Member Info for onceaday

A very sizeable grant given the total of 2023 awrds. The foundation is also actively promoting the Promising Pathways act in the US. This act could significantly reduce time to market for promising treatments that have been through a phase 2 trial.. It also ties in nicely with expanded access as this could provide a demonstration of real world efficacy.

This has probably already been discussed but for those who missed it (like myself), the animal trial publication (Jan.2024) is here:

https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1278157/full

Its worth a read to get some understanding of the science. Interesting to see the dosage level used (50mg/kg/day) which resulted in slowing of disease progression. This would suggest an equivalence in humans of 3750mg/day (assuming 75kg) which is significantly higher than the doses in the phase 1 used to date. It seems that the team were conservative in their choice of starting dosage (maube for very good reasons). It does beg the question as to whether the lower doses are likely to have an effect. Perhaps, they will only start to see a.signal at the higher doses now being tested - 2000mg and.above. I do recall that it has been stated upwards of 3000mg was tolerated by some patients in the original Titan Pharma trial of GaM (according to Dr..Chitambar).

This probably explains the sharp drop.

https://www.biospace.com/article/kazia-s-paxalisib-disappoints-in-global-glioblastoma-study/

I should point out that H.R.5708 has.jot yet been passed..

I imagine it will be extended again at the appropriate time. I did read that there was some debate about how effective the program is but nobody has come up with a better idea.

A similar voucher program exists to encourage the development of treatments for agents that present national security threats (thinl chemical, biological agents that can be weaponised). The bill to extend that program was renewed recently (google H.R.5708 if you want more info)

So, if the 2000mg is tolerated, that's 3 more patients, plus potentially 3(+3) at 2500mg (RP2D). I imagine that recriitment won't take too long now they have administered to 18(?) without any real safety issues.

Https://youtu.be/67D6MwSQc7U?si=FyoqNYKYyLzJJTE7

Latest with more info on dosing schedule. Good to see they are recruiting at 2000mg now. I believe its 3 more patients at this dose plus six at 2500mg if tolerable.

https://youtu.be/67D6MwSQc7U?si=FyoqNYKYyLzJJTE7

Very informative. The comments about trialing GaM in treating neurodegenerative disease is food for thought.

Sadly, many cancer drugs only extemd survival and are not a cure. These are animal experiments and its not clear what effect the drug may have in humans. We have to wait for the results of the phase 1 in adults for any early indication of efficacy.

The US Food and Drug Administration (FDA) granted accelerated approval of bevacizumab (Avastin) for people with glioblastoma with progressive disease following prior therapy in 2009. Possibly, the same woupd apply to Galpium Maltolatè if efficacy is demonstrated.

It's woeth bearing in mind that this application may allow for thw grant of a Rare Pediatric Disease Priority Review Vouchers upon approval. This was not the case for the adult population. These vouchers are intended to "reward" developers of srugs that treat rate conditions in children. These vouchers are generally sold onward to big pharma - typically for around $100million. IMHO this chanhed the economics of the development.

It's also worth noting that they have initially chosen to trial in patients that have failed prior treatments - in other words a treatmemt of last resort. They may think that the FDA will be open to granting Accelerated Approval bassd on a successfull phase 2 trial for such a therapy.

We did at least get some indication of the.phase 1 progress. Sounds like they are enrolling the last 12 patients at the highest dose. I assume the clinical trial status will be updated once enrolment has been completef.

NCT04319276 looks like the one. Status on clinicaltrials.gov is still "Not yet recruiting". Hopefully that will change soon as we are towards the end of Q4.

The time it has taken to treat only 9 patients in comparison in the Ph2a ext vs the larger sample in jCyte's completed Phase2b has, perhaps, brought home the commercial realities of using the two different techniques.

The commentary about "tough decisions" sounds similar to that used to justify abandoning the internal development of CTX stroke.

True. The last time the Chairman made a large (LSE) purchase the price jumped but I guess US investors are not impressed.

The price will likely move sideways until after the AIM delisting (Jan 10). Unfortunately, some LSE shareholders cannot hold the ADRs and so will be forced sellers on AIM.

Jim
Yes the CF trial results must be hotly anticipated by CF sufferers - let's hope the outcome is just as positive as for EB. IMHO, the real money-spinner could be Jeune Aesthetics. Krystal's aesthetics subsidiary is due to announce phase 1 data in early 2022 for "KB303, an innovative, investigational gene-delivery therapy designed to enable local, full-length elastin production in the skin". Ask yourself how much is spent worldwide on skin improvement products (that probably don't work). If KB303 really does rejuvenate the skin through gene therapy, it will be an undoubted winner!

I suspect the Chairman's purchase leaked last night given the NASDAQ after Hours price

10.39 +0.83 (+8.68%)
After hours: 07:25PM EST

The Krystal Phase 3 results are certainly grounds for optimism in the EB community. However, bringing novel gene therapy to market is likely to be significantly more fraught than an ointment made of birch bark and sunflower oil. I would expect the regulators to be heavily focused on safety and it's worth noting that the sample sizes in the Ph2 and 3 trials are relatively small. According to clinicaltrial.gov, Krystal is running a study entitled "A Long-term Treatment With B-VEC for Dystrophic Epidermolysis Bullosa" which won't read out until Dec 2022. This is probably an insurance policy against a safety knock-back from the regulators.

I did buy a few krystal last week and sold out on US market open this morning. It's almost covered my Amryt loss!

Before you dive into Krystal, it's worth noting that they are being sued (and countersuing) regarding the use of the core technology (the Herpes Simplex Virus) in their platform which further complicates the outlook. https://seekingalpha.com/article/4468950-krystal-biotechs-legal-risk-view

The effect on the CVR's

· FDA approval

o US$35,000,000 upon FDA approval

o 100% of the amount due if approval is obtained before December 31, 2021, with a sliding scale on a linear basis to zero if before July 1, 2022

· EMA approval

o US$15,000,000 upon EMA approval

o 100% of the amount due if approval is obtained before December 31, 2021, with a sliding scale on a linear basis to zero if before July 1, 2022

So, based on the above, and the new PDUFA date of Feb 28, 2022, I reckon that means a 30% haircut on the CVRs.