Wholesale inflation unexpectedly tumbles 0.5% in March, biggest drop in 3 years

 Inflation at the wholesale level posted another surprise decline in March, the latest sign that painfully high consumer prices are beginning to loosen their stranglehold on the U.S. economy.

The Labor Department said Thursday that its producer price index, which measures inflation at the wholesale level before it reaches consumers, fell 0.5% in March from the previous month. On an annual basis, prices are up 2.7%.

Those figures are both lower than the 3% headline increase and 0% monthly figure forecast by Refinitiv economists, a welcoming sign for the Federal Reserve as it seeks to cool price gains and tame consumer demand with the most aggressive interest rate hike campaign since the 1980s. 

Excluding the more volatile measurements of food, energy and trade, so-called core inflation rose % for the month — down from the 0.5% gain in January. The reading was up 4.4% on a 12-month basis, unchanged from the previous month. It marked the lowest level of inflation since February 2021.

Stock futures rose after the report on investor hopes that inflation is cooling more quickly than expected.

The data comes a day after the Labor Department reported that the consumer price index, which measures the prices paid directly by consumers, rose 0.1% in March, slightly less than expected. The annual inflation rate also came in lower than expected at 5%.

Both releases are considered to be important measurements of inflation, with the PPI believed to be a leading indicator of inflationary pressures as costs work their way down to consumers. The different gauges point to inflation that is still running well above the Fed's preferred 2% target, a troubling sign as the central bank has already raised rates nine straight times. 

The back-to-back inflation reports will have major implications for the Fed, which is tightening rates at the fastest pace in decades as it tries to cool the economy. Despite recent turmoil within the banking sector, markets still expect the U.S. central bank to raise interest rates during its next two-day meeting on May 2-3, with 64.5% of traders pricing in a 25-basis-point hike.

https://www.foxbusiness.com/economy/ppi-inflation-march-2023

Sarepta stock slides 11% premarket on report FDA was leaning toward rejecting its gene therapy for Duchenne

 Sarepta Therapeutics Inc. stock (SRPT) slid 11% in premarket trade Thursday, after a report said the U.S. Food and Drug Administration was leaning toward rejecting the company's experimental gene therapy for Duchenne muscular dystrophy, before a top official intervened and directed staff to schedule an advisory committee meeting. In early March, Sarepta cheered investors by saying the FDA would not require an advisory meeting, suggesting the treatment had a path toward approval. That uptrend reversed in mid-March, when the FDA contradicted the biotech company and said it would require one. On Thursday, STAT News reported that the reversal came at the direction of Peter Marks, a top FDA official, who is an advocate for faster gene therapy approvals. The specialized healthcare website cited three people familiar with the FDA's deliberations. Duchenne muscular dystrophy is an inherited disorder of progressive muscular weakness that typically affects boys. The company already markets three drugs for the condition. The advisory committee meeting has been scheduled for May 12. The stock has gained 65% in the last 12 months, while the S&P 500 has fallen 8%

https://www.morningstar.com/news/marketwatch/20230413333/sarepta-stock-slides-11-premarket-on-report-fda-was-leaning-toward-rejecting-its-gene-therapy-for-duchenne-muscular-dystrophy

Historic rain in South Florida causes severe flooding, closing schools and Fort Lauderdale’s airport

 More rain is in the forecast after substantial downpours inundated Fort Lauderdale and parts of South Florida in a 1-in-1,000 year rainfall event, leading to a flash flood emergency in Broward County that closed schools, forced drivers to abandon their cars and shut down the airport through Thursday morning.

While the rain Thursday won’t reach nearly the amounts that fell on Wednesday, it will be problematic and create additional flooding, the National Weather Service said. Gusty winds, small hail and even isolated tornadoes are possible.

Broward County is under a flood warning through 8 a.m. ET, the weather service in Miami said.

Between 14 and 20 inches of rain have drenched the greater Fort Lauderdale metro area since Wednesday afternoon, according to a Thursday morning update from the National Weather Service office in Miami. The deluge is the “most severe flooding that I’ve ever seen,” one mayor said.

Drivers try to navigate flooded roads in Fort Lauderdale on Thursday morning.

Sara Weisfeldt/CNN

“This amount of rain in a 24-hour period is incredibly rare for South Florida,” said meteorologist Ana Torres-Vazquez from the weather service’s Miami forecast office.

Rainfall of 20 to 25 inches is similar to what the area can receive with a high-end hurricane over more than a day, Torres-Vazquez explained. She described the rainfall as a “1-in-1,000 year event, or greater,” meaning it’s an event so intense, the chance of it happening in any given year is just 0.1%.

“Even though the heavy rain has concluded, numerous roads remain closed,” the weather service said, adding that flooding is expected to persist.

Earlier, Fort Lauderdale was “experiencing severe flooding in multiple areas of the city,” Fort Lauderdale Fire Rescue said on social media, warning to stay off the roads as vehicles may become stuck or submerged

A flash flood emergency – the highest level of flood warning – that was in effect for portions of South Florida, including Fort Lauderdale, expired early Thursday.

“This is a PARTICULARLY DANGEROUS SITUATION,” the NWS warned. “Move to higher ground now! This is an extremely dangerous and life-threatening situation. Do not attempt to travel unless you are fleeing an area subject to flooding or under an evacuation order.”

City crews in Hollywood, Florida, “are doing everything they can” to deploy pumps wherever possible and keep drains clear, Mayor Josh Levy told CNN.

“We’ve recorded over 12 inches of rain since midnight, and that’s on top of consecutive days of seemingly nonstop rain,” Levy said. “The ground was already saturated so there is extensive flooding all over our city and throughout South Florida. Many roadways are impassable. Lots of vehicles got stuck and left abandoned in the middle of our roadways.

“I’ve lived here my whole life. This is the most severe flooding that I’ve ever seen,” he said.

More rain and storms expected Thursday

South Florida could get inundated with more even rain as showers and strong storms are in the forecast Thursday.

“After a historic day of rainfall across portions of South Florida that many of us will not soon forget, another potential wet day is ahead for today,” the weather service in Miami said.

There is a slight risk, Level 2 of 5, for severe storms Thursday in parts of Florida, including Fort Lauderdale, Miami and Jacksonville, according to the Storm Prediction Center.

Floods inundate key parts of Broward County

Fort Lauderdale officials have activated its emergency operations center and will be issuing a proclamation of a local state of emergency, saying in a statement early Thursday morning that airboats and high-clearance buggies have been secured from the county sheriff’s office and the Florida Wildlife Commission.

“Staff is assessing park facilities to convert them to staging/reunification centers for individuals impacted by the flash floods. We expect to open these as soon as possible,” the city said. There is “no power at City Hall. We have reports of water flooding the first floor of the Transportation and Mobility (TAM) building.”

The city’s system is designed to take on at least 3 inches of rain in a 24-hour period but they’ve “had neighborhoods receive more than 12” of rain. Service crews will be out to respond to flooding reports and concerns.”

CNN has reached out to city and county officials for additional information.

Officials have asked residents to avoid driving or traveling in Fort Lauderdale amid the storms.

“Police and Fire Rescue continue to answer calls for service,” the city of Fort Lauderdale said in a news release on Wednesday evening. “Public Works staff are clearing drains and operating pumps to mitigate the water as quickly as possible. Efforts have been made to relieve traffic congestion through prioritized signaling to assist individuals leaving the City. We are requesting drivers to stay off the roads and avoid the City of Fort Lauderdale until the water has subsided.”

Drivers contend with standing water on roads in Fort Lauderdale Thursday morning.

Sara Weisfeldt/CNN

The flooding impacted rush hour traffic Wednesday and led to the closure of a tunnel, the city said.

“The Henry E. Kinney Tunnel is closed. Please avoid the area. The weather conditions combined with rush hour traffic are compounding issues in the downtown area,” the city said.

The Broward Sheriff’s Office said in a statement Wednesday it is “being inundated with non-emergency 911 calls regarding the inclement weather” and asks residents to use 911 only for “true emergencies,” also telling residents to avoid driving and to call a tow truck company if a vehicle is stranded and not in an emergency.

Some local services are shuttering Thursday. The Fort Lauderdale-Hollywood International Airport is closed due to ongoing flooding in the vicinity and will reopen at noon, according to an update from the airport. The airport’s departure level reopened to allow people to exit the area, the airport said early Thursday morning.

The Brightline train service has been temporarily suspended between Miami and Fort Lauderdale, the service said on social media.

Additionally, Broward County Public Schools announced the district will close Thursday.

https://www.cnn.com/2023/04/12/weather/florida-flash-flood-fort-lauderdale/index.html

PLx Enters Stalking Horse Asset Purchase Agreement to Sell VAZALORE, Substantially All Assets

 PLx Pharma Inc. (NASDAQ: PLXP) (“PLx” or the “Company”), is a commercial-stage drug delivery platform technology company focused on its clinically-validated and patent-protected PLxGuard™ and VAZALORE®, an FDA-approved liquid-filled aspirin capsule, available in 81 mg and 325 mg doses. The Company today announced that it entered into a stalking horse asset purchase agreement (the “APA”) with PLx Acquisition Company, LLC, a wholly-owned subsidiary of Greenwood Brands, LLC (“Buyer”), to acquire substantially all of the Company’s assets (the “Sale”).

The Company intends to file voluntary petitions for relief under Chapter 11 of Title 11 of the U.S. Code in the U.S. Bankruptcy Court for the District of Delaware (the “Bankruptcy Court”) within the next two business days. The Sale would also be subject to higher and better offers the Company may receive during an auction process.

Pursuant to the terms and subject to the conditions of the APA, the purchase price is $100,000 in cash, plus a credit bid of $3 million, plus Buyer’s assumption of certain liabilities.

The APA is subject to certain customary closing conditions, including certain orders being entered by the Bankruptcy Court.

The APA remains subject to higher and better offers, as well as approval of the Bankruptcy Court. The APA provides for a breakup fee equal to $100,000 and for reimbursement of up to $400,000 of the Buyer’s expenses incurred in connection with the APA, each of which is payable upon certain termination events as specified in the APA.

The above description of the APA and the transactions contemplated, including the Sale, does not purport to be complete. Please refer to the Company’s Form 8-K, filed with the U.S, Securities and Exchange Commission on April 12, 2023, for the full text of the APA.

https://finance.yahoo.com/news/plx-pharma-inc-enters-stalking-212400196.html

Takeda taps Innate for a new coeliac approach

 Takeda's interest in coeliac disease has been apparent for some years, though its work so far has focused on targeting gluten with small molecules. Last week’s deal with Innate Pharma takes it into new territory – antibody drug conjugates. But others are already testing biological projects.

The Innate research deal is still preclinical, with work due to start against an undisclosed target using a panel of Innate antibodies, so its specific direction is unknown for now. Chugai and Amgen are the other big names working in coeliac disease with antibody approaches, while Pfizer also has a couple of assets in early trials, albeit at arm's length.

Only Takeda has deployed real business development efforts in this disease, with the Innate deal its fourth since 2019. The tie-up is the first with disclosed terms: the French company receives $5m up front and a promise of up to $410m in milestones, depending on progress.

The Japanese developer’s other projects are believed to work by desensitising sufferers to gluten or by degrading it. The ADC deal adds another shot on goal rather than moving away from gluten as a target; phase 2 trials are ongoing with TAK-101 and TAK-062, and TAK-227 seems to still be in active development, although plans are unclear.

Takeda's coeliac disease effort
Project	Mechanism	Status	Origin
TAK-101	Gliadin inhibitor; T-cell inhibitor	Ph2 fully recruited, PCD early 2024	Takeda exercised option to license project from Cour in 2019
TAK-062 (zamaglutenase)	Glutenase	Large ph2 ongoing, PCD 2025	Bought via PVP Biologics in 2020
TAK-227 (ZED1227)	Transglutaminase 2 inhibitor	No new trials started since Takeda bought licence; ph2a published in NEJM	Bought US rights from Dr Falk Pharma and Zedira in 2022
ADC research project	Against undisclosed target	Preclinical	Licensed from Innate in 2023, $5m up front
PCD=primary completion date on clinicaltrials.gov. Source: Evaluate Pharma & company statements.

As for other industry approaches, work is still early and data some way off. Fellow Japanese developer Chugai looks to be committed, having moved a novel project into a large phase 1 trial last year.

DONQ52 is described as a multi-specific antibody covering more than 25 gluten-derived peptides, including all immune-dominant gluten peptides for coeliac disease. The MAb is said to work by directly inhibiting gluten-dependent T-cell activation; Chugai also started a large trial testing a novel digital biomarker of coeliac disease last year, which signals real interest in this disease.

Amgen and Calypso are both testing their IL-15 targeted MAbs in coeliac patients, with the former’s large phase 2b trial one of the largest ongoing coeliac studies. Data are unlikely to emerge before 2024, however. These agents are also in development in other autoimmune conditions.

Interestingly, Regeneron is running a TCR sequencing and transcriptional profiling study, which suggests that the US biotech might also be mulling antibody approaches to the disease.

A number of small private developers have ongoing early-stage efforts targeting gluten in various ways, including Immunogenx, Anokion and the Evotec spin-out Topas.

Anokion boasts Pfizer as partner of sorts, although the big pharma does not appear to have any rights over KAN-101. Pfizer injected $35m into Anokion last year and is named as a collaborator on its recently started trial. According to the private group, its project is designed to induce tolerance to gliadin, a core component of gluten, through natural pathways in the liver.

Pfizer’s Jac3/Tec inhibitor ritlecitinib, which is awaiting news on approval in alopecia, is in a small phase 2 academic trial in coeliac, with the pharma giant again listed as a collaborator.   

It will be some time before any of these projects moves into late-stage testing, a step that only one novel project has managed, in recent years at least. 9 Meters' lazarotide failed last year in phase 3. GSK also bowed out in 2022, as it abandoned work on a project bought from Sitari back in 2019.

The coeliac disease pipeline (ex-Takeda)
Project	Company	Mechanism	Status
Ordesekimab	Amgen/ Provention Bio	Anti-IL-15 MAb	Ph2 Proactive trial recruiting, PCD late 2023
TMP-502	Topas Therapeutics	Antigen targeting project	Ph2 recruiting, PCD 2024
IMGX-003/ latiglutenase	Immunogenx	Recombinant gluten-specific protease	Ph2 crossover study ongoing, PCD April 2024
Ritlecitinib	Pfizer	Jak3/Tec inhibitor	Ph2 recruiting, PCD January 2024 (academic sponsored)
DONQ52	Chugai	MAb against human leukocyte antigen-DQ2	Ph1 recruiting, PCD 2024
KAN-101	Anokion /Pfizer	Gliadin sensitizer	Ph1/2 recruiting, PCD 2024
CALY-002	Calypso Biotech	Anti-IL-15 MAb	Ph1 recruiting, PCD Sep 2023
PCD=primary completion date on clinicaltrials.gov. Source: Evaluate Pharma & company statements. List not necessarily exhaustive.  https://www.evaluate.com/vantage/articles/news/deals/takeda-taps-innate-new-coeliac-approach

U.S., Cuban officials discuss migration as COVID border restrictions set to end

 U.S. and Cuban officials discussed migration issues on Wednesday as the Biden administration braces for the end of COVID-era border restrictions that have blocked Cubans in recent months from crossing into the United States from Mexico.

The high-level meeting in Washington followed one held in Havana in November and comes a year after the Democratic administration of U.S. President Joe Biden resumed migration talks after a long hiatus under former President Donald Trump, a Republican seeking reelection in 2024.

The U.S. State Department offered few details about the latest discussions, saying in a statement the talks "highlighted areas of successful cooperation on migration, while also identifying issues that have been obstacles."

The head of the Cuban delegation, Deputy Foreign Minister Carlos Fernandez de Cossio, said beforehand that "extreme and inhumane measures" have hurt Cuban livelihoods and spurred emigration, a reference to the U.S. economic embargo of Cuba and other sanctions.

Asked about the accusation, a State Department official stressed that the embargo is enshrined in congressional law and includes exemptions for exports of food, medicine and other humanitarian goods heading to Cuba.

The U.S. embassy in Havana resumed full immigrant visa processing and consular services in January for the first time since 2017 in a bid to stem record numbers of Cubans trying to enter the United States from Mexico.

After Biden adopted more restrictive border security measures in January, the number of Cubans and other migrants caught at the border plummeted.

However, the Biden administration is preparing for a possible rise in illegal crossings with COVID restrictions at the U.S.-Mexico border set to lift on May 11.

https://www.yahoo.com/news/u-cuban-officials-discuss-migration-212902481.html

Vertex/CRISPR's gene editing therapy cost effective at $1.9 million - pricing review group

 Vertex Pharmaceuticals Inc and CRISPR Therapeutics AG's one-dose gene editing therapy for sickle cell disease would be cost effective if priced at up to $1.9 million, an influential U.S. drug pricing group said on Wednesday.

The two companies are hoping to get approval for the world's first therapy based on Nobel prize-winning CRISPR technology, for two types of blood disorders - sickle cell disease (SCD) and transfusion-dependent beta thalassemia.

They expect to potentially cure SCD through a single dose of the therapy. SCD is a genetic disorder that causes strokes, organ damage, severe pain and early death and affects roughly 100,000 people in the United States.

In its draft report, the Institute for Clinical and Economic Review (ICER) said a price range between $1.2 million and $1.7 million annually would meet some commonly used thresholds for cost effectiveness, in the health care system perspective.

ICER is not a government agency and has no say on the drug prices that manufacturers set, but many large health insurers take its reports into account when they negotiate prices with drug manufacturers and determine patient access.

Taking into account broader societal benefits of curing the disease, ICER said a price range between $1.3 million and $1.9 million would be cost effective.

Gene therapies have been pricey and their list prices have crossed the million-dollar mark in recent years.

Last year, Australian drugmaker CSL Ltd set the list price of its gene therapy for blood disorder hemophilia B at a record $3.5 million, while bluebird bio priced its gene therapy for beta thalassemia at $2.8 million.

More than half a dozen companies are developing cutting edge gene therapies for sickle cell disease after ignoring it for decades, despite calls from patient advocates to do more.

SCD occurs among about 1 out of every 365 Black or African-American births, according to the U.S. Centers for Disease Control and Prevention estimates.

Novartis AG, Sangamo Therapeutics and CRISPR Therapeutics and Vertex Pharmaceuticals are some of the drugmakers working on a gene therapy for SCD.

https://finance.yahoo.com/news/vertex-crisprs-gene-editing-therapy-213109534.html