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Approval does not require that the potential manufacturers are capable of addressing full demand. There have been plenty of drugs approved in the biologics era where full demand cannot be met at launch. Sometimes the fraction of demand addressed has been too small and a lottery system is set up to allow some fairness in the process of determining who is eligible for the limited supply, MD, RSV and MS were addressed this way initially. Sometimes, as in the case of Coronavirus vaccine and treatments, risk factors are used to determine who gets in line first. Sometimes it is pure luck. Either way, regulators don’t restrict from anyone just because everyone cannot initially be addressed .
I appreciate the detailed summary of the allogenic CAR-T landscape. I was not aware that Allogene was so far along. I will have to look more closely at them. It seems to me that CRSP and NKTX are at similar stages as DTIL with the first gene tech and I think the stealth cell technology for Prcision has promise that may leap frog the first generation allogenic therapies. I like DTIL relative to them both regarding the CAR-T platform, but you are more knowledgeable here and I would appreciate your opinion.
Although, my primary interest in DTIL is their gene editing platform which I believe is superior to CRSPR technology. I need to read more thoroughly the literature on NHP use of CRSPR, but my first pass leads me to believe that off target affects will always be a hurdle with the use of CRSPR to edit genes in vivo for large animals , and especially humans. It is one thing to create animal models of disease and quite another to treat disease without serious safety risk suitable for humans. I don’t consider their hemoglobinopathy programs to be in vivo editing as they are editing stem cells ex vivo and reintroducing them to the patient. This isn’t too dissimilar to the CAR-T approach. I do think DTIL should challenge them in that space, but they would be playing catch up and would need to differentiate in some way to capture significant market share, not being first to market. These diseases likely will not command the market size that the other programs will IMO. We shall see how the current treatments being launched and late stage development programs do commercially. Perhaps, I am wrong and biased but I think these diseases will not produce blockbuster or near blockbuster revenue. The payer mix here is mostly government.
Muscular Dystrophies are a different story., as are mitochondrial diseases. There are high cost treatments in some MDs and SMA has been quite lucrative. DMD has been handicapped by therapies without demonstrated efficacy that charge very, very high prices and target small subsets of the disease. The high prices, however, are a good thing when looking to price a one and done technology. Beyond these diseases you start to look at things that are not rare or ultra-rare. That could capture crazy big revenue for multiple diseases. This is why I believe DTIL is significantly undervalued. Eli Lilly’s move to me validates my thinking. The future royalties for the six diseases is on top of sales, not profits which to me could mean significant revenue. There are many more targets available beyond these six. That gets me excited about the potential here. The other CAR-T companies don’t have this.
To me CAR-T is the fuel, but gene editing is the rocket. Appreciate your feedback. Thanks,
Dendream
Never fear Senti. You and your daughter have invested wisely IMO.
When I was a youngish man with little to my name like your daughter, I went all in with every dime I had saved on Dendreon. I got out along the way of the short squeeze that rocketed it from a low of $1+change to beyond $50. Afterwards, I paid cash for a 4 bedroom lake front home and still had 4x that initial cash in savings. Personally, I believe you diversify when you have doubt but you consolidate when you have certainty. This is not my only stock investment, nor is DTIL my only other, but the two make up a large percentage of my holdings. I may have to wait out Precision Bio like I have had to here, but when I see a radically new and effective approach, I get very excited. I hope NWBO pops before DTIL so that I can load up there even more and do this bonanza for the fourth and fifth times. I have lost big in other sectors, but never in Biotech. So now, I stay focused on my expertise, and go conservative with the rest.
Thank you, sukus. I find the actions or inactions of management to logically fit the story that I believe started in August 2015 and ends with FDA approval. I find that Ex and LC to frequently make statements that defy logic.
The only deviation that I recall from this is the LP presentation on September 12th, 2020, but I do believe there is an adequate explanation for why she said what she said. Otherwise, everything fits the “this is good news” comment, the “all BP brings to the table is money” comment and the “going all the way to the end “ comment. I think at each point where we places a timeline on management, they referred to the timing of their next decision point and later decided not to take the risk of unblinding too early to show a statistically different effect in Early DCVax vs mostly Placebo plus Late DCVax on OS. Instead she stayed committed to taking us to the very end, just as she is committed to every step in the publication and application processes that was putlined.
I do not fear. I do not think this is delay in anything but a TLD PR which is not required, does not communicate to physicians or regulators, and would invite another phase 5 type article without appropriate backing of a journal or regulator.
LC earlier commented that the “delay” has opened them up to another Phase 5article. Well, I disagree and I haven’t seen one yet.
Yep, thanks for correcting, Senti.
Selection bias and retainment bias would not be insignificant. As well, cancers are fought and controlled by the patients immune system. The effects that emotion have on immune response is well understood.
A universally fatal disease still has the variable of timing. Anyone who has cared for oncology patients can tell you that a patients willingness to fight plays a role in how long they will survivr. Patients that give up hope die faster.
Only an amateur would publicly put words in the mouth of FDA. If they have not given you permission to quote them, doing so is a mistake that could lead to a change in opinion. If NWBO received a positive non-binding opinion from FDA about new endpoints, but did not get permission to share this opinion, then the only wise course of action is to remain tight lipped about FDA which is what we are seeing.
If they received a negative opinion, this is material and should be shared in a timely fashion with shareholders.
No news is good news.
It seems to me to be a lot of activity. For a company that is strapped for cash and focused on pulling together a regulatory package as well as a publication, it seems to me that the website should be an afterthought unless you have a need to make the updates. This seems more than coincidence to me.
Khrushchev is before my time. What did the hat symbolize?
Totally agree with you again, DD. They have been consistent on timing since October 5th and we have put boundaries to their guidance. Their guidance remains accurate and in no way is past due. I read that Anders believes in the coming months to end in June. The next segment of time would be coming Quartes which would extend to a full year. To me, coming months is anything less than 9 months or a third quarter
Wed, September 22 sounds good to me. I will look forward to ESMO, UK manufacturing approval, and a publication in the meantime. I will also look forward to regulatory package submissions, accelerated review announcements, and lots of other things between now and then.
Anyone new here wanting a synopsis of the past 8 months here, click back on this posting.
Thanks, Sir Swegen or Danish Dude! Now I am confused.
Doc, I do not doubt what you say about your friend. The bureaucracy that is our Republic has many flaws that are embedded in human behaviors. Humans lie, humans cheat, humans steal, humans deceive, humans are greedy, and some humans are just plain rotten to their core. We see these behaviors present to a high degree right now in our country’s financial markets and our stock price here. It reminds me that we need crusaders.
I knew in August of 2015 that this would be a bumpy ride. I did not know how far and how fast. I knew we were in for a long haul, but I refused to accept it at times. LP told us she was going all the way and I understood what she meant. I also knew what she meant when she said this was a good thing. I lost faith at times because of these bad seeds in humans, but I regained faith which is now stronger because of all that I went through. This summe will be bumpy too, but with only 16,000 investors and increasing attention, I think we will do just fine.
I will not care about the wait when I celebrate this Christmas. I will think this summer about Wes Christian and all that he is doing for retail investors and their mutual and pension fund holders of this world..
A name means something and it always has. It is no coincidence that this man’s name is Christian and that he likely allied himself with us, Linda and Linda.
I can’t remember if we liked Perlmutter here or not?
Thanks for posting, Truthfan
Wrong HappyLibrarian.no blind causes bias in every situation which has the ability to impact results. If patient and physician know the treatment they have bias on their communication which may discourage or encourage participation, may lead to selection bias, and all cancers are fought by the immune system which is the basis of the DCVAX hypothesis. Positive feelings have been shown to improve immune response. Stress does the reverse. Having no blind can cause either of these emotins to be greater in one population than the other.
With this logic and its associated evidence one can conclude that the Helmet has this bias but DCVAX data does not. The fact that there are no side effects improves the blinded assignment and the hybrid were blondly assigned and captured.
Hi Senti, I was actually referring to the LBI news. My guess is that when their study design comes out it too will be a hybrid design following the path of a recent competitor. To me this says two important things.
One is very good in that a second new GBM trial with a hybrid contemporaneous cohort design, hopefully with a better randomization scheme than 3:1. Something like 6:1 still gives a patient a 15% chance of nothingburger, but compromise is compromise and you can’t get it all when you compromise. This shows FDA has bought into hybrid cohort designs.
The other is not as good in that, maybe the reason for the hybrid moving forward in rGBM, especially a hybrid that only improves 2:1 up to 3:1 tells me that the faith in the rGBM contemporaneous control population is not super strong yet. Perhaps, the first secondary is the reason for the mulling and tinkering. It is not a large group on either side of the blind and the synthetic cohort has some swag to it. Looks to me like FDA may not be convinced it is the new SOC for rGBM and is allowing companies to compete in a similar fashion. This will help add new patients to the synthetic pool moving forward as well.
The fact that these are rGBM and not ndGBM is a very good sign to me. Very, very good. Very, very, very good.
I honestly don’t think the counter spin adds up to bad news if one uses logic.
Every time I watch a piece of this video, I get angry about what has happened to this great country of mine. We are literally letting people prosper in a career set out to destroy American and Western innovations. Literally profit from causing the opposite of progress.
Something tells me this video and NWBO management are connected. So, when I see things like VBI news a piece of me does get very angry that not only did the innovation of DCVAX brings to humanity get stalled (I have learned that I have to accept this), but also money has instead chased inferior technology in order to try to fill the gap which is called UNMET MEDICAL NEED.
Unmet mean that there is NOTHING that can be done for that person, Medical means it is a patient that is SUFFERING from something, need means that WE RECOGNIZE this suffering as a legitimate illness.
This video tells me the market is set up to chase medical bottom, the more innovative a small company gets the more likely to be attacked if not rapidly developed which is then back filled and funded in the form of a new company and new technology and if too promising do it all again.
This is quite honestly the ENEMY of capitalism which is one of two known allies to DEMOCRACY.
How does the government not see that this is hurting our people from every angle you look. Health, Jobs, Retirement savings, scientific advancement which fuels more scientific discovery. Think of how innovative this capitalist spirit has been since the turn of the century (20th century). Now think how much faster we could have climbed without this BS in the financial markets.
Good coverage of the Lilly deal here. Lilly seems pretty excited...
"This collaboration with Precision BioSciences represents another milestone in the realization of our vision to create medicines with transformational potential, using new therapeutic modalities such as gene editing to tackle targets and indications which were previously undruggable,” said Andrew Adams, Ph.D., vice president of new therapeutic modalities at Eli Lilly, in a statement Friday.
Lilly and Precision will use the latter’s ARCUS genome editing platform to develop new gene therapies. The technology is based on a natural enzyme called a homing endonuclease that can insert or delete a piece of DNA before shutting itself off using a built-in safety switch. The switch is designed to prevent unwanted, off-target edits elsewhere in the genome.
DD, I am really slow with IT. Are you suggesting that the press release page is being updated soon? Have you seen this before? With NWBO?
This seems like a high risk-reward situation, win or try again? Let’s all put a lot of positive vibes to the universe tonight.
Happy, I would like to respond to your statement a few days back about NWBO management and timing. The last projection for TLD given was in the coming months which still stands. Now this is a bit nebulous, but Q3 qualifies for me within a reasonable assumption for this statement. This to me is management providing forward looking guidance.
Then they told us that the submitted to MHRA for manufacturing approval and later gave Q3 as guidance for this production capability. This is a regulatory process that is required for marketing approval of a drug. You must have an approved production facility. This means that the UK regulatory process has begun. This to me is guidance.
the Company is hopeful that an initial license will be issued and production of GMP DCVax-L products in the Sawston facility may begin by around the end of Q3.
https://nwbio.com/uk-manufacturing-facility-phase-iii-trial-updates-from-northwest-biotherapeutics-otcqb-nwbo/
They have already prepared manufacturing in the USA through Cognate/CRL, and have the potential to expand with Franhaufer in Germany where they have 21 suites.
https://www.izi.fraunhofer.de/en/press/press-releases/fraunhofer_izi_and_novartis_continue_successful_collaboration_with_car-t_cell_therapy.html
On August 27, 2018, Novartis announced that the therapy had been approved by the European Commission (1). Over the next few years, prescription-only T-cell therapies will now also be manufactured on an interim basis in the Main Department of GMP Cell and Gene Therapy at Fraunhofer IZI
HappyLibrarian, I was looking back at old posts trying to find one that I replied to for information, but stumbled on this conversation. I don’t recall you responding, but if you did please summarize your reply. Otherwise, I will answer some of the questions that I posed to you.
How many chances at a submission package acceptance do we have and of those how many will accept the new endpoints? To this, I also say there remains some degree of uncertainty in the answer.
Want to place a bet on whether they use a full placebo group or comparison to blended hybrid contemporaneous controls?
That would say something, wouldn’t it?
I know the numbers are small, but the ORR for heavily pretreated r/rNHL that had previously received CAR-T (75%) and Stem Cell Transplantation (66%) is pretty impressive. They are focusing on eLD to delay immune response to CAR-T administration, but I think they are still looking at retreatment. Combining the two approaches could produce some strong long term results in these difficult to save patients.
Precision is leading the race to allogenic off-the-shelf CAR-T with solid phase I results. How CRSP is worth $6B and this company is only priced out at $650M is beyond me to understand. DTIL is looking at potentially $2.5B in milestone payments on the gene editing program, has $200M cash on hand and has one heck of an exciting pipeline and platforms.
Jester, For everyone with GBM will live longer....For now, we will have to accept just that. For my loved ones I am now growing impatient for colon, melanoma, bladder, lung, and eventually any other. Today I will rejoice that we are months away from her Majesty providing access to the world so long as CRL and/or Fraunhofer are ready.
Because 23.1 is bigger than 16, much bigger in fact. So 50% are living longer as are 25% living much longer The only reasons one would have any worry that this wasn’t would be because if DCVAX crossover gives nearly 100% efficacy but this group at that time wasn’t a big enough group to influence that number that much, or that the majority of the progressors before 23 months were on DCVAX. But this cannot be true because it took so long to reach 248 PFS events. You see, if treatment group of patients behaved as placebo or worse due to pseudo effects then placebo rate plus psuedo would have driven us to 248 way sooner adding in placebo. It took about 2 years and 7 or 8 months from 50% enrollment (31.5 mo), 1 year and 5 or 6 months from 90% enrollment (17.5 mo) and full enrollment 1 year a 2 or 3 months (14.5 mo) to reach 75% evented.
In the recent Bev trial, 75% placebo event PFS around 13 mo and 17 mo for treatment overall. The 75% for enrollment in this trial was about 22-24 months before reaching the trigger. Median PFS were 9 and 10 months.
https://www.nejm.org/doi/10.1056/NEJMoa1308345?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200www.ncbi.nlm.nih.gov
These numbers add up to only one answer.
The measurement that counts is data lock to approval. Nothing else matters.
Hope, I completely sympathize with this perspective and empathize as well since I have a friend currently living with GBM. For this dilemma, I point the finger at our health insurance industry. If NWBO were to produce vaccine for the RTT patient at cost of manufacturing plus distribution at R&D manufacturing costs. That is cost prohibitive to the patient and a wash for NWBO. But this isn’t he case, in order for NWBO to receive supply for that vaccine, the patient must have a successful resection, properly handled and a lymphopheresis to obtain Dendritic cells. This procedure costs approximately $2500, billed higher plus administration services and associated fees.
Commercial insurance will not pay for these additional services, not to mention the minor delivery charges on the back end. NWBO would need to foot this bill, or the institution, which in most cases means NWBO. Demand 100 patients is $500,000 we don’t have to be charitable with on top of free drug or drug at cost. An Early Access program takes infrastructure that we do not currently have. This too costs money to build and maintain. The costs of manufacturing are primarily due to Cognate/CRL so that is not free drug to NWBO it is highly priced drug. That is $15M we don’t have. A facility in operation for a few costs much more than one in operation for many. Although 100 is an underestimation of demand, it is not full demand by any stretch.
If you have $30-50M lying around to donate to the cause...
What every cancer patient, not just those with GBM need is for DCVAX to be approved in the US and adopted as SOC. This will lead to bigger and better things. A partially accepted often challenged regimen is not in anyone’s best interest in the short, mid or long term.
When I posted the equation and its assumptions gave the number for 3 years was 38% treatment. This is an over-estimate by a little. The second, crude ballpark method gives you 36.5% which validates the first and provides a range, this uses LL’s 15% estimate. Here is a third, you know for sensitivity analysis.
In 2017, the cohort produced a KM estimated 25.4% make it to 3 years. These are the originally randomized group of 331-12 LTFU-108 Saints Marching iIn. 108 isn’t my math, but I assume others are correct. That roughly give 53 patients. Now 87 cross at September 2018 collection (collect, analysis, presentation) which has 7 LTFU, 4 or 5 pending cross over 3 years, and a KM estimate of 0.282. KM would estimate 91 which looks just about right.
91-53=38/108 = 32.2% which is an underestimation because the 108 is somewhat blended.
So you have between 32.2% which we know is low and 37.8% which we know if high. Conveniently the middle is 35%. So 231 randomized to treatment minus 5 of 7 LTFU (guesstimate) times 35% This gives you 16.5% original placebo. Linda Liau says placebo should be about 14-15%. The low gives you 32.2% vs 17.5%.
Unfortunately, these numbers don’t bode as well for rGBM because treatment improves to about 19%. Linda’s numbers are are 0, 0, ~10%, ~16%.. This is a mean of means of 8.5% but a wide range. They have small N’s, both of them.
I am assuming that you had read my synopsis of the presentation plus paper. I did not see the Medicenna postings at that time. That study design essentially follows what I had outlined. It is an interesting way to internally validate the control arm as well as remove most placebo due to match and crossover. It can essentially be done with those that did not crossover. The difference in what was said and seen may just be semantics.
My mathematical assumption for this group size would be about 30 for DCVAX, but nothing says that you need to retain a 2:1 match. If you selected 202 captured randomly from the super cohort of placebos and these 202 placebo blinded matched randomly selected and captured could be done thrice for sensitivity analysis and then validated against the 30 before being combined with the 30. That is one heavily matched placebo control arm, I doubt you would see a single characteristic out of whack.
Here are two that did not add to the prior explanation of her talk and his paper that I wrote. First, now that you ran IDH mutation you can validate the study population randomness one last time. If IDH mutation in treatment essentially matched hybrid cohort mutations, then you have the perfect randomized, placebo-controlled blindly treated population ever built. That step may never be repeatable. But it will prove the theory. Second, this matched placebo cohort is now 1:1 meaning you have much more power comparing 232 v 232, than 232 vs 116. They originally powered the trial for PFS and OS at p<0.02. Now, it has lowered substantially this bar. The statistically different difference detectable now has dropped which impacts the new primary/primary but I don’t know exectly how because of the change in statistical approach.
Either way...that spells BOOM shaka laka shaka laka shaka BOOM!
5 years gives you quite a good chance at the original OS Hazards ratio due to the length of 5-12+ years. Think about the fact that when those last 108 come marching in and the numbers grow, it is like those saints coming marching in. I want to be in that number, when the 108 come marching in. Oh when the 108, come marching in, oh when the 108 go marching in. I want to be in that number.
BOOM shaka laka shaka laka shaka BOOM!
BOOM shaka laka shaka laka shaka BOOM!
BOOM shaka laka shaka laka shaka BOOM!
BOOM shaka laka shaka laka shaka BOOM!
BOOM shaka laka shaka laka shaka BOOM!
There it is.
Jondo, Did you see the last 5 minutes of Wednesday’s presentation? I try to watch and it freezes on me at 18:37 every time. If so, what does he say?
I love the CAR-T program and progress being made, but gene is where this game is played. The primates are adding up in numbers and years. That is very promising in my eyes. Milestones and CAR-T will not only carry this through but will likely be quite profitable. They only licensed 6 genes, only six. It doesn’t sound like T1DM is one of them???
DMD will be a very nice win, they haven’t said they have a gene yet but SMA has proof of concept and can now be ‘cured’ in babies. Type 1 Babies would show efficacy in weeks. Time is muscle in SMA and every day a Type 1 SMA baby goes without SMN, they lose muscle. Many never raise their heads, cry a cry or lift their arms without the new therapies. Spinraza and Vector gene are available but have drawbacks including IT administration or uncertainty about long term overproduction as their is an adult MD that is caused by over instead of under production. Vector could accumulate risk but natural production should be controlled. Arcus could be tried in utero even some day and they never would have to breath one diminished breath. Imagine how those 1000 parents would feel about never having to worry a single day each year. DMD is bigger. Not as bad, but not good at all. It is tough to watch your child slowly waste away.
aTTR is becoming an established market too. There is big money in curing MD of any kind but those three have cost determination for lesser technology. In the case of DMD, literally no proof of efficacy. The medical costs offset, the cost of current therapy, and the life years of income gained make quite a contribution to society. SMA kids have superior intellect. It is a unique correlation. One of them may just invent the hyperdrive or cold fusion.
New presentation available, showcasing 12 r/r NHL patients with eLD, as well as stealth technology findings.
https://investor.precisionbiosciences.com/static-files/d09d5708-74f5-438e-8f7b-3f26e4781a87
Thank you for expounding. I did not notice the difference but it could just be semantics. Thorlund suggests that you can use that small group of non-crossovers to internally validate the match and combine to build the comparative group. I am not sure that you need to do that or that it would change the results. It sounds like another trial is running with that modeling. Rather than eliminating placebos, you could drastically limit placebos to like a 1:9 randomization and apply the Thorlund concept, but to me that seems to be continuing a broken process, with a compromise.
They also don’t specify whether the grouped contemporaneous controls in total will serve as the comparison or if it will be a matched subgroup. I assume the later, but the former is possible with covariant adjustment. In the end, these may matter with future studies, but it is splitting hairs for this trial. The results will be unquestionably different and the minor magnitude changes, negligible. I like the idea of capturing a clean group, comparing them to the existing group, maybe sampling three capture groups for sensitivity, but keeping the comparison limited to contemporaneous controls. I am sure this is spelled out in detail in the SAP and was likely negotiated across regulators.
Is anyone registered for today’s presentation?
Can you elaborate on the lack of a hybrid synthetic control arm? This is the process Thorlund outlines using it also to internally validate the selected group. It seems an adequate population to use. How do we know this is not being done?
Legit concerns. I have seen many curious moves over the years. In what countries are Pfizer and Moderna based? I think this helps on both sides of the pond. I have seen small bios strike out only to get put back together by BP, but I have also seen small guys fight through and win. I like what I am seeing here, but that is just my opinion. This is always a risk which improves at least the odds making with data.
Kgeo, I am not going to deny that I feel like management has kept me on edge one way or another since August 2015. Whether it be a study milestone or a financing crisis, I always felt like I needed to stay focused. But I started with the idea that in about June of 2015, DSM went to FDA and called for a halt. The company repeatedly stated they never did an efficacy interim and I believe them. Since manufacturing could not be an issue as they enrolled patients in screening, and safety with drug could not be an issue since the study did not stop dosing at all, there is only one conclusion that I could reasonably draw. At that point, I and my friends/family could have sold, even should have, but we decided that we were right and dug in.
Put the drama of wolves and law suits aside, and look at study and regulatory decisions and company every time you face the future. Look at competition at those times. Listen to what is actually said. Each time we reached a milestone, I was put on edge and I inferred a timing, but what was actually said is this is the next milestone. The only exception for me is the verbal word which bc internet is the published word in September on a Saturday morning which I believe was 9/12/2020 around noon depending on where you live. I justify that with the understanding that we leapt from sub-0.040 to over $2.50 on speculation amongst a small tight group which gave me both comfort and a better brighter future outlook. i believe that made us all stronger in many ways which would be helpful during negotiations. That made me open the checkbook once more, but the news that I have gotten has not made me regret. My only regret is that I sold during a family crisis. I have tried to make up for that, but you can never make up for your bad decisions. You can only move forward.
The news I follow are PRs, SEC filings, Regulatory steps, and competitive landscape. Others have entered other diseases with some success. It is time to get the ball rolling , establishing a quick win and move forward with other indications quickly and swiftly. To do so requires a lot more of everything we don’t have.
Finances have never been my strength in this game but I can do math and Intrust others on this board, but form my own opinion. I think our best future path without question is CRL if they will take a reasonable offer which to me is about 50-50. They bring solid growth, solid infrastructure, manufacturing capabilities, free cash flow and more to the table. We bring DCVAX. Together we bring something much more, much faster, much stronger as well as a quick path to other M&A. Together we have SYNERGY. Those mergers have worked well in our industry. Competition should always be part of your equation. Does CRL have interest in us or do they just want to be a CMO? That is a growth game, but Novartis, Biogen, Amgen, Roche, Lilly and the like are CMOs for each other as well. It has much competition. Better to do both.
We are not set up to launch this drug outside of the UK without a partner of some sort. I choose CRL if they choose us, but to do so takes capital. We can dilute some more and take the slow path or do something else and give up capital. Our capital is DCVAX and it has competition. Time is ticking.
AeK, the answer to the 23.1 mo that I think you are asking is that it does not change because almost all patients had passed 23.1 mo by Oct 2018 (Those that did not are LTFU). But if you are asking what will they be broken out, here was my guesstimate from earlier, but I must update the 0.46 and 0.54 to be closer to 0.33 vs 0.67 as I now believe all crossed over immediately after August 2015. We originally worked with a different number from >90%. This changes the numbers a little bit...
https://investorshub.advfn.com/boards/read_msg.aspx?message_id=141582011
The top 100 question depends on how many you think were alive in 2018 and how many lived 2 more years after that. If more than 50 stayed alive, I believe the number to be between 55 and 66, then the median of that group grew by close to 24 months to 82 months.
In October of 2020 the fact that the last group of patients reached five years on trial is an amazing accomplishment, both to run a trial that lasts that long in today’s climate, and to have enough GBM patients alive in a group of 331 where only 20-25 should make it that far on study. A day like that, it should be marked in history...say by locking your database and submitting a PR.
All yall, who love to diss the timeline can choose whether or not to listen to and/or believe the rational explanation for how an why we are exactly where we are today, OR you can pay attention to the present moment and recent past.
On October 5, 2020 the database was locked. This is an official regulatory step.
On April 12, 2021 Linda Liau presented the statistical model with its validation. This is an official regulatory step revealed.
On May 12, 2021 the company submitted for MHRA approval of their UK manufacturing facility. This is an official regulatory step.
On May 18/19, 2021 Linda Liau presented the Statistical Analysis Plan overview. This is an official regulatory plan, at least in two regions.
Publication/presentation are for the scientists who already know the answer. I am quite pleased with the progress and do not see the Regulatory process slipping in any way. We are still right on track given COVID and the complicated nature of this process.
The question on my mind is whether FDA is planning to compete with their 3 month approval record or not. UK and EMEA are not questions for me with regards to those processes. I don’t need to be anxious about time when I know the outcome already. FDA is the question and an acceptance of a package would go a long way towards easing that anxiety.
Too graphic? I like the Highlander movies and TV show. Unfortunately, the Quckening comes after the violent act, but the movies and definitely the TV show made it seem more romantic than that. It was always about the journey that came before and the one that followed afterwards. The Quickening was just a crescendo of sorts.
Nonetheless, there can be only one SOC for GBM and only one right answer on the subject of NWBO and it’s direction. There will be a quickening and this story has its romance. There can be only one...
The Curious Case of Wallstreet and Science
Sometimes the street jumps in way too early, sometimes too late, sometimes they get it just right and sometimes they get it absolutely wrong. That is the truth about the street and their track record for science.
A randomized open label trial is really just two single arm studies. The patient and physician have bias. When it is blinded it is called the placebo effect. When it is not blind, the bias is opposite, those on treatment assume benefit and those not on treatment assume the opposite. This bias is estimated at about 30% in most diseases.
A randomly and blindly selected match from a randomly and blinded selected cohort does not have this bias. Selection bias can be evaluated by sensitivity analysis. You capture three populations and compare the results, you test an endpoint three different ways and look for congruence. This methodology is tried and true FDA practice for controlling bias. There is always bias in how endpoints are selected, just to be sure the bias isn’t running the show, one must look at sensitivity of the measure being used.
This is just good science, open label is questionable science without doubt. But it is acceptable in certain situations. It is nonetheless highly biased.
Is the street ahead of, behind or just plain wrong on the science here?
These are probably not part of the Eli Lilly deal.
https://www.nature.com/articles/s41467-021-23561-7
Currently, most mitochondrial disorders have no treatment and care is only palliative. The ability to shift mtDNA heteroplasmy is a promising treatment approach for severe heteroplasmic mitochondrial disorders. This can be done by decreasing levels of mutant mtDNA to below disease threshold levels, to ameliorate phenotypes.
In conclusion, mitoARCUS is a promising tool for eliminating mutant mtDNA. Its compact size, monomeric structure, ability to recognize new target sequences, and ability to produce large shifts with minimal negative effects suggest that it could be further developed for in vivo applications.