Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Register for free to join our community of investors and share your ideas. You will also get access to streaming quotes, interactive charts, trades, portfolio, live options flow and more tools.
Gerno Schmiedeknecht, Head of Main Department GMP Cell and Gene Therapy at Fraunhofer Institute for Cell Therapy and Immunology IZI, “likes” the 2018 SNO data.
https://www.linkedin.com/in/gerno-schmiedeknecht-9a289850/detail/recent-activity/
Conditional survival after a diagnosis of malignant brain tumour in Canada: 2000–2008.
http://www.current-oncology.com/index.php/oncology/article/view/3579/2543
The ABTA presents: Novel Designs for Brain Tumor Clinical Trials
American Brain Tumor Association
11/20/2018
This interactive webinar is presented by Dr. Timothy Cloughesy.
Dr. Cloughesy discusses the clinical development process for oncology drugs and focuses on how therapeutic development in Glioblastoma is different. He also provides examples on how to improve clinical development for Glioblastoma therapies. Dr. Cloughesy presents and answers questions at the end of his session in an interactive question and answer session.
This webinar has been sponsored by Celgene.
Sentiment,
I believe Flipper and ewwanabe are right, LL rounded up and was a tad sloppy in keeping the > sign when she should used the sign for "approximately equal to or greater than".
I looked it up and they rounded that figure up every time.
Journal of Translational Medicine.
Perhaps the 11 LTFU were not included in the first analysis in March 2017.
Meirluc,
There are no thirteen or more SOC progressing so very late. You will never find them on Sentiments curve because they don’t excist. Remember, only 25 SOC+ placebo in the final group of 108 patients.
Clinical trial endpoints for patients with gliomas.
Jennie W Taylor Annette M Molinaro Nicholas Butowski Michael Prados
Published:14 February 2017
https://academic.oup.com/nop/article/4/4/201/2996378
SNO data 2018 DCVAX-L trial.
3 year survival rate of the final 108 patients who had surgery between between September 2014 and August 2015 =39,81%
108 patients: probably 83 treatment and 25 placebo.
65 patients died before 36 months.
108 – 65 = 43 patients made it to 36 months.
43/108= 39.81%
NOOT:All 7 patients censored on the OS curve 2017 (all MGMT Methylated) made it to 36 months.
Source: The Journal and SNO presentation.
IMO
Data dcvax-l SNO 2018
Of the patients(alive) censored between 18 months and 24 months on the OS curve of 2017 (IMO 40 patients, others think 41), 35 patients lived beyond 24 months.
150 (data 2018) - 115 (data 2017) = 35 patients
Data 2018 SNO
The number of patients who lived 12-24-36 months. (on the OS curve at the time of the analysis 2018. IMO Aug.2018)
Day 0= 331
Month 12 = 293
Month 24 = 150
Month 36 = 91
IMO 3 patients censored between 34 months and 36 months. 2 Methylated and 1 unmethylated.
From @rago_carlo more to come. Seems like it's ahead of Optune pic.twitter.com/smkMT95TuK
— Michael Bigger (@biggercapital) November 17, 2018
Doingmybest,
I am aware of the position of RKmatters. (I believe June 2018)
I did a kind of verification and, in my opinion, the imbalance was not caused at the start of the study.
IMO RKmatters missed a small detail of the PR’s of the year 2011.
Flipper44,
I mean the 7 censors on Sentiments curve between 30 and 36 months at the time of the analysis March 2017. These patients had surgery between March 2014 and September 2014 and are still alive at the time of the analysis March 2017.
Suppose you did a new analysis in September 2017 ( 6 months later) and these 7 patients had all lived to 36 months than you had a group of 51 patients (44+7) of 223 who had lived at least 36 months.
Meirluc,
You are right. The first 38 patients did not do well. Only 5 or 6 of the “unknown” 38 patients had lived to 36 months.
That is 13.1% or 15.8% Survival at 3 years.
The next group of 144 (182-38) patients did much better.
38 or 39 of the 144 had lived to 36 months.
That is 26.4% or 27.1%.Survival at 3 years
And now it becomes interesting.
Seven patients were censored between 30 and 36 months on the OS curve March 2017 (censors 73-74-75-76-77-78 and 79 Sentiments curve).
https://investorshub.advfn.com/uimage/uploads/2018/10/22/gddzjCombined_charts_no_notes_revised_-lykiri.jpg
In the best case, all 7 patients had lived to 36 months. If so, we have a group of 51 (44 + 7) out of a total of 223 patients.(74 placebo and 149 treatment)
51/223 = 22.87% Survival at 3 years.
From the new data 2018 we know that the survival rate at 3 years = 28.2%. That is 93 patients (n=331).
From @rago_carlo more to come. Seems like it's ahead of Optune pic.twitter.com/smkMT95TuK
— Michael Bigger (@biggercapital) November 17, 2018
Congratulations Sentiment!
Date:September 24,2018
Looking4profit,
Doc logic,
a patient on twitter was recently in conversation with another cancer patient about his brain cancer treatment in 2011. He then received dcvax-l as treatment for his brain tumor. A few months ago he had a new lesion at a different location in his brain. He told the other patient that he was given the same vaccine again, but it was "the modern vaccine".
Data set 2018:
Methylated curve: i see 1 censor a few days before 35 months. IMO that censor is number 6 on Sentiments Methylated curve and censor 12 at 18 months on the OS curve. (Data 2017)
Unmethylated curve: i see 1 censor a few days before 35 months. IMO that censor is number 6 on Sentiments Unmethylated curve and censor 13 at 18 months on the OS curve.(Data 2017)
If this is correct, the analysis was done 17 months after the analysis of March 2017 = August 2018.
IMO censors 3,6,7,10 and 11 (Sentiments curve) are no longer LTFU.
This is possibly a partial explanation for the higher figure of 90% of the patients on Dcvax-l if these “no longer LTFU patients” belong to the placebo group.
Sentiment curve: https://investorshub.advfn.com/uimage/uploads/2018/10/22/gddzjCombined_charts_no_notes_revised_-lykiri.jpg
Sentiment,
Thank you for the transcription. Much appreciated. And indeed very instructive to view that video again with all the information we have discovered over the past 3 years.
Wise words from fellow panelists: Phil Vanek, PhD (GE Healthcare); Claudia Zylberberg, PhD (Akron Biotechnology); Joshua Hare, MD (Longeveron); Doug Doerfler (Maxcyte) participate in the “Realizing the Potential of Stem Cell Therapies” panel at the TEDCO Entrepeneur Expo.
November 9, 2018
Longfellow95,
Thank you for the information about Accelerated assessment!
You are right!
He publicly told who the real gem was. One that is being honored this month.
Thanks, and you are right:
Exwannabe,
Thanks for the clarification and thank you Sentiment, Flipper, doingmybest and Doc logic for your help.
I believe it is clear now and I found more evidence for your explanation in another paper from the EMA.
Exwannabe or someone else, maybe you can help me with this:
This year, in Europe, two Marketing Authorisation Applications (MAA) for ATMP's are submitted.
One between 16 March 2018 and 18 April 2018.
https://www.ema.europa.eu/documents/committee-report/cat-monthly-report-application-procedures-guidelines-related-documents-advanced-therapies-march-2018_en.pdf
https://www.ema.europa.eu/documents/committee-report/cat-monthly-report-application-procedures-guidelines-related-documents-advanced-therapies-april-2018_en.pdf
A second between 14 September 2018 and 10 October 2018.
https://www.ema.europa.eu/documents/committee-report/cat-monthly-report-application-procedures-guidelines-related-documents-advanced-therapies-september_en-5.pdf
https://www.ema.europa.eu/documents/committee-report/cat-monthly-report-application-procedures-guidelines-related-documents-advanced-therapies-october_en-5.pdf
Is there a way to find out if one of the two MAAs is for dcvax-l???
The following is from a letter from the European Commission- Advanced Therapies:
The concept of similarity in an ATMP setting.
This Q&A document addresses questions that have been raised by developers of ATMPs regarding the application of the concept of “similar active substance” in an ATMP setting. The Q&A document will be updated in light of accumulated experience during the assessment of these medicinal products.
https://ec.europa.eu/health/human-use/advanced-therapies_en
QUESTIONS AND ANSWERS RELATED TO THE ASSESSMENT OF SIMILARITY FOR ADVANCED THERAPY MEDICINAL PRODUCTS ("ATMPS") IN THE CONTEXT OF THE ORPHAN LEGISLATION.
FREQUENTLY ASKED QUESTIONS
VERSION 1
Date: 25 May 2018
It’s a small world!
Linda Powers- Mark Lowdell- Neil Woodford………………..Novamune Limited- Inmune Bio- Advent Bioservices- Autolus Limited (AUTL)- Northwest Biotherapeutics- Cognate Bioservices ………...Luminus Holdings.
Woodfordfunds.
Autolus is a clinical-stage biotechnology business at the forefront of a revolution in cancer treatment. The company was founded in 2014 based on advanced cell programming technology pioneered at University College London and operates in the fast-developing and rapidly growing immuno-oncology sector.
The business focuses on developing and commercialising a novel class of immuno-oncology treatments known as CAR-T (Chimeric Antigen Receptor T-cells) therapies, which harness the power of a patient’s immune system to combat cancers.
Autolus was founded in 2014 by Syncona, who introduced us to the company. Following more than six months of due diligence, we first invested in March 2016, leading the company’s series B funding round. The position has been held in the Woodford Equity Income Fund and Woodford Patient Capital Trust ever since. The company listed on the Nasdaq stock exchange in June 2018.
https://woodfordfunds.com/funds/holdings/autolus/
INMUNE BIO, INC.
Appendix A
List of companies involved in adoptive cell therapy / immunotherapy with which Professor Lowdell has extant consultancy agreements at the commencement of this contract
Achilles Therapeutics Ltd – co-founder, shareholder, member of SAB Autolus Ltd
Avectas – chair of SAB
Cell Medica Ltd – co-founder, shareholder, member of SAB Novamune Inc – member of SAB NWBio Inc
INKmune Research and Development
Joint Development Agreement
On September 3, 2016, we entered into a joint development agreement with Novamune, Inc. (“Novamune”) (the “Development Agreement”). Novamune had previously developed and licensed technology relating to ex-vivo activation of NK cells for the treatment of cancer and other diseases. The parties agreed to exclusively collaborate on the further development of technologies related to NK cells for therapeutic applications. We will share equally in the costs related to such joint development projects and will jointly own any intellectual property developed by the joint projects, provided that Novamune shall have an exclusive royalty free license to use any such intellectual property relating to ex-vivo applications, and we shall have an exclusive royalty free license to use any such intellectual property relating to in-vivo applications. The Development Agreement is subject to Novamune investing a total of $1,250,000 in our Company, of which $350,000 has previously been advanced through a convertible note payable. The balance of $900,000 was invested on February 9, 2018 in exchange for 400,000 shares of common stock. The Development Agreement ends on September 3, 2023 unless terminated sooner. The term of the Development Agreement may be extended for one year upon the written consent of both parties. The Development Agreement may be terminated prior to the end of the term by either party in the event of a material breach by the other party of the terms of the Development Agreement, provided that the terminating party is not in breach and has first given the defaulting party written notice of termination specifying the grounds for the terminating and if after giving the defaulting party 30 days to cure the breach, the breach was not cured.
INKmune Manufacturing
We intend to contract with third parties for the manufacture of our compounds for investigational purposes, for preclinical and clinical testing and for any FDA approved products for commercial sale. Pre-clinical and clinical material for the early clinical trials with INKmune has been manufactured under the direction of Mark Lowdell and Advent Bioservices International, our strategic partner, at a licensed GMP facility. The master cell bank, working cell bank and individual product doses were completed in July 2018. This clinical material is planned for use in the Phase I/II clinical trials in ovarian cancer. If we raise adequate capital to initiate the high-risk MDS Phase I/II trials, additional working cell banks and therapeutic product will be produced from the existing master cell bank. This process takes approximately 6 months and is not anticipated to delay the initiation of the high-risk MDS Phase I/II trials. We may transfer the manufacturing to a different commercial contract manufacturing organization after completion of these Phase II studies.
Joint Development Agreement between INmune Bio, Inc. and Novamune
https://www.nasdaq.com/markets/ipos/filing.ashx?filingid=12943861#INMUNE_EX106_HTM
NOVAMUNE LIMITED
2 officers: LOWDELL, Mark William, Prof.
POWERS, Linda
https://beta.companieshouse.gov.uk/company/11323970/officers
Mark Lowdell: https://www.terrapinn.com/conference/festival-of-biologics-usa/speaker-mark-LOWDELL.stmThe
All they need now is the Company's economic model....
A small update to the NICE Guidance for DCVax-L.
https://www.nice.org.uk/guidance/indevelopment/gid-ta10143
Added:
Evidence Review Group / Assessment Group -
Southampton Health Technology Assessments Centre
https://www.southampton.ac.uk/shtac/about/index.page
Skitahoe,
Read the story of the third patient enrolled in the phase1 DCVAX-L clinical trial and his booster vaccinations.
Tom Jones (not his real name) was the third patient enrolled in that trial and has survived eight years since his diagnosis………….
Thereafter, patients received booster shots every three months until tumor progression or until they ran out of tumor tissue to pulse with dendritic cells
……….
Jones received his first DCVax injection in June 2003 and his last booster vaccination in February 2009.
JerryCampbell,
The difference between SOC and SOC plus placebo is Leukapheresis.
Doc Logic,
Thank you!
Perhaps this is an interesting reading.
Guidance for Industry
" Potency Tests for Cellular and Gene Therapy Products."
I. INTRODUCTION
We, FDA, are issuing this guidance to provide you, manufacturers of cellular and gene therapy (CGT) products, with recommendations for developing tests to measure potency. These recommendations are intended to clarify the potency information that could support an Investigational New Drug Application3 (IND) or a Biologics License Application (BLA).
Cancer Immunology Research.
May 2016
[img][/img]
Volume 4, Issue 5
About the Cover
Cancer patients are often treated with immunotherapy; yet it is difficult to readily track the immune response to these treatments. Hsu, Sedighim, and colleagues have developed a clinically translatable platform that allows tracking of individual T-cell clones without prior knowledge of their specificity. By comparing sequences found in glioblastoma tumors to those found in the peripheral blood, the authors verified that the blood samples reflected the same specific T cells infiltrating into the tumors. T-cell receptor sequencing data could help distinguish glioblastoma patients that benefited, or could potentially benefit, from immunotherapy (specifically dendritic cell vaccination). The micrograph (right) upon which the cover this month is based shows, by multiplex immunohistochemistry, a tumor derived from one of the patients in this study. It is heavily infiltrated with T cells, which are critical for the immune response within the microenvironment. Photo by Shaina Sedighim. Artwork by Lewis Long. Read more starting on page 412 of this issue of Cancer Immunology Research.
http://cancerimmunolres.aacrjournals.org/content/4/5.cover-expansion
TCR Sequencing Can Identify and Track Glioma-Infiltrating T Cells after DC Vaccination
Melody S. Hsu, Shaina Sedighim, Tina Wang, Joseph P. Antonios, Richard G. Everson, Alexander M. Tucker, Lin Du, Ryan Emerson, Erik Yusko, Catherine Sanders, Harlan S. Robins, William H. Yong, Tom B. Davidson, Gang Li, Linda M. Liau and Robert M. Prins
DOI: 10.1158/2326-6066.CIR-15-0240 Published May 2016
Abstract.
Although immunotherapeutic strategies are emerging as adjunctive treatments for cancer, sensitive methods of monitoring the immune response after treatment remain to be established. We used a novel next-generation sequencing approach to determine whether quantitative assessments of tumor-infiltrating lymphocyte (TIL) content and the degree of overlap of T-cell receptor (TCR) sequences in brain tumors and peripheral blood were predictors of immune response and overall survival in glioblastoma patients treated with autologous tumor lysate–pulsed dendritic cell immunotherapy. A statistically significant correlation was found between a higher estimated TIL content and increased time to progression and overall survival. In addition, we were able to assess the proportion of shared TCR sequences between tumor and peripheral blood at time points before and after therapy, and found the level of TCR overlap to correlate with survival outcomes. Higher degrees of overlap, or the development of an increased overlap following immunotherapy, was correlated with improved clinical outcome, and may provide insights into the successful, antigen-specific immune response. Cancer Immunol Res; 4(5); 412–8. ©2016 AACR.
http://cancerimmunolres.aacrjournals.org/content/4/5/412
By the time all control PFS evented (probably November 2016), the ethics committee would have been made moot. Their services were essentially/pragmatically no longer required, imo.
Abstract
Patients with bevacizumab-refractory recurrent glioblastoma multiforme (GBM) have a poor prognosis. We propose that instead of continuing on bevacizumab, patients should switch to treatment with Optune™, a novel antimitotic Tumor-Treating Fields (TTFields) therapy approved in the United States for newly diagnosed and recurrent GBM. This would reserve bevacizumab for subsequent disease progression. In this case series, we describe 8 patients with recurrent GBM who had disease progression on bevacizumab, discontinued bevacizumab treatment, and were treated with TTFields therapy alone.
Methods
One patient participated in the phase 3 DCVax-L study for newly diagnosed GBM, receiving dendritic cell-based vaccine versus placebo.