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Lilly and EVA Pharma to expand baricitinib access in Africa

Yes, Baricitinib, also known by its brand name Olumiant, is becoming increasingly available in Africa through a partnership between Eli Lilly and EVA Pharma. This collaboration aims to expand access to the drug in 49 low- to middle-income African countries by 2030. The agreement involves EVA Pharma manufacturing and distributing baricitinib, with local production expected to begin by 2026. This initiative is part of Lilly's 30x30 strategy, which focuses on improving healthcare access in underserved regions.

Interesting with the ageing Baricitinib it's forecast for income is forecast to rise world wide.

I think were around 2.5 billion 2023 and forecast to be over 8 billion by 2030 ish

The SLE society were apparently upset when Eli Lilly discontinued Baricitinib development in SLE or say they say.

1801 run rings round it.

Regards

I reckon iou are pretty well spot on there HbD and mirrors my thoughts exactly.

We are well over half way through the long term tox study period.

We have no idea of the dosing.

No idea what the increase in dosing is likely to be.

An interested party will no more than us for sure.

Sareum will be very close to developments and an I terested pharma not far behind.

I am certain that we have more than 1 interested party.

One may look for total buyout or agreement with milestones leading to and the other to take 1801 up to commercialisation via on licence with associated up front payments and milestones.

Up front payment need to be at least moderate upfront for on licence due to the associated risk off target effects and long term usage via toxicology test being reduced to nigh zero.

There may well be offers in the process of being negotiated in informal discussions.

Effectively we are ok to go into any indication with no restrictions subject to toxicology results

Regards

Good morning HbD.

Good informative post re companies without jak inhibitors.

Most likely cause here is the fear of jak toxicity primarily due to due to lack of selectivity.

Is a pharma going to develop an inhibitor that is highly likely to be marred by boxed warnings.?

Tyk 2 on its own has proven to be immune from this albeit highly unlikely to have as good as efficacy as dual inhibition with a combined Jak inhibitor

Tyk2 inhibitors can be I.proved upon by the addition of Jak1.

100 % jak 1 does not exist as by the nature of the molecules they will inhibit jak 2 and jsk3 also bit generally to a far lesser extent.

As Tim said we believe we have a Tyk2 with the optimum amount of Jak1.

Results at end of phase 1a were better than expected and this was post 'wait until.the world sees what we have'.

How competitive are we against Deucravacitinib?

On satisfactory long term toxicology results allowing authorisation for long term use then this surely puts 1801 in first place.

It certainly all hinges on the toxicology results

We certainly would like to be informed of the result and l dare say so would any interested pharma.

We are on the home straight and a decent way in front.

HbD thanks for the correction

Not long to go now, the homeward straight.

Regards

Good morning C79. Great link either regards to Tyk2 inhibitors and growth forecast.

I note that they include Riovant as a company and Breprocitinib as an inhibitor along with a shortish list of Indications.

Since 1801 has a far superior safety profile with regards to off target effects and at dosages of 300mg per day, no observed increase in creatinine levels, we are clearly far more advantageous for the purposes of commercialisation than Breprocitinib.

With an establishing safety profile of Tyk 2 along with a 30% plus growth in income from Deuctavacitinib it paints a very rosy path for Tyk2 inhibitors especially those that have dual inhibition as with our Tyk2 Jak1 inhibitor 1801.

On a satisfactory long term toxicity report our inhibitor can be trialled in any listed indication.

Adverse events similar to placebo at maximum limited trial dose of 300mg per day.

Tim stated a while ago " wait until the world sees what we have'.

We will know for sure in a few weeks time.

More importantly so will interested parties

Regards

Good evening Krone a good post from.you as usual.

Cancer unless irradiated quickly will develop resistance to a treatment.

Call.it evolution as that in essence it what it is.

I doubt it is caused by the cytokine storm itself.

More than likely the virus will enter a cell and as the virus has a phenomenal.ability to mutate to raise its chances of survival (evolution of the virus itself)

For the virus to exist, it is in its interest not to destroy the host.

It requires cells to live off and multiply.

Ideally the virus would prefer a perfect cell or a cell that it sees perfect and surely one that can multiply rapidly.

If we look.at cancer cells they have no programmed cell death.

Develop resistance ho treatment.

Can remain dormant

Can multiply rapidly.

The virus in return may be able to offer the dormant cell a kick start in life and rapid multiplication. This round benefit the cancer and indeed the virus.

Viruses mutate

Cancers mutate and over come resistance to treatment.

Produced in the laboratory a bat virus with an added feron cleavage most probably HIV in some postulations and intercepted telephone conversations.

Also bare in mind that covid jabs contain mRNA and this can be absorbed by a cancer cell which initself can have differing effects on cancer mutation. Metastase and speed of mitosis ie replication .

Regards

Https://ir.acrivon.com/news-releases/news-release-details/acrivon-therapeutics-reveal-molecular-mechanisms-driving-strong

I would hazard a guess that acrivon will develop prexasertib with their own in house Wee1 PYKT inhibitor as a combo therapy.

Our Chk1 is CCT245737.

It's predecessor CCT244747 suffered from poor bioavailability but in early studies gave good results with brain tumours when combined with radiotherapy.

A vast improvement on bioavailability was a achieved by the reduction of a heterocyclic ring resulting in the compound CCT245737.

Increases in efficacy achieved too.

In HGSOC over 90% of cells have mutated P53 gene.

There are people that would benefit from a dual therapy or even triple combo therapy.

Chk1

PD-1 or Parpi OR Wee1

LDG.

Regards

The company is a minnow.

1801 is not.. it is a big threat to Deucravacitinib, a very big threat indeed.

Size of a whale at least.

Nothing is 100% certainty until.it happens.

There exists competitive pharmad to BMS who will want a share of the marker.

Should 2801 continue as it is going and proves to be as nigh safe as Deucravacitinib then a pharma will pay the asking price.

Safety and efficacy are related in that you have doze limiting toxicities.

As the dose rises so does the adverse events.

This in many cases means that as a dose approached that provides efficacy up go the risks of adverse events.

It renders the compound almost useless in that indication. Breprocitinib in Psoriasis will not be continued and that is a Tyk2 Jak1 inhibitor.

Not as selective as 1801.

When decent news released we will get a rerate.

That for sure

Regards

Good morning DP54.

Deucravacitinib failed in UC.

Initially put into Psoriasis. Reasonable efficacy, nothing breath taking but good safety and well tolerated.

The initial intended indication was good.

Next objective is to put to other Indications.

So these are intentions too, but not the original intention.

The bs put out by BMS about the allosteric Tyk2 regulating the active domain.

It didn't regulate the UC or CD to provide a satisfactory efficacy.

Perhaps they could try it in combo with SDC1802.

It would give a more efficacious result.

Bteprocitinib not good enough for its original intended purpose either.

Regards

Good evening HbD.

Yes a bit if bone throwing

I believe this is the 2nd attempt they have made in UC and CD.

No jak 2 activity so no inhibition of IL-2

No Jak 1 and Jak3 inhibition either.

Tofacitinib originally designated jak3 but inhibits more Jak1 and no shortage of Tyk2

Efficacy but off target effects not so good.

JAK1 and JAK3 are both involved in the signaling of cytokines that contribute to inflammation in IBD. Specifically, they are involved in the signaling pathways of cytokines like IL-2, IL-6, IL-12, IL-15, IL-21, and IL-23. These cytokines are crucial for the activation of T cells and the production of inflammatory mediators.

So Tyk 2 on its own in a sense is overly selective.

Hence there exists entry of room for top notch dual inhibitors.

Safety is of paramount importance as without it inhibitors become increasingly restricted.

Regards

Https://academic.oup.com/ecco-jcc/article/19/6/jjaf080/8129055

Deucravacitinib was forecast to generate 4 billion dollars turnover a year by 2030.

All they have is a so far , proven safety or to be more precise a not restricted by the limitations of the class of Jak inhibitors ie no jak1 jak and jak3 due to selectivity issues.

On its owns it is not going to achieve that solely on Psoriasis

Yes it went into Ulcerative colitus and failed dismally, the placebo gave better results.

The point here that is of the utmost importance is the commercialisation value of 1801.

The more Indications the greater potential commercialisation value.

If a compound is safe it can be approved for clinical trial in whatever indication the pharma chooses.

It is not safe then this is no longer the case.

They then look into areas where there is an urgent unmet need in a desperate bid to generate revenue from a compound.

Breprocitinib no longer to be developed in Psoriasis

Tyk2 Jak1 inhibitor

It looks bad on Tyk2 Jak 1 inhibitors of which 1801 is one. However, we have expressed a far superior safety profile than Breprocitinib.

Are we good in Psoruasis, UC, SLE or even the recent interest into ailments of the CNS.

Are we OK for Alzheimer's and or multiple sclerosis?

Areas of huge unmet need.

With regards to testing some pipelines are bought on the proof of concept alone.

Roll on completion of toxicology testing.

An excerpt from recent RNS.

Brain-penetrant" TYK2 inhibitors

'Sareum has recently conducted targeted preclinical studies to evaluate the potential of its TYK2/JAK1 compounds in central nervous system ("CNS") indications. This work reflects growing scientific and commercial interest in the role of TYK2 inhibition in neuroinflammatory diseases such as Multiple Sclerosis, Parkinson's Disease, and Alzheimer's Disease - all areas with significant unmet medical need.'

I believe it to be more than window dressing.

First info with regards to crossing the blood brain barrier Dec 24

Sdc 1801 difference to 1802 and ability to cross the brain barrier. 1801 believed to be less problematic in this area as TIm and John not wanting to cross or certainly limit the cross of Jak 1 to blood brain barrier.

This implies that more jak1 would cross the brain barrier on 1802 than 1801.

Is therefore 1802 a possibility for indications of CNS diseases?

When did he start work on this?

Regards

NO!

Hi HbD,

I terrorist g to note they say they are a small company prioritising where our limited cash is invested but at the same time looking at Blood Brain Barrier penetration and central nervous system.

A lack of clarification on what Sareums intentions are here.

I don't think they are particularly good at managing options

In a sense HbD it is a pipeline within a pill.

In addition we have 1802 that has recieved patent protection for immunotherapy and can be utilised as a back up for 1801.

No idea as to what part it plays in backup.

It would also suggest it could be used in combo therapy with 1801 but very little idea as to why.

1802 in patent description states it may be used as a supportive with pd-1 inhibitors, Parpi with many other compatabilities given and as such may become the major overiding treatment.

I think we tend to overlook the potential.of 1802 is greater than that of 1802

Unfortunately Sareum give very little away.

Be good to get a development update on 1802.

Regards

As for deals bring done.

GSK just don't pick up the phone and put a bid in like something for sale on ebay.

Negotiations take time.

The company looks to purchase the requirement it needs.

It clearly has been the class with the Hengrui pharma.

Primarily they can look for the required indications but of course 99% of importance will be safety and tolerability.

Once established as safe they can proceed to clinical trial whatever indication they want, normally the must lucrative first.

Emma not performing all that well. Should be looking a tad closer to home.

Let's see if we can get something developed on the chesp in china. Back home you are are not far from a company with a potential blockbuster of more than one inhibitor.

This looks to be a very similar course with Sareums changes of plan since July last year.

Regards and another day closer to toxicology completion.

Good morning all.

I don't think GSK have much in the way for Psoriasis.

AI below

GSK2982772, a RIPK1 inhibitor, and several Janus kinase (JAK) inhibitors, including tofacitinib, peficitinib, solcitinib, baricitinib, and itacitinib, have been explored as potential treatments for psoriasis. While some studies, like the one on GSK2982772, showed limited clinical improvement despite target engagement, others, like tofacitinib, have demonstrated efficacy in reducing psoriasis severity.

GSK298772 (RIPK1 inhibitor):

A study investigated the effects of GSK2982772, a RIPK1 inhibitor, on psoriasis.

RIPK1 is involved in the development of inflammation and cell death in psoriasis.

The study found that while GSK2982772 did not lead to meaningful clinical improvements in patients with moderate to severe plaque psoriasis, it did show a decrease in plaque lesion severity with increasing trough concentrations.

30x before and handed times before ha both been mentioned.

Where was the source of information?

Tim at Sareum

Ee have dosed at 30 x times.

We may have to go to 100 times with mentions of do we have enough compound.

Requirements are governed by the authorising bodies.

If they require a MTD then that is what they will have.

If they want, we'll its not if now, it is they want long term toxicology data.

This is what they will get or there will not be any authorisation.

It matters not what the excellent very likely class leading results we have obtained so far.

Yes we are all getting a tad impatient.

It is what it is and as MegRS300 stated we are half way through.

There is on reflection nothing to stop Sareum running long term toxicology test and a Maximum tolerated dose at the same time.

Regards

In essence we are looking at prolonged administration and applies particularly to immuno therapy as opposed to immuno oncology.

They are 2 different requirements that ideally need both to be established

We never achieved maximum tolerated dose

We achieved 30 times treatment dose with no adverse events.

Tim said in around 2020 it was a problem but a nice problem to have and may come back to bite us later.

Thoth2 did point out that 30x Treatment dosage is an acceptable valuation if mtd has not been established.

Somebody new to the MHRA very likely to be up on this. As they say no substitute for experience.

We have endured tge bad it of the problem but it is about time the good part of the problem shone through.

Regards