Member Info for Haywain

It is not DSMB’s role to worry about manufacturing site approval - that would be FDA. The DSMB’s decision on dose escalation will be based on clinical safety data from the first dose cohort. I think there would be a IND update submitted to FDA to register the new manufacturing site but I am not so sure that will be RNS’ed the plans are already clear and presumably the new site will be using the same G-Rex manufacturing process and analytical methods so relatively straight forward submission. I have no idea how long this has been going on for in the background but expect that they will be in a position to supply HG-CT-1 to next dose cohort patients following DSMB approval.

Correct ArchBishop - In fact BDPCN, a subset of ALL (B-ALL & T-ALL subsets) , Myelodysplastic Syndrome , Mixed -phenotype Acute Leukaemia (MPAL) in fact any blood cancer that expresses FLT3 .

Exactly - thank you Pingu - very informative.

In fact - not even limited to AML - read the RNS again “ Ivari Saar, Board Member of Cellin Technologies, said:"We are thrilled to partner with Hemogenyx Pharmaceuticals to bring next-generation CAR-T therapy to Estonia, marking a major milestone for patients with acute myeloid leukemia and other hard-to-treat blood cancers. This collaboration positions Estonia at the forefront of advanced cell therapy in Europe, combining scientific innovation with a commitment to accessible care. Together, we aim to demonstrate how CAR-T can deliver transformative outcomes for patients across the EU."

Regarding the scope of Cellin and associated Estonian hospital - they are not limited to the same scope as the clinical protocol defines. It will be up to the oncologist under the oversight of the Estonian board of health to decide which patients may recieve benefit where no other treatment option exisits. It is worthwhile to remember that over 70% of ALL AML over express FLT3 which means that HG-CT-01 may not be limited to the treatment of FLT3+ve r/r AML and could - all being well move to much larger patient populations.

Yes Vander

Especially with Trumps new bill that prioritises paediatric cancer patients - NIH with new paediatric oncology focused cash to distribute with Vlad recently presenting at the Capitol whose to say we wont see some of these funds finding their way to MD A and or Hemo.

Chemo and radiotherapy are effective but brutal tools, because they’re broadly cytotoxic — they damage all rapidly dividing cells, and cancer happens to fall into that category. Patients deserve better options, and that’s exactly where the field is heading: immunotherapies and cellular therapies are far more targeted. When well-designed, they attack only the cancer cells while sparing healthy tissue. Crucially, these approaches aren’t just about ‘buying time’ — they’ve already shown curative potential in diseases like leukemia and lymphoma, where patients remain cancer-free for years without further treatment. HG-CT-1 is showing similar signs to the success case that CAR-T brought to B-cell lymphoma.

Welcome - nice to have a pharma person interested. I am a protein biochemist but also studied haematology/immunology- latterly (20 years) working on Biopharma and more recently (15 years) in writing BLA’s,MAA’s in oncology biologics.

No worries - refreshing when someone actually wants to expand their understanding.

Two Co stimulatory domains in car design including CD28 and 4-1BB- Gen one expanded too quickly and cause safety events Gen 2 expanded very slowly but had longevity - Gen 3 is a best of both worlds - expands rapidly and has durability

They didn’t use it so no - didn’t need it : no off target toxicity thus far nor plausibly in the furture because there isn’t high levels of FlT3 expressed anywhere else

With the hundred of posts a day either you don’t have a job / shouldn’t have a job because you are constantly on LSE / this is your job and you are being paid to write this crap - don’t care which : I will just bin you

LSBM - out of curiosity is this A.I generated ? It simply isn’t a diagnostic tool end of.

Correct - it’s an anti-CD3/FLT3 bispecific antibody - CD3 is a protein complex that sits on the surface of T-Cells ie the bispecific antibody binds T-cells and brings them into contact with FLT3 positive cells - in other words CDX is an off the shelf version of HG-CT-1

Appreciate that, Diggit 👍. As for Boom, same old tactic — attack the poster, ignore the progress. Three patients in, clean safety, CMRs at floor dose, FDA green-light for paeds, Estonia LOI… but apparently the big story is me. Says it all really

Sadly those are the real world choices people are faced with when faced with these sorts of diseases and a medication is not approved and reimbursed by state/insurance which is why we are so privileged in the UK to have the NHS where in theory standard of care options are provided to the rich and poor alike. It underlines the importance of making sure the best medications are approved in as many markets as possible so the best standard of care is available to all. Its not a perfect world we live in as is evidenced by the morals of some of the posters on LSE but that doesn't mean we cant fight to make it a better one.

Kymriah (pALL) - FDA allowed Phase 1 to stop after a few dose cohorts once CRs were consistent - Then rolled into a pivotal phase 2. Yescarta (DLBCL) dose escalation was truncated ; pivotal Zuma-1 trial followed immediately, Tectartus (MCL) started phase 1, found starting dose safe + effective and jumped immediately to pivotal phase 2. Where it is a rare oncology indication (and especially with paediatric population) with no curative therapy available - Fast tracking is exactly what FDA do and have already done for HG-CT-1 with the paediatric greenlight.

I can only assume you can't read or have a slight mental impediment ?

With all due respect Pingu is right on this one - The traditional 3+3 dose escalation design is all about pushing until you find MTD, which makes sense in a solid tumour trial where efficacy is dose dependent and toxicity sets the ceiling. HG-CT-1 is different . In r/r FLT3+ AML the biology is such that FLT3 is highly expressed not just on blasts but also on leukaemic progenitors and that means (as we have seen) you can achieve deep, durable responses even at the lowest dose. That is why we have seen in P3 "undetectable AML blasts by conventional analytical methods" - Efficacy isn't being "left on the table" its already there. the FDA has effectively confirmed that by approving paediatric expansion after only 2 adult patients dosed - they only do this when safety and efficacy signals are compelling. In these situations regulators are open to collapsing cohorts or reducing patient numbers because the priority shifts from "find MTD" to " dont delay access to something transformative" - There are many precedents for exactly this like the paediatric CAR-Ts in ALL - Once deep remissions are proven with manageable saftey the trial design is addapted to accelerate development. This is why Pingu's point about fast-tracking and cohort reduction is spot on.