PIM2 / MYC · Multiple myeloma

Rethinking PIM2 biology

P2K Dynamics is investigating a dual-action approach to PIM2—one designed to address catalytic signaling and the emerging kinase-independent biology that connects PIM2 to MYC.

Dual channel Catalytic signaling and an emerging regulatory route connect PIM2 biology to MYC transcription.
Follow the evidence

01 Clinical context

Relapse keepschangingthe question.

Explore the clinical context

Multiple myeloma remains incurable for most patients, and most eventually relapse. Signals from the bone-marrow microenvironment can support myeloma-cell survival and contribute to drug resistance.

That makes durable control of core survival biology—not only another pass at a familiar signal—an important research goal.

Marrow niche

Diagnostic entry: ≥10% clonal marrow plasma cells or a biopsy-proven plasmacytoma, plus ≥1 myeloma-defining event. Biomarker: ≥60%; MRI: >1 focal lesion, each ≥5 mm.

IMWG criteria
Treatment pressure

2024 meta-analysis in newly diagnosed myeloma: PFS HR 0.55; OS HR 0.65; MRD-negative at 10⁻⁵ RR 1.39 for quadruplets vs triplets.

Blood Advances
Disease burden

2026 U.S.: 36,000 new cases; 10,850 deaths. Five-year relative survival: 63.7% (2016–2022).

NCI SEER

02 The dependency

A survival nodemyeloma keepsreturning to.

Explore the PIM2 evidence

PIM2 is highly expressed in malignant plasma cells and reinforced by signals from the bone-marrow niche. Genetic and pharmacologic studies support its role in myeloma-cell growth and survival.

PIM2 links marrow-derived cytokine signals to mTORC1-dependent protein translation and cell-survival pathways. Its contribution to treatment resistance is supported in myeloma models.

BMSC · IL-6 / STAT3 OC · NF-κB GROWTH + SURVIVAL MYELOMA SURVIVAL NODEPIM2

03 The driver

Central to cancer.Hard to approachdirectly.

Explore the MYC rationale

MYC helps coordinate proliferation, metabolism and survival across many cancers, including multiple myeloma. Its flexible, largely disordered structure offers few stable pockets for conventional small molecules.

P2K is studying whether PIM2 can serve as an indirect control point for MYC abundance and transcriptional output. This proposed route remains under study.

PARTNER-ENABLED FOLDFLEXIBLE bHLHZ → MYC–MAX HETERODIMER → E-BOX MYC bHLHZ · FLEXIBLE ALONE MOST OF MYC REMAINS DISORDERED MYC MAX CACGTG BASIC REGIONS · E-BOX DNA STATIC · DOMAIN-SPECIFIC ORDER ON PARTNER BINDING

04 The emerging circuit

PIM2 may offeran indirect routeinto MYC biology.

Explore the emerging circuit

Published studies connect PIM2 catalytic signaling to myeloma survival and place MYC at the PIM2 locus. Preliminary conference data propose a kinase-independent autoregulatory model involving MYC and an SP1 site; the exact molecular contacts remain under study.

Early clinical studies of ATP-site PIM inhibition showed limited single-agent activity. P2K is testing whether addressing catalytic signaling together with emerging kinase-independent biology can produce a different pharmacology profile.

EVIDENCE-BOUNDED LOOP MM TRANSCRIPTIONAL MODEL · DIRECT CONTACT NOT ASSUMED PIM2PROTEIN MYCOCCUPANCY SP1 PIM2 PROMOTER GENE EXPRESSION MYC ChIP SIGNAL REGULATORY RETURN

05 The P2K approach

One program.Two dimensions ofPIM2 control.

Explore the P2K126 program

PIM2 and MYC downregulation is the defining program outcome—and convergent internal evidence shows that it does not depend on inhibiting PIM2 kinase activity. Genetic, promoter-reporter, ChIP and pharmacologic studies support that separation across tested multiple-myeloma systems.

P2K126 anchors a related analogue series designed to combine kinase-independent downregulation of PIM2 and MYC with catalytic pathway suppression. Lead analogues are being optimized for oral exposure, selectivity and developability.

INDEPENDENT CONTROL AXES P2K126 + RELATED ANALOGUES · TWO ACTIVITY PROFILES · ONE OUTCOME P2K126DISCOVERY SERIES WITH KINASE INHIBITIONPIM2 KINASE INHIBITEDCATALYTIC SIGNALING SUPPRESSED WITHOUT KINASE INHIBITIONKINASE ACTIVITY RETAINED PIM2 + MYC DOWNREGULATIONDOES NOT REQUIRE KINASE INHIBITION

06 The evidence ladder

Mechanism, cellsand models musttell the same story.

Explore the evidence framework

P2K advances the program through linked biochemical, cellular, pharmacodynamic and in-vivo readouts. Every step asks whether activity remains connected to PIM2 and MYC biology.

Concordance across these orthogonal systems builds confidence in mechanism and guides progression of analogues whose PIM2 and MYC effects remain coherent across experimental scales.

01BiochemicalTarget engagement and catalytic output 02CellularPIM2, MYC and viability readouts 03TranslationalExposure-linked tissue pharmacology 04In vivoComplementary myeloma models

07 Frontier program

Pioneering dualPIM2–MYC controlin myeloma.

Explore the frontier program

P2K126 anchors a potential first-in-class program designed to suppress multiple-myeloma survival biology through coordinated PIM2 kinase inhibition and modulation of the emerging PIM2–MYC regulatory circuit.

The program is advancing a differentiated oral profile through orthogonal target engagement, dual-action cellular pharmacology, exposure-linked tissue pharmacodynamics, selectivity and tolerability.

  1. 01EngageOrthogonal PIM2 target engagement
  2. 02ModulateCatalytic + PIM2–MYC biology
  3. 03SuppressExposure-linked myeloma response
  4. 04LeadDifferentiated oral profile