Beam Therapeutics Shares Fall Premarket as FDA Puts Study on Hold

 Shares of Beam Therapeutics Inc. slipped more than 10% in premarket trading on Monday after the biotechnology company said the U.S. Food and Drug Administration placed its investigational new drug application for its BEAM-201 program on clinical hold.

The Cambridge, Mass., company said the FDA informed it of the hold via e-mail on Friday, adding that the agency indicated it will provide an official letter within 30 days.

According to the FDA's website, subjects can't be given an investigational drug when a proposed study is placed on clinical hold. The agency lists several potential reasons for putting an IND on hold, including the possibility that human subjects "would be exposed to an unreasonable and significant risk of illness or injury," or that the application doesn't contain enough information to assess the risks to subjects of the proposed studies.

Beam, which submitted its application to study BEAM-201 for the treatment of relapsed/refractory T-cell acute lymphoblastic leukemia/T cell lymphoblastic lymphoma in late June, said it will provide further updates pending talks with the FDA.

https://www.marketscreener.com/quote/stock/BEAM-THERAPEUTICS-INC-102685993/news/Beam-Therapeutics-Shares-Fall-Premarket-as-FDA-Puts-Study-on-Hold-41155001/

J&J Gets FDA OK of Stelara for Pediatric Patients With Active Psoriatic Arthritis

 Johnson & Johnson's Janssen Pharmaceutical Cos. unit on Monday said the U.S. Food and Drug Administration approved the expanded use of its blockbuster anti-inflammatory drug Stelara to treat children ages six and older with active psoriatic arthritis.

The company said two of the four FDA-approved indications for Stelara now include pediatric patients.

The agency first approved Stelara in September 2009 for adults with moderate to severe plaque psoriasis, and the drug has since been cleared for use in psoriatic arthritis, Crohn's disease and ulcerative colitis.

Johnson & Johnson reported second-quarter Stelara sales of nearly $2.6 billion.

https://www.marketscreener.com/quote/stock/JOHNSON-JOHNSON-4832/news/J-J-Gets-FDA-OK-of-Stelara-for-Pediatric-Patients-With-Active-Psoriatic-Arthritis-41156911/

Tonix Pharma Shares Rise 16% After Patent for TNX-1900 Migraine Treatment

 Tonix Pharmaceuticals Holding Corp. shares were up 16% to $1.95 Monday after the company said the U.S. Patent and Trademark Office issued a patent to the company on July 19.

The company said the patent, entitled "Magnesium-Containing Oxytocin Formulations and Methods of Use," claims methods and compositions for treating pain, including that incident to migraine headaches, using intranasal magnesium-containing oxytocin formulations.

The patent, excluding possible patent term extensions, is expected to provide Tonix with U.S. market exclusivity until January 2036, the company said.

In late 2021, Tonix received investigational new drug clearance from the U.S. Food and Drug Administration to support the initiation of a Phase 2 study of TNX-1900 intranasal potentiated oxytocin for the prevention of migraine headache in chronic migraineurs.

The company said it continues to expect to begin enrollment in the Phase 2 study during the second half of 2022.

https://www.marketscreener.com/quote/stock/TONIX-PHARMACEUTICALS-HOL-47362663/news/Tonix-Pharma-Shares-Rise-16-After-Patent-for-TNX-1900-Migraine-Treatment-41158376/

Most Americans will feel tax pain from Dem inflation bill despite Biden promises

 The vast majority of Americans will pay more in taxes as a result of Democrats' inflation bill despite President Biden's pledge not to raise taxes on those making under $400,000 per year.

The Inflation Reduction Act — unveiled Wednesday by Sen. Joe Manchin, D-W.Va., and endorsed by Biden — would increase tax revenue by $16.7 billion from Americans earning less than $200,000 a year, according to a nonpartisan analysis from the Joint Committee on Taxation (JCT) published Friday. Nearly every tax bracket would pay more in taxes with those making below $10,000 per year seeing the largest uptick, the analysis showed.

"The more this bill is analyzed by impartial experts, the more we can see Democrats are trying to sell the American people a bill of goods," Senate Finance Committee Ranking Member Mike Crapo, R-Idaho, said in a statement Saturday. "Non-partisan analysts are confirming this bill raises taxes on the middle class and produces no meaningful deficit reduction when gimmicks are removed and the full cost is accounted for." 

However, Biden has repeatedly pledged that Americans earning less than $400,000 per year would not experience any tax increase during his presidency. The president originally made the pledge during his 2020 campaign.

"This bill will not raise taxes on anyone making less than $400,000 a year," Biden remarked Thursday during a speech about the legislation. "And I promise — a promise I made during the campaign and one which that I ha- — that I’ve have kept."

In 2023, the year in which the legislation would increase tax revenue most, individuals making less than $10,000 per year would pay 3.1% more in taxes and those making between $20,000-30,000 per year would see a 1.1% tax increase, the JCT analysis showed. Tax revenue collected from those making $100,000 per year or less would increase by $5.8 billion in 2023 under the Inflation Reduction Act.

In addition, the share of tax revenue collected from all Americans making more than $200,000 per year would remain at the current percentage, according to the JCT. Taxpayers with an annual income of $200,000 or greater pay more than 57% of all federal income taxes.

The Inflation Reduction Act, though, boosts Internal Revenue Service enforcement, a provision that is expected to increase federal tax revenue by $124 billion. The bill also creates a minimum corporate tax rate of 15% which is expected to boost federal tax revenue by $313 billion.

"The proposed corporate alternative minimum tax is the largest revenue raising provision in the analysis," Thomas Barthold, the JCT's chief of staff, told FOX Business in an email.

It was not immediately clear how much each provision of the bill would lead to higher taxes. The JCT listed more than 20 of the legislation's provisions that it factored into its analysis.

"Democrats are clearly trying to pivot this as only a tax like on the wealthy," Mike Palicz, the federal affairs manager at Americans for Tax Reform, told FOX Business in an interview. "But you look at any of these taxes — take something like the [corporate minimum tax]. That's going to lower workers' wages, it's going to cost jobs."

"There's a $25 billion crude oil tax in this bill," he added. "That's something that's going to hit everyone. That's a regressive tax increase on poor people that raises their energy costs, raises the price of gasoline."

Transportation Secretary Pete Buttigieg previously said that a gasoline tax increase would violate Biden's pledge not to raise taxes on middle class Americans.

"This is Biden breaking his promise to the American people," Palicz said.

https://www.foxbusiness.com/politics/most-americans-feel-tax-pain-dem-inflation-bill-despite-bidens-past-promises

AAIC 2022: Vivoryan, Anavex and More Tout Innovation in Alzheimer's Space

 The ongoing 2022 Alzheimer's Association International Conference (AAIC) in San Diego has delivered a string of positive news for the AD space. We take a look at updates from Vivoryon, Anavex and Argentinian scientists below. 

Vivoryon Posts Promising Preclinical Evidence Of A Potential AD Drug

Vivoryon shared two sets of preclinical data showcasing its N3pE amyloid-targeting therapeutic strategy's potential in mono- and combination therapy for Alzheimer's disease. N3pE amyloid (pGlu3-Abeta) is a toxic type of Abeta that hastens plaque aggregation and seeding, thus making it an important therapeutic target. N3pE amyloid that has formed can be catalyzed by QPCT, an enzyme expressed mainly by the learning and memory centers of the brain. Toxic N3pE is not found in healthy individuals. 

The company's first preclinical report (Poster P1-457) showed that combining the QPCT/L inhibitor varoglutamstat and the N3pE amyloid-specific PBD-C06 can help lower N3pE amyloid in vivo. 

Vivoryon evaluated whether a similar additive effect can be achieved if varoglutamstat is combined with Abeta-plaque-specific antibody aducanumab in a double transgenic mouse model that over expresses a variant of the human amyloid precursor protein and human QPCT. The animals were then given either varoglutamstat, chimeric aducanumab (chAdu) or a combination of both for 16 weeks and analyzed for accumulation markers. 

The scientists found that single agent treatment with either varoglutamstat or chAdu reduced N3pE and total Abeta accumulation in the brain. The effect for chAdu also appeared to be greater on total Abeta, while varoglutamstat led to a stronger drop in N3pE amyloid levels. 

In its second report (Poster P1-04), they explored the effect of 07/2a-k compared to 3D6-L in mice with AD. 3D6-L is a murine analog of bapineuzumab, a classical anti-Abeta antibody, while 07/2a-k is a CDC-mutant version of the PBD-C06 precursor 07/2a. 

Results from the study on mice showed that 07/2a-k had no effect on the biochemical or pathological Abeta measures, but it modestly improved memory based on the Novel Object Recognition task. It did not have any impact when the Barnes maze metric was used. The good thing is that 07/2a-k did not result in any micro- or macro hemorrhages, whereas 3D6-L induced a high number. 

Vivoryon is working on more preclinical trials to further assess the potential of PBD-C06. 

Anavex Shares First Complete Gene Pathway Data on Parkinson's Disease Dementia Study

Anavex Life Sciences announced the first entire clinical gene pathway data from the Anavex 2-73-PDD-001 Parkinson's Disease Dementia PDD study. The randomized, placebo-controlled trial involved 132 PDD patients whose gene expressions were observed after 14 weeks. Pathway analysis showed the biological relevance of the PDD gene network and confirmed the effect of Anavex 2-73 on neurodegenerative illnesses, particularly PD and AD. 

"To my knowledge, this represents the first extensive transcriptomics analysis (RNAseq) of a therapeutic agent in patients with Parkinson's disease dementia (PDD). It is very intriguing to confirm this robust correlation of the clinical improvements of motor impairment (MDS-UPDRS) and cognition (CDR system) with compensation of expression levels of dysregulated neurodegenerative genes, especially Alzheimer's disease and Parkinson's disease, through the therapeutic effect of ANAVEX 2-73," Dr. Jaime Kulisevsky, M.D., Ph.D., the study's principal investigator said. 

"PDD is a debilitating disorder with significant co-morbidities and there has not been a mechanistically novel medication approved for PDD in over 20 years. Hence, new therapies are urgently needed to alleviate this suffering and disability," Kulisevsky added.

Trial participants had the option to enroll in a voluntary 48-week open-label extension trial after completing Anavex 2-73-PDD-001. This study is ongoing. 

Argentinian Scientist Says Loss Of Smell From COVID-19 May Predict Disease Severity

A group of scientists from Argentina found that persistent loss of the sense of smell related to COVID-19 may be a better indicator of the disease's severity and long-term effect in initial cases.

Working with the Alzheimer's Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 Infection, the scientists observed 766 adults ages 55 to 95 years who were exposed to COVID-19 for a year. After a series of physical, cognitive and neuropsychiatric tests were conducted, the researchers found that two-thirds of the participants showed functional memory impairment. 

Other metrics used showed similar outcomes, with 11.7% demonstrating memory-only impairment, 8.3% exhibiting attention and executive function impairment and 11.6% displaying multi-domain impairment. Of them all, persistent loss of smell was a common factor, especially in cognitive impairment.

"The more insight we have into what causes or at least predicts who will experience the significant long-term cognitive impact of COVID-19 infection, the better we can track it and begin to develop methods to prevent it," Gabriela Gonzalez-Aleman, LCP, Ph.D., a professor at Pontificia Universidad Catolica Argentina, Buenos Aires, commented.

Other notable findings that the scientists shared were the increased likelihood that intensive care unit stays will increase dementia risk and that introducing a positive life change amidst the pandemic may protect against symptoms of cognitive decline. 

"This study is an example of how investigators from diverse countries in Latin America and the United States, many of whom had never worked together before and had limited resources, came together under difficult circumstances but with a shared goal to advance scientific understanding about Alzheimer's, and the important contributions that such multicultural partnerships can yield," María Marquine, Ph.D., associate professor in the Departments of Medicine and Psychiatry and director of disparities research in the Division of Geriatrics, Gerontology and Palliative Care at the University of California, San Diego, noted. 

https://www.biospace.com/article/aaic-2022-updates/

Ipsen Invests Potential $1.6B to Turbo-Charge Marengo's Path to the Clinic

 Marengo Therapeutics and Ipsen announced Monday that they have entered into a strategic, multi-year partnership to usher two of Marengo’s precision T cell immuno-oncology candidates into the clinic.

At the core of the partnership are two candidates in the early preclinical assessment stage, both discovered using Marengo’s proprietary Selective T Cell Activation Repertoire (STAR) antibody fusion platform. The company's lead candidate STAR0602 is not covered by the partnership.

The deal will see Ipsen make an upfront payment of $45 million and pledge potential payments that could reach $1.592 billion if all milestones are met. Marengo will also be eligible to receive tiered royalties. Under the terms of the agreement, Marengo will take responsibility for preclinical development and will shoulder all expenses until it is able to submit Investigational New Drug applications for the two candidates. Meanwhile, clinical development and commercialization will fall to Ipsen.

“Both candidates will be developed for different solid tumor indications, as we believe there is significant opportunity to develop potent, durable and safe treatments for these patients,” Dr. Zhen Su, M.D., CEO of Marengo Therapeutics, told BioSpace in an email. “Both candidates are currently in the preclinical stage, and we will work with Ipsen to advance them quickly into the clinic.”

Based in Cambridge, Massachusetts, Marengo launched late last year, powered by $80 million in funding from the life science-focused venture capital firm ATP. The young biotech brings to the immuno-oncology space its unique approach to cancer: By generating antibodies that very specifically target the variable beta (Vb) chain of the T cell receptor, Marengo hopes to boost the anti-tumor activity of T cells, ultimately conferring long-term protection against different cancers.

The company is further combining this precision T cell approach with its proprietary STAR platform. The technology fuses the T cell-targeted antibodies with other elements, such as costimulatory factors, which allow for a more fine-tuned T cell response. Taken together, Marengo’s approach can activate and expand a subset of T cells with impressive selectivity, boosting their natural cancer-killing capabilities while also limiting toxic side effects.

Importantly, whereas other immune-oncology therapies struggle to induce durable responses, T cells activated by Marengo’s approach exhibit a central memory phenotype, leading to long-term protection.

“This is a new category of treatment built on novel insights for T cell activation. A unique feature of the STAR platform is the ability to optimally reprogram T cell responses to generate endogenous, highly functional, cancer-killing T cells for solid tumors,” Su explained. “ Our approach is akin to turbo-charging a car engine versus removing the brakes.”

It’s a platform Ipsen clearly feels confident buying into.

“Marengo’s foundational discovery of activation of T cell subsets via TCR Vβ is unprecedented and highly differentiated from the current immuno-oncology technologies we have seen,” Dr. Howard Mayer, M.D., EVP and head of R&D at Ipsen said in a statement, adding that the deal “provides a strong foundation for a productive and successful collaboration as we embark on a journey to develop novel and durable therapies that will strengthen our oncology pipeline and further enhance our commitment to people living with cancer.”

Separately, Marengo’s lead candidate, STAR0602, is a bispecific antibody that, after it binds to the Vb chain of T cell receptors, delivers a costimulatory signal to the same T cell. Preclinical studies have shown that this cis-targeting mechanism elicits a strong and durable anti-tumor T cell response, even when given as a single agent, pointing to the potential of Marengo’s antibodies to be administered as a monotherapy.

STAR0602 is currently wrapping up preclinical studies and is expected to begin clinical assessments later this year.

https://www.biospace.com/article/ipsen-invests-potential-1-6b-to-turbo-charge-marengo-s-cancer-killing-t-cells-/

Kavanaugh Assassin Suspect Identified As A Transgender Female

 by Paul Joseph Watson via Summit News,

The man who authorities say planned to assassinate Justice Kavanaugh in a bid to impact the Roe v Wade decision identified as a transgender female called Sophie, according to court documents.

Nicholas Roske traveled to Kavanaugh’s home after the address was leaked by leftists on social media armed with a gun and a knife.

A transcript of a conversation Roske had on Reddit confirms that he actually planned to kill at least three Supreme Court judges in a bid to “stop roe v wade from being overturned” and permanently alter the balance of the court in favor of liberals.

“I could get at least one, which would change the votes for decades to come, and I am shooting for 3,” said Roske.

“All of the major decisions for the past 10 years have been along party lines so if there are more liberal than conservative judges, they will have the power,” he added.

Roske, who was captured after calling the police on himself, is known to have suffered psychiatric problems.

One of those problems appears to have been his identifying as a woman.

Court documents show that Roske identifies as a male to transgender female called Sophie.

As part of his transition, the alleged killer devoted much time to trying to find a romantic partner who would be comfortable with him identifying as transgender.

In one post, Roske described himself as a “24 year old MtF college graduate” who was seeking “a woman to cuddle and watch movies with,” something that could escalate to “making out.”

The would-be assassin also revealed that he was uncomfortable around other men.

https://www.zerohedge.com/political/kavanaugh-assassin-suspect-identified-transgender-female