Ron Johnson: "Important Witness" Gal Luft Needs Immunity To Tell Story About Biden Family

 Sen. Ron Johnson told FNC Maria Bartiromo that Israeli Professor Gal Luft should be granted some kind of legal protection in order to testify about the Biden family's business deals with Chinese energy conglomerate CEFC.

Luft told The New York Post's Miranda Devine: "Over an intensive two-day meeting, I shared my information about the Biden family financial transactions with this [Chinese energy company] CEFC, including specific dollar figures. I also provided the name of Rob Walker, who later became known as Hunter Biden's bagman."

Johnson asked: "I mean, let's face it. What evidence are we going to have to develop before the mainstream media actually pays attention to the corruption of the Bidens?"

SEN. RON JOHNSON (R-WI): Miranda Devine did great work again. She got the video. What's very interesting about Dr. Luft is, he's an energy expert, had a think tank, consulted with people like CIA Director James Woolsey and Robert McFarlane, and he was consulting with CEFC, the same Chinese company connected to the Communist Party there was paying the Bidens millions of dollars.

When he heard that Joe Biden was going to be running for president, that alarmed him, because he knew how compromised Joe Biden would be. So he met with two prosecutors from the Southern District of New York and four FBI agents in Brussels for two days in March of 2019.

What's interesting about those individuals, one of the prosecutors from the Southern District of New York is the same prosecutor that prosecuted Patrick Ho, the money launderer that paid Hunter Biden a million dollars to defend him.

And, in that trial, he prevented the name of Bidens from being brought into court. Also, one of the FBI agents was the same agent then that signed the subpoena from the Hunter Biden laptop. So what Mr. -- Dr Luft has shown is the same financial transactions, the millions of dollars, the $100,000-per-month retainer for Hunter, $65,000 for James Biden paid by CEFC.

He's got a wealth of information. But they never followed up on that meeting. Instead, they arrested him in Cyprus to silence him.

They could have gone to Israel. He resides in Israel. We have extradition treaties. But they instead arrest him in Cyprus.

Now, he's literally fleeing for his life right now. He's on the run. He's an important witness. He needs to be granted immunity to be able to testify and tell his story.

...

We have to keep exposing the truth. We need more whistle-blowers coming forward.

But they have done a really good job of setting up their procedures in the FBI, in the Department of Justice to insulate themselves from scrutiny. I mean, look at the letters that David Weiss sent to Jim Jordan in June 7 -- June 7, June 30, basically giving Jim Jordan the middle finger: You can't investigate us because we have an active investigation.

That's what they always use as an excuse. So they have insulated themselves from scrutiny. It's very difficult. But one indication of the problem we have, in terms of the multiple-tier system of justice here, is, Robert Mueller, in less than two years, spent $32 million on his special counsel investigation on a complete hoax, on a false narrative that the Biden -- that the Obama administration knew was perpetrated by Hillary Clinton as a dirty trick, the Russian collusion with Trump hoax, 32 million bucks.

John Durham, in over three years, only spent $7.7 million and delivered virtually nothing, certainly prevented Senator Grassley and I from investigating the corrupt Russian collusion investigation. Now you have got Jack Smith in a few months has spent $5.5 million. Robert Hur, who's investigating Biden's classified documents, spent $616,000.

So, when you just see the resources and effort put behind targeting Republicans or Donald Trump versus what little resources and how corrupt and unthorough, unthorough, the investigations are against Democrats, it's pretty revealing.

BARTIROMO: Well, that's incredible. Those numbers are speaking for themselves. You're talking about $616,000 spent by Robert Hur to look at the Biden classified documents mess, compared with Jack Smith and $5.5 million ongoing, just in a couple of months.

...

I mean, let's face it. What evidence are we going to have to develop before the mainstream media actually pays attention to the corruption of the Bidens? One of the reasons John Durham wasn't able to get convictions is, I think the jury took a look at the bad actors in those cases were literally the FBI.

And so Michael Sussmann and Igor Danchenko got let off the hook because the juries recognized the people committing probably crimes were the FBI in those jury trials.

So, again, the FBI, the Department of Justice, they have insulated themselves from scrutiny. That's why what we need is, we actually need Democrats to be concerned about this as well.

We need the majority in the Senate, so I can be chairman of the Permanent Subcommittee on Investigations. And we need to hold these people accountable by first exposing the truth, which is difficult to dig up.

 https://www.realclearpolitics.com/video/2023/07/09/sen_ron_johnson_important_witness_gal_luft_needs_immunity_to_tell_his_story_about_biden_family_business.html

Acumen, BridgeBio, Arcus among BTIG's top healthcare picks for 2H 2023

 Acumen Pharmaceuticals (NASDAQ:ABOS), Establishment Labs (NASDAQ:ESTA), Arcus Biosciences (NYSE:RCUS) and BridgeBio Pharma (NASDAQ:BBIO) are four of BTIG's top picks for small and mid-cap healthcare stocks going into the latter half of 2023, replacing names Aldeyra, Esperion, Vaxcyte.

https://seekingalpha.com/news/3986343-acumen-bridgebio-arcus-among-btig-top-healthcare-picks-for-2h-2023

Black Diamond scales 8% as RA Capital Management buys $4.68M worth stock

 

• RA Capital Management acquires 935,850 shares of Black Diamond Therapeutics at $5 per share, worth ~$4.68M.
• This brings its total shareholding to ~3.21M shares.
• The stock price of BDTX has surged 7.8% during after hours trading.
• Source: Form 4

https://www.tradingview.com/news/seeking_alpha:5946cf458094b:0-black-diamond-therapeutics-scales-8-as-ra-capital-management-buys-4-68m-worth-stock/

Novartis will appeal Entresto patent setback

 Novartis has suffered a defeat in its legal defence of chronic heart failure therapy Entresto, which accounted for around 11% of its revenues last year, but has vowed to take the case to appeal.

Shares in the pharma group came under pressure ahead of the weekend after a US district court in Delaware ruled that a patent covering Entresto (valsartan/sacubitril) that expires in 2025 was invalid, raising the possibility of generic competition to the blockbuster drug in that year.

The patent in question (No. 8,101,659) covers the combination of sacubitril with valsartan and includes an extension awarded in return for carrying out studies of the drug in paediatric populations. It is due to expire on 15th July 2025.

The ‘659 patent is one of a series of patents expiring between 2023 and 2036 that Novartis says protect its brand in the US market, and the company immediately said it intended to elevate the case to the US Court of Appeals for the Federal Circuit in an attempt to reverse the ruling.

The decision came a day after Novartis won a patent infringement lawsuit brought against generic drugmaker Mylan in a West Virginia district court, which found that proposed Entresto generics infringed two other patents on the drug (Nos. 8,877,938 and 9,388,134). Litigation against Mylan and other companies hoping to bring generic versions of Entresto to the US market has been ongoing since 2019.

Shares in Novartis nevertheless fell around 3% in both the US and Europe as investors fretted that competition to Entresto could emerge in the US earlier than expected. The drug brought in $4.6 billion for Novartis last year, up by around a third on the prior year with the increase fuelled by use in heart failure with preserved ejection fraction (HFpEF), which was added to the drug’s label in 2021.

In a statement, Novartis said there are currently no generic Entresto products with either tentative or final FDA approval, adding that any launch of a copycat drug before the outcome of its appeal would be “at risk of later litigation development.”

It also said that despite the potential for earlier-than-expected arrival of generics, it is maintaining its 2023 guidance of group sales growing at a mid-single-digit rate, with average increases of 4% between 2022 and 2027.

The company pledged to “continue to defend vigorously its intellectual property rights relating to Entresto, including the combination patent as well as multiple patents covering additional innovations.”

Bank of America analyst Graham Parry said in a research note that generic Entresto launches ahead of the expiry of the ‘659 patent in 2025 “still seem unlikely” despite the Delaware judgment.

https://pharmaphorum.com/news/novartis-will-appeal-entresto-patent-setback

J&J snaps up Nanobiotix cancer radiotherapy in $2.5bn+ deal

 Johnson & Johnson has bolstered its oncology pipeline by licensing a drug from Nanobiotix designed to enhance the effectiveness of radiotherapy for solid tumours.

J&J’s Janssen unit is paying $60 million in upfront fees and funding for an exclusive worldwide license to NBTXR3, a radioenhancer that has been approved in Europe as Hensify as a treatment for locally-advanced soft tissue sarcomas since 2019.

The drug is an aqueous suspension of crystalline hafnium oxide (HfO2) nanoparticles designed for injection directly into a tumour before a patient’s first dose of radiotherapy. When exposed to ionising radiation, NBTXR3 amplifies the effect of the radiation within the tumour, while the dose passing through healthy tissues remains unchanged.

Sarcoma is a relatively small indication for the drug and J&J’s interest stems mainly from its potential as a treatment for head and neck cancer, currently being tested in the phase 3 NANORAY-132 study which started dosing patients last December.

Analysts at Jefferies have previously suggested that NBTXR3 could potentially be used in around two-thirds of all radiotherapy procedures used to treat cancer.

Crucially for Nanobiotix, bringing J&J on board includes near-term funding for the trial, due to read out in the second half of next year, as its own finances have started to dwindle and it has been forced to trim back its pipeline to conserve cash.

The French and US biotech ended the first quarter with around €30 million in cash, down from €40 million at the end of 2022, and said recently that would last it only into the third quarter of this year.

J&J is providing up to $30 million to complete NANORAY-132 as part of its upfront support and has also pledged up to $1.8 billion in development, regulatory and sales milestones in head and neck cancer.

Also on the table is another $650 million for up to five additional indications that J&J may choose to develop on its own – including a phase 2 programme in advanced lung cancer – and $200 million for joint development projects.

The deal covers all global markets except for China and a handful of other markets in Asia where Nanobiotix previously licensed NBTXR3 to LianBio.

Shares in Nasdaq-listed Nanobiotix barely moved after the announcement this morning, mainly because they had already skyrocketed in May after the company revealed it was in late-stage negotiations with a “major global pharmaceutical company.”

The biotech’s chief executive, Laurent Levy, said that the deal with J&J will help NBTXR3 potentially reach “millions of patients around the world.”

Nanobiotix held back from a commercial launch in Europe after the sarcoma approval, saying it would wait for additional uses to be added to its label, but has made it available to patients on a compassionate-use basis.

https://pharmaphorum.com/news/jj-snaps-nanobiotix-cancer-radiotherapy-25bn-deal

Novartis Backs 2023 Outlook Despite Court Red Light on Drug Patent.

 Novartis said late Friday that a U.S. court has issued a negative decision on the patent of its heart-failure drug Entresto, but backed its full-year outlook.

The Swiss pharma giant said the U.S. District Court for the District of Delaware has established that the patent on Entresto and combinations of two drug principles with the same purpose is invalid. The patent was set to expire in 2025 and held exclusivity for pediatric use, the company said, adding that it would appeal the decision.

The court's ruling may lead to an earlier-than-expected entry of generic versions of Entresto into the U.S. market.

Nonetheless, Novartis backed its outlook for 2023, saying it continues to expect group sales to grow mid-single digit in constant currencies, and operating income to grow high-single digit in constant currencies. The company also backed its mid-term outlook of 4% sales growth between 2022 and 2027, with a 40% core operating income margin excluding the generics unit Sandoz.

https://www.marketscreener.com/quote/stock/NOVARTIS-AG-9364983/news/Novartis-Backs-2023-Outlook-Despite-Court-Red-Light-on-Drug-Patent-44298108/

CRISPR on the Cusp: The Promise and the Pain Points

 Hereditary angioedema patients treated with Intellia’s NTLA-2002—an in vivo CRISPR-Cas9 therapy— had an average 95% reduction in the sudden, debilitating bouts of swelling that are a hallmark of the disease, with some patients remaining attack-free for more than a year, according to updated Phase I data presented in June. Despite the potential of gene editing to ease or even cure genetic diseases, questions about the safety and efficacy of the techniques remain.

Previous CRISPR trials have resulted in adverse side effects or, rarely, even death. In May, a participant in an N-of-1 Duchenne muscular dystrophy trial died after potentially reacting to the virus carrying the gene-editing therapy. 

When injected systemically, the liver takes up many gene editing delivery vectors. While most delivery vectors are well-tolerated in most people, at high doses, some can drive inflammation that can lead to toxicity. Designing vectors that reach organs besides the liver has posed significant hurdles for scientists. Another danger is off-target effects, where the editors inadvertently change portions of the healthy genetic code.

Despite these limitations, innovations in delivery methods and next-generation CRISPR technologies—such as base and prime editing—may increase the types of diseases that can be targeted and treated with gene editing.

Kiran Musunuru, a cardiologist at the University of Pennsylvania, told BioSpace that while still early, the results look promising for the limited number of patients who have received Intellia’s drug.

CRISPR Reaches the Clinic

CRISPR has advanced quickly since the technology was first invented 10 years ago. In a landmark decision expected later this year, the FDA could approve an ex vivo gene editing therapy for sickle cell disease (SCD). The biologics license applications—submitted in April for exagamglogene autotemcel (exa-cel) in SCD and transfusion-dependent beta thalassemia (TDT) by Vertex and CRISPR Therapeutics—were the first CRISPR gene editing filings to be accepted by the FDA. The regulator has set PDUFA dates of December 8, 2023, and March 30, 2024, respectively.

“The first FDA approval of a new type of technology—in this case, programmable gene editing drugs—is a huge milestone,” David Liu, a molecular biologist at the Broad Institute and Harvard professor, told BioSpace.

There are more than 50 in-human clinical trials for both in vivo and ex vivo gene editing technologies in the early stages, Liu said, and roughly 40 are CRISPR-based. These therapies are being tested for blood disorders, cancer, chronic infection, liver diseases, immune deficiencies and more.

But the in vivo space has progressed more slowly. The first patient to receive an in vivo CRISPR therapy did so in 2020 in a clinical trial for Editas Medicine’s treatment for Leber Congenital Amaurosis (LCA), a type of genetic blindness caused by a single nucleotide change in a retinal photoreceptor gene.

After treatment with EDIT-101, some patients had some visual acuity and a few had regained their ability to see color, according to an Editas press release issued in November 2022. None had adverse effects. While the therapy worked well for some patients, it failed in roughly half, and Editas eventually pulled the plug on the Phase I/II trial.

That means Intellia is the only company that has presented clinical data for in vivo trials that have met primary endpoints and the only company that has started Phase II trials, David Lebwohl, the company’s chief medical officer, told BioSpace. 

David Lebwohl

Musunuru and Liu agreed that Intellia’s treatment appears to work well, but due to its delivery method through lipid nanoparticles (LNPs), NTLA-2002 is limited to treating rare diseases that originate in the liver. If delivered intravenously, LNPs are taken up by the liver, which is true for many other delivery vectors for in vivo gene editing studies, Musunuru said.

The therapy also uses the original CRISPR-Cas9 system, which Musunuru said is useful for turning off genes, “but there is a limited set of diseases for which turning off a gene is therapeutically useful.” 

Base and Prime Editing

CRISPR-Cas9 was first developed by Jennifer Doudna’s lab at the University of California, Berkeley. Since then, base editing and prime editing have expanded the number of diseases that gene editing can potentially target.

The CRISPR-Cas9 system works by cleaving the DNA double helix at a specific nucleotide sequence, Liu explained. Cas9, a nuclease, cuts the cell’s DNA at a specific location, after which the cell’s endogenous repair enzymes glue the strands back together. Cas9 keeps cutting the DNA at the same location until, by chance, the cell’s repair machinery makes a mistake and inserts the wrong nucleotide.

The result is a genetically edited sequence of DNA, which Cas9 no longer recognizes. But crucially, you can’t control what the cell inserts, Liu said. This technology often works well if you want to eliminate the function of a dysfunctional protein but less so if you’re looking to replace a defective gene.

CRISPR-Cas9 has advantages. It is very modular, Lebwohl said, which allowed Intellia to change only a messenger RNA (mRNA) sequence to enable a whole new therapy.

However, Liu said one major limitation of this technology is that it causes double-stranded breaks, leading to unfavorable mutations and off-target effects. On the other hand, prime editing and base editing rely on simply nicking one strand of the double helix, allowing researchers to edit DNA without double-stranded breaks and potentially making them safer. “It’s estimated that every human cell undergoes maybe 10,000 nicks a day because nicking is a natural part of DNA repair and DNA replication,” he said.

Liu, who co-founded Prime Medicine and Beam Therapeutics—both gene editing companies—said base editing allows scientists to substitute certain single DNA nucleotides, which could enable the development of drugs for diseases caused by point mutations—where one single nucleotide base is added, deleted or changed.

This makes base editors well-suited to treat some forms of glycogen storage disease and one form of beta-thalassemia, both of which can occur due to pathogenic single nucleotide polymorphisms.

However, base editors can only change purines to purines and pyrimidines to pyrimidines and are vulnerable to also changing neighboring nucleotides. Older versions of the tech can have off-target effects on other portions of the DNA, Liu added, due to the promiscuous activity of the deaminase enzyme, which helps convert nucleotides to other nucleotides during base editing.

Prime editors allow researchers to replace stretches of genes and perform a diverse range of substitutions, insertions, and deletions, Liu said. They are extremely specific but less efficient than the other technologies.

“Prime editors are highly versatile,” Liu said. “Current generation prime editors can basically replace any DNA segment up to several hundred base pairs with any DNA segment [of the same length].” Because they allow researchers to insert long DNA sequences into cells, such technologies could be used to treat diseases such as Tay Sachs, caused by a large deletion mutation. 

CRISPR-Cas9, prime editing and base editing have been validated in animal models of human genetic disease, and the CRISPR-Cas9 and base editing have now entered human clinical trials. Liu said he expects Prime Medicine’s technology to reach the clinic next year.

The Delivery Dilemma

Musunuru said delivery is the area where innovation is most needed. Many in vivo therapies have targeted the eye and the liver, mainly due to the ease of vector delivery.

Once they enter the blood, LNPs and other delivery vectors—including adeno-associated viruses (AAVs)—get sucked up by the liver, Lebwohl said. They can efficiently deliver gene therapies to hepatocytes, but other organs have proven more difficult.

Viral vectors can be engineered to target specific cells but are immunogenic and potentially toxic at high doses, Liu said. Recently, scientists have begun designing AAVs specifically targeting organs such as the muscles so they can be used at lower doses. Researchers are also improving non-AAV technologies, searching for ways to get past the blood-brain barrier and potentially target the brain.

Lebwohl said Intellia expects to move to Phase III with NTLA-2002, but the company is still in the early stages of Phase II recruiting, which means it may be years before the therapy is approved. Whether NTLA-2002—and CRISPR-Cas9-based treatments in general—are well-tolerated long-term requires follow-up studies, he said. “We’re talking about five, six, seven decades of patients not needing a drug if this holds up in the long run.”

While there is still much work to be done, Liu said FDA approval of the first CRISPR gene editing therapy would represent a major step for humanity as it would mean humans have some say in their genetic features and are not held hostage by mutations.

https://www.biospace.com/article/crispr-on-the-cusp-the-promise-and-the-pain-points-/