Plutonian - I was going by this, and several other pages on the Beam website: - under BEAM-201: 'Delivery modality: Electroporation | Ex vivo'
Maybe they changed at some time in the development? I seem to remember that Maxcyte also quotes them as an electroporation customer. |
Harry, I greatly enjoy your Advent calendar countdown and look forward to each window opening. I am sure you will reap your rewards in the fullness of time. |
Plutonian you old tease - you're not supposed to do this unless I shine the giant "P" in the sky!
(thank you though) |
 Afternoon Super,
Doubtless you've seen my many warnings that I'm no scientist / doctor, but 201 is their only CAR-T. The rest of BEAM's pipeline seems to be very different from what we do.
That AI thing which is the top of any search these days was what I put into my post ("BEAM-201 is produced by base editing T cells from healthy donors at four genomic loci, and then transducing them with a lentivirus. The resulting cells are allogeneic, meaning they are universally compatible.") but I did spend some time looking at this link and pondering what it was all about.
Either search on "lentiviral" or scroll about halfway through it and you end up on a slide entitled "Allogenic multiplex edited CAR-T cell process". Look at the sequence and it says:-
Editor mRNA
gRNA #1
gRNA #2
gRNA #3
gRNA #4
Lentiviral CAR
Quite how that happens is beyond me, but tbh I don't really think it's important.
I put BEAM in the countdown (I have a lot of choices) partly because of Ygor asking about next-gen future proofing with OXB, but my honest opinion is that Novo will own OXB long before BEAM get that before the review committee for approval. |
supernumerary, with the greatest of respect, here is the correction you seek. Direct from the horses mouth...
"BEAM-201 is produced using a GMP-compliant, clinical-scale process in which T cells derived from healthy donors are simultaneously base edited at four genomic loci then transduced with a lentivirus coding for an anti-CD7 CAR"
hxxps://investors.beamtx.com/news-releases/news-release-details/beam-therapeutics-names-first-car-t-base-editing-development |
Harry - re yesterdays calendar entry, small point. I'm not convinced that Beam use viral vectors of any sort for BEAM-201 - they say they transfect the cells using electroporation (Maxcyte technology) rather than viral transduction. So I assume that oxb is providing bioreactor services for other stages of the process, and probably a lot of guidance too.
Correct me if I'm wrong! |
OK, the interim results working days countdown...
4 days to go - Kyverna Therapeutics.
OXB say very little about Kyverna. If you use the search facility on the OXB website you will find nothing. All OXB have ever said is a brief passage tucked away in the 2022 interims text to say that we signed them up sometime after 30th June 2022 to provide vectors / support for their CAR-T work.
This OXB link may or may not refer
This 3rd party link definitely refers
Why have I picked Kyverna for the number 4 spot? Their September presentation (just out)
It's brilliant and I would encourage anyone to read it, but selected points to note:-
Slide 19 - against Manufacturing and supply chain partnerships - "Oxford Biomedica supply agreement, enabling use of LentiVector"
Slide 4 - 8.3 million potential patients
Slide 6 - Zero serious reactions / complication in the clinical trials on the first 30 patients so far
Slide 9 - Note the Fast Track route to approval awards and the RMAT (regenerative medicine advanced therapy) designation (allows for accelerated approval based surrogate or intermediate endpoints).
Following slides show trial successes so far including a feature on a lady who is now fixed.
What more can we ask? |
Xoptimist,
Avid have more than 200m debt and little cash while the reverse is true for OXB. The revenue guide you cite for Avid is for FY25 whereas for OXB FY24. Taken together on an EV/fwd sales basis the valuation gap is significantly greater than what you've estimated. That is of course before even discussing other quantitative and qualitative differences. |
Well spotted Phil.
To me that all lines up with our past observations here (circumstantial evidence that they appear to have extended the "stopgap" Yarnton lease and the pretty much constant high volume recruitment), followed of course by the recent OXB RNS which included the line "With increasing demand for services, OXB to invest in talent to support future growth".
In less words they are a lot busier than they expected to be at this point and they needed to split that role which is now too much work for one.
I would say it's a very good sign. |
Xoptimist,
We can agree to disagree and I'm fine with that, but I'm in the same camp as Seb (and long before him JD who said much the same thing) in that looking around there is only really OXB which does what OXB does. Most of the people eyeing up and moving in on the business opportunity are fermenters, small molecule bashers or similar who fancy a piece of the CGT action.
I think I'm correct in saying that Avid decided to expand into viral vectors in 2021 and opened some suites in 2022?
That's great, but if true it's no time at all in this business and they will still be learning.
OXB spent 25 years perfecting their 4th generation lentiviral vector which is acknowledged as a world leader and offered to all our clients. Where is the Avid equivalent? From what I can see on their website they offer to grow on most popular vectors for customers but offer none of their own.
Unless they take a leaf out of OXB's book and spend a small fortune buying a good / proven AAV or similar (and then make it better using OXB tech which they likely don't have) then how are they going to catch up?
Remember Seb (who works for OXB but also advises IM) explaining why IM sold us ABL for so little? Because they had no vectors of their own, realised that developing their own would take too long / cost too much and finally (after accepting they would probably never catch up) decided to pay in kind to become part of the world leader in a "if you can't beat them, join them" move.
Avid's new viral vector facility is 53,000 sq ft
OXB have 183,000 sq ft in Oxford, 96,000 sq ft in Boston and 123,000 sq ft in France.
If Avid really are our nearest competitor then that should make us all feel an awful lot better about holding OXB. My guess would be Samsung are closer with their CGT division, but of course they trade on an enormous sales multiple. |
Hey Harry
I think we all fundamentally believe that OXB is undervalued by the current market and the share price continues to be weighed down by its past and the lack of any news.
I do however think we might need to retool our ideas around valuation multiples a little.
I think we all believe there are very few exact apples to apples industry comparables to OXB and in some way OXB is a unique company.
We have however often been told that the most clear comparable for OXB is Avid Biosciences of the US.
That’s a CDMO company which has a current forward revenue guidance for FY25 (year ending April 30th 2025) of $160-168m (mid point of $164m) – which serendipitously is exactly what OXB is guiding with our mid point of £130m. At today share price of around $11.20 and with 63.8m shares in issue that gives Avid a market cap of about $715m or GBP568m. The multiple to forward sales is 4.35 compared to our 2.83 multiple based on OXB market cap of GBP368m and forward guided sales this year of £130m.
Avid has three things going for it we don’t. Its profitable; it doesn’t have the kind of challenging back story we had in 2022 and 2023; and its U.S. listed.
So the extent to which it is a good comparable for OXB one would think that we should have a similar multiple of sales once we are profitable and have further buried our recent past in the rear view mirror. So lets say a 4-4.5 times multiple at the end of next year when hopefully based on Frank’s forward guidance we have booked £175m of revenue and have turned a profit – so a market cap of £175m x 4.5 = £787m or £7.50 per share. That would be a more than doubling of the share price over the next 15 months.
And then in 2026/2027 we will need to get to more traditional valuation metrics – multiples of earnings.
So what is the right valuation today? Until we are profitable and palpably out of the woods it makes sense to me that the market has a valuation discount. As investors get more confident about management’s forward guidance – which hopefully will be what happens next week – then the market will start closing the valuation and multiple gap.
Within the next 6 months what makes sense to me is that we get to, say, at least 3.5 times sales. So, we should be looking by the end of April at a market cap of around £612m. This would mean a 66% increase in the share price from where we are today - in seven months. That would be a handsome return without any need for a frothy valuation or multiple.
Fingers crossed there is no backsliding by management on forward guidance next Monday and if we are lucky, as you have suggested, Frank finally puts some flesh on the bone of our multiple myeloma deal or releases some other major news. And if its really good news then maybe we get to 3.5 times sales sooner than I currently anticipate.
Once again for me, assuming everything remains as guided, its just a matter of patience before the market plays catch up. |
Change in people page.
Thierry now COO only
Mark Caswell moved from US to UK site head
New US site head: John Maravich joined Oxford Biomedica as the VP of operations at the Bedford site in November 2023 and became Site Head of US Operations in September 2024. |
I think you are correct Sean.
I also think Frank learnt a lesson last year (after coming from years at a private company) that you can't just change full year guidance on interims day and think it will all be fine. Hence him telling us mostly what we already knew again on the 8th of last month, which would really be to reassure the market that the full year guidance for this year and the forecast of profitability next year is still on track or better.
There are several things looming with OXB now which are gamechangers. We know some as shareholders but there will be others we don't know about. The great thing of course about multiple eggs in multiple baskets is that we have very good odds of landing multiple deals, and of course we "know" we have a second commercial CAR-T deal already (they told us in March). They just haven't given any detail - which would be my guess for Frank's "big reveal" at the interims presentation, but we will see.
Regardless of if the market follows OXB's detail or not (likely not) the headline figures will be big news and for OXB the multiples are currently all wrong.
If you say £130m revenue for this year, then the market cap should be around £650m and yet we are £365m.
Frank has promised better than +35% for next year, so £175m sales would be a market cap nudging a billion on very average sector ratings.
If the new CAR-T deal (announced but still secret) is anything like what it should be, then OXB will be back in the FTSE250 at the last review of the year. |
Well Ive been in OXB and ridden its ups and downs for a very long time now and done my research (much of it having been greatly assisted by Harry - thank you Harry) but I have a sense that we are on the cusp of reaching the holy grail of sustained and significant profitability within a year or so. Maybe sooner. Which is very good news to all us LTHs although the downside of course is that could make us too much of a temptation for the likes of Novartis. However that is unlikely to happen without a very significant share price re rating. I think next week could be very interesting. |
Week 2 of the 10 working day interims countdown, "the final furlong":-
5 days to go - Beam Theraputics (allogeneic CAR-T for leukaemia and lymphoma).
Abridged version bullet points:-
* Beam's CAR-T is an allogeneic therapy (will be made in bulk / not individually).
* Beam use OXB's LentiVector to make their CAR-T in roughly the same way as Novartis use LentiVector to make their personalised CAR-T (Kymriah).
* First patients were treated with BEAM-201 just over a year ago now, which means they will be adding up 12 month data as the following patients all hit that point.
* Beam are to present findings at the ASH conference in December.
Unabridged version for those who can take it:-
Why are Beam featuring in this "selection of 10" highlights from the list of OXB partners?
Because if successful it's a non-personalised treatment - i.e. can be made in bulk - quicker / cheaper and so will be available to more patients as the personalised step in the process (after OXB) isn't required.
Bit of history:-
3rd August 2020 Beam sign with OXB to use our LentiVector Platform in their Next Generation CAR-T Therapeutics.
Beam's next gen CAR-T is BEAM-201 see
From the internet "BEAM-201 is produced by base editing T cells from healthy donors at four genomic loci, and then transducing them with a lentivirus. The resulting cells are allogeneic, meaning they are universally compatible.". (The lentivirus bit there being OXB's LentiVector and the first patient on the trial was dosed just over a year ago).
From their Q2 statement (see)
"Initial data from the Phase 1/2 clinical trial of BEAM-201, a multiplex-edited allogeneic CAR-T product candidate for the treatment of relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL)/T-cell lymphoblastic lymphoma (T-LL), have been submitted for presentation at the ASH Annual Meeting.". (American Society of Hematology (ASH) Annual Meeting takes place in December).
Without intending to sound flippant here, if something had gone horribly wrong there then we would already know as they would have halted / stopped this trial so it's just a matter of waiting to see how well it worked.
(Usual non-scientist warning) I don't think that any of the allogeneic (universal) CAR-T treatments tried so far have been anywhere near as effective (either efficacious or durable) as autologous (personalised - like our Kymriah work for Novartis). But there is a second chance here, in that even if it doesn't prove to be a better treatment than personalised, an "off the shelf" universal treatment available immediately in specialist hospital labs could be very useful to "buy time" for late stage patients where the wait for a better personalised treatment might be too long.
Why might Beam's try at allogeneic work when other have failed?
This is a good link
Selected quote:- "“multiplex editing,” in which several genes are edited. The edits are designed to eliminate expression of four genes known as CD7, TRAC, PDCD1 and CD52. Beam claims this approach could lead to a more powerful and durable treatment. In its statement, the company noted BEAM-201’s potential to sidestep a variety of issues associated with cell therapies, like propensity for the modified cells to kill one another, or become weaker as time goes on."
Egghead quote from this link
"BEAM-201 is an anti-CD7 CAR-T cell therapy candidate, which undergoes multiplex base editing to eliminate expression of the CD7, TRAC, PDCD1 and CD52 genes. Base editor mRNA and 4 single-guide RNAs that each target one of the aforementioned genes are delivered to healthy donor T cells via a single electroporation step, and the edited cells are then infused into patients.
What do all these edits do?
CD7 is a transmembrane protein that is naturally expressed on the surfaces of thymocytes and mature T cells. It is seen as an attractive target for immunotherapy of T-ALL/T-LL as well as acute myeloid leukaemia due to its widespread distribution on these cancers. BEAM-201 cells express a CD7-targeting CAR that is designed to target CD-7 expressing cells. To avoid T cell fratricide, i.e., a situation whereby the CAR-T cells target each other, BEAM-201 cells are base-edited to silence CD7.
TRAC disruption blocks endogenous TCR-mediated signalling, which enables the safe use of allogeneic T cells as the source of CAR-T without inducing life-threatening graft-versus-host disease (GvHD).
PDCD1 disruption eliminates the expression of the checkpoint inhibitor protein, PD-1. PD-1 and its ligand programmed cell death ligand 1 (PD-L1) are immune checkpoint proteins expressed on the surface of T cells. Under physiological conditions their interaction results in T cell immune suppression, but cancer cells can hijack this pathway to escape immune detection. However, this can be reversed by blocking PD-1’s interaction with PD-L1, in this case, through PDCD1 disruption.
CD52 disruption renders BEAM-201 cells resistant to therapeutic anti-CD52 monoclonal antibodies, which are used during lymphodepletion to reduce host rejection of allogeneic cells."
Interims results countdown do far:-
10 Sardocor (Cardiac gene therapy)
9 Cargo Therapeutics (Bicistronic and tricistronic CARs)
8 Oxford University labs (Lassa Fever vaccine)
7 Boehringer Ingelheim (Cystic Fibrosis)
6 Immatics (T-cell-redirecting cancer immunotherapies)
5 Beam Therapeutics (allogeneic CAR-T for leukaemia and lymphoma). |
I like that one PB (I'm a big fan of pictures painting a thousand words) but I think important to stress / remind that whilst most CAR-T uses some kind of viral vector, CAR-T is just one of a very long list of things which you can do with a viral vector. |
Nice chart HTTps://x.com/Larvol/status/1835036047178449300?s=19 |
We've either got some very short memories here (or I suppose it could be people who sensibly have me filtered), but I posted that 4 days ago in 8599.
Just out of curiosity, did anybody listen to the OXB Xtalks webcast which we got the invite to (aired last Wednesday 4pm)? |
The UK shares to own as interest rates fall
With borrowing costs down and expected to decline further, City writer Graeme Evans reveals one analyst’s tips to exploit looser monetary policy.
OXB included in article |
You obviously remember YMG too Cousin ;)
For those who might be wondering about Marcus's very interesting link with this photo embedded
Well OXB have simply guided "better than" 20% margin for EBITDA earnings by 2026. When cornered on what that meant and what it eventually could be by an analyst, Stuart replied with words to the effect (from memory - I haven't looked back to check) that better than 20% was a waypoint not the target and that it would eventually end up at an industry standard level somewhere towards 40%.
You can see on that photo from Marcus that the sector average is 35% with Samsung leading on 43%. 35% on the amount of future revenue which OXB are now guiding would be an enormous income - which imho inevitably now leads at some point to Novo offering a very generous multiple to secure it for themselves. |
Interest rates to fall to 3pc within a year, says Goldman Sachs
Good for shares. |
Sorry, meant for Scancell BB ! |
Moderna failed because of small trial and size of control arm and it was not powered properly (read attached article).
The advantage between it and available treatment was not shown clearly enough.
If iScib+ has brilliant data then early approval is possible (I think likely).
An assessment of study power is essential in determining both the statistical significance and clinical relevance of any study and has serious implications for any conclusions that can be drawn. |
You've done very well, Harry! |
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