UK follows through on doubling of statutory scheme rate

 The UK pharma industry has reacted angrily to the news that the government has doubled the rate that drugmakers must repay on the sales of newer products to the NHS under the so-called statutory scheme.

The Association of the British Pharmaceutical Industry (ABPI) said this morning that the government will hike the rate to 31.3% in the latter half of this year from 15.5% in the first half, despite its warnings that the move would threaten growth and investment in the UK life sciences industry.

The scheme sits alongside the Voluntary Scheme for Branded Medicines Pricing, Access and Growth (VPAG) in setting a yearly cap on the total allowed sales value of branded medicines to the NHS each year, with sales above the threshold paid back to the government via rebates.

The rate for the latter half of the year brings the full-year average to 23.4% – rising to 24.3% next year and 26% in 2027 – which the ABPI pointed out is "well over three times what is required in Germany […] and four times the average payment rate in France."

It also said that the UK now invests a smaller share of its overall healthcare budget on medicines than any comparable country, at just 9% compared to 17% in Germany and Italy, and 15% in France.

Most companies opt for the voluntary scheme, although, a massive increase in the rebate in the last few years prompted some to opt out and switch to the statutory scheme in protest.

The decision to press ahead with the steep increase comes after a consultation period with the industry, which appears to have ignored concerns raised, and despite an acknowledgement that the voluntary scheme needs to be reviewed to avert negative impacts on industry investment and the possibility that the UK may miss out on new product launches, according to the ABPI.

It has already been speculated that AstraZeneca's termination of a plan to invest £450 million in a new vaccine manufacturing plant in the UK came about in part because of the big increase in the VPAG rate for newer medicines from around 15% in 2024 and mid-single digits in the pre-pandemic era.

"The UK's sky-high and unpredictable payment rates send a terrible message to international investors at a time when the UK is trying to position life sciences research and development as an engine for health and growth," said ABPI chief executive Richard Torbett.

"We urge the government to chart a clear path to reverse the UK's historic underinvestment in medicines, through meaningful changes to both the voluntary scheme and statutory scheme," he added.

Research (PDF) commissioned by the trade organisation has claimed that, if rates stay above 20%, the UK could lose out on £11 billion ($14.8 billion) of R&D investment by 2033, but should they be maintained below 10%, that could increase GDP by £61 billion over the next 30 years.

https://pharmaphorum.com/news/uk-follows-through-doubling-statutory-scheme-rate

Vaxart stock soars after positive Phase 1 norovirus vaccine results

 Vaxart Inc (NASDAQ:VXRT) stock surged 70% after the clinical-stage biotechnology company reported positive topline results from its Phase 1 trial evaluating second-generation oral pill norovirus vaccine constructs.

The trial showed that Vaxart’s second-generation vaccine constructs significantly increased norovirus blocking antibody assay (NBAA) titers compared to first-generation constructs. The GI.1 construct demonstrated a 141% increase in NBAA titers, while the GII.4 construct showed a 94% increase at the higher dose level.

"Consistent with what we previously demonstrated in animal models, these clinical data prove that our second-generation constructs increased antibody titers in humans," said Sean Tucker, Vaxart’s Founder and Chief Scientific Officer. He added that these significant increases give the company "high confidence that our second-generation constructs will provide even greater protection against infection."

The open-label trial involved 60 healthy volunteers randomized into three groups of 20 each, receiving either first-generation constructs, an equivalent dose of second-generation constructs, or a lower dose of second-generation constructs. All vaccine candidates were well-tolerated with no vaccine-related serious adverse events reported.

Vaxart CEO Steven Lo stated that the company believes its second-generation norovirus oral pill vaccine candidate "has the potential to provide first-in-class or best-in-class protection" against norovirus, for which there is currently no approved vaccine.

The company plans to incorporate these results into ongoing discussions with potential partners. With appropriate funding or partnership, Vaxart expects to conduct a Phase 2b study potentially beginning in the second half of 2025, followed by a Phase 3 trial as early as 2026.

https://www.investing.com/news/stock-market-news/vaxart-stock-soars-after-positive-phase-1-norovirus-vaccine-results-93CH-4090958

Gilead’s HIV Combo on Hold, With No Impact on FDA’s Pending Lenacapavir Decision

 

Gilead underscored its faith in the combo therapy and pledged to work with regulators to resolve the hold, which has paused five clinical trials. Gilead also stressed that the hold does not impact any other assets in its HIV pipeline.

Five clinical trials for Gilead’s investigational weekly HIV combo pill have been placed on hold by the FDA after a safety signal emerged. While the combo includes a version of Gilead’s lenacapavir, which is approved as Sunleca for twice-yearly treatment of people with multi-drug-resistant HIV and currently under FDA review for the prevention of HIV, Jefferies analysts said the pause will not affect the looming decision date.

Gilead announced the clinical hold Tuesday morning, explaining in a release that two Phase II/III trials named WONDERS-1 and -2 had been paused, plus three Phase I studies. The combination therapy features the integrase strand transfer inhibitor GS-1720 and/or the capsid inhibitor GS-4182. While Gilead did not mention lenacapavir in the release, Jefferies analysts explained that GS-4182 is a pro-drug formulation of the investigational therapy, which is separately under review for HIV pre-exposure prophylaxis (PrEP).

“While it might increase some investor uncertainty into the all-important June 19 PDUFA for [lenacapavir] for PrEP, we see no major read-through and expect an on-time and clean FDA approval,” Jefferies wrote on Tuesday morning.

BMO Capital Markets agreed but said that Gilead’s shares could still face some pressure Tuesday as investors digest the news. The company’s stock declined 2% to $110.75 as of 10:50 a.m. ET.

Gilead said that the hold was placed after decreases in CD4+ T cell and absolute lymphocyte counts were identified in a subset of patients who received both drugs. This can be a signal of a weakened immune system in patients with HIV.

The Phase II/III WONDERS-1 trial is comparing the combo with Gilead’s approved HIV medicine Biktarvy in people with HIV who are taking medication to suppress the virus. The Phase II/III WONDERS-2 study similarly features Biktarvy as the comparator but has enrolled patients with HIV who are treatment-naive.

The company underscored its faith in the combo therapy and pledged to work with regulators to resolve the hold. Gilead also stressed that the hold does not impact any other assets in its HIV pipeline.

Jefferies agreed with this assessment, noting that had the FDA been concerned, it would have stalled more of Gilead’s formulations and integrase inhibitors currently under development.

Any Day Now

Gilead is seeking approval of lenacapavir as a twice-yearly injection for PrEP for HIV. The FDA’s decision, due June 19, has been eagerly anticipated by analysts, patients and Gilead, which is gearing up for a massive launch. The company is looking to the drug to build on its HIV empire, which is anchored by Biktarvy—a drug that recorded sales of $13.4 billion in 2024. BMO predicts peak sales of $6.5 billion for the PrEP indication. More broadly, Gilead is aiming to launch nine new HIV drugs by 2033.

Gilead backed lenacapavir’s latest application with data from the Phase III PURPOSE 1 and PURPOSE 2 studies. PURPOSE 1, which focused on cisgender women, demonstrated 100% efficacy in preventing HIV infection. PURPOSE 2 enrolled a more diverse population of cisgender men, transgender men, transgender women and nonbinary individuals who have sex with partners assigned male at birth. Results showed that twice-yearly lenacapavir cut HIV incidence by 96%.

Jefferies said this indication is very different from what the combo has been aimed at addressing in the now-stalled trials. It’s also unclear if the lenacapavir pro-drug is even the issue at this point.

Other companies in the HIV space have had similar safety signals arise. Merck, for example, had trials of Isentress, launched in 2007, placed on hold by the FDA after CD4 T cell count reductions were observed. A combo of Isentress and Gilead’s lenacapavir for HIV treatment was also placed on hold several years ago but was ultimately released in 2022 using lower doses of Merck’s drug.

Altogether, Jefferies is not too worried about the clinical hold. The firm places more weight on Phase I data for lenacapavir in combination with the injectable integrase inhibitors GS-1219 and GS-3242. Gilead intends to pick one of those medicines to move forward in a combo regimen with lenacapavir by the end of the year. The drugs are administered as a single dose at the first month and sixth month (Q6M).

“This would be the real game changer and value proposition for Gilead if they are able to swap the $15B Biktarvy market onto long-acting Q6M injectable in the later half of the decade,” Jefferies wrote.

https://www.biospace.com/drug-development/gileads-hiv-combo-on-hold-with-no-impact-on-fdas-pending-lenacapavir-decision

Lilly Bites Again in $650M Muscle-Preserving Treatment Pact With Juvena

 

The deal is Lilly’s second obesity tie-up in a week, after sinking up to $870 million into an agreement with Camurus to develop long-acting versions of molecules against GLP-1 and other incretins.

After signing a deal to create long-acting GLP-1 agonists last week, Eli Lilly is back with another biotech deal that aims to improve its weight loss empire. This time, the Zepbound maker is offering up to $650 million in milestones to leverage Juvena Therapeutics’ AI drug hunting platform for new treatments to preserve muscle mass and function.

Details of the deal were slim, with the financial breakdown not disclosed. Lilly is providing an undisclosed upfront payment, equity investment and milestones through the deal. The Indianapolis-based behemoth will receive an exclusive license to develop lead candidates for each target discovered. If the program moves forward, Lilly will take over research, development and commercialization.

This is the second deal that Lilly has signed in a week, after putting up to $870 million on the line with Camurus to create long-acting versions of molecules against GLP-1 and other incretins. Under the pact, which included $290 million upfront, Lilly gains access to Camurus’ long-acting delivery technology.

Through the Juvena deal, Lilly will gain access to the biotech’s AI-enabled screening platform called JuvNET, which maps the therapeutic potential of stem cell-secreted proteins to find new muscle-targeting drug candidates that can improve body composition and muscle health.

The companies did not disclose whether the resulting therapeutics will be combined with Lilly’s existing drugs, however, Juvena Chief Scientific Officer Jeremy O’Connell said in a statement that the collaboration will “aim to accelerate innovation that advances the standard of care in obesity management.”

Juvena, a member of BioSpace’s 2024 NextGen Class, emerged in 2022 with $41 million and a plan to use AI to find proteins secreted by regenerative stem cells. The biotech focused on myotonic dystrophy, sarcopenic obesity and obesity. Just last month, Juvena launched its first clinical program with JUV-161, a muscle regenerating endocrine therapy for myotonic dystrophy type 1 and sarcopenia. The initial first-in-human trial will feature healthy volunteers.

https://www.biospace.com/business/lilly-bites-again-in-650m-muscle-preserving-treatment-pact-with-juvena

Novo Ups Obesity Ante With $800M+ Deep Apple Pact for Oral, Non-Incretin Drugs

 

For $812 million, Novo Nordisk will enlist Deep Apple to discover and develop a non-incretin therapy for obesity, months after the Danish pharma’s amylin efforts underwhelmed investors.

Novo Nordisk is partnering with San Francisco’s Deep Apple Therapeutics to develop novel non-incretin oral drugs for obesity in a deal worth up to $812 million.

The partners did not provide a detailed breakdown of the financial terms in the Wednesday announcement, only revealing that the Danish drugmaker will pay an upfront fee plus research costs and milestone payments. Deep Apple will also be eligible to receive royalties on sales of any product that arises from the partnership.

In exchange for its investment, Novo will gain access to Deep Apple’s proprietary engine, which the biotech will use to discover and optimize potential drug compounds. Novo, in turn, will have the exclusive global right to take these assets through investigational new drug-enabling studies and into clinical development, as well as manufacture and commercialize them across all indications.

Seeking to stay at the forefront of innovation in the obesity space, Novo’s arrangement with Deep Apple will look for therapeutic targets outside the incretin family of hormones. Current weight-loss therapies—including Novo’s Wegovy and Eli Lilly’s Zepbound—mimic these gut-derived hormones, such as GLP-1 and GIP, in turn regulating blood sugar levels and suppressing appetite by inducing the feeling of fullness.

In recent months, however, drugmakers have been looking for ways to go beyond the incretin paradigm, potentially unlocking more effective and safe weight-loss therapies. Chief of these non-incretin targets is amylin, a pancreatic peptide that, like GLP-1, lowers blood glucose concentrations and slows the emptying of the stomach. Amylin-based weight-loss therapies could improve the quality of weight reduction, with less loss of lean mass by focusing on lowering fat.

Novo is chasing after amylin with CagriSema, a combo therapy that brings together its GLP-1 receptor agonist semaglitude—the active ingredient of Wegovy—with the long-acting amylin analog cagrilintide. But things haven’t been going smoothly, with Phase III data released in December 2024 that left investors disappointed. Results from the REDEFINE 1 trial demonstrated a 22.7% reduction in body weight at 68 weeks, below Novo’s own bar of 25% weight-loss.

Though the miss was modest, the effect on Novo’s shares was not: The readout triggered a massive selloff that wiped some $72 billion from the drugmaker’s market cap.

Regaining Footing With a Differentiated Engine

Wednesday’s Deep Apple partnership could be part of Novo’s attempt to steady its footing in the non-incretin race. In an email to BioSpace, Deep Apple CEO Spiros Liras said that the partners will go after a “novel” target that, “unlike most other obesity targets, is not represented by any program in clinical development.”

Without naming what this target was, Liras added that it “has the potential to impact both weight loss and weigh loss maintenance.”

In developing therapies for this target, the partners will leverage Deep Apple’s proprietary drug discovery platform, which uses cryoEM, a method that involves imaging frozen biomolecules to better visualize the target, Liras told BioSpace. This approach will let Novo and Deep Apple find novel pockets on the target molecule, which they can then use to screen for potential therapeutic molecules.

“A key differentiator here is that we rely exclusively on virtual screening for hit identification,” Liras continued, noting that the biotech also applies machine learning models to better assess each potential candidate and determine which have high chances of clinical success. The process takes about three to four months.

“Deep Apple’s work to date has yielded unique structural insights which provide opportunities to explore multiple pharmacological functions of the target,” Liras said, adding that the collaboration could also eventually cover adjacent indications. “Cardiovascular and metabolic disease is the scope of the collaboration—that includes obesity but is not limited to obesity.”

https://www.biospace.com/business/novo-ups-obesity-ante-with-800m-deep-apple-pact-for-oral-non-incretin-drugs

BMS Expands Radiopharma Presence With $1.35B Biobucks Deal for Philochem

 

Instead of homing in on PSMA—currently the most validated target in prostate cancer—BMS and Philochem will instead collaborate on an early-stage molecule that binds to a novel marker called ACP3.

Bristol Myers Squibb is trying to unlock an alternative pathway to treating prostate cancer. The company’s radiopharma-focused subsidiary RayzeBio has fronted $350 million to partner with Italian-Swiss biotech Philochem to advance an early-stage small-molecule radiotherapeutic targeting a novel biomarker.

BMS is also promising up to $1.35 billion in development, regulatory and commercial milestones, plus mid-single to low-double-digit royalties on global net sales. BMS and Philochem expect to close the transaction in the third quarter, pending customary clearances and approvals.

Philogen, Philochem’s parent company, surged 20% on Wednesday morning.

The star of Wednesday’s agreement is OncoACP3, a small-molecule radiotracer that targets a biomarker called ACP3. According to Philochem, ACP3 is highly expressed in prostate cancer—but not in healthy tissue—and at levels that match or exceed that of PSMA, which is currently the prevailing target of choice for prostate cancer therapies. “A side-by-side comparison between ACP3 and PSMA . . . has shown that ACP3 is more abundantly expressed in prostate cancer than PSMA,” the biotech wrote on its website.

OncoACP3 is a small-molecule ligand that has high affinity for the ACP3 protein. Notably, it can carry both Lutetium-177 and Actinium-225—both currently the most common payloads for radiopharmaceuticals.

In a statement on Wednesday, RayzeBio president Ben Hickey said that by potentially opening an alternative pathway to PSMA, the Philochem partnership “provides a differentiated entry” for BMS “into the prostate cancer arena.”

The decision to zero in on a novel prostate cancer target could also help BMS distinguish itself in a radiopharma field that is becoming increasingly crowded. Currently leading the pack is Novartis, which owns two FDA-approved therapies: Lutathera, indicated for gastroenteropancreatic neuroendocrine tumors, and Pluvicto, which targets PSMA and is approved for prostate cancer.

Another pharma trying to catch Novartis is AstraZeneca, which entered the ring in March 2024 with the $2.4 billion acquisition of Fusion Pharmaceuticals, which gave the pharma its lead radiopharma asset FPI-2265, an actinium-based radioconjugate that is being developed for prostate cancer—and targets PSMA.

Also in the running is Eli Lilly, which spent $1.4 billion to buy Point Biopharma in October 2023 and $1.1 billion for Aktis Oncology in May 2024. Anchoring its radiopharma pipeline is PNT2002, another PSMA-targeting candidate for prostate cancer.

https://www.biospace.com/business/bms-expands-radiopharma-presence-with-1-35b-biobucks-deal-for-philochem

Everything Soars Higher As Rate-Cut Odds Jump After CPI 'Miss'

 A 'disappointing' CPI print (cooler than expected) has promoted a surge higher in the market's expectation for rate-cut...

Source: Bloomberg

Prompting a surge higher in EVERYTHING.

Stocks spiked...

Treasuries were aggressively bid with 10Y yields sdown 5bps...

Source: Bloomberg

The dollar fell...

Source: Bloomberg

Helping gold to accelerate...

Source: Bloomberg

Goldman said that this would be a materially dovish print (<0.25% MoM for Core CPI) would prompt the bond market to add back at least 2x 25bp rate cuts (it already has) and for Equities to react positively (up 2-2.5%) to the bull steepening that likely ensues.

What excuse will Powell come up with next to NOT cut?

https://www.zerohedge.com/markets/everything-soars-higher-rate-cut-odds-jump-after-cpi-miss