Novartis iptacopan met Phase II study primary endpoint in rare kidney disease

 Phase II primary endpoint results for investigational iptacopan in IgAN

      demonstrated effective and clinically meaningful reduction of 
      proteinuria1 -- a key risk predictor in kidney disease progression2 
 
   -- Iptacopan also showed a trend toward stabilization of kidney function1; 
      Phase III clinical trial APPLAUSE is underway 
 
   -- There are no currently approved treatments for IgAN -- a rare and often 
      progressive kidney disease that mainly affects young adults and can 
      progress to kidney failure3-7 
 
   -- Iptacopan is in development for several complement-driven renal diseases 
      (CDRDs), including IgAN and C3 glomerulopathy (C3G), and the blood 
      disorder paroxysmal nocturnal hemoglobinuria (PNH), targeting a key 
      driver of these diseases 

https://www.marketscreener.com/quote/stock/NOVARTIS-AG-9364983/news/Press-Release-nbsp-Novartis-announces-iptacopan-met-Phase-II-study-primary-endpoint-in-rare-kidney-35531428/

‘Damning’ science shows COVID-19 likely engineered in lab

 “Damning” science strongly suggests that COVID-19 is a man-made monster, optimized in a lab for maximum infectivity before hitting the outside to catastrophic effect, two experts said Sunday.

Writing in an opinion piece for The Wall Street Journal, Dr. Steven Quay and Richard Muller pointed to two key pieces of evidence to support the claim, which has increasingly gained steam after long being derided as little more than speculation.

The first relates to the nature of gain-of-function research, in which microbiologists tweak a virus’ genome to alter its properties, such as making it more transmissible or more lethal.

Of the 36 possible genome pairings that can produce two arginine amino acids in a row — which results in boosting a virus’ lethality — the one most commonly used in gain-of-function research is CGG-CGG, or double CGG, wrote Quay and Muller.

Quay and Muller stated the double CGG sequence has never been found naturally among the entire group of coronaviruses that includes CoV-2.

Barcroft Media via Getty Images

“The insertion sequence of choice is the double CGG,” wrote Quay, the founder of Atossa Therapeutics, and Muller, a former top scientist at the Lawrence Berkeley National Laboratory, who now teaches physics at the University of California’s Berkeley campus.

“That’s because it is readily available and convenient, and scientists have a great deal of experience inserting it,” they wrote. “An additional advantage of the double CGG sequence compared with the other 35 possible choices: It creates a useful beacon that permits the scientists to track the insertion in the laboratory.”

The pair noted that the double CGG sequence has never been found naturally among the entire group of coronaviruses that includes CoV-2, which causes COVID-19.

But, in what Quay and Muller called a “damning fact,” it was found in CoV-2.

“Proponents of zoonotic origin must explain why the novel coronavirus, when it mutated or recombined, happened to pick its least favorite combination, the double CGG,” they wrote. “Why did it replicate the choice the lab’s gain-of-function researchers would have made?

“At the minimum, this fact — that the coronavirus, with all its random possibilities, took the rare and unnatural combination used by human researchers — implies that the leading theory for the origin of the coronavirus must be laboratory escape.”

Recently revealed emails by Dr. Anthony Fauci, the nation’s leading infectious disease expert, show that he was warned as early as Jan. 2020 that the virus may have been “engineered.”

In a Senate hearing last month, Fauci admitted that he couldn’t be certain that the Wuhan Institute of Virology in China — the nation from which COVID-19 sprang in late 2019 — didn’t put a pre-pandemic $600,000 grant from the National Institutes of Health toward gain-of-function research.

The stated purpose of the grant was determining whether coronaviruses could be transmitted from bats to humans, a scenario popularly suggested as the origin of COVID-19.

Beyond apparent signs of gain-of-function engineering, Quay and Muller wrote in the Journal that the evidence “most compelling is the dramatic differences in the genetic diversity of CoV-2, compared with the coronaviruses responsible for SARS and MERS.”

SARS and MERS, which were confirmed to be of natural origin, “evolved rapidly as they spread through the human population, until the most contagious forms dominated,” the pair wrote.

By contrast, COVID-19 proved to be highly contagious from the point it was first detected.

“Such early optimization is unprecedented, and it suggests a long period of adaptation that predated its public spread,” wrote Quay and Muller. “Science knows of only one way that could be achieved: simulated natural evolution, growing the virus on human cells until the optimum is achieved. That is precisely what is done in gain-of-function research.”

The two pieces of evidence led Quay and Muller to conclude that the possibility that COVID-19 was engineered should be viewed as the leading theory.

“The presence of the double CGG sequence is strong evidence of gene splicing, and the absence of diversity in the public outbreak suggests gain-of-function acceleration,” they wrote. “The scientific evidence points to the conclusion that the virus was developed in a laboratory.”

https://nypost.com/2021/06/06/damning-science-shows-covid-19-likely-engineered-in-lab/

Iovance: 33-Month Follow Up Data for Lifileucel in Advanced Melanoma at ASCO

 Median Duration of Response (DOR) Not Reached at 33.1 Months of Median Study Follow Up in Cohort 2 in C-144-01 Study

Early Intervention with Lifileucel Following Progression on Anti-PD-1 Therapy May Maximize Benefit

ASCO Update Conference Call and Webcast

Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel T cell-based cancer immunotherapies, today announced updated clinical data for lifileucel from Cohort 2 in the C-144-01 clinical study in patients with advanced melanoma. The data were presented in an oral presentation at the ASCO 2021 Annual Meeting.

Omid Hamid, M.D., Chief of Research/Immuno-Oncology, The Angeles Clinic & Research Institute, stated, “Anti-PD-1 therapy is a mainstay class of treatment offering several therapeutic options for metastatic melanoma. For patients who progress on anti-PD-1 therapy, there is an unfulfilled need for efficacious and durable treatment options. The latest results with lifileucel suggest that early intervention with lifileucel TIL therapy, immediately upon progression on anti-PD-1 therapy, may offer better outcomes and longer duration of response. These data offer evidence that patients have had positive treatment experiences with lifileucel, and I believe TIL therapy has the potential to become an important option within the melanoma treatment landscape.”

Friedrich Graf Finckenstein, M.D., Chief Medical Officer of Iovance, stated, “Our latest data for Cohort 2 in the C-144-01 clinical study are very exciting and continue to support the durability of responses after lifileucel in challenging to treat patients with melanoma. Median DOR has still not been reached at 33 months of median study follow up. We are also reporting the important observation that a shorter duration of prior anti-PD-1 therapy is associated with longer duration of response after lifileucel. We are committed to bringing lifileucel to patients as soon as we can.”  

The long-term follow-up data for Cohort 2 in the C-144-01 clinical study continue to demonstrate durability and depth of lifileucel TIL therapy response. Median DOR was not reached at 33.1 months of median study follow up (range: 2.2 to 38.5+ months) and Overall Response Rate, or ORR, remained at 36.4% (data extraction: April 2021). Responses deepened over time and one patient converted from partial to complete response at 24 months post lifileucel infusion.

A multivariable model showed that for every six-month decrease in cumulative duration of prior anti-PD-1 therapy, DOR to lifileucel will be nearly doubled. These results suggest that early intervention with lifileucel at the time of initial progression on anti-PD-1 therapy may maximize benefit.

All patients in Cohort 2 had high baseline disease burden and were heavily pretreated (3.3 mean prior therapies), including anti-PD1 and BRAF/MEK inhibitors if BRAFV600 mutation positive. The adverse event profile was consistent with the underlying advanced disease, lymphodepletion and IL-2 regimens, with no new safety risks identified for lifileucel during long-term follow-up.

Webcast and Conference Call
Iovance will host a webcast and conference call on Sunday, June 6, at 12:00 p.m. ET to discuss ASCO clinical data updates for lifileucel alone and in combination with pembrolizumab in patients with advanced melanoma. Iovance senior leadership, together with Dr. Hamid, will present a summary of the ASCO data from Cohort 1A in the IOV-COM-202 study as well as the oral presentation of updated Cohort 2 data from the C-144-01 clinical study.

The conference call dial-in numbers are 1-844-646-4465 (domestic) or 1-615-247-0257 (international) and the access code is 4858337. The live webcast can be accessed in the Investors section of the company’s website at http://www.iovance.com. The archived webcast will be available for a year in the Investors section at www.iovance.com.

https://www.globenewswire.com/news-release/2021/06/06/2242393/0/en/Iovance-Biotherapeutics-Announces-33-Month-Follow-Up-Data-for-Lifileucel-in-Advanced-Melanoma-at-ASCO-2021-Annual-Meeting.html

China three-child policy may not change national birthrate - or outlook: Moody's

 Rating agency Moody’s Investors Service said on Monday that China’s new policy allowing couples to have up to three children could support fertility, but was unlikely to dramatically change the national birthrate.

The rating agency said that the policy highlighted the risk of aging across emerging markets in Asia.

“And although China’s new policy allowing couples to have up to three children could support fertility, it is unlikely to dramatically change the national birthrate, meaning that aging will remain a credit-negative constraint”, Moody’s said in a statement.

https://www.reuters.com/article/china-society-populating-moodys/china-three-child-policy-may-not-change-national-birthrate-moodys-idUSFWN2NN067

GH Research files for a $100 million US IPO, targeting depression

 GH Research, a Phase 2 biotech developing DMT-based therapies for depression, filed on Friday with the SEC to raise up to $100 million.

The Dublin, Ireland-based company is developing its proprietary 5-MeO-DMT compound in a Phase 2 trial in the Netherlands for patients with Treatment-Resistant Depression. The company believes that its inhalable drug candidate has the potential to induce ultra-rapid remissions in certain patients, driven by the ultra-rapid onset of psychoactive effects and an intense and short-lived initial psychoactive experience.

Companies using psychoactive compounds to treat psychiatric disorders have received interest from investors recently. In September 2020, psilocybin-based biotech COMPASS Pathways (CMPS; +95% from IPO) went public. Another psychedelics biotech, ATAI Life Sciences (ATAI), filed for a US IPO in April 2021.

GH Research was founded in 2018 and plans to list on the Nasdaq under the symbol GHRS. GH Research filed confidentially on April 20, 2021. Cowen, and Stifel are the joint bookrunners on the deal. No pricing terms were disclosed.

Relevant Profile: GHRS

https://www.renaissancecapital.com/IPO-Center/News/82408/DMT-biotech-GH-Research-files-for-a-$100-million-US-IPO-targeting-depressio

Gene editing biotech Graphite Bio files for a $100 million IPO

 Graphite Bio, an early stage biotech developing gene editing therapies for sickle cell and other diseases, filed on Friday with the SEC to raise up to $100 million in an initial public offering.

Graphite Bio claims that its next-generation gene editing platform allows it to precisely correct mutations, replace entire disease-causing genes, or insert new genes into predetermined, safe locations. Its lead candidate, GPH101, aims to correct the mutation that causes sickle cell disease and restore normal adult hemoglobin expression. The company has received IND clearance for GPH101 and intends to enroll the first patient in a Phase 1/2 trial in the second half of 2021, with initial proof-of-concept data expected by the end of 2022.

The South San Francisco, CA-based company was founded in 2017 and plans to list on the Nasdaq under the symbol GRPH. Graphite Bio filed confidentially on April 16, 2021. Morgan Stanley, BofA Securities, Cowen, and SVB Leerink are the joint bookrunners on the deal. No pricing terms were disclosed.

Relevant Profile: GRPH

https://www.renaissancecapital.com/IPO-Center/News/82415/Gene-editing-biotech-Graphite-Bio-files-for-a-$100-million-IPO

Medline Deal Signals Return to Days of Huge Leveraged Buyouts

 The acquisition of Medline Industries Inc. that was agreed to over the weekend, the biggest leveraged buyout in over a decade, serves as the clearest sign yet that the appetite for megadeals is rising as the pandemic eases and private-equity firms look to deploy mountains of cash.

Blackstone Group Inc., Carlyle Group Inc. and Hellman & Friedman LLC said Saturday they struck a buyout deal that, according to people familiar with the matter, values the closely held medical-supply company at more than $30 billion -- or around $34 billion including debt. That makes it the largest leveraged buyout since the 2007-08 financial crisis.

Merger-and-acquisition activity has been busy across the board so far this year, with a string of large tie-ups lately including Discovery Inc.'s $53 billion deal to combine with AT&T Inc.'s Warner Media arm and Canadian National Railway Co. outbidding a rival to buy Kansas City Southern. In the U.S., $1.24 trillion of deals have been reached in 2021, up more than fourfold compared with the same period last year when lockdowns crimped economic activity and acquisition volume, according to Dealogic.

But private-equity firms, tasked with putting over a trillion dollars to work, had largely shied away from the biggest deals -- until now.

Big buyouts, which involve borrowing large amounts of money to amplify potential returns, all but disappeared after a number of the targets performed poorly or filed for bankruptcy in the wake of the financial crisis, weighed down by enormous sums of debt.

Between 2005 and 2007, private-equity firms sealed 18 deals worth $10 billion or more, according to Dealogic. Since then, they had only struck 10, before Medline.

There had been signs firms were regaining their taste for big buyouts, as they approached targets including Japan's Toshiba Corp. and Dutch telecommunications company Royal KPN NV. But until now no such deal had gotten over the finish line.

"This could be the transaction that opens up the floodgates," said Dusty Philip, co-chairman of global M&A at Goldman Sachs Group Inc., which advised Medline. "You have ideal conditions for large LBOs: low interest rates, aggressive financing markets and a significant amount of dry powder."

Indeed, buyout firms are now sitting on more than $1.6 trillion of unspent cash, according to data provider Preqin -- and that doesn't take into account the billions that big institutional investors are clamoring to invest directly in deals.

The fact that three private-equity firms came together -- they are equal partners -- harks back to an earlier era before the crisis, when so-called club deals were common. They fell out of favor as firms have generally preferred to partner with their biggest investors, but have started to appear more lately in another sign that the scope for megabuyouts is increasing.

The Medline deal capped a rapid-fire sales process that kicked off just over two months ago, attracting a field of bidders that is a who's-who of the biggest buyout firms. The size was part of the appeal, giving the firms the ability to put large amounts of capital to work without having to worry about competition from strategic bidders because of antitrust concerns. In a sign of how hungry the firms were for the deal, senior executives from the bidders made pilgrimages to Medline's suburban-Chicago headquarters to woo members of the family that founded the company.

The winners beat out a rival bid from the private-equity arm of the Canadian investing firm Brookfield Asset Management Inc. late Friday and signed the deal Saturday afternoon, the people said. The sales process had originally been expected to last several more weeks.

Based in Northfield, Ill., Medline is a little-known but major player in the field of medical equipment. It manufactures and distributes equipment and supplies used in hospitals, surgery centers, acute care and other medical facilities in more than 125 countries.

Medline's vast array of products include surgical gowns, examination gloves and diagnostic equipment, as well as consumer-facing brands such as Curad bandages. It has some $17.5 billion in annual sales.

The brothers James and Jon Mills founded the company in 1966, taking it public in 1972 before buying back the shares five years later. Since 1997, James's son Charlie has been Medline's CEO, working alongside President Andy Mills and Chief Operating Officer Jimmy Abrams, who is Andy's brother-in-law.

The family would remain the single largest shareholder in the company after the buyout and the management team would remain in place, the company said. GIC Pte Ltd., Singapore's sovereign-wealth fund, is also investing in the deal.

In addition to Goldman, BDT & Co. acted as financial adviser to Medline, and Wachtell, Lipton, Rosen & Katz was legal adviser. BofA Securities Inc., J.P. Morgan, Barclays, Morgan Stanley and Centerview Partners advised Blackstone, Carlyle and Hellman & Friedman. Simpson Thacher & Bartlett LLP was the group's legal adviser.

https://www.marketscreener.com/quote/stock/THE-BLACKSTONE-GROUP-INC-60951400/news/Medline-Deal-Signals-Return-to-Days-of-Huge-Leveraged-Buyouts-35531857/