Member Info for Haywain

Hello Mr. India,

Without specific details, it's difficult to estimate timelines accurately. It's feasible that Hemo/Wuxi could update the lentiviral vector, complete testing, resubmit the IND, and receive FDA approval within the year. However, unforeseen delays could extend this timeline into the next year. The critical issue to me isn't so much the timing (as some would suggest it is) but ensuring the IND meets approval standards and clinical trials begin. If these steps are met, the rest will fall into place.

"The splicing issue is a mirage/the Manufacturing process is the Reality !" So what are you saying here ? That Vlad lied in the recent RNS? Or that FDA fed back multiple concerns - splicing issue being one but additional concerns relating to the manufacturing process? - If that was the case how would you know? What we have been told is that there was a concern from FDA relating to the lenti-viral splicing and that Hemo/Wuxi have come up with a proposal that mitigates FDA's concern. There is nothing mentioned about the manufacturing process- please explain your thought process behind your statement.

One2one - nice to see you moving on from if Hemo Car-T will become clinical to when it will.

I think the poor share price is just a reflection that there are no (other than prevail) institutional investors currently. So the traded shares are in the hands of individual investors and traders. I do think it will be a different story when the IND is approved and clinicals start but that is my personal opinion.

Looks like sterility testing to me - absence of growth = positive result ie the sample tested is sterile

I would think that the only mechanism that a virus would have to evade Hemo CBR is to find an entirely new target protein for entry into the cell - The ability of the virus to bind a receptor for cellular entry is fundamental to its ability to replicate in host cell ie cause infection in the case of SARs Cov2 - it binds the ACE 2 receptor - so long as it does then ACE2-CBR will always work. Would like to know more about the other ACE2 treatment that DOD investigated. thanks H

I have had a 16 hour work day so far and that was quite a lot to process - Did I hear correctly CBR - developed into mRNA construct that will be combined with synthetic polymers to presumably be administered through some sort of aerosol to pneumocyte tissue which in turn would produce the protein chimeric bait receptor activating macrophage to respond to anything that binds the bait - Then secondly that they have demonstrated (ie proof of concept) that if they engineer human haematopoetic stem cells and inject them into mice that you can see the cells in the micro glia ( which I think is the immune system component specific to the brain (because of the blood brain barrier) - Additionally systemic immune cells dont cross the B/B barrier - So some how the haematopoetic stem cells when injected into mice inform the brain's immune system (new to me). They then plan to use this to engineer haematopoetic stem cells from the patient with CBR raised to a marker(s) of Glioblastoma brain tumours as a form of treatment. - I need to sleep on it and I promised my self that I have enough of these shares but I am considering dipping my toes in again.

Stu are you pinning your hopes on the FLT3 ligand being a no-goer because of potential adverse reactions?

FMS-like tyrosine kinase 3 (FLT3) is a class III transmembrane receptor tyrosine kinase involved in survival, proliferation, and differentiation of hematopoietic stem/progenitor cells. It is preferentially expressed on the leukemic cells of myeloid lineage including acute myeloid leukemia (AML) and is mutated in approximately one-third of patients with AML, resulting in constitutive signaling associated with poor disease prognosis. Although small molecule inhibitors targeting FLT3 have shown some success in clinical trials, they only work transiently while resistance develops in virtually all patients. The only proven curative treatment for the relapsed or refractory (R/R) AML is allogenic hematopoietic stem cell transplantation (HSCT) which requires highly toxic conditioning regimens often associated with fatal side effects. Thus, there still remains an urgent need for the development of safe yet effective new therapies for the treatment of AML.

We developed a novel chimeric antigen receptor modified T (CAR-T) cell therapy targeting FLT3 to eliminate FLT3+ R/R AML leukemia via cytotoxic T lymphocytes (CTL)-mediated cytolysis. Since FLT3 is also expressed on hematopoietic stem cells (HSCs) as well as on early hematopoietic progenitors (HPs), we evaluated the conditioning efficacy of our anti-FLT3 CAR-T in addition to its anti-leukemic activity.

We first discovered a novel mouse monoclonal antibody that binds to the extracellular domain of human FLT3 with high affinity (0.8 nM EC50 in FLT3+ leukemic cell line REH) while not competing with FLT3 ligand in order to achieve unobstructed and efficient binding to FLT3. We next generated humanized single-chain variable fragment (scFv) antibodies and characterized their binding affinities. The scFv clone that exhibited highest binding to FLT3 (3.42 nM EC50 in REH cells) was used to design a third generation CAR construct with CD28 and 4-1BB costimulatory and CD3ζ activation domains. T cells isolated from peripheral blood (PB) were transduced with a lentiviral vector encoding the FLT3-CAR. Transduced cells exhibited stable expression of CAR protein and expanded over 120-fold after 18 days in culture. We demonstrated high cytotoxicity of FLT3-CAR-T cells towards AML-derived cell lines in co-culture experiments, even at effector-to-target cells ratios as low as 1:10. In vivo functionality of FLT3-CART was determined by flow cytometry analysis of leukemia burden in the peripheral blood of mice engrafted with GFP+ MOLM-13 (FLT3+ AML cell line) and treated with two doses of 4x106 control or FLT3-CAR-T cells. Compared to control, the appearance of MOLM-13 cells in peripheral blood was significantly delayed in FLT3-CAR-T treated mice. AML progression in mice was also assessed by detection of physical symptoms such as cachexia and hind-leg paralysis in terminal stages. FLT3-CAR-T treatment extended the median survival to 47 days compared to 24 days in control.

Same here Gheko - It is not just a purely financial investment for me having lost several family members to cancer. It annoys me that we are not further along towards eradicating the disease all together. Hemo have such a compelling story here: likewise for the antiviral CBR - several cancers have been proven to be caused by viruses HCV, EBV, HPV, HBV, HIV, etc etc surely more effort should be directed toward tackling the cause rather than managing the ultimate disease state. I will back any company that is pioneering in these two fields but especially Hemo for reasons I have mentioned previously!

The details of the parent company are already visible to potential investors through the attendees list from the event organisers. I think it is more an attempt of branding what would represent a whole new class of drug to the industry - a bite sized concept that is memorable and understandable from its title

You are of course right one-one. I should have put IMO at the end of my post. Am i qualified to comment? : I think probably slightly more than most having spent 25 years in related fields - protein biochemistry, molecular biology, pharmaceutical development and regulatory affairs for biologic drug development. But there are always those who will have greater insight I am keen to learn and debate.

Short answer if they can edit epitopes on CD45 using crispr then they can edit epitopes on FLT3 (but why would they want to if CD45 is expressed in all blood cancers) - Long answer is that this will take years/ decades to come into clinical use as it is essentially gene editing - Think there will be many CAR-T's/ other therapies approved before this is used in a patient

It hasn't "failed" Pumpky - They have asked for additional work to be completed on the lentiviral vector.... Yawn

To add to that - Wuxi is easily one of the most impressive CMO's I have worked with both in terms of the caliber of scientists and the technology they poses they are truly world class and have a work ethic to match. I have worked with several CMO's across the world including UK, EU, US, and Wuxi is out front by a country mile IMO.

Predicted or knew about the placing?

I am confident that Wuxi will sort this out all of my interactions with them have been excellent but agree it will take some time. It can take a month or so just to clear Chinese customs for delivery of samples etc. Then presumably hemo would need to perform additional batches with the modified lentiviral vector for inclusion into the IND. All in all my take is that this is resolvable but may take a few months to resubmit the IND for Hemo-CART.

Seriously - Reproductive/developmental toxicity >>?? What is the average age of a patient with AML?

Interesting reading about the companies listed in the disclosures section relevant to the 2021 ASH presentation : Novartis, interius therapeutics and carisma therapeutics : Interius involved in next generation cellular manipulation (in-invivo) based on the inventions of Dr Saar Gill and carisma developing CAR-Macrophages - and Novartis doesn't need an introduction.

Normally you file the IND - then either you will get a list of questions within the 30days (or not) which your must satisfactorily address following that you will get a "study may proceed" letter or Clinical Hold letter. Normally with a clinical hold letter there are multiple opportunities to address the FDA's initial concern which leads to the study may proceed letter being issued or the issues are insurmountable and the clinical hold letter remains in place - I have never seen the latter.