Connect with us

International

News wrap: Equillium axes Metacrine merger; Two pharmas pen ADC deals

Immunobiology biotech Equillium announced a “mutual termination” of an anticipated merger with Rich Heyman-chaired Metacrine a little over three months…

Published

on

Immunobiology biotech Equillium announced a “mutual termination” of an anticipated merger with Rich Heyman-chaired Metacrine a little over three months after the initial announcement of the all-stock agreement.

According to SEC filings, neither Equillium nor Metacrine will pay a termination fee.

Bruce Steel

Equillium CEO Bruce Steel said in a statement on Dec. 23 that Equillium started looking into acquiring Metacrine in early 2022 in an attempt to add cash runway “in a very difficult financing market.” Back in September, the companies announced that a merger would add $33 million to Equillium’s balance sheet and extend the runway through 2024. But the company has since found a different partner in Ono Pharmaceutical.

“However, our recent strategic partnership with Ono Pharmaceutical is expected to extend our cash runway into 2025, and possibly further with potential option exercise and milestone payments,” Steel said.

Earlier this month, Equillium entered into an agreement with Ono that included a $26 million upfront payment. Ono will have the exclusive option to purchase the rights, including commercialization, to monoclonal antibody itolizumab in the United States, Canada, Australia and New Zealand.

There is a potential for up to another $138.5 million in milestone payments while Equillium continues R&D with itolizumab, including two studies of the drug’s impact on acute graft-versus-host disease and lupus nephritis.

Katherine Lewin

Merck KGaA and Amgen dish cash for biotech ADCs

Merck KGaA is hedging its bets on the STING pathway. It has tapped Mersana Therapeutics for a two-target deal for STING agonist antibody drug conjugates, or ADCs, a type of treatment that arms an antibody, which acts as an internal compass, with a cell-killing drug.

Mersana will get $30 million upfront, and will be eligible for up to $800 million in potential downstream milestones plus royalties.

GSK also has a pact with Mersana on STING agonist ADCs. Last year, AstraZeneca signed a STING deal with F-star, and recently BioNTech signed a deal with Ryvu Therapeutics. But these deals come after others left the field. Novartis walked away from its STING program in 2019 and Nimbus also culled its efforts.

Separately, Amgen has enlisted South Korean biotech LegoChem Biosciences for a five-target ADC deal. The duo did not disclose the upfront payment, but said the deal could be good for $1.25 billion in total.

Last year, Czech-based Sotio Biotech also paid $29.5 million upfront for a deal with LegoChem. That deal similarly was for five targets and worth a potential $1 billion.

— Lei Lei Wu 

Peptides get the spotlight in new Merck deal

Merck is tapping a partner to explore peptide-drug conjugates, or PDCs.

Japan’s PeptiDream is tasked with identifying peptide candidates for use in PDCs in a new pact worth as much as $2.1 billion, including an unspecified upfront payment, plus milestones. Merck will get exclusive rights to conjugate those peptides to cytotoxic payloads — bringing the payloads to specific cells — and take charge of all development.

Merck and PeptiDream have been collaborating on peptide discovery since 2015.

PeptiDream itself lists a dozen of PDCs in its own pipeline for both diagnostic and therapeutic purposes, including a PD-L1 diagnostic PDC partnered with Bristol Myers Squibb and other undisclosed programs with Novartis and RayzeBio.

— Amber Tong

Intercept resubmits NASH drug to FDA

Intercept Pharmaceuticals is moving another hopeful step forward with obeticholic acid as a treatment for nonalcoholic steatohepatitis (NASH), a progressive liver disease.

The biotech announced just before Christmas that it had resubmitted a new drug application to the FDA for obeticholic acid following two positive analyses of its Phase III REGENERATE study. Liver scarring, stiffness and blood levels of liver enzymes all showed improvements in patients that took the drug.

If the agency gives the thumbs-up, it would be the first time that obeticholic acid has been approved for the treatment of NASH “by any regulatory authority in any geography,” according to Intercept. Obeticholic acid is already approved for primary biliary cholangitis as Ocaliva.

The PDUFA target review time by the FDA is expected to be six months, the company said.

The FDA rejected the drug in 2020 for liver scarring due to NASH after disappointing Phase III trials.

Katherine Lewin

Zinc, silver nanocrystal drug fails Covid study

Clene Nanomedicine, which joined a long list of biotechs in testing compounds for Covid-19, has run into the same disappointing result as many others.

Its drug flunked a Phase II study involving non-hospitalized but symptomatic Covid-19 patients, the Salt Lake City-based biotech reported. The trial showed that the drug didn’t help patients’ symptoms resolve more quickly than a placebo.

Rob Etherington

In the trial, which was conducted in Brazil, 288 patients received either a low dose of Clene’s zinc and silver nanocrystal suspension, dubbed CNM-ZnAg, a high dose, or a placebo on top of standard supportive care for up to 21 days. They were then tracked through 28 days.

“No clinical benefit was observed versus placebo,” the company said.

“At this time, we will cease further development for COVID,” CEO Rob Etherington said in a statement.

Clene will focus on its lead asset, a gold nanocrystal-based drug, as a treatment for multiple sclerosis. The drug failed an ALS trial last year.

— Amber Tong

Brii drops one HIV candidate while FDA lifts hold on another

A year ago, in the wake of a safety scare around Merck’s HIV drug islatravir, the FDA placed a clinical hold on a prodrug of islatravir being developed by Brii Bio.

Brii Bio now says the agency has lifted the hold, clearing the way for a planned Phase I study that will test a lower once-weekly oral dose of BRII-732.

The biotech, which has presence in both Durham, NC and Beijing, China, said it’s also exploring partnership opportunities to continue developing the compound as a long-acting option for HIV patients.

Data from the healthy volunteers who were dosed before the study halted suggested an acceptable safety and tolerability profile, as well as promising pharmacokinetics, Brii added.

On the other hand, the same can’t be said about another HIV candidate, BRII-778. Brii said it is shuttering that program based on pharmacokinetic data from a completed Phase I study.

— Amber Tong

Minerva ‘disappointed’ in FDA’s refusal-to-file letter for schizophrenia symptoms treatment

The FDA told Minerva Neurosciences that its October refusal-to-file letter isn’t going away after a meeting in November.

Remy Luthringer

Minerva CEO Remy Luthringer said in a statement that he’s “disappointed” in the FDA’s spurning of roluperidone even after the Nov. 30 meeting to hash out the agency’s longstanding concerns.

Roluperidone is an experimental treatment for the symptoms of schizophrenia, such as the inability to complete tasks or feel pleasure, changes in sleep and a loss of interest and motivation in life.

Luthringer confirmed that the FDA “will not file our NDA for roluperidone for the treatment of negative symptoms of schizophrenia.”

The FDA has had concerns about the drug since 2020, but Minerva pushed ahead anyway. The FDA issued the letter only eight weeks after the company’s approval application in August 2022.

Katherine Lewin

French Biotech gets a €40M credit to fund R&D

André Choulika

France-based cell and gene therapy biotech Cellectis has entered a €40 million ($42.7 million) credit facility agreement with the European Investment Bank. Cellectis will use the funds to further develop its pipeline of CAR-T cell candidates.

The cash will be divided into three tranches. Cellectis will receive €20 million in the first tranche, €15 million in the second and €5 million in the third. The release of the funds will also be subject to certain conditions, which were not detailed.

The financing “is minimally dilutive for our shareholders, is excellent news for Cellectis and a recognition of the work accomplished by our teams,” Cellectis CEO André Choulika said in a statement.

-Tyler Patchen

Novartis to pay $245M to put an end to antitrust litigation — report

Novartis will pay $245 million to bring an end to an antitrust case.

According to a report from Reuters, the payment will end accusations that Novartis tried to delay the launch of generic forms of its hypertension drug Exforge in the US. Reuters said the litigation came from a 2011 licensing agreement between Novartis and Par Pharmaceuticals. Both Novartis and Par were accused of entering into an illegal agreement to delay the launch of less expensive and generic forms of Exforge.

Reuters stated that the plaintiffs had accused Par of agreeing not to launch the generic for two years after one of Novartis’ patents had expired, with the Swiss pharma alleging to have also agreed to not compete with Par by launching its own Exforge generic during the 180-day “exclusivity period” after Par entered the market.

The case saw groups such as CVS, Kroger, Walgreens and Rite Aid in the list of plaintiffs when litigation kicked off in 2018.

Tyler Patchen

Read More

Continue Reading

International

There will soon be one million seats on this popular Amtrak route

“More people are taking the train than ever before,” says Amtrak’s Executive Vice President.

Published

on

While the size of the United States makes it hard for it to compete with the inter-city train access available in places like Japan and many European countries, Amtrak trains are a very popular transportation option in certain pockets of the country — so much so that the country’s national railway company is expanding its Northeast Corridor by more than one million seats.

Related: This is what it's like to take a 19-hour train from New York to Chicago

Running from Boston all the way south to Washington, D.C., the route is one of the most popular as it passes through the most densely populated part of the country and serves as a commuter train for those who need to go between East Coast cities such as New York and Philadelphia for business.

Veronika Bondarenko captured this photo of New York’s Moynihan Train Hall. 

Veronika Bondarenko

Amtrak launches new routes, promises travelers ‘additional travel options’

Earlier this month, Amtrak announced that it was adding four additional Northeastern routes to its schedule — two more routes between New York’s Penn Station and Union Station in Washington, D.C. on the weekend, a new early-morning weekday route between New York and Philadelphia’s William H. Gray III 30th Street Station and a weekend route between Philadelphia and Boston’s South Station.

More Travel:

According to Amtrak, these additions will increase Northeast Corridor’s service by 20% on the weekdays and 10% on the weekends for a total of one million additional seats when counted by how many will ride the corridor over the year.

“More people are taking the train than ever before and we’re proud to offer our customers additional travel options when they ride with us on the Northeast Regional,” Amtrak Executive Vice President and Chief Commercial Officer Eliot Hamlisch said in a statement on the new routes. “The Northeast Regional gets you where you want to go comfortably, conveniently and sustainably as you breeze past traffic on I-95 for a more enjoyable travel experience.”

Here are some of the other Amtrak changes you can expect to see

Amtrak also said that, in the 2023 financial year, the Northeast Corridor had nearly 9.2 million riders — 8% more than it had pre-pandemic and a 29% increase from 2022. The higher demand, particularly during both off-peak hours and the time when many business travelers use to get to work, is pushing Amtrak to invest into this corridor in particular.

To reach more customers, Amtrak has also made several changes to both its routes and pricing system. In the fall of 2023, it introduced a type of new “Night Owl Fare” — if traveling during very late or very early hours, one can go between cities like New York and Philadelphia or Philadelphia and Washington. D.C. for $5 to $15.

As travel on the same routes during peak hours can reach as much as $300, this was a deliberate move to reach those who have the flexibility of time and might have otherwise preferred more affordable methods of transportation such as the bus. After seeing strong uptake, Amtrak added this type of fare to more Boston routes.

The largest distances, such as the ones between Boston and New York or New York and Washington, are available at the lowest rate for $20.

Read More

Continue Reading

International

The next pandemic? It’s already here for Earth’s wildlife

Bird flu is decimating species already threatened by climate change and habitat loss.

I am a conservation biologist who studies emerging infectious diseases. When people ask me what I think the next pandemic will be I often say that we are in the midst of one – it’s just afflicting a great many species more than ours.

I am referring to the highly pathogenic strain of avian influenza H5N1 (HPAI H5N1), otherwise known as bird flu, which has killed millions of birds and unknown numbers of mammals, particularly during the past three years.

This is the strain that emerged in domestic geese in China in 1997 and quickly jumped to humans in south-east Asia with a mortality rate of around 40-50%. My research group encountered the virus when it killed a mammal, an endangered Owston’s palm civet, in a captive breeding programme in Cuc Phuong National Park Vietnam in 2005.

How these animals caught bird flu was never confirmed. Their diet is mainly earthworms, so they had not been infected by eating diseased poultry like many captive tigers in the region.

This discovery prompted us to collate all confirmed reports of fatal infection with bird flu to assess just how broad a threat to wildlife this virus might pose.

This is how a newly discovered virus in Chinese poultry came to threaten so much of the world’s biodiversity.

H5N1 originated on a Chinese poultry farm in 1997. ChameleonsEye/Shutterstock

The first signs

Until December 2005, most confirmed infections had been found in a few zoos and rescue centres in Thailand and Cambodia. Our analysis in 2006 showed that nearly half (48%) of all the different groups of birds (known to taxonomists as “orders”) contained a species in which a fatal infection of bird flu had been reported. These 13 orders comprised 84% of all bird species.

We reasoned 20 years ago that the strains of H5N1 circulating were probably highly pathogenic to all bird orders. We also showed that the list of confirmed infected species included those that were globally threatened and that important habitats, such as Vietnam’s Mekong delta, lay close to reported poultry outbreaks.

Mammals known to be susceptible to bird flu during the early 2000s included primates, rodents, pigs and rabbits. Large carnivores such as Bengal tigers and clouded leopards were reported to have been killed, as well as domestic cats.

Our 2006 paper showed the ease with which this virus crossed species barriers and suggested it might one day produce a pandemic-scale threat to global biodiversity.

Unfortunately, our warnings were correct.

A roving sickness

Two decades on, bird flu is killing species from the high Arctic to mainland Antarctica.

In the past couple of years, bird flu has spread rapidly across Europe and infiltrated North and South America, killing millions of poultry and a variety of bird and mammal species. A recent paper found that 26 countries have reported at least 48 mammal species that have died from the virus since 2020, when the latest increase in reported infections started.

Not even the ocean is safe. Since 2020, 13 species of aquatic mammal have succumbed, including American sea lions, porpoises and dolphins, often dying in their thousands in South America. A wide range of scavenging and predatory mammals that live on land are now also confirmed to be susceptible, including mountain lions, lynx, brown, black and polar bears.

The UK alone has lost over 75% of its great skuas and seen a 25% decline in northern gannets. Recent declines in sandwich terns (35%) and common terns (42%) were also largely driven by the virus.

Scientists haven’t managed to completely sequence the virus in all affected species. Research and continuous surveillance could tell us how adaptable it ultimately becomes, and whether it can jump to even more species. We know it can already infect humans – one or more genetic mutations may make it more infectious.

At the crossroads

Between January 1 2003 and December 21 2023, 882 cases of human infection with the H5N1 virus were reported from 23 countries, of which 461 (52%) were fatal.

Of these fatal cases, more than half were in Vietnam, China, Cambodia and Laos. Poultry-to-human infections were first recorded in Cambodia in December 2003. Intermittent cases were reported until 2014, followed by a gap until 2023, yielding 41 deaths from 64 cases. The subtype of H5N1 virus responsible has been detected in poultry in Cambodia since 2014. In the early 2000s, the H5N1 virus circulating had a high human mortality rate, so it is worrying that we are now starting to see people dying after contact with poultry again.

It’s not just H5 subtypes of bird flu that concern humans. The H10N1 virus was originally isolated from wild birds in South Korea, but has also been reported in samples from China and Mongolia.

Recent research found that these particular virus subtypes may be able to jump to humans after they were found to be pathogenic in laboratory mice and ferrets. The first person who was confirmed to be infected with H10N5 died in China on January 27 2024, but this patient was also suffering from seasonal flu (H3N2). They had been exposed to live poultry which also tested positive for H10N5.

Species already threatened with extinction are among those which have died due to bird flu in the past three years. The first deaths from the virus in mainland Antarctica have just been confirmed in skuas, highlighting a looming threat to penguin colonies whose eggs and chicks skuas prey on. Humboldt penguins have already been killed by the virus in Chile.

A colony of king penguins.
Remote penguin colonies are already threatened by climate change. AndreAnita/Shutterstock

How can we stem this tsunami of H5N1 and other avian influenzas? Completely overhaul poultry production on a global scale. Make farms self-sufficient in rearing eggs and chicks instead of exporting them internationally. The trend towards megafarms containing over a million birds must be stopped in its tracks.

To prevent the worst outcomes for this virus, we must revisit its primary source: the incubator of intensive poultry farms.

Diana Bell does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

Read More

Continue Reading

International

This is the biggest money mistake you’re making during travel

A retail expert talks of some common money mistakes travelers make on their trips.

Published

on

Travel is expensive. Despite the explosion of travel demand in the two years since the world opened up from the pandemic, survey after survey shows that financial reasons are the biggest factor keeping some from taking their desired trips.

Airfare, accommodation as well as food and entertainment during the trip have all outpaced inflation over the last four years.

Related: This is why we're still spending an insane amount of money on travel

But while there are multiple tricks and “travel hacks” for finding cheaper plane tickets and accommodation, the biggest financial mistake that leads to blown travel budgets is much smaller and more insidious.

A traveler watches a plane takeoff at an airport gate.

Jeshoots on Unsplash

This is what you should (and shouldn’t) spend your money on while abroad

“When it comes to traveling, it's hard to resist buying items so you can have a piece of that memory at home,” Kristen Gall, a retail expert who heads the financial planning section at points-back platform Rakuten, told Travel + Leisure in an interview. “However, it's important to remember that you don't need every souvenir that catches your eye.”

More Travel:

According to Gall, souvenirs not only have a tendency to add up in price but also weight which can in turn require one to pay for extra weight or even another suitcase at the airport — over the last two months, airlines like Delta  (DAL) , American Airlines  (AAL)  and JetBlue Airways  (JBLU)  have all followed each other in increasing baggage prices to in some cases as much as $60 for a first bag and $100 for a second one.

While such extras may not seem like a lot compared to the thousands one might have spent on the hotel and ticket, they all have what is sometimes known as a “coffee” or “takeout effect” in which small expenses can lead one to overspend by a large amount.

‘Save up for one special thing rather than a bunch of trinkets…’

“When traveling abroad, I recommend only purchasing items that you can't get back at home, or that are small enough to not impact your luggage weight,” Gall said. “If you’re set on bringing home a souvenir, save up for one special thing, rather than wasting your money on a bunch of trinkets you may not think twice about once you return home.”

Along with the immediate costs, there is also the risk of purchasing things that go to waste when returning home from an international vacation. Alcohol is subject to airlines’ liquid rules while certain types of foods, particularly meat and other animal products, can be confiscated by customs. 

While one incident of losing an expensive bottle of liquor or cheese brought back from a country like France will often make travelers forever careful, those who travel internationally less frequently will often be unaware of specific rules and be forced to part with something they spent money on at the airport.

“It's important to keep in mind that you're going to have to travel back with everything you purchased,” Gall continued. “[…] Be careful when buying food or wine, as it may not make it through customs. Foods like chocolate are typically fine, but items like meat and produce are likely prohibited to come back into the country.

Related: Veteran fund manager picks favorite stocks for 2024

Read More

Continue Reading

Trending