CTL
CenturyLink, Inc.
stock NYSE

A lot of this seems to come from [your deleted responses to Sellasbuyorbust in that one comment thread from a month ago](https://www.reddit.com/r/biotech_stocks/comments/1ub3qy4/comment/ot34lrr/?screen_view_count=8), so I'll similarly *copy and paste* a lot of other users' (namely [Remarkable-Big-9849](https://www.reddit.com/user/Remarkable-Big-9849/), [Confident-Web-7118](https://www.reddit.com/user/Confident-Web-7118/), and [Sellasbuyoutorbust](https://www.reddit.com/user/Sellasbuyoutorbust/)) answers below to save myself some time. Feel free to respond to their ghosts. I'm actually far more interested in hearing what you think about a recently released AML CR1 BAT study: [https://haematologica.org/article/view/14308](https://haematologica.org/article/view/14308)
* **New vaccines rule, GPS drools.**
* *Yes, historical cancer vaccines failed, but they failed because they were tested against massive, active solid tumors. The immune system couldn't overpower advanced, macroscopic disease. GPS isn't trying to shrink a tumor. It is a maintenance therapy targeting minimal residual disease (MRD) in patients who are already in remission. Also, comparing GPS to Moderna's mRNA work is a weird flex—they are entirely different mechanisms for entirely different disease burdens. By the way, the National Cancer Institute (NCI) ranked WT1 (the target of GPS) as the #1 target for cancer immunotherapy. It's not a dead concept.*
* *You also claimed that the field "moved on" from cancer vaccines with BioNTech as proof. That is completely backward. BioNTech literally has a massive active pipeline of Phase 2 and Phase 3 cancer vaccines (like BNT111 and BNT112) targeting specific tumor-associated antigens. For someone claiming to work full-time in clinical drug development, missing massive Big Pharma WT1 partnerships while asking people to "post them here if I'm wrong" is a glaring blind spot.*
1. *Astellas Pharma (a massive Big Pharma company) actively developed and advanced ASP7517, a WT1-targeted immunotherapeutic vaccine, into Phase 1/2 clinical trials for AML, MDS, and solid tumors.*
2. *Regeneron (a $100B+ pharma giant) is heavily partnered with Inovio on INO-5401, an active therapeutic cancer vaccine in clinical trials for glioblastoma. One of the primary tumor antigens it targets? WT1.*
3. *Cue Biopharma is actively running Phase 1/2 clinical trials for CUE-102, a WT1-targeting IL-2 fusion protein for WT1-expressing cancers.*
* **GPS probably won't be able to induce responses. And if it did, then there** ***should*** **be a toxicity issue.**
* [80% of Randomly Selected REGAL GPS Patients Showed a Specific T-Cell Immune Response (January 2025)](https://ir.sellaslifesciences.com/news/News-Details/2025/SELLAS-Life-Sciences-Announces-Positive-Outcome-of-Interim-Analysis-for-its-Pivotal-Phase-3-REGAL-Trial-of-GPS-in-Acute-Myeloid-Leukemia/default.aspx)
* *GPS works best with a specific HLA type, and "cured" patients will most likely have it. However, existing literature does not support the idea that HLA-positive patients are near-deterministic durable responders and HLA-negative patients are near-deterministic failures. HLA compatibility plays a role, but helper support, baseline immune fitness, tumor burden, and suppressive biology decide how much of that potential actually turns into benefit.*
* *In* [*Oji 2023 WT1 Trio*](https://pmc.ncbi.nlm.nih.gov/articles/PMC9857088/)*, immune activation improved, but clinical translation was still limited and heterogeneous: WT1-235 IgG was positive in 88.0%, DTH was 62.9%, but only 15 of 45 patients, 33.3%, achieved stable disease at 3 months. The paper also explicitly shows disease-specific immune-response patterns and reports that pre-vaccine spontaneous IL-10 and WT1-332-specific IL-10 were associated with worse outcomes in malignant glioma, which is exactly the kind of “immune fitness / suppression” modifier you mentioned. If pre-vaccine spontaneous IL-10 is already predictive before treatment starts, it's a baseline patient characteristic reflecting the tumor microenvironment state at vaccination, not a downstream response variable. That means you could have an HLA-A\*02:01+ patient with strong CTL induction and still get poor clinical translation if the microenvironment is IL-10-high at baseline. So, HLA sets the ceiling on CD8 priming potential, but pre-existing suppressive tone may cap how much of that potential actually converts to durable benefit.*
* *Earlier* [*Oji 2016 GBM*](https://pubmed.ncbi.nlm.nih.gov/27170523/) *data points the same way: even in an HLA-matched WT1-235 setting, WT1-235 IgG appeared in 50.8%, DTH in 60.0%, disease control at 3 months was 44.9%, and the strongest long-survival signal came from the combined IgG-positive plus DTH-positive subset, not from HLA matching alone. The combined IgG+/DTH+ signal being the strongest long-survival predictor — stronger than either marker alone — suggests helper engagement isn't just broadening the reachable population by catching HLA-negative patients. It may be necessary for durability even in HLA-positive patients whose CD8 responses would otherwise activate and collapse without sustained CD4 support.*
* WT1 vaccines have generally been well-tolerated. GPS and its toxicity profile are consistent with other WT1 vaccine–adjuvant combinations. Concerns about hematologic and renal toxicity have been raised before ([H Menssen 1997](https://doi.org/10.1182/blood.V89.9.3486) & [Y Oka 2003](https://pubmed.ncbi.nlm.nih.gov/12894852/)), but those seem to be the exception, not the norm. Take a step back: Would it really make sense for GPS to be toxic if this is supposed to be a low-intensity maintenance therapy for people whose immune systems have been put through the wringer?
* **IDMC not stopping for futility doesn't mean anything other than the prespecified futility boundary wasn't met.**
* OK, but what does that mean? There must have been a reason that the IDMC let it keep going AND did not request any modifications after interim analysis (IA). If GPS and BAT worked the same/were both ineffective, then the trial would be over. There would have been no divergence between GPS and the BAT in the data and by extension no reason to continue. If GPS patients held out until IA, but the drug was still inferior or comparable to BAT, then the trial would also be over by this point. 80 people would have certainly died by now because historical data doesn't support AML CR2 patients surviving this long on BAT. But whatever. There's no way to know for sure at this point what the numbers will look like anyway.
* Note: The GPS Phase 2 data ([link to study](https://pmc.ncbi.nlm.nih.gov/articles/PMC5812332/#B21)) [you've been referring to](https://www.reddit.com/r/biotech_stocks/comments/1ub3qy4/comment/oswvxoh/?utm_source=share&utm_medium=web3x&utm_name=web3xcss&utm_term=1&utm_content=share_button) is for AML CR1 patients.
* **"Infinite dosing" doesn't mean much other than the pre-trial assumptions were wrong, GPS isn't particularly toxic, and FDA wants good data**.
* When Sellas and AML KOLs designed the trial protocols, they referenced personal experience and existing research to guide their decisions. Aside from "GPS works", they would have also considered things like how long the trial should reasonably be expected to last. Despite this, the REGAL trial kept going on and on. On and on and on and on and on. Far longer than anyone initially expected for this subset of the population. And that's why the protocol amendment request was made in the first place. If nothing else, that's pretty interesting.

A lot of this seems to come from [your deleted responses to Sellasbuyorbust in that one comment thread from a month ago](https://www.reddit.com/r/biotech_stocks/comments/1ub3qy4/comment/ot34lrr/?screen_view_count=8), so I'll similarly *copy and paste* a lot of other users' (namely [Remarkable-Big-9849](https://www.reddit.com/user/Remarkable-Big-9849/), [Confident-Web-7118](https://www.reddit.com/user/Confident-Web-7118/), and [Sellasbuyoutorbust](https://www.reddit.com/user/Sellasbuyoutorbust/)) answers below to save myself some time. Feel free to respond to their ghosts. I'm actually far more interested in hearing what you think about a recently released AML CR1 BAT study: [https://haematologica.org/article/view/14308](https://haematologica.org/article/view/14308)
* **New vaccines rule, GPS drools.**
* *Yes, historical cancer vaccines failed, but they failed because they were tested against massive, active solid tumors. The immune system couldn't overpower advanced, macroscopic disease. GPS isn't trying to shrink a tumor. It is a maintenance therapy targeting minimal residual disease (MRD) in patients who are already in remission. Also, comparing GPS to Moderna's mRNA work is a weird flex—they are entirely different mechanisms for entirely different disease burdens. By the way, the National Cancer Institute (NCI) ranked WT1 (the target of GPS) as the #1 target for cancer immunotherapy. It's not a dead concept.*
* *You also claimed that the field "moved on" from cancer vaccines with BioNTech as proof. That is completely backward. BioNTech literally has a massive active pipeline of Phase 2 and Phase 3 cancer vaccines (like BNT111 and BNT112) targeting specific tumor-associated antigens. For someone claiming to work full-time in clinical drug development, missing massive Big Pharma WT1 partnerships while asking people to "post them here if I'm wrong" is a glaring blind spot.*
1. *Astellas Pharma (a massive Big Pharma company) actively developed and advanced ASP7517, a WT1-targeted immunotherapeutic vaccine, into Phase 1/2 clinical trials for AML, MDS, and solid tumors.*
2. *Regeneron (a $100B+ pharma giant) is heavily partnered with Inovio on INO-5401, an active therapeutic cancer vaccine in clinical trials for glioblastoma. One of the primary tumor antigens it targets? WT1.*
3. *Cue Biopharma is actively running Phase 1/2 clinical trials for CUE-102, a WT1-targeting IL-2 fusion protein for WT1-expressing cancers.*
* **GPS probably won't be able to induce responses. And if it did, then there** ***should*** **be a toxicity issue.**
* [80% of Randomly Selected REGAL GPS Patients Showed a Specific T-Cell Immune Response (January 2025)](https://ir.sellaslifesciences.com/news/News-Details/2025/SELLAS-Life-Sciences-Announces-Positive-Outcome-of-Interim-Analysis-for-its-Pivotal-Phase-3-REGAL-Trial-of-GPS-in-Acute-Myeloid-Leukemia/default.aspx)
* *GPS works best with a specific HLA type, and "cured" patients will most likely have it. However, existing literature does not support the idea that HLA-positive patients are near-deterministic durable responders and HLA-negative patients are near-deterministic failures. HLA compatibility plays a role, but helper support, baseline immune fitness, tumor burden, and suppressive biology decide how much of that potential actually turns into benefit.*
* *In* [*Oji 2023 WT1 Trio*](https://pmc.ncbi.nlm.nih.gov/articles/PMC9857088/)*, immune activation improved, but clinical translation was still limited and heterogeneous: WT1-235 IgG was positive in 88.0%, DTH was 62.9%, but only 15 of 45 patients, 33.3%, achieved stable disease at 3 months. The paper also explicitly shows disease-specific immune-response patterns and reports that pre-vaccine spontaneous IL-10 and WT1-332-specific IL-10 were associated with worse outcomes in malignant glioma, which is exactly the kind of “immune fitness / suppression” modifier you mentioned. If pre-vaccine spontaneous IL-10 is already predictive before treatment starts, it's a baseline patient characteristic reflecting the tumor microenvironment state at vaccination, not a downstream response variable. That means you could have an HLA-A\*02:01+ patient with strong CTL induction and still get poor clinical translation if the microenvironment is IL-10-high at baseline. So, HLA sets the ceiling on CD8 priming potential, but pre-existing suppressive tone may cap how much of that potential actually converts to durable benefit.*
* *Earlier* [*Oji 2016 GBM*](https://pubmed.ncbi.nlm.nih.gov/27170523/) *data points the same way: even in an HLA-matched WT1-235 setting, WT1-235 IgG appeared in 50.8%, DTH in 60.0%, disease control at 3 months was 44.9%, and the strongest long-survival signal came from the combined IgG-positive plus DTH-positive subset, not from HLA matching alone. The combined IgG+/DTH+ signal being the strongest long-survival predictor — stronger than either marker alone — suggests helper engagement isn't just broadening the reachable population by catching HLA-negative patients. It may be necessary for durability even in HLA-positive patients whose CD8 responses would otherwise activate and collapse without sustained CD4 support.*
* WT1 vaccines have generally been well-tolerated. GPS and its toxicity profile are consistent with other WT1 vaccine–adjuvant combinations. Concerns about hematologic and renal toxicity have been raised before ([H Menssen 1997](https://doi.org/10.1182/blood.V89.9.3486) & [Y Oka 2003](https://pubmed.ncbi.nlm.nih.gov/12894852/)), but those seem to be the exception, not the norm. Take a step back: Would it really make sense for GPS to be toxic if this is supposed to be a low-intensity maintenance therapy for people whose immune systems have been put through the wringer?
* **IDMC not stopping for futility doesn't mean anything other than the prespecified futility boundary wasn't met.**
* OK, but what does that mean? There must have been a reason that the IDMC let it keep going AND did not request any modifications after interim analysis (IA). If GPS and BAT worked the same/were both ineffective, then the trial would be over. There would have been no divergence between GPS and the BAT in the data and by extension no reason to continue. If GPS patients held out until IA, but the drug was still inferior or comparable to BAT, then the trial would also be over by this point. 80 people would have certainly died by now because historical data doesn't support AML CR2 patients surviving this long on BAT. But whatever. There's no way to know for sure at this point what the numbers will look like anyway.
* Note: The GPS Phase 2 data ([link to study](https://pmc.ncbi.nlm.nih.gov/articles/PMC5812332/#B21)) [you've been referring to](https://www.reddit.com/r/biotech_stocks/comments/1ub3qy4/comment/oswvxoh/?utm_source=share&utm_medium=web3x&utm_name=web3xcss&utm_term=1&utm_content=share_button) is for AML CR1 patients.
* **"Infinite dosing" doesn't mean much other than the pre-trial assumptions were wrong, GPS isn't particularly toxic, and FDA wants good data**.
* When Sellas and AML KOLs designed the trial protocols, they referenced personal experience and existing research to guide their decisions. Aside from "GPS works", they would have also considered things like how long the trial should reasonably be expected to last. Despite this, the REGAL trial kept going on and on. On and on and on and on and on. Far longer than anyone initially expected for this subset of the population. And that's why the protocol amendment request was made in the first place. If nothing else, that's pretty interesting.