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Topline Abstract
Carisma Therapeutics (NASDAQ:CARM), previously Sesen Bio, is a developmental biotech exploring the potential of cell therapies for most cancers administration. They hope that by exploiting immune cells referred to as macrophages that they’ll proceed to push the sphere of cell therapies ahead. However money considerations and restricted scientific trial information make this one thing tough to suggest right now. For the risk-tolerant amongst you, although, the low valuation does sign room for a catalyst to maneuver the needle. It is simply unclear what that catalyst may be within the close to time period.
Pipeline Overview
CT-0508
The principle undertaking being developed by CARM right now is CT-0508, a cell product consisting of the affected person’s macrophages (versus T cells used within the at the moment accredited cell remedy approaches) expressing a chimeric antigen receptor [CAR] in opposition to HER2, which is a massively necessary goal in stable tumor oncology.
This remedy is at the moment in part 1 scientific research in sufferers with superior, HER2-overexpressing stable tumors. The most recent replace was offered again in September, which included 14 sufferers who obtained CT-0508 both as a multi-day infusion or as a single-day bolus infusion. No dose-limiting toxicities have been recognized so far, with no high-grade toxicities classically related to CAR-based therapies, like cytokine launch syndrome or neurotoxicity.
Out of the 14 sufferers, 28.6% skilled illness stabilization. No goal responses had been noticed.
A 3rd cohort of sufferers receiving extra pembrolizumab has but to be reported on. The bolus group and mixture group proceed to enroll sufferers. There was no phrase on when to count on the subsequent information replace for CT-0508, however it will be affordable to count on one other readout at ASCO in June.
Different notable preclinical developments
CARM additionally has a noteworthy collaboration with Moderna, searching for to make use of mRNA delivered by way of lipid nanoparticles to make their CAR macrophages. Just a few weeks in the past, CARM introduced that they’ve nominated a lead candidate to endure additional IND-enabling testing earlier than pursuing first-in-human research. This undertaking, CT-1119, targets mesothelin, and the primary in vivo information had been offered at this previous yr’s SITC assembly.
The corporate additionally introduced again in November the clearance of an IND for CT-0525, one other CAR-based remedy concentrating on HER2, however this time expressed in monocytes, that are the precursors to macrophages that may presumably be manufactured far more rapidly. It will likely be the primary such monocyte-based CAR remedy to be evaluated in stable tumors, and CARM expects to start the trial within the first half of 2024.
Monetary Overview
Per their newest quarterly submitting, CARM held $97.6 million in whole present belongings, together with $83.1 million in money and equivalents and one other $11 million in marketable securities. Their operational bills for the quarter had been $22.Three million after accounting for $3.eight million in collaboration income.
After curiosity revenue, the online loss for the quarter was $21.Four million. This offers CARM an operational runway of roughly 4-5 quarters.
Strengths and Dangers
CARM’s greatest weak point right now is definitely their money place relative to the place they stand within the scientific improvement pipeline. To date, the one information we have seen can’t be referred to as spectacular by any stretch, since illness stabilization is not actually a significant endpoint that strikes the needle. I will be fast to level out that this was a part 1 research, which is solely NOT designed to indicate efficacy, however you wish to see some sort of sign. The part 1 trial to date suggests feasibility with the strategy, however doesn’t give an concept that it will result in higher outcomes.
And I might not hitch my horse on including pembrolizumab being the deciding issue as as to if CT-0508 goes to work out. They’re now trying to lean on biomarker information and preclinical proof of synergy with anti-PD-1 remedy, however it will be a lot better to get a transparent sign that CT-0508 is working by itself earlier than we discover out whether or not including on pembrolizumab provides extra or not.
That stated, if it does work, there are attention-grabbing benefits with a macrophage or monocyte-based cell remedy. For starters, it doesn’t require lymphodepleting chemotherapy earlier than infusion, which ought to scale back the danger of significant toxicities related to wiping out the immune system. Moreover, the manufacturing time of those therapies is on the order of days, whereas accredited CAR T-cell therapies can take weeks.
The Moderna collaboration is one other potential power for CARM, because it lends some large pharma gravitas and backing to their ongoing efforts. Nevertheless, this isn’t a complicated collaboration price doubtlessly billions of {dollars} right now, and it is undoubtedly not clear how a lot, if, and when CARM will get when it comes to developmental milestones.
Backside-Line Abstract
In 2024, CARM themselves information catalysts which are tough to get too excited over, together with updates on their CAR part 1 trials, in addition to beginning different trials. Let me be clear; these are necessary developments. However for me, they sign an organization within the nascent levels the place issues are maybe at their riskiest. Moreover, a destructive catalyst they don’t promote is that 2024 goes to be a yr the place they’re going to want to handle money. It seems almost certainly that they will want to do that by means of an fairness elevate, and if their market cap of $100 million (give or take) holds, then this will likely be accomplished able of weak point, both creating a big chunk of dilution or failing to definitively tackle money challenges.
Furthermore, their operational bills are solely going to go up as they open extra trials. Given these info, and the early stage of the corporate, I am placing this as a “maintain” for me. I can not suggest shopping for it until you have an interest within the very high-risk, high-reward situation (and it will take a giant shock to appreciate that reward), however I additionally do not see a large draw back threat right now, both.