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Thursday, September 28, 2023

BioLineRx Touts Encouraging Data From Therapy Trial For First Line Pancreatic Cancer

 BioLineRx Ltd BLRX announced data from the single-arm pilot phase of the investigator-initiated CheMo4METPANC Phase 2 combination trial of motixafortide and gemcitabine and nab-paclitaxel versus gemcitabine and nab-paclitaxel alone, in first-line pancreatic cancer (PDAC).

The pilot phase of the Phase 2 study enrolled 11 patients with metastatic pancreatic cancer. 

As of May 2023, 6 patients (55%) experienced a partial response (PR), of which 4 (36%) were confirmed PRs, with one patient experiencing resolution of the hepatic (liver) metastatic lesion. 

Three patients (27%) experienced stable disease, resulting in a disease control rate of 82%. 

These findings compare favorably to historic partial response and disease control rates of 23% and 48%, respectively, reported with the current standard of care, the chemotherapy combination gemcitabine and nab-paclitaxel.

Based on these pilot data, earlier this year, the CheMo4METPANC Phase 2 trial was amended to become a randomized study, with planned enrollment increasing from 30 to 102 patients. 

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and is expected to be the second leading cause of cancer-related death in the U.S. by 2023. 

Earlier this month, the FDA approved BioLineRx's Aphexda (motixafortide) in combination with filgrastim (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma.

https://www.benzinga.com/general/biotech/23/09/34982010/biolinerx-touts-encouraging-data-from-therapy-trial-for-first-line-pancreatic-cancer


Fauci And The CIA: A New Explanation Emerges

 by Jeffrey A. Tucker via Brownstone Institute,

Jeremy Farrar’s book from August 2021 is relatively more candid than most accounts of the initial decision to lock down in the US and UK. “It’s hard to come off nocturnal calls about the possibility of a lab leak and go back to bed,” he wrote of the clandestine phone calls he was getting from January 27-31, 2020. They had already alerted the FBI and MI5. 

“I’d never had trouble sleeping before, something that comes from spending a career working as a doctor in critical care and medicine. But the situation with this new virus and the dark question marks over its origins felt emotionally overwhelming. None of us knew what was going to happen but things had already escalated into an international emergency. On top of that, just a few of us – Eddie [Holmes], Kristian [Anderson], Tony [Fauci] and I – were now privy to sensitive information that, if proved to be true, might set off a whole series of events that would be far bigger than any of us. It felt as if a storm was gathering, of forces beyond anything I had experienced and over which none of us had any control.”

At that point in the trajectory of events, intelligence services on both sides of the Atlantic had been put on notice. Anthony Fauci also received confirmation that money from the National Institutes of Health had been channeled to the offending lab in Wuhan, which meant that his career was on the line. Working at a furious pace, the famed “Proximal Origin” paper was produced in record time. It concluded that there was no lab leak. 

In a remarkable series of revelations this week, we’ve learned that the CIA was involved in trying to make payments to those authors (thank you whistleblower), plus it appears that Fauci made visits to the CIA’s headquarters, most likely around the same time. 

Suddenly we get some possible clarity in what has otherwise been a very blurry picture. The anomaly that has heretofore cried out for explanation is how it is that Fauci changed his mind so dramatically and precisely on the merit of lockdowns for the virus. One day he was counseling calm because this was flu-like, and the next day he was drumming up awareness of the coming lockdown. That day was February 27, 2020, the same day that the New York Times joined with alarmist propaganda from its lead virus reporter Donald G. McNeil

On February 26, Fauci was writing: “Do not let the fear of the unknown… distort your evaluation of the risk of the pandemic to you relative to the risks that you face every day… do not yield to unreasonable fear.”

The next day, February 27, Fauci wrote actress Morgan Fairchild – likely the most high-profile influencer he knew from the firmament – that “be prepared to mitigate an outbreak in this country by measures that include social distancing, teleworking, temporary closure of schools, etc.”

To be sure, twenty-plus days had passed between the time Fauci alerted intelligence and when he decided to become the voice for lockdowns. We don’t know the exact date of the meetings with the CIA. But generally until now, most of February 2020 has been a blur in terms of the timeline. Something was going on but we hadn’t known just what. 

Let’s distinguish between a proximate and distal cause of the lockdowns.

The proximate cause is the fear of a lab leak and an aping of the Wuhan strategy of keeping everyone in their homes to stop the spread. They might have believed this would work, based on the legend of how SARS-1 was controlled. The CIA had dealings with Wuhan and so did Fauci. They both had an interest in denying the lab leak and stopping the spread. The WHO gave them cover. 

The distal reasons are more complicated. What stands out here is the possibility of a quid pro quo. The CIA pays scientists to say there was no lab leak and otherwise instructs its kept media sources (New York Times) to call the lab leak a conspiracy theory of the far right. Every measure would be deployed to keep Fauci off the hot seat for his funding of the Wuhan lab. But this cooperation would need to come at a price. Fauci would need to participate in a real-life version of the germ games (Event 201 and Crimson Contagion). 

It would be the biggest role of Fauci’s long career. He would need to throw out his principles and medical knowledge of, for example, natural immunity and standard epidemiology concerning the spread of viruses and mitigation strategies. The old pandemic playbook would need to be shredded in favor of lockdown theory as invented in 2005 and then tried in Wuhan. The WHO could be relied upon to say that this strategy worked. 

Fauci would need to be on TV daily to somehow persuade Americans to give up their precious rights and liberties. This would need to go on for a long time, maybe all the way to the election, however implausible this sounds. He would need to push the vaccine for which he had already made a deal with Moderna in late January. 

Above all else, he would need to convince Trump to go along. That was the hardest part. They considered Trump’s weaknesses. He was a germaphobe so that’s good. He hated Chinese imports so it was merely a matter of describing the virus this way. But he also has a well-known weakness for deferring to highly competent and articulate professional women. That’s where the highly reliable Deborah Birx comes in: Fauci would be her wingman to convince Trump to green-light the lockdowns. 

What does the CIA get out of this? The vast intelligence community would have to be put in charge of the pandemic response as the rule maker, the lead agency. Its outposts such as CISA would handle labor-related issues and use its contacts in social media to curate the public mind. This would allow the intelligence community finally to crack down on information flows that had begun 20 years earlier that they had heretofore failed to manage. 

The CIA would hobble and hamstring the US president, whom they hated. And importantly, there was his China problem. He had wrecked relations through his tariff wars. So far as they were concerned, this was treason because he did it all on his own. This man was completely out of control. He needed to be put in his place. To convince the president to destroy the US economy with his own hand would be the ultimate coup de grace for the CIA. 

A lockdown would restart trade with China. It did in fact achieve that. 

How would Fauci and the CIA convince Trump to lock down and restart trade with China? By exploiting these weaknesses and others too: his vulnerability to flattery, his desire for presidential aggrandizement, and his longing for Xi-like powers over all to turn off and then turn on a whole country. Then they would push Trump to buy the much-needed personal protective equipment from China. 

They finally got their way: somewhere between March 10 or possibly as late as March 14, Trump gave the go ahead. The press conference of March 16, especially those magical 70 seconds in which Fauci read the words mandating lockdowns because Birx turned out to be too squeamish, was the great turning point. A few days later, Trump was on the phone with Xi asking for equipment. 

In addition, such a lockdown would greatly please the digital tech industry, which would experience a huge boost in demand, plus large corporations like Amazon and WalMart, which would stay open as their competitors were closed. Finally, it would be a massive subsidy to pharma and especially the mRNA platform technology itself, which would enjoy the credit for ending the pandemic. 

If this whole scenario is true, it means that all along Fauci was merely playing a role, a front man for much deeper interests and priorities in the CIA-led intelligence community. This broad outline makes sense of why Fauci changed his mind on lockdowns, including the timing of the change. There are still many more details to know, but these new fragments of new information take our understanding in a new and more coherent direction. 

Jeffrey A. Tucker is Founder and President of the Brownstone Institute. He is also Senior Economics Columnist for Epoch Times, author of 10 books, including Liberty or Lockdown, and thousands of articles in the scholarly and popular press. He speaks widely on topics of economics, technology, social philosophy, and culture.

https://www.zerohedge.com/political/fauci-and-cia-new-explanation-emerges

Dianthus' Monoclonal Antibody On Promising Pathway

 Raymond James initiated coverage on Dianthus Therapeutics Inc DNTH, a recent reverse merger with the old Magenta Therapeutics.

The analysts initiate with an Outperform rating and a price target of $24.

The lead asset, DNTH103, is an antibody designed to target active C1s, a key component in the classical pathway, and is protected by intellectual property rights until 2043.

This targeting strategy has been de-risked, especially in light of Sanofi SA's SNY approval of Enjaymo, an antibody targeting total C1s for Cold Agglutinin Disease (CAD). However, DNTH103's focus on active C1s offers distinct advantages, such as avoiding the protein sink associated with total C1s.

Dianthus is initiating a Phase 2 gMG study with a target product profile that will potentially offer dosing advantages and safety advantages over prevailing comps. Phase 2 data are expected by 2H25. With clear data precedents in gMG, it will be easy to know if DNTH103 is an active and promising drug for gMG. Based on disease biology and PK/PD data, analysts expect DNTH103 to be at least as efficacious as AstraZeneca Plc's AZN Soliris/Ultomiris or Ra Pharmaceuticals, a subsidiary of UCB SA UCBJY UCBJF Zilucoplan.

Dianthus is commencing a Phase 2 study for gMG, with a target product profile with the potential for improved dosing and safety advantages compared to current competitors. Anticipated Phase 2 data results are slated for 2H of 2025. Given the well-established data benchmarks within the gMG field, it will be straightforward to determine if DNTH103 demonstrates active and promising qualities for gMG treatment. Based on our understanding of the disease's biology and pharmacokinetic/pharmacodynamic data, DNTH103 is expected to exhibit efficacy at least on par with AstraZeneca Plc's (NASDAQ: AZN) Soliris/Ultomiris or Zilucoplan from Ra Pharmaceuticals, a subsidiary of UCB SA UCBJY UCBJF.

https://www.benzinga.com/general/biotech/23/09/34984163/dianthus-monoclonal-antibody-on-promising-pathway-to-gaining-the-upper-hand-analyst

Massive Short-Squeeze Lifts Stocks; Bitcoin Jumps As Bullion & Black Gold Dumped

 Inflation tumbling in Europe (German CPI), the American consumer hitting a wall (PCE), and the US housing market collapsing (pending home sales) were enough to actually - for once - drag Treasury yields lower on the day... and as yields decline so a bearish-sentiment-soaked equity market melted up to start the day.

'Hard' data keeps sliding (lowest since May) but 'hope' remains alive thanks to 'soft' survey data...

An initial spike in yields on the headline GDP revision data quickly reversed (led by the short-end) as 'humans' read the report. By the close, 2Y yields were down 7bps and the long-bond down 1bp...

Source: Bloomberg

Which steepened the yield curve (2s30s) to its least inverted since May (steepening for the 5th day in the last 6)...

Source: Bloomberg

Of course, lower yields supported stocks (especially with such a dramatically bearish sentiment embedded) and 'most shorted' stocks were immediately aggressively squeezed and ripped almost 4% higher (remember negative gamma swings both ways)

Source: Bloomberg

And that lifted all the majors higher, led by Small Caps and Nasdaq. The Dow lagged on the day (lowest duration) but ended green on the day...

VIX slipped back further near 17.00...

As yields declined, so the dollar slipped lower...

Source: Bloomberg

And as the dollar dropped, bitcoin popped, ramping back above $27,000...

Source: Bloomberg

But Gold legged lower again, back near the pre-SVB spike lows in March...

Source: Bloomberg

And so did crude oil, with WTI back below $92 (after tagging $95 overnight)...

Finally, despite the recent decline4 in stocks, there remains a long-way-down to reconnect equity markets to the significant tightening in financial conditions...

Source: Bloomberg

So how will that reconnect? Equity market re-rating lower or a recession-signal rushing through the long-end of the curve, dragging yields lower (but, wait, that's not good for stocks either?)

https://www.zerohedge.com/markets/massive-short-squeeze-lifts-stocks-bitcoin-jumps-bullion-black-gold-dumped

Bank Demands For Fed Emergency Funds Near Record Highs As Retail Money-Market Fund Inflows Continue

 After an unusual outflow last week, US money market funds saw a $6.3BN inflow this week, back up close to record highs...

Source: Bloomberg

Once again, retail funds saw inflows (no outflows since April) of $7.8BN while institutional funds declined $1.5BN...

Source: Bloomberg

That is the second week of institutional outflows as retail inflows send total retail funds to a new record high...

Source: Bloomberg

And the gap between money fund assets and bank deposits continue to grow...

Source: Bloomberg

After last week's huge drop, The Fed's balance sheet continued its shrinkage (down $22BN to its smallest since June 2021)...

Source: Bloomberg

With regard to the QT program, The Fed continues to sell securities, down 17.3BN last week to its smallest since June 2021...

Source: Bloomberg

Usage of The Fed's emergency funding facility for banks remains at record highs around $108BN (+$116MN last week)...

Source: Bloomberg

The detailed breakdown is as follows:"

  • Fed QT: $2.5BN drop in TSY securities; $15BN drop in MBS

  • Discount Window: up $100MM to $3.2BN

  • BTFP up $116MM to $107.7BN

  • Other credit Extensions (FDIC Loans) down $3.1BN to $81.9BN

The spread between US equity market cap and bank reserves at The Fed is starting to converge...

Source: Bloomberg

And finally, as we like to remind readers, there's an $108BN hole in my bucket... and bank stocks are starting to catch on to the reality that in 6 months, they'll have to fill it...

Source: Bloomberg

...or The Fed will simply keep the "emergency" facility open ad infinitum under pressure from the administration during an election year

https://www.zerohedge.com/markets/banks-demands-feds-emergency-funds-remains-near-record-highs-retail-money-market-fund

Biden Tells People To Stop Questioning COVID Shots

 by Steve Watson via Summit News,

In remarks made Wednesday, Joe Biden argued that people, including potential “leaders” should stop saying “inflammatory things” about COVID vaccinations and fall into line with what his administration is telling them to do.

What leaders say matter, in terms of people’s confidence in things they’re not sure about,” biden began.

He continued, “And one of those areas — you saw what happened with regard to the crisis — health crisis that we had that cost us — we lost well over a million people. And as time began to move on, you had more and more voices saying, “No, no, no. You don’t need to get that shot. You don’t need to be — get — you don’t need to.”

“We have a new strain of COVID now, and we have answers for it,” Biden contended, further stating “I just would urge those in public life and both political parties or no political party to be cautious about the ac- — the sometimes inflammatory things you say about this, because people’s lives are at stake.”

Watch:

That will be the COVID shots that don’t prevent anyone from getting COVID or stop transmission of the virus then will it? The ones that cause more serious side effects in children than they do save lives?

The comments come in the wake of revelations that Anthony Fauci was secretly escorted into CIA and State Department meetings to steer the direction of the COVID origins investigation away from the lab leak evidence.

https://www.zerohedge.com/political/watch-biden-tells-people-stop-questioning-covid-shots

Patient Death Likely from Virus Used to Deliver Gene-Editing Therapy: NEJM Study

 A paper published on Thursday in The New England Journal of Medicine suggests that the potential cause of the 2022 death of a Duchenne muscular dystrophy patient was due to an innate immune reaction triggered by the high dose of recombinant adeno-associated virus used to deliver the gene therapy.

In November 2022, 27-year-old Terry Horgan died after receiving an investigational CRISPR-based therapy for his rare form of Duchenne muscular dystrophy (DMD). The study had been given the go-ahead by the FDA.

According to Thursday’s report, the DMD patient developed mild cardiac dysfunction and pericardial effusion after receiving the CRISPR treatment, which was then followed by acute respiratory distress syndrome (ARDS) and cardiac arrest.

Post-mortem examinations revealed severe diffuse alveolar damage, but detected only low levels of the transgene therapy in the liver. There were also no signs of “adaptive humoral or cell-mediated immune responses” against the adeno-associated virus (AAV) used to deliver the therapy, or against the transgene product itself, according to the authors.

Taken together, these factors suggest that the death was caused by an innate immune reaction triggered by the high dose of recombinant AAV used to deliver the gene therapy, the researchers found.

The effects of the immune reaction were exacerbated by the advanced stage of the patient’s condition, which could have “limited his physiological reserve and decreased his ability to survive the cardiopulmonary stress associated with acute toxic effects” associated with the gene therapy, the authors wrote.

The NEJM study was funded by the non-profit biotech Cure Rare Disease (CRD), which also supported the FDA-sanctioned DMD trial. The patient who died was the brother of CRD’s founder.

Patient deaths have been a common stumbling block for investigational gene therapies in rare diseases. In September 2021, Astellas Pharma voluntarily paused its Aspiro study in X-linked myotubular myopathy, following reports of serious adverse events and mortalities after being treated with the AAV-based investigational gene therapy AT132. Ultimately, four patients died in the trial.

Pfizer has also run into safety issues. In December 2021, the pharma company revealed that one of the patients in its DMD trial had died after receiving its investigational gene therapy PF-06939926, which also uses an AAV delivery system. A few days later, Pfizer paused screening and dosing in the study.  

Both Astellas and Pfizer have presented some of their findings from these studies at medical congresses, though the companies have yet to publish the full investigations into the deaths, according to STAT News.

https://www.biospace.com/article/patient-death-likely-from-virus-used-to-deliver-gene-editing-therapy-nejm-study/