Member Info for Vander

All remains positive, but the basic tech transfer to made scientific will take some months and will need an amendment to the IND application. They need to show bio equivalence of the product

The RNS states this will be prioritised for the rest of year-however it will take longer- please feel free to disagree

Is the plan for made scientific to take over manufacture for the phase 1 trial, inc the paeds arm?

Three prognostic groups were defined with distinct 1-year OS in both development (favorable, 51% ± 3%; intermediate, 29% ± 3%; and poor, 14% ± 2%, respectively) and validation cohorts (51% ± 4%, 26% ± 5%, and 14% ± 3%, respectively). Validation confirmed the improved accuracy in predicting outcomes for patients with AML in first relapse. The revised AML relapse model improved on previous prognostic models for outcomes after first relapse. It provides stratification that might support tailoring second line treatment

https://ashpublications.org/bloodadvances/article/9/15/3853/537378/A-revised-prognostic-model-for-patients-with-acute

Participants in screening: NK

Ppts enrolled: 3

One CR (33%)

Two PR

No DLT

Durability of CR at 3, 6 months: NK

Median overall survival to date 3 months

FLT3

FLT3 is a very well-characterized receptor ligand for HSCs maintenance and differentiation. It is implicated in 30% of patients with AML (approximately 24% involving FLT3-ITD and 7-10% involving FLT3-TKD280). Some FLT3 inhibitors have already received FDA approval (midostaurin, gilteritinib) with an acceptable safety profile.281 Additional FLT3 inhibitors under investigation include quizartinib,282 sorafenib283 and crenolanib.284 To date, most data regarding CAR-T cell therapy is preclinical,285,286,287 and significant concerns have been raised regarding FLT3 expression in HSCs. In this context, some constructs in development include safety switches (described in the following sections) to reduce myeloablation.288

Other potential targets currently under investigation include CD19,289 ADGRE2,193,290 and ILT3.291 However, there is limited data available regarding their efficacy and safety.

If the fda approval threshold may be CR rate of 30-40% so we can keep a running tally. However the key outcome is safety

Also durability of CR of more than 6 months means using the 3rd patient as the first data point

The partial response patients are important in demonstrating biological activity but they will not factor in approval decisions

The nature article highlights manufacturing as

So far CR/CRi in one patient and PR in two patients with satisfactory safety signals

The protocol expectations is 18 patient in respective adult and paediatric studies

The recruit ment number may alter but the IRB expectation based on preclinical data is for minimum 3x3 dose cohorts plus subsequent expansion imho. Other disagree based on the rationale results may be better than the IRB expectation

Regulators will look for CR/CRi/CRh at 30-40% or above and durability at least 6 months , based on other fda approved targeted drugs (Ivosidenib 30%, Enasidenib 23%, Gilteritinib 21%)

Although bear in mind the more efficacy the more side effects

The shahzad SR/meta- analysis showed most aml car t-cell did not publish results or achieved lesser recruitment. Here are the pooled results for comparison

https://pmc.ncbi.nlm.nih.gov/articles/PMC10164930/?utm_source=chatgpt.com

57 patients from 10 clinical trials and 3 case reports. The pooled complete and overall response rates were 49.5% (95% CI 0.18-0.81, I2 =65%) and 65.2% (95% CI 0.36-0.91, I2 =57%). The pooled incidence of cytokine release syndrome, immune-effector cell associated neurotoxicity syndrome, and graft-versus-host disease was estimated as 54.4% (95% CI 0.17-0.90, I2 =77%), 3.9% (95% CI 0.00-0.19, I2 =22%), and 1.6% (95%CI 0.00-0.21, I2 =33%), respectively.

Https://www.dailymail.co.uk/news/article-15065369/Senior-lawyer-sexually-harassed-colleague.html

Andrew Greystoke, lead shareholder in WSG has been ordered to pay £20k in an employment tribunal

Https://www.nature.com/articles/s41392-025-02269-w

Hmm- yes- usually the whole point of the first part of these phase 1 AML studies is to find the max tolerated dose and Recommended dose for phase 2

Yes- an fda fast track would be very positive- with half the needed numbers

A dose escalation or paeds commencement is just part of the protocol however

Why is the enrollment delayed?

It’s a 3+3 design ie three patients per dose, with 3 planned dose levels. 18 adult patients and 18 paediatric, with children treated only once the adult cohort has completed.

The next dose escalation is likely to be approved- otherwise it will be a dose de-escalation

The aim is to find dose limiting toxicity in this 1st part of the trial, and then some indications of efficacy

The trial started in Jan 25- they need to get a move on to meet planned end by Jan 27- they planned for 1.5 patients per month ie 13 by now

Https://www.clinicaltrials.gov/study/NCT06786533

This is a useful reminder of the study design, objectives, primary outcomes, expected recruitment numbers and trial duration

The Estonian data is not fda admissible and the tech transfer for manufacture will take some months. After the phase 1 dose escalation cohorts (3-6 patient each?) they may expand - so total 9-30? It will take 12-24 months

Estonia will provide some income, shared with the local partner. It’s compassionate use and will follow trial results not lead but will provide more general data in a less selected patient group without the intensive monitoring of a clinical trial- it’s not designed to answer the scientific questions but may guide what future questions are/ the study design

They should try to be judicious in result announcements- individual patients is a bad idea- it will lead to massive volatility and beyond that may not be scientific/ethical and lack detail

Ok- for accuracy it’s a boardroom in HoP— really nice

Also I like the fence

The MP holds the Labour seat for Burnley and has recently returned from a 6 month suspension

He is holding up a certificate-presumably to mark attendance- also I can see no egg sandwiches and over boiled coffee in the boardroom- it’s part of Fowler’s cost cutting programme

Btw are Wsg being paid in Gabon or not (if Wsg tax has been suspended)?

I think it’s worth bringing these points up with Nigel and his team in his upcoming meetings - we need his answers

He has brought in a credible management team- their role is the regulatory side and actually developing/the lead product- the manufacturing has become more complicated with added components eg pei, ligand, multiple rna and it is unclear how well it will scale up without clumping. He reassures us that there are no off target side effects but it’s a new class of drug as well as novel class of delivery, in UC patients who already have well established treatments

The possibility of a targeted delivery vehicle for multiple chemotherapeutics is interesting but is still a very early preclinical stage- what indication, admin route, what rna- they don’t have the resources to develop multiple products

I am interested in wardle- he is on the board- and wants a higher SP

What will make a big difference is any evidence of talks with a commercial partner - they have experienced NEDs who can do the networking- but a hotel in Leeds is not where the partners are

Failing that any evidence of in house progress towards phase 1 - that’s why McLaughlin and Courtney have joined- this is time consuming and incurs expense

Nigel is trying to distract with other eye catching lab findings in cell cultures

Bear in mind this was a cellular finding- needing additional analysis- not yet tried even in rodents

They need a partner/licensing deal in the next 6-12 months or strong capital market pull- otherwise they won’t have money to develop any of the science

Nuvec is only one layer of the technology which needs proving- don’t forget the enteric coated capsule and mannose ligand. The new target ligand is for different epithelial/squamous cancers- which condition are they targeting?