Member Info for Haywain

That is why it is a requirement to perform visual inspection at release and test for visible and sub-visible particles per the unitied states pharmacopoeia. Its a difficult thing to control because unfortunately typically the particles come in with pre-Sterilised container closures or in this case with the cryobags. The problem being that they are supplied pre-sterilised usually through gamma irradiatiated in bags - The solution would be to pre-inpsect the bags but you cant without breaking the sterility assurance - typically that means sacrificing a lots of cryobags for inspection within a given batch. But that doesnt guarantee that you will not have visible particles at release because of unequal distribution of bags effected by particulate matter throughout the lot. So stringent is this requirement that every particle that is detected at batch release has to be identified added to a library and the library monitored for changes to the profile of visible particles. Its a very difficult problem to solve but it has nothing to do with CAR-T the problem lies with the container closure manufacturers.

Hemotruth - Particulate matter is a very common issue and not specific to CAR-T all sterile products are subject to the same issue.

I of course forgot to mention the very many applications that CBR could have for oncology targets which we are just starting to hear about. Again because this is being developed as a mRNA construct it removes a lot of the issues that you have with developing biotherapeutic proteins. It would effectively be a pro-drug using the body's own cellular machinery to create the CBR. This is important from a post-translational modification point of view and would significantly reduce the risks around immunogenicity that are common for therapeutic antibodies for example. I would be keen to hear more about the potential oncological uses of CBR as would most big pharma I imagine.

That is the thing I cant predict Mr I - If the animal studies are successful then I would imagine Hemo will be talking to lots of interested parties. The real value proposition though is always when you have human clincial data which will be expensive. I would think that Hemo will have to be selective around what virus they would target initially. If they do want to keep this in-house then I would see using the sale of CAR-T as seed funding as I think some have mentioned here. Hemo are in their infancy they have a long way to go if they ever did want to develop a product to licencure

Because of the nature of how CBR works it is a platform to develop CBR's against groups of viruses that use the same method of cellular entry- For example I imagine individual CBR's for the following:

ACE2 (Angiotensin-Converting Enzyme 2): Used by SARS-CoV-2 (the virus causing COVID-19) and SARS-CoV for entry into cells.

CD4: The primary receptor for HIV-1 and HIV-2, along with co-receptors CCR5 or CXCR4.

CCR5 and CXCR4: Co-receptors for HIV entry into cells.

Sialic Acid Receptors: Used by Influenza viruses for attachment to host cells.

ICAM-1 (Intercellular Adhesion Molecule 1): A receptor for major group rhinoviruses.

LDL Receptor (Low-Density Lipoprotein Receptor): Used by some viruses, such as Hepatitis C Virus (HCV), for entry

Nectin-1 and HVEM (Herpesvirus Entry Mediator): Used by Herpes Simplex Virus 1 and 2 for entry.

CD46: Used by certain strains of measles virus and adenoviruses.

Aminopeptidase N (APN): Receptor for some Coronaviruses.

DPP4 (Dipeptidyl Peptidase-4): Used by MERS-CoV (Middle East Respiratory Syndrome Coronavirus).

Nicotinic Acetylcholine Receptor: Used by Rabies virus.

Heparan Sulfate: Utilized by various viruses, including Human Papillomavirus (HPV) and certain adeno-associated viruses, as an initial attachment point.

Transferrin Receptor: Used by some strains of New World hemorrhagic fever arenaviruses.

Ephrin Receptors: Utilized by Nipah and Hendra viruses.

TfR1 (Transferrin Receptor 1): Used by certain strains of New World arenaviruses.

CAR (Coxsackie and Adenovirus Receptor): Used by Coxsackie B viruses and some adenoviruses.

ASGP-R (Asialoglycoprotein Receptor): Used by Hepatitis A Virus.

PVRL4 (Poliovirus Receptor-Related 4): Used by certain strains of Enteroviruses.

Glycosaminoglycans: Served as initial attachment sites for several viruses, including Herpes Simplex Virus.

TIM-1 (T-cell Immunoglobulin and Mucin-domain containing-1): Used by Hepatitis A Virus and Zika Virus.

Therefore it would only take one company to have an interest in developing one of these (or others not listed here) as a therapeutic to provide the funding for HEMO to be developing new CBR's - The DARPA governmental link could be a method of garnering governmental funds to develop anti-biological warfare based CBR's. If the model can be proven for any individual group of viruses that used the same cellular entry then I think there is a very good chance that it could work for all.

Yes - CDX is a bi-specific antibody for bone marrow conditioning, CBR - Chimeric Bait receptor : has applications as both an antiviral treatment and to target cancers - The antiviral treatment uses the protein that viruses bind to to gain cellular entry as a bait combined with a immune system engager ie will inform elements of the immune system to process viral information if it binds the bait. CBR will be an mRNA based product (which is the precursor to protein) so in a sense it is an instrcution to cells to make the CBR protein. It potentially has multiple applications across many different types of cancer and all viruses. CAR-T is chimerica antigen receptor -Tcell: which is a t-cell that is removed from the patients body by collection of plasma - programmed to express the antiFLT3 receptor binding domain through transfection of a lentiviral vector - those cells are then delivered back to the patient for treatment.

Yes please pumpky lets see!!!

This would certainly be groundbreaking if Hemo can pull this off. The best bit for me is that CBR is now an mRNA construct that means rapid development timelines that can be adapted to optimise for any oncology target. If the right mRNA construct can be found for a particular tumor type it is a straight forward manufacturing process with a very stable product more akin to a small molecule. CBR is a platform to potentially develop treatments to all viruses and is sounding like many forms of cancer. Mind boggling potential.

Well with 20,000 newly diagnosed AML patients in the US per annum and with Cohen Van Besien running the clinical study I would think the recruitment to the trial would be good. It does depend on what inclusion /exclusion criteria have been agreed by FDA and how many centres the trails will be recruiting from but Van Beisien is a part of the Weill Cornell haematology oncology centre and head of the wesley centre for haematology - (https://www.uhhospitals.org/for-clinicians/articles-and-news/articles/2022/05/new-hematology-chief-and-director-of-the-wesley-center-for-immunotherapy-named-for-uh-seidman) so I imagine if any AML clinical study can have good recruitment rates this is up there. Remember as well number of patients before first clinical interim readout could be as few as 10-20 patients

Hello Mr India, It isn't really a scientific view to make projections around timings but I would imagine that the PQ run is well underway - they will have to do some testing as well some of which (i imagine) would be external contract labs. So within the next few weeks we could have the "complete response" to FDA's concern. I am not really bothered about the timeline as I have said previously. With regard to whether or not Vlad will raise prior to the IND approval - only he can answer that but again the last raise was at 6p with prevail it makes sense that any raise would be conducted after IND approval in my opinion anything before that would be at a much lower price. With Hemo being a clinical company prevail could shortly see a return on their 6p investment and Hemo could raise at a much higher share price. Per the RNS lentiviral splicing during the manufacturing process was the only reason that FDA put the IND on clinical hold: that is now not an issue therefore once the PQ run is complete, tested, written up, response submitted there is no reason for the IND not to be approved. The timing of that could be anywhere from 1st Dec -30th Jan depending on the current unknowns. To guarantee this happening before the end of the year Hemo have a week to submit the IND but again they could submit later and FDA respond in a week so it is very hard to predict.

Good news re lentivirus splicing issues resolution: all moving in the right direction. I did think they would have to repeat the PQ x3 so really good to hear that FDA agreed to a single batch re-run with new lentivirus - that is twice in a day that FDA have surprised me with good news :)

JHFH -that is exactly what I think will happen too. I think that because of the mouse model (chimeric mouse with human immune system) that was developed in the pre-clinical stage we have as good as a projection of what may happen in the clinic as is possible so I am as certain as I could be at this stage that Hemo CAR-T will work. I imagine it will form the cash cow for the future CBR, CDX & huPhec development. Ironically exactly what one-one was mocking in every post with his mouse pictures - The mouse will have the last laugh IMO.

No I cant either dingo

Mickey - go and find another pharma company that has a CAR-T in oncology in any state of clinical development that is worth less than 100million M-CAP

One2one - You are referring to 9 approval decisions across multiple unrelated indications that have completed phase 3 clinical studies - We are trying to get an IND over the line - again fail to see the relevance.

Well - we are in the window for possible RNS according to Vlads RNS he would have 24 days to make the IND amendment submission to get the go ahead before the new year - this is information that I would think should be RNS'd. All I was saying is that I work in this space and even the best laid plans come up against unforeseen issues which delay the timeline. The important thing here is that Hemo become a clinical company not so much the timeline of when that happens give or take a few weeks.

I said at the time it looked like sterility/mycoplasma testing ie absence of growth is a positive result but I don't know why the plates would be in a 2-4oC incubator so I am not sure. It could be some aspect of testing the lentivirus but I would imagine that Wuxi would be doing the lentiviral testing prior to releasing it to Hemo. Or it could be testing of the CAR-T absence of aberrant protein if there was some issue with the lentiviral vector that effected the CAR protein expression.

Hi Mr India, I don't think the RNS said that FDA have given the nod for the CH to be lifted - Hemo said that they received a concern relating to the vector = they have presented to FDA how they would address those concerns and FDA have agreed that the approach proposed was satisfactory. So the steps to getting a study may proceed letter would be to make the changes to the lentiviral vector design, manufacture new lentiviral vector, demonstrate through testing that you have manufactured what you intended to manufacture. It might be enough to do the testing on the lentiviral vector itself depending on what the deficiency was or they could have to repeat the PQ batches for CAR-T with the new lentiviral vector, Test the batches and update the IND with all of the new information, Submit to FDA - 30day review as an IND update and they may get a decision within that window that the clinical study may proceed.

It seems that way unfortunately - I will desist : as a shareholder sometimes I flick through the posts here and find them frustrating at best. I can cope with misleading comments through ignorance but if it is as you say and it is deliberate I find that wholly unacceptable.

The reason you haven't had a response is because I have a life One2one that sometimes gets in the way- I would of course liked to address your post from earlier within minutes of you posting but I have been busy working on a BLA license application. I don't consider myself an expert in CAR-T (I have never said that I am) I am however a scientist and I am familiar which biopharmaceutical manufacturing and the regulatory process from pre-clinical to licensed biologic. When I see misleading posts if I have time I call it out. Let me just address a few of the points you made: the splicing of the lentiviral vector is relevant to the vector design and the Vector manufacturing process. Following the resolution of the splicing issues the vector essentially becomes a critical reagent in the CAR-T manufacturing process to be supplied from Wuxi to Hemo for the creation of CAR-T using Hemo's manufacturing process. I dont know where you are going with the rotting vegetation and the shipping of patient samples from Hemo to Wuxi and back and the length of time of the process etc etc. Hemo will be performing the transfection/transduction of patients t-cells so presumably a single thaw of the patient sample before expansion and testing. FDA's primary focus for phase 1 is safety - I could not decipher any reasonable argument in your post that implicates a safety concern other than those that have already been highlighted - Trust me as a shareholder here that is something I would want to know.