Member Info for HotblackDesiato

Just a quick update - the Regulating Study no longer shows up on the main Nucleus Network recruitment page so it's still progressing nicely. It's just annoying that they don't update the trial docs to indicate how many volunteers have been recruited; that way we'd know how close we are to the endpoint.

If anyone's in the process of contacting TM about anything, it might be worth a gentle nudge re updating the docs.

Hard to say how long it'll take to review the data. Sure they'll have automated processes to collate data from the blood work and the urine samples etc. but we don't know how many people are involved in the review process itself.

Also keep in mind the Nucleus Network are still recruiting for a psoriasis trial (may be ours, may be some one else) - https://www.nucleusnetwork.com/au/participate-in-a-trial/studies/the-regulating-study/

Hi Celtic - the main reason for a phase 1 trial is to check the safety of the drug. Part 1a is in healthy volunteers and 1b is in patients with psoriasis. Part 1b will only start once all data from 1a is reviewed. The sample size for the 1b trial will only be large enough that it'll indicate if 1801 is better than a placebo or not. If it is better then a much larger phase 2 trial will be required to learn how effective it really is in a variety of psoriasis patients.

I do like it when the word trillion gets used.

https://www.fiercepharma.com/pharma/2024-forecast-ma-saw-uptick-2023-expect-trend-continue

"Another factor favoring a bumper crop of M&A in 2024 is the dry power on hand. Companies in the industry have nearly $1.34 trillion at their disposal to invest, which is close to an all-time high, according to Arda Ural, EY Americas Industry Markets Leader, Health Sciences and Wellness."

It's clearly early days for the new license holder but one way we might be able to uncover who it is is by looking out for new patents. Sierra submitted about six 737-related patents covering everything from synthesis to combo treatments so although it may be that all bases have been covered, at least it's another angle for the researchers among us to track down who we're dealing with.

Hi Potnak - though stranger things have happened, I doubt the former SO team would be involved as you'd have to lure them from GSK with a big enough carrot and the material financing objectives referred to in the RNS implies there's no parent company ready to offer the funds for development.

We might get more info when SP gets back from the JP Morgan thing next week.

Hi PCS - I was thinking along the same lines i.e. renewed interest in 737 and 1801 progressing might appeal more to the city now with regard to a raise. The funds would pay off RF and hopefully get the SP back on an even keel assuming new shares would go to investors rather than 'lenders'.

The current fly in the ointment is we don't know who the licensee is and therefore what level of funding they have to back up the development of 737. The RNS notes, "...Licensee Company achieving certain commercial and material financing objectives", which might suggest they don't have the deepest pockets when it comes to having enough of their own money to progress 737 through whatever trials they intend for it.

So many questions, so few answers!

Sorry for the new thread, LSE throws a 'page not found' error when I try to reply to PCS's Step by Step thread.

As the BoD said at the AGM, they'd find out about a 737 deal at the same time as us - hmmmm, a wee white lie perhaps?!

We'll find out eventually who this private pharma is and perhaps one or more of their investment partners might now take a close look at SAR. Let's not forget that there are a number of large privately owned pharmas out there - the German firm Boehringer Ingelheim has over 47,000 employees so the license agreement isn't necessarily with a small start-up.

Interesting times ahead.

Https://www.edisongroup.com/research/sra737-new-partnership-to-kick-off-the-year/33096/

Sareum Holdings — SRA737 – new partnership to kick off the year: Sareum Holdings’ co-development partner CRT Pioneer Fund (CPF) has signed a new licensing agreement with an unnamed US-based private biopharma company for SRA737, its Phase II stage CHK1 inhibitor targeting the DDR network for the treatment of solid tumours. Deal terms include an upfront payment of $0.5m, additional fees of up to $1m in cash and 500,000 shares of the partner and potential milestone payments of up to $289m (comparable to the $290m allocated under its revised deal with Sierra Oncology in 2020, that has since been terminated). CPF will also be entitled to tiered high single-digit royalties on net sales. Sareum remains a passive partner in the programme with a 27.5% economic stake in SRA737, translating to $137.5k in upfront and a proportionate share of future payments. Given Sareum’s focus on progressing its lead clinical candidate SDC-1801 (Phase Ia trials ongoing), we expect any additional funds to be deployed in the asset’s development. We expect full safety data from the Phase Ia trial (expected H1 CY24) to be the next catalyst for the company.

As the deal is with a private firm I don't think we will ever get to see the contract agreement. I would hate to think this new deal has a similar clause to the ProNai/Sierra one re milestones i.e. payable on the first dosing of patients in the US; the get-out clause being just run the trial outside the US to circumvent these payments.

Can anyone here think of a way of finding out if such a clause appears in the agreement? I presume if the BoD have access to the doc they'll be under some sort of NDA re the contents. So what we need is someone in the Cambridge area to pose as the new office cleaner, if you catch my drift...

To find out who the private company is we just need to keep an eye on https://beta.clinicaltrials.gov/ to see who registers a new trial for SRA737 (assuming they don't change its name).

Hi PCS - Stand down, mission accomplished!!

And to those who insisted that 737 was dead in the water - up your butt with a coconut.

Hi PCS - As I don't see 1775 in AZ's pipeline it may be that no one at AZ knows anything of the combo research either.

Whilst there could be a 737 deal ready to be inked (a boy can dream) we're in a total information vacuum so your contact with the BoD might encourage SP to track down someone from AZ at the conference to discuss this new research. Even though we have no say in 737's progress, it might be enough for Parker to nudge AZ towards the CPF.

Further to the 737/1775 paper I posted earlier, I wonder if someone here could bring it to Stephen Parker's attention via Twitter/X?

We have to assume the BoD don't know of the work carried out by the two Pittsburgh Universities and as the BoD mentioned at the AGM, they're pretty much cut off from all 737-related talks with CPF so it might be an opportune moment to make SP aware of it ahead of the JP Morgan Conference next week.

I'd e-mail our IR/PR peeps but don't know if they'd do anything with the info - did someone say chocolate fireguard?

Thanks in advance and let's see if Stephen P can increase the 'Ra-Ra-Ra' that he alluded to at the AGM.

Yes, SOG, correct dosing is the key as the report notes, "However, in a pilot experiment, a 4-week combination treatment showed signs of severe toxicity, including rapid weight loss and death. Careful optimization of the combination is required to maximize the efficacy and minimize toxicity. Therefore, we evaluated several combination regimens by varying the frequency, duration, and sequence of drug administration, and found that a sequential 2-week schedule was well tolerated."

There's no question that 737 is proving to be very interesting based on the various trials that have been posted over the years however it's deeply frustrating that SO/GSK didn't take things further. It's really anyone's guess as to when (or indeed, if) a deal will materialise but at least we know 737 appears to work so that must surely pique the interest of big pharma.

Hi Celtic - from the Discussion section, "In our study, SRA737 exhibited significant single-agent activity in suppressing CRPC tumor growth and metastasis in a TRAMP mouse model. It was also well-tolerated in the 4-week treatment study, with no consequential body weight loss or gross toxicity. These preclinical data support the potential of SRA737 as a treatment for CRPC."

Hi SOG - the interesting thing is that although the AZ study you referred to was back in 2022, the 737/1775 study I posted made reference to data taken from the Cancer Genome Atlas in late May 2023 suggesting the scientists must've concluded that 1775 still has potential despite AZ stopping their own development.

I don't know if a drug's adverse effects would be universal irrespective of the type of cancer or if the patient is male or female. It may be that treating breast cancer with 1775 results in too many adverse events but it's excellent when used in men with prostate cancer.

Anyway, still all to play for, I think.

The paper below from Nov 2023 is still to be peer reviewed but it seems rather positive, "...both agents alone or in combination suppressed tumor growth, improved overall survival, and reduced the incidence of distant metastases, with SRA737 exhibiting remarkable single agent anticancer activity. Mechanistically, SRA737 synergized with AZD1775 by blocking AZD1775-induced feedback activation of CHK1 in prostate cancer cells, resulting in increased mitotic entry and accumulation of DNA damage. In summary, this preclinical study shows that CHK1 inhibitor SRA737 alone and its combination with AZD1775 offer potential effective treatments for castration-resistant (CRPC) and neuroendocrine prostate cancers (NEPC)"

and

"In our study, SRA737 exhibited significant single-agent activity in suppressing CRPC tumor growth and metastasis in a TRAMP mouse model. It was also well-tolerated in the 4-week treatment study, with no consequential body weight loss or gross toxicity. These preclinical data support the potential of SRA737 as a treatment for CRPC."

https://www.researchsquare.com/article/rs-3564450/v1

I wonder if there was a rep from AZ in the orderly queue that somebody once mentioned?

(And remember, as it's Hogmany if you're not in bed by 11pm you should probably just go home.)

Regards.

Hi Ben - scroll down to the 'outcomes' section for trial timings. What we don't know is if all recruits started at the same time as there is a 28-day screening window prior to the start of dosing.

https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385663&isReview=true

Hi Krone - I wouldn't put too much faith in what the website says; admin doesn't appear to be a strong point with the Nucleus Network e.g. our food effects trial entry on the website says 'not yet recruiting' despite the fact that element of the trial has started.