Member Info for HotblackDesiato

Hi Blastoid - their compound is TYK2 only whereas ours is TYK2/JAK1 so without looking through whatever the patents say, it's maybe apples to oranges with enough delineation between things.

Hmmmm, I see we have some competition from the Chinese -

https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=384816&isReview=true

https://www.pharmaceutical-technology.com/data-insights/ua-021-usynova-pharmaceuticals-psoriasis-likelihood-of-approval/?cf-view

On a side note, a bit of digging shows AstraZeneca has entered into an exclusive licence agreement with the same Chinese biotech company for global rights to their preclinical(!!!) cancer drug candidate UA022 for almost $420m.

https://www.pmlive.com/pharma_news/astrazeneca_gains_rights_to_usynovas_kras_inhibitor_in_deal_worth_almost_$420m_1504188

I see the Nucleus Network are advertising for volunteers for a 6-night stay at their clinic which would tally with the SAD/MAD phase of the trial. However what I don't know is if this is our trial or maybe another company is starting one. If it is 1801 then at least it's not been halted.

https://www.nucleusnetwork.com/au/participate-in-a-trial/studies/the-regulating-study/

Indeed, Ajithoth. 737 shouldn't be written off by anyone (insert names of usual suspects here) though it may prove to be more effective when used in combination with other treatments rather than as a monotherapy.

From the study - "Colorectal cancer (CRC) is the 3rd most common cancer worldwide, with an estimated 1.93 million new cases diagnosed in 2020 causing 0.94 million deaths worldwide. TP53 mutation occurs in approximately 40–50% of sporadic CRC, with the mutation status being closely related to progression and outcome; patients with MUT TP53 appear more chemo-resistance and have poorer prognosis than those with WT TP53.

Lung cancer is the second commonest cancer worldwide, with more than 2.2 million cases and nearly 1.8 million deaths being estimated in 2020. For NSCLC, mutations of the TP53 gene occur in about 50% of cases."

So around half of all CRC and LC patients have a mutated TP53 gene and the study suggests 737 could be effective here. This is why we shouldn't write off a 737 deal just yet.

The link below explains why TP53 is so important.

https://www.verywellhealth.com/the-p53-gene-its-role-in-cancer-2249349

Anyhoo, enough from me as there may be another box of chocolates to open.....

The report below was partially funded by a “Specialist Unit Agreement” between Cancer Research UK and the University of Leicester. I hope they've also been poking CPF to get some sort of commercial deal sorted.

Latest paper published on 21st Dec: Investigations of the novel checkpoint kinase 1 inhibitor SRA737 in non-small cell lung cancer and colorectal cancer cells of differing tumour protein 53 gene status.

https://www.explorationpub.com/Journals/etat/Article/1002193

Regards all.

Last day for voting via Halifax was yesterday for some reason.

Just had a look at N4 Pharma (I'm not invested) and see they're up about 34% due to their latest RNS. I wonder if we'll see our BoD take a leaf out of N4P's book and hopefully announce good results from the food effects study.

Hi PCS - thank you for asking the question and what a disappointing answer if I heard it correctly! I appreciate those attending in person should take priority over written questions but it's a shame there wasn't enough time to address at least a few more of them.

The meeting was not helped by the poor sound quality but I got the gist of what the attendees were saying to the BoD. I thought JR in particular looked as if he'd rather have been anywhere else than at the meeting. A pity since his scientific contribution to the company appears top-notch and I don't think he has anything personally to feel bad about, afterall it's his name on all the patents.

Not being able to hear Mr. Smith's initial statement clearly enough, I thought SP looked as if he quickly switched off to some degree whilst Mr. Smith spoke. Either SP recognised what was being said and took it personally or he was thinking 'no, you're wrong but I can't refute the things you're saying without giving away inside info.' Just my take on what I saw.

Whether or not the BoD take on board what was said remains to be seen - perhaps one of the attendees could confirm if, after the meeting was over, they spoke directly to SP or TM to drill home the need for our IR people to engage more widely with the investment community.

If any attendee has any snippetts of post-meeting info they feel they can share, it would be appreciated.

Regards.

I quite agree, Potnak.

Re my first question, "Can you confirm if Mike Owen sits on the Scientific Advisory Board of the CRT Pioneer Fund and if so, when was his most recent involvement with the fund with respect to SRA737?", I tried to ask it in a way that they could answer without giving away anything covered by an NDA e.g. "yes, Mike's still very much involved there and he attended a meeting last month." Something like that could hint 737 is still in play even if they can't officially disclose details.

On the flipside, if they say 'nah, his last involvement was over a year ago before Sierra even handed all the data back' then at least it's an update of sorts and we perhaps shouldn't get our hopes up too much for an imminent deal.

Fingers crossed we get acceptable answers to reasonable questions.

Although the Nucleus Network haven't advertised yet for psoriasis patients I wonder if some people have already registered their interest in taking part. The sample size is just 12 so even if they've not got a pre-registration list it shouldn't take too long to rustle up enough volunteers.

I'll ask the question during tomorrow's meeting, 'Do you know if any psoriasis patients have already registered their interest in participating in the next stage of the 1801 trial or are Nucleus Network still to advertise for recruitment?'

Regards all.

Hi Potnak - the thing about the RF shares is that none of us know their current position. Shepherddollar recently posted, 'I know that a no. of large sells were not RF on a no. of days . Someone sold for personal reasons.'

So without concrete proof, perhaps RF haven't been dumping quite as many as has been mooted.

The thing we all have to remember is that there must be quite a few shareholders with huge holdings but they just don't post on any forum - the silent majority, and all that.

I blame the glaring typo in my reply on the root canal treatment I've just had. Add the demise of my washing machine and it's almost too much for any man to bear.

Hi LJ - I posted this at the end of November

"...the food effects trial could be completed just prior to the AGM. The first dosing was announced on the 9th Nov and the final follow-up visit is 29 days later. If all 16 participants started dosing that same week then we could see a pre-AGM RNS to say the safety committee now have all the data required to make a decision on whether the trial can proceed or not.

If there had been any nasty adverse events then the food effects trial wouldn't have been given the go-ahead. This suggests the safety committee just have to decide on the dose to be given to psoriasis patients and whether or not 1801 should be taken with food or on an empty stomach."

As no one probablys wants to be in hospital over Xmas/New Year, I'm guessing the food effects study was planned so that it'll be completed in the next week or two. The safety committee will have to review all data gathered as a whole before giving the green light to the final stage of the trial so I don't expect that to be until January....unless Christmas comes early!

Thought I'd post the questions I've submitted for the AGM.

Question 1:

Can you confirm if Mike Owen sits on the Scientific Advisory Board of the CRT Pioneer Fund and if so, when was his most recent involvement with the fund with respect to SRA737?

Question 2:

If the company were to receive income from the sale or on-licence of SRA737 will the Board buy back any shares still held by RiverFort with a view to cancelling them and therefore reduce share dilution?

Question 3:

The translational studies for SDC-1802 have been ongoing for quite some time. Are you any closer to an endpoint? Shareholders appreciate that there can always be another test or experiment that can be carried out but sometimes you do just have to call a halt and move to the next stage of development.

Question 4:

Assuming the Board has a strategy in place for the commercialisation of SDC-1801, could you outline some of the factors taken into consideration during the planning?

For those attending in person, it'd be interesting to hear your thoughts on the BoD's general demeanor when they're off-camera. Unless there's news prior to the AGM they won't be able to say too much but if any of you can read body language, it might prove helpful to gauge their own sentiment.

Further extract -

However, AbbVie’s Skyrizi and Rinvoq are well placed to be leading successors to Humira. The seven big pharma companies responsible for these 12 drugs are the main players in treatments for autoimmune diseases and just five of these firms have had top-50 drugs approved within the last eight years.

Promising pipelines

We now look at the new drug pipelines of the five biopharma groups mentioned above with approved autoimmune drugs to see what new late-stage drugs they are developing to treat autoimmune diseases.

The average probability of successfully completing a Phase-III clinical trial (the final stage of clinical trials) is 70%. But for Phase II this figure falls to 30%. So an early Phase II drug has only a 21% chance of successfully exiting Phase III. We will therefore concentrate on drugs for autoimmune diseases already in Phase-III trials, which are those most likely to gain regulatory approval.

AbbVie has five Phase-III trials in progress to expand the number of approved indications for Skyrizi and Rinvoq, along with three Phase-II trials of other drugs. Novartis has three Phase-III trials to expand the approved indications for Cosentyx, two new drugs in Phase-III trials and nine in Phase II. J&J has six PhaseIII trials to expand indications for Tremfya, three new drugs in Phase-III trials and four in Phase II. Lilly has two new drugs in Phase III and three in Phase II. Roche has three new drugs in Phase III and two in Phase II.

Oncology drugs form a large proportion of the pipelines for all five companies. Indeed, 14 of the bestselling drugs of 2022 were for various forms of cancer. Oncology is an important area where global sales of cancer drugs are expected to rise from $156bn in 2022 to $272bn in 2030 (representing a compound annual growth rate of 7.2%). AbbVie has 24 compounds for oncology in its pipeline, Novartis has 11, J&J 24, Lilly 12 and Roche more than 70. But pipeline drug numbers do not tell the whole story, since some drugs are likely to have much greater sales potential than others.

Extract from article -

There are over 80 autoimmune diseases in total, with symptoms ranging from relatively minor to totally disabling. About 10% of people globally suffer from autoimmune diseases: 13% of women and 7% of men. Healthcare market research group iHealthcareAnalyst predicts the global market for drugs to treat autoimmune diseases will grow to $185bn by 2029, with the US accounting for half the total.

Leaders in the field

In 2022 almost 25% of the top-50 best-selling drugs in the world were for various autoimmune diseases. All boasted sales of more than $2.3bn per year. These 12 autoimmune drugs are: AbbVie’s Humira, with sales of $21.2bn (rheumatoid arthritis); Johnson & Johnson’s (J&J) Stelara, $9.7bn (psoriasis, psoriatic arthritis and IBD); Roche’s Ocrevus, $5.8bn (for MS); and AbbVie’s Skyrizi, $5.2bn (psoriasis and psoriatic arthritis).

Then there is Novartis’s Cosentyx, with sales of $4.8bn (psoriasis and psoriatic arthritis); Amgen’s Enbrel, $4.1bn (psoriasis, rheumatoid arthritis and psoriatic arthritis; Bristol-Myers Squibb’s Orencia, $3.5bn (rheumatoid arthritis); Johnson & Johnson’s Tremfya, $2.7bn (psoriasis); Roche’s Actemra, $2.6bn (rheumatoid arthritis); AbbVie’s Rinvoq, $2.5bn (rheumatoid arthritis, psoriatic arthritis, dermatitis and Crohn’s disease); Eli Lilly’s Taltz, $2.5bn (psoriasis and psoriatic arthritis); and J&J’s Remicade, $2.3bn (rheumatoid arthritis, psoriasis, and Crohn’s disease).

AbbVie’s Skyrizi and Rinvoq, Novartis’s Cosentyx, J&J’s Tremfya, Lilly’s Taltz and Roche’s Ocrevus were all approved within the last eight years. Looking at sales growth for these six drugs, we find that AbbVie predicts sales of $21bn in 2027 for Skyrizi and Rinvoq together. Novartis expects Cosentyx’s sales to grow by 4% per year to 2026, but a comparison reported by drug database drugs.com suggests that Taltz is more successful at treating psoriasis than Cosentyx. Taltz increased sales by 16% in the year to July 2023; Tremfya’s sales were up by 18% in the same time frame.

Ocrevus is likely to be the leading MS drug by 2030 with annual sales of $6.3bn.

The 12 drugs mentioned earlier had total sales of $67.1bn in 2022, to which Humira contributed 32%. Humira was first approved by America’s Food and Drug Administration (FDA) in 2002. Its patents expire in 2023 in the US, its largest market, and this will allow other companies to bring similar drugs to market late this year. This opens opportunities for biopharmaceutical companies to develop new patentable rheumatoid arthritis drugs with advantages over Humira.

No problem, glad to help.

Can I ask what makes you think RF haven't sold the majority of their shares? Have you heard something on the grapevine?

Hi Shepherd - the US patent application was recorded as 'ready for examination' on 15/10/21 and the EU patent office began its review on 11/2/22. Having now been granted in China & Japan it can't be too long until other jurisdictions get through the red tape.

300k shares? Well played!

Hi CJH - see link below re JNJ-2113 (also known as PN-235). Trials carried out in US/Canada/Europe.

https://beta.clinicaltrials.gov/search?intr=PN-235

Maybe more interesting for us though are the details of the on-license & milestones -

From 27/11/23: https://www.biospace.com/article/releases/protagonist-announces-two-new-phase-3-iconic-studies-in-psoriasis-evaluating-jnj-2113-in-head-to-head-comparisons-with-deucravacitinib/

and from 28/7/21: https://www.prnewswire.com/news-releases/protagonist-therapeutics-announces-amendment-of-agreement-with-janssen-biotech-for-the-continued-development-and-commercialization-of-il-23-antagonists-301343621.html

Just in case there're other studies currently on the go, I searched the ANZCTR website for all psoriasis trials registered or started this year in Oz - just 3 results: the SAD/MAD, food effects and Adults with Plaque Psoriasis trials run by SAR.

Onwards!