Marker Therapeutics Inc (MRKR)

[Phantom Lord]

I usually make an end of the year post and figure we are close enough so here it is. I’m going to start it off with a recap of 2023’s most important events as a lot happened that will hopefully provide a solid foundation for the company moving forward. A foundation that they seemed to have been lacking in previous years.

2023 Recap (the dates link to the PRs or SEC filings):

May 2023 - Peter Hoang “resigns” as CEO and Director. Juan Vera is appointed CEO. This move should suit the company better as Vera, being a co-founder of the company, has a vested interest to see it succeed. While Hoang came from an investment banking background, specifically mergers and acquisitions, Vera comes from a medical background and will be better suited to lead the clinical development which is where the growth will come from. I think under Hoang the company bit off a bit more than they could chew with the strong focus on manufacturing. They flew a bit too close to the sun and it didn’t quite work out.

May 2023 - Probably the biggest news of the year is the sale of the manufacturing facilities to CellReady. In addition to the ~$19M in cash from this transaction the company cut annual expenses by ~$11M. Given their relatively limited cash reserves this savings is a big deal. They believe this transaction provides them with enough cash to make it out to the end of 2025. More on this later.

May 2023 - Marker appoints Monic Stuart as Chief Medical Officer. Not the biggest news but a shake up to the management team that should be noted. I don’t know much about her but in talking to John Wilson earlier this year around the time of this announcement she was recommended by Nadia Agopyan. Not much is discussed about Agopyan but she has a solid background. I was excited when she was brought on back in 2019 and think she will be instrumental to Marker’s success going forward. For the uninitiated she came from Kite where she oversaw the global marketing authorization of Yescarta. If she thinks Stuart will make a good CMO I can get behind that. Something to watch more on this that will be an indicator of where the company stands is that Stuart was brought on in a consultant role. My understanding is that she is not the full time CMO but that will ultimately be the plan as Marker moves forward. If and when that transition happens it will be an indicator that Marker is preparing to take the next leap forward, IMO.

May 2023 - Marker reports pre-clinical data of MT-601 in lymphoma. HERE are the slides with the analysis. Up until this point we only had the BCM PI trial data to go off of and we all know that it was the most impressive of the data. What it didn’t show specifically is what this pre-clinical data does show. That MT-601 can work to control the growth of CD19 CAR resistant lymphoma cells. Obviously, this is the patient population Marker’s lymphoma trial is targeting and it is still a huge unmet need as 50% - 60% of patients treated with CD19 CAR-T relapse within the first year.

June 2023 – Marker reports MT-401 non-clinical data in AML cells after hypomethylating agent administration. HERE are the slides with the analysis. As earlier reported by the company they were not seeing the results they were looking for in the frank relapse group of the PII AML trial. I’ve said basically since the beginning that this would be the most difficult patient group to treat given the severity of their condition and the fact that by the time they get to Marker they have probably failed multiple different treatments. The addition of the hypomethylating agent shows that Marker is continuing to search for solutions to advance their therapy. Regardless, of whether it works or not in the clinic this at least shows that they aren’t just sitting back and hoping for the best. Either way, these non-clinical data do look fairly promising so it will be interesting to see how this trial moves forward. Side note, this data did get them a $2M grant from the NIH.

July 2023 - MT-401 granted Orphan Drug Designation by the Committee for Orphan Medicinal Products of the European Medicines Agency (EMA) for the treatment of patients with acute myeloid leukemia (AML). Not the flashiest of news but certainly nice to have.

August 2023 – Marker announced non-clinical data of MT-401 in an Off-the-Shelf (OTS) setting. HERE are the slides with the analysis. This is one I’ve been pretty excited about since it was announced. The biggest reason being that with an OTS product patients can be dosed in roughly three days. The standard MT-401 manufacturing time is nine days which is already many times better than the CAR-Ts which take multiple weeks to manufacture and return to the patient for dosing. Three days to dosing has the potential to do wonders for patients. Especially for the MRD+ patients who are on limited time before they experience relapse.

September 2023 – Marker announces the first patient treated with MT-601 after CAR-T relapse achieved a complete response. Multiple CRs should be expected here as the BCM PI trial showed a 40% CR rate. We all know that one patient is a meaningless data point but nonetheless it is great to see a CR. Especially if you are that one patient. I look forward to seeing more.

With the recap out of the way I’d like to touch a little on where the company stands now and what I expect from them moving forward.

Current financial position:

As of the end of Q3 2023 Marker is sitting on $17.5M of cash and cash equivalents. This is obviously not a ton of cash but as previously mentioned the company thinks it will be sufficient enough to carry them to the end of 2025. This is due to mainly their unloading of the manufacturing facilities as well as all of the manufacturing staff but also their cut down of the management team. They are running a bare bones operation strictly focusing on the clinical side of things with the expectation to get the company to important inflection points, i.e. data, before they begin to ramp up operations again. To be honest this is probably how they should have been running from the beginning. I’ve been a little skeptical that they can make their cash run to the end of 2025 but the last quarterly release showed me that they are taking the necessary steps to at the very least give it a valiant effort. Net loss for Q3 2023 was $3M. That’s down from $6.9M in Q3 2022. If they continue to run a quarterly net loss of around $3M that will take them to about the middle of 2025 with their current cash. This isn’t taking into account all of their grant funding recapped below:

August 2021 $13.1M from CPRIT to support MT-401 PII trial in AML. To date Marker has received $6.9M so have $6.2M remaining.

September 2022 $2M from FDA to support MRD+ group of MT-401 PII trial in AML. To date Marker has received $200K so have $1.8M remaining.

August 2021 $2M from NIH to support development of MT-401 in AML. This is the one granted based on the non-clinical data of MT-401 with the addition of a hypomethylating agent. To date Marker has received $0 so have $2M remaining.

So, in addition to their $17.5M in cash and cash equivalents they still have $10M in grant funding. If they use their current resources wisely, they can potentially make it to the end of 2025 with their current financial position. They will be cutting it close though. With that being said, I do fully expect to see them raise cash via a secondary offering well before then. If I had to take a guess, it will come following lymphoma data. If I am correct, I hope it comes at final data which I would expect by the end of next year pending any enrollment updates.

Clinical trials (trial names link to clinicaltrials.gov):

ARTEMIS This is the MT-401 AML PII trial. This trial was designed to be and has been presented as potentially pivotal so there is a possibility with decent results we can skip a PIII trial. MT-401 also has orphan drug designation so there should be an open dialogue with the FDA which could help their chances there. I think we see some big changes to this trial with the non-clinical data showing the increased effects of MT-401 with the addition of the hypomethylating agent. I expect this trial to head in that direction. Hopefully this change brings some results in the frank relapse group as to date the adjuvant and MRD groups have been promising but the frank relapse group has shown minimal to non-existent results. To reiterate what I said earlier the frank relapse group was always going to be a tough nut to crack. The patients in the BCM PI trial failed anywhere between 4 and 10 prior lines of treatment. They are in rough shape so even if the frank relapse group can achieve minimal results, with MT-401’s safety profile, I believe it will be enough to move it forward. We will also see the addition of the OTS therapy in 2024. Not sure if it will be an added arm to the ARTEMIS trial or a completely separate trial but we’ll find out soon enough.

Recap of all AML data we know about is below:

PI - 8 active patients treated, 1PR & 1CR (The PR patient saw enough of a reduction to allow a second cell transplant). 17 adjuvant enrollees treated. I believe 15 patients with two re-enrolling if I read it correctly. 6 relapsed at a median of 9.5 months and 11 patients experienced no relapse. Of the 6 who relapsed 1 was re-enrolled into the adjuvant arm and achieved CR which remained durable and 1 was moved to the active arm and became the 1 CR from the active group referenced above. As of the posting of the results in the American Society of Hematology Blood Journal (HERE) 11 of 15 patients remained alive at a median follow up of 1.9 years post infusion which compares favorably to with HCT outcomes for risk-matched AML/MDS patients post-HCT.

PII: 11 frank relapse patients treated, 0CR. 4 MRD+ patients treated, 2 CR MRD-. 1 remained in stable disease for six months allowing for a second transplant and the final one had MRD reduced by 70% four weeks post infusion and was still being monitored as of March 2023. Also as of March 2023 11 patients have been enrolled into the adjuvant arm but are too early for evaluation.

APOLLO This is the lymphoma PI of MT-601 in patients who have failed or are ineligible to receive anti-CD19 CAR T cell treatment. This is also the trial I believe will be the biggest driver of company growth and share price appreciation. Most of the HUGE volume days have been after lymphoma news so I expect that to continue. Not a lot of info on this one as of yet but I expect final data, depending on enrollment, end of next year and early 2025 at the latest. The BCM PI included patients with both Hodgkin and non-Hodgkin lymphomas in both active and adjuvant settings. The APOLLO trial will specifically focus on relapse/refractory (r/r) non-Hodgkin lymphoma (NHL) and I believe only in an active setting.

Recap of all active r/r NHL data we know about is below:

BCM PI - 8 patients treated, 4 CR. Of the 4 patients treated that did not achieve CR 2 of them saw progressive disease and 2 of them moved onto other therapies while in stable disease. 3 of the 4 CRs were achieved after a length of time in stable disease longer than these 2 patients experienced prior to starting another line of therapy. If they had stayed in the trial, it’s possible they could have seen CR at some point. This data recap comes from the American Society of Clinical Oncology (ASCO) Journal of Clinical Oncology HERE.

APOLLO PI - ? patients enrolled and treated but will be enrolling an estimated 37 patients. 1 CR achieved 8 weeks after second infusion. No adverse events.

Pancreatic This links to the BCM TACTOPS trial. No Marker sponsored trial has begun but the IND has been cleared to begin a pancreatic trial with MT-601. PR https://ir.markertherapeutics.com/news-releases/news-release-details/marker-therapeutics-announces-fda-clearance-ind-mt-601-its-six " rel="nofollow" target="_blank" >HERE. The BCM data is minimal so I expect them to run another PI to get additional data and then advance this to PII with a partner. No timeline expectation on this. I have just always thought this would be the best trial to bring on a partner if they were interested in doing so. This is just my opinion as I believe a PII will be large and probably fairly expensive. This trial will be lottery ticket for the company. With that thought it is great to see them taking a conservative approach to it in that they are waiting to advance it pending non-dilutive grant funding. I would not be surprised to hear nothing on this trial until lymphoma advances into PII.

Recap of all active pancreatic data we know about is below:

13 patients treated, 4 ORs. 1 CR & 3PR. The CR was observed well after a CR would have been seen from chemo alone. 6 patients with stable disease, 2 of which saw reversal of tumor growth. 9 of the 13 patients exceeded historical control of overall survival. FWIW, the CR in this trial was achieved at a time well beyond where one would expect to see a CR from chemo alone.



What we have to look forward to:

DATA!!! It’s fairly clear to me that Vera has a focus on getting these trials progressing so that we can see data before needing additional cash. As such, based on previous information we were given and where the trials are currently standing, I expect plenty of data next year. Additional lymphoma data is set to be released in the first half of 2024 and as I’ve alluded to, depending on enrollment, I believe we could have the final data by years end. If not, then very early 2025. If they get or have already gotten the updates to the AML trial approved, then we should have more MRD data which I have always been excited for even though I seem to be the only one. I’ll either be a genius in holding my expectations or a dumbass but either way I think turning MRD+ patients MRD- will be a big deal. We could also be getting frank relapse data with the addition of the hypomethylating agent. Non-clinical data looked promising so if they can translate that into clinical success it should also provide a nice boost given how hard AML is to treat. Since we are looking primarily for CRs they will either happen or they won’t. Data should come relatively quick. It would be nice to get an update on the adjuvant enrollment numbers. As of March, this year it was 11 patients enrolled. Since those patients need to be dosed and then monitored for at least 12 months it is possible we see some adjuvant data by the end of 2024. This group was always going to take a bit so I won’t be surprised if we don’t though.

We also have the clinical review that was effectively promised for this year that seems will be delayed into next year. I’m giving Vera a pass on this as he is a new CEO and there have been a lot of advancements already under his watch. I don’t believe it was ever said in an official release and only alluded to in interviews. This should be a learning experience for him to be a little more careful about how he is conveying things. I did follow up with him on this a couple of times and accept his explanation. That being, with the changes they are making to the trials, specifically the AML trial, they need to make sure that all entities with any stake in them are aware of and approve of the changes being made. The AML trial has grants attached to it from three different entities so they need to ensure those entities are ok with the changes as to not put in danger the remaining grant funds. Additionally, trial changes need to be discussed and approved by the FDA. I think we all know how fast the FDA moves. Until all of these things are in place they can’t just go telling everyone about all the changes they are making. With this being said I expect the clinical review to come sooner rather than later next year. I’m looking at two timeframes. The J.P. Morgan Healthcare Conference is January 8th – 11th next year. It’s the first big investment conference of the year and as they put it “connects global industry leaders, emerging fast-growth companies, innovative technology creators and members of the investment community.” If they are looking to make a splash early in the year then this is the place to do it. If not there then I would expect it to come during their annual release with is usually toward the end of March each year. I would hope this would come with a conference call and then hope those would continue on a regular basis. I did bring this up with the company and it is something I was told they are looking into bringing back.

Well, I think that’s it. Some good progress was made this year and they have some potentially major inflection points coming up next year. I will be looking to see if these bring the growth I expect them to as well as can that growth be sustained.

As always, I try my best to post factual and verifiable information with links if possible. Anything else is obviously my opinion and should be taken as such. It is always advisable to do your own DD.

Good luck out there everyone.