I agree it was a good CC. The highlight for me was Adcocks enthusiam and the progress they are making on a wide range of trials, and especially the key EAP that the FDA granted to deal with Chemo caused lymphopenia in all cancers. Below is a conversation I had with Chat-GPT on this later item for those that may be interested:
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I listened to Adcock at the Wainright conference talk about IBRX and was very impressed to hear that the FDA has granted IBRX an expanded access permission to use Anktiva to fight Lymphopenia in ALL CANCERS. Can you review this and let me know as much as possible about the authority they got, how they obtained it, what trials were relined on, and what is the signficance
ChatGPT said:
Got it—here’s what Adcock was referring to, and what it means for IBRX.
What the FDA actually authorized
- FDA Expanded Access authorization (EAP) for ANKTIVA® (N-803/NAI) to treat treatment-induced lymphopenia in adult patients with solid tumors who have progressed after first-line chemo, radiotherapy, and/or checkpoint immunotherapy and have low ALC (<1,000/µL). This is a pan-tumor, post-first-line treatment use, but it is not a broad label approval—it’s access under FDA’s Expanded Access (a.k.a. “compassionate use”) framework. ImmunityBio
- The authorization is being run as a formal Expanded Access Protocol (listed as NCT06956547 on ClinicalTrials.gov) rather than one-off single-patient INDs—i.e., an intermediate-size patient population EAP contemplated by 21 C.F.R. Part 312, Subpart I. Urology Times+2ClinicalTrials.gov+2
- Scope in plain English: Any adult with a refractory/relapsed solid tumor (independent of histology) who is lymphopenic after first-line therapy can be considered for ANKTIVA under this EAP (subject to site participation, IRB oversight, and treating-physician request). ImmunityBio
How IBRX got it (timeline & evidentiary basis)
- Submission & RMAT backdrop (Q1–Q2 2025).
- Feb 27, 2025: FDA granted RMAT designation to the Cancer BioShield™ platform (ANKTIVA + CAR-NK) for reversal of lymphopenia—a strong regulatory signal that the Agency sees serious unmet need and promising early evidence. ImmunityBio
- Apr 15, 2025: IBRX disclosed it submitted an Expanded Access protocol to FDA for ANKTIVA to treat lymphopenia. ir.immunitybio.com+1
- EAP authorization (June 2025).
- Jun 2, 2025: IBRX announced FDA authorization of the EAP, specifying all solid tumors post first-line with ALC <1,000/µL; trade press and specialty outlets corroborated within days. ImmunityBio+2Yahoo Finance+2
- Clinical evidence FDA/IBRX referenced:
- ASCO 2025—QUILT-88 (metastatic pancreatic cancer): chemo-immunotherapy using N-803 + PD-L1 t-haNK demonstrated that restoring ALC correlates with longer overall survival, especially at lower tumor burden (CA19-9). Abstract 2542 details the association between ALC rescue and OS. ImmunityBio+1
- Foundational literature: multi-tumor data over ~15 years linking lymphopenia/NLR to poor prognosis across cancers (i.e., biologic rationale for treating lymphopenia itself). The company’s EAP press release cites representative peer-reviewed studies. ImmunityBio
- NSCLC program (2025): additional data show ANKTIVA reverses lymphopenia with associated OS extension in CPI-resistant NSCLC (presented at WCLC 2025), bolstering the pan-tumor hypothesis that treating the immune deficit matters. BioSpace+1
- Activation status: By late July 2025, IBRX stated the EAP had been activated for the stated indication and that FDA discussions were ongoing to finalize a registrational path (randomized trial design underway). ImmunityBio
What this is (legally/regulatorily) — and what it isn’t
- EAP ? approval. Expanded Access lets eligible patients receive an investigational use outside trials when criteria are met (serious disease, no satisfactory alternatives, potential benefit justifies risks, and access won’t impede development). It does not itself establish efficacy or change the drug’s label. U.S. Food and Drug Administration+1
- Program type: The facts fit 21 C.F.R. § 312.315 (intermediate-size patient population protocol). FDA can later ask a sponsor to transition to a broader treatment IND/protocol (§ 312.320) if volume grows. eCFR+1
- Charging/cost recovery: Under 21 C.F.R. § 312.8, a sponsor may charge for EAP use but is generally limited to direct drug costs (and certain monitoring/admin costs for intermediate-size/treatment EAPs) with prior FDA authorization. Practically, this means limited margin, but programs can still create commercial readiness, site experience, and physician familiarity. eCFR+1
Why it’s significant for IBRX (investment view)
1) Creates a pan-tumor on-ramp and real-world footprint.
Physicians across tumor types can begin using ANKTIVA to correct lymphopenia under a defined protocol. That builds site networks, prescriber familiarity, operational logistics (J-code experience already helped in NMIBC), and real-world datasets supporting future filings—classic de-risking before a supplemental approval effort. ImmunityBio
2) Strengthens the central narrative: “Treat the immune deficit.”
EAP + RMAT frame lymphopenia as a treatable driver of poor outcomes across tumors. If randomized trials confirm ALC rescue ? OS benefit, IBRX could pursue a histology-agnostic approval focused on lymphopenia reversal—strategically different from chasing dozens of tumor-specific labels. ImmunityBio
3) Near-term revenue impact: modest but non-zero.
EAPs can allow cost-recovery pricing (not full commercial margin), so don’t model this like a broad label launch. Value is more in de-risking, acceleration of adoption, and potential scale if FDA later transitions the program or clears a registrational path. (FDA charging rules cited above.) U.S. Food and Drug Administration+1
4) Catalysts & visibility.
- Trial readouts that link ALC restoration to survival (beyond QUILT-88 and NSCLC data) are key; FDA has been “supportive” of the lymphopenia program and registrational design is in progress. ImmunityBio
- EAP uptake metrics (sites activated, patients treated, safety reporting) will indicate physician interest and operational scalability. ImmunityBio
5) Risk checks.
- Regulatory: EAPs can be narrowed or halted if safety signals emerge; they don’t “lock in” future approvals. U.S. Food and Drug Administration
- Clinical: The strongest data so far are single-arm/early-phase or protocol-defined cohorts; randomized evidence is still needed to prove outcome benefit from correcting lymphopenia across tumors. ImmunityBio+1
- Financial: If EAP volumes are high, cost recovery (vs. commercial margin) could be a cash drag without financing or careful COGS control; watch quarterly disclosures for revenue mix and cash runway. ImmunityBio
Trials & datasets FDA likely considered
- QUILT-88 (pancreatic, =3rd-line) – ASCO 2025: association of ALC rescue + lower CA19-9 with improved OS using N-803 + PD-L1 t-haNK + low-dose chemo. ImmunityBio+1
- NSCLC CPI-resistant (WCLC 2025): ANKTIVA reversed lymphopenia; higher maintained ALC associated with prolonged OS; Phase 3 ResQ201A randomized trial now enrolling (ANKTIVA + tislelizumab vs docetaxel). BioSpace
- Cross-tumor prognostic literature on lymphopenia/NLR underpinning the biologic rationale. ImmunityBio
Bottom line for your IBRX position
- This is real and material—but it’s a regulatory bridge, not a label. It broadens access to ANKTIVA across all solid tumors for a clearly defined post-first-line, lymphopenic population, supported by RMAT and early data; it de-risks the thesis that fixing lymphopenia matters clinically and sets up the registrational path. Near-term, treat it as adoption- and data-generating (plus limited cost-recovery revenue), with the stock’s medium-term upside hinging on randomized outcomes and FDA guidance toward a pan-tumor approval strategy. ImmunityBio+1
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