Alvotech: Feb. goal date for Humira biosimilar approval

 Alvotech (NASDAQ: ALVO, or the “Company”), a global biotech company specializing in the development and manufacture of biosimilar medicines for patients worldwide, announced today that the U.S. Food and Drug Administration (FDA) has accepted Alvotech’s resubmitted Biologics License Application (BLA) for AVT02, a high-concentration, interchangeable biosimilar candidate to Humira^® (adalimumab). The FDA has also announced a Biosimilar User Fee Act (BsUFA) goal date for approval of the resubmitted AVT02 BLA.

The BsUFA goal date provided by the FDA is February 24, 2024. The FDA indicated that Alvotech’s resubmission is considered to be a complete response to the agency’s June 28, 2023, action letter, given the additional Chemistry, Manufacturing and Controls information submitted by the Company with the BLA to address manufacturing facility deficiencies identified earlier by the FDA.

https://www.biospace.com/article/releases/alvotech-provides-u-s-regulatory-update-on-avt02-a-high-concentration-interchangeable-biosimilar-candidate-to-humira-adalimumab-/

Relmada" Positive Efficacy and Safety Results in Phase 3 Long-Term Study in Major Depressive Disorder

 

• Patients newly treated with REL-1017 for up to one year experienced rapid, clinically meaningful, and sustained improvements in depressive symptoms and associated functional impairment
• Long-term dosing with REL-1017 was well-tolerated, with low rates of adverse events and discontinuations due to adverse events, and no new safety signals were detected

https://www.biospace.com/article/releases/relmada-therapeutics-announces-efficacy-and-safety-results-from-the-phase-3-long-term-study-of-rel-1017-in-major-depressive-disorder/

Fresh Tracks, Histogen to Shutter Businesses in Absence of Viable Options

 Colorado-based pharma Fresh Tracks announced Tuesday that its board of directors had unanimously agreed to dissolve the company and liquidate its assets, while California biotech Histogen on Monday also announced that it was dissolving and liquidating its business.

Fresh Tracks will discontinue all its clinical and preclinical development programs as well as lay off “most employees,” which is set to happen by early October 2023, according to the company’s announcement.

The news comes after the company’s search for potential strategic alternatives to save its business had turned up empty. However, Fresh Tracks will retain consultants, advisors and certain employees who are involved in the company’s dissolution. The company’s liquidation is still pending final approval from its shareholders.

A day before Fresh Tracks announced its closure plans, San Diego-based Histogen said that it was dissolving and liquidating its business. Like its Colorado counterpart, Histogen has opted to discontinue all clinical development programs and has drastically slimmed down its workforce as part of its dissolution plan. Most employees will be laid off by the end of September 2023, according to the company’s announcement.

Fresh Tracks was launched in September 2022 from a sweeping rebranding of Brickell Biotech. At the time, former CEO Robert Brown said that the company’s new name reflects the company’s mission “to develop groundbreaking, novel therapies that have the potential to restore immune balance.” Brown retired in January 2023 and was succeeded by Andew Sklawer.

The company has since advanced a pipeline of immunology assets, including the DYRK1A inhibitor FRTX-02, which was in Phase I assessments for atopic dermatitis and was also being proposed for rheumatoid arthritis and type 1 diabetes. The company also owned an oral STING inhibitor, dubbed FRTX-10, which was in preclinical development for systemic lupus erythematosus, dermatomyositis and non-alcoholic steatohepatitis.

In its most recent earnings report, posted August 2023, Fresh Tracks announced that it had “paused substantially all of its research and development activities in order to conserve capital resources.” In a previous earnings call soon after its rebrand, the company indicated that it was looking at strategic options including financing, merger or reverse merger, business combination or the sale of part of the company.

Under its plan of dissolution, Histogen is considering selling off its pipeline assets—the proceeds from which would be distributed to stockholders along with its remaining cash. The proposed dissolution is still pending approval from the company’s stockholders, for which it expects to convene a special meeting in the fourth quarter of this year.

Prior to the announcement, Histogen was advancing its experimental bacterial skin infection treatment emricasan. It had received the FDA’s go-ahead in March 2023 to conduct clinical trials for the candidate.  

https://www.biospace.com/article/fresh-tracks-histogen-shutter-businesses-in-absence-of-viable-options/

Bausch Health upped to Buy from Hold by Jefferies

 Target to $16 from $9

https://finviz.com/quote.ashx?t=BHC&p=d

Exscientia Announces AI Drug Discovery Collaboration with Merck KGaA

Collaboration will leverage Exscientia’s precision design capabilities to focus on previously unsolved drug design challenges

Exscientia is eligible to receive up to $674 million in discovery, development, regulatory and sales-based milestones for three projects, in addition to single to double digit royalty payments on net sales

Up to $113 million of potential milestone payments in the discovery phase, with $20 million upfront at initiation for three projects

https://finance.yahoo.com/news/exscientia-announces-ai-drug-discovery-050000497.html

Seelos: Suicide study too small to meet endpoints

 

• SLS-002 demonstrated early and persistent clinically meaningful reductions in symptoms of depression and acute suicidality

• Robust Response and Remission Rates were observed using the Montgomery-Åsberg Depression Rating Scale (MADRS)

• Results demonstrate the therapeutic potential of SLS-002 to address imminent suicidality

• SLS-002 was well-tolerated, with no evidence of new or unique adverse events and there were no deaths reported in the study

• The Company will host a webcast with Dr. David V Sheehan, today, Wednesday, September 20th at 8:00 a.m. ET

Seelos will host a webcast today, Wednesday, September 20th, at 8 a.m. ET, to discuss the results. On the call from Seelos will be Raj Mehra, Ph.D., Chairman and CEO, and Tim Whitaker, M.D., Chief Medical Officer.

Additionally, David V. Sheehan, M.D., the Distinguished University Health Professor Emeritus at the University of South Florida College of Medicine, will be on the call as well to discuss this data.

Webcast for live and replay: https://lifescievents.com/event/seelos-2

A replay of the webcast will be available shortly following the presentation.

https://finance.yahoo.com/news/seelos-therapeutics-announces-top-line-110000268.html

New Study Detects Spike Protein 6 Months After COVID-19 Vaccination

 by Megan Redshaw via The Epoch Times (emphasis ours),

According to the Centers for Disease Control and Prevention (CDC), mRNA from COVID-19 vaccines is “broken down within a few days after vaccination and doesn’t last long in the body”—a position it has adhered to since the pandemic's beginning, despite research suggesting otherwise (pdf). The CDC refers to mRNA as “messenger RNA,” whereas regulatory documents and Pfizer refer to the mRNA in COVID-19 vaccines as “modified RNA.”

Yet a new study published on Aug. 31 in Proteomics Clinical Applications found spike protein in the biological fluids of people who received an mRNA COVID-19 vaccine six months after vaccination, suggesting mRNA may be integrated or retranscribed in some cells.

The study group included 20 subjects who received two doses of an mRNA COVID-19 vaccine, 20 who were unvaccinated and tested negative for COVID-19 or antibodies indicating they had previously been infected, and a control group of 20 unvaccinated participants who tested positive for COVID-19.

Researchers then tested to differentiate synthetic spike proteins originating from mRNA vaccines from natural spike proteins in biological fluids, such as blood, urine, saliva, and bronchoalveolar lavage fluids of study participants and monitored vaccine-induced spike protein following vaccination.

Spike Protein From mRNA Differs from Post-Infection Spike Protein

According to the study, spike proteins originating from the translation of mRNA vaccines differ from natural spike proteins that circulate in biological fluids post-infection because two proline amino acids replaced the amino acids lysine and valine to help stabilize the synthetic spike generated by vaccination. This double amino acid variation removed a tryptic digestion site (a necessary part of protein absorption) on the natural spike protein. Because of this, researchers said it is possible to differentiate between natural and synthetic spike protein in biological fluids using tryptic digestion followed by mass spectrometry analysis.

Utilizing these techniques, researchers detected specific fragments of synthetic spike protein in about 50 percent of subjects who received mRNA vaccines. The synthetic spike protein was detected from 69 to 187 days following vaccination. All samples from the unvaccinated control group were negative, including the 20 individuals who had tested positive after contracting COVID-19.

3 Hypotheses for Persistent Synthetic Spike Protein in Vaccinated

Based on the results of the study, researchers suggested three possible hypotheses to explain why synthetic spike protein persisted in the vaccinated:

• The mRNA from COVID-19 vaccines may be integrated or retranscribed in some cells.
• Pseudouridines at a particular sequence position may induce the formation of a spike protein, although the researchers stated this was a remote possibility.
• The mRNA-containing nanoparticles may be picked up by bacteria ordinarily present at the basal level in the blood and produce spike protein.

Although researchers said all three hypotheses need further study, they concluded that their initial observations could aid in an individual’s decision about whether to take boosters.

Other Studies

In a recently published paper in Biomedicines, data show the design of the mRNA COVID-19 vaccines allows uncontrolled biodistribution, durability, and persistent bioavailability of the spike protein inside the body after vaccination.

“The lipid-nanoparticle matrix permits widespread biodistribution of mRNA gene codes to cells in most or all organs” and could potentially damage tissues and cause disease, researchers concluded.

A study published in November 2021 in the Journal of Immunology found exosomes expressing spike protein 14 days after vaccination with mRNA COVID-19 vaccines. A spike protein increase was observed four months following the second vaccine dose and increased following booster doses.

In a January 2023 study published in the Journal of Pathology, Microbiology, and Immunology, researchers found full-length or traces of SARS-CoV-2 spike mRNA in some patient samples up to 28 days after COVID-19 vaccination, indicating prolonged spike protein production.

A study published in March 2022 in Cell found vaccine mRNA in lymph nodes on days 7, 16, and 37 following vaccination, with lower but still appreciable levels at day 60. Immunohistochemical staining for spike antigen in mRNA-vaccinated patient lipid nanoparticles in some individuals showed an abundant amount of spike protein 16 days after the second dose, with spike antigen “still present as late as 60 days post-second dose,” researchers said.

A Pfizer Japanese biodistribution study showed COVID-19 vaccine spike protein can travel from the injection site through the blood and accumulate in organs and tissues, including the spleen, bone marrow, liver, adrenal glands, and ovaries. Vaccine mRNA was present from the day of vaccination and persisted in the bloodstream for weeks after vaccination.

CDC Says Vaccines Do Not Affect DNA, Despite Conflicting Evidence

The CDC, in addition to claiming mRNA from COVID-19 vaccines quickly break down within the body, also states on its website that these vaccines “do not affect or interact with our DNA”—the genetic material contained within the nucleus of cells—because these vaccines do not “enter the nucleus of the cell.”

The agency says “messenger RNA” COVID-19 vaccines work by “delivering instructions (genetical material) to our cells to start building protection” against SARS-CoV-2, and that the body discards all vaccine ingredients after producing an immune response just as it discards “any information cells no longer need.” According to the CDC, this process is a “part of normal body functioning.”

The current analysis and previous studies challenge this position. A February 2022 study published in Current Issues in Molecular Biology shows reverse transcription of vaccine mRNA into DNA using human liver cell lines. Additional studies have shown RNA from SARS-CoV-2 can be reverse-transcribed and integrated into the genome of cultured human cells—and expressed in patient-derived tissues or by virus-infected cells.

To date, pharmacokinetic and pharmacodynamic data on mRNA COVID-19 vaccines is limited. Pharmacokinetics is the study of how the body responds to administered substances throughout the entire duration of exposure. Pharmacodynamics assesses the drug’s effect on the body more closely. Understanding how long spike protein is produced by the body and how long it is present in biological tissues could explain the unprecedented number of adverse events that appear to be associated with the spike protein produced by vaccines.

https://www.zerohedge.com/covid-19/new-study-detects-spike-protein-6-months-after-covid-19-vaccination