NorthWest Biotherapeutics Inc (NWBO)

[The Danish Dude]

I am quite sure you know what RISK language is regarding a 10-K, so even though you are paid to ignore many things, let's give you the benefit of the doubt regarding that.

This is the 10-K from 2018 and 2020 respectively.

DO YOU NOTICE ANYTHING THAT LOOKS SUSPICIOUSLY THE SAME AS WHAT YOU JUST LINKED TO FROM THE 10-K FROM 2023?

How about .... everything?




Ok, great. Then let's conclude, that what stands here, is bullshit RISK language (look at end of page for a description)

Below we find MHRA and FDAs guidance going forward regarding proving biosimilarity and not needing efficacy trials.

THIS is how it is!

There are very good reasons not to expect NWBO to be needing efficacy trials to prove biosimilarity. Neither from MHRA nor FDA.

This is MHRAs "Guidance on the licensing of biosimilar products", Updated 7 November 2022

FDA guidance documents outline how biosimilars may be approved based on pharmacokinetic (PK) data and PD biomarker data without a comparative clinical efficacy study. Reliance on PK and PD data allows for shorter and less costly clinical studies that can often be conducted in healthy participants

https://www.centerforbiosimilars.com/view/biorationality-fda-advice-to-biosimilar-developers-on-using-pd-markers-avoid-clinical-efficacy-testing

On 10 April 2023, the FDA added a new page to its website, titled “The Role of Pharmacodynamic Biomarkers in Biosimilar Drug Development,” presenting a summary of the extensive efforts that the FDA has made, including conducting multiple clinical trials reporting the findings in the January 2023 special issue in Clinical Pharmacology and Therapeutics.

It is worth noting that 18 years after the first biosimilar approval in the United States, the FDA has continuously applied scientific approaches to revise and add more approval guidelines. Significant changes include the removal of the term “animal toxicology” and replacing it with “nonclinical” testing;[1] allowing waiver of immunogenicity testing where immunogenicity does not impact pharmacokinetics, such as in the case of insulins; allowing waivers of clinical efficacy testing in patients where pharmacodynamic (PD) biomarkers are available; and continuously updating and adding advice on the conduct of clinical trials that directly add to 138 guidelines, addressing a myriad of issues like ethics, modeling, data collection, and analysis.

The FDA has concluded that to demonstrate that a PD marker is sufficient to establish clinical efficacy. These new findings expand the scope of the initial guideline, titled “Scientific Considerations in Demonstrating Biosimilarity to a Reference Product,” issued in April 2015.

Without a comparative clinical efficacy study, the FDA has clarified that biosimilars may be approved based on pharmacokinetic (PK) data and PD biomarker data. Reliance on PK and PD data allows for shorter and less costly clinical studies that can often be conducted in healthy participants. PD biomarkers are indicators of a drug’s pharmacological effect on its target or targets. For example, the target might be a receptor molecule that initiates a complex signaling cascade. Changes in the levels of proteins along the signaling cascade or modifications to them could be considered pharmacodynamic responses. Therefore, these proteins could be considered PD biomarkers and used to help establish biosimilarity.

An examination of the FDA-licensed biosimilars shows that only a limited number of biosimilar approvals have been based on PK and PD similarity data from clinical pharmacology studies without a large comparative clinical study using efficacy endpoints. These biosimilar products used previously well-established and sensitive PD biomarkers associated with known pharmacology for the reference product. In addition, these PD biomarkers had been closely associated with or demonstrated to be surrogates for clinical outcomes.

However, an established relationship with clinical outcomes is unnecessary for a PD biomarker to be used in biosimilar development. This last statement is of great significance that will push the pendulum back to analytical assessment as a vital consideration.

PD biomarkers that reflect the mechanism of action of the biological product have the potential to be more sensitive endpoints for detecting clinically meaningful differences between 2 products. This provides opportunities for biomarkers previously used as secondary and exploratory endpoints to play essential roles in biosimilar development programs. There is also an opportunity to identify new PD biomarkers with novel methodologies if the information on a suitable PD biomarker is unavailable.

The FDA also suggests focusing on biosimilar innovations, including proteomics research for identifying PD biomarkers for biologics. Large-scale proteomic methods would allow developers to simultaneously study changes in the expression of thousands of proteins after administering a drug or biologic. Biomarker research has been revolutionized by the availability of proteomic technologies to measure the thousands of proteins in the body and changes in their levels or molecular modifications caused by pharmacologic interventions. Transcriptomics and metabolomics are analogous technologies that allow one to do the same for RNA molecules and metabolites, respectively. These progressively maturing technologies could potentially provide the scientific evidence needed to identify candidate PD biomarkers or a signature of PD biomarkers that could support a demonstration of biosimilarity.

Under circumstances where an established and sensitive PD biomarker is not known, other “omic” technologies like transcriptomics and metabolomics may provide an opportunity to identify new, sensitive, and robust candidate biomarkers for further investigation as PD biomarkers for future use in clinical pharmacology studies. This work could expand biosimilar products for which comparative clinical studies with efficacy endpoint(s) would not be needed to demonstrate biosimilarity, ultimately broadening patient access to advanced treatment.

I strongly urge stakeholders to take an active role in pursuing the suggestions made by the FDA and continue to develop novel PD and PK comparisons that will significantly reduce the time and cost of biosimilar approval. The FDA amount took the steps to a significant paradigm shift. It is now up to the developers to reap the benefits from the scientific teachings of the FDA.

RISK LANGUAGE

The language in SEC filings often includes a section dedicated to discussing risks associated with a company's business. This section, known as the "Risk Factors" section, is intentionally included to provide investors and stakeholders with a comprehensive understanding of the potential risks and uncertainties that could adversely affect the company's operations, financial performance, and future prospects.

The primary purpose of highlighting risks in SEC filings is to ensure transparency and provide investors with relevant information to make informed investment decisions. By disclosing potential risks, companies aim to fulfill their legal obligations and protect themselves from potential lawsuits or allegations of withholding crucial information.

Furthermore, the inclusion of risk factors also helps companies manage expectations and mitigate any potential backlash from investors if adverse events or challenges arise in the future. It serves as a precautionary measure to alert investors about the uncertainties and variables that could impact the company's performance and to caution against placing undue reliance on forward-looking statements.

By thoroughly disclosing risks, companies demonstrate their commitment to open and honest communication with shareholders and stakeholders. It allows investors to assess the potential downside of investing in the company and helps them evaluate risk-reward ratios more effectively.