NorthWest Biotherapeutics Inc (NWBO): Recap ATL-DC and Keytruda. I'm qu...

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The Danish Dude

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Saturday, 02/12/2022 11:54:58 AM

Saturday, February 12, 2022 11:54:58 AM

Recap ATL-DC and Keytruda.

I'm quite tired of the constant arguing or insinuations, that ATL-DC in the combo trial with Pembrulizumab (Keytruda) is not DCVax-L.

It is.

BEYOND doubt.

I've now been through a lot of postings in search of when the debate started and in search of how many times, these insinuations have been refuted. I've tried to make a resumé below.

It's a lot, but its time to lay the insinuations to rest and move forward and have a point in time from where we can once and for all refute that.

ATL-DC in that GBM combo trial at UCLA with Keytruda, IS DCVAX-L.

Flipper started out in January 2021 mentioning this:

"Current on their website as of today. (Note: UCLA’s brain tumor website, unlike NWBO, keeps all areas current)

Immunotherapies available at UCLA include:

Vaccines: Vaccines are among the most promising immunotherapies. Researchers at UCLA developed the first personalized vaccine for brain tumors (dendritic cell-based vaccine, or DCVax®). DCVax® has extended survival of many of our glioblastoma patients for more than a year, and some are thriving more than 10 years after their initial diagnosis.

Immune checkpoint (PD-1) inhibitors: We are exploring ways to stimulate certain white blood cells (T-cells) so they become more effective in attacking and destroying cancer cells. This therapy helps patients who have not had success with other treatments or are at risk for building a treatment resistance.

We lead and participate in multi-center trials for developing the next generation of brain cancer immunotherapies. Your physician will let you know if you are eligible for a trial. Learn more about our research and clinical trials."

https://www.uclahealth.org/braintumor/biologics

"I personally think UCLA wants the process to move forward. Patients are waiting."

And followed up with

"Safety matters a lot too, and the combo trial likely started out first year enrollment slowly to observe, study and evaluate trial parameters going forward. My guess here is that it is very tricky to time completion of a phase three trial with enrollment timing of the combo trial. I could expound, but I guess most people already know what those might be. I do see the recent UCLA PR on the combo trial as an indication it is ok to move toward enrollment completion for the combo trial now. I suspect they are witnessing something historic."

ATLnsider commented

"It is very telling that on this website page, UCLA lists the only 2 current immunotherapy treatment options at UCLA for brain cancer as: DCVax & PD-1 inhibitors.

Especially, considering that the only current open clinical trial, that is currently recruiting at UCLA for recurrent Glioblastoma, is ATL-DC (DCVax) plus Pembrolizumab (Keytruda).

It is all so plain to see, unless you refuse to see it, as some Bears on this board have chosen not to see this."

ATLnsider had another post

"When we take a closer look at the UCLA - Merck Phase I clinical trial for recurrent Glioblastoma Multiforme (rGBM), with a treatment that combines an autologous tumor lysate-pulsed (ATL)-dendritic cell (DC) vaccine with Pembrolizumab (Keytruda), we can see the obvious fact that ATL-DC is the generic name for DCVax-L.

DCVax-L is the trademarked name for NWBio’s autologous tumor lysate (ATL) dendritic cell (DC) vaccine. ATL-DC is the generic name for DCVax-L. NWBio is not producing DCVax-L for this UCLA trial, through its commercial CMOs (Cognate & Advent Bioservices). This is a small Phase I clinical trial with only 40 patients, and there is only 1 clinical trial site (UCLA). There is no need for large-scale commercial production capacity for this trial. UCLA has the production capacity to make the vaccines on-site, in its own laboratory.

I personally believe that UCLA, Merck & NWBio want to purposely hide, obscure & downplay the connections between the 3 entities, and hide this DCVax-L + Keytruda combination clinical trial in plain sight. This allows NWBio to focus on releasing TLD, and prevent Merck & NWBio from having to answer questions about the interest they may have in each other.

Take a look at how DCVax-L is described and named in the 2018 Journal of Translational Medicine article by Liau et. al., that published the interim blinded and blended results for the DCVax-L Phase III trial. Also, take a look at how ATL-DC is described and named on the clinical trials.org website. The 2 are exactly the same:"

Ex commented

"Was there really a UCLA PR I missed? Or are you talking a tweet that noted UCLA had it listed on their site with all the other trials they run?"

Senti also commented

"To your point that it’s time to complete enrollment in the combo trial... You’ll likely remember from the other day the Twitter post by the recurrent GBM patient Matt Henkel from Illinois who recently received the call from UCLA that he could enter the combo trial. He was most excited to know that he was sure to now receive DCVax-L, and hoped to get Pembro, too. But was most excited to be receiving DCVax. One might also note that Henkel did not reference the treatment as an “autologous dendritic cell vaccine”, but specifically called the treatment he’d be receiving “DCVax-L.”

Flipper answered

"Good point. I was just verifying from a UCLA public relations page, but of course I have no doubt Mr. Henkel is also proof positive, as is your conversation with Dr. Liau and Atlnsder’s links."

Flipper:

https://www.uclahealth.org/neurosurgery/art-vision-steve-lyons

Branster

"Flipper, seems that is the new trial with the anti-PD1 immune checkpoint inhibitor (Keytruda) from the statements LP is making.

"we recently opened a novel clinical trial to investigate the safety and efficacy of combining a personalized dendritic cell vaccine with an anti-PD1 immune checkpoint inhibitor, said Dr. Liau. Although we had tested both agents independently in the past, this is the first-in-human trial combining the two approaches in order to harness the immune system against brain cancer"

You would think Merck is in engaged with NWBO at this point...."

Flipper, here is the trial I believe.

https://clinicaltrials.gov/ct2/show/NCT04201873?term=cloughesy&draw=2

Flipper

"Again thanks. It never hurts to repost the trial link."

Branster

"flipper, oh okay gotcha, so what your make of the relationship between Merck and ULCA and NWBO and the TLD ?"

Flipper

"In the very recent PR, Dr. Liau confirmed the Autologous DC vaccination used in current combination trial is the same one they used before. The one they used before was DCVax-l. UCLA has a contract with NWBO regarding the DCVax platform."

ATLnsider then chimed in with Merck CEO Kevin Fraziers words from this article

https://www.fiercepharma.com/pharma/jpm-merck-not-complacent-but-we-re-not-desperate-for-deals-ceo-says

"For one, the company is looking ahead to coformulations, combinations and other routes of administration for Keytruda that could lengthen the PD-1 king’s patent life, to continue to focus on getting the best external science we can, both in oncology and outside oncology, to diversify our portfolio, and we’re going to continue to focus on that.”

Poor Man

"The four big questions for whether Merck or another BP will acquire NWBO:

1) Does DC Vax have value in its own right and how much
2) Does DC Vax have value in combo with another treatment
3) Does DC Vax threaten market share for Keytruda or any other treatment
4) How much would Merck or another BP pay that will still provide a meaningful risk adjusted return for shareholders

The bonus question is how many BP are in play for DC Vax?

The answer to question 3 is critical, since Merck has so much value hanging on Keytruda, they can’t afford to take a meaningful risk on Keytruda’s market share."

nsgmd5:

"here is a notable absence of NWBO on the clinical sponsor site - it looks like they have switched to Oncovir, Inc. Can someone give some color as to why UCLA would switch vaccine providers?"

ATLnsider:

"Also, nsgmd5, if you can read between the lines, and you know where to look, you will see the obvious connections between: UCLA, NWBio, Merck, DCVax & Keytruda. Take a look at the ATL-DC + Keytruda trial Sponsors & Collaborators on the clinical trials.org site link below:

UCLA - Jonsson Comprehensive Cancer Center
National Cancer Institute (NCI)
Merck Sharp & Dohme Corp.
Phase One Foundation
Oncovir, Inc

https://clinicaltrials.gov/ct2/show/NCT04201873

Then take a look at who is the Phase One Foundation, and the money ($400,000) they gave to UCLA to conduct this study:

https://www.phaseonefoundation.org/latest-news/cancer-researchers-develop-immunebased-therapies-for-deadly-brain-tumors

Then, go to the above link and look for this paragragraph:

The funding will help open a clinical trial testing a combination treatment strategy using checkpoint inhibitors in conjunction with a personalized dendritic cell vaccine, which was developed by Liau at UCLA

Then, touch the blue link in this paragraph, it says: “was developed by Liau”. This blue link will take you to this page:

https://newsroom.ucla.edu/releases/personalized-vaccine-increase-long-term-survival-glioblastoma

This page clearly shows you that the ATL-DC vaccine developed by Dr. Linda Liau is DCVax-L. It says the following:

The vaccine, known as DCVax-L, uses a person’s own white blood cells to help activate the immune system to fight cancer

Ex commented February 8th. clearly wrong about "the Keytruda combo"

"In the trial ae_kust posted the arms were

ATL-DC + placebo : 11 months
ATL-DC + PolyICLI : 54 months
ATL-DC + Resquimid : 17 months

We can debate if ATL-DC "is" DCVax-L, but whatever it is UCLA likes to use PolyICLI with it. That is why the Keytruda combo also uses PolyICLI"

ATLnsider

"Jack, the reasons UCLA is not using the name DCVax-L, and is using the name ATL-DC are:

(1) ATL-DC stands for autologous tumor lysate-pulsed (ATL)-dendritic cell (DC) vaccine. ALT-DC is the generic name, and DCVax-L is the trademarked name.

(2). DCVax-L trademark is owned by NWBio. NWBio is not formally participating in, or putting money in this trial with UCLA. NWBio is devoting its current resources to completing the TLD for the DCVax-L Phase III, and soon getting DCVax-L approved in 4 countries.

(3) The ATL-DC used in the current UCLA trail, is being manufactured by the UCLA GMP lab on its campus. It is not being manufactured by NWBio or its U.S. CMO, Cognate.

(4) The UCLA GMP lab is only authorized by the FDA to make small quantities of ATL-DC (DCVax-L) for small clinical trials. UCLA is not authorized or licensed to make mass commercial quantities of ATL-DC (DCVax-L). That will be done by Cognate (Charles River Laboratories).

I believe that (these are my opinions Jack), if the UCLA Phase I recurrent GBM trial using ATL-DC plus Keytruda proves successful, then UCLA, NWBio & Merck, will conduct a larger Phase II/IIII trial using approved DCVax-L plus Keytruda. Also, I believe they will probably test this combination (DCVax-L + Keytruda) in various other solid tumor cancers."

ATLnsider

ATLnsider

Here is more evidence that UCLA is using DCVax in the combo trial with Keytruda (Pembrolizumab). Most of us already know that UCLA is using DCVax combined with Keytruda, by there are a few here trying to spread FUD.

Quote:
"patients will all receive the DCVax, but they may or may not receive the Pembrolizumab"

You can hear this around the 43:10 minute mark:

https://vimeo.com/529196354

Exwannabe in June 2021

Merck is not "footing the bill" for the UCLA combo trial. They are providing the drug and presumably some tech support.

I would estimate the number of other trials is over 500.

EDIT: By the way, Pembrolizumab is not the brand name. It is the formal "chemical" name and what many would call the "generic" name. Keytruda is the brand name.

And ATL DC is not a generic name, it is just a description. There is no formal generic name and not even a brand name. There is no way in the world "ATL DC" would be the generic name nor "DCVax-L" would be the brand name

Dr. Bala answer to Ex

"No need to confuse the issue. ATL DC is the same as DCVax-L. ATL DC is being used by UCLA in their Project I Combo Trials."

Longfellow95 answers Ex:

No need to confuse the issue. ATL DC is the same as DCVax-L. ATL DC is being used by UCLA in their Project I Combo Trials./quote]

Biosectinvestor

ATL-DC is definitively DCVax-L and here is why…

Here is the clinical trial:

https://clinicaltrials.gov/ct2/show/NCT04201873

Sponsor:
Jonsson Comprehensive Cancer Center
Collaborators:
National Cancer Institute (NCI)
Merck Sharp & Dohme Corp.
Phase One Foundation
Oncovir, Inc.

Key collaborator is Phase One Foundation.

Here is the press release for Phase One’s finding of this trial.

https://www.phaseonefoundation.org/latest-news/cancer-researchers-develop-immunebased-therapies-for-deadly-brain-tumors

“The funding will help open a clinical trial testing a combination treatment strategy using checkpoint inhibitors in conjunction with a personalized dendritic cell vaccine, which was developed by Liau at UCLA. The team hopes by combining the two treatments they will be able to create a new way to treat people with brain cancer, as well as develop new ways to track the immune response.

“We already have had preliminary success using checkpoint inhibitors to treat patients in a previous clinical trial,” said Cloughesy, who is also a scientist at the Jonsson Cancer Center. “By combining the two immune-based treatments, we hope to bring in more T-cells that will attack cancer cells that would otherwise go unnoticed by the body’s immune system.””

There is a link to the relevant “dendritic cell vaccine, which was developed by Liau at UCLA”, and that link goes here:

https://newsroom.ucla.edu/releases/personalized-vaccine-increase-long-term-survival-glioblastoma

“An international study led by UCLA researchers has found that a personalized vaccine may help people with glioblastoma, the deadliest form of brain cancer, live longer. The vaccine, known as DCVax-L, uses a person’s own white blood cells to help activate the immune system to fight cancer.”

The reference to the checkpoint inhibitor in that PR links here:

https://newsroom.ucla.edu/releases/recurrent-glioblastoma-immunotherapy-before-surgery

“Dr. Timothy Cloughesy, Aaron Mochizuki, Robert Prins and scientists at six other centers found that people treated with pembrolizumab prior to surgery lived for an average of more than a year.”

It is relatively easy to draw the connections.

Additionally, see this clarification via UCLA

https://investorshub.advfn.com/boards/read_msg.aspx?message_id=164217398

Hspooner

I took it right off her slides from the last talk, 35:15, when she was talking about the trial.
https://www.youtube.com/watch?v=fMxjVRRSdXE/quote]

Exwannabe January 2022

Will we see data from that [combo] trial? Will there be updates? If so, when? I remember Flip talking about certain milestones/days that we might get some info?

You are asking about this trial run by UCLA that combines DC with Poly-ICLI and Keytruda. A 40 patient 3 arm P1 in rGBM.

Presently listed as recruiting with an estimated primary completion date Aug 2024.

That does not mean you get the results then. As has been documented here repeatedly, schools are slower to get results published than corporations. I would think mid 2026 would be about the earliest to hope for.

As a comparison, the earlier P1 combo by UCLA started recruiting in Aug 2011. It completed recruitment Jan 2015. Interim results presented at SNO in 2017(?).

The next update you will get should be about March '22. UCLA follows the law and provides the required annual updates to the US trial registry.

BTW, Flipper argues this trial completed enrollment in late 2020. I find this hard to believe as they subsequently updated the registry and it still says enrolling, also the UCLA website itself lists the trial as open and enrolling. Scroll about half way down

Lykiri

exwannabe,

Last patient in the UCLA-Merck combo trial was enrolled around May 21, 2021.
Happy New Year!

May 21, 2021
Officially enrolled in the clinical trial! For anyone wondering, the trial has 3 components. 1. Surgery 2. Personalized vaccine made with my tumor cells (you can google DCVAX If you want to know more!) 3. An immunotherapy drug called Keytruda (it’s possible that I will be in the control group and only receive a placebo).

On Tuesday I’ll have my first infusion of the immunotherapy drug and surgery is scheduled for June 7. About a month after the surgery I’ll receive three doses of the vaccine across 6 weeks. I’ll be spending most of the summer in Los Angeles.

Thank you all for helping me to manifest this and for reaching out about places to stay while I am here! We are excited and relieved to have arrived here finally!

May 28, 2021
Two years ago today, May 28, 2019, I had my first craniotomy to remove a large brain tumor in my right frontal lobe (yes, it looks like it's on the left in the MRI images). I had ZERO clue how my life would change from that point forward. After surgery the tumor was confirmed as a Grade IV Glioblastoma (GBM), which is a highly aggressive brain cancer. Needless to say, I've learned a lot about the medical field since then. As most of you know, 2019 brought a series of hell-ish experiences - a surprise second craniotomy for an infection, the SHINGLES (the icing on the cake I didn't order) complete with severe pain from post herpetic neuralgia, a blood clot, lymphedema, not to mention six weeks of daily chemotherapy and radiation. Somehow, I survived. With the love and support of my EXTRAORDINARY COMMUNITY of family and friends. I am incredibly grateful for everyone who helped me through this journey.

Here we are in 2021 and I'm preparing for my third craniotomy on June 7th at UCLA Medical Center in Los Angeles, CA. I'm still in shock that this is happening again and so relieved that I was able to be given the LAST SPOT in the clinical trial, which I hope will lead to a cure for Glioblastoma. We need it - too many people are suffering from this horrible disease. I'll be honest - I kinda feel pissed off AF that I'm even climbing this mountain. AGAIN. I dream of the day when I'm not an "inspiring," "brave," and "resilient" "warrior." I'm ready to be "Just Jenn" again!

Housing update: Thanks to my awesome support in Southern California, we have found places to stay while my mom and I out there for the majority of the summer. There aren't enough words to express how profoundly grateful I am.

MY WORDS about bidding war.

BMY acquired Celgene in 2019 for $74B and in this article from Jan. 2021

https://www.cnbc.com/2019/01/03/bristol-myers-to-buy-celgene-in-a-74-billion-deal.html

It says

https://www.fiercepharma.com/pharma/jpm-21-m-a-still-a-top-priority-at-bristol-myers-as-ceo-eyes-midsize-deals

“We will continue to look for midsize bolt-on deals that further strengthen our object to grow the company into the second half of the decade,” he said. As of the third quarter, Bristol Myers had about $22 billion in cash, and it expects to have $45 billion to $50 billion in free cash flow around 2021 to 2023."

A gallimaufry of pulchritudinous terpsichorean burlesque, followed by a veritable floribundum of perfect and plentitudinous prestidigitation and a show of verisimilitudinous, violent, ventriloquial virtuosity.