u/AverageUnited3237

Any highly esteemed or must try restaurants ?

So I've been digging into the study protocol on the EU clinical trial website to understand the level of MNPI that SELLAS as the sponsor of the REGAL study has access to. I will lay out my findings below - it shines a whole new light on Sterg's bullishness to me, particularly in his recent LinkedIn post about their "proprietary modeling." EDITING: I was just rereading Sterg's post again after what i shared on reddit. "We do not disclose real-time blinded metrics. We do not share proprietary modeling and our detailed statistics." -> the detail about "real-time blinded metrics" is something i overlooked the first time and I also have a new perspective on after compiling this protocol audit.

1. Toxicity and death ledger (Pages 43 & 56)

"All deaths, whether considered study related or not, must be reported immediately to SELLAS and its designee..." (p. 56) AND "Any AE that meets AESI criteria... or SAE criteria... must be reported to SELLAS... immediately (i.e., within 24 hours)..." (p. 56)"

So SELLAS is being notified in almost realtime of the number of deaths in the study.

"The period of active treatment is until disease relapse." (page 27)

During the active treatment phase (until a patient relapses) SELLAS doesn't wait for unblinding to see the toxicity profiles. SELLAS is notified of any AE in the active treatment phase. Given GPS's favorable safety profile in prior studies, one would expect a disproportionate share of serious treatment related toxicities to arise in the BAT arm, although the protocol itself does not attribute events by arm. What this means is that if a patient suffers sepsis or requires an ICU trip, that SAE hits a central inbox within 24 hours. No wonder why Sterg is saying Venetoclax shortens lifespan on LinkedIn - SELLAS's safety operations receive these reports in near real time - and again, the AEs will be almost entirely restricted tot he BAT arm

2. Long term survival status & post relapse tracking

"Subjects are then followed until week 91, every 3 months, via telephone... for the following: Recording of new AML therapy. Survival Status OS (alive/dead status)."

Once a patient relapses, exits active treatment, and routine AE reporting stops, they enter LTF (long term follow up). The CRO tracks their exact survival status and any "new AML therapy" (like a transplant) every 3 months. Combined with the immediate death reporting mandate, Sellas has an ongoing (blinded) view of the post relapse survival curves and subsequent therapies for the REGAL population.

3. The blinded number of relapses (Pages 50, 58, 61, 62)

"Relapse or recurrence of a patient's leukemia will be documented on forms provided to the site... The patient will be discontinued from the on-treatment portion..." (Section 6.4.7, p. 58)"

"Investigative site personnel will enter patient data into eCRFs. The eCRFs are used to record study data... The eCRFs must be kept current to reflect patient status at each phase..." (Section 7.7, p. 61)

"SELLAS Life Sciences Group or its designee will review all eCRFs for completeness. The investigator will be contacted for corrections and/or clarifications. Intensive efforts will be made to minimize missing data." (Section 7.7, p. 62).

"These subjects will complete the Relapse Visit that includes the following procedures within 14 days from received confirmation of subject’s relapse..." AND "Data captured on the eCRFs will be reviewed by a SELLAS clinical monitor..."

When a patient relapses the local site will halt treatment and log a the relapse in the eCRF. SELLAS has near real time blinded knowledge of the cumulative number of relapses within the trial.

4. Pre randomization genetic matrix (Pages 34 & 68)

"Patients will be randomized 1:1... stratified by: duration of the subject's historical CR1... baseline cytogenetics risk... CR2 vs CRp2 status and presence or absence of MRD..." AND "Significant deviations can include... enrollment of the patient without prior sponsor approval..."

Enrollment requires sponsor approval, meaning SELLAS necessarily has access to each patient's eligibility information and stratification profile before randomization. So SELLAS are the ultimate gatekeepers of the transplant ineligible criteria in REGAL - if they think someone isnt "ineligible enough", they can deny their entry into REGAL. Additionally, this proves that SELLAS already possesses the patient's stratification profile at the time of randomization.

5. T-cell & mechanism telemetry (Pages 44-45)

"The SECOND trephine biopsy core cylinder... should be sent to Central Lab A for bone marrow stroma immunocyte IHC..." AND "Peripheral blood samples for WT1-peptide specific CD4+ and CD8+ T-cell activation, collected as per study Laboratory Manual."

Local hospitals arent running biomarker assays themselves; they mail the samples directly to SELLAS contracted lab parters. those contracted central laboratories then generate WT1 specific CD4/CD8 immunogenicity data together with marrow immune microenvironment assays, which would provide a direct readout of whether GPS is inducing the intended immune response. Does Sellas see this data? Yes. Table 4 Note 18 (p. 45) explicitly states the T cell activation draws are for "US Patients only randomized to GPS arm." Because this specific assay is only run on the vaccine arm, there isnt even any unblinding require here here. Section 7.7 (p. 61) dictates that "The analysis data sets will be a combination of these [eCRF] data and data from other sources (e.g., laboratory data)." According to my understanding here, SELLAS knows the immune response the drug is generating.

6. Continuous MRD surveillance

"For subjects that are non-progressors, between week 53 and week 91, every 3 months, +/- 14d they will perform the following procedures: Bone Marrow Aspirates for MRD. Peripheral blood for MRD." (p. 51) AND "Bone marrow aspirate for MRD testing... should be sent to Central Lab A." (p. 44/45)

Similar to 5 - Non progressing patients undergo serial MRD surveillance approximately every three months..

Putting this together, The protocol paints a very clear picture that SELLAS has access to key information that the rest of the world is blind to - SELLAS's clinical operations and CRO have ongoing visibility into:

• immediate individual death and SAE reports,
• current patient status eCRFs,
• documented relapses,
• new AML therapies,
• transplant related discontinuations,
• source verified clinical records,
• MRD laboratory data,
• marrow immune environment assays,
• GPS specific WT1 T cell response data
• Exact enrollment dates

When Stergiou refers to proprietary modeling he is not talking about a model built from public assumptions. He is referring to a model calibrated using the actual blinded operational characteristics of REGAL itself including patient mix, relapse burden, survival follow up, transplant activity, molecular biomarkers, and treatment exposure...

The level of MNPI has really shined an entirely new light on the confidence of the CEO for me personally. Though I know not everyone here believes management is credible - his makes his confidence more understandable with this level of MNPI. If Redditors such as CW, Thetamancer, myself, etc are able to model things with 95%+ POS based on limited and incomplete information - what do you think SELLAS internal models are showing? Obviously they still don't know the final hazard ratio before unblinding, but they know far, far more than the market appreciates.

Sharing this with the community in case ive misinterpreted anything (please i hope people will correct me if anything up above is incorrect!), but also because I personally find this information to be very comforting given the communication and confidence from the CEO

My source is the study protocol from https://euclinicaltrials.eu/ctis-public/view/2024-516405-23-00?lang=en (trial documents tab -> first one - D1_SELLAS_ SLSG18-301_Protocol_2024-516405-23_Public)

"Patients may be removed from study treatment... but continue to be monitored in the study for the following reasons:"
"• Receiving a hematopoietic stem cell transplant (autologous or allogeneic, with any degree of match donor)" (page 32)

"Notification of early patient discontinuation from the study and the reason for discontinuation will be made to the sponsor, and will be clearly documented on the appropriate electronic case report form (eCRF)." (page 33)

"The reason for patient withdrawal or date of death and new AML therapies (if appropriate) will be recorded." (page 52) So even if the patient relapsed first and then got a transplant later during the survival follow up period, the CRO still tracks it.

They can't see the arm that the patient was in, but they can 100% see the aggregate integer of how many eCRFs have been filed with transplant listed as the reason for discontinuation

This combined with their access to other non public information (exact enrollment dates + EAP data) shines a whole new on Sterg's commentary and tone for me. Everything is obviously secondary to the modeling and the actual calendar for the REAGL trial, but to me this speaks volumes on his LinkedIn/investor conference victory laps... “mathematically, scientifically, clinically” believes GPS is driving the increased survival in REGAL.

Just my opinion, but the CEO of a publicly traded biotech company wont use words like "mathematically" and "scientifically" if his internal dashboard shows a huge wave of protocol violating transplants.

I haven’t been here in years but back in 2018-2021 it was the only sub focused on esselstyn type diets, low fat vegan with no or minimal oil. That doesn’t seem to be the case nowadays in 2026.

Is there another sub to discuss oil free vegan food? And the health benefits of eating that way?