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LONDON – The Jefferies Global Healthcare Conference may have found its groove. While last year’s long queues may be gone, the buzz is still palpable as thousands arrive in London to what observers describe as a key confab to plant seeds that could mature into deals in the coming months. This year, the conference ran for four days instead of three. There are more venues to meet outside the Waldorf Hilton, like a nearby pub with large Jefferies signage draped by the entrance. There are free umbrellas on hand (essential when rushing between buildings during unpredictable weather) and ginger and apple shots by the door (as temperatures hit single digits this week — that’s Celsius, not Fahrenheit). An earlier draft of the program shows that former FDA official George Tidmarsh was scheduled to make an appearance, but that has disappeared in the latest version since he left his post as CDER director earlier this month. But there was still plenty to attend: GSK announced its LTZ Therapeutics deal on the same day it hit the stage. During its session, Pfizer’s CFO indicated what’s likely to be its next move now that it has won the bidding war for Metsera. Endpoints News attended sessions featuring Alkermes (which is in the middle of its own bidding contest) and WuXi XDC. Endpoints also met with execs from cancer biotech Light Chain Bioscience and dementia drugmaker Vesper Bio. Here are the highlights: On Wednesday morning, Alkermes increased its bid for Avadel in its ongoing bidding war for Lundbeck. During Alkermes’ slot at Jefferies later that day, CEO Richard Pops was asked how the strategic value for Avadel has changed over the past several weeks. Pops said that the initial deal announcement on Oct. 22 was made before Alkermes knew about its mid-stage data in narcolepsy type 2 for its drug candidate called alixorexton. That trial, when it reported three weeks later, yielded underwhelming results . Still, Pops said Alkermes had “a tremendous amount of confidence” that alixorexton would enter the market based on its results in narcolepsy type 1 , which it reported earlier in the year. Pops said that it ultimately wants Avadel because its narcolepsy drug Lumryz is already on the market. That would allow Alkermes to tap into its existing network of clinicians and payers even before it could potentially launch alixorexton. There’s also the commercial value of Lumryz itself and the potential of drug combinations, he added. But Takeda, which has a drug with a similar mechanism to alixorexton, is likely to reach the market sooner . “We’ll see where Takeda prices the first product … but there are plenty of orphan diseases that are being well-reimbursed for on-label use at very high prices if they have a very profound impact on people’s lives,” Pops said. Light Chain executives made their case to Endpoints as to why targeting CD47 is still a promising approach in oncology. The CD47 space has seen many high-profile flops in recent years, with Gilead effectively ending development of magrolimab in 2024, and ALX Oncology’s lead asset evorpacept flunking a Phase 2 study earlier this year. CD47 is a surface protein expressed by healthy cells that gives off a “don’t eat me” signal. It’s also overexpressed by some cancers to help evade the immune system. “With a monospecific approach, you will hit CD47 on tumors but also everywhere else,” Light Chain CEO Nicolas Fischer said. “This has posed major challenges that led to the termination of previous programs — mainly toxicity, but also a huge ‘sink effect’ where you have to put enough antibody to be able to bind all the CD47 in the body.” By contrast, Fischer said Light Chain’s bispecific antibody approach features one arm that targets a tumor-associated antigen with high affinity and a second arm that blocks CD47. The CD47-targeting arm has a weaker affinity: In practice, it can only block the protein in the setting of a cancer cell, he added. One of Light Chain’s lead candidates is a mesothelin x CD47 bispecific called NI-1801, which is being developed for platinum-resistant ovarian cancer. The biotech presented early data from the candidate alone and in combination with Merck’s Keytruda at the European Society for Medical Oncology’s annual congress in October. Like Light Chain, Vesper Bio was also keen to defend its approach in light of a recent high-profile failure for a rival candidate backed by big pharma. Its CEO, Jacob Falck Hansen, met Endpoints at a flexible office space down the road from the Waldorf Hilton. Vesper is developing a medicine called VES001 for a genetic form of frontotemporal dementia. The drug is designed to restore levels of a neuron-protecting protein, progranulin, which is naturally lacking in these patients. Some onlookers have been skeptical of this approach after GSK and Alector’s candidate latozinemab significantly increased levels of progranulin in the blood but failed to improve disease progression in a Phase 3 study. But Hansen argued that nuances in exactly how these two candidates go about restoring progranulin could make all the difference to disease progression. Latozinemab was an antibody designed to degrade a receptor called sortilin that’s found on the surface of neurons. Progranulin binds to the sortilin receptor, which then transports it to the lysosomes for degradation. But sortilin also serves as the binding site for many other proteins and lipids besides progranulin, including APOE4, APOE3 and TrkB, Hansen explained. “If you want to interfere with sortilin, it’s important to do it in a targeted manner given the many important roles that sortilin has,” Hansen said. That’s where VES001 could prove itself. Instead of directly degrading the sortilin receptor, Vesper’s small-molecule drug is designed to inhibit progranulin binding to the sortilin receptor selectively. The China-headquartered ADC manufacturer will consider building in the US, if pharmaceutical companies continue to focus their manufacturing to the country, CEO Jimmy Li said during a presentation on Wednesday. After spinning out of its parent company WuXi Biologics in 2023, WuXi XDC currently operates from WuXi and Shanghai in China. It is also in the process of constructing a building in Singapore, which is expected to be operational by the end of the year. WuXi XDC does not yet have a Western footprint, but Li noted that the company’s Singapore site will be advantageous as the country currently has a very low US tariff rate. Editor’s note: A quote from Alkermes CEO Richard Pops was clarified to note that he said “on-label” rather that “unlabeled.”

All told, Alkermes' souped-up bid values Avadel Pharmaceuticals at $2.37 billion, contingent upon a Lumryz regulatory milestone being triggered. Facing the fact that Lundbeck’s unexpected offer for Avadel Pharmaceuticals was sweeter, Alkermes has come back to the negotiating table with a higher bid it believes can seal the deal.Alkermes and Avadel have reached an accord on a new offer that would see Alkermes pay up to $22.50 per Avadel share to acquire the company, according to a Nov. 19 press release. The upgraded bid features $21 per Avadel share in cash as well as a $1.50 per share contingent value right (CVR) tied to the potential FDA approval of Avadel’s narcolepsy drug Lumryz in idiopathic hypersomnia by the end of 2028.All told, the souped-up bid values Avadel at $2.37 billion, contingent upon the Lumryz milestone paying out, Alkermes said in its release.Both companies’ boards have blessed the amended deal and currently expect the acquisition of Avadel to close in 2026’s first quarter. Meanwhile, Lundbeck, which cut in on Alkermes’ courtship of Avadel last week, has yet to tender an adjusted offer of its own.At the start of the month, Alkermes appeared set to purchase its Dublin compatriot Avadel for up to $2.1 billion. Last week, Lundbeck made a surprise bid reportedly valuing the company at up to $2.4 billion. The terms of Lundbeck’s offer differed slightly from Alkermes’, which floats a potential cash sweetener exclusively around Lumryz’s regulatory success. For its part, Lundbeck put up a bid consisting of $21 per ordinary Avadel share and a CVR that could have triggered two more $1 per share payments tied to future sales of Lumryz and Avadel’s recently acquired sleep asset valiloxybate.Earlier this week, before Alkermes had beefed up its pitch, Avadel acknowledged that Lundbeck’s unsolicited bid constituted a “superior company proposal.” That distinction was critical as it gave Alkermes five business days to sit back down at the negotiating table with Avadel to potentially improve its proposal under the companies’ original transaction agreement.While Lundbeck’s offer had a slightly higher overall value than the new bid proposed by Alkermes, Avadel has determined that "the terms of the CVR in Alkermes' increased offer are superior to the terms of the CVR included in the Lundbeck proposal, which was determined to be unlikely to be achieved," according to Alkermes' release. Alkermes first unveiled its Avadel acquisition plan in late October, at the time floating $18.50 per share for Avadel with a $1.50 per share CVR based on Lumryz’s prospective idiopathic hypersomnia nod. The Dublin-based company is hoping to use the acquisition as a springboard into the sleep market, where Avadel’s narcolepsy drug Lumryz is expected (PDF) to reel in sales between $265 million and $275 million this year.By leveraging Lumryz’s existing spot in the market, Alkermes is hoping to carve out a niche for itself ahead of the potential future launch of its sleep disorder asset alixorexton. Alkermes currently plans to kick off a phase 3 trial of alixorexton in narcolepsy in next year’s first quarter.