Oxford Biomedica Share Discussion Threads

[harry s truman] 11/5/2024 18:08

From the transcript:-

Charles Weston: Thank you. And just last question, you've talked about the pipeline in terms of early stage being up to phase two and then phase three and commercial. But obviously, for cell therapies and gene therapy, sometimes phase twos are actually the pivotal trials. Could we think that even in that early stage there are actually some pivotal studies or do you classify them as phase three in your chart?

Dr. Frank Mathias: No, they are classified as phase two. There is still a probability of failure that is quite high still. But one of the projects that you do not see as late stage right now went from early stage to late stage in less than six months. But I prefer to classify them in early stage and have a good surprise than put them in late stage and have a bad surprise.

[harry s truman] 11/5/2024 18:04

I agree Plutonian, but, (and I realise I'm splitting hairs here) if you recall that breakdown in the results:-

Programme stage April 2024 (including France)

35 clients
51 client programmes
46 Pre-clinical through to early-stage clinical
3 Late stage clinical
2 Commercial agreements (meaning Novartis + 1 about to be announced).

Then one of the analysts asked if that 3 at late stage is just Phase 3 or if it's Phase 3 + Phase 2 going the BLA route. The reply was that it's just Phase 3 and that they don't distinguish in this table between Phase 2 going to Phase 3 and Phase 2 going to BLA.

The difference between BLA and IND is complicated, but as I understand it then if the drug is made from living material (like altered T-Cells) and if it also meets certain other requirements, then there is the BLA shortcut from Phase 2 to review committee. If I'm correct then it makes sense that we would have many more Phase 2 trials heading for BLA than those going the full IND route via Phase 3.

In less words I think we likely have more at late stage than that table suggests.

[dominiccummings] 11/5/2024 15:36

It never had the politics little bird. Only when you visit.

[small crow] 11/5/2024 13:31

Ah yes, it's a much better thread without the politics .....

[plutonian] 11/5/2024 12:58

Harry,

I totally agree wrt BMS. We are obviously well-connected there.

All the known work (about unknown programmes) is early stage.

But, we don't know how much (if at all) we are working on late-stage programmes (approved or not), where they do not have enough in-house capacity.

... perhaps Donald Rumsfeld could explain this better :)

[harry s truman] 11/5/2024 11:33

I think it was always going to be something like this - as no government can punish so many of its own companies collaterally with sanctions on another country.

This of course isn't solely WuXi, they are simply the biggest, but what the US is proposing here is to give enough time for those locked in to get out with as little damage as possible.

I would have thought that whilst there will probably be some work for OXB in that long transition phase, the bigger change short term will be that US linked companies looking to place new contracts will now cross the Chinese companies off their shortlists, which of course gives OXB a bigger piece of the pie.

Meanwhile the Chinese will be hoping that before 2032 there's another president with an artist son selling paintings at half a million a pop.

[mirabeau] 11/5/2024 11:09

'WuXi Advanced Therapies is one of the top 3 cell and gene therapy CDMOs in the world'

[harry s truman] 11/5/2024 10:58

Plutonian,

I'm sure you appreciate this very well already, but by simply following the partners we know about it's surprising how many times BMS crop up with the funding and an option.

Hugely wealthy companies and I suppose they have to play the field to be sure of future success with something, but certainly from my digging around BMS seem to crop up most.

It does suggest that at some future point we will be hearing a lot more about them, but whether they are in with the late stage / preparing for commercial supply groups which OXB have told us about? Time will tell.

[harry s truman] 11/5/2024 10:53

You nearly had me there PB ;)

Oxford BioTherapeutics is a different company.

[pharmaboy3] 11/5/2024 10:51

I guess this is out of date info?HTTps://www.kitepharma.com/news/press-releases/2021/1/kite-and-oxford-biotherapeutics-establish-cell-therapy-research-collaboration-in-blood-cancers-and-solid-tumors

[plutonian] 11/5/2024 10:41

... but we know we are developing CART-ddBCMA for Arcellx in collaboration with Kite (a Gilead company).

We really do have a finger in every pie!

[harry s truman] 11/5/2024 10:14

PB,

If we have anything with Kite then it's on the secret list. I'll not say it's impossible, but we do know it's very difficult to change vector mid trial stage and even harder once approved.

As of the results we had 35 current partners.

With what they have told us over previous years we only really have a clue about 14 of them:-

Arcellx = CAR-T ongoing with a pivotal P2 trial
AZ = Obviously the covid vaccine has gone, but they wanted to continue the contract?
Beam Therapeutics = CAR-T clinical data H2 this year.
Bioverative = Bought by Sanofi who deprioritised (dropped the programme).
BMS (Juno) = Mega deal at least 6 programmes. I have my guesses but OXB never say.
Boehringer Ingelheim = Cystic Fibrosis. Very exciting. Human trials start this summer.
Cabaletta Bio = Biggest partner we know of with 9 programmes. Data from 2 in H1.
CARGO Therapeutics = Partner with CD22 CAR-T data in H1 '25.
Homology = ran out of money / no longer exists.
Immatics = Partner on TCR-T
Immune Design = Bought by Merck who said they would continue but it's secret.
Kyverna = Partnered on KYV-101 which is ongoing.
Novartis = Brilliant commercial partner for OXB + multiple T-Charge to come.
Orchard Therapeutics = Using LentiStable in P3 + our vector in P2.
Oxford University = Lassa fever + MERS + likely Malaria + Junin vaccines.
Sardocor = newest deal we know of - heart disease technology transfer.
Sio/Axovant = ran out of money / no longer exists.

So 14 of those are current which meant that a fortnight ago they had another 21 partners where we have no idea who it is. Could one of the 21 be Kite? Yes, but if they have a working vector they are already established with then they are unlikely to change that unless there is a major problem. Could they be trialling LentiStable (like Orchard) to improve a non-OXB process? Absolutely.

But I do enough wild guessing about things where we actually know names...

[plutonian] 11/5/2024 09:58

pharmaboy3,

That is Gilead's Tecartus (a reworked version of Yescarta for other indications). It has been marketed for some while now. The approval is just for some labeling amendments.

We already have 3 approved CD19 directed CAR-T:
* Kymriah - Novartis
* Yescart/Tecartus - Gilead
* Breyanzi - Bristol Myers Squibb

There are several more in the clinic now.

[harry s truman] 11/5/2024 09:44

takeiteasy,

There is no fixed value. It all depends upon the market.

FTSE100 are obviously the top 100 most valuable companies by market cap. If at any quarterly review another company from the top of the FTSE250 (the division below the 100) has grown in market cap to be the 90th most valuable company or above, then they will get promoted and boot the ones they have replaced down into the FTSE250.

The FTSE250 sat beneath the FTSE100 combine together to make the FTSE350.

On any quarterly review, if OXB is the 325th most valuable company or better by market cap at close of the date, then they will be promoted.

When they dropped below 376th place on the back of the economic disaster we know as the pandemic, then they were out.

Last time we were promoted from FTSE Smallcap into the FTSE250 the economy was much better and OXB needed to be £7 something to get promoted. Right now London values aren't there and at the moment just under £6 would do it at the end of this month.

[pharmaboy3] 11/5/2024 07:51

I'm not sure if OXB still has a manufacturing deal with Kite,but apparently, they have FDA approval Making it a third car t alongside Yescarta and KymriahHTTps://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/tecartus

[takeiteasy] 11/5/2024 06:28

Then, beyond 400p, thoughts of 350/250 inclusion will begin to beckon.

Has anyone here calculated more precisely what the entry level 250 equates to share price wise here....

[mirabeau] 11/5/2024 06:13

HIC Demonstrates Promising Separation of Deaminated and Non-Deaminated AAV Capsids (ASGCT 2024)
Published on: May 10, 2024
Feliza Mirasol

Studies conducted by a team at Oxford Biomedica demonstrated that HIC can be used to effectively separate non-deamidated capsids from deamidated capsids.

In a presentation given at the American Society of Gene and Cell Therapy’s (ASGCT’s) 27th Annual Meeting, Alex Meola, associate director of AAV Downstream Process Development at Oxford Biomedica, shared results from a study he and his team conducted in which theydemonstrated that hydrophobic interaction chromatography (HIC) can be used to separate non-deamidated capsids from deamidated capsids. The ASGCT annual meeting is occurring on May 7–11, 2024 in Baltimore, Md.

Meola emphasized how the focus on post-translational modification of capsid proteins of the adeno-associated virus (AAV) is growing in the process and analytical development space for gene therapies. The industry has been particularly focusing on how the deamidation of capsid protein from viral protein 1 (VP1)-specific residues, including the N57 domain, is linked to a loss of in-vivo potency (1).

“Temperature, pH, and storage time have been identified as key factors causing this phenomenon,” Meola. “In our quest at Oxford Biomedica—to try and resolve this—we have a static binding capacity residence screening protocol that we run where we look at a variety of different residents. In this case, we decided to look at salt-tolerant residents,” he stated.

Besides process control to prevent deamidation, Meola’s team hypothesized (2) that extrusion of VP1 and deamidation of N57 are related phenomenon and result in generating empty, partial, and full capsids, which significantly influences the ability of the anion exchange chromatography (AEX) process. AEX’s ability to remove empty capsids and deliver functional AAV is thus compromised.

Meola noted that charge-driven separation techniques have not provided the resolution required to differentiate between deamidated and non-deamidated capsid species. Because of this, his team highlighted novel approaches that can be applied to the AEX process to address the complex challenge of removing both empty capsids and deamidated intact capsids. “Controlling strategies in the upstream and downstream processes should be studied and defined at the early stage of process development to limit onset of deamidation in order to minimize product related impurities and loss of vector functionality,” Meola stated.

One of the team’s first approaches was to use HIC to separate distinct peaks with near baseline resolution. After separation, each peak was isolated and individually reprocessed with AEX. “Surprisingly, we discovered that HIC resolved two different species of AAV capsids with near baseline resolution. Each species was reprocessed on AEX, and all product quality attributes were assessed for the intermediate peaks that were generated. We found that the capsids that were more hydrophobic were also more negatively charged,” he explained.

Furthermore, data from liquid chromatography–mass spectrometry analysis demonstrated that the more hydrophobic and more negatively charged capsids exhibited significant levels of VP1-specific N57 deamidation, which has been linked to a loss in gene expression. It was demonstrated, therefore, that the extrusion of VP1 exposes the hydrophobic phospholipase A2 domain on the VP1 unique region, a phenomenon that would make VP1 N57 residue exposed to solvent and thus susceptible to deamidation.

The team was thus able to demonstrate that HIC can be a useful method to separate non-deamidated capsids from deamidated capsids. Meola also stated that the team is working on a novel, patent-pending method to remove deamidated species while simultaneously enriching full capsids on the AEX process.

[marcusl2] 10/5/2024 15:47

The STING agonist IMSA101 enhances chimeric antigen receptor T cell function by inducing IL-18 secretion

[boadicea] 10/5/2024 14:18

Relatively quiet since the last of the million-plus days on 7th May.
However, the price remains fairly steady; no large retrace - implying that buyers are waiting to take up trader's profit selling. It has not yet formed a significant characteristic pennant and may not be given time to do so.

If next news is good (odds on that), those waiting on the sidelines hoping for a test of a floor (at 300p?) may all rush to get in, reigniting momentum. Then, beyond 400p, thoughts of 350/250 inclusion will begin to beckon.

[dominiccummings] 10/5/2024 10:32

I don't have access to trade details but I suspect we are now in a pattern where each morning we get a big deal that they have to pay a premium for followed by a number of small sellers taking the share price down.

[harry s truman] 10/5/2024 10:04

Surely we all know the answer to that one? Big news.

Nobody needs the full history of OXB to know that they were battered by the coronavirus pandemic restrictions on trials, because most of their customers were either working from home (i.e. not working) or had their trials put on hold because the hospital beds which need to be on standby for trials were reserved for covid.

Happily that is consigned to history now and will hopefully never be repeated.

We know from what Stuart has previously told us that OXB's costs for everything are somewhere around £130m per year.

Sales of around that and we roughly breakeven. Anything above that and our EBITDA margin rises ever upwards until we hit full capacity. So better than 20% on 2026 revenue and maybe eventually 30+%.

A couple of minor problems for small shareholders here are that OXB have told us for over a year now that they aren't routinely going to announce normal sized contract wins anymore - unless the customer specifically wants to.

(and)

They will instead keep us up to date with regular updates on this KPI table, but without actually telling us where and when we will get to see it.

So not for the first time we are in a position where all seems good (very good in fact), but we have to trust that it actually is going as OXB have told us (which it should be).

Out of the ordinary (i.e. big) news would help a lot, not just because it changes all previous guidance, but because the last paragraph of any RNS like that is usually a mini trading update on everything else.

Are we due something like that with the directors not buying? Probably. Will it happen sooner rather than later? Probably. Are biotech deal timeframes very long? For a big deal definitely.

I can only repeat my experience of the original Novartis tie-up. That was excitement on prospects, then impatience and repeat, with the price up and down accordingly. Eventually that got us to about £10 pre-covid (remember that much smaller company is no France, no Boston and only a handful of contracts) then covid changes everything (knocked us right down to £3(ish), built us up to £16(ish), knocked us right back down to £3(ish) again) meanwhile 6,000+ people with no previous hope got the Novartis treatment thanks to OXB.

You will have worked out long ago that I think the key to market success for OXB investors is getting back into the FTSE250. That seems to guarantee more of everything - more news coverage in the papers, more broker interest, more institutions who can buy (some in the trackers have to) and so on - and I'm convinced that eventually OXB will get there.

When? I don't know. My target is this year, but it might need the interim results showing that all is well and on track first. Meanwhile a lot of small investors are likely to have got fed up and sold (again).

Next index review is the end of this month but to double the price in 3 weeks would take some epic news. Could a really big deal (big enough for OXB to be in a closed period and big enough for them to have to announce because of changed guidance) do that in such a short time when OXB are in this sandwich year here between loss and profit?

I'm sure it's possible. Will it happen in the next 3 weeks? No idea.

[marcusl2] 09/5/2024 21:11

Besides the potential detriment to drug access as a result of an immediate severance from Chinese CDMOs, industry respondents estimated that it would take up to eight years to switch manufacturing partners, according to a copy of BIO’s report obtained by Fierce Pharma.

[harry s truman] 09/5/2024 19:51

Just for interest:-



Key takeaway 5 -

While the legislation is only under consideration at this point, given the strong bipartisan support for the bill and concerns from the national security community, it is expected that some form of the bill will become law in 2024.

OXB webcast Final question:-

Miles Dixon Question - Thank you and then secondly, if I could ask, I think it was Sébastien that mentioned about biotech still being difficult. I was just wondering if it was too early to see yet or if you are in fact seeing any new emerging pen profile of potential clients given the challenges at WuXi? Thank you.

Dr. Sébastien Ribault Answer - I have not personally been exposed to anyone coming to us and saying we absolutely want to leave competition and we want to work with you because of US political reasons, to put it that way. Are there people concerned about the situation? The answer is yes. Are they looking for backup plans? The answer is yes. Since we're talking about a text that has not been voted yet, we're still talking about people looking for backup plans, but there's nothing that I would consider as an active discussion as of now.