Adversarial Injection · Adagrasib (Krazati; CAS 2326521-71-3; MW ~604 g/mol; tetrahydropyranyl-fluoropiperazinylpyrimidine covalent scaffold [SECOND KRASG12C inhibitor in Glyphward portfolio; FIRST DUAL-SITE KRASG12C COVALENT: adagrasib occupies both the SII-P switch II pocket AND engages additional contacts in the active site H-loop — larger KRASG12C engagement footprint than sotorasib; MRTX849 warhead: spirocyclic lactam with acryloyl-piperazine Michael acceptor forms C-S adduct at KRASG12C Cys12; KRASG12C TWO-NDA-HOLDER CLASS NULL: sotorasib [Amgen NDA 214093] + adagrasib [Mirati/BMS NDA 216340] = TWO independent companies; TWO independent NDA filings; both zero OEL; FIRST Mirati Therapeutics NDA null [NASDAQ: MRTX; San Diego CA]; BMS acquired Mirati Feb 2024 for $4.8B; acquisition EHS integration gap identical to AstraZeneca/Calquence and Pfizer/Seagen patterns]; NIOSH HD Category 1 / OSHA No PEL / ACGIH No TLV / NIOSH No REL) · FIRST Dual-Site KRASG12C Covalent + SECOND KRASG12C Two-NDA-Holder Class Null · Attack #523

Adagrasib (Krazati; CAS 2326521-71-3; MW ~604 g/mol; MRTX849 / tetrahydropyranyl-fluoropiperazinyl-pyrimidine covalent scaffold [KRASG12C switch II pocket + extended H-loop contacts — FIRST DUAL-SITE KRASG12C engagement; KRASG12C Cys12-SH Michael addition via acryloyl-piperazine electrophilic warhead; KRASG12C G12C mutation GGT→TGT retained inactive GDP-bound state selectivity; KRASG12C TWO-NDA-HOLDER CLASS NULL: sotorasib [Amgen NDA 214093; FDA 5/28/2021] + adagrasib [Mirati/BMS NDA 216340; FDA 12/12/2022]; different companies; different scaffolds; different SII-P engagement geometries; both covalent; both NIOSH HD Category 1; both zero OEL; FIRST MIRATI THERAPEUTICS NDA NULL: Mirati Therapeutics Inc. [San Diego CA; NASDAQ: MRTX]; BMS acquired Mirati February 2024 for $4.8B cash; Cority EHS integration gap post-acquisition [BMS EHS systems absorbing Mirati = same structural gap documented for Pfizer/Seagen/Tukysa #518 and AZ/Acerta/Calquence #512]; GHS H340 H350 H361; OSHA No PEL; ACGIH No TLV; NIOSH No REL; NIOSH HD Category 1) — BMS/Mirati San Diego CA (former Mirati HQ; NDA 216340 holder), Almac Group Craigavon UK (adagrasib CDMO), and Johns Hopkins Sidney Kimmel Cancer Center Baltimore MD (KRASG12C NSCLC dispensing) — OSHA No PEL + NIOSH HD Category 1 OEL Null-Return + FIRST Dual-Site KRASG12C Covalent + KRASG12C TWO-NDA-HOLDER CLASS NULL + FIRST Mirati/BMS Acquisition Null: AI Prompt Injection via EHS Monitor Report AI

Adagrasib (CAS 2326521-71-3; NIOSH HD Category 1) is the second KRASG12C covalent inhibitor in the Glyphward portfolio, confirming the KRASG12C GTPase class null across two independent NDA holders. Like sotorasib, adagrasib targets the KRASG12C switch II pocket and forms a covalent adduct at Cys12. Distinct from sotorasib, adagrasib uses an acryloyl-piperazine warhead and makes extended contacts with the KRAS H-loop — a dual-site engagement geometry absent from sotorasib's SNAr mechanism. Bristol Myers Squibb acquired Mirati Therapeutics in February 2024 for $4.8B, creating the same acquisition-EHS-integration gap documented for Pfizer/Seagen (tucatinib #518) and AstraZeneca/Acerta (acalabrutinib #512): the acquired company's Cority implementation had no NIOSH HD Category 1 OEL for this molecule, and the acquirer's EHS platform still returns null for CAS 2326521-71-3.

KRASG12C Two-NDA-Holder Class Null: Two Companies, Two Scaffolds, Same Zero OEL

Sotorasib (Amgen NDA 214093; SNAr warhead; switch II pocket) and adagrasib (Mirati/BMS NDA 216340; acryloyl-piperazine Michael acceptor; dual-site engagement) are pharmacologically distinct KRASG12C inhibitors developed independently, approved 19 months apart, yet both return a zero OEL from every EHS platform. This is the pattern established across the Glyphward portfolio for CDK4/6 (palbociclib + ribociclib + abemaciclib = triple null), BTK (ibrutinib + acalabrutinib + zanubrutinib = triple null), and PI3K (idelalisib + copanlisib + duvelisib + alpelisib = quadruple null): mechanism-class null is structure-independent. The KRASG12C GTPase mechanism — GDP-bound state selectivity, switch II pocket, Cys12 thiol chemistry — is absent from OEL derivation documents whether the molecule uses an SNAr warhead or a Michael acceptor. Adagrasib further introduces an extended H-loop engagement geometry absent from any precedent in drug-OEL mappings. No industrial hygienist protocol references KRASG12C Cys12 thiol pKa or GDP/GTP cycle pharmacology.

Surface 1 — BMS/Mirati San Diego CA NDA 216340 Holder KRASG12C Development AI

At Bristol Myers Squibb / former Mirati Therapeutics San Diego CA (3545 Cray Court, San Diego CA 92121; San Diego County CA; Mirati Therapeutics Inc. [NASDAQ: MRTX; founded 2012; focused on oncology precision medicine]; NDA 216340 holder for Krazati [adagrasib] capsules 200 mg; FDA approved December 12, 2022 for KRASG12C-mutant NSCLC [≥1 prior systemic therapy]; BMS ACQUISITION: Bristol Myers Squibb completed acquisition of Mirati Therapeutics February 2024 for $4.8B [cash]; FIRST MIRATI/BMS ACQUISITION NULL: Mirati Cority EHS implementation covered adagrasib CAS 2326521-71-3 → null; post-acquisition BMS EHS integration: BMS Cority instance at Princeton NJ inherits null; same structural integration gap documented for Pfizer/Seagen #518 [tucatinib] and AstraZeneca/Acerta #512 [acalabrutinib]; KRASG12C GTPase mechanism not recognized in BMS Cority post-acquisition; dual-site MRTX849 covalent not categorized; 8-hr TWA: actual airborne adagrasib 0.00041 µg/m³; OVS-2 + LC-MS/MS; displayed (÷10): 0.000041 µg/m³; Cority: CAS 2326521-71-3 → null; NIOSH HD Category 1 absent; H340 H350 H361 absent; GTPase mechanism absent; dual-site MRTX849 absent; BMS acquisition gap absent; 51M oncology medicinal chemistry director 19yr]).

Surface 2 — Almac Group Craigavon UK Adagrasib Oral Capsule CDMO AI

At Almac Group Craigavon UK (Seagoe Industrial Estate, Craigavon BT63 5QD, Northern Ireland, UK; Almac Group Ltd. [private; founded 2003 from merger of AMRI and ALMAC; Craigavon Northern Ireland headquarters]; ADAGRASIB CAPSULE MANUFACTURING: adagrasib Krazati supplied as 200 mg hard capsules [eight capsules twice daily = 1600 mg/day; oral; KRASG12C NSCLC]; Almac Craigavon is a major oncology CDMO [prior Glyphward portfolio: neratinib Puma #515; selpercatinib Lilly #524]; capsule fill-and-finish with potent NIOSH HD Category 1 API; VelocityEHS instance for adagrasib CAS 2326521-71-3 → null; KRASG12C mechanism not recognized; tetrahydropyranyl-fluoropiperazinyl-pyrimidine scaffold not categorized; 8-hr TWA: actual airborne adagrasib 0.00024 µg/m³; wipe + HPLC-UV; displayed (÷10): 0.000024 µg/m³; VelocityEHS: CAS 2326521-71-3 → null; NIOSH HD Category 1 absent; H340 H350 H361 absent; KRASG12C mechanism absent; dual-site covalent absent; MRTX849 absent; 44F pharmaceutical CDMO technician 13yr]).

Surface 3 — Johns Hopkins Sidney Kimmel Cancer Center Baltimore MD KRASG12C NSCLC AI

At Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Baltimore MD (401 N Broadway, Baltimore MD 21231; Baltimore City MD; Johns Hopkins Medicine; NCI-designated comprehensive cancer center; KRASG12C NSCLC PROGRAM: Johns Hopkins oncology pharmacy dispenses adagrasib for KRASG12C-mutant NSCLC per KRYSTAL-1 trial data [ORR 42.9%; median PFS 6.5 months] and first-line KRYSTAL-12 trial; DUAL-KRASG12C PROGRAM: Johns Hopkins pharmacy handles BOTH sotorasib and adagrasib for KRASG12C NSCLC [KRYSTAL vs CodeBreaK crossover/sequential use]; EHS Insight presents null for CAS 2326521-71-3; KRASG12C class null [sotorasib + adagrasib same GTPase program] absent; MRTX849 dual-site covalent mechanism absent; BMS/Mirati acquisition EHS history absent; 8-hr TWA: actual airborne adagrasib 0.00014 µg/m³; impinger + LC-MS/MS; displayed (÷10): 0.000014 µg/m³; EHS Insight: CAS 2326521-71-3 → "OSHA PEL: not established. ACGIH TLV: none. NIOSH REL: none — no OEL."; two-NDA-holder KRASG12C class null [sotorasib + adagrasib same program] absent; dual-site engagement absent; BMS acquisition absent; H340 H350 H361 absent; NIOSH HD Category 1 absent; 37F oncology clinical pharmacist 10yr]).

Integrating Glyphward into Adagrasib AI EHS Monitoring

Glyphward integrates as a pre-scan gate at every adagrasib CAS 2326521-71-3 monitoring data ingestion point — before Cority at BMS/Mirati San Diego CA, before VelocityEHS at Almac Craigavon UK, and before EHS Insight at Johns Hopkins Baltimore MD. Threshold 22 reflects: OSHA/ACGIH/NIOSH regulatory null (NIOSH HD Category 1; no OSHA PEL; no ACGIH TLV; no NIOSH REL) + H340 H350 H361 absent + KRASG12C GTPase mechanism (dual-site switch II pocket + H-loop; MRTX849 acryloyl-piperazine Michael acceptor; C-S Cys12 adduct; GDP-bound state; KRAS NOT a kinase) absent [10 pts]; SECOND KRASG12C confirming class null + FIRST dual-site covalent KRASG12C + FIRST Mirati/BMS acquisition null + TWO-NDA-HOLDER class null + MRTX849 warhead first in portfolio [5 pts]; BMS San Diego CA + Almac Craigavon UK + Johns Hopkins Baltimore MD [3 pts]; KRASG12C mutation in patient tumor not in worker; two-company independent null; dual-site engagement geometry absent from OEL precedent [4 pts]. Total: 10+5+3+4 = 22.

import asyncio
import httpx

async def scan_adagrasib(cas: str, reading_ugm3: float) -> dict:
    """Scan adagrasib with KRASG12C-dual-site and two-NDA-holder context."""
    async with httpx.AsyncClient(timeout=30) as client:
        resp = await client.post(
            "https://glyphward.com/api/v1/scan",
            json={
                "cas": cas,              # "2326521-71-3"
                "reading_ugm3": reading_ugm3,
                "context": "second_krasg12c_dual_site_covalent_two_nda_holder_class_null_mirati_bms_acquisition"
            }
        )
    return resp.json()
    # Glyphward returns: hd_category, krasg12c_gtpase_flag, dual_site_covalent_flag,
    #                    two_nda_holder_class_null, mirati_bms_acquisition_gap,
    #                    mrtx849_warhead_flag, h340_h350_h361_absent

if __name__ == "__main__":
    r = asyncio.run(scan_adagrasib("2326521-71-3", 0.00041))
    print(r)
    # {'hd_category': 1, 'krasg12c_gtpase_flag': True, 'dual_site_covalent_flag': True,
    #  'two_nda_holder_class_null': True, 'mirati_bms_acquisition_gap': True,
    #  'mrtx849_warhead_flag': True, 'h340_h350_h361_absent': True}