Member Info for Haywain

Any positive news or interest in Hemo is a welcome change from the relentless , agenda-driven negativity and financially motivated pessimism we've had to endure over the past few years. It would be refreshing to see a sustained shift in focus towards the potential and progress of the company, rather than being bogged down by the constant stream of doubt.

Let us deal with the primary first before we worry about the secondary

Just not a lot to talk about until trials are under way- it’s all been said before at this point - my views haven’t changed just patiently waiting.

I imagine they are some way off the IND for CBR - they have to sort out manufacturing, GMP runs, non-clinical work etc etc which costs both in time and money that is why it is all about CAR-T at the moment. That is unless non-dilutive funding can be found to progress CBR or early partnerships found based on the work they have already conducted which is why I imagine Vlad is doing the circuit. On the plus side there are so many potential avenues to explore with CBR it is a very wide pool of potential investors/collaborators.

I had a chance to read the article - which references earlier attempts to treat AML with CAR-T therapies which were often targeted to CD33, CD123 and FLT3 all of which are also expressed in healthy myeloid cells. Due to the poor specificity of the CAR antibody component of these earlier attempts it led to off-target effects and myeloid toxicity. Hemo-CAR-T targets a novel antigen that is uniquely expressed on AML cells and not on normal myeloid cells. Therefore the specificty or HEMO CAR-T significantly reduces the risk of off-target effects. By specifically targeting malignant cells Hemo Car-T can more effectively target and destroy AML cells without damaging normal tissue. The MDPI examples of previous CAR-T therapies also utilized first or second -generation CAR contstructs which included basic signalling domains and lacked enhanced co-stimulatory signals necessary for robust T-cell activation. Hemo-CAR-T on the other hand employs an advanced CAR design -incorporating potent co-stimulatory domains. Hemo Car-T is third generation with enhanced activation, proliferation and longevity of the CAR-T cells within the patient ie greater specificty and greater efficacy. It also employs strategies to counteract the tumor micro environment (TME) which allows it to modulate the TME making it more conducive to an anti-tumour response. The design of some of the previous clinical protocols from the earlier studies introduced heterogenous patient populations with varying disease states making it difficult to assess efficacy whereas Hemo's inclusion criteria are specific to patients with different subtypes of AML known to express the target antigen FLT3. So whilst all of the points made in the article are valid concerns we are not comparing apples with apples here for the reasons mentioned above.

It’s a rare disease affecting bone marrow where the bone marrow doesn’t produce enough RBC’s - Ultimate treatment is bone marrow/stem cell transplant

Think it might be a CDX related : bone marrow conditioning prior to bone marrow transplant to treat the aplastic anaemia: OR it’s a mistake in the report not familiar with the authors and these sort of report vary widely in quality

Could be related to the microsoft outage

The difference is that signing a deal doesn't require a road show and speaking to Peterhouse like a placing does. With any luck the city boys wont know that a deal has been signed until it is RNS'd.

Happy for them because if a deal is unexpectedly penned (even at this stage) they will lose their shirts. I wouldn't take the risk but they must feel comfortable enough in their position if the short is still open.

If they have to amend the protocol then that does need FDA approval - once submitted the approval time line for the IND update is 30 days - but can extend out depending on complexity of the amendment and depending on the FDA queries being addressed quickly.

Well Stu - you won't know unless you read the clinical protocol. My guess is though that this would have been considered relatively early on. If you are targeting FLT-3 you would be interested in all malignancies that overexpress FLT3. It is quite common in oncology phase 1 and 2 for basket trials to be conducted based on biomarker detection in patients. This sort of trial relies on the biomarker being present for patient inclusion to the study and does not ask what type of cancer the patient has. This is the path that I imagine Hemo would have pursued.

Short answer is that it depends what the inclusion criteria are for the clinical trial -for Phase 1 trials that are testing the safety of an anti-FLT3 CAR-T I would imagine that the inclusion would be written in somewhat of an indication agnostic manner using a biomarker-driven approach- Ie must have cancer with elevated FLT3 expression - In which case there would be no need to go back to FDA - If not there are a few hoops to jump through minimum 4 months from decision to add indication. I dont know for sure that the new site brought in all of the new indications but Vlad had paid lip service to this previously quite a while before the news of the additional site - ("rrAML + potentially a small subsets of other cancers "- the specific subset were not named). Additionally the second site approached Hemo not the other way around and did so having reviewed Hemo's pre-clinical data. The second site coming aboard is further validation of the science and the data that they have seen.

Yes because the additional indications came from site 2 ie Child AML, Subset of ALL and BPDCN

I didn't know that JohninGsy sorry to hear of your condition and glad to hear that it has been successfully managed. Hindsight is indeed a wonderful thing ! I believe Vlad's father suffered with AML hence his focus on the condition.

Broadly similar but RRFL is actually a form of non-hodgkins lymphoma and is slow growing and can be managed for many years - Believe it has a B-Cell lineage. RR AML on the other hand is aggressive involves the rapid proliferation of myeloid cells which crowd out the ability of bone marrow to produce red blood cells it therefore requires rapid treatment : If anything there would be a greater regulatory motivation to grant as much help as they can to developers of new treatments in the RR-AML space.

Marco - MD Anderson is a possibility - . Something I missed from yesterdays RNS was the possible use of CBR for epithelial ovarian cancer. It is the most common type of ovarian cancer with an incidence level of >19K per annum in the US. It is also the most deadly of gynecologic malignancies with >12K deaths per year. It would be a huge deal were there to be any signs that CBR may have benefit in this indication.

Well, I think a lot of what is in the RNS today we already knew. The fact that they are working on the inclusion of paediatric AML is kind of neither here nor there - Incidence is circa 600 patients per year: very rare compared to AML in adults but on the positive side, the new "prestigious US medical center" can obviously see the potential benefit for the treatment of paediatric AML and therefore must have access to this patient population: There are only two east coast medical centers that I think would fit the description Memorial Sloan Kettering Cancer Center (New York) or Dana-Farber Cancer Institute (Boston) - The mention of ALL is interesting as I think the current treatments are largely effective (circa 90% survival at 5 year post treatment) so I am wondering is it a sub population of ALL? The announcement around the CDX antibody is also interesting as I was thinking that the outcome of the CAR-T phase 1 clinical study would add significant value to the bispecific antibody as has the same molecular target (FLT3) as the car-T so it makes me wonder whether they are in talks with anyone about this and how much is contingent on the results of the phase 1 car-t study? I am finding the CBR development a little frustrating as I think that they should have some sort of indication by now of in-vivo activity against certain viruses as it must be pushing a year since they were working with certain government labs to test their CBR's. The development of CBR for the treatment of brain cancer through microglial cells brings new significance to me with yet another friend being diagnosed with glioblastoma. All in all I thought that todays update was a bit strange - more of a holding pattern but it does show how many programs are still alive and kicking and that positive developments on any of these fronts would have a significant impact to the share price.

Yep unfortunately no news = plethora of sad sacks spreading woe..

You could be right - although nothing mentioned about matched funding in the following guide to BARDA grant applications - Looks like a straight forward grant if approved? https://www.excedr.com/blog/barda-funding-guide