Search This Blog

Thursday, August 5, 2021

MyMD Pharma COVID-19 Candidate Effective In Suppressing Cytokine Storm

 

  • MyMD Pharmaceuticals Inc MYMD 5.97% announces that a human cell research study of its lead compound MYMD-1 found the drug to effectively suppress the cytokine storm, a major cause of severity and death in COVID-19 patients.
  • Cytokine storm causes an overreaction of the immune system that can cause the body to attack its tissues and organs, leading to a high proportion of deaths from COVID-19. The primary cytokine that MYMD-1 inhibits is TNF-α (tumor necrosis factor-alpha). 
  • MYMD-1 has been shown in laboratory tests of human cells to block TNF-α production. The cytokine storm of COVID-19 that it produces has been implicated in causing injury and death from the coronavirus disease.
  • MyMD is collaborating with a medical school for a Phase 2 trial to investigate the effectiveness of MYMD-1 to treat immune-mediated depression and cytokine elevation in patients affected with COVID-19.
  • The Company is planning to launch a second Phase 2 trial of MYMD-1 in the near term.

CVS Health Stops Administering JNJ COVID-19 Shot In Several Locations

 

  • Drugstore chain CVS Health Corporation CVS 2.39% is no longer offering Johnson & Johnson's JNJ 0.27% COVID-19 vaccine in many of its retail locations, the company told CNBC on Wednesday.
  • According to CVS spokesman Mike DeAngelis, retail locations continue to offer either the Moderna Inc MRNA 1.14% or Pfizer Inc PFE 0.54% - BioNTech SE BNTX 2.3% vaccine.
  • DeAngelis said the change was implemented "several weeks ago and helps us manage our vaccine supply across the chain, both in our pharmacies and clinics."
  • He added that the Johnson & Johnson vaccine is still offered at almost 1,000 of its MinuteClinic locations in 25 states and Washington, D.C. 
  • The Johnson & Johnson vaccine was touted as a potential game-changer when it was initially authorized, being a single-dose shot, and can be stored at normal refrigerator temperatures.
  • But the vaccine has been beset by production issues and concerns about its effectiveness against the delta variant. 

Bayer beefs up discovery work with Vividion buyout

 Discovery-stage deals rarely involve big up-front fees, so the $1.5bn Bayer has agreed to pay for the private group Vividion catches the eye. But the US developer is active in a very hot space – protein degradation – and had filed to float; compared against valuations achieved recently by similar companies at IPO the terms start to make more sense. 

It is also notable that Vividion will be run at arm's length, mirroring the German company’s strategy in its cell and gene therapy units. This is a big bet on some very early  science, however: Bayer hopes to start filing INDs next year, presumably involving NRF2 modulation, which was the only specifically named target in the press release.

NRF2 is a transcription factor thought to be involved in regulating oxidative stress, and active in many disease areas. Bayer intends to explore the role of antagonists and activators of NRF2 in cancer and inflammatory disorders.

Vividion says its technology can generate small-molecule modulators or degraders of targets considered undruggable, a claim widely made in protein degradation. This approach initially involved tagging disease-causing proteins for disposal by the cell, but has expanded to encompass the activation, modulation or protection of targets, and even the clearance of extracellular proteins.

Essentially, this is achieved by simultaneously binding a target and an enzyme that can alter that target, sometimes by using two molecules linked together, or by using molecules capable of both functions.

Interest in this approach is high across biopharma, with numerous deals struck by big developers to access the work being done by young biotechs. And those transactions are getting richer: last month Pfizer paid $650m up front to license Arvinas’s oestrogen receptor degrader ARV-471. The project is one of the most advanced protein degraders in the clinic, and further data due later this year will be closely watched.

Targeted protein degradation: notable players and progress
Company ValuationNotable deals/progress in protein degradation
VividionBought for up to $2bn by Bayer; had raised $271m in VC cash since 2017Preclinical; 2019 Roche discovery deal ($135m up front); 2018 Celgene discovery deal ($110m up front)
ArvinasMarket cap $4.7bn (Nasdaq listed)Licensed ph2 ARV-471 to Pfizer for $650m up front; 2019 Bayer deal (incl agriculture applications) for $110m up front
Kymera$2.7bn market cap (Nasdaq listed)Irak4 degrader KT-474 in ph1, being developed under broad deal with Sanofi ($150m up front)
Nurix$1.5bn market cap (Nasdaq listed)BTK degrader NX-2127 in ph1; 2020 Sanofi deal ($55m up front); 2019 Gilead deal ($45m up front)
C4 Therapeutics$2.1bn market cap (Nasdaq listed)IKZF1/3 degrader CFT7455 in ph1; 2016 discovery deal with Roche extended in 2019
Monte Rosa Therapeutics$1.3bn market capWork preclinical
RoivantDue to float via Spac with estimated proforma EV $5bnBought Silicon Therapeutics to boost platform for $450m in stock
Seed TherapeuticsBeyondspring subsidiary2020 discovery deal with Lilly ($10m up front)
CullgenRaised $81m in VC cash since 2018Plans IND later this year for TRK protein degrader CG001419
PlexiumRaised $63m in VC cash since 2019Preclinical
Lycia TherapeuticsLaunched in 2020 with $50m VC cashPreclinical
Mission TherapeuticsRaised $184m in VC cash since 2011Research deal with Abbvie over deubiquitylating enzymes to treat Alzheimer’s and Parkinson’s
Palleon PharmaceuticalsRaised $148m in VC cash since 2017Lead project to enter clinic 2021
Frontier MedicinesRaised $155m in VC cash since 2019Preclinical
Note: list not exhaustive. Source: Evaluate Pharma & company statements. 

Interestingly, Bayer struck a deal with Arvinas in 2019 to explore targeted protein degradation in oncology, gynaecology and cardiovascular areas, and this is still active. Perhaps this tie-up persuaded Pfizer that this was a technology it needed in house.

Other big pharma names that come up frequently here include Sanofi, Bristol Myers Squibb and Roche. In fact the last two already have deals in place with Vividion that will continue, Bayer says. The deal with Roche over a “well-known but difficult to drug” cancer target recently completed preclinical development.

Only Bayer has pulled the trigger on an acquisition, however, and the valuations of some of the independent players – despite the vast majority of their work being preclinical – helps to explain why.

Nurix, Kymera and Monte Rosa – all of which boast targeted protein modulation or degradation platforms – floated this year, with upsized and oversubscribed offerings. All now sport market caps well north of $1bn. Bayer presumably took the view that buying Vividion would be cheaper now than after the public markets put an acquisition premium on the stock.

Still, Vividion’s backers, which include the venture firms Cardinal, Versant and Arch, will be enjoying this substantial payday. A further $500m is on the table should milestones be hit.

Considering that this area still requires much development work, even before clinical proof of concept can be achieved, $1.5bn in the bank was clearly an offer that could not be refused.

https://www.evaluate.com/vantage/articles/news/deals/bayer-beefs-discovery-work-vividion-buyout

STAAR Surgical Company Q2 adjusted earnings Beat Estimates

 Below are the earnings highlights for STAAR Surgical Company (STAA):

-Earnings: $8.57 million in Q2 vs. -$1.17 million in the same period last year. -EPS: $0.17 in Q2 vs. -$0.03 in the same period last year. -Excluding items, STAAR Surgical Company reported adjusted earnings of $13.54 million or $0.27 per share for the period. -Analysts projected $0.03 per share -Revenue: $62.37 million in Q2 vs. $35.19 million in the same period last year.

-Guidance: Full year revenue guidance: $227 - $230 Mln

https://www.nasdaq.com/articles/staar-surgical-company-q2-adjusted-earnings-beat-estimates-2021-08-04

Hospitals with higher Medicare shares were more likely to close or be acquired from 2010-16

 Hospitals with a higher portion of Medicare patients had worse financials and were more likely to close or be acquired than facilities less reliant on Medicare payments, according to data published this week in Health Affairs.

The performances of these Medicare-reliant hospitals deteriorated even further during the later part of the analysis’s study period when Medicare inpatient price increases lagged hospitals’ growing costs, Harvard Medical School researchers found.

The increased rate of closures and consolidation that followed suggests hospitals were unable to offset insufficient revenue by reducing expenses or cost-shifting—a compensatory practice that was previously thought to be responsible for higher industrywide commercial prices.

“The cost-shifting narrative and the empirical strategies used to evaluate it typically assume no connection between public prices and the number of hospitals operating in the market,” the researchers wrote in Health Affairs. “We raise the possibility of ‘consolidation-induced cost-shifting,’ which recognizes that changes in public prices for hospital care can affect market structure and, through that mechanism, affect commercial prices.”

The researchers’ analysis included a sample of 2,986 hospitals’ cost reports from 2010 to 2016, which were collected from Medicare’s Healthcare Provider Cost Report Information System. They also collected supporting data on hospital closures and characteristics from the American Hospital Directory, Census Bureau and other sources.

Facilities with a higher share of Medicare patients were more often rural, nonteaching public hospitals, the researchers found. They often had fewer beds, lower wage indices and were located in counties with smaller and older populations.


Hospitals with Medicare share exceeding 65% in 2010 had a -0.38 operating margin versus the 4.46 margin seen among those with Medicare shares below 35%, the researchers found. By 2016, that operating margin gulf widened to -3.45 and 5.32. The negative relationship between Medicare share and operating margin persisted during a regression analysis controlling for differences in hospital and market characteristics.

Overall, the analysis found that a hospital with a 65% Medicare share had a roughly 24% chance of being closed or acquired during the study period, compared to a roughly 16% chance for an identical hospital with a 35% Medicare share, the researchers found.

While the findings are reason for caution when scheduling public prices, the researchers wrote that the threat of closures shouldn’t keep public payers from reducing prices.

Prior policy literature suggests lower payments generally lead to more efficient operations, they wrote, and not all poor performers should be given a lifeline.

“Paying more than needed for most care to preserve access to some care and to forestall consolidation-induced commercial price increases would exacerbate the fiscal challenges facing Medicare,” the researchers wrote.

Critical access hospitals and others that provide services addressing unmet needs can be supported by existing programs, they said. As such, policymakers looking to tackle consolidation and rising commercial prices will be better served tackling those issues via antitrust initiatives and other regulations.

“Essentially, the existence of consolidation-induced cost-shifting must be a consideration in public fee setting but not a barrier to policy action,” the researchers wrote. “Payment levels and payment models must be designed to encourage the efficient production of care, while, simultaneously, policy must be designed to limit the deleterious consequences of market power.”

https://www.fiercehealthcare.com/hospitals/hospitals-higher-medicare-shares-were-more-likely-to-close-or-be-acquired-from-2010-2016

WCG Clinical postpones massive IPO that sought $720M raise

 An eye-popping $720 million in proceeds and a $6.1 billion valuation? Yeah, that won't happen Thursday for WCG Clinical, the company's chief executive confirmed in a statement to Fierce Biotech. 

The nine-year-old company, which offers trial help to biopharmas and CROs, is postponing its debut on the Nasdaq, Donald A. Deieso, Ph.D., executive chairman and CEO said. The company "may reevaluate in the future when conditions are more conducive to sharing our unique story and market opportunity," he added. 

After filing for the customary $100 million IPO on July 1, WCG Clinical had aimed for $720 million in proceeds, the midpoint of the range set forth in a Securities and Exchange Commission filing dated Aug. 2. That would value WCG at about $6.1 billion after selling 45 million shares at $16 apiece.


That's a hefty price tag for the Princeton, New Jersey-based company, putting it closer in value to CRO Parexel than newer players like Science 37, which tapped a blank check company to go public in May at a $1 billion valuation. Parexel got the big bucks last month when EQT and Goldman Sachs said they would dish out $8.5 billion in an acquisition. 

In its regulatory filings, WCG revealed the price tags on its recent acquisitions. WCG bought VeraSci on July 20 for $330 million in cash to boost its trial capabilities for central nervous system disorder drugs. That was funded in part by a $140 million revolving credit facility. 

The IPO proceeds would have been used to repay all outstanding borrowing from that $140 million credit facility. The remainder will go toward paying down other debts from the first lien loan. 


WCG also acquired medical imaging and cardiac safety lab services company Intrinsic Imaging in June. That deal, at a price tag of $80 million, was funded entirely by cash on hand and could include earn-outs totaling $12.1 million. WCG also used $36 million cash on hand to buy life sciences consulting firm Avoca Group in April. 

Those are just three of the 31 acquisitions the 4,000-employee WCG has closed since 2012. 

WCG made about $463 million last year, a 12% increase over 2019. For the three months ended March 31, 2021, WCG generated $137 million, a 33% jump year over year. 

The COVID-19 pandemic, which is once again swelling with the spread of the delta variant, has had a big impact on clinical trials. WCG acknowledged in its prospectus that the pandemic could continue hampering the biopharma industry and its customers. 

WCG boasted that it supported 723 COVID-19 trials, including "many of the most highly impactful vaccines and antivirals." Across the company's entire portfolio, WCG-supported studies have enrolled about 2.5 million patients.

WCG had planned to trade under the symbol "WCGC."

https://www.fiercebiotech.com/cro/wcg-clinical-to-begin-trading-thursday-to-raise-up-to-765m

Moderna abandons mid-stage mRNA cancer asset for similar triple-attack candidate

 Moderna has ditched a phase 2 asset in development for solid tumors, lymphoma and ovarian cancer to instead focus on a similar therapy that could put up a triple attack.

The biotech, of COVID-19 vaccine fame, revealed in a second-quarter earnings release Thursday that the standalone OX40L candidate mRNA-2416 will be shelved in favor of mRNA-2752, which codes for OX40L as well as IL23 and IL36γ. OX40L is a ligand that regulates cytokine production from T cells as part of a large group of proteins, while IL23 and IL36γ are pro-inflammatory cytokines.

Both therapies are part of Moderna’s mRNA intratumoral immuno-oncology portfolio. These drugs are designed to treat cancer by transforming the tumor microenvironment to spur anticancer T-cell responses that attack the tumors. The therapies can be designed to be injected directly into the tumor to cause an attack on itself and linked tumors, meaning drugs that could otherwise be toxic to the patient can be delivered safely.

On Moderna's pipeline, mRNA-2752 has been listed as a phase 1 asset only for solid tumors and lymphoma. mRNA-2416, on the flip side, was the only cancer candidate specifically listed for ovarian cancer. 


In a letter to shareholders last year, CEO Stéphane Bancel touted the dosing of patients in a phase 2 expansion trial for mRNA-2416. At the time, Bancel said a phase 1 trial for the triplet therapy mRNA-2752 was ongoing, and no further update was provided in its earnings report.

In other Moderna news, enrollment has completed in a phase 1 study for a next-generation COVID-19 vaccine that the company hopes will be refrigerator-stable. This could help facilitate easier distribution and storage. Both Moderna and Pfizer-BioNTech’s mRNA COVID vaccines have extreme cold storage requirements, which has hampered roll-out in some areas of the world.

Studies of the original COVID-19 vaccine, which the company is hoping to call Spikevax, are underway in children aged 6 months to 11 years old.

A slight update was also offered on when a phase 3 study for the cytomegalovirus vaccine candidate mRNA-1647 will get underway. The biotech is now aiming to kick that off sometime this year.

https://www.fiercebiotech.com/biotech/moderna-abandons-mid-stage-cancer-asset-favor-similar-triple-attack-candidate