REGAL Survival & HR Explorer

How this works

Fact SELLAS reports pooled death counts (60 → 72 → 78, still <80) from an ITT trial (NCT04229979) — not which arm each death belongs to. Those event anchors are the only certain inputs; everything else (BAT mOS, GPS cure fraction, HR) is inferred. Model We draw survival curves for BAT (Weibull + long-survivor tail) and GPS (mixture-cure plateau + uncured exponential, optional onset delay), add a shared post-enrollment transplant tail, and check whether expected deaths match those anchors. GPS cure fraction is swept in inverse mode (cw35/cw42/cw50 presets + inversion MC), not picked arbitrarily.

What the chart shows: Kaplan–Meier–style overall-survival curves from randomization — not patient-level resimulation. Pooled = 50/50 average of both arms.

Hazard ratio (HR): Pike/O–E ratio of observed vs expected deaths in each arm — an approximate log-rank HR, not the final stratified Cox from the SAP. Interim OBF efficacy floor HR ≲0.547 (@ 60 events); final win threshold HR < 0.636 (@ 80 events) from the design paper (Jamy & Cicic 2025).

Monte Carlo P(win): Sample prior uncertainty on each slider → weight draws by Poisson likelihood of the event increments → score significance via stratified log-rank Z at 80 deaths (or cutoff). P(win) = fraction of posterior weight with Z ≥ 2.01 — a model output, not a company forecast.

Anchor-constrained inversion: Mandatory constraint = reproduce event anchors (60/72/78). GPS cure fraction is the swept structural assumption (cw35/cw42/cw50 + inversion MC); least-squares solver derives implied BAT median/tail and GPS uncured mOS. HR and mOS are outputs — still non-identifiable along the GPS-cure ↔ BAT-heterogeneity ridge (critique thread).

Show math

Expected deaths @ T = Σ_enrollment N_arm · w_enroll · (1 − S(T − enroll)) · (1 − censor/2)

HR ≈ (O_GPS/E_GPS) ÷ (O_BAT/E_BAT) · Z = (Σ w(O−E)) / √(Σ w²V) · √η_strat

MC weight ∝ Pois(60|λ₄₆) · Pois(12|λ₅₈−λ₄₆) · Pois(6|λ₆₃−λ₅₈) · P(Δ≤1 @ m65)

Binding interim: weight × P(continue) · win = conditional power with ρ = √(60/80)

Full derivation: click Methodology. Tags: fact primary source · model simulation · assumption undisclosed slider.

Limitations caveats — Blinded pooled death counts fix the timeline but not the arm split (GPS vs BAT): many parameter sets fit 60/72/78, including HR ≈ 1 null-effect worlds. HR gauges and curves are model outputs (Pike/stratified log-rank approximations), not the SAP stratified Cox. Anchor-constrained inversion assigns durable survivors to GPS by assumption — CW's Weibull k≈0.85 grid differs from this app's exponential BAT (k=1) least-squares solver. Calendar months assume trial month 0 = 8 Feb 2021 (NCT04229979).

What this tab computes. Given arm-level survival curves you set, it (1) checks them against the announced blinded event counts, (2) estimates the hazard ratio and its statistical significance, and (3) runs a Bayesian Monte-Carlo posterior over the final HR.

1 · Survival & events

BAT arm = Weibull (shape k, k=1 → exponential) + a long-survivor "cure" fraction; GPS arm = mixture-cure (plateau c + uncured exponential) with an optional onset delay; optional post-enrollment transplant tail (ITT) added to both. Expected deaths by calendar month T = Σ over the enrollment S-curve of (1 − S(T − enroll)), ×(1 − censoring/2).

2 · Hazard ratio & significance

HR via the Pike/O–E estimator. Significance via the proper stratified log-rank score Z = (Σ w·(O−E))/√(Σ w²·V) · √(strat-efficiency) computed from the curves — so a late-loaded effect is correctly penalized (unweighted w=1; Fleming-Harrington w=1−S_pool). Win = Z ≥ 2.01 (the O'Brien-Fleming final boundary, design paper). Schoenfeld: 90% power at HR 0.636 needs ~205 events (calculator), so 0.636 at 80 events is the ~50%-power bar. The output panel shows these as two separate readouts: model-implied interim HR @ m46 vs the OBF efficacy floor ≈0.547 (IDMC continued Jan 2025), and projected readout HR vs the final 0.636 win threshold @ 80 events — they are not the same bar.

3 · Monte-Carlo posterior

Sample priors (slider = center, 1σ band = spread) → weight each draw by the Poisson likelihood of the observed event increments (60, +12, +6, still <80) → for a binding efficacy interim, soft-condition on "no early stop" (weight = P(continue); win = conditional power via the Brownian-motion correlation √(t₁/t₂)) — power-neutral, banks early wins. P(win) = Σ(w·p_win)/Σ(w).

4 · Anchor-constrained inversion (inverse mixture-cure fit)

Direct parameterization sets arm survival parameters and asks whether they reproduce the blinded event counts. Anchor-constrained inversion flips this: anchor the announced pooled events (60 @ m46, 72 @ m58, 78 @ m63, still <80) and treat the GPS cure fraction as the primary structural assumption (long-tail survivors assigned to GPS). With BAT constrained by biology (3-yr OS cap ~15–18%, Kurosawa whole-cohort no-HCT ~14% [Haematologica 2010]; CR2 subgroups higher), a least-squares solver derives implied BAT median/tail and GPS uncured median — mOS and HR fall out. Same mixture-cure machinery; direction of fit is reversed. Still non-identifiable along the GPS-cure ↔ BAT-heterogeneity ridge — honest about that. Practitioner framing: u/Confident-Web-7118 Part 1 · IRM tables: randomization window post; critique: u/uhdisj41.

Poke holes: the arm split is unidentifiable (blinded); priors do heavy lifting; the log-rank z is an expectation, not a patient-level resimulation; stratification/futility/test-weighting are undisclosed (adjustable). Full citations in References below.

Math verification (Jul 2026)

Audited inline functions against the formulas above: mixture-cure / Weibull survival (S_BAT=c+(1−c)·exp(−(t/λ)^k), median scale λ=bat/ln2^1/k); ITT transplant mix; enrollment-weighted expected deaths; Pike HR (O/E)_GPS/(O/E)_BAT at m58; stratified log-rank Z + OBF conditional power (ρ=√(60/D)); Poisson increment likelihood; inverse least-squares fit; SLS-009 fold/HR-equiv bench/arm under exponential assumption; valuation peak=starts×pen×years×price, EV=peak×multiple+platform. Spot checks: “No effect” preset HR≈1.000; CW cure preset HR≈0.19; inverse solver hits 72 events @ m58. Regression harness: node verify_math.js.

Scenario controls

Start here

Model-implied interim HR is below the early-stop floor (≈0.547) but IDMC continued — so either the IA was non-binding, the model overstates effect at IA, or both. Point P(win) under biology-first is high (~100%); neutral-prior MC is a separate ~50–78% band.

Binding interim IA Toggle only — same survival as Best Available Guess. MC weights P(continue) when checked.

Core CW stress tests

Each preset stress-tests one specific concern from u/Confident-Web-7118 or u/uhdisj41 DD — not arbitrary slider positions.

Identifiability edge cases

Identifiability ridge demo: fits mandatory event anchors but fails biological BAT caps — pedagogical, not a live scenario.

Upper strip = prior plausibility from the literature (1σ darkest → 3σ lightest).
Lower strip = values that still fit the announced 60/72/78-event timeline, given your other sliders. Black tick = current value.
Red hatch = biologically implausible (no supporting dataset). Not marked "impossible" — biology has outliers, and transplant crossover can legitimately extend a tail.
👆 Hover any band for the reasoning + numbered sources (see References at the bottom).

Auto-fit GPS cure fraction to hit 72 events @ m58 (1 degree of freedom in direct parameterization)

BAT arm (control)

BAT median — excl. long-survivors 13.0 m

Median of non-tail BAT component (from randomization). Design assumes 8.0m (Jamy & Cicic 2025); ven-era CR2 ~8–12m (Stahl 2021).

BAT long-survivor plateau 0%

Mixture-model cure plateau (batc) — flat long-term survivors added on top of the Weibull decline. Not the same as 3-yr OS (see readout): at 13-mo BAT median, batc=0 still yields ~15% at 3yr from the tail alone. Kurosawa ~14% is a 3-yr OS biology cap, not a plateau prior (Haematologica 2010).

CR2→rand lead-time (sensitivity) 3.0 m From-randomization clock is primary (event fit, chart, verdict). This slider only maps IRM medians → implied CR2-onset mOS ≈ max(0, IRM − lead). REGAL ≤6 mo CR2→rand + >6 mo life expectancy; Suissa 2008 left-truncation; CW IRM panel. Does not change eventsAt / passesVerdict / chart fit, and does not relax IA non-stop.

GPS arm (vaccine)

GPS cure fraction 42%

GPS patients on permanent plateau. Phase 2 CR2: no plateau (Brayer 2015); CR1 ~47% 3-yr (design paper). Highly uncertain.

GPS uncured median OS 47.5 m

Survival of non-cured GPS patients. Phase 2 CR2 whole-arm mOS 16.3 mo (Brayer 2015). m63 events pull fits high (78-event update).

GPS onset delay 3.0 m

Months before GPS separates from BAT (immune ramp-up). GPS primes over ~3 mo per protocol (design paper).

Trial parameters

Transplant after enrollment 0%

% of EACH arm transplanted post-enrollment (eligibility at entry only). Transplanted CR2 ~40–50% long-term (Forman & Rowe 2013). Shared tail shrinks GPS gap.

OS handling 🔒 locked

ITT — death from any cause (transplant survival counts, not censored)

Fixed: REGAL primary = ITT OS from randomization (NCT04229979; design paper).

Censoring / dropout 0%

Lost-to-follow-up before death. Phase 2 GPS ~15% (Brayer/OncLive). Differential dropout by arm not modeled.

Advanced

Advanced: enrollment shape

Enrollment midpoint (trial month) 25 m

Enrollment steepness 0.15

First patient = trial month 0 (8 Feb 2021, NCT04229979). Enrollment done ~m38 (Apr 2024, Apr 2024 PR), N=127.

Method & structural assumptions (all adjustable — none of these are disclosed)

Fleming-Harrington late-weighted test (FH 0,1) OFF = unweighted stratified log-rank (design paper). ON = Fleming-Harrington late-weight (Hasegawa 2014). REGAL's actual test-weighting is NOT public.

BAT hazard shape (Weibull k) 1.00 1.0 = constant hazard (exponential). <1 = declining hazard (biologically favored for AML; fattens the BAT tail).

Stratification efficiency 0.90 Info retained by the 16-cell stratified log-rank vs unstratified (sparse-strata power cost). 1.0 = no loss.

Interim futility strictness (z) 0.40 How clearly the interim had to beat futility. 0 = essentially none; higher = the interim ruled out weaker worlds. REGAL's exact futility rule is not public.

Binding-vs-non-binding efficacy is toggled in the Monte Carlo panel. OBF Z-values (2.34 / 2.01), 0.636 threshold, N=127, event counts, and 80-event trigger are locked facts (design paper).

Survival curves (from randomization)

Model output ITT overall-survival curves: GPS (mixture-cure), BAT (Weibull + tail), pooled 50/50 average. Vertical dashed line = 36 months. Medians and HR below are derived from these curves — not unblinded trial data. Hover/tap curve for survival values.

BAT median OS (from rand / IRM)

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CR2-onset: –

GPS median OS (from rand / IRM)

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CR2-onset: –

BAT 3-year OS (from-rand clock)

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GPS 3-year OS (from-rand clock)

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Pooled median OS (from rand / IRM)

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CR2-onset: –

RMST gain, GPS−BAT (48-mo horizon)

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Projected 80th event

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Lead-time sensitivity: event fit is a post-selection cohort; lead-time does not relax IA non-stop.

Interim efficacy check @ m46 (60 events)

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0.0Early-stop floor 0.547 (@ 60 events, Z=2.34)1.0

At the Jan 2025 interim, IDMC continued — so the actual stratified interim cleared the OBF boundary (Z=2.34, HR≲0.547; Jamy & Cicic 2025). The gauge below shows a model-implied Pike HR at m46, which can differ. This is a different bar than the final win threshold below.

Projected readout HR –

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0.0Final win 0.636 (@ 80 events, Z=2.01)1.0 (no effect)

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Consistency with announced numbers model-implied counts vs PR anchors

Events @ m46 (announced 60) [source]– –

Events @ m58 (announced 72) [source]– –

Events @ m63 (announced 78) [source]– –

Events @ m65 (must be <80 — today) [source]– –

Pooled median OS (announced >13.5m) [source]– –

Patients with ≥36-mo follow-up @ m63–

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Monte Carlo — final-HR distribution

Samples the priors — each slider = the prior CENTER, its blue 1σ band = the spread — and weights each draw by a Poisson likelihood of the observed event increments (60 @ m46, +12, +6, still <80). Win = stratified log-rank significance; HR < 0.636 threshold from design paper. Model output — only as good as the priors.

Sensitivity tornado — which inputs move P(win) most? model

One-at-a-time perturbation of key parameters (±20% or ±1σ band) from the current scenario. Bars show ΔP(win) in percentage points — green = higher win probability when perturbed in the favorable direction. Uses a fast approximate MC (5k draws per perturbation). assumption

Bayes factor — strawman null vs heterogeneous BAT null model

Compares two competing null hypotheses against observed pooled event counts. CW's ~62× Bayes factor (Part 1 DD) uses a strawman (everyone dies fast, no tail). Under a heterogeneous BAT null with a long tail (uhdisj41 critique), marginal BF collapses toward ~1× because blinded pooled counts cannot discriminate the shapes. Approximate Poisson likelihood ratio — honest caveats apply.

Strawman null (CW implicit)

Exponential BAT (mOS ~8m), no GPS cure, no long tail

Heterogeneous BAT null (critique)

BAT Weibull + 18% long-survivor tail (Kurosawa 2010 range), GPS weak (5% cure) — assumption

Observed events @ m58 72

GPS cure fraction (alternative hypothesis) 42%

Interactive IRM table — REGAL-report ↔ TRUE CR2 conversion assumption

Uses the CR2→rand lead-time slider (BAT controls, 0–6 mo). IRM = from-randomization medians (primary clock: event fit / chart / verdict). Implied CR2-onset ≈ max(0, IRM − lead). Lead-time does not change eventsAt / passesVerdict / chart fit and does not relax IA non-stop — event fit is a post-selection cohort. Sources: CW IRM post · Suissa 2008 · REGAL ≤6 mo CR2→rand + >6 mo life expectancy.

Parameter	Model (current)	CW / literature	Δ / note

Time-to-80th-event simulator model

Monte Carlo simulation of months until the 80th death from the confirmed 78 @ m63 anchor — model increments only for the remaining 2 events. PR pace reference: linear extrapolation from 72→78 (+6 in 5 mo). Sources: 60 @ m46, 72 @ m58, 78 @ m63.

Compare scenarios model

Side-by-side comparison of two presets or share-URL states. Green/red deltas favor higher P(win) / lower HR (GPS bull case). Uses paramsFromPreset() for forward and inverse presets.

Scenario A

Scenario B

Or paste share URL hashes (optional):

Metric	A	B	Δ (B−A)

Final events timing sensitivity model

Hypothetical calendar months when the 79th and 80th deaths occur — vs company PR deceleration pace (12 deaths in 12 mo from 66 at risk @ 72-event update, Dec 2025 PR). Baseline anchor: 78 @ m63 (May 2026 PR).

79th event @ month 65

80th event @ month 68

Preset comparison dashboard model

All REGAL forward and inverse presets computed side-by-side — no clicking through one by one. P(win) uses the same fast approximate MC as the tornado panel (3k draws per preset). May take a few seconds.

Show only presets that fit 60/72/78 anchors + biological BAT caps

Preset	Mode	Fit	HR	e46 (mod)	e58 (mod)	e63 (mod)	P(win)	BAT 3yr	GPS cure
Click Compute all presets

Milestone backtest — what would P(win) have been then? model

At each historical milestone, shows HR and P(win) using a truncated Poisson likelihood (only event counts announced by that date) while holding today’s slider values fixed — it does not re-fit parameters with hindsight. Honest caveat: retrospective structure + current priors, not what was knowable or modeled in real time.

Community DD — u/Confident-Web-7118 IRM / lead-time analysis assumption

Replication note Tables below quote u/Confident-Web-7118's published modeling outputs (not our solver). This app's anchor-constrained inversion uses the same event anchors and mixture-cure framing but different parameterization — implied medians/HR may differ slightly; use the sliders/MC to compare. Primary sources: IRM / randomization window ↗ · Part 1 DD ↗ · Part 2 DD ↗ · Biology/stats update ↗ · Critique (uhdisj41) ↗

IRM definition

IRM (Implied Randomization Median) = median OS measured from randomization — what REGAL will report at topline. Differs from TRUE CR2-onset median (literature clock starts at second remission). REGAL's ≤6-month CR2→randomization window excludes early deaths → positive selection lifts reported BAT mOS ~1.5–4 mo vs underlying biology; HR is unchanged (same lead-time on both arms). [CW IRM post] · Suissa 2008

Topline BAT mOS → TRUE CR2-onset (CW conversion)

What REGAL reports (IRM)	≈ TRUE CR2-onset mOS
BAT mOS = 13 mo	9–10 mo
BAT mOS = 14 mo	10–11 mo
BAT mOS = 15 mo	11–12 mo
BAT mOS = 16 mo	12–13 mo

Example (CW): TRUE CR2-onset median 11 mo, Weibull k=0.85, avg lead time D=3 mo → IRM ≈ 14.7 mo (+3.7 mo inflation). [source]

Scenario fits to 60 / 72 / 78 events (CW tolerance sweep)

Scenario	Event tolerance	IRM	HR @ 80th	BAT 3-yr OS S(36)	Pooled mOS
Data-precise	±1 event	15.9	0.58	22%	19.2
Biology-consistent	±1.5 events	10.3	0.23	14%	18.7
Compromise (weighted)	—	~13	~0.40	~18%	~19

CW argues ±1 event is too strict (Poisson σ ≈ 7–9 per anchor); ±1.5 admits biologically plausible BAT 3-yr OS 5–15%. [source]

Three constraint scenarios @ 80th event (CW preferred = Scenario C)

Constraint set	Best fit	IRM	HR @ 80th	BAT S(36)	HR @ IA	BAT alive	GPS alive
Data only (±1)	M=13, k=0.85	16.04	0.59	25.7%	0.85	15.1	30.9
Biology only (S(36)≤15%, ±1.5)	M=8, k=0.85	9.85	0.22	13.0%	0.32	7.2	38.8
OBF + S(36)≤20% (±1.07)	M=10, k=0.85, p_bridge=5%	12.61	0.37	19.6%	0.59	11.3	34.7

Scenario C is CW's coherent pick: OBF-compatible interim (HR_IA≈0.59, no early stop), biologically defensible tail, ~35 GPS / ~11 BAT alive at 80th. Alive counts of 63/arm. [source]

Best biology+data fits (±1.5 events, before randomization lift)

M	k	p_bridge	Residual	IRM	HR @ 80th	BAT S(36)	Pooled
9	0.95	5%	1.18	10.33	0.23	13.6%	18.66
9	0.95	3%	1.27	9.92	0.20	11.3%	18.79
8	0.85	3%	1.17	9.85	0.22	13.0%	18.63
7	0.85	5%	1.37	9.14	0.21	13.5%	18.45
10	0.95	5%	1.37	10.55	0.25	14.1%	18.85

CW Part 1 anchored cure model (reverse-engineered from 72 @ m58)

Parameter	CW published value	This app preset
BAT median (from rand)	10 mo (historical anchor)	10 mo — Optimistic cure (~85%)
GPS cure fraction	42–48% (output ≈42% anchored)	42% fixed (+ optional auto-fit)
GPS uncured median	34–39 mo	36 mo
Expected topline Cox HR	0.35–0.50 (press release range)	Model-derived; MC with non-binding IA → ~85%+ P(win)
Model-internal HR (cure MC)	0.13–0.30 (NPH distortion)	Lower under mixture-cure — not headline HR
P(success) posterior	99.9% (Part 2, all BAT uncertainty)	Run MC — differs by priors & IA binding

Part 1: 72 events @ m58 + deceleration ⇒ cure-fraction on GPS arm; unconstrained grid search pushed BAT to ~14.5 mo with ~64% cure (identifiability ridge). Part 2: Bayesian synthesis → BAT mOS 11.4 mo (99% within 10–13). Event deceleration: 12 deaths in 12 mo from 66 at risk. [Part 1] · [Part 2]

Bayes factor (~62×) — honest caveat

CW's cure-structured alternative vs a no-cure exponential null reportedly yields Bayes factors on the order of ~62× (data much more likely under mixture-cure than under null). That comparison is a strawman if the null ignores BAT long-survivor tails — along the GPS-cure ↔ BAT-heterogeneity ridge, marginal BF collapses toward 1 because blinded pooled counts cannot discriminate the two shapes. [uhdisj41 critique] · see Explain tab (PhD).

BAT biology cap (3-yr OS)

CW caps BAT long-tail at ~15–18% 3-yr OS (Kurosawa CR2 transplant-ineligible ~14%; intermediate-risk ~19%). Anchor-constrained inversion preset Default (~42%) uses 17% cap — matches CW biology-consistent framing. TRUE CR2-onset BAT biologically ~8–11 mo before randomization lift; topline IRM ~12–15 mo is not "world-record BAT." [CW biology post]

Excluded as fact Part 2 posterior P(success) ≈ 99.9% and headline Bayes ~62× vs a no-cure null — 🔬 model outputs only; see Community perspectives (validated) below and the Bayes-factor panel.

Community perspectives (validated) primary-checked

Expand to load contributor synthesis (lazy). Tags: ✅ verified · ⚠️ partial · ❌ not as fact · 🔬 model/opinion

Known facts & the bet verified from PRs/filings · unknown not disclosed

Trial: REGAL Phase 3, N=127 actual (~63–64/arm), AML CR2/CRp2, transplant-ineligible, open-label, start 8 Feb 2021 verified [NCT]

Primary endpoint: OS = death from ANY cause since randomization → ITT, transplant NOT censored; final analysis at 80 events verified [design]

BAT arm (weak by design): investigator's choice of observation/HMA/venetoclax/LDAC; FLT3- & IDH-maintainable patients EXCLUDED verified [NCT]

Design: HR < 0.636 = significance BAR (~50% power), NOT the design alternative (~0.48–0.53 for 90% power). 80 deaths, 1-sided α=0.025 verified [design]

Test: Lan-DeMets O'Brien-Fleming (interim Z≈2.34, final Z≈2.01) + unweighted stratified log-rank primary verified [design]

Interim design: O'Brien-Fleming, reviewed efficacy + futility + safety verified [design]

Enrollment: first patient Feb 2021; 126 completed ~Apr 2024 verified [PR]

Event timeline: 60 (Jan'25) · 72 (26 Dec'25) · 78 (11 May'26) · still <80 (no 80th-event PR through Jul 2026) verified [Jan'25] · [Dec'25] · [May'26]

Interim (60 deaths): OBF efficacy boundary NOT crossed → not stopped early ⇒ actual interim HR >≈0.547; futility cleared. "Continue w/o modification" Jan'25 & Aug'25 verified [Jan'25] · [Aug'25]

Computed OBF boundaries: interim Z=2.34 → HR≤0.547 to stop early; final Z=2.01 → win needs HR≤0.636 derived [design]

Blinding: open-label at sites; sponsor blinded to aggregate results verified [NCT]

Follow-up @ interim: median 13.5 mo; pooled median OS >13.5 mo; <50% deceased verified [PR]

Nov 2022 blinded pooled read: pooled mOS "~two-fold longer than originally anticipated" (design 10.3m → ~20m) verified [PR]

Lead-time / left-truncation: CR2→randomization window + entry criteria lift from-rand median ~1–3 mo above from-CR2 literature derived [Suissa 2008]

Dosing: pivotal core = 15 injections over 52 wks; Y2/Y3 maintenance by amendment verified [design]

Phase 2 CR2 (Brayer, n=10): GPS mOS 16.3 vs 5.4 mo (p=.02); NO plateau verified [PubMed]

Phase 2 CR1: ~47% 3-yr plateau; immune-response rate ~64% verified [design]

Historical BAT (Kurosawa): 3-yr OS 14% for ALL relapsed / no-HCT / survived ≥2 mo (includes non-CR2) — CR2/no-HCT subgroups higher (intermediate ~19%, unfavorable ~35%, favorable ~50–78%); ven-era median ~8–12m verified [Kurosawa] · [Stahl]

Enrollment (back-loaded): 105 (ex-China) by Nov 2023 · N=127 by ~Apr 2024 verified [PR]

Discontinuations: 66 pts stopped TREATMENT by Mar 2024 (blinded) — relapse-driven, NOT OS censoring verified [PR]

Cash: ~$107M (Mar 2026) + $7.5M warrants; ~$7M/qtr burn verified [Q1'26 PR]

WT1 platform value: modeled in Tab 3 — GPS (WT1 vaccine) + SLS-009 (separate CDK9 asset); shared sponsor only see Tab 3

Arm-level split of the 72–78 deaths: unknown (blinded) — the crux unknown

% censored / differential dropout: not disclosed (Phase 2 GPS CR2 was ~15%); could bias KM/HR unknown

Actual BAT median in-trial: unknown; could exceed historical if enrolled population is healthier unknown

Real stratified Cox HR & p-value: unknown until 80th event + unblinding unknown

The bet in one line: the announced event pace (78 events @ m63) is the only certain constraint — it implies pooled survival above historical CR2 (Stahl 2021). A no-effect HR≈1 world can still fit the anchors with a shared ~28% tail, but that requires BAT mOS ~24 m (biologically rejected; see Ridge preset). GPS cure fraction must be swept, not picked arbitrarily. The magnitude (HR) and arm split remain unidentifiable pre-unblind. Win threshold 0.636 is modest (design paper).

References (sources for every band & fact)

REGAL design paper — Jamy O, Cicic D. Future Oncol 2025 (PMC11760237). Design assumptions (BAT 8.0m vs GPS 12.6m, HR 0.636, 80 deaths, "90% power" as stated by the design paper — but note this is internally inconsistent: Schoenfeld gives ~50% power at HR 0.636 with only 80 events; 90% power at HR 0.636 needs ~205 events), O'Brien-Fleming interim, GPS dosing, Phase 1/2 summaries. pmc.ncbi.nlm.nih.gov/articles/PMC11760237
ClinicalTrials.gov NCT04229979 — eligibility (transplant-ineligible at entry; FLT3/IDH-maintainable excluded), N=127, OS = death from any cause (ITT), BAT options, start 8 Feb 2021. clinicaltrials.gov/study/NCT04229979
SELLAS interim (60 events) — 23 Jan 2025; IDMC "continue without modification." globenewswire.com (Jan 2025) · IR
SELLAS IDMC (Aug 2025) — second "continue without modification" after 60-event interim. IR (Aug 2025)
SELLAS 72-event update — 29 Dec 2025; remains blinded. globenewswire.com (Dec 2025)
SELLAS 78-event / Q1 2026 — 12 May 2026; 78 events as of 11 May 2026, cash ~$107M. globenewswire.com (May 2026)
QUAZAR AML-001 — oral azacitidine maintenance; CR1-placebo median OS 14.8m (a healthier population → BAT ceiling). CancerNetwork · Am J Hematol (long-term)
GPS Phase 2 CR2 (Brayer et al. 2015) — n=10; GPS median OS 16.3 vs 5.4m (p=.02); PFS 10.5 vs 4.3m NS; no plateau. OncLive summary · PubMed (Brayer 2015)
Forman SJ, Rowe JM. "The myth of the second remission of acute leukemia in the adult." Blood 2013 — 5-yr OS from first relapse ~10%; AML no-prior-transplant post-relapse ~12%; CR2-transplant cure ~40–50% (selected minority). PubMed (Forman & Rowe, Blood 2013)
Kurosawa S et al. Haematologica 2010 — 158 AML in CR2 ineligible for transplant: 3-yr OS 14% overall for the whole cohort (all relapsed, no-HCT, survived ≥2 mo — not a pure CR2 figure); CR2/no-HCT subgroups run higher (intermediate ~19%, unfavorable ~35%, favorable CBF ~50–78%). Conservative BAT anchor. Haematologica 2010 (PMID 20634493)
Stahl M et al. — venetoclax-era R/R AML salvage — modern CR2/salvage OS medians ~8–12m by mutation (NPM1/FLT3/TP53); durable survival still gated on transplant. Blood Adv 2021
REGAL enrollment & discontinuation milestones — first patient Feb 2021; 105 pts (ex-China) by Nov 2023; full enrollment ~Apr 2024; 66 patients had discontinued treatment by Mar 2024 (blinded; relapse-driven, not OS censoring). Apr 2024 IDMC/enrollment PR
SELLAS Nov 14, 2022 update — blinded pooled mOS "approximately two-fold longer than originally anticipated" (design pooled 10.3m → ~20m). globenewswire.com (Nov 2022)
AVALON — Todisco et al. Cancer 2023 — Italian real-world Ven+HMA cohort (190 pts incl. relapsed/refractory AML); R/R median OS in the single digits, durable survival gated on transplant. Cancer 2023 · 2025 transplant-bridge subanalysis
Community due-diligence — u/Confident-Web-7118 (REGAL) Cure-fraction mixture model, event deceleration (72 @ m58), IRM / lead-time tables, BAT mOS prediction (~11.4 mo), non-binding interim framing. Part 1 DD ↗ · Part 2 DD ↗ · IRM / randomization window ↗ · Biology update ↗ · 24/7 Wall St. ↗. Incorporated as Optimistic cure (~85%) forward preset and anchor-constrained inversion mode (assumption).
Independent critique of Confident Web DD (u/uhdisj41) — identifiability ridge, Bayes-factor inflation, BAT-tail biology. Reddit critique ↗ · DD questions (May 2026) ↗. Informed the "Critique (~⅔)" preset.
Community DD — u/Thetamancer — event-fit Monte Carlo stress tests (Memorial Day DD). Memorial Day DD ↗
Community DD — u/uhguy85 — framing of 99.99% model output; enrollment-cadence / median-enrollment derivation. 99.99% explainer ↗ · Enrollment cadence ↗
Community DD — u/Remarkable-Big-9849 — BAT heterogeneity / transplant-bridge debate; biology rebuttals. COVID frailty hypothesis ↗ · Bear-thread biology ↗
Community DD — u/neo2551 — scientific-process / community-rigor synthesis; links this webapp. Scientific process DD ↗ · Webapp post ↗
Control-arm overperformance meta-analysis — Nalin et al., Cancer 2026 (PMC12882696): 385 phase 3 oncology RCTs; 43% with >10% control-arm overperformance; OS-primary trials higher. Cited by Thetamancer for BAT-cap argument.
Interim & design-power computation (this analysis) — Lan–DeMets O'Brien-Fleming, one-sided α=0.025, looks at t=0.75 & 1.0: interim Z=2.34 (HR≤0.547), final Z=2.01 (HR≤0.636 to win). Schoenfeld check: 90% power at HR 0.636 needs ~205 events, so 80 events at 0.636 ≈ 50% power ⇒ 0.636 is the significance BAR, the ~90%-power alternative is ~0.48.

Statistical methods (primary sources)

Log-rank / score test (our U/√V significance): Mantel 1966; Peto & Peto, JRSS A 1972. Cox PH model: Cox, JRSS B 1972. Mantel · Cox
Events-for-power (Schoenfeld): D = (z_α+z_β)² / [r(1−r)(ln HR)²]. Schoenfeld, Biometrika 1981 & Biometrics 1983. calculator · PubMed
α-spending & group-sequential boundaries: O'Brien & Fleming, Biometrics 1979; Lan & DeMets, Biometrika 1983. OBF · Lan-DeMets
Conditional power & sequential-statistic correlation √(t₁/t₂): Jennison & Turnbull (2000); Proschan & Hunsberger, Biometrics 1995. Proschan-Hunsberger
RMST (NPH-robust effect measure): Uno et al., J Clin Oncol 2014. PubMed · RMST vs HR
Weighted log-rank / Fleming-Harrington: Fleming & Harrington (1991); Hasegawa, Pharm Stat 2014. PubMed
Mixture-cure / plateau models: Boag, JRSS B 1949; Berkson & Gage, JASA 1952. Boag
Lead-time / left-truncation bias: Suissa, Am J Epidemiol 2008. AJE 2008
Approximate Bayesian Computation (likelihood-weighting): Beaumont, Zhang & Balding, Genetics 2002. PubMed

Tags: verified = stated in a primary source above · derived = computed here · unknown = not disclosed (blinded).

How this works

Fact SLS-009 Phase 2 is open-label, single-arm SLS-009 + AZA/VEN in post-venetoclax r/r AML-MR (NCT04588922). ASH 2025: ORR 46% (35 evaluable), mOS 8.9 mo (least pretreated) vs ~2.5–2.6 mo historical (ASH PR · Zainaldin 2022). Model Exponential curves compare arm mOS to external benchmark — not a randomized HR.

OS fold-improvement = arm median ÷ benchmark median (e.g. 8.9 ÷ 2.8 ≈ 3.2×). Under constant hazard, OS ratio (≈ HR under exponential) = benchmark ÷ arm (inverse of fold). This is a shorthand — not a randomized log-rank HR.

Phase 3 power (Monte Carlo): Hypothetical frontline trial SLS-009+Aza/Ven vs Aza/Ven alone. Sample projected medians, compute OS ratio = control ÷ treatment, estimate P(significant) via Schoenfeld-style Z at assumed event count (default 250 deaths). Assumption — proxy from median ratio, not SAP log-rank; event count and effect size are user-set priors.

Show math

S(t) = exp(−ln2 · t / mOS) · fold = mOS_arm / mOS_bench

HR_equiv = mOS_bench / mOS_arm · Z ≈ −ln(HR) · √(D/4) · P(win) ≈ Φ(Z − 1.96)

SLS-009 + AZA/VEN in relapsed/refractory AML-MR after prior venetoclax — Phase 2, single-arm vs historical. Green-tagged numbers are the reported Phase-2 readouts; move the sliders to stress them.

Blue = prior plausibility (1σ→3σ). Red = biologically implausible. ◆ = reported/anchor value. Hover a band for the source.

Scenarios

Observed = exact Ph2 anchors (ASH 2025). Best Available Guess = reported data with conservative benchmark drift adjustment.

Relapsed / refractory AML-MR (Phase 2)

SLS-009+AZA/VEN median OS 8.9 m

Reported 8.9m AML-MR least-pretreated; 8.8m @ 1 prior line (July PR). ASH 2025 · Jul 2025 PR · SEC 8-K

Historical post-venetoclax benchmark OS 2.8 m

Company cites ~2.4–2.6m (1 prior line). Literature range 1.7–6.1m by cohort. Zainaldin 2022 · Maiti 2021 · Stahl 2021

Overall response rate (ORR) 46 %

Reported 46% (35 evaluable); 58% with 1 prior line; CR/CRi 29%. Blood 2025 · Jul 2025 PR

Frontline (newly diagnosed) — Phase 2b → 3

Aza/Ven baseline mOS 14.7 m

Verified 14.7m VIALE-A. DiNardo, NEJM 2020

+SLS-009 frontline mOS (projected) 20 m

Projection — not observed. Randomized 80-pt frontline Ph2 enrolling (Mar 2026).

TP53-mut Aza/Ven baseline 5.3 m

Verified ~5.3m VIALE-A TP53 subgroup. PubMed

TP53-mut +SLS-009 (projected) 13 m

Projection — early signal only. ASH 2025

SLS-009 vs historical benchmark (r/r)

Model Exponential OS curves: treatment (reported mOS) vs historical benchmark. Fold-improvement and OS ratio assume constant hazard — a simplification for single-arm vs external control.

OS fold-improvement

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OS ratio (≈ HR exp.)

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Months gained

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ORR

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Monte Carlo — SLS-009

Propagates prior uncertainty (each slider = center, 1σ band = spread) through r/r fold-improvement and a hypothetical frontline Phase 3 (SLS-009+Aza/Ven vs Aza/Ven alone). Frontline arm uses projected mOS uplift vs VIALE-A (mOS 14.7 mo, HR 0.66). Power uses Schoenfeld-style Z at assumed death count — assumption, not a trial design. The r/r arm is single-arm-vs-historical (Zainaldin 2022 benchmark), so its "signal" ≠ a randomized win.

Frontline OS ratio distribution (green = < 0.75; proxy from median ratio, not SAP log-rank):

Historical benchmark — where ~2.4–2.8 mo comes from primary-checked

SELLAS compares SLS-009 mOS to external historical controls, not an in-trial comparator. The ~2.4–2.6 mo figure in ASH/July PRs maps to post-venetoclax failure cohorts; broader R/R ven+HMA literature spans ~1.7–6.1 mo depending on prior lines and salvage treatment.

Population	Median OS	Source	Use in app
R/R after HMA+Ven (company benchmark, 1 prior line)	2.4 mo	Zainaldin 2022 (cited in Jul 2025 PR)	Observed preset: 2.5m
R/R after HMA+Ven (ASH PR wording)	~2.5–2.6 mo	ASH 2025 PR	Observed preset anchor
Frontline Ven+HMA failure (European real-world)	2.3 mo	Haematologica 2022	Lower bound of range
Frontline Ven+HMA failure (MD Anderson)	2.3 mo overall; 2.4 vs 1.8 by setting	Maiti 2021	Corroborates ~2.4m
R/R Ven combinations (Stahl cohort, all-comers)	6.1 mo (aza/ven 8.1 mo)	Stahl, Blood Adv 2021	Upper bound if healthier salvage pool
R/R Ven+HMA (comprehensive center)	5.5 mo (4.3 if prior HMA)	Tenold 2021	Drift-adjusted bear case: 3.5m
>1 prior line (company benchmark)	1.8 mo	Jul 2025 PR	Heavily pretreated subset

Best Available Guess uses 2.8m benchmark — modest upward drift from company’s 2.5m to reflect that historical-control comparisons often undercount modern salvage/transplant and healthier trial selection. Bear pushes benchmark to 3.5m (Stahl-like salvage-treated subset). Neither is a randomized control.

Bear case & trial limitations caveats

Single-arm Phase 2 efficacy is judged against external history — the FDA may accept it for accelerated approval in ultra-high-unmet settings, but confirmatory randomized data are still required. Community bull posts often overstate certainty; items below are what bears and methodologists flag.

Single-arm design — no concurrent control; all patients receive SLS-009+AZA/VEN (NCT04588922). Efficacy vs history, not vs live BAT.
Selection bias — trial sites (academic centers) and inclusion criteria (fit for triplet, post-Ven AML-MR) may enroll healthier patients than real-world post-Ven failure (European RW).
Immortal time / response bias — responders who achieve CR contribute disproportionately to mOS; ORR 46% ≠ 46% long-term cure. mOS in 1-prior-line subset was not reached with shorter follow-up (ASH 2025).
Historical-control drift — benchmarks from 2020–2022 may not match 2025 salvage mix (more post-transplant, different ven exposure). Using Stahl-like 6m benchmark collapses apparent fold-improvement (Stahl 2021).
Small N / subset fishing — ASH 2025 reports n=35 evaluable; ASXL1/TP53 subgroup ORRs are hypothesis-generating (48%/57%) not independently validated (Blood 2025).
ORR ≠ OS guarantee — Phase 2 target was ORR ≥20% and mOS ≥3 mo (Jul 2025 PR); meeting bar ≠ registrational proof.
Community overclaims excluded — "100% CR ASXL1+" (Reddit) superseded by 44–50% at optimal dose; "guaranteed FDA approval" is ❌ not supported as fact.

r/sellaslifesciences bear framing (bear cases thread) focuses mostly on GPS, not SLS-009 biology — SLS-009-specific skepticism centers on single-arm vs historical and commercial timing vs REGAL.

Comparables — frontline SoC & other CDK9 programs cited

Program	Setting	Key outcome	Relevance to SLS-009
Aza + Ven (VIALE-A)	Frontline unfit ND AML	mOS 14.7 vs 9.6 mo; HR 0.66	DiNardo, NEJM 2020 — frontline control anchor in Tab 2
VIALE-A TP53-mut subgroup	Frontline	mOS ~5.3 mo (ven arm)	PubMed — TP53 slider baseline
Vyxeos (CPX-351)	Frontline AML-MRC	mOS 9.6 mo	Lancet 2018 — community compares r/r SLS-009 OS to frontline Vyxeos (Reddit); different line of therapy
Voruciclib (CDK9i) + Ven	R/R AML	Early Ph1/2 signals at ASH 2024	Community ASH 2024 — competing CDK9 mechanism
QHRD107 (CDK9i)	R/R AML	ASH 2024 poster	Community
Regor (CDK inhibitor)	Ph1 AML	~$850M upfront deal on ~28% CR	Community comp — M&A ceiling reference, not clinical equivalence
GPS (galinpepimut-S)	AML CR2 maintenance	Phase 3 REGAL (blinded)	Same sponsor; complementary not competing (NCT04229979)

Catalysts & related trials verified registry/SELLAS · community unverified · model not in valuation

Separate from SELLAS-run AML trials modeled in Tabs 2–3. A positive PTCL readout is a biology/tolerability signal for the CDK9 class (same molecule as GFH009/SLS-009), not a direct input to OS-ratio sliders or AML peak-sales math.

GenFleet PTCL Ph Ib/II: GFH009 = SLS-009 / tambiciclib (same molecule) — open-label single-arm monotherapy in r/r PTCL, ~95 pts; Phase II primary = ORR verified [NCT05934513]

Sponsor: GenFleet Therapeutics (China) — not SELLAS-run; SELLAS lists trial as GenFleet-sponsored and fully funded verified [SELLAS trials]

Registry timing (estimates): primary completion Dec 30, 2025; study completion Jun 30, 2026 — registry projections, may lag verified [NCT]

Community timing: r/sellaslifesciences claims DB lock ~Jun 30 → topline Jul–Aug 2026 — not verified community

SELLAS AML trials (distinct timeline): r/r combo + frontline Ph2 (NCT04588922) are SELLAS-run; months away from new registrational readouts verified [NCT] · [Mar 2026]

Phase 1 historical (different trial): NCT04588922 lymphoma cohort — SELLAS cites 36.4% response in PTCL subset at RP2D 100 mg weekly; early dose-finding, not the dedicated PTCL Ph Ib/II verified [SELLAS trials] · [NCT04588922]

Not in this model: PTCL ORR read-through is not folded into Tab 2 OS-ratio sliders or Tab 3 AML peak-sales inputs model

Community DD — SLS-009 (validated) primary-checked

Expand to load r/sellaslifesciences synthesis for SLS-009. Tags: ✅ verified · ⚠️ partial · ❌ not as fact · 🔬 model/opinion

SLS-009 facts & sources verified from PRs/filings · unknown not disclosed

Trial ID: NCT04588922 — Phase 2, open-label, single-arm, multi-center verified [NCT]

Drug: SLS-009 / tambiciclib (GFH009) — selective CDK9 inhibitor, GenFleet license verified [SEC 8-K]

Population: r/r AML-MR after prior venetoclax-based therapy; 87% AML-MR, 43% ASXL1-mut (Jul PR) verified [Jul 2025]

Enrolled / evaluable: 54 evaluable treated (Jul PR); 35 evaluable at ASH 2025 cut verified [ASH]

Dosing: Optimal 30 mg IV twice-weekly (BIW) + AZA/VEN; also tested 45 mg, 60 mg QW verified [Jul 2025]

Primary endpoint: ORR (target ≥20% at optimal dose); key secondary OS, safety verified [Jul 2025]

ORR (ASH 2025): 46% all (CR+CRi+MLFS); 29% CR/CRi; 58% with 1 prior line verified [Blood 2025]

mOS: 8.9 mo least-pretreated; NR in 1-prior-line cohort; vs ~2.5–2.6 mo historical verified [ASH]

Biomarkers: ASXL1 ORR 48% (19% CR/CRi); TP53 ORR 57% (29% CR/CRi) verified [Blood 2025]

Safety: No DLTs, no treatment-related deaths; hematologic tox consistent with AZA/VEN alone verified [ASH]

Historical benchmark: ~2.4 mo (1 prior line), 1.8 mo (>1 line) per Zainaldin 2022 verified [Zainaldin]

FDA guidance: Advance to trial incl. newly diagnosed + early ven resistance cohorts verified [Jul 2025]

Frontline Ph2: Randomized ~80 pts (US + ~40 EU via IMPACT-AML); 1st patient Mar 2026 verified [Mar 2026] · [IMPACT-AML]

Frontline cohorts: (1) biomarker-predicted non-responders to AZA/VEN; (2) confirmed no response after 2 cycles AZA/VEN verified [corp deck]

Frontline control anchor: Aza/Ven mOS 14.7 mo (VIALE-A); TP53-mut ~5.3 mo verified [NEJM]

Projected frontline + TP53 uplift: not observed — slider projections only estimate

Median DOR / transplant rate: not disclosed in ASH headline PR unknown

Randomized r/r confirmatory trial: not yet started unknown

SELLAS Phase 2 — Jul 2025 topline — 54 evaluable, ORR 33–44%, mOS 8.8–8.9 mo, FDA frontline guidance. GlobeNewswire · IR
ASH 2025 presentation — n=35 evaluable, ORR 46%, CR/CRi 29%, mOS 8.9 mo, ASXL1/TP53 subsets. IR · Blood abstract
Dec 2024 OS/ORR PR — earlier cut of Phase 2 data. GlobeNewswire
SEC 8-K exhibit (Mar 2026) — Phase 2 data summary for investors. SEC
ClinicalTrials.gov NCT04588922 — trial design, eligibility, sites. clinicaltrials.gov
Historical benchmark — Zainaldin et al. 2022 — post-Ven failure mOS ~2.4 mo (company-cited). Leukemia & Lymphoma
Maiti et al. Haematologica 2021 — frontline Ven+HMA failure outcomes. Haematologica · European RW 2.3 mo: Haematologica 2022
Stahl et al. Blood Adv 2021 — R/R ven combinations, mOS 6.1 mo (upper benchmark bound). PubMed
Frontline control — VIALE-A — DiNardo et al., NEJM 2020 (mOS 14.7 mo, HR 0.66). NEJM
Frontline Ph2 enrollment — first patient Mar 2026; IMPACT-AML EU expansion. Mar 2026 IR
ASH abstracts (prior) — Blood 2024 Ph2a · OncLive
Community DD — r/sellaslifesciences — Promise of SLS009 · Bull case · Bear cases · 300% OS post · Potential buyers

Claim	Primary source	Status
ORR 46% (35 evaluable, ASH 2025)	Blood 2025	✅
ORR 58% / mOS NR with 1 prior line	ASH PR	✅
mOS 8.9 mo (least pretreated)	ASH PR	✅
Historical benchmark ~2.4–2.6 mo	Zainaldin 2022	✅
Single-arm, no randomized control	NCT04588922	✅
Frontline Ph2 first patient Mar 2026	Mar 2026 IR	✅
3–4× OS vs historical (community)	8.9 ÷ 2.5 ≈ 3.6× arithmetic	⚠️ depends on benchmark
100% CR / "guaranteed FDA approval"	Reddit bullish posts	❌ superseded
Frontline mOS 20+ mo projection	Tab 2 slider	🔬 not observed

How this works

Assumption-heavy Back-of-envelope buyout math — not a DCF or price target.

Peak sales: At steady state, patients on therapy = annual new starts × penetration × average years on drug. Longer survival ⇒ larger prevalent pool. Peak revenue = starts/yr × penetration × years × price.

Enterprise value: EV = total peak sales × multiple + risk-adjusted WT1 platform. Multiple (~4–8×) reflects oncology M&A convention (Venclexta ~$2.6B; Gilead–Forty Seven ~$4.9B pre-approval).

WT1 platform: GPS targets WT1 — NCI's #1-ranked cancer antigen (Cheever 2009) — with follow-on trials in ovarian cancer and mesothelioma plus potential CR1 expansion. The platform slider captures option value beyond modeled AML peak sales.

Risk adjustment (Monte Carlo): Optionally multiply each engine's peak by P(approval) from Tabs 1–2 — user-set priors (default P(GPS)≈65%, P(SLS)≈55%), not regulatory forecasts.

Show math

Peak_GPS = (CR2 + CR1 starts/yr) × pen × years × price

Peak_SLS = (frontline + r/r pool) × pen × years × price

EV = (Peak_GPS + Peak_SLS) × multiple + platform · equity $/sh = (EV + cash) / FD shares

Peak-sales × multiple, with a survival-driven prevalence pool.

The key dynamic (population grows if patients survive)

At steady state, patients on therapy = annual new starts × penetration × average years on therapy. Longer survival ⇒ more years on drug ⇒ a larger prevalent pool. Peak annual revenue = new-starts/yr × penetration × avg-years × annual price.

Valuation

Enterprise value = total peak sales × multiple + risk-adjusted platform value. Oncology assets historically trade at ~4–8× peak sales (market convention, not a fixed fact). Equity per share = (EV + cash) ÷ fully-diluted shares (basic outstanding ~181.3M; model FD default 222M).

WT1 platform

WT1 was ranked the #1 cancer antigen by an NCI working group (Cheever 2009) and is over-expressed across 20+ tumor types including AML, MDS, ovarian, and mesothelioma (SELLAS corp deck). GPS is the lead WT1 immunotherapy (MSK license, patent to ≥2033); SLS-009 is a separate CDK9 program — not WT1-targeted. The platform slider is a single risk-adjusted lump for GPS follow-on indications (CR1 label expansion, solid tumors, GPS-Plus) and manufacturing/IP — deliberately crude.

P(approval) risk adjustment

Monte Carlo optionally multiplies each engine's peak by P(GPS) and P(SLS-009) — user-set priors from Tabs 1–2, not regulatory forecasts. Defaults (65% / 55%) reflect REGAL event pace + SLS-009 single-arm stage; stress-test freely.

Poke holes: penetration, price, duration and the multiple are all assumptions; the addressable pools are estimates; this ignores time-value/discounting, competition, and dilution beyond the share count; it is a back-of-envelope, not a DCF.

A transparent back-of-envelope. Set the addressable pools, pricing, penetration and how long patients stay on therapy (which grows with survival), and a peak-sales multiple. Everything here is an assumption except the anchored facts (US AML incidence, Venclexta comp).

Blue = plausible range (1σ→3σ from comps/literature). Red = aggressive/hard to defend. Hover a band for its source.

Buyout scenarios

Risk-adjusted peak sales × multiple. Best Available Guess = moderate penetration with Onureg/Gilead-Forty Seven caution (QUAZAR, Gilead–FS). Optimistic DD = u/Confident-Web TAM/pen (CW Part 1).

GPS engine (AML CR2 + CR1 maintenance)

New CR2, transplant-ineligible / yr (US) 2,800

Estimate ~3K/yr (Confident Web). Derived from SEER ~20.8K AML/yr.

New CR1, transplant-ineligible / yr (US) 5,500

Estimate ~6K/yr. SEER · >60% relapse.

Penetration 45 %

Assumption first-in-class maintenance; Onureg caution (QUAZAR).

Annual price / patient $145 K

Assumption US orphan-oncology pricing comps (AbbVie SEC).

Avg years on therapy (↑ with survival) 2.8 yr

Derived from GPS survival (Tab 1) — assumption.

SLS-009 engine (frontline + r/r AML)

Frontline addressable / yr (US) 9,000

Estimate unfit newly-dx AML. SEER.

r/r addressable / yr (US) 3,500

Estimate post-Ven r/r AML-MR. SEER; >60% relapse (ACS).

Penetration 38 %

Assumption add-on to SoC — no primary source.

Annual price / patient $145 K

Assumption US oncology pricing comps.

Avg years on therapy 1.4 yr

Derived active-disease duration — assumption.

Platform & valuation

Risk-adjusted WT1 platform value $2.5 B

WT1 breadth — Cheever 2009 (NCI #1 antigen); early-stage assumption.

Multiple (× peak sales) 5.0×

Convention Oncology M&A ~4–8× peak. Comp: Gilead–Forty Seven ~$4.9B.

Fully-diluted shares 222 M

Fact ATM up to $150M authorized, unused to date (Q1 2026 PR). Dilution stress bumps the share denominator only; the model does not auto-issue against ATM capacity.

Verified Basic outstanding ~181.3M (Mar 31, 2026) + warrants/options/RSUs → FD modeled ~222M. Q1 2026 10-Q · Q1 2026 PR

Cash ($M) $107.1 M

Verified $107.1M cash Mar 31, 2026. Equity $/sh = (EV + cash) / FD shares. Q1 2026 10-Q · Q1 2026 PR

Result

GPS peak sales

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SLS-009 peak sales

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Total peak sales

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Prevalent GPS pool (on therapy)

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Enterprise value model output

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Equity value EV + cash

–

≈ – equity/sh · – · buyout range –

Monte Carlo — Valuation

Propagates every input's prior uncertainty (slider = center, 1σ band = spread) through the peak-sales × multiple model. Optionally risk-adjusts each engine's revenue by its probability of approval — P(GPS) default 65% reflects REGAL posterior / community MC synthesis (Vola Corvidae ~77% PoS; Tab 1 P(win) slider); P(SLS-009) default 55% reflects single-arm r/r signal + frontline uncertainty (Tab 2). Platform value is not risk-adjusted separately — it is already a discounted lump.

Enterprise-value distribution ($B):

P(GPS) is a user prior (default 65%) for risk-adjusting valuation — not a company forecast and not equal to Tab 1 clinical P(win). Neutral-prior MC on Tab 1 is a separate ~50–78% band (binding vs non-binding IA); biology-first Best Available Guess is a separate clinical scenario with high point P(win). P(SLS-009) default 55% — single-arm Ph2 + FDA frontline guidance; confirmatory Ph3 not started. Risk-adjusted EV = Σ(peak × P(approval)) × multiple + platform. model

WT1 antigen platform — GPS scope & what "platform value" means primary-checked

GPS (galinpepimut-S) is a heteroclitic multivalent WT1 peptide vaccine licensed from Memorial Sloan Kettering. SLS-009 (tambiciclib) is a separate CDK9 inhibitor — commercial value is modeled in its own engine; only GPS and follow-on WT1 programs feed the platform slider.

Evidence / asset	Detail	Source
WT1 antigen ranking	#1 priority cancer antigen (NCI working group)	Cheever et al., Clin Cancer Res 2009
WT1 expression	Over-expressed in AML, MDS, ovarian, mesothelioma, 20+ solid/heme tumors	SELLAS Feb 2026 deck · Cheever 2009
GPS mechanism	25 WT1 epitopes; CD4/CD8 responses across HLA types; monotherapy or + I/O	Corp deck
IP / manufacturing	Composition-of-matter patent to ≥2033; 3PL manufacturing in place post-interim	Q1 2026 PR · corp deck
REGAL (lead)	Phase 3 AML CR2/CRp2 maintenance — 78/80 events (blinded)	NCT04229979
CR1 expansion	Phase 2 CR1 data (~47% 3-yr plateau); potential label expansion if REGAL wins	Design paper
2nd/3rd-line ovarian	Completed Ph2 + pembrolizumab / nivolumab	Corp deck
Mesothelioma / solid tumors	Early-stage / completed studies; platform optionality	Corp deck
China license (3D Medicines)	Upfront + milestones received; up to $191.5M additional	Corp deck
GPS-Plus (heptavalent)	Next-gen WT1 construct in pipeline	Corp deck

What the platform slider captures: risk-adjusted value of WT1 follow-on indications, GPS-Plus, ex-US partnerships, and manufacturing know-how beyond the AML peak-sales engines above. Set $0 if you believe GPS is a single-indication asset; $2–5B is a moderate optionality case; >$8B requires multiple solid-tumor successes — assumption, not derived from disclosed forecasts.

TAM math — SEER incidence × penetration explained model

Addressable pools are not SEC-disclosed. They derive from US AML incidence (~20,800/yr SEER) × clinical funnel estimates. Community DD (u/Confident-Web-7118) uses ~3K CR2 and ~6K CR1-nontransplant new patients/yr — incorporated as slider defaults with wide bands.

Step	Best Available Guess preset	Arithmetic
US AML incidence	~20,800/yr	SEER 2024
CR2 + CR1 starts (GPS)	2,800 + 5,500 = 8,300/yr	estimate — ~40% of incident AML reaches maintenance-eligible CR
GPS prevalent pool	8,300 × 45% pen × 2.8 yr	= ~10,458 patients on therapy at steady state
GPS peak sales	10,458 × $145K/yr	= ~$1.52B model
SLS-009 pool	(9,000 + 3,500) × 38% × 1.4 yr × $145K	= ~$0.96B model
Total peak	~$2.48B	GPS + SLS-009 engines (unadjusted)
EV @ 5× + $2.5B platform	$2.48B × 5 + $2.5B	= ~$14.9B EV → ~$68 equity/sh @ 222M FD + $107.1M cash gross @100%
Risk-adj equity $/sh (header default)	peaks × P(GPS) 65% / P(SLS) 55%	→ ~$10.1B EV → ~$46 equity/sh = (EV + $107.1M) / 222M FD
Onureg ceiling check	QUAZAR CR1 mOS 24.7 vs 14.8 mo	Clinical win but BMS bundles Onureg in ~$1.6B "Other Growth" bucket — no standalone peak disclosed (BMS SEC)
Venclexta ceiling	~$2.58B global 2024	AML combo upside comp (AbbVie 10-K)

Longer GPS survival (Tab 1) ⇒ higher years on therapy ⇒ larger prevalent pool — that link is real but capped at steady state. Penetration above ~50% in maintenance AML is aggressive given Onureg precedent.

M&A comparables — AML/onc deals with cautionary notes cited

Deal / asset	Price / sales	Stage & setting	Lesson for SLS
Gilead → Forty Seven (magrolimab)	~$4.9B (SEC EX-99.1, closed Apr 2020)	Pre-approval AML/MDS CD47 mAb	Buyers pay big pre-Ph3 — but Ph3 ENHANCE discontinued 2023 (Gilead). Cautionary comp.
AbbVie Venclexta (venetoclax)	~$2.58B sales 2024 (AbbVie SEC)	Approved AML/CLL/MDS combo	Blockbuster ceiling for AML-active therapy; GPS/SLS would compete in overlapping lines
BMS Onureg (CC-486)	Not broken out; in ~$1.6B "Other Growth" group (BMS SEC 2024)	Approved AML CR1 maintenance; QUAZAR mOS 24.7 vs 14.8 (NEJM 2020)	Closest GPS analog — strong trial, modest commercial uptake; caps maintenance TAM optimism
Regor CDK inhibitor (community)	~$850M upfront on Ph1 ~28% CR (Reddit)	Early AML	M&A ceiling reference for CDK-class assets; not clinical equivalence to SLS-009
Voruciclib / QHRD107 (CDK9)	No disclosed M&A	R/R AML Ph1/2	Competing CDK9 mechanisms — class not unique (community)
Community buyer lists	🔬 opinion	—	Gilead, BMS, AbbVie, J&J, Pfizer cited in buyers thread — logical AML/onc strategics, ❌ no disclosed talks

Bear case & valuation limitations caveats

Binary REGAL — GPS peak engine collapses to ~$0 if HR ≥ 0.636; entire platform thesis resets (design).
Onureg commercial disappointment — QUAZAR statistically positive but maintenance AML uptake limited; GPS penetration assumptions >40% may be optimistic (QUAZAR · BMS SEC).
Magrolimab M&A failure — $4.9B pre-approval deal did not predict clinical success (Gilead 2023).
Single-asset dependency — REGAL outcome drives near-term EV; SLS-009 is earlier and single-arm in r/r (NCT04588922).
Dilution — basic outstanding ~181.3M Mar 2026 vs ~90M a year prior; ATM up to $150M authorized, unused (Q1 2026 PR). Model uses fully-diluted ~222M — future raises not modeled.
Cash runway ≠ valuation floor — ~$107M + $7.5M warrant proceeds; 10-Q going-concern: ≥12 months from filing date (~$9M/qtr opex) — not the same as commercialization funding (Q1 2026 10-Q).
Platform risk — WT1 is validated antigenically (Cheever) but GPS has mixed Ph2 (CR2 n=10, no plateau); solid-tumor programs early/completed without registrational path disclosed.
Community overclaims excluded — "$5–20B guaranteed buyout" (bull case); "SLS worth $50+/sh on REGAL alone" — 🔬 opinion, not primary data.

Conservative preset encodes GPS fail/modest uptake: 30% penetration, 4× multiple, $0.5B platform. Use it as the bear anchor.

Preset assumptions — what each scenario encodes cited

Preset	Key inputs	Rationale & source
Best Available Guess	GPS pen 45%, SLS 38%, 5×, $2.5B platform, 222M sh	Moderate maintenance uptake with Onureg caution (QUAZAR); central M&A multiple; modest WT1 option value
Conservative	GPS 30%, SLS 22%, 4×, $0.5B platform, 225M sh	REGAL fail or Onureg-like modest uptake; higher dilution assumption
Bull	GPS 58%, SLS 50%, 6.5×, $4B platform, 218M sh	Both assets succeed; first-in-class premium multiple; solid-tumor optionality priced in
Optimistic DD	GPS 58%, SLS 45%, 5.5×, $4B platform, 220M sh	u/Confident-Web TAM/pen (Part 1 · Part 2) — high but below max Reddit bull posts

Presets set slider centers only — Monte Carlo propagates ±1σ uncertainty around each. P(GPS)/P(SLS-009) risk-adjustment is separate (MC toolbar).

Community DD — valuation & buyout (validated) primary-checked

Expand to load r/sellaslifesciences valuation synthesis. Tags: ✅ verified · ⚠️ partial · ❌ not as fact · 🔬 model/opinion

Valuation facts & sources verified from PRs/filings · unknown not disclosed

Cash (Mar 31, 2026): $107.1M + $7.5M warrant proceeds in Q2 to date verified [Q1 2026]

Runway: ≥12 months from Q1 2026 filing (going concern); ~$9M/qtr opex verified [10-Q]

Basic shares outstanding: ~181.3M (Mar 31, 2026) verified [10-Q] · [Q1 2026 PR]

Fully diluted (model default): ~222M incl. warrants/options/RSUs (basic ~181.3M + ~30–40M dilutives) estimate [10-Q]

ATM facility: up to $150M authorized; no shares sold to date verified [Q1 2026]

Q1 2026 net loss: $8.4M (~$9.3M/qtr opex) verified [Q1 2026]

Pipeline: GPS REGAL Ph3 (AML CR2); SLS-009 Ph2 r/r (NCT04588922) + Ph2 frontline enrolling Mar 2026 (NCT04588922) verified [REGAL] · [Mar 2026]

WT1 platform scope: GPS in AML, ovarian (completed Ph2), mesothelioma; GPS-Plus; China out-license verified [corp deck]

US AML incidence: ~20,800/yr (SEER 2024); ~22,720 (ACS 2026) verified [SEER] · [ACS]

Relapse/refractory: >60% of CR patients relapse verified [ACS]

Venetoclax (Venclexta) 2024 sales: ~$2.58B global verified [AbbVie SEC]

WT1: #1-ranked cancer antigen (NCI); over-expressed in 20+ tumors verified [Cheever 2009]

CR2 ~3K & CR1-nontransplant ~6K new/yr pools: community DD estimate estimate [CW DD]

Onureg peak sales: not disclosed by BMS (bundled) unknown

Executive CIC severance amendments: lump-sum change-in-control payouts (May 2026) verified [8-K]

Pricing, penetration, duration, multiple, platform value: user assumptions / market convention assumption

SELLAS Q1 2026 financials — cash, burn, ATM, REGAL 78 events. GlobeNewswire · IR
SELLAS corporate overview (Feb 2026) — WT1 platform, pipeline, China license. PDF
AML incidence — SEER Stat Facts · ACS Key Statistics
Venetoclax sales — AbbVie SEC
Gilead–Forty Seven acquisition — SEC EX-99.1 · magrolimab discontinuation Gilead 2023
Onureg / QUAZAR AML-001 — Wei et al., NEJM 2020 · BMS revenue grouping SEC
WT1 antigen ranking — Cheever 2009
TAM pools & peak-sales framing — u/Confident-Web-7118 DD. Part 1 · Part 2
Community valuation / buyout — Potential buyers · Bull case · Bear cases

Claim	Primary source	Status
WT1 #1-ranked cancer antigen (NCI)	Cheever 2009	✅
Cash $107.1M (Mar 31, 2026)	Q1 2026 PR	✅
Basic outstanding ~181.3M (Mar 31, 2026)	Q1 2026 10-Q	✅
FD modeled ~222M (warrants/options)	Tab 3 default	🔬
Venclexta ~$2.58B 2024 sales	AbbVie 10-K	✅
Gilead–Forty Seven ~$4.9B	SEC EX-99.1	✅
Magrolimab Ph3 discontinued	Gilead 2023	✅
QUAZAR mOS 24.7 vs 14.8 mo	NEJM 2020	✅
Onureg modest commercial uptake	BMS bundles; no standalone sales	⚠️ qualitative
CR2 ~3K / CR1 ~6K patients/yr	Community DD from SEER	⚠️ estimate
EV = peak × 4–8× + platform	Tab 3 model	🔬
$5–20B buyout / bidding war	Reddit bull case	🔬 opinion
Disclosed acquirer talks	—	❌ none public

REGAL/GPS, SLS-009, and valuation — six depth levels. Sources linked throughout.

How this works

This tab explains the biology behind SELLAS' two drug candidates from the target up: what the target molecule does, then how the drug is designed to act on it. Diagrams are hand-built inline SVG (no AI images), labeled and on the same color tokens as the rest of the app.

Every mechanistic claim links a primary source (peer-reviewed paper, ClinicalTrials.gov record, or company filing). Where the biology is textbook-established we say so; where a step is the drug's intended mechanism rather than a proven clinical result, we flag it; and clinical numbers that are single-arm or still blinded are flagged as company-reported.

Tags: Established textbook / peer-reviewed biology · Theoretical MOA intended mechanism, not a proven clinical outcome · Company-reported single-arm or blinded data from SELLAS.

See REGAL model →

Overview Two shots on goal, two different mechanisms

SELLAS is developing two mechanistically unrelated cancer drugs, both aimed at acute myeloid leukemia (AML) and related myeloid cancers. One is an immunotherapy that trains the patient's T cells against a leukemia antigen; the other is a targeted small molecule that shuts off a survival gene program inside the cancer cell.

GPS (galinpepimut-S) — immunotherapy

A WT1-directed peptide vaccine. It teaches CD4⁺ and CD8⁺ T cells to recognize and kill cells that overexpress the WT1 protein — used to keep patients in remission. Established

SLS-009 (tambiciclib) — targeted small molecule

A selective inhibitor of the kinase CDK9. Blocking CDK9 collapses the short-lived survival transcripts MCL-1 and MYC, pushing leukemic blasts into apoptosis. Established Theoretical MOA

Honest framing: these are two independent programs, not a single combination product. There is no human trial combining GPS + SLS-009 — the "platform" is a two-asset pipeline, discussed in the last section. The REGAL Phase 3 (GPS) remains blinded pending its 80-event final analysis, and the SLS-009 data are from an early single-arm study.

Evidence tags: Established peer-reviewed / textbook Theoretical MOA intended mechanism Company-reported single-arm / blinded

Target 1 WT1 — the leukemia antigen GPS goes after

WT1 (Wilms' tumor 1) is a zinc-finger transcription factor. It is largely switched off in healthy adult tissue but is overexpressed in the majority of AML and MDS blasts, which makes it a tumor-associated antigen the immune system can, in principle, be pointed at. Established

In 2009 an NCI pilot project ranked 75 cancer antigens against pre-set criteria (therapeutic function, immunogenicity, specificity, oncogenicity, expression). WT1 ranked #1 — the single highest-priority target antigen for cancer immunotherapy. That ranking is the core rationale for a WT1 vaccine. Established

Why a transcription factor makes a usable antigen

Even though WT1 sits inside the cell (and its nucleus), fragments of it are continuously chopped up and displayed on the cell surface bound to MHC molecules. A T cell that has been trained on those WT1 peptide-MHC complexes can therefore recognize a WT1⁺ blast from the outside — no need for the protein to be on the surface itself. Established

Overexpressed, not neo-antigen: WT1 is a normal self-protein overexpressed by the tumor, so the immune response has to overcome tolerance — the design problem GPS tries to solve (next section). Established
Broad applicability: WT1 is expressed across AML, MDS, and several solid tumors, which is why SELLAS frames it as a platform antigen. Established

Diagram 0 — WT1 as a usable antigen. WT1 never sits on the cell surface, but proteasomal fragments are loaded onto MHC — the basis for peptide vaccines like GPS. Established · Cheever 2009 NCI #1 ranking.

Cheever et al. 2009, Clin Cancer Res — NCI antigen prioritization, WT1 ranked #1: PubMed 19723653
SELLAS science overview (WT1 biology / NCI ranking): sellaslifesciences.com/science
Jamy & Cicic 2025, REGAL design review (WT1 antigen rationale): PMC11760237

Drug 1 GPS / galinpepimut-S — a WT1 peptide vaccine

GPS is a mixture of four WT1-derived peptides: two are heteroclitic (deliberately mutated by a single amino acid to look "non-self" and break tolerance), and two are longer native WT1 peptides. Together they cover both CD8⁺ (MHC class I) and CD4⁺ (MHC class II) responses across a broad range of HLA types. Established

The peptides are given with the adjuvant Montanide and pre-dosing with GM-CSF, which recruits and activates antigen-presenting cells (APCs) so the peptides are presented efficiently. The intended result is a population of WT1-specific CD8⁺ cytotoxic T lymphocytes (CTLs), helped by CD4⁺ T cells, that patrol for and lyse WT1⁺ residual leukemic cells. Established Theoretical MOA

Diagram 2 — GPS vaccine flow. Peptides + Montanide + GM-CSF activate an APC, which primes CD4⁺ help and CD8⁺ CTLs; the CTLs lyse WT1⁺ minimal-residual-disease blasts. This is why GPS is positioned in the maintenance / second-complete-remission (CR2) setting — clearing residual cells to delay relapse, not debulking active disease. Theoretical MOA

Diagram 1 — WT1 antigen presentation → priming → killing. WT1 is intracellular, but fragments are displayed on MHC, so trained CD8⁺ CTLs (with CD4⁺ help) can recognize and lyse WT1⁺ cells. Established immunobiology.

Honesty flag: immunogenicity (T-cell responses to WT1) is well documented for GPS, but the pivotal REGAL Phase 3 (NCT04229979) overall-survival readout is still blinded — the final analysis triggers at 80 events (78 reported as of the May 2026 update). Whether the immune mechanism translates into a survival benefit is the open question. Company-reported / blinded

Jamy & Cicic 2025 — GPS peptide composition (WT1-A1, WT1-427 long, WT1-331 long, WT1-122A1 long), Montanide + GM-CSF rationale: PMC11760237
REGAL Phase 3 trial record: NCT04229979
SELLAS science page — heteroclitic principle, CD4/CD8 design: sellaslifesciences.com/science
Kurosawa et al. 2010, Haematologica — AML survival after first relapse (context for the maintenance setting): haematologica.org/article/view/5781

Target 2 CDK9 / P-TEFb — the transcription switch SLS-009 flips off

CDK9 is the catalytic subunit of P-TEFb (positive transcription elongation factor b; CDK9 paired with cyclin T). Its job is to phosphorylate serine-2 (Ser2) of the RNA polymerase II C-terminal domain (CTD), which releases paused polymerase into productive transcriptional elongation. Established

Why cancer cares: the genes most dependent on this elongation step are ones with short-lived mRNAs and proteins — above all MCL-1 (an anti-apoptotic BCL-2-family protein) and MYC. Because MCL-1 protein turns over in roughly an hour, its level tracks ongoing transcription almost in real time. Shut off CDK9 and MCL-1 falls fast, removing a key brake on apoptosis. Established

Diagram 3 — CDK9/P-TEFb axis. Top: CDK9 phosphorylates Pol II CTD Ser2, driving elongation of short-lived MCL-1/MYC transcripts that keep the blast alive. Bottom: SLS-009 blocks CDK9, Ser2 phosphorylation stops, the labile MCL-1 protein falls within hours, and the cell dies. Established mechanism; the CDK9→MCL-1 dependency is the drug's rationale. Theoretical MOA

Anshabo et al. 2021 — CDK9: a comprehensive review (P-TEFb, CTD Ser2, MCL-1/MYC): PMC8143439
Fu et al. 2021 — CDK9 keeps RNA polymerase II on track: PMC8257543
Boffo et al. 2018 — CDK9 inhibitors in AML (MCL-1/MYC dependency): J Exp Clin Cancer Res 37:36
Bewersdorf & Zeidan 2019 — transcriptional silencing of MCL-1 via CDK inhibition in AML: Front. Oncol.

Drug 2 SLS-009 / tambiciclib — a selective CDK9 inhibitor

SLS-009 (tambiciclib; formerly GFH009) is a highly selective, potent CDK9 inhibitor. By blocking CDK9 it suppresses transcription of MCL-1 and MYC, tipping leukemic blasts toward apoptosis (Diagram 3). SELLAS positions it as a differentiated CDK9 inhibitor with improved selectivity/toxicity versus earlier, non-selective compounds. Established Company-reported

Why it pairs with azacitidine + venetoclax

Azacitidine + venetoclax (AZA/VEN) is the standard of care for older/unfit newly-diagnosed AML. Venetoclax inhibits BCL-2, but leukemic cells commonly escape by leaning on MCL-1 — a different anti-apoptotic protein venetoclax does not touch. Upregulated MCL-1 is a well-documented driver of venetoclax resistance. Because SLS-009 pulls MCL-1 down, adding it to AZA/VEN is a dual BCL-2 + MCL-1 blockade: close both apoptosis escape routes at once. Established Theoretical MOA

Diagram 4 — dual apoptosis blockade. Venetoclax neutralizes BCL-2; SLS-009 (via CDK9 inhibition) strips away MCL-1. With both anti-apoptotic guards gone, pro-apoptotic BAX/BAK drive mitochondrial outer-membrane permeabilization (MOMP) and the blast dies. This is the rationale for adding SLS-009 to AZA/VEN, especially after venetoclax failure. Theoretical MOA

ASXL1 / TP53 relevance

In the Phase 2 study (r/r AML with MDS-related changes, after prior venetoclax), responses were enriched in patients with ASXL1 mutations — a subgroup with historically poor prognosis — and preclinical work shows activity in ASXL1-mutated and TP53-knockout AML lines. SELLAS reports the combination met its primary endpoints in that r/r setting and is moving toward a frontline study. Company-reported Theoretical MOA

Honesty flag: the SLS-009 efficacy data are from an early, single-arm Phase 2 (no randomized control); response rates and the ASXL1 signal are promising but not yet confirmed against a comparator. Frontline benefit is a hypothesis a randomized trial would have to test. Company-reported / single-arm

Related catalyst (not modeled here): GenFleet runs a separate Phase Ib/II monotherapy trial of GFH009 (same molecule) in r/r PTCL (NCT05934513) — see Tab 2 · Catalysts for timing and scope. PTCL ORR read-through ≠ AML valuation inputs. model

SLS-009 (GFH009) trial record — CDK9 inhibitor + AZA/VEN, ASXL1 cohorts: NCT04588922
Zeidan et al., ASH 2024 abstract — Phase 2a SLS-009 + AZA/VEN in r/r AML: ASH 2024 #198686
Blood 2025 abstract — Phase 2 SLS-009 + AZA/VEN in AML-MR after prior venetoclax: Blood (2025) 10.1182/blood-2025-3423
SELLAS PR (ASH 2025; tambiciclib naming, ASXL1/TP53 preclinical): SELLAS ASH 2025 release
MCL-1 as a venetoclax-resistance escape (RAS/MAPK → MCL-1): PMC8858957 · resistance review PMC12071220
AZA/VEN frontline standard (VIALE-A): DiNardo et al., NEJM 2020

Platform fit Where each drug acts — and what is NOT proven

The two programs are mechanistically independent and act at different points in the AML disease course. GPS is an antigen-directed immunotherapy best suited to low-disease-burden maintenance; SLS-009 is a cell-intrinsic apoptosis primer suited to active or resistant disease alongside AZA/VEN.

Diagram 5 — disease-course fit. SLS-009 targets active/resistant disease with AZA/VEN (studied in relapsed/refractory; frontline planned); GPS targets minimal residual disease in second remission (REGAL). Frontline SLS-009 and the entire GPS→SLS-009 sequencing idea are strategy, not trial-proven. Theoretical MOA

GPS — immune / maintenance

Antigen-directed, works best against low-burden residual disease; positioned as CR2 maintenance to delay relapse. REGAL blinded

SLS-009 — targeted / active disease

Cell-intrinsic apoptosis primer; restores/deepens response to AZA/VEN by removing the MCL-1 escape. Single-arm Phase 2

Combined platform

Shared WT1/AML focus and a two-asset story — but no human trial combines GPS + SLS-009. Strategy only

Bottom line — what is and isn't established: The biology of both targets (WT1 as an antigen; CDK9→MCL-1/MYC) is well established. The drug mechanisms (GPS priming WT1-specific T cells; SLS-009 collapsing MCL-1 to overcome venetoclax resistance) are sound theoretical MOAs with supporting data. What remains unproven: GPS's survival benefit (REGAL blinded, final at 80 events), SLS-009's efficacy versus a randomized control (single-arm), and any GPS + SLS-009 combination (does not exist in the clinic).

REGAL Phase 3 (GPS, CR2 maintenance): NCT04229979 · design: PMC11760237
SLS-009 (r/r AML + AZA/VEN; frontline planned): NCT04588922
SELLAS pipeline / two-asset platform: sellaslifesciences.com/science

1 · Survival & events

2 · Hazard ratio & significance

3 · Monte-Carlo posterior

4 · Anchor-constrained inversion (inverse mixture-cure fit)

Math verification (Jul 2026)

Scenario controls

BAT arm (control)

GPS arm (vaccine)

Trial parameters

Advanced

Survival curves (from randomization)

Monte Carlo — final-HR distribution

Strawman null (CW implicit)

Heterogeneous BAT null (critique)

IRM definition

Topline BAT mOS → TRUE CR2-onset (CW conversion)

Scenario fits to 60 / 72 / 78 events (CW tolerance sweep)

Three constraint scenarios @ 80th event (CW preferred = Scenario C)

Best biology+data fits (±1.5 events, before randomization lift)

CW Part 1 anchored cure model (reverse-engineered from 72 @ m58)

Bayes factor (~62×) — honest caveat

BAT biology cap (3-yr OS)

Known facts & the bet verified from PRs/filings · unknown not disclosed

References (sources for every band & fact)

Statistical methods (primary sources)

Effect measures

Regulatory path (heuristic)

Frontline (the bigger prize)

Relapsed / refractory AML-MR (Phase 2)

Frontline (newly diagnosed) — Phase 2b → 3

SLS-009 vs historical benchmark (r/r)

Monte Carlo — SLS-009

Catalysts & related trials verified registry/SELLAS · community unverified · model not in valuation

SLS-009 facts & sources verified from PRs/filings · unknown not disclosed

The key dynamic (population grows if patients survive)

Valuation

WT1 platform

P(approval) risk adjustment

GPS engine (AML CR2 + CR1 maintenance)

SLS-009 engine (frontline + r/r AML)

Platform & valuation

Result

Monte Carlo — Valuation

Valuation facts & sources verified from PRs/filings · unknown not disclosed

Overview Two shots on goal, two different mechanisms

GPS (galinpepimut-S) — immunotherapy

SLS-009 (tambiciclib) — targeted small molecule

Target 1 WT1 — the leukemia antigen GPS goes after

Why a transcription factor makes a usable antigen

Drug 1 GPS / galinpepimut-S — a WT1 peptide vaccine

Target 2 CDK9 / P-TEFb — the transcription switch SLS-009 flips off

Drug 2 SLS-009 / tambiciclib — a selective CDK9 inhibitor

Why it pairs with azacitidine + venetoclax

ASXL1 / TP53 relevance

Platform fit Where each drug acts — and what is NOT proven

GPS — immune / maintenance

SLS-009 — targeted / active disease

Combined platform