more dynamic and consumer-driven obesity market."