Member Info for inanaco

worse news of the day ... England just lost to SA ...

Ruck ... we all invest with this knowledge

to early to think about funding again ...

plenty of water to flow under the bridge .... and the last funding round sent the share up not down ..

so if you follow historical events ... ? 10p after funding

If at first Ivy and Knowlesi fail ... roll out Ruck to help with Team Damp ...

this is just getting boring now ...

In Checkmate 067, the most common (=20%) adverse reactions in the OPDIVO plus YERVOY arm (n=313) were fatigue (62%), diarrhea (54%), rash (53%), nausea (44%), pyrexia (40%), pruritus (39%), musculoskeletal pain (32%), vomiting (31%), decreased appetite (29%), cough (27%), headache (26%), dyspnea (24%), upper respiratory tract infection (23%), arthralgia (21%), and increased transaminases (25%).

In Checkmate 067, the most common (=20%) adverse reactions in the OPDIVO arm (n=313) were fatigue (59%), rash (40%), musculoskeletal pain (42%), diarrhea (36%), nausea (30%), cough (28%), pruritus (27%), upper respiratory tract infection (22%), decreased appetite (22%), headache (22%), constipation (21%), arthralgia (21%), and vomiting (20%).

https://news.bms.com/press-release/corporatefinancial-news/five-year-survival-observed-longest-follow-date-advanced-melan

IMPORTANT SAFETY INFORMATION

WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS

YERVOY can result in severe and fatal immune-mediated adverse reactions. These immune-mediated reactions may involve any organ system; however, the most common severe immune-mediated adverse reactions are enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. The majority of these immune-mediated reactions initially manifested during treatment; however, a minority occurred weeks to months after discontinuation of YERVOY.

Assess patients for signs and symptoms of enterocolitis, dermatitis, neuropathy, and endocrinopathy, and evaluate clinical chemistries including liver function tests (LFTs), adrenocorticotropic hormone (ACTH) level, and thyroid function tests, at baseline and before each dose.

Permanently discontinue YERVOY and initiate systemic high-dose corticosteroid therapy for severe immune-mediated reactions.

yes it has been raised and still is ......... but its not in competition with Scancell

point of Ivy's post was a reason to sell or a reason for SP drift down in knowlesi case ...

but the issue as i have explained Braf inhibitors is a stage a delay ... before the cancer progresses .. so they are not a bar that scancell has to consider just a delay before that group move onto PD-1 , ctl4, or combos with Vaccines ..

the point i am making these combos can still gain benefit again by adding a vaccine

but the toxicity of all this .. may become a bigger burden on quality of life hence the high drop outs and AE events

Rats as Nice stated

From NICE

The combination of cobimetenib + vemurafanib OR trametenib+ dabrafenib
appear to represent a significant step change improvement with higher
probability and longer duration of response, longer PFS and longer OS
compared to single agent therapy. At this point in a rapidly changing field,
this improvement can make a major difference in allowing fit patients to
continue for longer working and caring for dependents as well as potentially
allowing them access to future improved immunotherapy options that look like
impacting on long term survival.

notice "allowing them access"

seems it could actually increase the patients that would otherwise be to sick to benefit from immunotherapy

lol

braf inhibitor "mixture" it does not like a 007 martini

I would also point out that Scancell combination is with the "current standard of care" ie patient prescribed Keytruda

you will see many trials posting data at phase 1/2 but they are not approved like the "Braf inhibitor ****tail" so its not possible to run any trial at present with non approved drug combo ..

The Braf inhibitors have been around for a while now and are successful in slowing down progression

however

BRAF-V600E as a therapeutic target in melanoma (Introduction) Current therapies for the treatment of metastatic melanoma, the most lethal form of skin cancer, """"offer limited clinical benefit"""" Patients with advanced disease have a poor prognosis and a 5-year survival rate of less than 20%

they still will fall into the "pd-1" arena as the decease progresses

""""lets try again .. what combo has produced 70% response rate in melanoma"""

"""""""""""which is"""""""""""""

"""1/ a vaccine combination """

Now why did i use that criteria for a response .......... ??????????????

simple any combination that gets approved without a vaccine in that combination

its possible to "ADD" SCib1 providing the patient met SCIb1 criteria

we don't add to toxicity

Ivy you did not answer

""""lets try again .. what combo has produced 70% response rate in melanoma"""

"""""""""""which is"""""""""""""

"""1/ a vaccine combination """

The issue is .... ref your link

All 39 patients in the triple combination cohort experienced at least one treatment-related side effect. The more serious grade 3-4 treatment emergent adverse events occurred in 26 patients (66.7%).

Overall, the investigators note that adverse events were managed with dose delays and reductions. Eleven events led to discontinuation of a study drug with eight of those involving elevated liver enzymes.

Three fatal adverse events were reported, caused by sepsis, respiratory distress and inflammation of the duodenum, none of which were considered related to treatment.

"""" Eleven events led to discontinuation of a study drug with eight of those involving elevated liver enzymes.""""

if you start adding back in to the numbers these kind of incidents you % crash from 71%

what you have done is taken a head line figure from a very restricted criteria of entry which """does not""" have a vaccine in it ...

so when we talk about these 70% response rates ... actually only 20% had the cancer disappear which is not that far of Pd-1 rates anyway ie a ""Complete response "" which is why Wild said this headline figure is miss leading

I see that was the response by Bermuda anyway .. pity he did not read the post and reply with a ""vaccine combo"" as asked rather than a raft of inhibitors

Scancell

US IND for SCIB1 gives Phase II study the green light

Lighthouse | 3 February 2020

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Scancell has announced that the FDA has cleared the SCIB1 IND (Investigational New Drug) application. This means that both the UK and US arms of the Phase II trial, evaluating the SCIB1 vaccine in combination with the checkpoint inhibitor pembrolizumab (Keytruda) in metastatic melanoma, can now start.
The US element of the trial had been delayed due to the FDA having a number of questions regarding Ichor Medical Systems’ TriGrid v2.0 electroporation delivery device. This is a newer commercial version of the device that was employed in earlier clinical work. The resolution allows Scancell to initiate US site activities and patient enrolment, alongside UK clinical site expansion.
The study will examine the tumour response rate, progression-free survival and overall survival in 25 patients with advanced melanoma. The aim is to explore if combination with a checkpoint inhibitor will improve treatment response with acceptable toxicities.
Scancell’s second ImmunoBody, SCIB2, uses a novel lipid nanoparticle formulation. The forthcoming CRUK-funded Phase I/II study will employ this via a standard injection, rather than using electroporation. Preclinical studies suggest the nanoparticle formulation is at least comparable to, and could be better than, using electroporation.
Trinity Delta view: ImmunoBody is the most clinically advanced of Scancell’s three technology platforms. ImmunoBody vaccines have an elegant design that targets dendritic cells. They achieve efficient direct and cross-presentation of specific epitopes (peptide sequences from proteins), and a consistently strong anti-tumour immune response. Promising activity was seen in a SCIB1 monotherapy Phase I/II melanoma study, but the real potential, in our view, is in combination with checkpoint inhibitors. The FDA’s green light for the US arm of the Phase II study is a welcome step forward and allows management to re-build momentum.

We maintain our valuation of £82.0m, equivalent to 17.2p a share. There are various likely catalysts over the coming year; including further AvidiMab collaborations, the SCIB1 UK trial being underway, and news flow on the timings of the first SCIB2 and Moditope clinical studies.

Scancell only needed one UK site so that our labs can monitor the patient biopsy / blood and scan etc having achieved success with the NHS to pay for Keytruda at one uk site

US patients cover the cost of Keytruda hence the trial is well suited to the US based system, plus the distinguished level of interest shown by the leading clinicians in the US based on our Trial results in Adjuvant and solid tumor

Scancell is not holding back patients in the UK arm clearly the competition for patients in the field is very high and its only a very few that will consider trials anyway .... even that gets slimmed down because of criteria .. exactly the same happened when the phase 1 trail of SCIB1 started years ago .. patient recruitment was slow

all good ... best forget about SCIB1 for a few months give Scancell a bit of breathing space ..

so all we are now waiting for is the Modi1 confirmation of all three conjugates , then all this "technical" delay is behind us

I agree with Bob

No value attributed to

Avidmab
SCIB2 with CRUK
Modi1
Modi2 including the discovery of homocitruline
TCR ....

SCIB1 with its trial data should easily be worth £50m on its own today as an upfront payment on a license without keytruda data

because Keytruda is a Mab that """locks on to T cells"" .............. and Scancells T cells are superior because of Avidity better than any T cell produced by the patient indeed the adjuvant trial results prove that

which is why The US Oncology guys are so interested ...

Depends ........ it gives Merck the advantage and the incentive to take it to a phase 3 .... exclusivity = big bucks

however non exclusive would allow scancell the opportunity to run trial with second generation of bi specific Pd-1 ... MABS

BioNtech

Checkpoint Immunomodulators
Following the success of immune checkpoint blocking antibodies targeting CTLA-4, PD-1 or PD-L1 in cancer treatment, bispecific antibody formats represent the next generation of emerging immunotherapies with the potential to further improve clinical efficacy. We are developing, in collaboration with Genmab, bispecific antibodies that function as dual immunomodulators, applying Genmab’s proprietary DuoBody technology in combination with our target identification expertise. These next-generation checkpoint immunomodulators are thought to induce beneficial co-stimulation, promoting specific T cell activation, survival, proliferation and T cell effector functions.

At a glance: Our Next-generation Checkpoint Immunomodulators
Concept: Bispecific antibodies for dual immunomodulation, initially targeting 4-1BB, an immune checkpoint that is expressed on T cells and NK cells and can enhance immune cell proliferation and activation, in combination with simultaneous checkpoint inhibition.
Mechanism: Conditional activation of 4-1BB checkpoint only upon simultaneous binding of PD-L1 or CD40 (in the case of our initial candidates), potentially avoiding toxicities seen in prior attempts at 4-1BB agonism by localizing 4-1BB activation to the tumor environment.
Development Approach: 50:50 cost and profit share with Genmab, combining our and Genmab’s immunostimulatory antibodies and extensive immunology expertise with Genmab’s DuoBody bispecific antibody platform.
Lead Candidate: GEN1046 (BNT311), our PD-L1x4-1BB product candidate for multiple solid tumors.

Don't forget the Mark 2 version of SCIB1

exclusive or Non exclusive ........... both routes have a very valuable end because exclusive must include valuations based on second generation PD-1 potential ..

At Last we are in trial with a current a "standard of care"

you cannot get a more "commercial advantage" than that at this early stage if synergy is demonstrated because its an Approved therapy ...

Commercial advantage = License

this data will also give you a base line of what we might see in the SCIB2 trial ... in other words "synergy" will be shown with Immunobody providing Scib2 hits the correct T cells ..

that's because Knowlesi keeps pressing the buy button ... Gf ..

Resulting situation on the date on which threshold was crossed or reached

LGIM - Below 5%

-

LGIM - Below 5%

384,611,936

Resulting situation on the date on which threshold was crossed or reached

UTM - Below 5%

-

UTM - Below 5%

384,611,936

that was the result after the open offer so are far as we know they still hold, but because they don't have to disclose we don't know

TF ... they may have just fallen below the requirement to declare after scancell issued more shares .. can't remember an RNS announcing Disclosure Requirements, have you seen one ? if you have not they maybe still holding

TF

l & G have not topped up in the market or placed a Non exec on the BOD or placed a senior Prof into Scancell for Due Diligence ie on the science as presented so far