Sanofi strikes $1bn deal with Fulcrum for muscular dystrophy drug

 Fulcrum Therapeutics has signed a $1bn exclusive licence deal with Sanofi to develop and commercialise the investigational facioscapulohumeral muscular dystrophy (FSHD) drug losmapimod.

Under the agreement, Sanofi gains exclusive commercialisation rights for losmapimod outside of the US. Fulcrum will receive an upfront payment of $80m and is eligible to receive up to $975m in specified regulatory and sales-based milestones, totalling the deal value to more than $1bn.

The drug is currently being investigated in the Phase III REACH clinical trial (NCT05397470), with topline data expected at the end of this year.

Fulcrum exclusively in-licensed the small-molecule drug from GSK in April 2019. Losmapimod is a selective inhibitor of p38α/β mitogen-activated protein kinase (MAPK). The compound has previously been assessed for a wide variety of indications, including rheumatoid arthritis, depression, and Covid-19.

FSHD is a genetic disorder causing progressive weakening and loss of muscle tissue. It primarily affects the muscles of the face, shoulders, and upper arms, but can also involve muscles in other body parts. The condition is caused by a mutation in the DUX4 gene, leading to the production of a protein that is toxic to muscle tissue. Preclinical studies have indicated that losmapimod demonstrated downregulation of DUX4 in patient-derived cell models and restored a healthy muscle phenotype.

The drug was studied in the Phase IIb ReDUX4 trial (NCT04003974), which in 2021 had failed to meet its primary endpoint of change in DUX4-driven gene expression. However, the company said losmapimod was associated with potential improvements in muscle fat infiltration, and functional outcomes such as Reachable Workspace (RWS) compared to the placebo, which informed the Phase III design. The primary endpoint of the 260-patient trial is the absolute change from baseline in RWS.

According to GlobalData’s Pharma Intelligence Center, losmapimod is forecast to generate $269m in 2030.

GlobalData is the parent company of Pharmaceutical Technology.

Fulcrum has other programmes in development, including the drug pociredir, previously named FTX-6058, a small-molecule inhibitor of embryonic ectoderm development (EED) for sickle cell disease. In February 2023, the US Food and Drug Administration (FDA) placed a clinical hold on the investigational drug after finding evidence of haematological malignancies in submitted preclinical data. Consequently, Fulcrum suspended dosing in the Phase Ib trial of pociredir until the FDA lifted the clinical hold in August 2023.

https://finance.yahoo.com/m/ebd5032e-3dd4-3339-bc74-158863619428/sanofi-strikes-%241bn-deal-with.html

Chi Mayor Ups Concerns on What Side He's On If DNC Protesters Break Law, Challenge Cops

 By Mark Glennon of Wirepoints

Whose side will Chicago Mayor Brandon Johnson be on if protesters become lawbreakers at the August Democratic National Convention in Chicago, and how will he direct police to respond?

Concerns that Johnson will side with lawbreakers already are common, and Johnson’s  interview published Sunday by the Chicago Tribune should increase those concerns.

The interviewers asked Johnson whether he agreed with police who forcibly broke up a recent protest at the Chicago Art Institute, arresting many protesters. Johnson answered that his primary concern was protesters’ rights. The reporters pressed further, asking, “Was the final response, the outcome — which led to dozens of arrests — was that necessary?”

Johnson’s answer:

Well, in some instances — and I’ve been a part of these demonstrations — in some instances, arrests are part of the objective. I’ll say it like that. I’ve taken arrest before. It’s not unprecedented for demonstrators to take arrest. The most important thing, though, here is that the First Amendment? Protected. Keeping people safe, it’s the primary goal, and we’ve done both of those.

In other words, getting arrested for breaking the law while protesting is no biggie.

The Chicago Tribune’s editorial board recognized the concern about what side Johnson will be on. “Democratic bosses,” their editorial says, “have figured something else out too. Chicago’s activist mayor is sympathetic to the pro-Palestinian protesters and likes to refer to the police as an entity separate from himself rather than under his control. Thus, he cannot be counted on to protect the convention and the party’s prospects.”

Others noting the same concern include the Wall Street Journal. A column there asked last week whether Democrats can trust Johnson to protect the convention. The city’s weak response to protests at the University of Chicago, the Journal said, added to questions about the political will to enforce the law.

The deliberate weakness in that response is now clear. In a Saturday MSNBC interview with Rev. Al Sharpton, Johnson said expressly that he opposed the university’s plan to clear the camp and assistance from the Chicago police.

Even left-leaning Politico wrote in some detail last week about concerns over what side Johnson will be on. From Politico: “There’s already a joke going around Democratic strategist circles that the main difference between 2024 and 1968 is that the Chicago mayor this year will be on the side of the protesters, not the cops.”

It’s no joke.

https://www.zerohedge.com/economics/mayor-johnson-deepens-concerns-about-what-side-he-will-be-if-dnc-protesters-become

Hezbollah head says displaced Israeli northerners will not return home if Gaza war persists

 The head of powerful Lebanese armed group Hezbollah said on Monday that residents of northern Israel would not be able to return home for the start of the next school year if their government pressed on with its offensive in the Gaza Strip.

Hezbollah has been exchanging fire with the Israeli military across Lebanon's southern border in parallel with the Gaza war. The armed group has said it is launching rockets at Israel both to support its ally, Palestinian armed group Hamas, and to deter Israel from launching an attack on Lebanon.

In a televised address on Monday, Sayyed Hassan Nasrallah repeated that his group would keep fighting as long as Israel continued its assault of Gaza.

"The link between the supportive Lebanese front and Gaza is definitive, final and conclusive," he said. "No one will be able to de-link them."

The fighting has displaced tens of thousands of people on both sides of the border and prompted fears of a bigger war between the heavily-armed adversaries.

Israel has said it wants to secure the north for residents to return home, either through a mediated diplomatic agreement or a military attack against Lebanon. Families displaced from northern Israel had been hoping to return home by September 1 for the start of the academic school year.

Nasrallah addressed the displaced on Monday, saying: "if you want to solve the issue, go to your government and tell them to stop the war on Gaza."

Efforts by Egypt and Qatar to secure a ceasefire in Gaza faltered last week, after Israel effectively spurned a plan from international mediators.

Israeli forces on Monday pushed deep into the ruins of Gaza's northern edge to recapture an area where they claimed to have dismantled Hamas months ago, while in the south tanks and troops pushed across a highway into Rafah.

The Israeli military also continued strikes on Lebanon over the weekend and on Monday, security sources said. Hezbollah has responded with rocket fire, and Nasrallah said his group was "continuing to develop its operations in quantity and quality".

https://www.yahoo.com/news/hezbollah-head-says-displaced-israeli-170118615.html

'New breast cancer genes found in women of African ancestry, may improve risk assessment'

 Twelve breast cancer genes identified in women of African ancestry in a large study published on Monday may one day help better predict their risk for the disease and highlights potential risk differences from women of European descent.

Studies to identify genetic mutations linked with breast cancer have previously mainly focused on women of European ancestry.

The new findings are drawn from more than 40,000 women of African ancestry in the United States, Africa and Barbados, including 18,034 with breast cancer.

Some of the mutations identified had not previously been linked with the disease, or were not as strongly linked as in this new analysis, indicating that genetic risk factors "may differ between females of African and European ancestry," the researchers wrote in Nature Genetics.

One newly identified mutation in particular was linked with the disease with a strength "rarely observed" in the field of cancer genetics, the researchers said.

Certain other genes known to increase breast cancer risk in white women were not associated with the disease in this study, the report also noted.

Black women in the United States have higher rates of breast cancer before age 50, a higher incidence of harder-to-treat breast cancers, and a 42% higher breast cancer death rate than white women, according to the American Cancer Society.

Adding the newly identified genes to previously recognized breast cancer genes such as BRCA1 and BRCA2 that are linked with the disease in all populations, the researchers developed a breast cancer risk score for women of African ancestry that was significantly more accurate than currently available tools, they said.

Six of the abnormal genes were associated with an elevated risk for so-called triple-negative breast cancer, the most aggressive form of the disease. Black women have nearly a three-fold increased risk for this type of breast cancer compared to white women, previous research has shown.

Women in the study carrying all six genes were 4.2 times more likely to be diagnosed with triple-negative breast cancer than those with none or only one of the variants, the study found.

The usefulness of the new variants needs to be further evaluated before testing for them becomes routinely available, said study leader Dr. Wei Zheng of Vanderbilt University Medical Center in Nashville.

The American Cancer Society says many genetic mutations previously identified as breast cancer risk factors in white women are also strongly linked with disease risk in Black women, and advises genetic testing for all patients regardless of race.

But U.S. Black women are less likely than white women to undergo breast cancer genetic testing, largely owing to differences in physician recommendations or access to care, the society notes.

https://www.yahoo.com/news/breast-cancer-genes-found-women-161843186.html

Turkey Treating Over 1,000 Wounded Hamas Members In Hospitals: Erdogan

 The NATO country with the second largest military in the alliance has just admitted to aiding and abetting a US-designated terror organization.

Turkish President Recep Tayyip Erdogan in surprisingly frank statements acknowledged that Turkey is currently treating over 1,000 Hamas members in various hospitals across the country. In the remarks he stressed that Turkey does not consider them terrorists, but as part of a "resistance movement" against Israel.

Also surprising is that such an admission, which is sure to anger other Western allies, came as Greek Prime Minister Kyriakos Mitsotakis was on an official visit with Erdogan in the capital city of Ankara.

"Hamas is a resistance organization whose lands have been occupied since 1947, and it has protected its lands after the occupation," Erdoğan said, clashing with Greece's view of the militant organization currently fighting Israel.

"I do not see Hamas as a terrorist organization. On the contrary, I see Hamas as people struggling to protect their own land and their own people," Erdogan added.

According to more from the exchange:

Speaking at a press conference after talks with Greek Prime Minister Kyriakos Mitsotakis in Ankara, Erdogan also said he was saddened by the Greek view that deems Hamas a terrorist organization.

Greece and Turkey cannot agree on all issues related to the war in Gaza but they can agree that violence must end and a long-term ceasefire is needed, Mitsotakis said.

“Let’s agree to disagree,” Mitsotakis said, responding to Erdogan.

Erdogan at one point told his Greek counterpart that terrorist organizations "should have no place in the region's future" and that there is "growing unity" on this, but that Turkey differs on the definition when it comes to Hamas.

But, Erdogan explained, "we are in agreement that a ground operation in Rafah would be unacceptable."

Since the Gaza War started in the wake of the Oct.7 Hamas terror attack, Erdogan has been a constant critic of both Israel and Prime Minister Netanyahu personally. 

Turkey has also cut trade with Israel over what it called the "worsening humanitarian tragedy" currently unfolding. Israel has in turn accused Erdogan of being a "dictator". 

As for treating hardline jihadists in hospitals, this also happened during the war in Syria, but in that case even Israel at one point had been giving medical aid to anti-Assad militants on its soil, most of which were linked to al-Qaeda.

https://www.zerohedge.com/markets/turkey-treating-over-1000-wounded-hamas-members-hospitals-erdogan

Raymond James partners with Todd Boehly's investment firm for private credit push

 Raymond James will partner with billionaire Todd Boehly's investment firm Eldridge Industries to expand into the $1.7 trillion private credit market, mirroring attempts by other banks.

The bank said on Monday the new venture will invest in private equity-backed companies across four primary sectors - consumer, diversified industrials, healthcare and technology & services.

Private credit refers to financing provided by non-bank companies that are not subjected to the same degree of regulation as banks.

Such loans are processed quicker and can be an important source of funds for borrowers deemed too risky by traditional lenders.

But traditional lenders such as JPMorgan Chase, Wells Fargo and Citigroup are also rushing to grab a slice of the booming market by teaming up with investment firms.

Such partnerships can provide banks with extra financial firepower and flexibility to invest.

Eldridge manages nearly $80 billion in total assets across its investment and insurance subsidiaries.

https://finance.yahoo.com/news/raymond-james-partners-todd-boehlys-140222058.html

'Twist Launches Multiplexed Gene Fragments to Enable High-throughput Screening Apps'

 Twist Bioscience Corporation (NASDAQ: TWST), a company enabling customers to succeed through its offering of high-quality synthetic DNA using its silicon platform, today announced the launch of Twist Multiplexed Gene Fragments (MGFs), pools of directly synthesized double-stranded DNA (dsDNA) up to 500 base pairs in length with no limit on sequence number to enable high throughput screening applications.

“Using our chemical synthesis platform we are able to directly synthesize Twist Multiplexed Gene Fragments as fragment pools of up to 500 bp in length. By offering Twist's high-quality gene fragments in a pooled format at prices that scale with the number of sequences, Twist is enabling customers to conduct applications that may have been previously unfeasible or cost-prohibitive, facilitating high-throughput screening in a way that is far more accessible to researchers across industry segments,” said Emily M. Leproust, Ph.D., CEO and co-founder of Twist Bioscience. “The capability of pooling directly synthesized fragments with high uniformity and representation allows for rapid screening of diverse targets for CRISPR and genome engineering, facilitates entire antibody variable coding regions for antibody discovery, and supports long coding stretches of protein variants for protein engineering applications.”

Twist MGFs are synthesized from customer-defined sequences up to 500 base pairs in length, generating an unlimited number of high-quality DNA fragments in parallel. Twist MGFs encompass a region large enough to span entire antibody variable domains and UTRs, providing customers with a purpose-built product to meet their needs. The expansive coding region also allows for customer customization and multifaceted design options. The pooled format of the fragments enables large-scale high-throughput screening.

https://www.businesswire.com/news/home/20240513372494/en/