Hi all,I guess all the blokes still discuss IMM here are the...

Hi all,
I guess all the blokes still discuss IMM here are the ones still put hope in this pipeline and we just do not live easy these days with all the data going so great and yet price dripping down day after day.
I did a full retro review into IMM's history and post my thoughts here.
Let's be fair on management on talking the 'deal'. I can't say this team is super efficient on take things down, but they are not bad either.
If we look back to the history of IMM's trials, there was a very big bump in AIPAC in 2020. I think that was the main reason we come to this disappointed situation.
Back in 2018, followed the great announcement of nobel prize in immuotherapy using PD1/PD-L1 as target(s), Prof. Lieping Chen in Yale commented that PD1 pathway may not address the whole checkpoint oncology therapy issues. Instead, he did pointed LAG3 maybe the viable target for next one as a checkpoint target. It was around that time, Immutep's pipelines came into my research. I started the first bought in this company based on their phase 1 study on metastatic breast cancer (https://clinicaltrials.gov/ct2/show/study/NCT00349934).
The full paper of that ph1 study can be downloaded here
https://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-8-71

That phase1 study was a total of 30 patients trial (33 recruited with 3 dropped out because of safty issue. so less than 10%, very good), again, not those small number phase1. They did aim big and tried to make it through quickly.
Back then, the study design was to have both chemo and efti treatment together for 6months and then looked for safty and efficacy.


The main efficacy readout to me was really impressive. By what they reported, only 3 patients (yellow) progressed at 6months mark. With a historical chemo alone cohort, 50% would have progressed and only 25% patial responsed (red) by 6months.

So in 2018, based on this 2010 paper, and their timely announced Merck partnership in TACTI002, I bought in Immutep for the first time, only a small pack though (remember was like 100K share before consolidation).

Then things came to a critical point with this AIPAC trial in early 2020, of which that big drop event everyone of us knew.
The team jumped straight into phase 2B from phase 1 in this AIPAC, with 227 patients.
This AIPAC was a registrational relevant one if back then the primary endpoint reached.
Also, as we know that the trial design was to have chemo treated only for the first 6month and efit coninuned till progress. I think the team was very ambitious. They aimed to have EFTI to be eligible for mono-therapy with that design. And that make sense, at that time (the starting of AIPAC was 2015), PD1 treatment was not approved for this type of cancer and so there was not a PD1 option for them to combine for a large cohort trial.
Also noted here, the phase 1 study started 2006 and completed 2010; though, the phase 2B did not start untill 2015. We can see how hard it was for a small start-up biotech jumped straight into a registrational trial. Prof. Tribel even paid his own money for a lot of things to make this happen.

So March 2020, it was the first real data readout for AIPAC study and we all know that the progress free survival did not come significant.

However, what they saw was that the two lines did separate in the first 6months and then suddenly closed up after, just too perfectly matching the stop of chemo treatment at 6months.
Consistantly in the final OS we saw later on in 2021, there was a close up period for that two lines after 6months upto 12 months (for survival events, there would be a delay compared to progress free, as they progressed but not immediately pass away)

If we pretent the team chose the path that they had chemo treatment all the way with EFTI till progress and we see the PFS lines separated in 2020, then see something like this,

That kind of separation would make Immutep just looking like BMS, in 2020, EFTI was validated and FDA would drop after the data announcement in late 2021.
For this one, I think I can't blame the management of choosing this particular type of design (EMA preferred design i think?). There might be political reason, they might have their big ambitous to tackle mono-treatment, they have good will in human health of trying reduce nasty chemo.......
During all those time, I am sure there were talks and offers along, we just could not see it. The management must have done things and all the scientists have done their best to maximise EFTI's potential. Anyway, the bottom line is that with things in 2021/2022, more PD1 treatments and better targeting chemo solutions available, the AIPAC results with some subgroups significance, are less likely to get approval granted.
Again, this is more science related, management could not have changed mcuh of that.

IMO, that event in March 2020 was a very big determining factor to make IMM so drible today. All the big guys know that a) EFTI is deemed most likely not mono therapy possible (as a matter of fact, mono therapy is not even preferred these days, as no a single agent could do all the job); b) IMM is going to need time to come to such a registrational relevant point, as we all see later on, we passed through TACTI-Mel and this one directed the TACTI002 and 003 to move forward; c) IMM is gonna need loads of money to make things happen, other words multiple CR.

For all these reason, between 2020 and 2022 Immutep is almost 90% relaying on TACTI002 in terms of new development (insight study is a relatively small number trial). Such profile makes this company so easy to get played up. All the pump and dump during 2021 and 2022 were so nicely timed bacause this is a single pipe. It is very easy to predict the event and also easy to foresee potential outcome of the next stage. And importantly, TACTI002 is far from reaching the registrational relevant point. The institution holders, they have large amount of shares on hand (potentially lending to Hedge fund for playing short), they have sufficient fund, then why not? With all these P/D activities, they earned a lot.

As we are into 2023, another critical point is approching for Immutep. This TACTI003 is again registrational possible. With the ph2, the HNNSC cohort was 36 patients (not a small number ph2) and the efficacy of that is trippling of the efficacy of Keytruda mono. In TACTI003, the 154 patients cohort is about 4.3 times bigger than 36 pts. To me, the statistical chance we can see the maintain of efficacy is very good (did a mock run of modelling previous data from Merck's ph2 comparison with ph3, all looking very good with this 4.3 times enlarge in cohort size).

The interim readout for TACTI003 in the 1H of 2023 is more of a deadline for the big pharma. They gonna have to come up with something by then.
Before that, the OS readout for TACTI002 1st line NSCLC (survival data for this line has not been reported yet) (somewhere mid year?) is same critically important, if not more.
TACTI002 1st line NSCLC is a 114 patients cohort, a very large number for a ph2 trial, big enough for triggering the 'deal' if comes real good.
Considering the conference achievements, FDA fast track, this is best of the best so far for an aussie biotech.
As a matter of fact, the daily trade volume in Immutep these days keeps decreasing.

Took a look of the volume in weekly basis,

even with the couple pump and dump last year, the size was no where comparable as before. As for the whole month of Feb 2023, the trade volume is only 24mil and only 13.7mil for Jan.

So that means even for the guys who can play up retails, the P/D they did last year, the timing or risk accessing was much harder than before. With multiple catalyst events on the horizon and no a particular time is given, the play has to shrink down.
on the other hand, as the buy up activities is not there, just like today, even with only 258k share volume, the price was pushed down.
With these kind of things, I have been keeping my truck loaded up lately.

All in all, i hope or i think the darkest time of play up is close to the end. We shall see the light by the end of tunel.

Just all my opinion only.