Sekėjai

Ieškoti šiame dienoraštyje

2023 m. spalio 25 d., trečiadienis

The ‘Devil’s Playground’ of Urban Combat That Israel Is Preparing to Enter.

 

"Heavy fire from rooftops and booby-trapped apartments. Armor-piercing projectiles blowing up troop carriers. Fighters blending in with civilians, launching drone ambushes or surging from tunnels full of enough ammunition, food and water to sustain a long war.

As the Israeli army gathers tanks at the Gaza Strip border for a threatened invasion aimed at crushing Hamas, experts are warning that the country’s troops could face some of the fiercest street-to-street combat since World War II in Gaza City and other densely packed areas.

Urban warfare studies and American officials offer dire comparisons to Iraq: Think of Fallujah, Iraq, in 2004, the most intense battles that U.S. troops had faced since Vietnam; or the nine-month fight to defeat the Islamic State group in Mosul, Iraq, in 2016, which led to 10,000 civilian deaths. Then multiply the destructive toll, possibly exponentially.

Hamas has three to five times as many fighters — perhaps 40,000 in all — as the Islamic State had in Mosul. It can draw reserves from a young, restive population and has international support from countries like Iran. Even on its own, Hamas’ leadership has had years to prepare for battle across Gaza, including in city streets, where the superiority of tanks and precise munitions can be stymied by guerrilla tactics.

“It’s going to be ugly,” said Lt. Col. Thomas Arnold, a U.S. Army strategist who has published studies on urban operations in the Middle East. “Cities are the devil’s playground; they make everything infinitely more difficult.”

Benjamin Netanyahu, Israel’s prime minister, has vowed to “demolish Hamas.” Without sharply defining what that means, he pledged to remove the group from Gaza after its Oct. 7 attack on Israel killed 1,400 people and led to the kidnapping of more than 200 others.

But Gaza, heavily urbanized, with Hamas deeply entrenched, is an especially complex battlefield. Concerned about the challenges ahead, the Biden administration has sent senior military officers to provide advice to the Israelis, based on their own experiences in Iraq, while pressing Israel to delay the invasion to leave more time to negotiate the release of hostages taken by Hamas and to deliver more humanitarian aid. American officials worry that Israel lacks a plan with clear, achievable objectives that would prevent an enormous loss of life among Gaza’s more than 2 million Palestinian civilians.

“I’ve encouraged them to conduct their operations in accordance with the law of war,” Defense Secretary Lloyd Austin said Sunday.

With history as a guide, three factors would most likely shape a ground war in Gaza’s cities: the urban environment, the interaction between fighters and civilians, and political pressures.

The Landscape

The Gaza Strip is about 140 square miles, a narrow band slightly larger in area than Las Vegas, with a cluster of urban population centers. Gaza City, the capital, has around 700,000 people packed into around 20 square miles, with more tall buildings than U.S.-led forces faced in the battle for Mosul, creating a more dangerous three-dimensional front.

Many urban invasions — from the Middle Ages to modernity — have started off with a rapid advance, only to later bog down in districts that favor defenders. Mosul is a prime example.

Cities can also be malleable. Israel has destroyed hundreds of Gaza buildings in airstrikes. Hamas, long before its assault on Israel this month, had built hundreds of miles of tunnels under Gaza City that can be used to move among attack positions, hide hostages and protect supplies.

Additional surprises — rocket factories under schools, weapons stored in mosques — are likely to be found if Israel invades.

In Mosul, where the Islamic State had less time to dig in, fighters punched holes through walls so they could fire at tanks through buildings. They used cheap drones with cameras to guide car-bomb drivers and stretched tarps over streets to hide supply runs.

There and elsewhere, explosives have been wired to rubble and apartment doors. Refrigerators, burning trash and engine blocks have been used to impede military vehicles.

“Cities can mitigate your technological advantages,” said Arnold, who is completing a doctorate at the University of Virginia. “While Israel is biding its time — setting the conditions, dropping buildings, getting its troops ready — the other side is almost certainly getting ready as well.”

The People

Civilian or combatant? Urban warfare tends to blur the line more often, in deadly ways.

Israel has already been accused of killing thousands of civilians in air attacks, including 1,200 children, according to the Hamas-run Ministry of Health in Gaza. Those figures could not be independently verified, but the risk to civilians clearly remains high.

Even as Israel encourages people in Gaza City to move south to safer areas, many are obeying instructions by Hamas or religious leaders to stay, or saying they cannot afford to go.

It’s a familiar problem. In 2004, the Bush administration gave U.S. Marines only 72 hours to plan an invasion of Fallujah after four American contractors were killed, their mutilated bodies lashed to a bridge. Commanders warned that a revenge-driven operation would endanger civilians and fail, and they pulled back after heavy losses, giving Iraqis six months to flee before a second push.

An estimated 30,000 to 90,000 stayed.

“A lot of the innocent civilians were not allowed to leave,” said Freddie Blish, a retired U.S. Marine lieutenant colonel who was deployed to Fallujah as a combat engineer. “And that’s what’s going to happen with Hamas; they’re going to use them as human shields.”

Israel has emphasized that it does not target civilians. But in urban battles, commanders often take fire from structures housing both fighters and families, forcing a judgment call: Clear the rooms with troops, putting them at risk, or call in a heavier response that might kill civilians.

The tolerance for troop losses tends to decrease as urban warfare drags on.

In Mosul, after casualty rates for Iraqi troops reached 50%, airstrikes increased. The Iraqis often demanded that their U.S. partners take down more than just one building.

“They wouldn’t move forward until we leveled the block,” said Amos Fox, a U.S. military planner in Iraq during the Mosul operation.

It took 252 days and 100,000 Iraqi troops, with U.S. air support, to rid Mosul of ISIS. Along with 10,000 civilian deaths, 8,200 Iraqi soldiers suffered casualties, and at least 13,000 buildings were made uninhabitable, according to the United Nations.

Israeli troops, while better trained than the Iraqi army, with years to prepare invasion plans and special engineering units for challenges like tunnels, will face a tougher adversary.

There were 3,000 to 5,000 ISIS fighters in Mosul at the start of the operation, according to initial U.S. military estimates, and a few thousand more came later. Hamas’ military wing, the Al Qassam Brigades, is estimated to number 30,000 to 40,000, not including thousands of militants with other groups like Palestinian Islamic Jihad.

Most ISIS fighters were also from other countries. Hamas fighters grew up in Gaza. Their units are bonded together by location, family, faith and shared frustration with Israel.

“They know the streets. They know the tunnels,” said Blish, the retired lieutenant colonel. “It’s going to be a tough slog.”

Geopolitics

Recent wars have rarely gone as quickly as either side expected: Mosul was supposed to be cleared in three months, not nine. And as the death toll mounts and economies crater, international support often weakens.

Israel also has experience with the political and military challenge that comes with extended conflict. Israel’s last ground invasion in Gaza, in 2014, lasted less than three weeks. As Spencer at West Point’s Modern War Institute recently pointed out, Israel “has fought almost every war of its history in a race against time, seeking to achieve its goals before international pressure forces it to stop operations.”

In the current case, Israeli officials have warned that they are expecting several months of fighting, if not years. That would mean a spike in demand for weapons, and added global volatility. American officials are worried about the potential for the war to spread to Lebanon and Iran, along with possible attacks on U.S. troops in Iraq. Those concerns could affect how Washington advises Israel as the conflict evolves.

In past wars, the Israeli public supported military operations as long as they showed progress, with evidence of destroyed weapons stockpiles and other tangible results. Casualties — 66 Israeli soldiers died in the 2014 war — mattered less than “perceptions of the campaign’s success,” according to a Rand Corp. report from 2017.

Now, however, polls show that Israelis have less faith in their government under Netanyahu’s divisive leadership and after his failure to prevent the recent attack. The definition of success is also broader this time and may be harder to achieve in part because Hamas has grown stronger with Iran’s help, vastly increasing its rocket stockpiles and deploying new technology like drones.

Hamas and Israel have already engaged in a contest for sympathy that has spurred angry protests around the world and again made the Middle East a source of international anxiety. How both sides fight with arsenals of weapons in crowded cities will create an even more transformative test of competing narratives and willpower as long as the war lasts." [1]

1.  The ‘Devil’s Playground’ of Urban Combat That Israel Is Preparing to Enter. Cave, Damien.  New York Times, Late Edition (East Coast); New York, N.Y.. 25 Oct 2023.

Pfizeris pražiopsojo milijardus dolerių biotechnologijoje. Lietuvoje - tyla. Tik varlės kurkia pavasarį


„Negalite visiškai kaltinti tik Pfizerio vadovus, tačiau Roche įsigijimas už 7 milijardus dolerių žarnyno ligų gydymo priemonę, kuri Pfizer priklausė iki praėjusių metų, nėra puikus vaizdas.

 

Sudarant sandorį, kuris dabar atrodo, kaip „Moneyball“ biotechnologinė versija, Roivantas paskelbė parduodantis turtą, kurį tik prieš 11 mėnesių nemokamai gavo iš „Pfizer“.

 

(The Wall Street Journal pranešė apie derybas dar liepos mėn.) Didelės farmacijos įmonės, orientuotos į vaistų pramonės atitikmenį laisvųjų agentų pasirašymui, dažnai nepastebės vienos iš savo perspektyvių.

 

Pernai gruodį „Pfizer“ licencijavo monokloninį antikūną „Roivant“, turėdamas idėją, kad biotechnologijos įmonė „Roivant“ padengs dideles vaisto, skirto, su uždegimu susijusiam, baltymui, vadinamam TL1A, kūrimo išlaidas, o „Pfizer“ turėtų 25% akcijų. Greitis, kuriuo vaistas pateko iš „Pfizer“ į „Roivant“, o paskui į „Roche“, pribloškė net Volstryto veteranus, ilgai įpratusius matyti, kaip farmacija perduoda daug žadančius junginius. „Pfizer“ tikrai nesitikėjo, kad vienas iš savo didelių konkurentų farmacijos srityje taip greitai smogs.

 

Barclays analitikas Carteris Gouldas per antrojo ketvirčio pajamų pokalbį su Pfizer vadovybe nepatogiai apsikeitė nuomonėmis po to, kai WS žurnalas pranešė apie Roche derybas: „Praėjusių metų pabaigoje išleidote savo TL1A licenciją. Tada jūsų partneris atsigręžia ir parduoda ją gerokai brangiau... . Ar tokia įvykių eiga buvo naudinga „Pfizer“ akcininkams?

 

Atsakydamas Pfizer verslo inovacijų vadovas Aamiras Malikas sakė, kad sandoris buvo dalis sprendimo dėl mokslinių tyrimų ir plėtros prioritetų nustatymo ir, kadangi Pfizer pasilieka visas teises į vaistą už Japonijos ir JAV ribų, bei 25 % akcijų paketą, bendradarbiavimas su „Roivant“ vis tiek padidintų „Pfizer“ pajamas be papildomų mokslinių tyrimų ir plėtros išlaidų.

 

Tačiau galiausiai Roivantas neturėjo jokių papildomų išlaidų. Kaip pažymi „TD Cowen“ analitikas Yaronas Werberis, Roivantas patyrė 15 mln. dolerių išlaidų ir gauna daugiau nei 5 mlrd. dolerių grynųjų.

 

Pagal sandorio sąlygas Šveicarijos farmacijos milžinė iš anksto sumokės 7,1 mlrd. dolerių už „Telavant Holdings“ ir artimiausiu metu sumokės 150 mln.dolerių, pasiekus tarpinį tikslą.  Roivantas turi paimti grynuosius pinigus ir panaudoti juos naujoms investicijoms.

 

Sąžiningai kalbant, Pfizer atžvilgiu, gydymas vis dar nėra patvirtintas Maisto ir vaistų administracijos ir dar reikia pamatyti, koks gali būti tikrasis jo potencialas. Tačiau kai tik Pfizer atsisakė terapijos, TL1A taikomi vaistai staiga tapo populiariausiu dalyku.

 

„Pfizer“ paskelbė apie savo sandorį su „Roivant“ 2022 m. gruodžio 1 d. Gruodžio 7 d. konkuruojančios biotechnologijos „Prometheus Biosciences“, kuriančios panašų vaistą, akcijos išaugo po to, kai tyrimai, tiriantys jos vaistą nuo opinio kolito ir Krono ligos, buvo teigiami. Tada sausio mėn. Roivantas pranešė apie teigiamus vidurinės stadijos opinio kolito tyrimo rezultatus. Iki balandžio mėnesio „Merck“ sutiko sumokėti 10,8 mlrd. dolerių už „Prometheus“ įsigijimą.

 

Didelės šių kainų etiketės atspindi farmacijos susidomėjimą vaistais, kurie veikia nuo autoimuninių ligų, nes kai kurios didžiausių šios kategorijos populiariųjų – AbbVie Humira ir Johnson & Johnson Stelara – praranda patentinę apsaugą. Tokių vaistų esmė yra ta, kad jie dažnai veikia, esant kelioms indikacijoms, todėl sukuria didžiulį farmacijos potencialą. Interviu žurnalui Roche farmacijos vadovė Teresa Graham teigė, kad vaisto veikimo mechanizmas reiškia, kad jis gali turėti potencialo dermatologijoje, reumatologijoje ir ginekologijoje.

 

"Tai yra 15 milijardų JAV dolerių rinka tik JAV ir tai tik [uždegiminės žarnyno ligos]. Ši molekulė aiškiai turi megablokų potencialą", - sakė Graham.

 

Priimdama sprendimą licencijuoti savo vaistą, „Pfizer“ galėjo nukentėti nuo laiko šališkumo. 2021 m. „Pfizer“ išleido 6,7 milijardo dolerių, kad įsigytų bendrovę „Arena Pharmaceuticals“, kuri davė jai geriamąsias piliules opiniam kolitui gydyti, kurios rinkoje pasirodys pirmos. Šis vaistas buvo patvirtintas anksčiau šį mėnesį ir bus greitesnis Pfizer pinigų uždirbimas. „Leerink Partners“ analitikas Davidas Risingeris prognozuoja, kad 2030 m. pardavimai sieks 2,2 mlrd. dolerių. 

 

„Pfizer“ iš šio sandorio gauna apie 1,4 milijardo dolerių ir gautų naudos iš vaisto komercializavimo. Tačiau matome, kad potencialus blokbasteris nuslysta tuo metu, kai jam sunku papildyti mažėjančias pajamas iš Covid-19, o investuotojai gali nuryti karčią piliulę." [1]

 

Lietuvoje biotechnologijose nedaroma nieko, tik išnaudojami kadaise Janulaičio iš rusų pavogti biotechnologiniai pasiekimai. Tai prie ko čia varlės pavasarį?

 

1. Pfizer Misses Out on a Biotech Home Run. Wainer, David.  Wall Street Journal, Eastern edition; New York, N.Y.. 25 Oct 2023: B.14.

Pfizer Misses Out on a Biotech Home Run. Silence in Lithuania. Only frogs croak in spring


"You can't completely blame Pfizer's executives, yet Roche's $7 billion acquisition of a bowel-disease treatment that Pfizer owned until last year isn't a great look.

In a deal that now feels like a biotech version of "Moneyball," Roivant announced it was selling an asset that only 11 months ago it got for free from Pfizer. (The Wall Street Journal had reported the talks back in July.) Big pharma companies focused on the drug industry equivalent of free agent signings will often overlook one of their own hot prospects.

Pfizer licensed the monoclonal antibody to Roivant last December with the idea that the biotech would shoulder the heavy costs of developing the drug, which targets a protein linked to inflammation called TL1A, while Pfizer would hold on to a 25% equity stake. The speed at which the drug went from Pfizer to Roivant and then to Roche stunned even Wall Street veterans long accustomed to seeing pharma pass on promising compounds. Pfizer certainly didn't anticipate one of its big pharma rivals swooping so quickly.

Barclays analyst Carter Gould had an awkward exchange with Pfizer management during its second quarter earnings call after the Journal reported the Roche talks: "You out-licensed your TL1A late last year. Your partner then turns around and sells it for quite substantially more . . . Were Pfizer shareholders well served by this course of events?"

In response, Pfizer Chief Business Innovation Officer Aamir Malik said that the deal was part of a research-and-development prioritization decision and that since Pfizer was keeping full rights to the drug outside Japan and the U.S. plus the 25% stake, the collaboration with Roivant would still give Pfizer upside without incremental R&D costs.

But in the end there were barely any additional costs for Roivant. As analyst Yaron Werber at TD Cowen notes, Roivant incurred $15 million in expenses and is getting more than $5 billion in cash.

Under the terms of the deal, the Swiss pharmaceutical giant will pay $7.1 billion up front for Telavant Holdings and make a near-term milestone payment of $150 million. Roivant gets to take the cash and use it for new investments.

In fairness to Pfizer, the treatment still isn't approved by the Food and Drug Administration and it remains to be seen what its true potential could be. But as soon as Pfizer let go of the therapy, TL1A-targeting drugs suddenly became the next hot thing.

Pfizer announced its deal with Roivant on Dec. 1, 2022. On Dec. 7, shares of Prometheus Biosciences, a rival biotech developing a similar drug, soared after studies testing its drug in ulcerative colitis and Crohn's disease were positive. Then in January, Roivant reported positive results from a midstage study in ulcerative colitis. By April, Merck agreed to pay an eye-popping $10.8 billion to buy Prometheus.

The high price tags reflect pharma's interest in drugs that work in autoimmune diseases as some of the biggest blockbusters in that category, AbbVie's Humira and Johnson & Johnson's Stelara, lose patent protection. The thing about such drugs is they often work for multiple indications, creating blockbuster potential for big pharma. In an interview with the Journal, Roche's pharma chief, Teresa Graham, said the drug's mechanism of action means it could have potential in dermatology, rheumatology and gynecology.

"This is a $15 billion market just in the U.S. and that's just in [inflammatory bowel disease]. This molecule clearly has megablockbuster potential," said Graham.

In making the decision to license its drug, Pfizer may have been suffering from immediacy bias. Pfizer in 2021 spent $6.7 billion to acquire Arena Pharmaceuticals, which gave it an oral pill for ulcerative colitis that would hit the market first. That drug was approved earlier this month and will be a more immediate moneymaker for Pfizer. David Risinger, an analyst at Leerink Partners, projects 2030 sales of $2.2 billion.

Pfizer is getting about $1.4 billion from this deal and would benefit from the drug's commercialization. But seeing a potential blockbuster slip away at a time when it is struggling to replenish diminishing Covid-19 revenue is a bitter pill for investors to swallow." [1]

  In Lithuania, nothing is being done in biotechnology, only the biotechnological achievements once stolen from the Russians by Janulaitis are being exploited. So what about the frogs in the spring?

1. Pfizer Misses Out on a Biotech Home Run. Wainer, David.  Wall Street Journal, Eastern edition; New York, N.Y.. 25 Oct 2023: B.14.