Member Info for Vander

Regarding dose-safety relationships:

Increased incidence and/or severity of CRS/ICANS was observed in 23 (68%) studies, and 11 (32%) studies noted no association between dose and toxicity (table 2). Out of 11 studies with cohort size over 50 patients, seven (64%) studies observed higher adverse events,10 71 72 75 one (9%) study noted no association with dose77 and three (27%) studies did not comment on dose–safety association.11 76

As haywain mentions- other than dose- disease burden/no of diseased cells , flt3 density of expression, T cell expansion fitness make ad difference

This makes interpretation of results less straightforward for a ‘living drug’

Here are the trial dose levels:

Dose Levels Dose level 1: 7x10^7 Transduced CAR+ HG-CT-1 Dose level 2: 1.4x10^8 Transduced CAR+ HG-CT-1 Dose level 3: 3.5x10^8 Transduced CAR+ HG-CT-1 If Dose level 1 is found not to be safe, dose will be de-escalated to 3.5 x 10^7 Transduced CAR+ HG-CT-1. (Dose level -1)

The systematic r/v comments:

Within the studies that showed association between dose and ORR, the starting dose was comparatively lower (

Here is a good article to explain

Increasing dose may not improve beyond a certain threshold, although toxicity may increase without added benefit- based on ALL studies which may (or may not) guide AML

A big factor in predicting efficacy is the disease burden of each patient- plus others- see article

https://jitc.bmj.com/content/10/12/e005678

Vlad’s tone was measured- positive but not over exuberant. Ultimately this is a trial with life and death consequences for patients

He acknowledged that we have got through the first hurdle with no DLTs at the lowest dose- it could gave immediately failed and so now there is something to work with, but higher doses mean more risk

He has given an expected timetable from which to be judged- one patient per month in adult and paeds trials, but delays if DLTs. He suggests phase 2 trial will follow the 18 patient accrual- with expansion of sites, and cost and logistics. In my view hemo won’t cope with that on its own

What follows he does not know- that’s why it’s a trial- the safety part is important- it’s harder to optimise a dangerous product vs one that needs to be more effective

The post was in response to pingu’s survival data on r/r aml patients who receive basic support only- obviously the trial patients can’t be compared to them

There are multiple prognostic factors and we have such a small sample size- I am interested how overall survival used as a outcome measure

The two FLT mutations have different prognoses- one worse than the other- I am interested to know if hg ct 1 binds differentially to these and the normal flt phenotype- it will make a difference to on/ off target effects also

Regarding overall survival data this will be affected by various prognostic factors- however the trial patients are also receiving standard lymphodepleting chemotherapy consisting of fludarabine and cyclophosphamide prior to hg ct 1

They are not receiving BSC only

We don’t know the ages of the trial patients- but know they are flt3 positive (no info on presence or type of mutation).

Here is the summary of CAR t- cell studies presented at ASH 24- see table 1

It helps to compare and contrast with the stage hemo is at

https://ehoonline.biomedcentral.com/articles/10.1186/s40164-025-00651-6#:~:text=Infection%20after%20CAR%20T%2Dcell,001)%20may%20expand%20targetable%20epitopes.

Vlad is playing an interesting game if he announces the result of each individual patient

It’s also get your roulette out

The next updates will be on manufacture and funding

P4 will be dosed maybe in Jan or feb 26- if no manufacture delay?

NCT05023707

NCT05445011

NCT03904069

NCT05432401

Three in China. Two in USA

Amgen 553 trial discontinued

Hemo first to announce any results

Do they have a funding runway?

Someone mentioned 2.7 million is available

Presumably they want to transfer manufacture before starting the next cohort

Hence no rush with DSMB approval

Of course adherence to GCP is essential, and greater funding means better quality compliance and more intensive follow up

How long did comparable trials take in ALL? -the first one took 6yrs for 83 pts (2010 to 2016) and others have varied in duration.

A bane of aml cart trials have been slow recruitment, poor publication of data and non progression beyond phase 1 despite some positive results

The trial site opened 30/12/24

It’s taking a year to recruit 3 patients

The initial results are positive- not clear if following the example of cart for ALL trials or previous duff aml ones

However, the crucial manufacture is changing mid trial and funding is piecemeal

Isn’t this a bit half arsed because hemo is a small outfit? What do they need to power ahead?

At least we will get a clinical answer sooner, whether good or bad

Hemo are doing complex testing including flow cytometry based on the objective:

Secondary scientific objectives:

i. Describe the persistence and trafficking of HG-CT-1. ii. Describe HG-CT-1 bioactivity and its predictors.

Some of the data will relate to the patients ongoing ‘treatment as usual’ which is provided and presumably owned by the site/mda?Eg work up for hsct, ongoing long term follow up- these impact on overall survival

I am surprised that data (and associated costs) such as mrd status are not the responsibility of hemogenyx - presumably they do not see it as a critical phase 1 trial outcome (safety is)- mda have lots of competing trials (see Al)- I doubt they will find extra tests which should be funded by the sponsor- but it s an interesting question

Are you saying that the DSMB are not going to notice that they are planning to change manufacturer when they approve dose escalation for the next three pppts

From the half year report

Our priorities for the remainder of 2025 are clear:

3.Manufacturing scale-up; progress technology transfer with Made Scientific and deploy the G-Rex® grant to strengthen manufacturing efficiency and scalability.

Delays in the trial are avoided if in-house manufacture is allowed until the transfer process is complete

However, changing manufacturer mid trial is not ideal in the eyes of the regulator whose role is to protect patients and the scientific integrity of the trial

Part of the process is filing a manufacturing amendment to the IND/CTA

Btw the move to made scientific is very positive- in fact essential

Digittt- ok forget the need for an amendment- although manufacture is so crucial you would imagine some sort of notification to the IRB is needed

How long will the manufacturer tech transfer and qualification take?

Will it delay p4 ?