Mate, agree peer review adds credibility. But I don’t see material public institutional volumes coming until an uplift. So this would need to be private funds that are being (re?)enticed to the stock.

We are still sitting at only 1.25m usd of shares changing hands (roughly). Can’t imagine what would happen in an uplisting where public institutionals might need to add to their index ETFs/mutuals.

Agree but the Nature pre-print we all know about. That should be priced in.

FDA would definitely be interesting but I thought everyone was speculating about Orbis+ or whatever for review.

Just feels suspicious. We aren’t at crazy volumes (yet) but could still land at like 2x 52 week average vols.

Yeah…. So what leaked? There have been many patents these guys have secured around the world. Never seen a plus 10% intra day price rise in any of the other times they secured one.

I hate to say this, but it is half-term week(s) coming up in England shortly.

Many Americans might not fully get European’s devotion to their scheduled holidays. But it’s definitely a thing.

Not shocked at today’s turn of events - but not happy about it either.

Revenues - I think 10Q revenue ramp will be the only thing that breaks the stock out from where it is. If we have xxx patients treated at xyz k per case, then we will have irrefutable evidence about the traction against the addressable market.

AE / Mike00h… yeah nothing. So strange. There weren’t even tweets of clinicians who had sat through the presentation.

Twitter is full of #CNS2023 posts. Mayo, Stanford, GWU, a bunch of institutions clearly have their own coordinated “at the conference” social media campaigns running.

UCLA posts at the conference? Nothing as far as I can tell. Not one live tweet. Not one picture. No in session podium shot.

Does anyone else find that a little strange?

I also would be keen to hear the key messages from her presentation. Nothing on Twit... I mean 'X' today about it.

I have no idea why anyone would remain short at scale. They have 20+ days of shorts outstanding against average (normalised) volumes.

Even if some short term trading profit takers wanted to lock in 20-30 percent returns (only if they locked in at 40 cent / share lows), it’s just an untenable position.

At some point, actual operational, regulatory, and financial outcomes do matter in valuation. It looks like (Ie almost certainly with 95+% expected value confidence) that we have reached that point.

Private financial backers would not let the company go out of business at this point. Not with the company holding the JAMA Onc article plus MAA complete submission plus SPORE interim results.

So what on earth are short holders doing? Hoping that MHRA someone decides that NWBO needs another trial? This for a large molecule treatment that extended the tail survival by 3x and that has interim results in combo with other approved indications improved mOS by around 10x?? For a disease that kills the vast overwhelming and almost entire population that contracts the disease???

Sorry for the rant but, like, this short trade went sideways guys. Time to close out and let the company have a natural return to senior market listing.

Quoting Hamilton: “so what did I miss?”

Clearly I missed something… I wish we could just get the MAA done and have an unrestricted ability to market and sell this thing to patients who need it and clinicians who want it.

Ex,

Since Advent is taking the larger employee count and capital expenditures right now, I think those pre-pay balances aren’t super healthy either.

Neither the contract manufacturer nor the IP holder are going to make much money until real financial results start to roll in.

Hoffmann,

The Forbes article, regrettably, feels mostly on the mark. I have never believed in huge amounts of naked shorting of the stock. On the margin? Yes. There’s enough FtDs and other things that on the margin there is some unhelpful stuff going on.

The reality is, our Enterprise Value (EV) is staying roughly constant as shares dilute and the negative Shareholders Equity account builds. It’s the nature of the funding mechanism management has used to get this treatment into approval.

So what turns the share price around and drives EV higher? In my view:
1. Material evidence in the 10-Q that specials demand is increasing and driving meaningful revenue
2. The MAA approval for marketing in the uk
3. FDA and/or NICE approval to drive health insurer / health system payor coverage of the treatment in SoC.

Those are really it. Everything else (including SPORE results) will be “scientific noise” in terms of the share price for the most part.

Once the three milestones are met above, it’ll find a new level - especially with an uplist and institutional buyers.

Anyway, I think we are getting there… but it’s taken us a long long time.

Jerry,

Yes I’ve been tracking this revenue balance sheet line and we don’t see it.

My guess is that Advent takes the pre-pay onto their balance sheet and NW recognises it only once the dose is delivered.

It’s not great for working capital mgmt. but I do not think it’s terribly unusual given the distribution of the operating costs in their arrangement.

Happy for someone with better understanding of large molecule contract manufacturing to shed more light here.

Flipper / friends,

So I’ve also read the article on trial design. Overall, it’s a pretty good article. However, its critique of the DCVax results feels a little statistically lazy.

If someone has the skills and time (I’d have to remind myself of the technique and I don’t have time), you can do some hypothesis testing of what you’d have to believe about trial participant exclusion to make the p values and hazard ratios be statistically the same as chance against the ECAs. As a reminder, both of these values strongly indicate a survival benefit in the current trial. In addition, by systematically eliminating each trial in turn (see ASCO slides for the best table on this), they also demonstrate that there is unlikely to be an underlying methodological reason for the positive KM and robust p values they reported.

So in short… I think the author is overly cautious in reporting the outcome of this trial. Add the interim SPORE results we have seen, and it feels like the article reinforces the overall thrust of DCVax development: activation of dendritic response to a broad spectrum of tumour expressed antigens with the support of checkpoint inhibitors may really change the game in treatment of GBM. We have the mechanism of action lab top results supporting the hypothesis. And I’d say that narrow spectrum mRNA and other targeting tech is likely to be less effective than the broad spectrum alternatives.

Anyway, just my two cents. Until we get the final SPORE results with mOS clocking in at something like 100-120 months will we get the unequivocal signal (rightly) cautious epidemiologists will want to hail the breakthrough. My guess is clinicians won’t wait that long and will add the vax plus ICIC plus a checkpoint to their recommended SoC pretty soon.

Scotty, agree. I’m keen to see where the final SPORE results land. If they are anywhere close to the interim results that have been flashed in various presentations, then we really might be getting somewhere amazing.

Scotty,

It also advances through lab top research into specific mechanisms of action which explain why trials work / don’t work and guide clinician scientists into their next wave of protocol development.

As we’ve seen with the is it Tau is not Tau journey around early and late adult dementia illness families, without a good understanding of the underlying pathways and then the indication’s proposed mechanism of action, we don’t know if the thing actually works.

What was exciting about the mechanism of action was not that the vax just worked as they thought, but that it worked across a broader range of targets than had been previously known, activated a deeper / broader native immune response than expected, and that it could be reenergised again and again to keep the immune response primed and ready to regulate reoccurrence.

Unless I’m missing something, those 3 things are new news and critical to gaining clinical (and regulatory) acceptance moving forward.

Happy to be corrected by people with greater scientific or medical insight than I have, but until I hear from a group of them correcting my understanding, I’m going to be a little more optimistic about these treatments than I was on Friday.

Onco,

Definitely don’t hate your perspective. EBS is super important. It’s even more important in a disease category which generally has killed 95-99.9 percent of patients that clinicians have treated for it within 5 years. Families (and their clinical caretakers) have had many snake oil sales experiences of products that had no or extremely limited efficacy at very high cost and/or with very bad Adverse Events.

The Phase 3 results in JAMA were definitely good. The materials presented by the CTIO broke down the different sensitivities found in that paper and reconfirm that there is highly unlikely to be known or unknown statistical basis in the results relative to ECAs from other studies.

What the results also show is that for a subset of Phase 3 trial (primary and cross over arms), there was a very meaningful response to treatment which more than doubled 5 year survival. But that figure was still far far too low (roughly 13-15 percent iirc).

People on this board, and far more importantly families struggling with this hideous disease, get a lot more excited by the SPORE results which combine check points, poly icic and dcvax to overwhelm systematically the tumours’ abilities to evade immune (and potentially chemo) response. It’s this systematic attack and ongoing regulation that apparently has shown emerging results of 50% + survival past five years.

Much like the methodological and grinding approach clinician scientists took to overcoming the HIV death sentence, it seems that for n/rGBM we might be getting close.

How close and when will really be determined by the quality of evidence that PIs and NWBO submit to the RAs, the specific protocols agreed to launch a revised SOC in clinic, and the understanding of the next building blocks (and btw the removal of historic blocks that may have promoted accidentally tumour regrowth) needed to drive up survival rates.

Anyway, I remain hopeful - I’m not invested in this for money, I’m invested in it because I’ve seen this disease strike close to home and that dear friend is still with us today (and hopefully will be for a great many years more).

Doc,

Cheers. Very helpful.

I agree without automation en masse we are going to struggle to both meet demand (especially on a compassionate use or even blanket all solid tumour basis) and confirm bio-similarity if we switch up the manufacturing process mid flight.

So you’re right (if you’re implying) that we are better off getting the automated lines confirmed from Day 1 rather than having to do a reconfirmation submission of the automated technique versus the manual clean room one for MHRA / FDA approval.

Profound apologies. You’re absolutely right. Grapefruit juice indeed.

So looking at the very detailed “mechanism of action” chapter in the slide deck, it feels like the PIs and company can now be very specific why the vax works. In addition, it appears they’ve stumbled on some additional attributes of GBM which are curious, especially CMV/EBV sensitivity of these tumours. Interestingly, CMV/EBV infection has also been associated with higher risk of falling ill with other brain-inflammatory associated disease like MS.

This mechanism of action materials combined with the SPORE data have to make MHRA approval a fait accompli, no? Regulators are reluctant to approve anything that is just “fruit juice” but in this case:
1. The “fruit juice” seems to actually work - especially when combined with checkpoint inhibitors
2. The “fruit juice” has almost zero material CAEs associated aside from a low grade fever (when the patient otherwise is about 100 percent likely to die of this illness within 5 years otherwise)

Honestly, what are we missing now? NWBO needs to get a really well packaged submission into the RAs and then we can start kicking this horrible illness (and other solid tumours also apparently) in the butt. No?

JM, helpful review of Series C Growth Equity. We need to stop confusing “series c” preferred share issuance with a “vc funding round”. Totally different things.

Flipper,

Just to clarify, this stock issuance is labelled “C” because the prior two tranches of preferred stock were “A” & “B”. We shouldn’t confuse this with VC/Private Equity funding rounds. Arguably, NWBO remains a “pre-revenue” company. So even though it has public equity already, it would be considered an A/B in venture terms. Growth equity starts at round “C” but those investments are generally for commercial growth (marketing, sales force, etc) for an established and rapidly growing company (annual revenues of 50-100m usd).

Of course, all of these definitions are arguably loose, but I don’t want all of us to conflate the preferred stock issuance with a much different question of our funding sources. The danger of going IPO as early as NWBO did (taken in retrospect - as I’m sure they wanted faster approval cycle than we have ultimately witnessed). Had they stayed in private markets, growth equity firms could have invested. Many growth firms are not allowed to do PIPES (private investment in public equities) although a few are.

I’m not sure that the existing mgmt team would want to have an active private equity style investor in their corporate governance - as I’m sure they’d want a strong if not controlling position on the Board.

I should really stop torturing myself like that.

No NEJM.

Back to hold and wait!

Crash, it is Wednesday after all.... 1701 eastern time? Or is that too big a leap of faith.

Bob, just to clarify the approval process in the UK for biotech. It's not an 'all or nothing' kind of submission. It's more like the commissioning process of a naval ship. The UK regulators make you go through progressively more difficult requirements. I can't remember how many stage gates they will have had to go through already, but it's a lot. As the PR indicates clearly, they are almost to final finish and fill for scale production.

Yes, it takes forever to get one of these things going (I know a simple bioreactor industrial lab that wasn't doing tailored indications but just bulk and it took 2.5 years for them to get full US FDA approval).

FeMike, they know we are not that naive.

Crash / others, why did the PR drop the standard 'awaiting publication of TLD in an academic journal' language that has been their standard boilerplate to date? They talked about 'TLD presented recently by a key investigator at an academic conference'.... maybe I'm reading too much into the omission of the publication mention combined with the, we haven't submitted an application for commercial approval of DCVax-L yet.

Crash (Bio FYI), I largely agree with your maths.

You might even get a bit higher reimbursement if the SoC with DCVax allows the NHS to avoid some other interventions. Plus the low toxicity profile means there won’t be a meaningful adverse events ‘tax’ from NICE, either.

Bio, I’m not a registered financial advisor or a personal financial planner, but at this point… you’d have to be crazy to sell us you were facing personal margin calls or wanted to de-risk your portfolio after running up gains from 0.30 usd a share.

Otherwise, you’ve rode it this far, why not keep going??? Makes zero sense otherwise.

Hoffman, Guzzi, the Chancellor’s fund just helps create a ring-fenced set of public monies for reimbursement. Independent Funding Agreements can always be struck with the local reimbursement authorities even without these funds. It just makes it a heck of a lot easier (assuming DCVax qualifies in after MHRA approval).

Hoffman, Valor, Ex follow up on my posts earlier about UK commercial potential. The Chancellor is giving away monies for cancer treatment here in the uk in the new budget. This is always politically popular. Yet to be seen if DCVax will qualify, but I have to imagine if the MHRA approves, it would be hard to exclude the treatment.

https://bit.ly/3O2xdaB

Hoffman, how long is a piece of string? In all seriousness, the NICE process takes a minimum of 40 or so weeks (this is off the head, apologies). It can take a lot longer. The NHS (well for England only, but that’s the bulk of uk public health spending) then must pay for any NICE qualified treatment 26 weeks after approval.

Now all that sounds horrifically drawn out.

In practice, for “orphan” indications like this one, NICE will start making appropriate noises earlier. Cancer clinicians and charities will then help patients get an IFR completed so that they can access the treatment faster (proton beam tech has recently seen a lot of this) and get it reimbursed by govt. It is not the ideal process but bluntly, it still sounds easier than the nightmares of US medical insurance authorisations.

So practically, NWBO needs to get the MHRA to approve, get NICE to start making the right noises (probably after public media pressure) and then nGBM / rGBM patients will start gaining access. The company has got most of the right academic trusts involved in this trial already. Hopefully, they are working hard on the various cancer charities simultaneously.

Valor, health pricing in the UK is tricky. When MHRA authorises the treatment, then private health insurers will incented to reimburse for treatment (often at the private oncology wing of the academic medical centre hospitals). Since many nGBM patients are men in their 50s, I would not be surprised to see a meaningful number of private insurers driven to cover the treatments - roughly at ‘sticker price’.

Then comes the NICE value for money evaluation which is required for the treatment to be offered “on the nhs”. Biologics often negotiate around a price per patient which often is around 20-30k gbps per QALY added. However, given the age demographic involved and the low toxicity / limited additional treatment required to administer / deal with follow ups, it is possible to push that price northwards. Let’s say that the TLD adds an average of 6 months (QALY calculates average improvements a little differently than mOS of academic journals), then low end you’d say 10k price would be acceptable to the NHS. But with all the extenuating factors above, you might get the NHS to a significantly higher number.

If you haven’t looked at it, the NHS has been very lukewarm to some of the RA biologics recently, with NICE assessing that they aren’t good value for money (as they only slightly improve the quality of life for the average rheumatoid arthritis suffer). Given that DCVax may be an outright “cure” for the long-tail of nGBM sufferers, my guess is you’ll get a much warmer NICE reaction.

PS. Th uk oncology world is not large. All these clinician-scientists are know the MHRA, NICE and the NHS. They also all know each other and the cancer charities which support both their translational work as well as the individual patient funding agreements which often support cancer patients being treated by NHS funds.

Ex, I’m a long. I can be English about it and say “marginally” if I want given how distorted the shorts are about their use of language.

I have read some, but not all, of the recent academic papers about the use of ECA. I have found these compelling but I am NOT a PhD trained natural scientist.

However, I do have multiple advanced degrees in social sciences and business and have helped academic medical centres on their oncology strategies and uk-based cancer charities on their investment roadmaps. I also have extensive experience in public and private capital markets and how operating businesses must navigate that complex world of investor expectations, risk profiles, regulatory/investor agreement restrictions, amongst other things.

What I find profoundly distressing about the language of the naysayers about NWBO is that they consistency twist normal financial disclosure practices to create unnecessary anxiety about NWBO relative to other, also risky early-stage biomedical companies. What I find disappointing about longs is that they fail to be extremely precise about their claims about NWBO’s future prospects (eg confounding is a likely reality which drives the ECA requirement).

All of these financial debates are really irrelevant to the underlying science. PFS has become an illegitimate measure for most modern oncology therapies. In fact, many of the most promising checkpoint and immunotherapies appear to have a critical inflammatory promotion mechanism as part of their efficacy.

I know some on this board and in Twitter have taken extraordinary long equity positions in this company (hi Danish!). I love their profound conviction and support for a company that may have found a breakthrough treatment for this g*dd@mn disease. I am not one of those people. I have a tiny position relative to my overall portfolio, as that is appropriate for my risk tolerance. It does, however, align a small amount of my financial interest to a deeply emotional and personal connection for a dearly close relations be cured of their nGBM (or absent that) another alternative should their suffer rGBM.

I hope that’s helpful calibration to my comments and to my (infrequently active) participation here.

Unrestricted FDA approval for use of DCVax-L in nGBM and rGBM.

Valor, you have to imagine that hiring a seasoned biotech executive is in their near future. The age profile of exec leadership makes it hard to believe they wouldn’t reinforce the team as they carry on into commercialisation (although this fact also might be what drives a buy out in the future instead).

Valor, I get it. But the (marginally legitimate) fear of institutional investors will be: show me a time when the FDA approved a treatment using exclusively an ECA approach. The financial equity markets are deeply risk averse. That’s why we have such great embedded upside value left in the shares that is not yet reflected in its market price. Increasingly, I’m of the view that until the FDA says “yes” (beyond any compassionate use waivers that exist in the UK), we are going to be frustrated by the reasonable stubbornness in the SP. But once we get there, we will be off to the races.

Phy, I would add two things to your list (first legitimate, second much less legitimate):

1. Dilution. There is still meaningful dilution left in the various financing agreements outstanding. So whilst the SP has “crashed” over the past year, on a fully diluted enterprise value basis, the company is worth the same / more than it was one year ago (I could go do all the maths to figure this out, but frankly I can’t be asked right now).

2. Confounding / Bet on ECA. Those of us holding have complete conviction that the FDA will accept an ECA argument on mOS and long-tail survival for approval. What you see on iHub and on Twitter and other places are Fudders using the uncertainty of FDA approval of such an approach to approve an extremely expensive large molecular indication. Yes, we can point to papers supporting ECA strategies in terminal illnesses, etc. But until the FDA actually does it (Btw I think that the UK will have less nausea on this element, and NICE should probably like the long tail survival for their “qualies” analysis assuming the cost per qualie isn’t too high). Adding to this second concern is the nonsense noise around how the SEC filings are written in the risks section (confounding, failed endpoints etc) which show up in all 10k/qs in pharma companies. If I were to rewrite the risks section, I would have just said “NWBO needs the FDA to accept an ECA comparison on mOS increase. They have not historically done so but recent evidence suggests they may in the near future for diseases like nGBM and rGBM.”

In short, our equity holding here continues to be priced on a “real option” (binary pass/fail on FDA approval of EXA) with a slowly rising Enterprise Value offset by continuing dilution from warrant issuing, etc. The good thing is that if and when the binary event passes, the company immediately becomes valued on a future DCF basis for GBM and an option value for other tumour types (DCVax-Direct). In my view / hope, that will be a very compelling valuation indeed, especially with the automation of manufacturing and IP patent protections which will make NWBO the go-to producer of anti-cancer immunotherapies for the foreseeable future.

Extremist, I haven’t written the original protocol in sufficient detail to know, but if the 99 was reduced by Covid deaths in the control arm (or really any other entirely non-cancer linked CoD), what happens to those participants? Do they get thrown out entirely or are the accounted for using some other KM curve fit factor?

Extremist, I haven’t written the original protocol in sufficient detail to know, but if the 99 was reduced by Covid deaths in the control arm (or really any other entirely non-cancer linked CoD), what happens to those participants? Do they get thrown out entirely or are the accounted for using some other KM curve fit factor?