Member Info for HotblackDesiato

Who's for an 11am RNS?

On the other hand, if the expected timeframe for a final response is 60 working days rather than calendar days then...

Morning Krone - yup, if GSK announce the known capabilities of 737 and commit to progressing it asap then their (and our) sp will benefit.

I'm not convinced we'll see another placing. If GSK were to state their confidence in 737 and publish plans to take it forward in a number of trials then the sp should increase markedly, possibly triggering the warrants available to the HNW investors. Once we see 1801 derisked after the P1a trial then I expect a license deal to appear soon after - a large enough upfront payment would help 1802 along quite nicely.

As for TR1s, whoever is in the market for that scale of share ownership will either keep their anonimity behind a trust fund or spread ownership between individual family members so that a TR1 isn't required.

However I expect to be proven wrong on all the above!

Below are a couple of useful links for anyone just joining the SAR party or considering jumping in. Both cover Sierra Oncology's trial with 737 -

https://www.clincosm.com/trial/advanced-solid-tumors-spain-united-kingdom-sra737-gemcitabine

https://www.clincosm.com/trial/advanced-solid-tumors-or-non-hodgkins-lymphoma-nhl-united-kingdom

Hi Potnak - "...if you put yourself in the shoes of a potential investor, would you buy or would you wait?"

That depends very much on the scale of the intended investment but let's look at what we know so far -

1. CTA could get full approval in the next week or so. I think we'd know by now if it was dead in the water therefore some element of the approval might already be priced into the current sp. Assuming good news is announced along with a target start date for the 1a trial, the sp should respond well but no one knows if it'll be a quick spike or form a new plateau.

2. The next GSK pipeline update is due at the end of Oct. but will 737 get a mention? No idea but our friend in the labcoat says GSK are password protecting almost everything concerning 737. This isn't done on a whim and therefore GSK must place a significant value on it if they fear a spot of industrial espionage - https://www.pharmaceuticalonline.com/doc/corporate-espionage-is-real-even-in-the-pharma-industry-0001

3. We won't know the results of the P1a trial until next spring but figures suggest around 70% of autoimmune drugs pass this stage - https://www.acsh.org/news/2020/06/11/clinical-trial-success-rates-phase-and-therapeutic-area-14845
Good news here will send the sp north.

So unless we have a complete disaster I don't see the sp dropping by a significant factor from where we currently sit. A license deal could happen at any time so I'd suggest investing at current levels would be a bit of a bargain.

As a slight aside, I've just come across this http://www.bigpharmagame.com/ and wondered if WIP plays it in his lunch break.

Afternoon Potnak - there shouldn't be any problem starting the P1a trial this year. Although the plan is to recruit about 120 volunteers overall, a Phase 1a clinical trial targets healthy subjects and therefore only needs 20 or 30 participants for there to be enough safety data.

Yes, the Phase 1b trial in patients with psoriasis will be at some point next year and it'll require additional funding but with solid P1a data I doubt sourcing money will be an issue.

Morning Ahfam - I also fully expect GSK to make an offer on our share of 737 as, whilst they'd maybe tolerate a drug's co-creator receiving future royalties, they'd hate to see those royalties going to a competitor. If they take that approach then they might want to buy the whole shop too since 1802 may prove to be the most synergistic compound to work with 737.

Add 1801 and the SKIL platform into the mix and GSK could potentially dominate large sectors of the market for a long time.

Let's start the bidding...

Looking at the links below, GSK clearly have many oncology candidates to play with but it can't be too long until 737 is added to the list. However what might be more interesting to know is if SDC-1802 is on their top 10 list of 'ones to watch'.

https://us-trials.gskoncologypipeline.com/therapy-class

https://gskoncologypipeline.com/pdf/GSK-Oncology-Pipeline-Wall/_GSK-Oncology-Pipeline-Wall.pdf

Hi Ahfam - I'd argue that by this stage of the game there shouldn't be any need to attend this type of event. If we're not on big pharma's radar by now then what have the BoD been up to?

GSK must be aware of who we are and if they know, then so will others.

Hi Baton - within the next two weeks if we go with a 60-day turnaround however it could be extended if further info is required by those reviewing the application.

Evening Potnak - I see your guesstimate and raise you WIP's own, '...I'm estimating end of P1 in healthy patients, maybe just entering p1b in psoriasis we'll be worth more than the Sierra deal.'

I can understand your figure based on what's happened in those other deals however does SAR provide more scope for larger deals thanks to the potential for each compound to treat multiple diseases when compared to the competition?

Based on a single indication for each e.g. 1801 - psoriasis, 1802 - lymphoblastic leukaemia and 737 - ovarian cancer, £2bn might be reasonable (I have no idea) but if we add far more potential indications then how do we factor that in?

(I've not looked into whatever other indications the various competitor compounds may treat but assume SAR are on firm ground thanks to the overarching reach of our patents.)

Thought it might be worth posting this from a 2019 RNS re the sums that could head our way if we can attract the right partner -

"Sareum's view has been formed based on the progress of molecules in clinical development by Bristol-Myers Squibb (BMS-986165; TYK2 inhibitor) and Pfizer (PF-06700841; TYK2/JAK1 inhibitor) in psoriasis and other autoimmune diseases, which has been promising but also shown signals that suggest there is an opportunity for a molecule with best-in-class properties.

Furthermore, several licensing deals for preclinical and clinical-stage assets have been completed recently in the sector with highly attractive economic terms, such as:

· TD-1473 (a pan-JAK inhibitor) - licensed by Janssen from Theravance (2018) at the end of Phase 1 studies for $100M cash up-front, up to $900M in milestone payments, plus royalties*

· Filgotinib (JAK1 inhibitor) - licensed by Gilead from Galapagos (2015) at the end of Phase 2 trials for $300M cash and $425M equity investment up-front, up to $1,350M in milestone payments, plus 20%+ royalties*

· Undisclosed TYK2 inhibitor (plus other assets) - Celgene formed an alliance with Nimbus Therapeutics (2017) in preclinical stage for undisclosed up-front and milestone payments

Approved products targeting the JAK family with blockbuster sales potential, despite warnings based on side effects related to JAK2/JAK3 activity, include:

· Xeljanz® tofacitinib (Pfizer) (JAK1/JAK3 inhibitor) - approved for rheumatoid and psoriatic arthritis and ulcerative colitis, with 2018 sales of $1.77Bn, despite black box warnings for serious infections and lymphoma. More recently, dose-related cardiac safety issues were reported in a post-marketing study in rheumatoid arthritis patients

· Olumiant® baricitinib (Eli Lilly) (JAK1/JAK2 inhibitor) - approved for rheumatoid arthritis, with 2018 sales of $202.5 million and expected peak sales of approximately $1Bn*, but with black box warnings for serious infections, lymphoma and thrombosis

· Jakafi® ruxolitinib (Incyte/Novartis) (JAK1/JAK2 inhibitor) - approved for myelofibrosis and polycythemia vera (a type of blood cancer) with 2018 sales of $1.4Bn despite warnings of infections and blood cell counts

The scale of the deals and sales delivered/forecast for these candidates and products targeting TYK2 and related JAK family members give Sareum confidence in the exciting, high-value market opportunity for SDC-1801."

So will the start of the P1a trial lead to formal offers or will pharma decide to wait for the results first to confirm safety and to see which other diseases it might treat?

Thanks for clarifying your thoughts Potnak.

Though I would say JR can still add value by tweaking things to extend patent protection - however I'd hope we've been taken over by that stage.

Hi Potnak,

You wrote, "the science isn't proven yet and it will be a long time before it will be." You then went on to say, "We're past the science bit". Pick one, not sure you can have both!

Anyway, as for using 'the science trope as a comfort blanket', you may see it as a such but how else should punters gauge progress in lieu of any RNS? Perhaps only by comparing this forum's 'science briefings' (for want of a better expression) against competitors drugs, we can either reassure ourselves that we're on the right path or maybe get advance warning that we're heading down a blind alley.

For example, the recent RNS re Sotyktu (also known as deucravacitinib) tells us there is a tyk2 drug targeting psoriasis that has no black box warning. However on the flip side, the link below notes that the deucravacitinib is disappointing re ulcerative colitis. So what to make of this? My interpretation is that SAR are probably on solid ground by targeting psoriasis first with 1801. If they were initially targeting ulcerative colitis I might be concerned. However I remind myself that 1801 also has a bit of JAK1 therefore it isn't going to be exactly like deucravacitinib therefore it may also prove effective in ulcerative colitis. Once P1a results are in, we'll know what indications it's most likely to treat.

https://www.evaluate.com/vantage/articles/news/snippets/pfizer-bows-out-tyk2-race

What you may see as a comfort blanket, others may see as confirmation that SAR are on the right path (or not).

Regards.

https://www.lse.co.uk/news/correct-sareum-notes-us-fda-approval-of-bristol-myerss-sotyktu-pvdg06r9595lvbs.html

Glad they've woken up.

Cheers WIP - I know you're in a tricky position and just want to thank you for your contributions here.

I'll just keep an eye out for you mentioning any further investment here :-)

Hi WIP - always good to read any updates from you. If data on 737 is password protected, would that suggest GSK consider it to be at the highest level of commercial sensitivity?

Is it just me or does the Alliance News article that's just popped up give the impression that Sotyktu is ours?

Quality reporting.

Came across the following websites and thought it worth posting them here. Despite 99% of the data being behind a paywall (you can get a free trial), at least we might be able to track progress via the 'recent events' section.

1801 P1a - https://adisinsight.springer.com/trials/700354947

1801 P1b - https://adisinsight.springer.com/trials/700354948

SRA737 - https://adisinsight.springer.com/drugs/800045596
- https://profiles.biocentury.com/products/sra737_(cct245737_pnt737)

If anyone here already has access to these sites, maybe, uh, via their own workplace, cough once for yes.

Morning Silver - my interpretation is a new TYK2 drug for psoriasis has been given the go-ahead by the FDA and the key thing is there are no black box warnings associated with it.

HOWEVER!

Patients with psoriasis taking the drug may develop pneumonia and COVID-19. Our 1801 might just be able to treat psoriasis AND respiratory diseases therefore, on paper at least, we look as if we might be in with a chance of beating Sotyktu.

We're far behind in the development stakes but look at the figures RMM proposed. Now what would, say, AbbVie, pay to get their hands on a drug with the potential to top Sotyktu?