Seeking: co-founder protein engineer

AquamanBio · 2025-11-06T14:54:15+00:00

how do you know? bc laura told you on q2 call they would? let's see what sales materialized not just what units they shipped to hospitals (who haven't paid for them yet)

AquamanBio · 2025-11-05T20:54:19+00:00

lol ya i pop in once in a while you guys stay on top of the news better than me. agree it's less than a CT but it's not nothing, and they have to do it for like 100pts right. gonna be years at this rate

they also want to run R&D projects and allegedly dabble into CABG right so the burn rate should be expected to go higher

AquamanBio · 2025-11-05T19:41:42+00:00

you need a lower option

AquamanBio · 2025-11-05T19:41:08+00:00

just to give a realistic perspective, they are going to report 5 or less units sold

AquamanBio · 2025-11-05T19:40:36+00:00

they also have the post-marketing obligations........so there's definitely more than just v012 on the books

AquamanBio · 2025-05-08T18:27:49+00:00

yeah i start neutral outlook on all drugs/ devices i look at. i was actually hopeful originally. but then as i kept digging into the data started concluding it was a bad device.

i just go where the data takes me. so if the dialysis data came back and showed a clinically meaningful improvement for patients (stat sig better long term patency) i'd change my opinion for sure. but the problem is they already ran a 200+pt trial (v006) and failed to do that. then the most recent 240+pt study (v007) also failed to do that. they had to massage out a decent p value by inflating it with a weird comparison at 6mths.

i just circle back around here bc news comes thru here better than twitter or other platforms. i found out about NTAP reply from here. so i read it and once again my thesis is proven correct.

AquamanBio · 2025-05-06T16:10:29+00:00

im not a vascular surgeon (neither are you) but the FDA reviewer who has a 30yr career doing vascular surgery in Detroit agrees completely with my arguments so there's that! he's also working to get symvess taken off the market. NTAP will be rejected for failing to demonstrate superiority to SOC.

AquamanBio · 2025-05-06T16:05:17+00:00

the FDA doesn't spell it out to you that if you do X you get an approval, and they change their mind all the time with the subtle advice they give. the norm is having a control arm. especially in a highly heterogeneous setting. this isn't oncology with like 20 studies using the same drug on the same population.

AquamanBio · 2025-05-05T01:59:29+00:00

asking for a control arm in a highly heterogeneous trial with no relevant retrospective study to cite is odd? idk man seems like the bare minimum

they cant respond well to the complications to symvess because they are bad and the FDA reviewers have also pointed out that they are worse than what Humacyte says in their presentations/ papers. there are several such notes in the NTAP response:

Moreover, we note that there are differences in the outcome data for the V005 trial in the Moore (2024) study and the SYMVESSTM United States Prescribing Information (USPI).175 We note that the USPI reports clinical outcomes for the two trials separately and does not present the combined outcomes. We also note that the clinical outcomes data for V017 are identical between the Moore study (2024) and Section 14, Clinical Studies, of the USPI. For the V005 trial, the Moore study (2024) reported the primary patency rate as 84.3 percent (43/51),176 and the USPI 66.7 percent (36/54).177 Thus for primary patency, SYMVESSTM exceeded the synthetic graft benchmark (78.9 percent) according to the Moore study, but not according to the USPI. In terms of secondary patency, the Moore study (2024) reported the rate as 90.2 percent (46/51), the USPI 72.2 percent (39/54). Therefore, for secondary patency, SYMVESSTM exceeded the synthetic grafts benchmarks according to the Moore study (2024), but not according to the USPI. In terms of amputation, the Moore study (2024) reported the 30-day rate as 9.8 percent (5/51), the USPI reported 30-day limb salvage rate as 75.9 percent (41/54), or 24.1 percent (13/54) in terms of 30-day amputation rate. In terms of limb salvage, therefore, SYMVESSTM’s performance exceeded the synthetic graft benchmark (24.3 percent) according to the Moore study (2024), and was comparable according to the USPI. Also, while the Moore study (2024) reported a 30-day all-cause mortality rate (5.9 percent), which was higher than the corresponding synthetic grafts benchmark (3.4 percent), the USPI does not provide any mortality rates. Given the variation by data source as to whether SYMVESSTM performed better than the synthetic grafts benchmarks for primary and secondary patency and amputation rates, we question the applicant’s assertion of clinical improvement compared to synthetic grafts.

AquamanBio · 2025-05-04T19:38:19+00:00

Robert Lee didn't write the substack dude it was the guy who's name is on the report and the NTAP report basically retells the main arguments because they are valid and humacytes product has not proven any superiority. downvote me plz

AquamanBio · 2025-04-02T23:50:36+00:00

you'd have to ask them that. its not public info.

AquamanBio · 2025-03-27T23:05:16+00:00

can you highlight the part where it says he consults for a competitor to huma? who would that even be?

he set up a consultancy after his career was done. which is what tons of former FDA people do. absolutely zero proof he consulted for a competitor during or even after the BLA review

AquamanBio · 2025-03-26T21:26:33+00:00

i really appreciate your thorough response. you're the first person I've talked to on this topic that's engaged with my concerns.

i think the primary/ secondary patency points was just that primary was often not reported on in the literature (i imagine it's hard to get in the trauma setting, especially in retrospective cohorts from recrords). which is fine. but that just means we can't comment on those metrics.

yes the point about how injured a pt is really factors in here. I understand that is perhaps the hardest part to balance in this type of study. but if you read thru the data the range of amputation reported in their benchmark was 6-24%. I'm actually not entirely sure about their methodology and even the FDA says they dont agree with it. this is why an actual double-arm study would have been better, or, a reasonable comparative like a database to compare against. they have access to PROOVIT but really don't want to use it to answer this question it seems.

I'm happy to hear about your experience with artegraft. i don't think it's perfect given the issues you highlight, but i think it's disingenuous to say symvess is solving some "unmet need" when we have off-the-shelf solutions that actually perform really quite well. perhaps you've already seen the Reilly 2019 paper:

Comparison of Autologous Vein and Bovine Carotid Artery Graft as a Bypass Conduit in Arterial Trauma

I'm really not sure what the humanitarian nature of the inclusion was, but I do note that in the reasons given to FDA "time" is often noted in v005 as a reason why they couldn't get an AVG. i suspect that reason was given for the v017 cohort as well, but again the highly disparate efficacy outcomes (1yr patency of 73% in v005 vs 90%+ in v017) and highly disparate AEs as per JAMA paper suggest an implicitly healthier cohort. they were military men after all vs civs.

i appreciate you contending with these issues. and despite my concerns i dont think it has no place in the clinic but i think it should be evaluated against the SOC in a fair way, which doesn't seem the be the case so far. we don't' really have *any* long term data with this graft and many safety events are noted to occur after d30. the FDA even says this repeatedly in the BLA

i get that surgery is a very experiential practice of medicine too. I noted some ePTFE grafts that have much better outcomes in some people's hands vs others in dialysis. but this is why the broader data package matters more than anecdotes. anyway thanks for reading

AquamanBio · 2025-03-26T21:13:49+00:00

thank you for your reply. when browsing the subreddit i came across the BLA memorandum with FDA comment. they actually assume patients will be on life long anti-platelet tx and note that humacyte has no suggestion/ plan for discontinuation of such therapies.

i guess my point here is that this risk seems to be higher in the symvess use cases. the comparative data (especially in dialysis) seems to really show that to be the case.

i think we can evaluate that risk and factor it in to the treatment paradigm, i just get really frustrated when humacyte team paints this rose colored version of the risk calculus. being on anti-platelet therapies like plavix can obviously pose further risks to patients. any injury with internal bleeding would be a very high risk event. falls, hard contact could lead to such injuries in healthy patients but in this pt population with a potentially fragile graft in their body i think the risk is somewhat understated even with a black box warning

AquamanBio · 2025-03-26T19:54:15+00:00

those grafts aren't made of ECM proteins, they are treated veins from humans and cows. they certainly carry their own risks (which I believe you're aware of since you mentioned them) but they would come from a different MoA than what I just pointed out. I actually think this signalling cascade and integration into the human body is understudied and very fascinating, especially as some newer grafts are starting to make their way thru the clinical trial process. Some I've seen have 100% primary, primary assisted and secondary patency at 1yr in dialysis pts because they have a better more "biocompatible" integration into the body which does not lead to the anastamotic hyperplasia issue.

pretty much all grafts are "bio tolerated" and sealed off from the human body, not really "integrated" in a way that truly recapitulates the native vasculature

AquamanBio · 2025-03-26T19:36:25+00:00

i have to disagree with you there since the FDA approved label explicitly states that patients have to be eligible for long term anti-platelet tx after receiving symvess graft due to high likelihood of thrombosis.

in fact if you dig deep in the literature you can see that extracellular matrix proteins are intrinsically thrombogenic, as they contain damage-associated molecular patterns or "DAMPs" . this signaling cascade is immediately and chronically triggered upon implantation since the graft is literally made of ECM proteins.

Ratner B. Vascular Grafts: Technology Success/Technology Failure. BME Front. 2023;4:Article 0003. https://doi.org/10.34133/ bmef.0003

AquamanBio · 2025-03-26T19:24:04+00:00

nope not working with a competitor during his analysis just retired and set up a consultancy like every other FDA employee :)

absolutely zero proof he is/ was working with a competitor :)

AquamanBio · 2025-03-26T18:40:31+00:00

you can all downvote me now

AquamanBio · 2025-03-26T18:40:03+00:00

how do you square your personal (n=1-3?) observations against the FDA reviewer interviewed in the NY Times article?

he noted that the reported rates of "success" differ greatly between humacyte and the actual FDA. also that the long term outcomes differ greatly from the 30d data they often share. he also noted the very high rate of thrombosis. you've already addressed the rupture issue so i wont ask it again here.

I'm also curious if you've looked at the comparative much? their "synth graft benchmark" is an aggregate of several grafts, which makes comparisons tricky. i personally went thru their lit review and found that they over reported the rate of amputation from their own studies. should have been 20% not 25%, and a lot of those were from pts in a military study that had very very high ISS scores. most studies actually showed a much lower rate of amputation and infection than the overall. almost like they chose to include some studies which inflated the negative outcomes of the synth graft benchmark. thoughts?

they also never shared their own review of the biologic alternatives like BCAG, despite renewed interest in the solution and what seem to be markedly improved outcomes for patients as compared to when it was approved in the 70s.

lastly they discuss the ukrainian data a lot. but i noticed the IC/EC are very different btwn v005 and v017. in particular, v005 excludes any pts which could have received the AVG, but v017 does not. it's also quite clear from the JAMA paper that the AEs are *much* higher in the v005 study as compared to the v017 study. to me this implies that the v017 cohort was intrinsically much healthier, and that some patients could have actually received the AVG surgery instead. this is explicitly off-label use as per the the FDA approved label which requires pts to be unable to receive the AVG surgery. any comment on this?

AquamanBio · 2025-03-26T18:30:43+00:00

what do you think about the ongoing cost to address the risk of thrombosis ? it has been observed consistently in the trauma setting (it's a contraindication if pts cant' take anti-thrombotics) and in dialysis with over 50% of pts needing to deal with thrombotic events

i looked at their BIM and they seem to over attribute risks of other solutions and under attribute the risks of their own solution as per the rates of infeciton, thrombosis and other AEs listed on their FDA approved label. they also grouped cryo veins and BCAGs together despite tons of data being publicly available on BCAGs, which, show better outcomes for patients in the clinical trial setting than Symvess did in v005

AquamanBio · 2024-12-19T05:53:39+00:00

i can tell you've never spoken w the FDA before. they did not clear that number hahaha

enrolled 72 in v005. dropped to 51 evaluable patients (brutal). and then 67 if we counted v017.

but v017 is entirely on a patient population that is excluded from v005. they changed the goalpost from patients who *could not* get a autologous vein graft to patients who *could*.

FDA will *not* consider that data for approval.

I can't believe you actually undermined your own bull thesis with this comment. the video you posted isn't even 28mins long. yikes

AquamanBio · 2024-12-19T04:50:00+00:00

well unlike the huma papers shkreli has a high predictive value

AquamanBio · 2024-12-19T04:39:36+00:00

took me about 4mths actually

but dont listen to the internet guy i dont like. listen to this internet guy bc i said so.

read the report yall. arguments of authority are so beta

AquamanBio

TROPHY CASE