SkyLimit2022
3 minutes ago
Gary,
A member of the Nobel committee mentioned the possibility of DC technology playing a role in the treatment of other diseases such as MS and diabetes (pasted below), so the question you raised is an excellent one. There was also a recent Lancet paper about a French/Swiss study involving DC technology for HIV. I would also mention that I believe the novel DC technology at Roswell (that NWBO now owns) does not have to be loaded with antigens from the tumor and might have the potential for broader application. I believe I read that it is easier to make too.
Some love Halloween time 🎃 and the beginning of the fall season. As a science enthusiast, I love October because it’s Nobel season!
It’s a great time to remember that NWBO is a company that was built on a rock-solid foundation of Nobel Prize-winning science, and brilliant physicians like Dr. Linda Liau and Dr. Pawel Kalinski could also one day be candidates for the Nobel Prize for their ground-breaking discoveries of novel combination therapies to overcome tumor resistance!
Dr. Steinman was awarded the Nobel Prize for discovering the dendritic cell. In 2018, James P. Allison and Tasuku Honjo were awarded the Nobel Prize in Physiology or Medicine for their pioneering work in cancer therapy through the discovery of immune checkpoint inhibitors.
Today, Dr. Linda Liau and Dr. Pawel Kalinski are combining dendritic cell technology with checkpoint blockade technology to reach new levels of efficacy and healing for patients! UCLA and Roswell are studying how these two Nobel Prize-winning discoveries can be combined to treat multiple distinct cancers!
Recently, we commemorated the loss of the great Dr. Ralph Steinman 13 years ago on September 30th.
“We know he will live on through his scientific contributions.”
Dr. Steinman’s legacy is changing the field of cancer immunotherapy today, and his invaluable Nobel Prize-winning work lives on at UCLA, King’s College and Roswell Park, among other cutting-edge institutions.
The recent evolution of dendritic cell technology has been vast, and Dr. Steinman’s prophetic words foreshadowed the future and DCVax-L. In the last 3 minutes of the YouTube video, Dr. Steinman describes the “first generation of this approach” which used only ONE single antigen. Consider that DCVax-L can present HUNDREDS of distinct antigens today!
The Nobel Prize in Physiology or Medicine has proven significant historically, and a great number of the discoveries that were awarded the prize have proven quite impactful.
The award represents the credible collective opinion of the 50 distinguished members of the Nobel Assembly and the opinions of any number of distinguished international medical experts whom the members may choose to consult. By their own published criteria, their decision to award the prize means that they believe the medical breakthrough will impact humanity globally.
To put the relatively recent awards for dendritic cell discovery and PD-1 in perspective, consider that checkpoint inhibitors have only existed commercially for 10 years. Drugs such as Keytruda have been blockbusters, and the full impact of PD-1 as a drug class is yet to be realized as the technology continues to evolve to include additional new products, such as subcutaneous versions.
Other examples of Nobel Prize-winning medical breakthroughs include:
X-Ray Technology, 1901
Penicillin, 1945
Insulin, 1923
MRI Imaging Technology, 2003
Monoclonal Antibodies, 1984
CRISPR Technology, 2020
These discoveries and many others that won the Nobel Prize have gone on to either revolutionize medical practice or create entire industries around their commercialization.
https://www.nobelprize.org/prizes/medicine/
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=175149927
Horseb4CarT
31 minutes ago
I see, thanks for explaining it to me. Sometimes i’m a little slow.
RevImmune is also a coinventor on a patent (nwbo, ucla, revimmune, and the former nwbo CDMO that CRL acquired - having a senior moment trying to remember the name) and it may be the original combination treatment patent, but I could be mistaken.
I believe LP is directly associated with nwbo, advent, revimmune, and more! One of the companies LP is assovisted with added Dr Liau to their Scientific Advisory Panel I think, and I believe Bigger Capital has a large position in it.
I rely too much on memory and my retention and recall isn’t what it used to be. If I weren’t so lazy I would diagram all this stuff out and collect it in a file or database. But since I’m only invested in the nwbo part of LP’s world I figure I can get away with being lazy and I am strictly buy side for the duration with the exception of about 10% for personal family needs that I will need to sell, letting the rest ride and fulfill the greater potential.
The disclaimer: this is not investment advice
Lykiri
4 hours ago
European Medicines Agency pre-authorisation procedural advice for users of the centralised procedure.
4 October 2024
EMA/821278/2015
Human Medicines Division
5.2.2. When can I expect a pre-approval GCP inspection and how are they conducted? Rev. Oct 2024
Clinical trials included in any marketing authorisation application (MAA) in the EU and in any subsequent application to the initial one are required to be conducted in accordance with Good Clinical Practices (GCP). GCP inspections are conducted in accordance with Article 15 of Directive 2001/20/EC and Article 78 of Regulation (EU) No 536/2014. The requirements which apply for the conduct of clinical trials included in a MAA are set out in Recital 16 and Article 6(1) of Regulation (EC) No 726/2004 as well as in Annex I to Directive 2001/83/EC, as amended (Introduction and general principles - sections 4 and 8 - and Part I - Module 5). Requirements for the conduct of clinical trials and GCP inspections are published in Volume 10 of the Rules governing Medicinal Products in the European Union.
The EMA relies for the scientific review of centralised applications for marketing authorisations for medicinal products on the expertise located in the Member States. The same approach exists in the area of inspections, where inspections are conducted by Member States' inspectorates if requested by the CHMP. These inspections are co-ordinated by the EMA if they pertain to centralised applications and in the case of GCP inspections, they are conducted by Member States' inspectorates in accordance with Article 15 of Directive 2001/20/EC and Article 78 of Regulation (EU) No 536/2014. There is a GCP Inspectors Working Group, composed of GCP inspectors from the Member States, which meets quarterly at the EMA.
EMA inspection sector reviews all new applications for evidence of GCP compliance and other validation aspects. All new applications are examined to assess the need for GCP inspection(s). The EMA Inspections Sector liaises closely with the Product Lead, Rapporteur and Co-Rapporteur during the presubmission phase and in the period during and after validation to discuss the need to request GCP inspection(s). A need for inspection(s) may be identified at this stage, based on previous relevant experience of the Inspections Sector and the Member States’ national inspectorates. In addition, a need for GCP inspection(s) may also be identified during the review by the assessors, in particular during the initial assessment phase up to day 120. In case a need for inspection is identified for an application under accelerated assessment, the inspection will be requested as early as possible. Please refer also to question “Is my product eligible for an Accelerated Assessment”.
GCP inspection issues are usually addressed in the List of Questions (although the inspection may commence earlier once adopted by CHMP), and therefore are usually adopted at Day 120. The GCP inspection(s) of the concerned site(s) can then take place in parallel with the “clock stop” period.
However, GCP inspection(s) may be requested by CHMP at any stage of the assessment.
It should be noted that clinical data submitted as a result of specific obligations/follow-up measures, or within variations, extensions or other information received after the initial authorisation (e.g. in relation to safety updates, risk management plan etc...) may also trigger a GCP inspection request.
The Reporting Inspector appointed is usually from the inspectorate of the Member State of the CHMP Rapporteur or Co-rapporteur unless the site(s) to be inspected are located in a single EEA state (or small number (3 or less) of EEA states), in which case that Inspectorate is usually designated as the Reporting Inspectorate.
In addition to the Reporting Inspector, one Lead Inspector is designated per site to be inspected. The Lead Inspector is usually from the Inspectorate of the Member State where the site to be inspected is located (for inspections in the EEA). The Reporting Inspector may also be the Lead Inspector for one or more sites.
In the case of third country inspections, the Reporting Inspectorate and the inspectors are usually from the Rapporteur/Co-Rapporteur country inspectorates.
The applicant is asked to provide information in the application in order to facilitate the review and where needed the preparation of GCP Inspections. This information should be provided in the Individual Clinical Study Reports and their Appendices (Module 5) in line with the “Note for Guidance on the Inclusion of Appendices to Clinical Study Reports in Marketing Authorisation Applications” (CHMP/EWP/2998/03), and the “Note for Guidance on Structure and Content of Clinical Study Reports” (CPMP/ICH/137/95).
Some of the key information to be provided for each study are listed below with the specific references to the section numbers given in the “Note for Guidance on Structure and Content of Clinical Study Reports” (CPMP/ICH/137/95). Please note that some of this key information also needs to be extracted and included in the form “Information required for identification of a need for pre-authorisation GCP inspections”, which should be appended to the cover letter.:
• A clear description of the study administrative structure (clear identification of the sponsor and of the parties who have performed the monitoring, data management, statistics, laboratory assessments, randomization, site(s) of manufacture, site of release in Europe, medical writing, other applicable activities and the location of the trial master file) preferably in a tabular form and indicating name and address of the site where each activity was performed, responsibilities and scope of each activity. These should be identified in the clinical study report of each study, for instance in section 6, or appendix 16.1.4.
• A list of investigators (name, address, country), preferably in a tabular form, showing the number of patients enrolled by each site, and the total number of sites. In addition, a table with the number of patients enrolled per country should be included. These should be identified in the clinical study report of each study, for instance in section 10.1 or appendix 16.1.4.
• Audit certificates (indicating the sites audited, the dates of audit, the type of audit and the auditor). These should be identified in the clinical study report of each study, for instance in appendix 16.1.8.
• Signature of the principal or coordinating investigator(s) according to Annex I to Directive
2001/83/EC as amended and in line with the “Note for Guidance on Structure and Content of Clinical Study Reports” (CPMP/ICH/137/95), and not only the signature of the sponsor’s responsible medical officer. These should be identified in the clinical study report of each study, for instance in appendix 16.1.5.
A list of inspection(s) conducted or planned by other regulatory authorities, related to the product and trial sites involved, should also be provided, as part of the form “Information required for identification of a need for pre-authorisation GCP inspections”, which should be appended to the cover letter.
Each clinical study report should contain a statement indicating whether the study was performed in compliance with Good Clinical Practices (GCP), including the archiving of essential documents.
According to the Notice to Applicant, Volume 2B, the clinical overview (Module 2), should assess the quality of the design and performance of the studies and also include a statement regarding GCP compliance.
In addition, in accordance with Article 6(1) of Regulation (EC) No 726/2004, a statement should be provided, where applicable, in Module 1.9 to the effect that clinical trials carried out outside the European Union meet the ethical requirements of Directive 2001/20/EC or Regulation (EU) No 536/2014. This statement should indicate that “clinical trials carried out outside the European Union meet the ethical requirements of Directive 2001/20/EC or Regulation (EU) No 536/2014,” together with a listing of all trials (protocol number) and countries (outside the EU) involved.
Regarding the importance of GCP compliance for marketing authorisation applications, applicants/marketing authorisation holders are invited to refer to the EMA Position paper on the nonacceptability of replacement of pivotal clinical trials in cases of GCP non-compliance in the context of marketing authorisation applications in the centralised procedure.
References
• The Rules governing Medicinal Products in the European Union, Volume 2B, Notice to Applicants, Common Technical Document
• Directive 2001/20/EC
• Directive 2001/83/EC, as amended
• Regulation (EC) No 726/2004
• “Note for Guidance on the Inclusion of Appendices to Clinical Study Reports in Marketing Authorisation Applications” (CHMP/EWP/2998/03)
• “Note for Guidance on Structure and Content of Clinical Study Reports” (CPMP/ICH/137/95)
• “Clinical trials”, The Rules governing Medicinal Products in the European Union, Notice to Applicants, Volume 10
• Regulation (EU) No 536/
Lykiri
4 hours ago
I’m not sure how things work in the UK, but I do know that for a GMP inspection conducted by the EMA, there are strict timelines. For example, as mentioned in this text, inspections related to a marketing authorisation application must be conducted, and the final report submitted to the EMA and CHMP within the 210-day evaluation period. The inspection team works with the company to agree on dates, and the report is finalized within specific deadlines, such as by Day 181 for standard 210 days assessment.
European Medicines Agency pre-authorisation procedural advice for users of the centralised procedure.
4 October 2024
EMA/821278/2015
Human Medicines Division
5.2. Inspections.
5.2.1. When can I expect a pre-authorisation GMP inspection and how are they conducted?
5.2.1.9. Timetable for Inspections.
Inspection(s) requested in connection with an application for a marketing authorisation must be carried out and the final report(s) sent to EMA and submitted to the CHMP in accordance with the 210-day time limit for the evaluation of the application by the CHMP.
Once an inspection request is adopted by the CHMP, EMA will write to:
• the applicant explaining that an inspection(s) will take place, giving details (target date for carrying out the inspection, inspection team, scope of the inspection, contact person in the relevant authority responsible for arranging the inspection)
• the Rapporteur and Co-Rapporteur for information.
The Inspection Team will contact the Company to agree inspection dates within the agreed target date.
Inspections usually take place in parallel with the “clock stop” period.
5.2.1.10. Inspection Reports
Inspectors will send the draft Inspection Report to the manufacturer within fifteen days of the Inspection for comments on major factual errors, point of disagreement or remedial actions. Where necessary, the manufacturer should respond within a further fifteen days to provide comments and, if necessary, an action plan with a timetable for implementation. This will be considered during the finalisation of the Inspection Report.
The timing of any discussions, further actions and/or the provision of additional information arising from the inspection will be agreed with the Inspectors and communicated by the Inspectors to the Rapporteur, the Co-Rapporteur and EMA.
Inspectors will finalise the report and send it to EMA by Day 181 (or by Day 121 in case of product or process related inspections) at the latest and the Rapporteur, Co-Rapporteur will receive a copy. In case of a non-satisfactory inspection outcome, a non-compliance statement may be issued, and it will not be possible to have a positive opinion until the relevant issues have been resolved.
dstock07734
7 hours ago
I asked a couple of posters on this board to do some investigation on Baker Brothers' portfolio as a way to verify if there is a possibility that Baker Brothers may have something to do with NWBO. But none would do it. Is it so boring subject? Anyway I did the preliminary investigation on my own. Note that I only share something I truly believe.
As shown in one of the Dr. Liau's publications, the inclusion of PD1 inhibitor and CSF1R-I into the combination of DCVax-L with poly-iclc makes tremendous difference in the final efficacy of the treatment. Note that DCVax-L in the figure is actually the combination of DCVax-L with poly-iclc. The combination of CSF1R-I and Keytruda/Opdivo with DCVax-L has been investigated thoroughly by UCLA research team.
https://academic.oup.com/neuro-oncology/article/19/6/796/2927952
There are several PD1/PDL1 inhibitors approved by FDA and more are ready for RA filing. But when it comes to CSF1R inhibitor, there are very few FDA approved drugs. As a matter of fact, there used to only one drug approved by FDA and it is PLX3397 from Daiichi Sankyo. But in August 2024, FDA approved an IV version of CSF1R inhibitor which is Axatilimab from Incyte.
What I found more interesting is that Baker Brothers are the largest share holder of Incyte which accounts for 25% of their portfolio. Axatilimab was originally developed by Syndax and in September 2021 Incyte formed a collaboration with Syndax to develop Axatilimab together and the collaboration was concluded with FDA approval in August 2024. Is that interesting for Incyte to reach out another company to develop CSF1R inhibitor from which Daiichi has not generated any significant revenue? As the largest share holder, Baker Brothers must push for or at least approve the move. Again when was the last time Dr. Timothy Cloughesy had a meeting with Merck? March 2021!
IMO, it seems like Baker Brothers have been trying to empty all their positions in precision medicine as listed below. Note that I only took a look at companies which focus on cancer and accounts for over 0.1% of their portfolio, and the timeline started from June 2022. It should be pointed out that if a company has pd1 inhibitor under clinical trial, they would keep its position. Is precision medicine the direction of cancer treatment that makes all the BPs jump on board over the past a couple of years? What could make Baker Brothers dislike precision medicine?
My conjecture is that Baker Brothers' investment decisions might be connected to the breakthrough from $NWBO. Time will tell if my conjecture is right.
https://fda.gov/drugs/resources-information-approved-drugs/fda-approves-axatilimab-csfr-chronic-graft-versus-host-disease
https://incyte.com/our-company/our-leadership
https://whalewisdom.com/filer/baker-bros-advisors-llc
Syndax Pharmaceuticals and Incyte Announce Global Collaboration to Develop and Commercialize Axatilimab for Chronic Graft-Versus-Host Disease and Other Fibrotic Diseases
https://ir.syndax.com/news-releases/news-release-details/syndax-pharmaceuticals-and-incyte-announce-global-collaboration
List of companies
Merus (T-cell engagers)
https://merus.nl/pipeline/
Legend Biotech (CAR-T)
https://legendbiotech.com/research-development/pipeline/
ImmunoGen Inc. (ADC)
https://immunogen.com/what-we-do/our-pipeline/
Cue Biopharma (T-cell engagers) George Zavoico used to be Vice President, Investor Relations and Corporate Development of the company before joining $NWBO.
https://cuebiopharma.com/pipeline/product-candidates/
SpringWorks Therapeutics Inc
https://springworkstx.com/pipeline/
Day One Biopharmaceuticals
https://dayonebio.com/clinical-trials/