Persimmonstree over AFM24
Notes from Earnings Call, my Affimed Opus:
AFM24 + atezolizumab
AFM24 now takes pole position as lead candidate in corporate presentation, which is notable.
Taking stock of the big picture, if AFM24 can show that it can safely & durably sensitize and/or potentiate atezolizumab (or perhaps any PD-1, PD-L1) in 2L+ NSCLC, it would be a blockbuster, and Affimed is worth multiples of current market cap on those prospects alone.
Beyond the sheer size of the NSCLC 2L+ need (214k annually, per slide deck), let's review the big pharma market dynamics -- PD-1/PD-(L)1s have been the out and out cash kings for big pharma, with Merck's king Keytruda leading the way, and Bristol's Opdivo following on the king's coattails. However, despite PD-1 success, it faces two challenges -- one from the very beginning, and one on the horizon:
From the beginning, PD-1s are limited by the patient population in which they prove to be efficacious, only a fraction of the total intent to treat. The reasons for limited efficacy are various, including checkpoint score (how much PD-1 is endogenously available to block) and immunogenicity of the tumor/histology itself.
The challenge on the horizon is none other than oncoming loss of exclusivity, with $MRK alone expected to lose many billions of annual revenue from Keytruda generics by the end of decade.
Now consider AFM24 within this milieu -- again, if the efficacy and durability bears out (a huge IF), it could very well address both of PD-(L)1s' challenges: 1) Increasing the percentage of patients that meaningfully respond to PD-1, and 2) Offering a combo administration route that could effectively extend exclusivity for the PD-(L)1 with which it is combined (atezo, for now...).
And all of that before even considering other possibilities for therapeutic combinations, for which AFM24's safety profile (to date) seems well suited. Just to name a couple, how about AFM24 + a targeted ADC, perhaps in triplet with PD-1? And to any and all of these combos, what about adding some allogeneic NK cells (Artiva's or otherwise) to boost the patient's endogenous innate capabilities/response?
Again, the greenfield opportunity for AFM24 is, in a word, vast.
Now, taking our heads out of the clouds to return to the here and now -- in AFM24-102 EGFRwt cohort, we have seen some initial promise. Although latest corporate deck doesn't feature a swimmer plot, recalling from prior decks, it seems that a "mature" median PFS could fall at around 6.5 to 8.5 months. If so, that would arguably represent relatively strong results (of course pending safety, as well) given the current standard of care in 2L+ NSCLC.
Note that in current corporate slides, $AFMD's language regarding SoC's PFS: "Current standard of care provides less than 6 months PFS" could be something of a "tell" that management expects AFM24-102 EGFRwt to show PFS that clearly bests 6 months, which could point to a figure closer to the 8.5mo side of the range.
Interestingly, with respect to ORR, I think that AFM24 might just have a surprise up its sleeves in EGFRwt. Again, no swimmer plot to see the details, but I believe that some of the "near-RECIST responders" could still be on therapy, with the possibility of deepening tumor regression that could meet the 30% reduction RECIST bar on subsequent efficacy scan. Also, remember that one of the cohort's 16 total N had not yet received first efficacy scan, which could skew ORR up (or down) as that patient is not yet in the ORR denominator. A quick side note that Slide 9 seems to have a discrepancy in the total N overall, with the safety chart on the righthand side showing N=17. It's hard to say where that final patient is coming from to bring the number to 17, as my numbers show: efficacy evaluable of 15 + 1 not yet evaluated should = 16...
Either way, we should know more about EGFRwt (and initial ORR on EGFRmut) soon. According to a response to question in conference call, it appears that $AFMD has submitted AFM24-102 data to ASCO, with the company expecting to hear the results of that submission sometime in the coming week. If the submission results are positive (Oral presentation?), this could lead to a PR that serves as upward catalyst to share price in its own right.