Protagonist Therapeutics (NASDAQ:PTGX) has announced the nomination of PN-477, a novel GLP-1, GIP, and GCG receptor triple agonist peptide, as a development candidate for obesity treatment.
The drug candidate features both oral (PN-477o) and injectable (PN-477sc) formulations, designed for once-daily and once-weekly administration respectively.
The company reports that PN-477 has demonstrated potent in vitro activity in activating all three targeted receptors and has shown robust preclinical proof-of-concept in various animal studies, including diet-induced obesity mouse models, normal dogs, and cynomolgus monkeys.
The candidate is engineered to be orally stable with balanced potencies against the three receptors to potentially maximize weight loss benefits while minimizing adverse effects.
Protagonist has initiated IND-enabling studies and expects to begin Phase 1 clinical trials in the second quarter of 2026. The company positions PN-477 as a potential best-in-class treatment option, aiming to offer weight loss comparable to the best injectable treatments while providing the flexibility of both oral and injectable administration routes
Preauthorization, also called prior authorization (PA), is a process where healthcare insurance companies must approve before paying for medications, procedures, surgeries, or other medical services.
These are usually standard and approved therapies. For medications, PA approval is required for many FDA-approved (though expensive) drugs, used according to label, meaning in accordance with the detailed package insert.
MAHA rainmaker, Health and Human Services Secretary Robert F. Kennedy Jr, is trying to fix this problem.
This process started in the 1960s as part of Medicare and Medicaid’s “utilization review” to reduce unnecessary hospital stays and manage costs. It comes from an intentional effort to establish a third-party payer system, separating the patient from the service providers, meaning physicians and hospitals.
Such disconnection exists in few other spheres. If you hire a plumber, lawyer, or tennis coach, they charge by the hour or job and you pay them directly.
Education is one area besides healthcare where this disconnect exists. Taxpayers fund education, either directly or through grants, subsidies, and loan guarantees; however, they are often disconnected from the consumers, namely students and their parents. Those providing the education, teachers, are disconnected from the payers and consumers.
As a result, both education and medical inflation grow faster than overall inflation, with education inflation leading the way. But quality metrics are going the other way resulting in a dumber and unhealthier population.
The main issue is that when someone else covers the cost, the consumer becomes insensitive to price and value. Meanwhile, the provider must serve the payer rather than the patient, which leads to inefficiency, overuse, and lower quality.
Or as I tell my patients, “He who pays the piper calls the tune” with the insurance company paying me as the piper and telling me and my patient that the tune is a Rolling Stones classic, “You can’t always get what you want.”
In defense of insurance companies, in our current healthcare delivery scheme, large systems are vulnerable to misuse. Think of military procurement and $10,000 toilet seats.
A Finnish study found that “The probability of unscheduled C-section increases substantially during the normal working hours (8am-4pm) on working days that precede a leisure day.”
Such behavior is the military equivalent of an endless war. However, in the medical field, such behavior is more the exception than the norm. But it happens and drives unnecessary costs.
PA might restrict the use of higher-risk, more expensive procedures for convenience. But the flipside is that PA also may deny the patient the treatment they need when they need it.
What happens when the pendulum swings too far in the other direction?
In my retina world, many payers require the initial use of an often inferior off-label cancer drug, packaged in a compounding pharmacy, to treat macular degeneration and diabetic retinopathy, rather than one of a few FDA-approved drugs in prefilled syringes used as indicated on-label and often with better results.
My staff then must contact the insurance company, begging them to approve the use of a more effective but more expensive drug to improve or preserve my patient’s eyesight. Yes, high-cost drugs are part of the issue, but that’s a separate discussion.
Medicare and most payers reimburse physicians 4.3% of the drug cost (6% reduced via budget sequestration) to cover the entire supply chain of office purchase, distribution, preparation, and of course making us get PA. That is our “profit”. The drug reimbursement goes directly back to the pharmaceutical company.
Additionally, there is a 2025 3% across-the-board cut in Medicare payments to physicians, something unlikely to be fixed in the Big Beautiful Bill still languishing in Congress. At some point, the business of medicine barely breaks even, or runs at a loss, for independent physicians and practices.
PA along with reimbursement not keeping pace with costs, increases the cost of doing business to a breaking point, pushing physicians into private equity or corporate employment, turning the practice and profession of medicine into another service, like getting your car repaired or signing up for a cell phone plan.
Enough of my problems. How does PA work for all physicians?
A 2022 AMA survey found some disturbing facts about PA that RFK Jr and Dr Oz cited in their recent announcement about PA reform. “86% of respondents reported that prior authorizations resulted in increased use of healthcare resources, leading to waste rather than the cost savings claimed by insurers.”
Furthermore, “Practices complete 45 prior authorizations per physician per week on average, with physicians and their staff spending an average of 14 hours weekly on prior authorizations.”
Who pays for this extra labor cost? Medicine operates under government price controls, leaving medical practices to eat these additional costs and unfunded mandates.
Besides costs, there are also treatment delays. In the same survey, “94% of physician respondents said the process led to delays in care for patients.”
For elective care, a delay might not always be problematic. If it takes a week or two for PA for a cataract surgery or hip replacement, that’s built into the surgeons who schedule a month or two out.
However, for urgent or timely treatments, it can be life threatening. “33% had seen a prior authorization requirement led to a serious adverse event for a patient, including 25% who reported prior authorization leading to a patient’s hospitalization.”
Delayed care risks patient harm and paradoxically increases costs for insurance companies, as the cheaper mandated treatment often leads to more costly care and prolonged hospitalization down the road. Insurance companies play the “penny-wise pound-foolish” game, frustrating physicians and patients, and in many cases, resulting in costlier care.
Health and Human Services Secretary Robert F. Kennedy Jr. announced last week that several large insurance companies, “pledged to make the changes, which will be implemented across private insurance, Medicare Advantage and Medicaid.”
AHIP, a health insurance trade group, said the changes “could benefit 257 million people in the United States.” These reforms include,
1. Standardized electronic submissions for real-time decisions by the end of 2026.
2. Reduce services requiring PA: From approximately 6,000 to 2-3,000 by next year.
3. Continuity across insurers: Existing authorizations remain valid for 90 days after the patient switches plans.
4. Public dashboard: Monitor denials and delays for transparency and peer review.
5. Real-time decisions and peer-to-peer reviews
These are welcome changes, but since they are voluntary, they might not happen. I am not a fan of extra government regulations, but without clear timelines and enforcement, compliance could be as unlikely as asking teenagers to do their homework and clean their rooms.
But PA also helps control overall costs. PA is a form of care rationing. Removing it will lead to higher overall costs, often passed on to patients and employers who pay for insurance.
This raises the bigger question of fixing or replacing our flawed system. In 2017, I proposed a solution that might work, but no one in Washington, D.C., has the appetite to tackle the healthcare beast. Writing checks for endless wars is all Congress can handle these days.
PA began as a cost-control gatekeeper but has evolved into a complex obstacle that burdens providers and patients. RFK Jr.’s voluntary approach tackles many digitization issues, like fewer approvals and greater transparency. However, major challenges include enforcement, logistics, and costs.
While not a cure-all, PA reform is at least a step in the right direction. Unfortunately, a market-based overhaul of healthcare is unlikely, and it could be worse: Senator Bernie Sanders has his “Medicare-for-all” plan ready to deploy on an unsuspecting public when the political climate aligns.
Despite what protesters claimed a few weeks ago, we have no king. Otherwise, the king could fix healthcare delivery with the stroke of a pen or sword. But at least RFK Jr is nibbling at the beast, rather than continuing to feed it as most elected officials do.
Brian C. Joondeph, M.D., is a physician and writer.
Vertex Pharmaceuticals Incorporated (NASDAQ:VRTX) ranks among thebest fundamental stocks to buy according to hedge funds. With a price target of $550, H.C. Wainwright reaffirmed its Buy rating on Vertex Pharmaceuticals Incorporated (NASDAQ:VRTX) on June 23. The update comes after the American Diabetes Association (ADA) conference featured updated data from Vertex’s zimislecel program.
According to the clinical findings, 10 out of 12 patients, or 83% of the total, became insulin independent. Furthermore, as evidence of the treatment’s potential efficacy, H.C. Wainwright reported that all research participants achieved primary composite endpoints with sustained C-peptide restoration.
Notably, as Vertex Pharmaceuticals Incorporated (NASDAQ:VRTX) seeks to expand its therapeutic areas, the zimislecel program represents a component of the company’s pipeline beyond its primary cystic fibrosis therapies.
Vertex Pharmaceuticals Incorporated (NASDAQ:VRTX) is a global biotechnology company that is involved in the discovery and development of small-molecule medications for the treatment of severe illnesses, including cystic fibrosis.
Idaho killer Wess Roley posted a chilling online photo of himself masked in camouflage with a belt of rifle shells, along with a Bjork song with lyrics ominously warning, “I’m going hunting’’ — just hours before his deadly ambush, officials said Monday.
The creepy post was among a slew of new details about the horror revealed at a sheriff’s press conference.
Authorities said Roley had been living out of his car before his heinous attack, which left two firefighters dead and another critically wounded.
A firefighting aircraft drops water on a wildfire the day after a shooter ambushed and killed multiple firefighters responding to a wildfire at Canfield Mountain.AP
Roley, 20, had been confronted by the smoke-eaters about his vehicle before he opened fire on them, according to police.
More than 300 law enforcement officers from various agencies responded to the scene once the shots started and spent hours trying to neutralize Roley.
His abandoned car was even rolled off a mountain ledge to prevent him from escaping, while fire engine wheels were deflated to keep him from stealing one and slipping away.
No motive has been identified in the attack, but officers have not yet searched Roley’s vehicle. Authorities do not believe he left a manifesto, and he has known no ties to any Mideast terror group, Norris said.
Authorities said Roley had been living out of his car before his heinous attack, which left two firefighters dead and another critically wounded.
The killer, who was born in California, had been in living in the Coeur d’Alene area since 2024, Kootenai County Sheriff Robert Norris said.
During that time, he had at least five interactions with local police ranging from trespassing to welfare checks, most of which stemmed from reports of him living in his car and parking it on other peoples’ property.
The interactions were “very, very minor,” Norris said, explaining that investigators had identified no criminal record in Idaho or where Roley had previously lived California and Arizona.
Roley died of a self-inflicted gunshot wound Sunday after he appeared to intentionally start a fire in the woods of Canfield Mountain just after 1 p.m. and opened-fire on firefighters who responded to the scene.
It remains unclear if the blaze was used to lure the firefighters to the mountain for an ambush or if the bloodbath was sparked by a disagreement during the interaction over his car.
Roley used a shotgun loaded with slugs during the gunfight.
The fire he started is still burning over 26 acres, but officials expect it will be contained by Monday night.
This is a developing story. Please check back for more information.
A wave of new California laws will take effect on July 1, touching nearly every corner of life, from subscriptions and short-term rentals to wages and student mental health.
Part of a broader package signed by Gov. Gavin Newsom during his latest legislative session, the measures aim to boost transparency, expand health coverage, raise wages, and improve access to legal and mental health support.
Here are some of the new laws.
Short-Term Rental Chores
AB 2202 requires short-term rental hosts, platforms, and anyone else listing the property to disclose all extra charges or penalties—such as cleaning fees—that will apply if guests fail to complete end-of-stay chores.
Rental hosts must detail those tasks before a booking is made. According to the legislation, platforms such as Airbnb are also responsible for ensuring that disclosures are made.
Violators face fines of up to $10,000 per offense.
The legislation builds on a 2023 law requiring all mandatory costs—including service and cleaning fees—to be listed upfront in rental and hotel listings.
Subscription Cancellations
AB 2863 mandates that companies offering subscriptions—such as streaming services or memberships—make it as easy to cancel as it is to sign up.
Companies must also send annual reminders with pricing and cancellation details, including a direct “click-to-cancel” link. Renewals after free trials or initial contract periods now require customer approval.
The law applies to contracts entered into, amended, or extended on or after July 1.
Stolen Goods Sales
SB 1144 targets retail theft by requiring online marketplaces such as eBay and Facebook Marketplace to verify the identity of high-volume sellers, defined as those who complete 200 or more transactions involving at least $5,000 in new or unused goods annually.
The law also requires the online platform to notify law enforcement agencies when it identifies potentially stolen item sellers.
Drink Lids in Bars
AB 2375 requires bars and nightclubs with Type 48 licenses to provide drink lids upon request and post signage informing patrons of their availability.
The measure, intended to combat drink spiking, follows a 2023 law requiring such establishments to offer drug-testing kits, including test strips or straws that detect substances such as Rohypnol and ketamine.
This law applies to more than 2,500 bars and nightclubs across the state, where minors are not allowed, and whether or not the business serves food.
Minimum Wage Increases
Several cities and counties will raise their minimum wage on July 1 as follows:
The statewide minimum remains $16.50. Some industries—such as the hotel and fast food sectors—have higher local minimums.
Domestic Workers
SB 1350 extends Cal/OSHA health and safety protections to domestic workers—such as house cleaners, caregivers, and cooks—regardless of whether they are employed temporarily or permanently.
Student ID Cards
SB 1063 requires middle and high school ID cards to display the 988 Suicide & Crisis Lifeline number. Schools are also encouraged to add QR codes linking to local mental health resources.
Special Education Planning
AB 438 moves up the start of postsecondary planning for students with special needs to the beginning of high school, rather than age 16, when deemed appropriate by their Individualized Education Program (IEP) team.
CARE Court Updates
SB 42 requires that family members or caretakers be notified and kept informed about proceedings under the CARE Act, which allows them to petition for court-mandated treatment plans for individuals with certain mental health conditions.
Fertility Coverage
SB 729 requires most employers that offer health insurance to include coverage for infertility diagnosis and treatment, including in vitro fertilization (IVF).
Religious employers are exempt from the law, and the California Public Employees’ Retirement System (CalPERS)—the agency that manages pension and health benefits for state workers—will not be required to offer this coverage until July 1, 2027.
At Newsom’s request, implementation was delayed until January 2026 to allow time to update California’s benchmark plan and clarify insurer obligations.
MIT researchers have invented a new water-harvesting device — a high-tech version of “bubble wrap” — that can pull safe drinking water straight from the air, even in extreme environments like Death Valley, the driest desert in North America,according to LiveScience.
In a study published June 11 in Nature Water, the team described how their innovation could help address global water scarcity. “It works wherever you may find water vapor in the air,” the researchers wrote.
The device is built from hydrogel, a material that can absorb large amounts of water, sandwiched between two glass layers resembling a window. At night, the hydrogel draws moisture from the air. During the day, a special coating on the glass keeps it cool, allowing water to condense and drip into a collection system.
The hydrogel is molded into dome shapes — likened to “a sheet of bubble wrap” — that swell when absorbing moisture. These domes increase surface area, helping the material absorb more water.
LiveScience writes that the system was tested for a week in Death Valley, a region spanning California and Nevada that holds the record as the hottest and driest place in North America.
Despite the harsh conditions, the harvester consistently produced between 57 and 161.5 milliliters of water daily — about a quarter to two-thirds of a cup. In more humid regions, researchers expect even greater yields. According to MIT representatives, this approach outperforms earlier water-from-air technologies and does so without needing electricity.
One major breakthrough was solving a known problem with hydrogel-based water harvesters: lithium salts used to improve absorption often leak into the water, making it unsafe. The new design adds glycerol, which stabilizes the salt and keeps leakage to under 0.06 parts per million — a level the U.S. Geological Survey deems safe for groundwater.
Though a single panel can’t supply an entire household, its small footprint means several can be installed together. The team estimates that eight 3-by-6-foot (1-by-2-meter) panels could provide enough drinking water for a household in areas lacking reliable sources. Compared to the cost of bottled water in the U.S., the system could pay for itself in under a month and remain functional for at least a year.
“We imagine that you could one day deploy an array of these panels, and the footprint is very small because they are all vertical,” said Xuanhe Zhao, an MIT professor and co-author of the study. “Now people can build it even larger, or make it into parallel panels, to supply drinking water to people and achieve real impact.”
The researchers plan to continue testing the device in other low-resource areas to better understand its performance under different environmental conditions.
The US will start reopening ports to Mexican livestock in phases, after trade along the southern border had been halted in May by the spread of a parasitic fly.
The port in Douglas, Arizona, will be the first to reopen as soon as July 7, after live imports of cattle, horses and bison were suspended as the flesh-eating New World screwworm threatened animals, the US Department of Agriculture said Monday. Additional ports in New Mexico and Texas are scheduled to follow suit until mid-September, with the agency evaluating potential risks and impacts after each reopening.
