Sunshine Biopharma mRNA Molecules Effective v. Multidrug Resistant Cancer Cells

 Sunshine Biopharma, Inc. (NASDAQ: “SBFM” and “SBFMW”), a pharmaceutical company focused on the research, development and commercialization of oncology and antiviral drugs, today announced that two of its newly designed mRNA molecules are effective at destroying cancer cells grown in culture.

The cytotoxicity tests were performed on a variety of cancer cells including multidrug resistant breast cancer cells (MCF-7/MDR), ovarian adenocarcinoma cells (OVCAR-3), and pancreatic cancer cells (SUIT-2). Toxicity studies using non-transformed (normal) human cells (HMEC cells) showed that these mRNA molecules had little or no cytotoxic effects. These new mRNA molecules are readily adaptable for delivery into patients using the mRNA vaccine technology. The Company anticipates filing a patent application in connection with these results soon.

https://finance.yahoo.com/news/sunshine-biopharma-newly-designed-mrna-120000056.html

ACC 2022 – Astra’s cholesterol lowerer surprise comes just a little late

 A little-known antisense oligonucleotide, Astrazeneca/Ionis’s AZD8233, has surprised in a mid-stage trial, showing cholesterol lowering well in excess of Amgen and Sanofi/Regeneron’s anti-PCSK9 MAbs and Novartis’s RNAi therapy Leqvio. 50mg once monthly, the middle of three AZD8233 doses tested in the Etesian study, prompted 73% LDL cholesterol reduction from baseline at 12 weeks, the ACC meeting heard yesterday. Astra had licensed AZD8233, a subcutaneously dosed inhibitor of PCSK9 expression, from Ionis back in 2016, five years before the companies tied up over eplontersen. The group played up AZD8233’s best-in-class efficacy and monthly dosing convenience; Leqvio is given every six months, but on a cross-trial basis appears less efficacious. Still, the real threat could come not from established anti-PCSK9s but from Merck & Co’s investigational MK-0616, which not only is given orally but also has shown LDL-C lowering of around 65%. A further caveat is safety: some patients given AZD8233 90mg experienced liver enzyme elevations. Two other phase 2 AZD8233 trials, the 28-week Solano study and Hyate, a Japan trial, are due to read out later this year.

Convenience and efficacy in PCSK9 inhibition
Product/project	Company	Description	Dosing	LDL-C lowering
Marketed
Leqvio (inclisiran)	Novartis	SC anti-PCSK9 RNAi	Twice-yearly SC	50-52%
Repatha	Amgen	SC anti-PCSK9 MAb	Two-weekly SC	55%
Praluent	Sanofi/Regeneron	SC anti-PCSK9 MAb	Two-weekly SC	58%
Phase 2
MK-0616	Merck & Co	Oral anti-PCSK9	Once-daily oral	~65%
AZD8233	Astrazeneca/Ionis	SC anti-PCSK9 antisense	Monthly SC	73%*
All on top of background statins; Repatha, Praluent & Leqvio data placebo-adjusted; SC=subcutaneous; IV=intravenous; *middle, 50mg dose. Source: product labels, AHA 2021 & ACC 2022. https://www.evaluate.com/vantage/articles/news/trial-results-conferences/acc-2022-astras-cholesterol-lowerer-surprise-comes

HDT Bio Demonstrates RNA Vaccines Matched to SARS-CoV2 Variants Protect Against Infection

 HDT Bio Corp., a developer of immunotherapies for oncology and infectious diseases, announced today publication in eLife of results of preclinical research that demonstrate its RNA vaccine targeting specific SARS-CoV2 variants protects against infection in the upper respiratory tract, reducing potential for transmission. In addition, the animal studies showed that even when not matched against variants, HDT Bio’s RNA vaccine protects against lower respiratory tract infection and disease regardless of viral strain.

“Our research demonstrates that targeting vaccines to a dominant strain, such as delta and omicron, could significantly slow the spread of the virus by reducing transmission from breakthrough infections,” said Steve Reed, Ph.D., HDT Bio CEO. “If you add to that the fact our LIONTM system enables us to deliver a cassette of as many as five self-replicating RNA molecules, each targeting a different variant, we have the potential to make one vaccine that affords broad protection against SARS-CoV2.”

HDT Bio’s COVID-19 vaccine is significantly different from current mRNA vaccines. Using self-replicating RNA, which is designed to amplify itself inside the body, generates effective activation of the immune system at a much lower dose than current vaccines. The advantage of using a lower dose of RNA not only is improved overall safety, but also enables HDT Bio to deliver multiple RNA molecules in one vaccine targeting multiple variants of the virus. In order for vaccines using mRNA to deliver multiple RNA molecules, the dosage level of each molecule would have to be lowered to ensure safety, reducing the vaccine’s ability to generate effective immunity.

The preclinical research, titled “SARS-CoV2 variant-specific replicating RNA vaccines protect from disease and pathology and reduce viral shedding following challenge with heterologous SARS-CoV2 variants of concern,” was conducted in collaboration with the National Institute of Allergy and Infectious Diseases at the National Institutes of Health. It was published February 22, 2022, online by eLife a not-for-profit peer-reviewed open access scientific journal for the biomedical and life sciences.

https://www.businesswire.com/news/home/20220405005060/en/HDT-Bio-Demonstrates-RNA-Vaccines-Matched-to-SARS-CoV2-Variants-Protect-Against-Infection-of-Upper-Airways-Important-for-Preventing-Transmission

Obesity may alter inflammation on a molecular level, throwing current treatments into question

 In a quest to understand why some obese people don’t react to treatment for inflammation, a team of California scientists says it may have uncovered the first glimmer of an answer. 

In a new study published last week in Nature, researchers from the Gladstone Institute, UCSF and the Salk Institute for Biological Studies reported that among obese mice, there were molecular changes in the immune response to atopic dermatitis that likely impacted their response to treatment. 

To examine the impact of obesity on immune response, the team used mice fed a high-fat diet and compared them to lean mice. After being infected, the obese mice had significantly more inflammation than the control group and worse disease severity even after weight loss. The scientists more closely examined the T-cell response among the two cohorts and found that among obese mice, there was an “unexpected and prominent” response among T helper 17 (TH17) cells. What’s notable is that atopic dermatitis is driven by the onslaught of T helper 2 cells (TH2), thrusting into question obesity’s impact on the immune response on a molecular level. 

Additional data from a cohort of 59 human patients with atopic dermatitis in addition to a longitudinal study of patients with asthma corroborated the top-line findings, namely that obese patients were more likely to have indications of TH17 inflammation.  

To further investigate the impact of this change, the researchers treated the mice with monoclonal antibodies that block the IL-4 and IL-13 cytokines released by Th2. Lean mice elicited a strong immune response whereas for obese mice, not only did they not respond, the disease got worse. 

“The treatment became a robust anti-treatment,” said Dr. Sagar Bapat, M.D., Ph.D., one of the lead authors of the study in a release. “This suggests that you can have identical twins show up to the hospital with the same disease, but if one is obese and one is lean, maybe the same drug won’t work on both.”

The implications of these results are wide-ranging for biotechs and pharmas, particularly Sanofi and Regeneron with their FDA-approved drug Dupixent for atopic dermatitis. Dupixent first received FDA approval in 2017 for adults with moderate-to-severe AD but has since expanded its use, most recently to kids six to 11. It’s become nothing short of a cash cow for the French pharma, particularly in 2021 when sales grew more than 50% from the year before, topping €5 billion. Its stunning revenue has attracted competition, specifically from Eli Lilly, which has invested more than $1 billion in lebrikizumab. The potential rival posted phase 3 data last month that analysts called “compelling”. 

The results of the mouse study beg the question: How do you then treat obese patients with severe allergies or inflammation? The positive news is that researchers found that adding an anti-diabetes drug to the treatment regimen was able to stymie TH17 development and improve the response to anti-TH2 treatments. In other words, potentially useful combination therapies could be deployed quickly. 

Nonetheless, the researchers say these results are just scratching the surface and have led to a fresh round of questions regarding the science behind this biological tweak. 

“What we’d like to know more about now is exactly how the T cell switch happens,” said Ye Zheng, Ph.D., another lead author of the study and an associate professor at Salk. “There are more details here to uncover that could have relevance for a host of diseases related to allergy and asthma.”

https://www.fiercebiotech.com/biotech/obesity-may-alter-inflammation-molecular-level-throwing-current-treatment-options-question

GOP eyes linking Title 42 to coronavirus deal

 Republicans are eyeing an attempt to link a Trump-era immigration policy to a coronavirus relief deal that senators are hoping to pass by the end of the week. 

GOP senators are pushing for a vote targeting the Biden administration’s decision to end Title 42 — which allowed migrants at the border to be ​summarily expelled from the country instead of being processed under regular immigration rules and allowed to exercise their right to claim asylum — as part of a debate over a $10 billion coronavirus relief deal announced earlier Monday. 

In order to pass the $10 billion coronavirus aid deal before the chamber leaves for a two-week break, Senate leadership is going to need cooperation from all 100 senators. That could give Republicans leverage to push for an amendment vote.

“It seems like there’s kind of critical mass behind that idea. How the Democrats want to handle that issue may have some bearing on how and when the COVID bill proceeds,” said Sen. John Thune (S.D.), the No. 2 Senate Republican. 

Thune added that if Democrats want to pass the coronavirus bill this week, they are going to have to negotiate with Republicans to speed things up. 

Republicans would need a decision by the Senate parliamentarian but think an amendment related to Title 42 would qualify for getting a simple majority vote — if Democrats let it come up. 

That could put Democrats in a politically awkward spot. Several Senate Democrats have been critical of the administration’s decision to end the Trump-era policy. Because of the 50-50 Senate, Republicans would need only one of those Democrats to vote for their amendment to get it added into a coronavirus relief bill. 

In addition to trying to get changes into the coronavirus bill, Republicans are expected to focus on the border heading into November. 

The administration on Friday rescinded Title 42, the Trump-era policy that allows for the rapid expulsion of migrants at the border and blocks them from seeking asylum.

The order from the Centers for Disease Control and Prevention lifts Title 42 on May 23. 

Sen. Joe Manchin (D-W.Va.) called its striking “a frightening decision” for an administration “nowhere near prepared” for an influx at the border.

Meanwhile, Sen. Mark Kelly (D-Ariz.), who is up for reelection, called it “the wrong decision.”

“It’s unacceptable to end Title 42 without a plan and coordination in place to ensure a secure, orderly, and humane process at the border,” Kelly wrote. 

https://thehill.com/news/senate/3259087-gop-eyes-linking-title-42-to-coronavirus-deal/

White House proposes fix to ‘family glitch’ in ObamaCare

 The Biden administration is proposing a rule change to the Affordable Care Act (ACA) to fix the so-called “family glitch” that blocks millions of people who receive health care through a family member’s work from qualifying for assistance with coverage.

During a press call, a senior administration official said the Treasury Department on Tuesday will release a proposal to change ObamaCare’s rules, allowing individuals in households that spend more than 10 percent of their income on health insurance to qualify for financial assistance.

Under the current rules, the ACA provides financial assistance to single customers who spend more than 9.83 percent of their income on their company’s health plan premium.

Spouses and children who are covered by a family member’s company-provided health plan are considered to have affordable coverage by the ACA, regardless of what percentage of their income they put towards their health insurance. This rule prevents an estimated 5 million people from qualifying for subsidized healthcare plans.

WIth the Treasury’s “modified interpretation” of the ACA, if coverage costs more than 10 percent of a household’s total income, then non-employee family members will be eligible for financial assistance during the next open enrollment period.

The Biden administration’s plan to address the “family glitch” was first reported by Politico.

According to the administration official, this rule change is expected to help around 200,000 uninsured people gain coverage for the first time and lower the premiums for nearly a million others. However, they acknowledged that some families may find it more convenient to stay under one health plan and not opt to move to a more affordable coverage plan under the proposed rule change.

Along with the rule change, President Biden will also be signing an executive orders that “directs agencies to continue their efforts to strengthen access to affordable high quality health care,” according to the senior administration official.

The proposed update to ObamaCare will be marked by an event at the White House on Tuesday, with former President Obama expected to be in attendance. It will be Obama’s first trip to the White House since leaving office in January 2017.

The senior White House official declined to specify what Biden’s executive order would include, but said it would include measures to make it easier for people to enroll, better understand their coverage options and protect them from “low quality health insurance.”

https://thehill.com/policy/healthcare/white-house-proposes-fix-to-family-glitch-in-obamacare/

argenx Presents Interim Results in Myasthenia Gravis Trial

 

• Interim data suggest long-term treatment with VYVGART provides improvementin generalized myasthenia gravis (gMG) disease scores that remainsconsistent over multiple treatment cycles
• Long-term safety profile of VYVGART treatment consistent with Phase 3 ADAPT study
• VYVGARTis the first-and-only approved neonatal Fc receptor (FcRn) blocker

https://www.biospace.com/article/releases/argenx-presents-interim-results-from-adapt-open-label-extension-study-evaluating-vyvgart-efgartigimod-alfa-fcab-in-generalized-myasthenia-gravis-at-2022-aan-annual-meeting/