Design Cells
Topline Abstract
Autolus Therapeutics (NASDAQ:AUTL) is a member of an more and more giant group of firms creating cell-based immunotherapy for most cancers. On this case, their most important goal is CD19 in ALL, a illness that’s already served by a couple of completely different CAR T-cell therapies on the market. Their hope is that through the use of a tweaked model of this method, they’ll enhance efficacy whereas lowering the notable toxicities related to different cell therapies on this line. For me, the potential approval of a remedy we nonetheless want extra manufacturing capability for is sufficient to be tempting, and I’d positively take into account a purchase on this inventory presently.
Pipeline Overview
Obecabtagene autoleucel (obe-cel)
Obe-cel is the flagship developmental product that AUTL is engaged on. It’s a CD19-directed CAR T-cell remedy related in precept to the opposite CAR T-cell therapies which can be accredited for various B-cell cancers, together with B-cell acute lymphoblastic leukemia (ALL).
AUTL submitted a BLA to the FDA for approval in sufferers with relapsed/refractory B-cell ALL. This submission might be based mostly largely on the findings from the part 1b/2 FELIX research, which was just updated at ASH 2023. Obe-cel was efficiently manufactured and administered in 83% of the 152 sufferers who had been enrolled and underwent leukapheresis.
The entire response price in these sufferers who had therapy was 78%. Minimal residual illness was eradicated in 96% of evaluable sufferers. Grade 3 cytokine launch syndrome occurred in 2% of sufferers, and grade 3 ICANS was noticed in 7% of sufferers. In sufferers with low illness burden, none of those grade 3 occasions occurred.
These findings nominally examine favorably with different CD19 CAR T-cell approaches, which demonstrated comparable response rates in sufferers with relapsed/refractory B-cell ALL, however with grade 3/4 CRS and neurologic hostile occasions extra within the vary of 48% and 22%, respectively, giving a sign that obe-cel possibly be related to much less toxicity, a serious concern of those therapies.
Obe-cel can also be being evaluated in different settings, together with B-cell non-Hodgkin lymphoma (B-NHL), power lymphocytic leukemia (CLL), and first CNS lymphoma. All of those are the topic of assorted part 1 trials which can be ongoing. At ASH 2023, AUTL offered an replace of ALLCAR19, which enrolled sufferers with relapsed/refractory B-NHL and CLL. The corporate touted excessive charges of sturdy response in these ailments, with low frequency of grade 3 or greater CRS or ICANS.
AUTO8
The following most up-to-date replace additionally got here at ASH 2023, centered on a dual-targeted BCMA/CD19 CAR T-cell remedy known as AUTO8. The part 1 MCARTY research is enrolling sufferers with relapsed/refractory a number of myeloma. A complete of 11 sufferers had been included within the research, half of whom had been infused with CAR T cells expressing simply the BCMA chimeric antigen receptor, and the opposite half being handled with AUTO8. All sufferers achieved a response to remedy, most of which had been full responses.
No grade 3 or greater CRS or ICANS was noticed with both therapy method. Whereas it’s extremely early to speak about how this pertains to, say, accredited therapies (part 1 research are approach too small to make definitive conclusions), if the outcomes bear out, they is likely to be an enchancment over different BCMA CAR T cell therapies like ide-cel, since they’re additionally related to some high-grade CRS and neurotoxicity.
Monetary Overview
As of their Q3 2023 submitting, AUTL held $308 million in complete present belongings, together with $256.4 million in money and equivalents. In the meantime, their complete working bills reached $47.8 million, and after curiosity expense, curiosity earnings, and license income, the online loss earlier than earnings tax was $50.8 million for the quarter.
At this price, AUTL has roughly 6-7 quarters of money left as a runway to fund operations. They haven’t had a public providing since December 2022.
Strengths and Dangers
Contemplating we’re speaking about trial designs on the order of tens of sufferers in measurement, it is tough to think about AUTL as something however a moderately early-stage firm. Nevertheless, the FDA has made it clear within the path that they are prepared to enormously speed up the pipeline for CAR T-cell remedy if they’ve promising information, which AUTL does. Furthermore, the FDA might proceed with an perspective of “the more the merrier” within the CAR T area that has been tormented by long wait times due to manufacturing capacity in recent times.
Are these CAR T therapies higher than the accredited flavors? I do not know that you may say that. The grade 3 toxicities of notice do look like decrease, however and not using a head-to-head comparability, even seemingly slam-dunk comparisons throughout trials cannot actually be taken that severely.
I believe the primary concern I’ve with AUTL is money. 6 quarters of funds is loads to see via among the huge information it’s best to count on for some time, however it may not be sufficient to get them via approval and into an enormous launch of their drug, which itself could also be sluggish to penetrate the market since there are a number of accredited CD19-directed CAR T-cell therapies.
Some sort of financing association is probably going earlier than they attain approval, and their present valuation may not develop with the identical momentum with the danger of dilution on the desk. There’s additionally the gnawing specter not too long ago uncovered to the opportunity of a second cancer with at present accredited CAR T-cell therapies. I do not know what to make of this information, nor do lots of the specialists within the fields. However, actual or not, the danger of uncommon however very critical complication could possibly be sufficient for the FDA to demand extra proof from CAR T cell builders sooner or later, and that information could be catastrophic for AUTL.
Backside-Line Abstract
AUTL is already on the cusp of drug approval within the CAR T-cell area, which is predicted to grow to over $80 billion by 2032. There’s nonetheless room for a “me too” within the CD19 and BCMA areas, to say nothing in regards to the risk that AUTL’s method is likely to be much less poisonous whereas sustaining efficacy. Primarily based on that, there are a number of causes to be enthusiastic about AUTL’s prospects. They’re at present valued at a premium for a part 2 biotech, but when they get approval, I consider there’s not less than a 100% upside right here. Whereas the dangers are actual, I believe it’s best to take into account a place on this one.
