Scancell Share Discussion Threads

[sci102] 06/2/2024 07:14

They may be ahead in clinical development but unless they show over 65% ORR they'll have to wait for another couple of years for meaningful PFS/OS data before any significant developments. Then, if good, they can hope to replace CPI combo with pembro + UV on the basis of reduced toxicity. SC is aiming higher than that, but I agree it remains to be seen if that's the case. For the record, are you invested in UV? That'd be fine but best to disclose it.

[ruckrover] 06/2/2024 07:09

TF,Sally Adams is only 63.

[3nobody] 06/2/2024 07:08

marcus,

Do you have any referance where Lindy states she thinks Scib is probably better than Ultimovacs? Is this from a presentation that is available anywhere?

The objective response rate from Scib1 is remarkable high. It would be really interesting if this also can be shown with iScib1+ in unresectable melanoma.

But Scib is a long way from showing data in a randomized controlled trial. Ultimovacs will by Q3 this year have result from three (of five planned) randomized controlled trials.

[sci102] 06/2/2024 05:52

3n. Good stuff. I only note that in the UV study, there are still patients with new lesions (minimum 4 but surely a few of the clearly PD ones at first scan as well). To me absence of new lesions during treatment is potentially a leading indicator of good efficacy. In the SCIB study there is currently 0% new lesions vs about 20% in the other studies (in UV it's somewhere between 13-20%). But we do need more data.

[marcusl2] 05/2/2024 22:56

3no,


SCIB1 – Phase 1/2 reduced recurrence and turned cancer into a
chronic disease
88% of patients remained disease-free for 5+ years
14/16 patients with resected tumours were disease free after 5 years

13 patients receiving SCIB1 in the ongoing SCOPE trial, with an objective response rate of 85%

Hopefully data on 43 advanced unresectable melanoma patients who will receive iSCIB1+ with doublet therapy, consisting of ipilimumab (Yervoy®) plus nivolumab (Opdivo®) by Q3.


Lindy thinks Scib is probably better than Ultimovacs but we won`t have long to wait and everyone is hoping Ultimovacs works well.

[3nobody] 05/2/2024 19:36

The comparison between Scib and Ultimovacs, presented below (03/2/2024 22:05), is intriguing. The study is an older safety study with small sample size (n=12) done with ipilimumab only.

Ultimovacs have done another larger Ph 1 study combining with pembrolizumab (n=30) yielding an ORR=56.7%,CR=33%, PR=23.3% and noteworthy CR=35.7% in PD-L1 negative patients. (Subgroup not responding well to Pembro mono).
[hxxps://ultimovacs.com/content/2022/10/SMR_Presentation.pdf]

It seems Scib1 have limited data available from small populations and there is no reason to beleive Scib1 is better than UV1 from Ultimovacs as assumable stated by Lindy.

Anyway, Ultimovacs will present topline result from their anticipated Ph II study INITIUM this March, combining UV1 (UV as in Universal Vaccine) with both nivolumab plus ipilimumab in Melanoma.

I would recommend to pay close attention to the Initium result this March. A RCT trial [NCT04382664] with 156 patients comparing with nivolumab plus ipilimumab. The result could potentially shift the spotlight onto the vaccine space.

Additionally, Ultimovacs just received Fast Track in Mesothelioma (a very challenging indication) based on result from their Ph II NIPU trial, showing the risk of death reduced by 27% in second line malignant mesothelioma. A very big achievement.
[hxxps://newsweb.oslobors.no/message/609798]

This is one of many reasons topline result from Initium is most anticipated.

[ruckrover] 05/2/2024 18:38

MT,I didn't think that the actual cancer type had been made public. What makes you think that would help?

[markingtime] 05/2/2024 18:30

I see King Charles has been diagnosed with cancer. Where is SC129 when it is needed?

[marcusl2] 05/2/2024 08:55

Best wishes to Sally Adams.

Dr Callum Scott, Head of Development, commented: "Joining Scancell when SCIB1 and Modi-1 cancer vaccines are making highly promising clinical progress is very exciting, with further data from the SCOPE study expected in mid-2024 and ModiFY trial later this year. I look forward to contributing to the rapid advancement of these innovative and high-value assets through the clinic and towards commercialisation and working with Lindy and the Scancell team."

[inanaco] 05/2/2024 08:21

Tf and the choice of words "standard practice"

Scancell Holdings plc (AIM: SCLP), the developer of novel immunotherapies, today announces that John Chiplin intends to resign his role as Executive Chairman and Non-Executive Director of the Company for personal reasons but is staying on for an interim period until a new Chair is appointed.

[inanaco] 05/2/2024 08:06

retiring ....... Sally was 53 when she joined Scancell . full time in 2014

before the conspiracy starts

[inanaco] 05/2/2024 07:16

Best wishes Sally ....... and Thankyou ........

for those unsure about Moditope seems the company is still very confident

Prof Lindy Durrant, Chief Executive Officer of Scancell, commented: "Firstly, on behalf of the Scancell Board, I would like to express our sincere gratitude to Sally for her expertise and support over the last 15 years, both on the Board and leading clinical development. She has been instrumental in establishing a highly motivated development team and has worked tirelessly to bring our highly differentiated and valuable cancer vaccines through to the clinic. We wish her all the best for the future.



"I would also like to warmly welcome Callum to Scancell. His understanding of the challenges involved in developing, registering, and commercialising novel biologics will be of great value to Scancell as we continue to develop our lead assets SCIB1 and Modi-1 through later stage clinical development."



Dr Sally Adams, Chief Development Officer, said: "It has been a privilege to work with Lindy and the Scancell team for the last 15 years, helping to develop successful manufacturing processes and quality systems and to take three products into the clinic. The recent clinical successes with SCIB1 and Modi-1 have been the culmination of a huge team effort across the Company, and I have every confidence that these results will be built upon in the future. I wish Lindy and the Company every success."



Dr Callum Scott, Head of Development, commented: "Joining Scancell when SCIB1 and Modi-1 cancer vaccines are making highly promising clinical progress is very exciting, with further data from the SCOPE study expected in mid-2024 and ModiFY trial later this year. I look forward to contributing to the rapid advancement of these innovative and high-value assets through the clinic and towards commercialisation and working with Lindy and the Scancell team."

[marcusl2] 04/2/2024 21:59

Dom,

hopefully a big hitter like BMS, Roche, Eli Lilly or Merck will license Immunobody or buy Scancell to do that fighting for us!

[chilltime] 04/2/2024 19:25

Scib potential further update timelines from previous news.

19th Sept news

All 16 received their first dose.

Initial scans happen at week 13, 19, 25 and 37.

19th update, 11 patients week 13 scan, 2 of which week 25, and 2 week 37.


28th Nov update

2 more at week 13, partial responses to be confirmed in another scan which means week 19.

So based on the numbers given and dates.


Week 13 for all (16 patients) was no later than 19th Dec.
Week 19 for all (including 2 new ones and missing 3) no later than 30th Jan.


So in theory Scancell now have the data for all 16, with the first scans and 2nd confirmation scans done. 9 of the responders are now past the week 25 scan

So they can now give an update (should they wish) on all 16 of the first cohort. I suspect they will.

The scan timelines are a week or two prior to the news dates, as they would need to assess the data and report on it, as in the presentation given.

So the week 19 2nd scan for patient 16 may well have been mid Jan 24.


Feb update on the point ??? and possibly very shortly

[dominiccummings] 04/2/2024 19:15

Moderna have the money to crush competition with marketing.

[chilltime] 04/2/2024 13:18

Breaking down results so far known on Scib we know the following.

I can add the detail if required but it’s in various releases which allows the following conclusion.

Data on 4 patients that have the the 37 week scan are available.

So for the first 4 treated the 37 week result is.

3 are fairly obvious -88% -94% and complete response. The 4th likely -81%.

So that’s -81%, -88%, -94% and a complete response, for the first 4 treated.


I’d wager the one listed as patient 9 in Sept is the complete response.

Patient 9 was about -72% week 13 -59% on a reversal week 19, and a strong response week 19 to 25 taking them to -81%.

The strength of the second turn down makes them look like the complete response by the 37 week scan.

[chilltime] 04/2/2024 12:56

Sci

The notes on Ultimovacs by brokers reflect what Lindy said.

A hope that it will throw the spotlight onto the vaccines.

The CPI crew moved from single to double therapies having recognised the gains possible.

Now news is due this year on combo therapies. Which could, going by Scib early indicators, considerably excite the sector.

It’s quite fortunate that a current comparison trial includes the ipilimumab and nivolumab combo in 78 patients, due to report within months.

That means Bristol Myers will have fresh data to compare to Scib results.

[marcusl2] 04/2/2024 12:32

ImmunoBody: CD8 T cells for a range of tumours

The ImmunoBody platform creates DNA vaccines that encode a human antibody framework, but the parts of the antibody that would normally bind to the target protein, the complementarity determining regions (CDRs), are replaced with carefully selected cytotoxic T lymphocyte (CTL) and helper T cell epitopes from a cancer antigen (Exhibit 10). Each vaccine can be engineered with several selected cancer associated T cell epitopes to create a genetic antigen/antibody complex. The direct and cross presentation of antigens generates high avidity T cells with a broad and potent anti-tumour effect.

Therapeutic vaccines require targeting and activation of dendritic cells (DCs) to stimulate both CD4 and CD8 T cell responses. DCs are considered the most efficient APC (antigen presenting cells) being able to initiate, coordinate, and regulate adaptive immune responses. ImmunoBody constructs are flexible, but with core features that include:

epitopes selected so they bind to both MHC I (for the CD8 T cell response) and MHC II (for the CD4 Th-cell response);
an Fc region of the protein form that targets activated DCs.
ImmunoBody vaccines activate DCs through two distinctly different and complementary mechanisms that maximise T cell activation and avidity: direct- and indirect/cross-presentation. There are various pathways by which DCs can process antigens, and the highest avidity T cell responses are generated if more than one pathway is used to present the same epitope.

Primarily, the DNA element is taken up directly by the DCs, via transfection, and the resulting protein is processed in the APC. This direct presentation produces the appropriate immune response but generates only moderate T cell avidity and the anti-tumour response is too weak in the typical immunosuppressed TME. However, an identical protein component is secreted by muscle cells (which is produced at the site of the injection from the DNA) that binds to the Fc receptors on DCs leading to the cross presentation of epitopes (Exhibit 11). This dual approach generates both a cytotoxic CD8 cell response and a Th CD4 response that, importantly, is up to 100 times greater than either presentation alone with potent high avidity T cells generated. This amplified immune response is now sufficient to generate the required broad anti-tumour response in the TME.

The ImmunoBody vaccines have been designed so that epitopes for both MHC I and MHC II complexes are produced once they have been broken down by the proteasome. Epitopes for MHC I are normally 8-11 amino acids in length and generate a CD8 response, and epitopes for MHC II are usually 13-17 amino acids long and result in a CD4 response. The generation of both a Th and Tc cell response is important, as the Tc cells only become activated and able to destroy the tumour cells once Th cells recognise the appropriate epitope and secrete cytokines and chemokines to activate and recruit T cells.

[marcusl2] 04/2/2024 12:29

Moderna / Pfizer is getting an amazing amount of good press about their Melanoma mRNA vaccine.

Scib-1 on its own had at least as good results in resected metastatic melanoma (Stage III and IV), 88% still alive after 5 yrs. That corresponds with dose dependent T cell response in 88% of patients.

Scib-1 with doublet looks superior at 85% orr in non-resected.

Moderna presenter has said that if Lindy is correct then they are in trouble.

So Moderna targets 34 patient neoantigens with the personalised vaccine and apparently only about three of those work. Expensive and time consuming.

SCIB1 incorporates specific epitopes from the proteins gp100 and TRP-2, which were identified from the cloning of T cells from patients who achieved spontaneous recovery from melanoma skin cancers. Both proteins play key roles in the production of melanin in the skin.

iScib+ may lift the orr rate higher and covers all patients.

Scancell is definitely under the radar atm.

[ivyspivey] 04/2/2024 11:59

Morning interesting reading

[...]

[sci102] 04/2/2024 09:27

Their result is not that bad, given they only used ipilimumab. Pretty close to having the same efficacy as double CPI. As the company said, a good result would be positive for the field in general.

[chilltime] 03/2/2024 22:05

Sharing some info found.

Lindy said Ultimovacs have a phase 2 running and good results would be good news for vaccines (due March)


She also said she doesn't believe theirs is as good as Scib.

Here is an Ultimovacs phase 1/2 result which was their vaccine with ipilimumab

11 patients, 3 partial response, 1 complete response.


The complete response took over 2.5 years.the graph and results are nowhere near on the scale of Scib with the combo.

The study is similar to the one Scancell are doing with patients, a similar split on the Melanoma types.


Study Design
This was an open-label, single-armed, single-center phase I/IIa clinical trial [NCT02275416]. The primary objective was to investigate the safety of combining UV1 with ipilimumab in patients with unresectable metastatic melanoma.