Member Info for Haywain

I agree HFH -but I am almost sick of saying it : just waiting patiently on the sidelines!

Yes - that is monumental should it happen

I don't know where to start - Maybe here : anything I post on this bulletin board is out of a genuine interest in the science behind Hemo's CAR-T (except from a single post where I referred to certain posters as F'wits). Am I invested in the company - YES do I believe that based on the evidence presented that Hemo CAR-T has a really good chance of being effective in the treatment of FLT3 + r/r AML - Yes I do and I have explained why I think that. Am i excited to see the clinical data - Yes I am see above- Boom I suggest you read through what I have posted again and if there is anything that you don't understand in there I will be happy to explain, again.

Unpick away - tell me where I am wrong Boom

Well it certainly hasn't been a cure for my bank balance - I can tell you that much! But i have faith in the science for reasons that I have previously explained and the science is being proven up as we speak (you can't un-inject a patient). There are some on here that would rather kill the company before it has the chance to prove the science which I find extremely sad.

Do you mean CRS? Thought their lead candidate was a suppressor of MAP kinase ? : it is kind of interesting as if proven in clinic I would see that as an adjunct therapy to many disorders that cause hyperinflamatory reactions as a potential immune response modulator

That’s the whole point Boom - people don’t challenge with reasoned and researched opinions and they are more than welcome to do so. All the information is in the public domain so anyone can validate or disprove what I have said and are welcomed to do so as is the nature of debate. Instead they try to attack and discredit the person rather than engaging the debate - I wonder why?

Sorry I missed the second part - do I think it would cause concerns for the trial moving forward? There are differing grades of CRS and ICANs most of which are treatable in the clinic but these conditions can also be fatal so I would think that so long as the condition is recognised and treated and isn't above level III (I think from memory) then it should not stop the progression of the trial. There will be patient specific factors as well and differences between patients in terms of burden of disease and just because it hasn't happened in the first patient it doesn't rule it out for the next but all in all we are in a good spot with zero AE's reported following week 3 post infusion in patient 1.

Openthebox - sorry to hear that you have experienced this first hand. In short yes there is a strong relationship between level of residual disease and the probability of experiencing ICAN's/CRS when the AML birden is high, CAR-T cells encounter and engage more cells causing a massive release of inflammatory cytokines (IL-6, IFN-g, TNF-a etc) which drive the CRS and contribute to neurotoxicity.

Blastoid - almost universally ICAN's and CRS happen early in the treatment cycle and are immune mediated. Previous CAR-T's used GEN1/GEN2 CAR design that had single stimulatory domains which lead to rapid t-cell expansion and can cause a immune reaction that if not spotted and treated can lead to severe neurological inflammation (ICANS) or through a different mechanism cytokine storm reactions. both of the above conditions appear to be related to the expansion phase of CAR-T which happens within 14 days of infusion - Hemogenyx use GEN3 CAR design which has co-stimulatory domains and tends to have a more controlled T-cell expansion which reduces the prevalence and severity of the above conditions. Put it this way if the above were an issue in patient 1 we would already know as this would have to be reported to FDA and therefore would need to be RNS'ed to the market.

Money really does bring out the worst in people. Essentially so long as Hemo can keep the lights on an continue with their clinical program our investment will do fine. Somehow we are now in a place where the market cap of the company is well below the asset value of a single asset. The share price is an illusion created by the fact that Hemo have thus far relied on the market for money they now realise they can't. At some point they will not be reliant on the market to fund their clinical study and the money they receive to continue will be based on an evaluation of the asset value of CAR-T. I can give you a hint for a CAR-T in phase 1 for r/r AML the asset value ain't 6M quid. Time is on our side now as a patient has been dosed and second patient selected. All the fearmongering will come to naught and I will then say I told you so. I will leave you with a tid bit: FLTT3 is an inherently better target for r/r AML CAR-T therapy because of several key biological and clinical factors : previous CAR-T therapies have suffered from a process called antigen escape which sees a return of the condition in some patients . This is where previous CAR-T therapies for r/r AML have targeted markers on the cell surface of AML blasts that are non-essential to cell survival such as CD123 or CD33. Because these markers are not essential the AML blast can downregulate the receptor to survive. FLT3 on the other hand is an oncogene that has an essential role in AML cell survival and therefore cant be simply down regulated for AML blast survival. FLT3 is also present in the progenitor leukemic stem cells (whose malfunction are considered the root cause of AML). So from my perspective the design of Hemo CAR-T hits at the root cause of AML in a way that those that have come before do not. Can't wait for results!

Look Stu - months ago you were spouting multiple reasons why this would never get to clinical trials and why it would fail if it did well guess what all is still going well. previous treatments of AML whether CAR-T or other have failed for multiple reasons including difficult tumour microenvironment , tcell exhaustion, antigen escape, off target actions etc etc etc - all risks yes but this is why you develop new treatments and test them. I am well aware of the risks and I still think (for me) it is a risk worth taking based on stellar preclinical results - MD Anderson agree and were keen to trial Hemo CAR-T and here we are - every day that ticks past and every week is meaningful to the patient and long may it continue.

To prove efficacy yes 6M but does that mean measures of efficacy have not already been observed : No it doesn’t : as I stated many moons ago they will see a reduction of AML blasts in the peripheral blood and at day 28 they will perform bone marrow aspirate and compare burden of disease to samples taken prior to treatment which will show either a reduction in AML blasts or it won’t - but yes for absolute proof of efficacy it is 6M plus and hopefully many years later as the patient will be monitored periodically for years to come if successful.

My calculation is next Thursday - they can not start the lymphodepletion in second patient before the 28day result and it takes 4-5 days for lymphodepletion so all being well they will initiate treatment of second patient the following week

I am somehow responsible for your mental health? I was actually on a pharmaceutical manufacturing site the last few days so couldn't respond to any of this - Bad timing. As I have said what I have posted on here accurately reflect my views - I am not part of a consortium of rampers and yes my money is invested along side yours and I have never sold any shares and I have had many opportunities to do so. I for one would not be placing my mental health in the hands of others but certainly if this is affecting your mental health then you do have my sympathy.

Boom - the difference is I am who I say I am. My thoughts accurately reflect what I think and I wouldn't change anything that I have written on the science side- That is what I am qualified to talk about.

If it is any consolation to you (which I expect it might be ) I am in the same plight - I don't ignore it because I have directly referenced the reason for this plight in my response _ Science impeccable finances influenced by the likes of you -who would rather make a quick buck on the downward share performance rather than find out whether or not we have a cure for cancer., I have largely commented on the likelihood that hemogenyx may have succeeded or at least have generated something that in my opinion has a bloody good chance - we have a difference of opinion on the science ( but you are a financial man what do you know about the science?).I don't argue that the financial market ahs been very difficult for hemo but I am not in control of that whereas I suspect that you may have mor influence (or be directly involved) - that being the case do the right thing mate value life more than money- in the end it is more improtant

Oh contraire Stu - Show of hands who believes this ??? You attacked on the science (and were beaten), you attracted on the financing (may have a point???) but I rest well at night because unlike most on here that have clear financially driven agendas- I don't and I actually want to help people suffering with incurable cancer - If that makes me a bad person in your eyes I totally accept that (well done you win). By the way I have dedicated most of my life to developing drugs targeted towards the very same cancers which may be why i have a little more insight into the science behind it. My conclusion - science impeccable: finances questionable but largely influenced by ***** like you.

You particularly Peterpharma are an absolute disgrace (for reasons known to you)- I don't agree with their financial decisions but I absolutely stand up for the science behind their CAR-T and development programs. Its imperative that they are allowed to collect the clinical data that they need and that prospective patients need.

F'wits are out to poor petrol on the flames of a company trying to cure terminal cancer - really well done! hope you feel great about yourselves!