Member Info for Haywain

Marco - I agree that potential suiters will be waiting for clinical data before declaring any sort of interest publicly. But the preclinical data points to their being a manageable safety profile for hemo CAR-T and significant efficacy (granted there will be an added risk for the first patient because even the best pre-clinical models (which Hemo have IMO) cant perfectly predict what will happen in human) - the most probable outcome is that the first patient will experience some form of manageable adverse reaction witch can be controlled with appropriate medical intervention (this is not the clinicians first CAR-T gig and the side effects and interventions are known). Also the first patient may also experience complete or partial response. My money (quite literally) is on this outcome.

1-2 years with first read after 3 patients 3-6M from initiation of the study would be my best guess. I think even if 100% complete response was observed in the initial dose they would probably want to continue with the dose escalation as there may be advantages at the higher doses that would not be obvious like enhanced CAR-T persistence for example. But dose escalations can be skipped under adaptive clinical trial design.

This will be

The example you chose Islandgirl was for kymriah which was the very first CAR-T to go through the regulatory process. It was a totally new treatment modality for FDA therefore took a lot longer to be green lighted vs current applications that typically take approx 5 years from start of non-clinical development to approval (including phase 1-3) We have the benefit of many of the potential issues already being known due to the pioneering work of others. Because we are treating rare diseases this will be fast tracked if safety/ efficacy allow and in all likely hood it will be sold to the highest bidder prior to phase 2/3 exciting times.

The optimised transduction efficiency offers a higher percentage of T-cells expressing the CAR therefore more efficacious on a per cell basis. Higher efficacy gives more wriggle room with dose optimisation i.e easier to hit an optimal window of therapeutic effect while minimising adverse events. From a logistics and manufacturing perspective the single day manufacturing process approximately halves the cost of manufacture . All good IMO

This to my knowledge is a scientific breakthrough the ability to program myeloid cells with a durable response is something that has not been successfully achieved before (attempted using retrovirus but durable response was not achieved). The significance is that CAR-T cells don't do so well for solid tumours because of the hostile nature of the tumour microenvironment therefore the T-Cells don't tend to infiltrate. Myeloid cells are the precursors for the innate immune system which includes macrophages (macrophages are used to being in a hostile environment as body's first line of defense) so this is a mechanism for programming the innate immune system with the ability to recognise and attack solid tumours. Because the technology is RNA based this is essentially a license to print stable CAR-M using the bodies own machinery rather than producing it in a lab (like CAR-T) to target multiple use cases and disease states. This also has applications for infectious disease because of the durability this could be used to preemptively protect against Virus X or as a treatment post infection. For autoimmune diseases macrophages play a role in exacerbating the condition through the release of pro-inflammatory cytokines there is an application for the ability to be able to turn that off or reprogram towards M2 macrophages (tissue repairing phenotype). All in all pretty bloody significant IMO

I don't know who you are talking to Me or Tilly but the fact that you need to state that you are a woman annoys me - It doesn't matter what or who you are.

Not that I feel that I should justify myself "Boom07!" but the reason I have not posted on this site regularly over the course of the last year is because I was leading a BLA application for a new bispecific antibody for which we have just received FDA approval. (a) I have not had a lot of spare time (b) I don't comment on financial discussions as it isn't really my bag and that for the last 6M has pretty much been the sole topic for discussion on here. (c) the science has been discussed ad infinitum. The reason I have started posting again is because I am genuinely excited for the start of the phase 1 study. Does that satisfy your question?

It can vary according to the tumour type and location how quickly CAR-T can take effect (blood cancers being quickest) but I know for example Tisagenlecleucel (Kymriah) for ALL - some patients expericened significant reductions in tumour burden within 1-2 days post -infusion. and for Axixatagene Ciloleucel (Yescarta) in patients with aggressive DLBCL symtompatic relief was observed within the first week of treatment

This is my best guess MC - I posted it a while back : Baseline data is collected from the patient prior to treatment pre-dosing probably covering (1) blast percentage in bone marrow and peripheral blood (2) FLT3 mutation type (ie ITD or TKD) and variant allele frequency, (3) Cytogenetic and molecular risk profile (4) organ function tests (5) Cytokine and biomarker levels - The reason you collect the baseline data is to have something to compare to post dose and will be available before we know a patient has been selected. If you are referring to the data collection post treatment then the following will probably be collected (1) 0-48 hours early signs of infusion related reactions/ hypersensitivity or other immediate toxicities (2) Cytokine Monitoring (3) PK monitoring - initial CAR-T cell expression in peripheral blood. 1-7 days post infusion: all of the above with the additional Car-T expansion and persistence data - Flow cytometry data to measure the CAR-T cell proliferation and persistence in the peripheral blood, (2) First indications on disease biomarkers ie FLT3ligand levels, blast counts in peripheral blood. (3) Initial efficacy signals - reduction in leukaemic burden. 7-28 days 1) Efficacy Assessment bone maroow biopsy and aspirate to assess blast reduction and minimal residual disease (MRD) status/ cytogenetic/ molecular testing for FLT3 mutation clearance. (2) CAR-T pharmacodynamics data monitoring for persistence and expansion in both blood and bone marrow (3) continued safety monitoring - Post 28 days I imagine it will be a monthly check up on all of the above until/if the patient relapses. When we will know is another matter but the people running the study will know and we will find out soon enough.

Https://www.youtube.com/shorts/cA-MYE6KB2U

Here are some examples of other phase 1 CAR-T studies - proof that you do see efficacy in phase 1 in many ongoing clinical CAR-T studies - if you fancy a bit of light bedtime reading that is - enjoy:

(1) City of Hope PSCA-CAR T Cell Therapy in Metastatic Castration-Resistant Prostate Cancer : Patients treated with PSCA-targeted CAR-T cells showed minimal side effects and promising therapeutic activity. One patient experienced a positive response lasting approximately eight months. https://www.cityofhope.org/study-car-t-for-prostate-cancer-shows-efficacy

(2) Anixa Biosciences - CAR-T Therapy for Recurrent Ovarian Cancer: https://www.pharmabiz.com/NewsDetails.aspx?aid=173658&sid=2&utm

(3) Poseida Therapeutics - P-BCMA-ALLO1 in Relapsed/Refractory Multiple Myeloma: Early efficacy and safety results demonstrated the potential of P-BCMA-ALLO1, an allogeneic CAR-T therapy, in treating multiple myeloma. https://investors.poseida.com/news-releases/news-release-details/poseida-therapeutics-presents-positive-early-results-its-phase-1.html

(4)Caribou :CB-010 ANTLER Phase 1 Trial in Relapsed/Refractory B-NHL- Long-term follow-up data showed a 94% overall response rate, with 69% achieving complete responses following a single dose of CB-010. : https://www.globenewswire.com/news-release/2023/07/13/2704702/0/en/Caribou-Biosciences-Reports-Positive-Clinical-Data-from-Dose-Escalation-of-CB-010-ANTLER-Phase-1-Trial-in-r-r-B-NHL.html

(5) UPenn: AT101 CAR-T Cell Therapy Targeting CD19 - B-Cell Malignancies - Early results indication 100% complete response at higher dose levels phase 1: https://www.sciencedaily.com/releases/2023/12/231210233253.htm

(6) Mass General Cancer Center: CARv3-TEAM-E T Cells in Recurrent - Initial cases from the Phase 1 INCIPIENT trial showed dramatic and rapid tumor regression in patients with recurrent glioblastoma. - https://www.massgeneral.org/news/press-release/clinical-trial-results-show-dramatic-regression-of-glioblastoma-after-next-generation-car-t-therapy

(7) Baylor College of - CAR T Cells Armed with IL-15 for Solid Tumors Expressing GPC3 - First-in-human Phase 1 trials reported promising results using CAR T cells armed with IL-15 in treating solid tumors expressing glypican-3.  - https://medicalxpress.com/news/2024-11-car-cells-armed-il-solid.html

(8) Mustang Bio - MB-106 in Indolent Lymphoma - Phase 1 study demonstrated high response rates and durable remissions, leading to FDA breakthrough therapy designation for this novel CAR-T therapy. https://ir.mustangbio.com/news-events/press-releases/detail/166/mustang-bio-announces-first-data-from-ongoing-multicenter

(9) Stanford University - CD22 CAR-T Cells in Relapsed/Refractory Large B-Cell - Phase 1 study demonstrated high response rates and durable remissions, leading to FDA breakthrough therapy designation for this novel CAR-T therapy. https://med.stanford.edu/news/all-news/2024/07/cell-based-therapy-lymphoma-fda-breakthrough-designation.html?trk=public_post_

Yes but dose escalation is necessary to define optimum therapeutic benefit and offset any potential risks of the initial dose being too high with respect to the potential adverse effects. There will be some therapeutic benefit throughout the dose escalation until they find the optimum.

Very good point JHFH - Hemogenyx HG-CT-1 represents a beacon of hope to those few who otherwise have no remaining treatment options but that are lucky enough to be enrolled into the study. With any luck HG-CT-1 will treat the condition so that these patients have longer with family and loved ones. A lot of people who post on here would do well to remember that.

Excellent !

Normally in phase 1 it is a small amount of patients which ramps up as you progress to phase 2 and 3 studies. I dont know the exact number here but there was some mention of 20 patients- I would have thought it could have been less patients but FDA possibly dont agree. I am unclear whether that is across indications or within indications and whether the 30 day gap between patients is across indication or not but all of that will play into the overall length of the phase 1. The beauty with it not being blinded you can get early reads on the saftey tolerability and initial efficacy - that is to say earlier than you might in a double blinded placebo controlled study. Very exciting as an investor, hemogenyx, the clinicians and most importantly the patients that stand to benefit from this treatment - good luck all.

Island girl - you asked when you would expect to see data from patient #1 - The answer depends on what data you are talking about. Baseline data is collected from the patient prior to treatment pre-dosing probably covering (1) blast percentage in bone marrow and peripheral blood (2) FLT3 mutation type (ie ITD or TKD) and variant allele frequency, (3) Cytogenetic and molecular risk profile (4) organ function tests (5) Cytokine and biomarker levels - The reason you collect the baseline data is to have something to compare to post dose and will be available before we know a patient has been selected. If you are referring to the data collection post treatment then the following will probably be collected (1) 0-48 hours early signs of infusion related reactions/ hypersensitivity or other immediate toxicities (2) Cytokine Monitoring (3) PK monitoring - initial CAR-T cell expression in peripheral blood. 1-7 days post infusion: all of the above with the additional Car-T expansion and persistence data - Flow cytometry data to measure the CAR-T cell proliferation and persistence in the peripheral blood, (2) First indications on disease biomarkers ie FLT3ligand levels, blast counts in peripheral blood. (3) Initial efficacy signals - reduction in leukaemic burden. 7-28 days 1) Efficacy Assessment bone maroow biopsy and aspirate to assess blast reduction and minimal residual disease (MRD) status/ cytogenetic/ molecular testing for FLT3 mutation clearance. (2) CAR-T pharmacodynamics data monitoring for persistence and expansion in both blood and bone marrow (3) continued safety monitoring - Post 28 days I imagine it will be a monthly check up on all of the above until/if the patient relapses. When we will know is another matter but the people running the study will know and we will find out soon enough.

Hemo-CAR-T will 100% be awarded orphan designation as both AML and ALL qualify as orphan indications in their own right - a subset of ALL and AML that are particularly hard to treat would certainly qualify IMO.

Hemo were working with Lilly on SLE

Ssccss/Tuan - why has nobody replied to you? I can't fathom why- I mean it is not as if you have been constantly trolling a company on the brink to bringing its potentially life saving medicines to patients that otherwise have no treatment option; day after day for years with the sole aim of quenching/quelling any positivity that perspective investors might have in said company.- Oh wait, that is exactly what you have been doing. Why? for a few quid? I am not surprised most have you filtered.